Dott. Russo Claudio Francesco
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Against Odds of Prolonged Warm Ischemia: Early Experience With DCD Heart Transplantation After 20-Minute No-Touch Period.
Circulation2024 Oct;150(17):1391-1393. doi: 10.1161/CIRCULATIONAHA.124.071239.
Gerosa Gino, Battista Luciani Giovanni, Pradegan Nicola, Tarzia Vincenzo, Lena Tea, Zanatta Paolo, Pittarello Demetrio, Onorati Francesco, Galeone Antonella, Gottin Leonardo, Boffini Massimo, Zanierato Marinella, Marro Matteo, Martin Suarez Sofia, Botta Luca, Lilla Della Monica Paola, Feccia Mariano, Olivieri Guido Maria, Terzi Amedeo, Oliveti Alessandra, Feltrin Giuseppe, Cardillo Massimo, Russo Claudio Francesco, Pacini Davide, Rinaldi Mauro
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Neurologic complications in patients receiving aortic versus subclavian versus femoral arterial cannulation for post-cardiotomy extracorporeal life support: results of the PELS observational multicenter study.
Crit Care2024 Aug;28(1):265. doi: 265.
Chiarini Giovanni, Mariani Silvia, Schaefer Anne-Kristin, van Bussel Bas C T, Di Mauro Michele, Wiedemann Dominik, Saeed Diyar, Pozzi Matteo, Botta Luca, Boeken Udo, Samalavicius Robertas, Bounader Karl, Hou Xiaotong, Bunge Jeroen J H, Buscher Hergen, Salazar Leonardo, Meyns Bart, Herr Daniel, Matteucci Sacha, Sponga Sandro, Ramanathan Kollengode, Russo Claudio, Formica Francesco, Sakiyalak Pranya, Fiore Antonio, Camboni Daniele, Raffa Giuseppe Maria, Diaz Rodrigo, Wang I-Wen, Jung Jae-Seung, Belohlavek Jan, Pellegrino Vin, Bianchi Giacomo, Pettinari Matteo, Barbone Alessandro, Garcia José P, Shekar Kiran, Whitman Glenn J R, Lorusso Roberto,
Abstract
BACKGROUND:
Cerebral perfusion may change depending on arterial cannulation site and may affect the incidence of neurologic adverse events in post-cardiotomy extracorporeal life support (ECLS). The current study compares patients' neurologic outcomes with three commonly used arterial cannulation strategies (aortic vs. subclavian/axillary vs. femoral artery) to evaluate if each ECLS configuration is associated with different rates of neurologic complications.
METHODS:
This retrospective, multicenter (34 centers), observational study included adults requiring post-cardiotomy ECLS between January 2000 and December 2020 present in the Post-Cardiotomy Extracorporeal Life Support (PELS) Study database. Patients with Aortic, Subclavian/Axillary and Femoral cannulation were compared on the incidence of a composite neurological end-point (ischemic stroke, cerebral hemorrhage, brain edema). Secondary outcomes were overall in-hospital mortality, neurologic complications as cause of in-hospital death, and post-operative minor neurologic complications (seizures). Association between cannulation and neurological outcomes were investigated through linear mixed-effects models.
RESULTS:
This study included 1897 patients comprising 26.5% Aortic (n?=?503), 20.9% Subclavian/Axillary (n?=?397) and 52.6% Femoral (n?=?997) cannulations. The Subclavian/Axillary group featured a more frequent history of hypertension, smoking, diabetes, previous myocardial infarction, dialysis, peripheral artery disease and previous stroke. Neuro-monitoring was used infrequently in all groups. Major neurologic complications were more frequent in Subclavian/Axillary (Aortic: n?=?79, 15.8%; Subclavian/Axillary: n?=?78, 19.6%; Femoral: n?=?118, 11.9%; p?0.001) also after mixed-effects model adjustment (OR 1.53 [95% CI 1.02-2.31], p?=?0.041). Seizures were more common in Subclavian/Axillary (n?=?13, 3.4%) than Aortic (n?=?9, 1.8%) and Femoral cannulation (n?=?12, 1.3%, p?=?0.036). In-hospital mortality was higher after Aortic cannulation (Aortic: n?=?344, 68.4%, Subclavian/Axillary: n?=?223, 56.2%, Femoral: n?=?587, 58.9%, p?0.001), as shown by Kaplan-Meier curves. Anyhow, neurologic cause of death (Aortic: n?=?12, 3.9%, Subclavian/Axillary: n?=?14, 6.6%, Femoral: n?=?28, 5.0%, p?=?0.433) was similar.
CONCLUSIONS:
In this analysis of the PELS Study, Subclavian/Axillary cannulation was associated with higher rates of major neurologic complications and seizures. In-hospital mortality was higher after Aortic cannulation, despite no significant differences in incidence of neurological cause of death in these patients. These results encourage vigilance for neurologic complications and neuromonitoring use in patients on ECLS, especially with Subclavian/Axillary cannulation.
© 2024. The Author(s).
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Post-cardiotomy extracorporeal life support: A cohort of cannulation in the general ward.
Artif Organs2024 Nov;48(11):1355-1365. doi: 10.1111/aor.14818.
Bari Gabor, Mariani Silvia, van Bussel Bas C T, Ravaux Justine, Di Mauro Michele, Schaefer Anne, Khalil Jawad, Pozzi Matteo, Botta Luca, Pacini Davide, Boeken Udo, Samalavicius Robertas, Bounader Karl, Hou Xiaotong, Bunge Jeroen J H, Buscher Hergen, Salazar Leonardo, Meyns Bart, Mazeffi Michael, Matteucci Sacha, Sponga Sandro, MacLaren Graeme, Russo Claudio, Formica Francesco, Sakiyalak Pranya, Fiore Antonio, Camboni Daniele, Raffa Giuseppe Maria, Diaz Rodrigo, Wang I-Wen, Jung Jae-Seung, Belohlavek Jan, Pellegrino Vin, Bianchi Giacomo, Pettinari Matteo, Barbone Alessandro, Garcia José P, Shekar Kiran, Whitman Glenn, Lorusso Roberto,
Abstract
OBJECTIVES:
Post-cardiotomy extracorporeal life support (ECLS) cannulation might occur in a general post-operative ward due to emergent conditions. Its characteristics have been poorly reported and investigated This study investigates the characteristics and outcomes of adult patients receiving ECLS cannulation in a general post-operative cardiac ward.
METHODS:
The Post-cardiotomy Extracorporeal Life Support (PELS) is a retrospective (2000-2020), multicenter (34 centers), observational study including adult patients who required ECLS for post-cardiotomy shock. This PELS sub-analysis analyzed patients´ characteristics, in-hospital outcomes, and long-term survival in patients cannulated for veno-arterial ECLS in the general ward, and further compared in-hospital survivors and non-survivors.
RESULTS:
The PELS study included 2058 patients of whom 39 (1.9%) were cannulated in the general ward. Most patients underwent isolated coronary bypass grafting (CABG, n?=?15, 38.5%) or isolated non-CABG operations (n?=?20, 51.3%). The main indications to initiate ECLS included cardiac arrest (n?=?17, 44.7%) and cardiogenic shock (n?=?14, 35.9%). ECLS cannulation occurred after a median time of 4 (2-7) days post-operatively. Most patients' courses were complicated by acute kidney injury (n?=?23, 59%), arrhythmias (n?=?19, 48.7%), and postoperative bleeding (n?=?20, 51.3%). In-hospital mortality was 84.6% (n?=?33) with persistent heart failure (n?=?11, 28.2%) as the most common cause of death. No peculiar differences were observed between in-hospital survivors and nonsurvivors.
CONCLUSIONS:
This study demonstrates that ECLS cannulation due to post-cardiotomy emergent adverse events in the general ward is rare, mainly occurring in preoperative low-risk patients and after a postoperative cardiac arrest. High complication rates and low in-hospital survival require further investigations to identify patients at risk for such a complication, optimize resources, enhance intervention, and improve outcomes.
© 2024 The Author(s). Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.
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Prognostic Value of APACHE IV Score in Patients Bridged to Heart Transplantation on ECMO.
Clin Transplant2024 Jun;38(6):e15370. doi: 10.1111/ctr.15370.
Lechiancole Andrea, Russo Claudio F, Olivieri Guido M, Maccherini Massimo, Valente Serafina, Pacini Davide, Suarez Sofia Martin, Boffini Massimo, Marro Matteo, Pelenghi Stefano, Totaro Pasquale, Isola Miriam, Martino Maria De, Bortolotti Uberto, Livi Ugolino, Vendramin Igor
Abstract
BACKGROUND:
Methods for risk stratification of candidates for heart transplantation (HTx) supported by extracorporeal membrane oxygenation (ECMO) are limited. We evaluated the reliability of the APACHE IV score to identify the risk of mortality in this patient subset in a multicenter study.
METHODS:
Between January 2010 and December 2022, 167 consecutive ECMO patients were bridged to HTx; they were divided into two groups, according to a cutoff value of APACHE IV score, obtained by receiver operating characteristic curve analysis for 90-day mortality. Kaplan-Meier survival curves were plotted, and compared through the log-Rank test. Cox regression model was used to estimate which factors were associated with survival.
RESULTS:
The 90-day mortality prediction of the APACHE IV score showed an area under the curve of 0.87 (95% CI: 0.80-0.94), with a cutoff value of 49 (specificity 91.7%-sensibility 69.6%). 125 patients (74.8%) showed an APACHE IV score value
CONCLUSIONS:
The APACHE IV score represents a powerful predictor of survival in patients bridged to HTx on ECMO support, and could guide candidacy of patients on ECMO.
© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Characteristics and Outcomes of Prolonged Venoarterial Extracorporeal Membrane Oxygenation After Cardiac Surgery: The Post-Cardiotomy Extracorporeal Life Support (PELS-1) Cohort Study.
Crit Care Med2024 Oct;52(10):e490-e502. doi: 10.1097/CCM.0000000000006349.
Bunge Jeroen J H, Mariani Silvia, Meuwese Christiaan, van Bussel Bas C T, Di Mauro Michele, Wiedeman Dominik, Saeed Diyar, Pozzi Matteo, Loforte Antonio, Boeken Udo, Samalavicius Robertas, Bounader Karl, Hou Xiaotong, Buscher Hergen, Salazar Leonardo, Meyns Bart, Herr Daniel, Matteucci Sacha, Sponga Sandro, MacLaren Graeme, Russo Claudio, Formica Francesco, Sakiyalak Pranya, Fiore Antonio, Camboni Daniele, Raffa Giuseppe Maria, Diaz Rodrigo, Wang I-Wen, Jung Jae-Seung, Belohlavek Jan, Pellegrino Vin, Bianchi Giacomo, Pettinari Matteo, Barbone Alessandro, Garcia José P, Shekar Kiran, Whitman Glenn J R, Gommers Diederik, Dos Reis Miranda Dinis, Lorusso Roberto,
Abstract
OBJECTIVES:
Most post-cardiotomy (PC) extracorporeal membrane oxygenation (ECMO) runs last less than 7 days. Studies on the outcomes of longer runs have provided conflicting results. This study investigates patient characteristics and short- and long-term outcomes in relation to PC ECMO duration, with a focus on prolonged (> 7 d) ECMO.
DESIGN:
Retrospective observational cohort study.
SETTING:
Thirty-four centers from 16 countries between January 2000 and December 2020.
PATIENTS:
Adults requiring post PC ECMO between 2000 and 2020.
INTERVENTIONS:
None.
MEASUREMENTS AND MAIN RESULTS:
Characteristics, in-hospital, and post-discharge outcomes were compared among patients categorized by ECMO duration. Survivors and nonsurvivors were compared in the subgroup of patients with ECMO duration greater than 7 days. The primary outcome was in-hospital mortality. Two thousand twenty-one patients were included who required PC ECMO for 0-3 days ( n = 649 [32.1%]), 4-7 days ( n = 776 [38.3%]), 8-10 days ( n = 263 [13.0%]), and greater than 10 days ( n = 333 [16.5%]). There were no major differences in the investigated preoperative and procedural characteristics among ECMO duration groups. However, the longer ECMO duration category was associated with multiple complications including bleeding, acute kidney injury, arrhythmias, and sepsis. Hospital mortality followed a U-shape curve, with lowest mortality in patients with ECMO duration of 4-7 days ( n = 394, 50.8%) and highest in patients with greater than 10 days ECMO support ( n = 242, 72.7%). There was no significant difference in post-discharge survival between ECMO duration groups. In patients with ECMO duration greater than 7 days, age, comorbidities, valvular diseases, and complex procedures were associated with nonsurvival.
CONCLUSIONS:
Nearly 30% of PC ECMO patients were supported for greater than 7 days. In-hospital mortality increased after 7 days of support, especially in patients undergoing valvular and complex surgery, or who had complications, although the long-term post-discharge prognosis was comparable to PC ECMO patients with shorter support duration.
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.
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Morpho-physiological adaptations to weed competition impair green bean () ability to overcome moderate salt stress.
Funct Plant Biol2024 May;51():. doi: FP23202.
Cirillo Valerio, Esposito Marco, Lentini Matteo, Russo Claudio, Pollaro Nausicaa, Maggio Albino
Abstract
The two stresses of weed competition and salt salinity lead to crop yield losses and decline in the productivity of agricultural land. These constraints threaten the future of food production because weeds are more salt stress tolerant than most crops. Climate change will lead to an increase of soil salinity worldwide, and possibly exacerbate the competition between weeds and crops. This aspect has been scarcely investigated in the context of weed-crop competition. Therefore, we conducted a field experiment on green beans (Phaseolus vulgaris ) to investigate the combined impact of weed competition and salt stress on key morpho-physiological traits, and crop yield. We demonstrated that soil salinity shifted weed composition toward salt tolerant weed species (Portulaca oleracea and Cynodon dactylon ), while it reduced the presence of lower tolerance species. Weed competition activated adaptation responses in green bean such as reduced leaf mass per area and biomass allocation to the stem, unchanged stomatal density and instantaneous water use efficiency, which diverge from those that are typically observed as a consequence of salt stress. The morpho-physiological modifications caused by weeds is attributed to the alterations of light intensity and/or quality, further confirming the pivotal role of the light in crop response to weeds. We concluded that higher yield loss caused by combined salt stress and weed competition is due to impaired morpho-physiological responses, which highlights the negative interaction between salt stress and weed competition. This phenomenon will likely be more frequent in the future, and potentially reduce the efficacy of current weed control methods.
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Features and outcomes of female and male patients requiring postcardiotomy extracorporeal life support.
J Thorac Cardiovasc Surg2024 May;():. doi: S0022-5223(24)00435-5.
Mariani Silvia, Ravaux Justine Mafalda, van Bussel Bas C T, De Piero Maria Elena, van Kruijk Sander M J, Schaefer Anne-Kristin, Wiedemann Dominik, Saeed Diyar, Pozzi Matteo, Loforte Antonio, Boeken Udo, Samalavicius Robertas, Bounader Karl, Hou Xiaotong, Bunge Jeroen J H, Buscher Hergen, Salazar Leonardo, Meyns Bart, Mazzeffi Michael A, Matteucci Sacha, Sponga Sandro, Sorokin Vitaly, Russo Claudio, Formica Francesco, Sakiyalak Pranya, Fiore Antonio, Camboni Daniele, Raffa Giuseppe Maria, Diaz Rodrigo, Wang I-Wen, Jung Jae-Seung, Belohlavek Jan, Pellegrino Vin, Bianchi Giacomo, Pettinari Matteo, Barbone Alessandro, Garcia José P, Shekar Kiran, Whitman Glenn J R, Lorusso Roberto,
Abstract
OBJECTIVES:
Although cardiogenic shock requiring extracorporeal life support after cardiac surgery is associated with high mortality, the impact of sex on outcomes of postcardiotomy extracorporeal life support remains unclear with conflicting results in the literature. We compare patient characteristics, in-hospital outcomes, and overall survival between females and males requiring postcardiotomy extracorporeal life support.
METHODS:
This retrospective, multicenter (34 centers), observational study included adults requiring postcardiotomy extracorporeal life support between 2000 and 2020. Preoperative, procedural, and extracorporeal life support characteristics, complications, and survival were compared between females and males. Association between sex and in-hospital survival was investigated through mixed Cox proportional hazard models.
RESULTS:
This analysis included 1823 patients (female: 40.8%; median age: 66.0 years [interquartile range, 56.2-73.0 years]). Females underwent more mitral valve surgery (females: 38.4%, males: 33.1%, P = .019) and tricuspid valve surgery (feamales: 18%, males: 12.4%, P
CONCLUSIONS:
This study demonstrates that female and male patients requiring postcardiotomy extracorporeal life support have different preoperative and extracorporeal life support characteristics, as well as complications, without a statistical difference in in-hospital and 5-year survivals.
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
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Long-term survival after surgical treatment for post-infarction mechanical complications: results from the Caution study.
Eur Heart J Qual Care Clin Outcomes2024 Feb;():. doi: qcae010.
Matteucci Matteo, Ronco Daniele, Kowalewski Mariusz, Massimi Giulio, De Bonis Michele, Formica Francesco, Jiritano Federica, Folliguet Thierry, Bonaros Nikolaos, Sponga Sandro, Suwalski Piotr, De Martino Andrea, Fischlein Theodor, Troise Giovanni, Dato Guglielmo Actis, Serraino Filiberto Giuseppe, Shah Shabir Hussain, Scrofani Roberto, Kalisnik Jurij Matija, Colli Andrea, Russo Claudio Francesco, Ranucci Marco, Pettinari Matteo, Kowalowka Adam, Thielmann Matthias, Meyns Bart, Khouqeer Fareed, Obadia Jean-Francois, Boeken Udo, Simon Caterina, Naito Shiho, Musazzi Andrea, Lorusso Roberto
Abstract
BACKGROUND AND AIMS:
Mechanical complications (MCs) are rare but potentially fatal sequelae of acute myocardial infarction (AMI). Surgery, though challenging, is considered the treatment of choice. The authors sought to study early and long-term results of patients undergoing surgical treatment for post-AMI MCs.
METHODS:
Patients undergone surgical treatment for post-infarction MCs between 2001 through 2019 in 27 centers worldwide were retrieved from the database of CAUTION study. In-hospital and long-term mortality were the primary outcomes. Cox proportional hazards regression models were used to determine independent factors associated with overall mortality.
RESULTS:
The study included 720 patients. The median age was 70.0 [62.0-77.0] years, with a male predominance (64.6%). The most common MC encountered was ventricular septal rupture (VSR) (59.4%). Cardiogenic shock was seen on presentation in 56.1% of patients. In-hospital mortality rate was 37.4%; in more than 50% of cases, the cause of death was low cardiac output syndrome (LCOS). Late mortality occurred in 133 patients, with a median follow-up of 4.4 [1.0-8.6] years. Overall survival at 1, 5 and 10 years was 54.0%, 48.1% and 41.0%, respectively. Older age (p
CONCLUSIONS:
Contemporary data from a multicenter cohort study show that surgical treatment for post-AMI MCs continues to be associated with high in-hospital mortality rates. However, long-term survival in patients surviving the immediate postoperative period is encouraging.Trial registration number: NCT03848429.
© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.
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Impact of COVID-19 on incidence and outcomes of post-infarction mechanical complications in Europe.
Interdiscip Cardiovasc Thorac Surg2023 Dec;37(6):. doi: ivad198.
Ronco Daniele, Matteucci Matteo, Ravaux Justine Mafalda, Kowalewski Mariusz, Massimi Giulio, Torchio Federica, Trumello Cinzia, Naito Shiho, Bonaros Nikolaos, De Bonis Michele, Fina Dario, Kowalówka Adam, Deja Marek, Jiritano Federica, Serraino Giuseppe Filiberto, Kalisnik Jurij Matija, De Vincentiis Carlo, Ranucci Marco, Fischlein Theodor, Russo Claudio Francesco, Carrozzini Massimiliano, Boeken Udo, Kalampokas Nikolaos, Golino Michele, De Ponti Roberto, Pozzi Matteo, Obadia Jean-François, Thielmann Matthias, Scrofani Roberto, Blasi Stefania, Troise Giovanni, Antona Carlo, De Martino Andrea, Falcetta Giosuè, Actis Dato Guglielmo, Severgnini Paolo, Musazzi Andrea, Lorusso Roberto
Abstract
OBJECTIVES:
Post-acute myocardial infarction mechanical complications (post-AMI MCs) represent rare but life-threatening conditions, including free-wall rupture, ventricular septal rupture and papillary muscle rupture. During the coronavirus disease-19 (COVID-19) pandemic, an overwhelming pressure on healthcare systems led to delayed and potentially suboptimal treatments for time-dependent conditions. As AMI-related hospitalizations decreased, limited information is available whether higher rates of post-AMI MCs and related deaths occurred in this setting. This study was aimed to assess how COVID-19 in Europe has impacted the incidence, treatment and outcome of MCs.
METHODS:
The CAUTION-COVID19 study is a multicentre retrospective study collecting 175 patients with post-AMI MCs in 18 centres from 6 European countries, aimed to compare the incidence of such events, related patients' characteristics, and outcomes, between the first year of pandemic and the 2 previous years.
RESULTS:
A non-significant increase in MCs was observed [odds ratio (OR)?=?1.15, 95% confidence interval (CI) 0.85-1.57; P?=?0.364], with stronger growth in ventricular septal rupture diagnoses (OR?=?1.43, 95% CI 0.95-2.18; P?=?0.090). No significant differences in treatment types and mortality were found between the 2 periods. In-hospital mortality was 50.9% and was higher for conservatively managed cases (90.9%) and lower for surgical patients (44.0%). Patients admitted during COVID-19 more frequently had late-presenting infarction (OR?=?2.47, 95% CI 1.24-4.92; P?=?0.010), more stable conditions (OR?=?2.61, 95% CI 1.27-5.35; P?=?0.009) and higher EuroSCORE II (OR?=?1.04, 95% CI 1.01-1.06; P?=?0.006).
CONCLUSIONS:
A non-significant increase in MCs incidence occurred during the first year of COVID-19, characterized by a significantly higher rate of late-presenting infarction, stable conditions and EuroSCORE-II if compared to pre-pandemic data, without affecting treatment and mortality.
© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.
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Innovative Phospholipid Carriers: A Viable Strategy to Counteract Antimicrobial Resistance.
Int J Mol Sci2023 Nov;24(21):. doi: 15934.
Nicolosi Daria, Petronio Petronio Giulio, Russo Stefano, Di Naro Maria, Cutuli Marco Alfio, Russo Claudio, Di Marco Roberto
Abstract
The overuse and misuse of antibiotics have led to the emergence and spread of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) bacteria strains, usually associated with poorer patient outcomes and higher costs. In order to preserve the usefulness of these life-saving drugs, it is crucial to use them appropriately, as also recommended by the WHO. Moreover, innovative, safe, and more effective approaches are being investigated, aiming to revise drug treatments to improve their pharmacokinetics and distribution and to reduce the onset of drug resistance. Globally, to reduce the burden of antimicrobial resistance (AMR), guidelines and indications have been developed over time, aimed at narrowing the use and diminishing the environmental spread of these life-saving molecules by optimizing prescriptions, dosage, and times of use, as well as investing resources into obtaining innovative formulations with better pharmacokinetics, pharmacodynamics, and therapeutic results. This has led to the development of new nano-formulations as drug delivery vehicles, characterized by unique structural properties, biocompatible natures, and targeted activities such as state-of-the-art phospholipid particles generally grouped as liposomes, virosomes, and functionalized exosomes, which represent an attractive and innovative delivery approach. Liposomes and virosomes are chemically synthesized carriers that utilize phospholipids whose nature is predetermined based on their use, with a long track record as drug delivery systems. Exosomes are vesicles naturally released by cells, which utilize the lipids present in their cellular membranes only, and therefore, are highly biocompatible, with investigations as a delivery system having a more recent origin. This review will summarize the state of the art on microvesicle research, liposomes, virosomes, and exosomes, as useful and effective tools to tackle the threat of antibiotic resistance.
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?-Casein-Loaded Proteo-liposomes as Potential Inhibitors in Amyloid Fibrillogenesis: Effects on a Model of Alzheimer's Disease.
ACS Chem Neurosci2023 Nov;14(21):3894-3904. doi: 10.1021/acschemneuro.3c00239.
Paterna Angela, Santonicola Pamela, Di Prima Giulia, Rao Estella, Raccosta Samuele, Zampi Giuseppina, Russo Claudio, Moran Oscar, Manno Mauro, Di Schiavi Elia, Librizzi Fabio, Carrotta Rita
Abstract
According to the amyloid hypothesis, in the early phases of Alzheimer's disease (AD), small soluble prefibrillar aggregates of the amyloid ?-peptide (A?) interact with neuronal membranes, causing neural impairment. Such highly reactive and toxic species form spontaneously and transiently in the amyloid building pathway. A therapeutic strategy consists of the recruitment of these intermediates, thus preventing aberrant interaction with membrane components (lipids and receptors), which in turn may trigger a cascade of cellular disequilibria. Milk ?-Casein is an intrinsically disordered protein that is able to inhibit A? amyloid aggregation , by sequestering transient species. In order to test ?-Casein as an inhibitor for the treatment of AD, it needs to be delivered in the place of action. Here, we demonstrate the use of large unilamellar vesicles (LUVs) as suitable nanocarriers for ?-Casein. Proteo-LUVs were prepared and characterized by different biophysical techniques, such as multiangle light scattering, atomic force imaging, and small-angle X-ray scattering; ?-Casein loading was quantified by a fluorescence assay. We demonstrated on a AD model the effectiveness of the proposed delivery strategy . Proteo-LUVs allow efficient administration of the protein, exerting a positive functional readout at very low doses while avoiding the intrinsic toxicity of ?-Casein. Proteo-LUVs of ?-Casein represent an effective proof of concept for the exploitation of partially disordered proteins as a therapeutic strategy in mild AD conditions.
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The current clinical practice for management of post-infarction ventricular septal rupture: a European survey.
Eur Heart J Open2023 Sep;3(5):oead091. doi: oead091.
Ronco Daniele, Ariza-Solé Albert, Kowalewski Mariusz, Matteucci Matteo, Di Mauro Michele, López-de-Sá Esteban, Ranucci Marco, Sionis Alessandro, Bonaros Nikolaos, De Bonis Michele, Russo Claudio Francesco, Uribarri Aitor, Montero Santiago, Fischlein Theodor, Kowalówka Adam, Naito Shiho, Obadia Jean-François, Martín-Asenjo Roberto, Aboal Jaime, Thielmann Matthias, Simon Caterina, Andrea-Riba Rut, Parra Carolina, Folliguet Thierry, Martínez-Sellés Manuel, Sanmartín Fernández Marcelo, Al-Attar Nawwar, Viana Tejedor Ana, Serraino Giuseppe Filiberto, Burgos Palacios Virginia, Boeken Udo, Raposeiras Roubin Sergio, Solla Buceta Miguel Antonio, Sánchez Fernández Pedro Luis, Scrofani Roberto, Pastor Báez Gemma, Jorge Pérez Pablo, Actis Dato Guglielmo, Garcia-Rubira Juan Carlos, de Gea Garcia Jose H, Massimi Giulio, Musazzi Andrea, Lorusso Roberto
Abstract
AIMS:
Many historical and recent reports showed that post-infarction ventricular septal rupture (VSR) represents a life-threatening condition and the strategy to optimally manage it remains undefined. Therefore, disparate treatment policies among different centres with variable results are often described. We analysed data from European centres to capture the current clinical practice in VSR management.
METHODS AND RESULTS:
Thirty-nine centres belonging to eight European countries participated in a survey, filling a digital form of 38 questions from April to October 2022, to collect information about all the aspects of VSR treatment. Most centres encounter 1-5 VSR cases/year. Surgery remains the treatment of choice over percutaneous closure (71.8% vs. 28.2%). A delayed repair represents the preferred approach (87.2%). Haemodynamic conditions influence the management in almost all centres, although some try to achieve patients stabilization and delayed surgery even in cardiogenic shock. Although 33.3% of centres do not perform coronarography in unstable patients, revascularization approaches are widely variable. Most centres adopt mechanical circulatory support (MCS), mostly extracorporeal membrane oxygenation, especially pre-operatively to stabilize patients and achieve delayed repair. Post-operatively, such MCS are more often adopted in patients with ventricular dysfunction.
CONCLUSION:
In real-life, delayed surgery, regardless of the haemodynamic conditions, is the preferred strategy for VSR management in Europe. Extracorporeal membrane oxygenation is becoming the most frequently adopted MCS as bridge-to-operation. This survey provides a useful background to develop dedicated, prospective studies to strengthen the current evidence on VSR treatment and to help improving its currently unsatisfactory outcomes.
© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.
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Patient and Management Variables Associated With Survival After Postcardiotomy Extracorporeal Membrane Oxygenation in Adults: The PELS-1 Multicenter Cohort Study.
J Am Heart Assoc2023 Jul;12(14):e029609. doi: e029609.
Mariani Silvia, Heuts Samuel, van Bussel Bas C T, Di Mauro Michele, Wiedemann Dominik, Saeed Diyar, Pozzi Matteo, Loforte Antonio, Boeken Udo, Samalavicius Robertas, Bounader Karl, Hou Xiaotong, Bunge Jeroen J H, Buscher Hergen, Salazar Leonardo, Meyns Bart, Herr Daniel, Matteucci Marco L Sacha, Sponga Sandro, MacLaren Graeme, Russo Claudio, Formica Francesco, Sakiyalak Pranya, Fiore Antonio, Camboni Daniele, Raffa Giuseppe Maria, Diaz Rodrigo, Wang I-Wen, Jung Jae-Seung, Belohlavek Jan, Pellegrino Vin, Bianchi Giacomo, Pettinari Matteo, Barbone Alessandro, Garcia José P, Shekar Kiran, Whitman Glenn J R, Lorusso Roberto,
Abstract
Background Extracorporeal membrane oxygenation (ECMO) has been increasingly used for postcardiotomy cardiogenic shock, but without a concomitant reduction in observed in-hospital mortality. Long-term outcomes are unknown. This study describes patients' characteristics, in-hospital outcome, and 10-year survival after postcardiotomy ECMO. Variables associated with in-hospital and postdischarge mortality are investigated and reported. Methods and Results The retrospective international multicenter observational PELS-1 (Postcardiotomy Extracorporeal Life Support) study includes data on adults requiring ECMO for postcardiotomy cardiogenic shock between 2000 and 2020 from 34 centers. Variables associated with mortality were estimated preoperatively, intraoperatively, during ECMO, and after the occurrence of any complications, and then analyzed at different time points during a patient's clinical course, through mixed Cox proportional hazards models containing fixed and random effects. Follow-up was established by institutional chart review or contacting patients. This analysis included 2058 patients (59% were men; median [interquartile range] age, 65.0 [55.0-72.0] years). In-hospital mortality was 60.5%. Independent variables associated with in-hospital mortality were age (hazard ratio [HR], 1.02 [95% CI, 1.01-1.02]) and preoperative cardiac arrest (HR, 1.41 [95% CI, 1.15-1.73]). In the subgroup of hospital survivors, the overall 1-, 2-, 5-, and 10-year survival rates were 89.5% (95% CI, 87.0%-92.0%), 85.4% (95% CI, 82.5%-88.3%), 76.4% (95% CI, 72.5%-80.5%), and 65.9% (95% CI, 60.3%-72.0%), respectively. Variables associated with postdischarge mortality included older age, atrial fibrillation, emergency surgery, type of surgery, postoperative acute kidney injury, and postoperative septic shock. Conclusions In adults, in-hospital mortality after postcardiotomy ECMO remains high; however, two-thirds of those who are discharged from hospital survive up to 10?years. Patient selection, intraoperative decisions, and ECMO management remain key variables associated with survival in this cohort. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03857217.
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On-Support and Postweaning Mortality in Postcardiotomy Extracorporeal Membrane Oxygenation.
Ann Thorac Surg2023 Nov;116(5):1079-1089. doi: 10.1016/j.athoracsur.2023.05.045.
Mariani Silvia, Schaefer Anne-Kristin, van Bussel Bas C T, Di Mauro Michele, Conci Luca, Szalkiewicz Philipp, De Piero Maria Elena, Heuts Samuel, Ravaux Justine, van der Horst Iwan C C, Saeed Diyar, Pozzi Matteo, Loforte Antonio, Boeken Udo, Samalavicius Robertas, Bounader Karl, Hou Xiaotong, Bunge Jeroen J H, Buscher Hergen, Salazar Leonardo, Meyns Bart, Herr Daniel, Matteucci Sacha, Sponga Sandro, MacLaren Graeme, Russo Claudio, Formica Francesco, Sakiyalak Pranya, Fiore Antonio, Camboni Daniele, Raffa Giuseppe Maria, Diaz Rodrigo, Wang I-Wen, Jung Jae-Seung, Belohlavek Jan, Pellegrino Vin, Bianchi Giacomo, Pettinari Matteo, Barbone Alessandro, Garcia José P, Whitman Glenn, Shekar Kiran, Wiedemann Dominik, Lorusso Roberto,
Abstract
BACKGROUND:
Postcardiotomy venoarterial extracorporeal membrane oxygenation (VA ECMO) is characterized by discrepancies between weaning and survival-to-discharge rates. This study analyzes the differences between postcardiotomy VA ECMO patients who survived, died on ECMO, or died after ECMO weaning. Causes of death and variables associated with mortality at different time points are investigated.
METHODS:
The retrospective, multicenter, observational Postcardiotomy Extracorporeal Life Support Study (PELS) includes adults requiring postcardiotomy VA ECMO between 2000 and 2020. Variables associated with on-ECMO mortality and postweaning mortality were modeled using mixed Cox proportional hazards, including random effects for center and year.
RESULTS:
In 2058 patients (men, 59%; median age, 65 years; interquartile range [IQR], 55-72 years), weaning rate was 62.7%, and survival to discharge was 39.6%. Patients who died (n = 1244) included 754 on-ECMO deaths (36.6%; median support time, 79 hours; IQR, 24-192 hours), and 476 postweaning deaths (23.1%; median support time, 146 hours; IQR, 96-235.5 hours). Multiorgan (n = 431 of 1158 [37.2%]) and persistent heart failure (n = 423 of 1158 [36.5%]) were the main causes of death, followed by bleeding (n = 56 of 754 [7.4%]) for on-ECMO mortality and sepsis (n = 61 of 401 [15.4%]) for postweaning mortality. On-ECMO death was associated with emergency surgery, preoperative cardiac arrest, cardiogenic shock, right ventricular failure, cardiopulmonary bypass time, and ECMO implantation timing. Diabetes, postoperative bleeding, cardiac arrest, bowel ischemia, acute kidney injury, and septic shock were associated with postweaning mortality.
CONCLUSIONS:
A discrepancy exists between weaning and discharge rate in postcardiotomy ECMO. Deaths occurred during ECMO support in 36.6% of patients, mostly associated with unstable preoperative hemodynamics. Another 23.1% of patients died after weaning in association with severe complications. This underscores the importance of postweaning care for postcardiotomy VA ECMO patients.
Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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The importance of timing in postcardiotomy venoarterial extracorporeal membrane oxygenation: A descriptive multicenter observational study.
J Thorac Cardiovasc Surg2023 Dec;166(6):1670-1682.e33. doi: 10.1016/j.jtcvs.2023.04.042.
Mariani Silvia, Wang I-Wen, van Bussel Bas C T, Heuts Samuel, Wiedemann Dominik, Saeed Diyar, van der Horst Iwan C C, Pozzi Matteo, Loforte Antonio, Boeken Udo, Samalavicius Robertas, Bounader Karl, Hou Xiaotong, Bunge Jeroen J H, Buscher Hergen, Salazar Leonardo, Meyns Bart, Herr Daniel, Matteucci Sacha, Sponga Sandro, Ramanathan Kollengode, Russo Claudio, Formica Francesco, Sakiyalak Pranya, Fiore Antonio, Camboni Daniele, Raffa Giuseppe Maria, Diaz Rodrigo, Jung Jae-Seung, Belohlavek Jan, Pellegrino Vin, Bianchi Giacomo, Pettinari Matteo, Barbone Alessandro, Garcia José P, Shekar Kiran, Whitman Glenn, Lorusso Roberto,
Abstract
OBJECTIVES:
Postcardiotomy extracorporeal membrane oxygenation (ECMO) can be initiated intraoperatively or postoperatively based on indications, settings, patient profile, and conditions. The topic of implantation timing only recently gained attention from the clinical community. We compare patient characteristics as well as in-hospital and long-term survival between intraoperative and postoperative ECMO.
METHODS:
The retrospective, multicenter, observational Postcardiotomy Extracorporeal Life Support (PELS-1) study includes adults who required ECMO due to postcardiotomy shock between 2000 and 2020. We compared patients who received ECMO in the operating theater (intraoperative) with those in the intensive care unit (postoperative) on in-hospital and postdischarge outcomes.
RESULTS:
We studied 2003 patients (women: 41.1%; median age: 65 years; interquartile range [IQR], 55.0-72.0). Intraoperative ECMO patients (n = 1287) compared with postoperative ECMO patients (n = 716) had worse preoperative risk profiles. Cardiogenic shock (45.3%), right ventricular failure (15.9%), and cardiac arrest (14.3%) were the main indications for postoperative ECMO initiation, with cannulation occurring after (median) 1 day (IQR, 1-3 days). Compared with intraoperative application, patients who received postoperative ECMO showed more complications, cardiac reoperations (intraoperative: 19.7%; postoperative: 24.8%, P = .011), percutaneous coronary interventions (intraoperative: 1.8%; postoperative: 3.6%, P = .026), and had greater in-hospital mortality (intraoperative: 57.5%; postoperative: 64.5%, P = .002). Among hospital survivors, ECMO duration was shorter after intraoperative ECMO (median, 104; IQR, 67.8-164.2 hours) compared with postoperative ECMO (median, 139.7; IQR, 95.8-192 hours, P
CONCLUSIONS:
Intraoperative and postoperative ECMO implantations are associated with different patient characteristics and outcomes, with greater complications and in-hospital mortality after postoperative ECMO. Strategies to identify the optimal location and timing of postcardiotomy ECMO in relation to specific patient characteristics are warranted to optimize in-hospital outcomes.
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
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Acute kidney injury in patients with acute decompensated heart failure-cardiogenic shock: Prevalence, risk factors and outcome.
Int J Cardiol2023 Jul;383():42-49. doi: 10.1016/j.ijcard.2023.04.049.
Bottiroli Maurizio, Calini Angelo, Morici Nuccia, Tavazzi Guido, Galimberti Luca, Facciorusso Clorinda, Ammirati Enrico, Russo Claudio, Montoli Alberto, Mondino Michele
Abstract
BACKGROUND:
Acute Kidney Injury (AKI) represents a major complication of acute heart failure and cardiogenic shock (CS). There is a paucity of data on AKI complicating acutely decompensated heart failure patients presenting with CS (ADHF-CS). We aimed to investigate AKI prevalence, risk factors and outcomes in this subgroup of patients.
METHODS:
Retrospective observational study on patients admitted for ADHF-CS to our 12-bed Intensive Care Unit (ICU), between January 2010 and December 2019. Demographic, clinical, and biochemical variables were collected at baseline and during hospital stay.
RESULTS:
Eighty-eight patients were consecutively recruited. The predominant etiologies were idiopathic dilated cardiomyopathy (47%), followed by post-ischemic (24%). AKI was diagnosed in 70 (79.5%) of patients. Forty-three out of 70 patients met the criteria for AKI at ICU admission. On multivariate analysis, a central venous pressure (CVP) higher than 10 mmHg (OR 3.9; 95%CI 1.2-12.6; p = 0.025) and serum lactate higher than 3 mmol/L (OR 4.1; 95%CI 1.01-16.3; p = 0.048) were identified to be independently associated with AKI. Age and AKI stage were independent predictors of 90-day mortality.
CONCLUSION:
AKI is a common and early complication of ADHF-CS. Venous congestion and severe hypoperfusion are risk factors for AKI development. Early detection and prevention of AKI could lead to better outcome in this clinical subgroup.
Copyright © 2023 Elsevier B.V. All rights reserved.
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Extracorporeal life support in mitral papillary muscle rupture: Outcome of multicenter study.
Artif Organs2023 Aug;47(8):1386-1394. doi: 10.1111/aor.14541.
Massimi Giulio, Matteucci Matteo, De Bonis Michele, Kowalewski Mariusz, Formica Francesco, Russo Claudio Francesco, Sponga Sandro, Vendramin Igor, Colli Andrea, Falcetta Giosuè, Trumello Cinzia, Carrozzini Massimiliano, Fischlein Theodor, Troise Giovanni, Actis Dato Guglielmo, D'Alessandro Stefano, Nia Peyman Sardari, Lodo Vittoria, Villa Emmanuel, Shah Shabir Hussain, Scrofani Roberto, Binaco Irene, Kalisnik Jurij Matija, Pettinari Matteo, Thielmann Matthias, Meyns Bart, Khouqeer Fareed A, Fino Carlo, Simon Caterina, Severgnini Paolo, Kowalowka Adam, Deja Marek A, Ronco Daniele, Lorusso Roberto
Abstract
BACKGROUND:
Post-acute myocardial infarction papillary muscle rupture (post-AMI PMR) may present variable clinical scenarios and degree of emergency due to result of cardiogenic shock. Veno-arterial extracorporeal life support (V-A ECLS) has been proposed to improve extremely poor pre- or postoperative conditions. Information in this respect is scarce.
METHODS:
From the CAUTION (meChanical complicAtion of acUte myocardial infarcTion: an InternatiOnal multiceNter cohort study) database (16 different Centers, data from 2001 to 2018), we extracted adult patients who were surgically treated for post-AMI PMR and underwent pre- or/and postoperative V-A ECLS support. The end-points of this study were in-hospital survival and ECLS complications.
RESULTS:
From a total of 214 post-AMI PMR patients submitted to surgery, V-A ECLS was instituted in 23 (11%) patients. The median age was 61.7?years (range 46-81?years). Preoperatively, ECLS was commenced in 10 patients (43.5%), whereas intra/postoperative in the remaining 13. The most common V-A ECLS indication was post-cardiotomy shock, followed by preoperative cardiogenic shock and cardiac arrest. The median duration of V-A ECLS was 4?days. V-A ECLS complications occurred in more than half of the patients. Overall, in-hospital mortality was 39.2% (9/23), compared to 22% (42/219) for the non-ECLS group.
CONCLUSIONS:
In post-AMI PMR patients, V-A ECLS was used in almost 10% of the patients either to promote bridge to surgery or as postoperative support. Further investigations are required to better evaluate a potential for increased use and its effects of V-A ECLS in such a context based on the still high perioperative mortality.
© 2023 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.
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The Relation Between Obesity and Mortality in Postcardiotomy Venoarterial Membrane Oxygenation.
Ann Thorac Surg2023 Jul;116(1):147-154. doi: 10.1016/j.athoracsur.2023.03.025.
Heuts Samuel, Mariani Silvia, van Bussel Bas C T, Boeken Udo, Samalavicius Robertas, Bounader Karl, Hou Xiaotong, Bunge Jeroen J H, Sriranjan Kogulan, Wiedemann Dominik, Saeed Diyar, Pozzi Matteo, Loforte Antonio, Salazar Leonardo, Meyns Bart, Mazzeffi Michael A, Matteucci Sacha, Sponga Sandro, Sorokin Vitaly, Russo Claudio, Formica Francesco, Sakiyalak Pranya, Fiore Antonio, Camboni Daniele, Raffa Giuseppe Maria, Diaz Rodrigo, Wang I-Wen, Jung Jae-Seung, Belohlavek Jan, Pellegrino Vin, Bianchi Giacomo, Pettinari Matteo, Barbone Alessandro, Garcia José P, Shekar Kiran, Whitman Glenn, Lorusso Roberto,
Abstract
BACKGROUND:
Obesity is an important health problem in cardiac surgery and among patients requiring postcardiotomy venoarterial extracorporeal membrane oxygenation (V-A ECMO). Still, whether these patients are at risk for unfavorable outcomes after postcardiotomy V-A ECMO remains unclear. The current study evaluated the association between body mass index (BMI) and in-hospital outcomes in this setting.
METHODS:
The Post-cardiotomy Extracorporeal Life Support (PELS-1) study is an international, multicenter study. Patients requiring postcardiotomy V-A ECMO in 36 centers from 16 countries between 2000 and 2020 were included. Patients were divided in 6 BMI categories (underweight, normal weight, overweight, class I, class II, and class III obesity) according to international recommendations. Primary outcome was in-hospital mortality, and secondary outcomes included major adverse events. Mixed logistic regression models were applied to evaluate associations between BMI and mortality.
RESULTS:
The study cohort included 2046 patients (median age, 65 years; 838 women [41.0%]). In-hospital mortality was 60.3%, without statistically significant differences among BMI classes for in-hospital mortality (P = .225) or major adverse events (P = .126). The crude association between BMI and in-hospital mortality was not statistically significant after adjustment for comorbidities and intraoperative variables (class I: odds ratio [OR], 1.21; 95% CI, 0.88-1.65; class II: OR, 1.45; 95% CI, 0.86-2.45; class III: OR, 1.43; 95% CI, 0.62-3.33), which was confirmed in multiple sensitivity analyses.
CONCLUSIONS:
BMI is not associated to in-hospital outcomes after adjustment for confounders in patients undergoing postcardiotomy V-A ECMO. Therefore, BMI itself should not be incorporated in the risk stratification for postcardiotomy V-A ECMO.
Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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Fulminant Lymphocytic Myocarditis During Pregnancy Treated With Temporary Mechanical Circulatory Supports and Aggressive Immunosuppression.
Circ Heart Fail2022 Dec;15(12):e009810. doi: 10.1161/CIRCHEARTFAILURE.122.009810.
Veronese Giacomo, Nonini Sandra, Cannata Aldo, Aresta Francesca, Olivieri Guido, Montrasio Elisa, De Caria Daniele, Perna Enrico, Calini Angelo, Bottiroli Maurizio, Cislaghi Francesca, Pedrazzini Giovanna, Baltaro Federica, Quattrocchi Giuseppina, Pedrotti Patrizia, Russo Claudio F, Garascia Andrea, Mondino Michele, Ammirati Enrico
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Low-Density Lipoprotein Receptor-Related Protein 8 at the Crossroad between Cancer and Neurodegeneration.
Int J Mol Sci2022 Aug;23(16):. doi: 8921.
Passarella Daniela, Ciampi Silvia, Di Liberto Valentina, Zuccarini Mariachiara, Ronci Maurizio, Medoro Alessandro, Foderà Emanuele, Frinchi Monica, Mignogna Donatella, Russo Claudio, Porcile Carola
Abstract
The low-density-lipoprotein receptors represent a family of pleiotropic cell surface receptors involved in lipid homeostasis, cell migration, proliferation and differentiation. The family shares common structural features but also has significant differences mainly due to tissue-specific interactors and to peculiar proteolytic processing. Among the receptors in the family, recent studies place low-density lipoprotein receptor-related protein 8 (LRP8) at the center of both neurodegenerative and cancer-related pathways. From one side, its overexpression has been highlighted in many types of cancer including breast, gastric, prostate, lung and melanoma; from the other side, LRP8 has a potential role in neurodegeneration as apolipoprotein E (ApoE) and reelin receptor, which are, respectively, the major risk factor for developing Alzheimer's disease (AD) and the main driver of neuronal migration, and as a ?-secretase substrate, the main enzyme responsible for amyloid formation in AD. The present review analyzes the contributions of LDL receptors, specifically of LRP8, in both cancer and neurodegeneration, pointing out that depending on various interactions and peculiar processing, the receptor can contribute to both proliferative and neurodegenerative processes.
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Bidirectional Control between Cholesterol Shuttle and Purine Signal at the Central Nervous System.
Int J Mol Sci2022 Aug;23(15):. doi: 8683.
Passarella Daniela, Ronci Maurizio, Di Liberto Valentina, Zuccarini Mariachiara, Mudò Giuseppa, Porcile Carola, Frinchi Monica, Di Iorio Patrizia, Ulrich Henning, Russo Claudio
Abstract
Recent studies have highlighted the mechanisms controlling the formation of cerebral cholesterol, which is synthesized in situ primarily by astrocytes, where it is loaded onto apolipoproteins and delivered to neurons and oligodendrocytes through interactions with specific lipoprotein receptors. The "cholesterol shuttle" is influenced by numerous proteins or carbohydrates, which mainly modulate the lipoprotein receptor activity, function and signaling. These molecules, provided with enzymatic/proteolytic activity leading to the formation of peptide fragments of different sizes and specific sequences, could be also responsible for machinery malfunctions, which are associated with neurological, neurodegenerative and neurodevelopmental disorders. In this context, we have pointed out that purines, ancestral molecules acting as signal molecules and neuromodulators at the central nervous system, can influence the homeostatic machinery of the cerebral cholesterol turnover and vice versa. Evidence gathered so far indicates that purine receptors, mainly the subtypes P2Y, P2X and A, are involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer's and Niemann-Pick C diseases, by controlling the brain cholesterol homeostasis; in addition, alterations in cholesterol turnover can hinder the purine receptor function. Although the precise mechanisms of these interactions are currently poorly understood, the results here collected on cholesterol-purine reciprocal control could hopefully promote further research.
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Cutaneous Ulcer Caused by Apixaban Treatment Is Resolved after Replacement with Dabigatran.
Medicina (Kaunas)2022 May;58(5):. doi: 691.
Medoro Alessandro, Passarella Daniela, Mignogna Donatella, Porcile Carola, Foderà Emanuele, Intrieri Mariano, Raimo Gennaro, La Floresta Pancrazio, Russo Claudio, Martucci Gennaro
Abstract
Nowadays, novel oral anticoagulants (NOACs) have shown improved safety profile and efficacy compared to vitamin K antagonists in the prevention of thromboembolic events occurring during different pathological conditions. However, there are concerns and safety issues, mostly related to adverse events following interactions with other drugs, in real-world practice. We report the case of an 83-year-old woman who developed a non-bleeding leg ulcer not caused by trauma or other evident pathological conditions after 10 days of treatment with apixaban 5 mg/q.d. She was switched from apixaban to dabigatran and the leg ulcer rapidly improved and completely cicatrized in 40 days. The resolution of the ulcer and the toleration of dabigatran therapy suggest an apixaban-specific reaction; however, the pathological mechanism of ulcer onset is currently unclear. Careful evaluation of hospital databases of Molise region (Southern Italy) hospitals identified two similar cases between 2019 and 2021. These cases underline the necessity of careful post-marketing surveillance, considering the rapidly increasing number of patients treated with NOACs and patient's risk factors such as old age, high polypharmacy rate, co-morbidities, and peculiar genetic background related to NOACs pharmacokinetic features.
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[ANMCO Position paper: Care pathway for advanced heart failure patients candidate for heart transplantation/ventricular assist device].
G Ital Cardiol (Rome)2022 May;23(5):340-378. doi: 10.1714/3796.37817.
Iacoviello Massimo, Cipriani Manlio, Valente Serafina, Marini Marco, Ammirati Enrico, Benvenuto Manuela, Cassaniti Leonarda Rosaria, De Maria Renata, Gori Mauro, Municinò Annamaria, Navazio Alessandro, Amodeo Vincenzo, Aspromonte Nadia, Barili Fabio, Casolo Giancarlo, Clemenza Francesco, Di Eusanio Marco, Di Lenarda Andrea, Di Tano Giuseppe, Domenicucci Stefano, Faggian Giuseppe, Francese Giuseppina Maura, Frongillo Doriana, Gilardi Rossella, Iacovoni Attilio, Imazio Massimo, Livi Ugolino, Maiello Ciro, Milano Aldo, Mondino Michele, Moreo Antonella Maurizia, Mortara Andrea, Murrone Adriano, Palmieri Vittorio, Pelenghi Stefano, Pini Daniela, Pistono Massimo, Porcu Maurizio, Potena Luciano, Rinaldi Mauro, Romanò Massimo, Roncon Loris, Rossini Roberta, Russo Claudio Francesco, Scotto di Uccio Fortunato, Urbinati Stefano, Zecchin Massimo, Caldarola Pasquale, Oliveti Alessandra, Frigerio Maria, Musumeci Francesco, Gulizia Michele Massimo, Oliva Fabrizio, Gabrielli Domenico, Colivicchi Furio
Abstract
Heart failure is a complex clinical syndrome with a severe prognosis, despite therapeutic progress. The management of the advanced stages of the syndrome is particularly complex in patients who are referred to palliative care as well as in those who are candidates for cardiac replacement therapy. For the latter group, a prompt recognition of the transition to the advanced stage as well as an early referral to the centers for cardiac replacement therapy are essential elements to ensure that patients follow the most appropriate diagnostic-therapeutic pathway. The aim of this document is to focus on the main diagnostic and therapeutic aspects related to the advanced stages of heart failure and, in particular, on the management of patients who are candidates for cardiac replacement therapy.
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Long-term effects of primary graft dysfunction after heart transplantation.
J Card Surg2022 May;37(5):1290-1298. doi: 10.1111/jocs.16364.
Settepani Fabrizio, Pedrazzini Giovanna L, Olivieri Guido M, Merlanti Bruno, Cannata Aldo, Lanfranconi Marco, Frigerio Maria, Russo Claudio F
Abstract
BACKGROUND:
We studied the incidence of primary graft dysfunction (PGD), its impact on in-hospital and follow-up outcomes and searched for independent risk factors.
METHODS:
During an 18-year period, 508 individuals underwent heart transplantation at our institution. Patients were diagnosed with none, mild, moderate or severe PGD according to ISHLT criteria.
RESULTS:
Thirty-eight patients (7.5%) met the ISHLT criteria for mild PGD, 92 (18.1%) for moderate PGD and 23 (4.5%) for severe PGD. Patients were classified into none/mild PGD (77.4%) and moderate/severe PGD (22.6%) groups. In-hospital mortality was 12.4% (7.8% for none/mild PGD and 28.7% for moderate/severe PGD; p?.001). Survival at 1, 5, and 15 years was 85.5?±?1.9% versus 67.2?±?4.5%, 80?±?2.2% versus 63.5?±?4.7%, and 60.4?±?3.6% versus 45.9?±?8.4%, respectively (p?.001). Excluding the events occurring during the first month of follow-up, survival was comparable between the two groups (93.1?±?1.4% vs. 94.7?±?2.6 at 1 year and 65.6?±?3.8% vs. 70.4?±?10.4% at 15 years, respectively; p?=?.88). Upon multivariate logistic regression analysis preoperative mechanical circulatory support (odds ratio [OR]?=?5.86) and preoperative intra-aortic balloon pump (IABP) (OR?=?9.58) were independently associated with moderate/severe PGD.
CONCLUSIONS:
Our results confirm that PGD is associated with poor in-hospital outcome. The poor outcome does not extend beyond the first month of follow-up, with comparable survival between patients with none/mild PGD and moderate/severe PGD in the short and long-term. Mechanical circulatory support and preoperative IABP were found to be independent risk factors for moderate/severe PGD.
© 2022 Wiley Periodicals LLC.
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Organ Care System Heart? in donors requiring high-risk excision of suspected neoplastic lesions.
Int J Artif Organs2022 Mar;45(3):337-339. doi: 10.1177/03913988221075040.
Olivieri Guido Maria, Carrozzini Massimiliano, Lanfranconi Marco, Russo Claudio Francesco
Abstract
Although Heart Transplant is still the gold standard treatment for end-stage heart failure patients, the limitation of this procedure is the discrepancy between the amount of waiting list patients and donors. Organ Care Systems, preventing the detrimental effects of cold ischemia, potentially increase donor pool. Herein we report three cases where high-risk excisions were required to clarify the nature of suspected lesions in donors. We decided to retrieve the organs and to place them in the devices before performing the excision. Our experience confirm the possibility to utilise this device as a time buffer in these peculiar scenarios.
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Reply to Sagliocco, O.; Betelli, M. Comment on "Fierro et al. Severe Hypotension, Bradycardia and Asystole after Sugammadex Administration in an Elderly Patient. 2021, , 79".
Medicina (Kaunas)2022 Jan;58(1):. doi: 136.
Fierro Carmen, Medoro Alessandro, Mignogna Donatella, Porcile Carola, Ciampi Silvia, Foderà Emanuele, Flocco Romeo, Russo Claudio, Martucci Gennaro
Abstract
We thank Dr. Sagliocco and Dr. Betelli for their comments [...].
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Surgical treatment for post-infarction papillary muscle rupture: a multicentre study.
Eur J Cardiothorac Surg2022 Jan;61(2):469-476. doi: 10.1093/ejcts/ezab469.
Massimi Giulio, Ronco Daniele, De Bonis Michele, Kowalewski Mariusz, Formica Francesco, Russo Claudio Francesco, Sponga Sandro, Vendramin Igor, Falcetta Giosuè, Fischlein Theodor, Troise Giovanni, Trumello Cinzia, Actis Dato Guglielmo, Carrozzini Massimiliano, Shah Shabir Hussain, Coco Valeria Lo, Villa Emmanuel, Scrofani Roberto, Torchio Federica, Antona Carlo, Kalisnik Jurij Matija, D'Alessandro Stefano, Pettinari Matteo, Sardari Nia Peyman, Lodo Vittoria, Colli Andrea, Ruhparwar Arjang, Thielmann Matthias, Meyns Bart, Khouqeer Fareed A, Fino Carlo, Simon Caterina, Kowalowka Adam, Deja Marek A, Beghi Cesare, Matteucci Matteo, Lorusso Roberto
Abstract
OBJECTIVES:
Papillary muscle rupture (PMR) is a rare but potentially fatal complication of acute myocardial infarction. The aim of this study was to analyse the patient characteristics and early outcomes of the surgical management of post-infarction PMR from an international multicentre registry.
METHODS:
Patients underwent surgery for post-infarction PMR between 2001 through 2019 were retrieved from database of the CAUTION study. The primary end point was in-hospital mortality.
RESULTS:
A total of 214 patients were included with a mean age of 66.9 (standard deviation: 10.5) years. The posteromedial papillary muscle was the most frequent rupture location (71.9%); the rupture was complete in 67.3% of patients. Mitral valve replacement was performed in 82.7% of cases. One hundred twenty-two patients (57%) had concomitant coronary artery bypass grafting. In-hospital mortality was 24.8%. Temporal trends revealed no apparent improvement in in-hospital mortality during the study period. Multivariable analysis showed that preoperative chronic kidney disfunction [odds ratio (OR): 2.62, 95% confidence interval (CI): 1.07-6.45, P?=?0.036], cardiac arrest (OR: 3.99, 95% CI: 1.02-15.61, P?=?0.046) and cardiopulmonary bypass duration (OR: 1.01, 95% CI: 1.00-1.02, P?=?0.04) were independently associated with an increased risk of in-hospital death, whereas concomitant coronary artery bypass grafting was identified as an independent predictor of early survival (OR: 0.38, 95% CI: 0.16-0.92, P?=?0.031).
CONCLUSIONS:
Surgical treatment for post-infarction PMR carries a high in-hospital mortality rate, which did not improve during the study period. Because concomitant coronary artery bypass grafting confers a survival benefit, this additional procedure should be performed, whenever possible, in an attempt to improve the outcome.
CLINICAL TRIAL REGISTRATION:
clinicaltrials.gov: NCT03848429.
© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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Surgical Treatment of Postinfarction Ventricular Septal Rupture.
JAMA Netw Open2021 Oct;4(10):e2128309. doi: e2128309.
Ronco Daniele, Matteucci Matteo, Kowalewski Mariusz, De Bonis Michele, Formica Francesco, Jiritano Federica, Fina Dario, Folliguet Thierry, Bonaros Nikolaos, Russo Claudio Francesco, Sponga Sandro, Vendramin Igor, De Vincentiis Carlo, Ranucci Marco, Suwalski Piotr, Falcetta Giosuè, Fischlein Theodor, Troise Giovanni, Villa Emmanuel, Dato Guglielmo Actis, Carrozzini Massimiliano, Serraino Giuseppe Filiberto, Shah Shabir Hussain, Scrofani Roberto, Fiore Antonio, Kalisnik Jurij Matija, D'Alessandro Stefano, Lodo Vittoria, Kowalówka Adam R, Deja Marek A, Almobayedh Salman, Massimi Giulio, Thielmann Matthias, Meyns Bart, Khouqeer Fareed A, Al-Attar Nawwar, Pozzi Matteo, Obadia Jean-François, Boeken Udo, Kalampokas Nikolaos, Fino Carlo, Simon Caterina, Naito Shiho, Beghi Cesare, Lorusso Roberto
Abstract
IMPORTANCE:
Ventricular septal rupture (VSR) is a rare but life-threatening mechanical complication of acute myocardial infarction associated with high mortality despite prompt treatment. Surgery represents the standard of care; however, only small single-center series or national registries are usually available in literature, whereas international multicenter investigations have been poorly carried out, therefore limiting the evidence on this topic.
OBJECTIVES:
To assess the clinical characteristics and early outcomes for patients who received surgery for postinfarction VSR and to identify factors independently associated with mortality.
DESIGN, SETTING, AND PARTICIPANTS:
The Mechanical Complications of Acute Myocardial Infarction: an International Multicenter Cohort (CAUTION) Study is a retrospective multicenter international cohort study that includes patients who were treated surgically for mechanical complications of acute myocardial infarction. The study was conducted from January 2001 to December 2019 at 26 different centers worldwide among 475 consecutive patients who underwent surgery for postinfarction VSR.
EXPOSURES:
Surgical treatment of postinfarction VSR, independent of the technique, alone or combined with other procedures (eg, coronary artery bypass grafting).
MAIN OUTCOMES AND MEASURES:
The primary outcome was early mortality; secondary outcomes were postoperative complications.
RESULTS:
Of the 475 patients included in the study, 290 (61.1%) were men, with a mean (SD) age of 68.5 (10.1) years. Cardiogenic shock was present in 213 patients (44.8%). Emergent or salvage surgery was performed in 212 cases (44.6%). The early mortality rate was 40.4% (192 patients), and it did not improve during the nearly 20 years considered for the study (median [IQR] yearly mortality, 41.7% [32.6%-50.0%]). Low cardiac output syndrome and multiorgan failure were the most common causes of death (low cardiac output syndrome, 70 [36.5%]; multiorgan failure, 53 [27.6%]). Recurrent VSR occurred in 59 participants (12.4%) but was not associated with mortality. Cardiogenic shock (survived: 95 [33.6%]; died, 118 [61.5%]; P?.001) and early surgery (time to surgery ?7 days, survived: 105 [57.4%]; died, 47 [35.1%]; P?.001) were associated with lower survival. At multivariate analysis, older age (odds ratio [OR], 1.05; 95% CI, 1.02-1.08; P?=?.001), preoperative cardiac arrest (OR, 2.71; 95% CI, 1.18-6.27; P?=?.02) and percutaneous revascularization (OR, 1.63; 95% CI, 1.003-2.65; P?=?.048), and postoperative need for intra-aortic balloon pump (OR, 2.98; 95% CI, 1.46-6.09; P?=?.003) and extracorporeal membrane oxygenation (OR, 3.19; 95% CI, 1.30-7.38; P?=?.01) were independently associated with mortality.
CONCLUSIONS AND RELEVANCE:
In this study, surgical repair of postinfarction VSR was associated with a high risk of early mortality; this risk has remained unchanged during the last 2 decades. Delayed surgery seemed associated with better survival. Age, preoperative cardiac arrest and percutaneous revascularization, and postoperative need for intra-aortic balloon pump and extracorporeal membrane oxygenation were independently associated with early mortality. Further prospective studies addressing preoperative and perioperative patient management are warranted to hopefully improve the currently suboptimal outcome.
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Successful recovery from severe inverted Takotsubo cardiomyopathy after liver transplantation: the efficacy of extracorporeal membrane oxygenation (ECMO).
Minerva Anestesiol2022 Mar;88(3):199-201. doi: 10.23736/S0375-9393.21.16140-1.
Lauterio Andrea, Bottiroli Maurizio, Cannata Aldo, DE Carlis Riccardo, Valsecchi Mila, Perricone Giovanni, Colombo Stefania, Buscemi Vincenzo, Zaniboni Matteo, Pedrazzini Giovanna, Mondino Michele, Russo Claudio, Fumagalli Roberto, DE Carlis Luciano
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Nonoperative Management of a Recurrent Postoperative Inguinal Lymphatic Leak via Negative-Pressure Wound Therapy: A Case Report.
Adv Skin Wound Care2021 Oct;34(10):1-3. doi: 10.1097/01.ASW.0000775928.63723.3b.
Cannata Aldo, Ordanini Marco, Sesana Giovanni, Russo Claudio Francesco
Abstract
Lymphatic leaks are common following common femoral vessel exposure for cardiac surgical procedures. The management of this complication can be difficult and is often uncomfortable for the patient. This case report describes the successful nonoperative treatment of a recurrent lymphatic leak from an inguinal surgical wound via negative-pressure wound therapy. Negative pressure may be considered a minimally invasive, effective, and acceptable way to treat postoperative lymphatic leaks at the groin.
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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Cardiovascular implantable electronic device therapy in patients with left ventricular assist devices: insights from TRAViATA.
Int J Cardiol2021 Oct;340():26-33. doi: 10.1016/j.ijcard.2021.08.033.
Darden Douglas, Ammirati Enrico, Brambatti Michela, Lin Andrew, Hsu Jonathan C, Shah Palak, Perna Enrico, Cikes Maja, Gjesdal Grunde, Potena Luciano, Masetti Marco, Jakus Nina, Van De Heyning Caroline, De Bock Dina, Brugts Jasper J, Russo Claudio F, Veenis Jesse F, Rega Filip, Cipriani Manlio, Frigerio Maria, Liviu Klein, Hong Kimberly N, Adler Eric, Braun Oscar Ö
Abstract
BACKGROUND:
There is conflicting observational data on the survival benefit cardiac implantable electronic devices (CIED) in patients with LVADs.
METHODS:
Patients in whom an LVAD was implanted between January 2008 and April 2017 in the multinational Trans-Atlantic Registry on VAD and Transplant (TRAViATA) registry were separated into four groups based on the presence of CIED prior to LVAD implantation: none (n = 146), implantable cardiac defibrillator (ICD) (n = 239), cardiac resynchronization without defibrillator (CRT-P) (n = 28), and CRT with defibrillator (CRT-D) (n = 111).
RESULTS:
A total of 524 patients (age 52 years ±12, 84.4% male) were followed for 354 (interquartile range: 166-701) days. After multivariable adjustment, there were no differences in survival across the groups. In comparison to no device, only CRT-D was associated with late right ventricular failure (RVF) (hazard ratio 2.85, 95% confidence interval [CI] 1.42-5.72, p = 0.003). There was no difference in risk of early RVF across the groups or risk of ICD shocks between those with ICD and CRT-D.
CONCLUSION:
In a multinational registry of patients with LVADs, there were no differences in survival with respect to CIED subtype. However, patients with a pre-existing CRT-D had a higher likelihood of late RVF suggesting significant long-term morbidity in those with devices capable of LV?lead pacing post LVAD implantation.
Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.
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Sudden Cardiac Death Caused by a Fatal Association of Hypertrophic Cardiomyopathy (, p.Arg719Trp), Heterozygous Familial Hypercholesterolemia (, p.Gly343Lys) and SARS-CoV-2 B.1.1.7 Infection.
Diagnostics (Basel)2021 Jul;11(7):. doi: 1229.
Marziliano Nicola, Medoro Alessandro, Mignogna Donatella, Saccon Giovanni, Folzani Stefano, Reverberi Claudio, Russo Claudio, Intrieri Mariano
Abstract
Hypertrophic cardiomyopathy (HCM) and heterozygous familial hypercholesterolemia (HeFH), two of the most common genetic cardiovascular disorders, can lead to sudden cardiac death. These conditions could be complicated by concomitant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as in the case herein described. A young amateur soccer player died in late October 2020 after a fatal arrhythmia and the autopsy revealed the presence of HCM with diffuse non-obstructive coronary disease. The molecular autopsy revealed a compound condition with a first mutation in the gene (p.Arg719Trp) and a second mutation in the gene (p.Gly343Cys): both have already been described as associated with HCM and HeFH, respectively. In addition, molecular analyses showed the presence of SARS-CoV-2 lineage B.1.1.7 (UK variant with high titer in the myocardium. Co-segregation analysis within the family ( = 19) showed that heterozygous mutation was maternally inherited, while the heterozygous genetic lesion was de novo. All family member carriers of the mutation ( = 13) had systematic higher LDL plasma concentrations and positive records of cardiac and vascular ischemic events at young age. Considering that HCM mutations are in themselves involved in the predisposition to malignant arrhythmogenicity and HeFH could cause higher risk of cardiac complications in SARS-CoV-2 infection, this case could represent an example of a potential SARS-CoV-2 infection role in triggering or unmasking inherited cardiovascular disease, whose combination might represent the cause of fatal arrhythmia at such a young age. Additionally, it can provide clues in dating the presence of the SARS-CoV-2 lineage B.1.1.7 in Northern Italy in the early phases of the second pandemic wave.
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Clinical and Hemodynamic Outcomes of Rapid-Deployment Aortic Bioprostheses.
Semin Thorac Cardiovasc Surg2022 ;34(2):453-461. doi: 10.1053/j.semtcvs.2021.04.006.
D'Onofrio Augusto, Tessari Chiara, Cibin Giorgia, Lorenzoni Giulia, Martinelli Gian Luca, Solinas Marco, Gerosa Gino, , Gregori Dario, Alamanni Francesco, Polvani Gianluca, Massetti Massimo, Eusanio Marco Di, Merlo Maurizio, Vendramin Igor, Mangino Domenico, Mignosa Carmelo, Russo Claudio, Rinaldi Mauro, De Paulis Ruggero, Pacini Davide, Luzi Giampaolo, Antona Carlo, Salvador Loris, Musumeci Francesco, Maselli Daniele, Colli Andrea, Portoghese Michele, Alfieri Ottavio, De Filippo Carlo Maria
Abstract
Aim of this retrospective, multicenter study was to evaluate early and mid-term clinical and hemodynamic results of patients who underwent surgical aortic valve replacement (SAVR) with Intuity rapid-deployment bioprostheses (RDB) (Edwards Lifesciences, Irvine, CA). We analyzed data from the Italian Registry of Intuity Valve (INTU-ITA registry) that is a national, real-world and independent from the industry registry. Preoperative variables were defined according to EuroSCORE and postoperative outcomes according to Valve Academic Research Consortium (VARC). Survival distribution was evaluated using the Kaplan-Meier approach. A Cox-Proportional Hazard Model was employed to assess the effect of the covariates on patients' survival. The registry included 1687 patients from 23 centers (June 2012-September 2019). Aortic cross clamp time for isolated SAVR was 55 minutes (IQR: 45-70 minute). Postoperative pace-maker rate was 6.3%. At discharge transaortic peak and mean gradients were: 18 mm Hg (IQR: 14-23 mm Hg) and 10 mmHg (IQR: 8-13 mm Hg), respectively. Indexed effective orifice area was 1.10 cm/m (IQR: 0.91-1.31 cm/m) and the incidence of severe patient-prosthesis mismatch was 0.6%. Hemodynamic data for all valve sizes remained stable during follow-up. Thirty-day overall mortality was 1.8% (30 patients), and at follow-up it was 5.3% (89 patients). Kaplan-Meier overall survival was 95.5% (94.3-96.7%); 90.7% (88.3-93.1%); 86.4% (82.6-90.4%) at 1, 3, and 5 years, respectively. Serum creatinine (HR: 1.36; 95%CI: 1.04-1.81; p?=?0.0397) and cross-clamp time (HR: 1.01; 95%CI: 1.002-1.017; p?=?0.0077) were identified as independent predictors of mortality. According to our data from the INTU-ITA registry, SAVR with RDB provides good early clinical and hemodynamic results that are confirmed at follow-up.
Copyright © 2021 Elsevier Inc. All rights reserved.
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Mechanical Hemolysis Complicating Transcatheter Interventions for Valvular Heart Disease: JACC State-of-the-Art Review.
J Am Coll Cardiol2021 May;77(18):2323-2334. doi: 10.1016/j.jacc.2021.03.295.
Cannata Aldo, Cantoni Silvia, Sciortino Antonio, Bruschi Giuseppe, Russo Claudio Francesco
Abstract
Mechanical intravascular hemolysis is frequently observed following procedures on heart valves and uncommonly observed in native valvular disease. In most cases, its severity is mild. Nevertheless, it can be clinically significant and even life threatening, requiring multiple blood transfusions and renal replacement therapy. This paper reviews the current knowledge on mechanical intravascular hemolysis in valvular disease, before and after correction, focusing on pathophysiology, approach to diagnosis, and impact of other hematological conditions on the resultant anemia. The importance of a multidisciplinary management is underscored. Laboratory data are provided about subclinical hemolysis that is commonly observed following the implantation of surgical and transcatheter valve prostheses and devices. Finally, clinical scenarios are reviewed and current medical and surgical treatments are discussed, including alternative options for inoperable patients.
Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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Percutaneous RVAD with the Protek Duo for severe right ventricular primary graft dysfunction after heart transplant.
J Heart Lung Transplant2021 Jul;40(7):580-583. doi: 10.1016/j.healun.2021.03.016.
Carrozzini Massimiliano, Merlanti Bruno, Olivieri Guido Maria, Lanfranconi Marco, Bruschi Giuseppe, Mondino Michele, Russo Claudio Francesco
Abstract
Right ventricular primary graft dysfunction after heart transplant is a serious life-threatening condition. The severe form, refractory to maximal medical therapy, has traditionally required temporary mechanical support through veno-arterial extracorporeal membrane oxygenation or central right ventricular support. The Protek Duo is a dual lumen cannula recently introduced in the market, which allows for the institution of a percutaneous right ventricular support. We present the first promising case series of the use of this novel support in patients with right ventricular primary graft dysfunction after heart transplant.
Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
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Severe Hypotension, Bradycardia and Asystole after Sugammadex Administration in an Elderly Patient.
Medicina (Kaunas)2021 Jan;57(1):. doi: 79.
Fierro Carmen, Medoro Alessandro, Mignogna Donatella, Porcile Carola, Ciampi Silvia, Foderà Emanuele, Flocco Romeo, Russo Claudio, Martucci Gennaro
Abstract
Sugammadex is a modified ?-cyclodextrin largely used to prevent postoperative residual neuromuscular blockade induced by neuromuscular aminosteroid blocking agents. Although Sugammadex is considered more efficacious and safer than other drugs, such as Neostigmine, significant and serious complications after its administration, such as hypersensitivity, anaphylaxis and, more recently, severe cardiac events, are reported. In this report, we describe the case of an 80-year-old male with no medical history of cardiovascular disease who was scheduled for percutaneous nephrolithotripsy under general anesthesia. The intraoperative course was uneventful; however, the patient developed a rapid and severe hypotension, asystole and cardiac arrest after Sugammadex administration. Spontaneous cardiac activity and hemodynamic stability was restored with pharmacological therapy and chest compression. The patient was stabilized and discharged uneventfully on postoperative day 10. The potential causes of cardiac arrest after Sugammadex administration have been carefully considered, yet all indications point to Sugammadex as the direct causative agent. On the basis of laboratory and clinical tests, we can exclude among the cause of bradycardia, Kounis syndrome, acute myocardial infarction, coronary spasm and other arrhythmias, but not anaphylaxis. Although Sugammadex is considered an increasingly important option in the prevention of postoperative residual neuromuscular blockade, anesthesiologists should consider it a causative agent of cardiac arrest during surgery. This case highlights the necessity of increased pharmacovigilance and further studies to examine Sugammadex safety and mechanism through which it may cause severe bradycardia, hypotension and cardiac arrest.
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COVID-19 in Heart Transplant Recipients: A Multicenter Analysis of the Northern Italian Outbreak.
JACC Heart Fail2021 Jan;9(1):52-61. doi: 10.1016/j.jchf.2020.10.009.
Bottio Tomaso, Bagozzi Lorenzo, Fiocco Alessandro, Nadali Matteo, Caraffa Raphael, Bifulco Olimpia, Ponzoni Matteo, Lombardi Carlo Maria, Metra Marco, Russo Claudio Francesco, Frigerio Maria, Masciocco Gabriella, Potena Luciano, Loforte Antonio, Pacini Davide, Faggian Giuseppe, Onorati Francesco, Sponga Sandro, Livi Ugolino, Iacovoni Attilio, Terzi Amedeo, Senni Michele, Rinaldi Mauro, Boffini Massimo, Marro Matteo, Jorgji Vjola, Carrozzini Massimiliano, Gerosa Gino
Abstract
OBJECTIVES:
The aim of this study was to assess the clinical course and outcomes of all heart transplant recipients affected by coronavirus disease-2019 (COVID-19) who were followed at the leading heart transplant centers of Northern Italy.
BACKGROUND:
The worldwide severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic has created unprecedented challenges for public health, demanding exceptional efforts for the successful management and treatment of affected patients. Heart transplant patients represent a unique cohort of chronically immunosuppressed subjects in which SARS-CoV-2 may stimulate an unpredictable clinical course of infection.
METHODS:
Since February 2020, we enrolled all 47 cases (79% male) in a first cohort of patients, with a mean age of 61.8 ± 14.5 years, who tested positive for SARS-CoV-2, out of 2,676 heart transplant recipients alive before the onset of the COVID-19 pandemic at 7 heart transplant centers in Northern Italy.
RESULTS:
To date, 38 patients required hospitalization while 9 remained self-home quarantined and 14 died. Compared to the general population, prevalence (18 vs. 7 cases per 1,000) and related case fatality rate (29.7% vs. 15.4%) in heart transplant recipients were doubled. Univariable analysis showed older age (p = 0.002), diabetes mellitus (p = 0.040), extracardiac arteriopathy (p = 0.040), previous PCI (p = 0.040), CAV score (p = 0.039), lower GFR (p = 0.004), and higher NYHA functional classes (p = 0.023) were all significantly associated with in-hospital mortality. During the follow-up two patients died and a third patient has prolonged viral-shedding alternating positive and negative swabs. Since July 1st, 2020, we had 6 new patients who tested positive for SARS-CoV-2, 5 patients asymptomatic were self-quarantined, while 1 is still hospitalized for pneumonia. A standard therapy was maintained for all, except for the hospitalized patient.
CONCLUSIONS:
The prevalence and mortality of SARS-CoV-2 should spur clinicians to immediately refer heart transplant recipients suspected as having SARS-CoV2 infection to centers specializing in the care of this vulnerable population.
Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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Minimally Invasive vs Conventional Aortic Valve Replacement With Rapid-Deployment Bioprostheses.
Ann Thorac Surg2021 Jun;111(6):1916-1922. doi: 10.1016/j.athoracsur.2020.06.150.
D'Onofrio Augusto, Tessari Chiara, Lorenzoni Giulia, Cibin Giorgia, Martinelli Gianluca, Alamanni Francesco, Polvani Gianluca, Solinas Marco, Massetti Massimo, Merlo Maurizio, Vendramin Igor, Di Eusanio Marco, Mignosa Carmelo, Mangino Domenico, Russo Claudio, Rinaldi Mauro, Pacini Davide, Salvador Loris, Antona Carlo, Maselli Daniele, De Paulis Ruggero, Luzi Giampaolo, Alfieri Ottavio, De Filippo Carlo Maria, Portoghese Michele, Musumeci Francesco, Colli Andrea, Gregori Dario, Gerosa Gino
Abstract
BACKGROUND:
The aim of this multicenter retrospective study was to compare early and midterm clinical and hemodynamic results of aortic valve replacement with rapid-deployment bioprostheses performed through conventional full-sternotomy vs mini-sternotomy.
METHODS:
Data from the Italian multicenter registry of aortic valve replacement with rapid-deployment bioprostheses (INTU-ITA registry) were analyzed. Patients were divided into 2 groups: full sternotomy (FS) and ministernotomy (MS). Primary endpoint was the comparison of early and midterm mortality. Secondary endpoints were: comparison of intraoperative variables, complications, and hemodynamic performance. A propensity score weighting approach was used for data analysis.
RESULTS:
A total of 1057 patients were analyzed: 435 (41.2%) and 622 (58.8%) in group FS and MS, respectively. Thirty-day mortality was 1.6% and 0.6% in FS and MS groups, respectively (P = .074). cardiopulmonary bypass time was 78.5 minutes and 83 minutes in FS and MS groups, respectively (P = .414). In the overall cohort, the incidence of intraoperative complications and of device success was 3.8% (40 patients) and 95.9% (1014 patients), respectively, with no significant differences between groups. Survival at 1, 3, and 5 years was 94.1%, 98.1%, 88.5% and 91.8%, 85.2%, and 84.8% in FS and MS groups, respectively (P = .412). The 2 groups showed similar postoperative gradients (median mean gradient, FS: 10.0 mm Hg, MS: 11.0 mm Hg; P = .170) and also similar incidence of patient-prosthesis mismatch (FS: 7%, MS: 6.4%, P = .647).
CONCLUSIONS:
According to our data, rapid-deployment bioprostheses allow the performance of minimally invasive aortic valve replacement with similar surgical times and similar clinical and hemodynamic outcomes to conventional surgery and should be considered the first choice in these procedures.
Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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Outcome of patients on heart transplant list treated with a continuous-flow left ventricular assist device: Insights from the TRans-Atlantic registry on VAd and TrAnsplant (TRAViATA).
Int J Cardiol2021 Feb;324():122-130. doi: 10.1016/j.ijcard.2020.09.026.
Ammirati Enrico, Brambatti Michela, Braun Oscar Ö, Shah Palak, Cipriani Manlio, Bui Quan M, Veenis Jesse, Lee Euyhyun, Xu Ronghui, Hong Kimberly N, Van de Heyning Caroline M, Perna Enrico, Timmermans Philippe, Cikes Maja, Brugts Jasper J, Veronese Giacomo, Minto Jonathan, Smith Saige, Gjesdal Grunde, Gernhofer Yan K, Partida Cynthia, Potena Luciano, Masetti Marco, Boschi Silvia, Loforte Antonio, Jakus Nina, Milicic Davor, Nilsson Johan, De Bock Dina, Sterken Caroline, Van den Bossche Klaartje, Rega Filip, Tran Hao, Singh Ramesh, Montomoli Jonathan, Mondino Michele, Greenberg Barry, Russo Claudio F, Pretorius Victor, Liviu Klein, Frigerio Maria, Adler Eric D
Abstract
BACKGROUND:
Geographic variations in management and outcomes of individuals supported by continuous-flow left ventricular assist devices (CF-LVAD) between the United States (US) and Europe (EU) is largely unknown.
METHODS:
We created a retrospective, multinational registry of 524 patients who received a CF-LVAD (either HVAD or Heartmate II) between January 2008 and April 2017. Follow up spanned from date of CF-LVAD implant to post-HTx period with a median follow up of 44.8 months.
RESULTS:
The cohort included 299 (57.1%) EU and 225 (42.9%) US patients. Although the US cohort was significantly older with a higher prevalence of comorbidities, survival was similar between the cohorts (US 63.1%, EU 68.4% at 5 years, unadjusted log-rank test p = 0.43).Multivariate analyses suggested that older age, higher body mass index, elevated creatinine, use of temporary mechanical circulatory support prior CF-LVAD, and implantation of HVAD were associated with increased mortality. Among CF-LVAD patients undergoing HTx, the median time on CF-LVAD support was shorter in the US, meanwhile US donors were younger. Finally, the pattern of adverse events (stroke, gastrointestinal bleedings, late right ventricular failure, and driveline infection) during support differed significantly between US and EU.
CONCLUSIONS:
Although waitlisted patients in the US on CF-LVAD have higher risk comorbid conditions, the overall outcome is similar in US and EU. Geographic variations with regards to donor characteristics, duration of CF-LVAD support prior to transplant, and adverse events on support can explain the disparity in the utilization of mechanical bridge to transplant strategy between US and EU.
Copyright © 2020 Elsevier B.V. All rights reserved.
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Switch from minimally invasive biventricular mechanical support to cardiopulmonary bypass during heart transplant.
Eur J Cardiothorac Surg2021 Jan;59(1):271-273. doi: 10.1093/ejcts/ezaa343.
Settepani Fabrizio, Marianeschi Stefano Maria, Costetti Alessandro, Russo Claudio Francesco
Abstract
An easily reproducible surgical technique to switch from percutaneous minimally invasive biventricular mechanical support to cardiopulmonary bypass during heart transplantation is illustrated. After cannulation of the distal ascending aorta with a standard arterial cannula, the ProtekDuo® cannula and the ProtekSolo® Transseptal cannula were partially retracted to reach the superior and inferior vena cava, respectively, and connected to the pump circuit for the venous drainage. With this cardiopulmonary bypass configuration, orthotopic heart transplantation was routinely performed and, at the end of the procedure, the 2 cannulas were uneventfully removed.
© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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Cardiac Surgery in Patients With Liver Cirrhosis (CASTER) Study: Early and Long-Term Outcomes.
Ann Thorac Surg2021 Apr;111(4):1242-1251. doi: 10.1016/j.athoracsur.2020.06.110.
Garatti Andrea, Daprati Andrea, Cottini Marzia, Russo Claudio F, Dalla Tomba Margherita, Troise Giovanni, Salsano Antonio, Santini Francesco, Scrofani Roberto, Nicolò Francesca, Mikus Elisa, Albertini Alberto, Di Marco Luca, Pacini Davide, Picichè Marco, Salvador Loris, Actis Dato Guglielmo M, Centofanti Paolo, Paparella Domenico, Kounakis Giorgios, Parolari Alessandro, Menicanti Lorenzo,
Abstract
BACKGROUND:
Patients with liver cirrhosis (LC) undergoing cardiac surgery (CS) face perioperative high mortality and morbidity, but extensive studies on this topic are lacking.
METHODS:
All adult patients with LC undergoing a CS procedure between 2000 and 2017 at 10 Italian Institutions were included in this retrospective cohort study. LC was classified according to preoperative Child-Turcotte-Pugh (CTP) score and Model for End-Stage Liver Disease (MELD) score. Early-term and medium-term outcomes analysis was performed in the overall population and according to CTP classes.
RESULTS:
The study population included 144 patients (mean age 66 ± 9 years, 69% male). Ninety-eight, 20, and 26 patients were in CTP class A, in early CTP class B (MELD score 12), respectively. The main LC etiologies were viral (43%) and alcoholic (36%). Liver-related clinical presentation (ascites, esophageal varices, and encephalopathy) and laboratory values (estimated glomerular filtration rate, serum albumin, and bilirubin, platelet count) significantly worsened across the CTP classes (P = .001). Coronary artery bypass grafting or valve surgery (87% bioprosthesis) were performed in 36% and 50%, respectively. Postoperative complications (especially acute kidney injury, liver complication, and length of stay) significantly worsened in advanced CTP class B (P = .001). Notably, observed mortality was 3-fold or 4-fold higher than the EuroSCORE (European System for Cardiac Operative Risk Evaluation) II-predicted mortality, in the overall population, and in the subgroups. At Kaplan-Meier analysis, 1-year and 5-year cumulative survival in the overall population was 82% ± 3% and 77% ± 4%, respectively. The 5-year survival in CTP class A, early CTP class B, and advanced CTP class B was 72% ± 5%, 68% ± 11%, and 61% ± 10%, respectively (P = .238).
CONCLUSIONS:
CS outcomes in patients with LC are significantly affected in relation to the extent of preoperative liver dysfunction, but in early CTP classes, medium-term survival is acceptable. Further analysis are needed to better estimate the preoperative risk stratification of these patients.
Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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A call to action becomes practice: cardiac and vascular surgery during the COVID-19 pandemic based on the Lombardy emergency guidelines.
Eur J Cardiothorac Surg2020 Aug;58(2):319-327. doi: 10.1093/ejcts/ezaa204.
Bonalumi Giorgia, Giambuzzi Ilaria, Barbone Alessandro, Ranieri Camilla, Cavallotti Laura, Trabattoni Piero, Naliato Moreno, Polvani Gianluca, Torracca Lucia, Pelenghi Stefano, Ragni Franco, Russo Claudio Francesco, Guerra Francisco, Trimarchi Santi, Civilini Efrem, Romani Federico, Bellosta Raffaello, Losa Sergio, Roberto Maurizio, Alamanni Francesco
Abstract
OBJECTIVES:
During the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pandemic, Northern Italy had to completely reorganize its hospital activity. In Lombardy, the hub-and-spoke system was introduced to guarantee emergency and urgent cardiovascular surgery, whereas most hospitals were dedicated to patients with coronavirus disease 2019 (COVID-19). The aim of this study was to analyse the results of the hub-and-spoke organization system.
METHODS:
Centro Cardiologico Monzino (Monzino) became one of the four hubs for cardiovascular surgery, with a total of eight spokes. SARS-CoV-2 screening became mandatory for all patients. New flow charts were designed to allow separated pathways based on infection status. A reorganization of spaces guaranteed COVID-19-free and COVID-19-dedicated areas. Patients were also classified into groups according to their pathological and clinical status: emergency, urgent and non-deferrable (ND).
RESULTS:
A total of 70 patients were referred to the Monzino hub-and-spoke network. We performed 41 operations, 28 (68.3%) of which were emergency/urgent and 13 of which were ND. The screening allowed the identification of COVID-19 (three patients, 7.3%) and non-COVID-19 patients (38 patients, 92.7%). The newly designed and shared protocols guaranteed that the cardiac patients would be divided into emergency, urgent and ND groups. The involvement of the telematic management heart team allowed constant updates and clinical discussions.
CONCLUSIONS:
The hub-and-spoke organization system efficiently safeguards access to heart and vascular surgical services for patients who require ND, urgent and emergency treatment. Further reorganization will be needed at the end of this pandemic when elective cases will again be scheduled, with a daily increase in the number of operations.
© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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On the definition of geometric orifice area.
J Thorac Cardiovasc Surg2020 May;159(5):e303. doi: 10.1016/j.jtcvs.2019.11.138.
Cannata Aldo, Russo Claudio Francesco
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Long-term clinical outcome and performance of transcatheter aortic valve replacement with a self-expandable bioprosthesis.
Eur Heart J2020 May;41(20):1876-1886. doi: 10.1093/eurheartj/ehz925.
Testa Luca, Latib Azeem, Brambilla Nedy, De Marco Federico, Fiorina Claudia, Adamo Marianna, Giannini Cristina, Angelillis Marco, Barbanti Marco, Sgroi Carmelo, Poli Arnaldo, Ferrara Erica, Bruschi Giuseppe, Russo Claudio Francesco, Matteo Montorfano, De Felice Francesco, Musto Carmine, Curello Salvatore, Colombo Antonio, Tamburino Corrado, Petronio Anna Sonia, Bedogni Francesco
Abstract
AIMS:
In the last decade, transcatheter aortic valve (TAV) replacement determined a paradigm shift in the treatment of patients with severe symptomatic aortic stenosis. Data on long-term TAV performance are still limited. We sought to evaluate the clinical and haemodynamic outcomes of the CoreValve self-expandable valve up to 8-year follow-up (FU).
METHODS AND RESULTS:
Nine hundred and ninety inoperable or high-risk patients were treated with the CoreValve TAV in eight Italian Centres from June 2007 to December 2011. The median FU was 4.4?years (interquartile range 1.4-6.7?years). Longest FU reached 11?years. A total of 728 died within 8-year FU (78.3% mortality from Kaplan-Meier curve analysis). A significant functional improvement was observed in the majority of patients and maintained over time, with 79.3% of surviving patients still classified New York Heart Association class ? II at 8?years. Echocardiographic data showed that the mean transprosthetic aortic gradient remained substantially unchanged (9?±?4?mmHg at discharge, 9?±?5?mmHg at 8?years, P?=?0.495). The rate of Grade 0/1 paravalvular leak was consistent during FU with no significant change from post-procedure to FU ?5?years in paired analysis (P?=?0.164). Structural valve deterioration (SVD) and late bioprosthetic valve failure (BVF) were defined according to a modification of the 2017 EAPCI/ESC/EACTS criteria. In cumulative incidence functions at 8?years, moderate and severe SVD were 3.0% [95% confidence interval (CI) 2.1-4.3%] and 1.6% (95% CI 0.6-3.9%), respectively, while late BVF was 2.5% (95% CI 1.2-5%).
CONCLUSION:
While TAVs are questioned about long-term performance and durability, the results of the present research provide reassuring 8-year evidence on the CoreValve first-generation self-expandable bioprosthesis.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.
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Enzymatic production of bioactive peptides from scotta, an exhausted by-product of ricotta cheese processing.
PLoS One2019 ;14(12):e0226834. doi: e0226834.
Monari Stefania, Ferri Maura, Russo Claudio, Prandi Barbara, Tedeschi Tullia, Bellucci Paolo, Zambrini Angelo Vittorio, Donati Emanuela, Tassoni Annalisa
Abstract
The present work reports the enzymatic valorisation of the protein fraction of scotta, a dairy by-product representing the exhausted liquid residue of ricotta production. Scotta was subjected to ultra-filtration with membrane cut-offs from 500 to 4 kDa and the obtained protein-enriched fractions were used for the optimization of enzyme-based digestions aimed at producing potentially bioactive peptides. Nine different commercial proteases were tested and the best digestion conditions were selected based on protein yield, fraction bioactivity and foreseen scale up processing costs. Scale up of the 3% Pancreatin or 5% Papain processes was performed up to 2 L (37°C or 60°C respectively, 1 h incubation), and the digestion efficiency increased with the reaction volume as well as antioxidant activity (up to 60 gBSA eq/L and to 1.7 gAA eq/L). Retentate 1 digested fractions also showed, for the first time in dairy-based peptides, anti-tyrosinase activity, up to 0.14 gKA eq/L. Digested proteins were sub-fractionated by means of physical membrane separations and 30-10 kDa fraction from Papain treatment showed the highest antioxidant and anti-tyrosinase activities. The peptide sequence of the most bioactive fractions was achieved.
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Emergency Intraoperative Implantation of ECMO for Refractory Cardiogenic Shock Arising During Liver Transplantation as a Bridge to Myocardial Surgical Revascularization.
Transplantation2019 Oct;103(10):e317-e318. doi: 10.1097/TP.0000000000002826.
Lauterio Andrea, De Carlis Riccardo, Cannata Aldo, Di Sandro Stefano, De Gasperi Andrea, Russo Claudio, De Carlis Luciano
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Sequencing of NOTCH1 gene in an Italian population with bicuspid aortic valve: Preliminary results from the GISSI OUTLIERS VAR study.
Gene2019 Oct;715():143970. doi: 10.1016/j.gene.2019.143970.
Pileggi Silvana, De Chiara Benedetta, Magnoli Michela, Franzosi Maria Grazia, Merlanti Bruno, Bianchini Francesca, Moreo Antonella, Romeo Gabriella, Russo Claudio Francesco, Rizzo Stefania, Basso Cristina, Martinelli Luigi, Maseri Attilio,
Abstract
BACKGROUND:
Bicuspid aortic valve (BAV) formation is genetically determined, with reduced penetrance and variable expressivity. NOTCH1 is a proven candidate gene and its mutations have been found in familial and sporadic cases of BAV.
METHODS:
66 BAV patients from the GISSI VAR study were genotyped for the NOTCH1 gene.
RESULTS:
We identified 63 variants, in heterozygous and homozygous states. Fifty-two are common polymorphisms present in almost all patients. Eleven variants are new and never yet reported: two are non-synonymous substitutions, Gly540Asp in exon 10 and Glu851Gln in exon 16; one is in the 3'UTR region and seven in introns, one corresponds to a T allele insertion in intron 27. We selected four statistically noteworthy and seven new variants identified in six BAV patients and correlated them with clinical and demographic variables and with imaging and histological parameters. Preliminary data show that four were BAV patients with isolated stenosis in patients over 60 aged. These variants may correlate with a later need for surgery for the presence of stenosis and not aortic valve regurgitation or ascending aortic aneurysm.
CONCLUSIONS:
Completing the genotyping of 62 BAV patients we found 11 new variants in the NOTCH1 gene never yet reported. These findings confirm that the identification of new, clinically remarkable biomarkers for BAV requires a deeper genetic understanding of the NOTCH1 gene variants, which could be targeted by future diagnostic and therapeutic strategies.
Copyright © 2019 Elsevier B.V. All rights reserved.
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Surgical aortic valve replacement with new-generation bioprostheses: Sutureless versus rapid-deployment.
J Thorac Cardiovasc Surg2020 Feb;159(2):432-442.e1. doi: 10.1016/j.jtcvs.2019.02.135.
D'Onofrio Augusto, Salizzoni Stefano, Filippini Claudia, Tessari Chiara, Bagozzi Lorenzo, Messina Antonio, Troise Giovanni, Tomba Margerita Dalla, Rambaldini Manfredo, Dalén Magnus, Alamanni Francesco, Massetti Massimo, Mignosa Carmelo, Russo Claudio, Salvador Loris, Di Bartolomeo Roberto, Maselli Daniele, De Paulis Ruggero, Alfieri Ottavio, De Filippo Carlo Maria, Portoghese Michele, Bortolotti Uberto, Rinaldi Mauro, Gerosa Gino
Abstract
OBJECTIVES:
The aim of this retrospective multicenter study was to compare early clinical and hemodynamic outcomes of Perceval-S sutureless (Livanova, London, United Kingdom) and Intuity rapid-deployment (Edwards Lifesciences, Irvine, Calif) bioprostheses.
METHODS:
Data from patients who underwent isolated or combined aortic valve replacement with Perceval-S and with Intuity bioprostheses at 18 cardiac surgical institutions were analyzed. Propensity matching was performed to identify similar patient cohorts.
RESULTS:
We included 911 patients from March 2011 until May 2017. Perceval-S and Intuity valves were implanted in 349 (38.3%) and in 562 (61.7%) patients, respectively. Propensity score identified 117 matched pairs. In the matched cohort, device success was 99.1% and 100% in Perceval-S and Intuity group, respectively (P = 1.000). Thirty-day Valve Academic Research Consortium mortality occurred in 2 (1.7%) and 4 (3.4%) patients in the Perceval-S and in Intuity group, respectively (P = .6834). The rate of postoperative new permanent pacemaker implantation was 6% (7 patients) and 6.8% (8 patients) in the Perceval-S and in Intuity group, respectively (P = .7896). Perceval-S valve implantation requires significantly shorter aortic crossclamp and cardiopulmonary bypass times than Intuity valve implantation (aortic crossclamp time for isolated, 52 ± 14 minutes vs 62 ± 24 minutes; P
CONCLUSIONS:
Sutureless Perceval-S and rapid-deployment Intuity bioprostheses provide good and similar early clinical and hemodynamic outcomes. Perceval-S valve implantation requires shorter crossclamp and cardiopulmonary bypass times, whereas Intuity valve implantation provides lower transaortic peak and mean gradients.
Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
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Rheological and Mechanical Characterization of Dual-Curing Thiol-Acrylate-Epoxy Thermosets for Advanced Applications.
Polymers (Basel)2019 Jun;11(6):. doi: 997.
Russo Claudio, Fernández-Francos Xavier, De la Flor Silvia
Abstract
Mechanical and rheological properties of novel dual-curing system based on sequential thiol-acrylate and thiol-epoxy reactions are studied with the aim of addressing the obtained materials to suitable advanced applications. The crosslinking process is studied by rheological analysis in order to determine conversion at gelation and the critical ratio. These parameters are used to discuss the intermediate material structure for each acrylate proportion and their possible application in the context of dual-curing and multi-step processing scenarios. Results from dynamo-mechanical analysis and mechanical testing demonstrate the high versatility materials under investigation and revealed a wide range of achievable final properties by simply varying the proportion between acrylate and thiol group. The intermediate stability between curing stages has been analysed in terms of their thermal and mechanical properties, showing that these materials can be stored at different temperatures for a relevant amount of time without experiencing significant effects on the processability. Experimental tests were made to visually demonstrate the versatility of these materials. Qualitative tests on the obtained materials confirm the possibility of obtaining complex shaped samples and highlight interesting shape-memory and adhesive properties.
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Safety of centrifugal left ventricular assist device in patients previously treated with MitraClip system.
Int J Cardiol2019 May;283():131-133. doi: 10.1016/j.ijcard.2019.02.039.
Ammirati Enrico, Van De Heyning Caroline M, Musca Francesco, Brambatti Michela, Perna Enrico, Cipriani Manlio, Cannata Aldo, Mondino Michele, Moreo Antonella, De Bock Dina, Pretorius Victor, Claeys Marc J, Adler Eric D, Russo Claudio F, Frigerio Maria
Abstract
INTRODUCTION:
No data regarding the safety of continuous-flow left ventricular assist device (CF-LVAD) implantation in patients with previous MitraClip have been reported. Thus, it remains unknown whether an initial treatment strategy with MitraClip therapy might complicate future heart failure management in patients who are also considered for CF-LVAD.
METHODS:
We retrospectively identified 6 patients (median age of 62?years; 2 women) who had been treated with MitraClip, that were eventually implanted with a CF-LVAD (all Heartware HVAD) in 3 hospitals between 2013 and 2018.
RESULTS:
Patients were treated in 4 cases with 2 clips, and in 2 cases with 1 clip. Median time from MitraClip implantation to CF-LVAD implant was 282?days (interquartile range 67 to 493), and median time on CF-LVAD support was 401?days (interquartile range 105 to 492?days). Two patients underwent a heart transplant, 3 patients died on support, and 1 is alive on support. In all cases, there was a reduction of functional mitral regurgitation without MitraClip-related complications.
CONCLUSIONS:
Based on this small case series, implantation of a CF-LVAD appears safe in patients with a previously positioned MitraClip system, at least, with 1 or 2 clips in place, with no need for additional mitral valve surgery.
Copyright © 2019 Elsevier B.V. All rights reserved.
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Proteases Upregulation in Sporadic Alzheimer's Disease Brain.
J Alzheimers Dis2019 ;68(3):931-938. doi: 10.3233/JAD-181284.
Medoro Alessandro, Bartollino Silvia, Mignogna Donatella, Marziliano Nicola, Porcile Carola, Nizzari Mario, Florio Tullio, Pagano Aldo, Raimo Gennaro, Intrieri Mariano, Russo Claudio
Abstract
Certain proteases are involved in Alzheimer's disease (AD) and their erroneous control may contribute to the pathology onset and progression. In this study we evaluated the cerebral expression of eight proteases, involved in both A?PP processing and extracellular matrix remodeling. Among these proteases, ADAM10, ADAMTS1, Cathepsin D, and Meprin ? show a significantly higher mRNAs expression in sporadic AD subjects versus controls, while ADAMTS1, Cathepsin D, and Meprin ? show an increment also at the protein level. These data indicate that transcriptional events affecting brain proteases are activated in AD patients, suggesting a link between proteolysis and AD.
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Coping, Mood, Quality of Life, and Outcomes in Recipients of Left Ventricular Assist Devices: A Cluster Analysis.
Psychosom Med2019 ;81(2):192-199. doi: 10.1097/PSY.0000000000000658.
Modica Maddalena, Minotti Anna, De Maria Renata, Scaglione Anna, Bordoni Bruno, Cipriani Manlio, Russo Claudio, Racca Vittorio, Ferratini Maurizio
Abstract
OBJECTIVE:
Left ventricular assist devices (LVADs) are increasingly used for temporary circulatory support until transplant or as destination therapy for patients with end-stage heart failure. Understanding patients' attitudes and resources is crucial to support them.
METHODS:
Sixty-one LVAD recipients (55 [10] years, 10% women, 15% destination therapy) participating in cardiac rehabilitation (CR) postimplant underwent assessment of coping styles (Coping Orientation for Problem Experiences), quality of life (Medical Outcomes Study Short-Form 36, Minnesota Living with Heart Failure Questionnaire), and mood (Hospital Anxiety and Depression Scale).
RESULTS:
Cluster analysis identified two homogeneous groups: C1 (n = 18) patients had higher anxiety (9.6 [5.0] versus 4.0 [2.7], p
CONCLUSIONS:
Among patients discharged from CR after LVAD implant, one third show a profile characterized by worse perceived quality of life, mood disorders, and dysfunctional coping that is associated with long-term mortality, and these factors are potential targets for post-LVAD intensive support.
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Mycotic coronary aneurysms.
J Cardiovasc Med (Hagerstown)2019 Jan;20(1):10-15. doi: 10.2459/JCM.0000000000000734.
Buono Andrea, Maloberti Alessandro, Bossi Irene M, Piccaluga Emanuela, Piccalò Giacomo, Oreglia Jacopo A, Moreo Antonella, Russo Claudio F, Oliva Fabrizio, Giannattasio Cristina
Abstract
: Mycotic coronary aneurysm is a rare infective disease of arterial vessel walls. Their development could be linked to the presence of an infective endocarditis or could represent a primary infection at the site of an implanted intracoronary stent. Bacterial agents, particularly Staphylococcus aureus, are the most common etiological agents. Due to an aspecific clinical presentation and examination, diagnosis could be challenging. Multiple imaging techniques (both invasive and noninvasive) are often required to reach the final diagnosis. Prognosis is characterized by high morbidity and mortality rates and, in fact, a tempestive treatment is required, although, to date, scanty data concerning the optimal treatment choice are present in literature.
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Management of cardiogenic shock in acute decompensated chronic heart failure: The ALTSHOCK phase II clinical trial.
Am Heart J2018 Oct;204():196-201. doi: 10.1016/j.ahj.2018.07.009.
Morici Nuccia, Oliva Fabrizio, Ajello Silvia, Stucchi Miriam, Sacco Alice, Cipriani Manlio Gianni, De Bonis Michele, Garascia Andrea, Gagliardone Maria Pia, Melisurgo Giulio, Russo Claudio Francesco, La Vecchia Carlo, Frigerio Maria, Pappalardo Federico
Abstract
Management of acute decompensated heart failure patients presenting with cardiogenic shock (CS) is not straightforward, as few data are available from clinical trials. Stabilization before left ventricle assist device (LVAD) or heart transplantation (HTx) is strongly advocated, as patients undergoing LVAD implant or HTx in critical status have worse outcomes. This was a multicenter phase II study with a Simon 2-stage design, including 24 consecutive patients treated with low-moderate epinephrine doses, whose refractory CS prompted implantation of intra-aortic balloon pump (IABP) which was subsequently upgraded with peripheral venoarterial extracorporeal membrane oxygenation. At admission, patients had severe left ventricular dysfunction and overt CS, 7 patients could be managed only with inotropic therapy, and 16 patients were transitioned to IABP and 1 to IABP and venoarterial extracorporeal membrane oxygenation; the median duration of epinephrine therapy was 7?days (interquartile range 6-15), and the median dose was 0.08 ?g/kg/min (interquartile range 0.05-0.1); 21 patients (87.5%) survived at 60?days (primary outcome); among them, 13 (61.9%) underwent LVAD implantation, 2 (9.5%) underwent HTx, and 6 (28.6%) improved on medical treatment, indicating that early and intensive treatment of CS in chronic advanced heart failure patients with low-dose epinephrine and timely short-term mechanical circulatory support leads to satisfactory outcomes.
Copyright © 2018 Elsevier Inc. All rights reserved.
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Early and Mid-Term Results of Rapid Deployment Valves: The Intuity Italian Registry (INTU-ITA).
Ann Thorac Surg2018 Dec;106(6):1742-1749. doi: 10.1016/j.athoracsur.2018.07.002.
D'Onofrio Augusto, Tessari Chiara, Filippini Claudia, Bagozzi Lorenzo, Diena Marco, Alamanni Francesco, Massetti Massimo, Livi Ugolino, Di Eusanio Marco, Mignosa Carmelo, Russo Claudio, Rinaldi Mauro, Di Bartolomeo Roberto, Salvador Loris, Antona Carlo, Maselli Daniele, De Paulis Ruggero, Luzi Giampaolo, Alfieri Ottavio, De Filippo Carlo Maria, Portoghese Michele, Musumeci Francesco, Bortolotti Uberto, Gerosa Gino
Abstract
BACKGROUND:
Rapid deployment bioprostheses (RDBs) have been recently introduced into clinical practice for the treatment of severe aortic valve stenosis. The aim of this retrospective multicenter study was to assess early and mid-term clinical and hemodynamic outcomes of patients undergoing RDB implantation.
METHODS:
Data from a national registry that included patients who underwent isolated or combined aortic valve replacement with RDB in Italy were analyzed. Definitions of the European System for Cardiac Operative Risk Evaluation were used for preoperative variables and updated definitions from the Valve Academic Research Consortium were used for postoperative outcomes assessment. Univariable and multivariable analyses were performed to identify independent predictors of mortality. Follow-up was performed with clinical and echocardiographic examinations at each study site and, if this was not possible, through telephonic interviews. The Kaplan-Meier method was used for survival analysis.
RESULTS:
A total of 902 patients (December 2012 through November 2017) from 20 national centers were included in the registry. Device success was 95.9%, and 30-day all-cause mortality was 2.8%. Postoperative pacemaker implantation was needed in 63 patients (6.9%). At discharge, peak and mean transaortic gradients were 19 ± 7 mm Hg and 11 ± 4 mm Hg, respectively. Mild and moderate aortic regurgitation were found in 71 patients (8.2%) and in 10 patients (1.2%), respectively. Median follow-up time was 357 days (interquartile range: 103 to 638 days). Survival at 4 years was 86% ± 1%. Preoperative conduction disturbances and history of previous myocardial infarction were independently associated with mortality.
CONCLUSIONS:
Aortic RDBs provide good early and mid-term clinical and hemodynamic outcomes. These devices may be considered as a reasonable alternative to conventional bioprostheses, especially in minimally invasive and combined operations.
Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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MYLK pathogenic variants aortic disease presentation, pregnancy risk, and characterization of pathogenic missense variants.
Genet Med2019 Jan;21(1):144-151. doi: 10.1038/s41436-018-0038-0.
Wallace Stephanie E, Regalado Ellen S, Gong Limin, Janda Alexandra L, Guo Dong-Chuan, Russo Claudio F, Kulmacz Richard J, Hanna Nadine, Jondeau Guillaume, Boileau Catherine, Arnaud Pauline, Lee Kwanghyuk, Leal Suzanne M, Hannuksela Matias, Carlberg Bo, Johnston Tami, Antolik Christian, Hostetler Ellen M, Colombo Roberto, Milewicz Dianna M
Abstract
PURPOSE:
Heritable thoracic aortic disease can result from null variants in MYLK, which encodes myosin light-chain kinase (MLCK). Data on which MYLK missense variants are pathogenic and information to guide aortic disease management are limited.
METHODS:
Clinical data from 60 cases with MYLK pathogenic variants were analyzed (five null and two missense variants), and the effect of missense variants on kinase activity was assessed.
RESULTS:
Twenty-three individuals (39%) experienced an aortic event (defined as aneurysm repair or dissection); the majority of these events (87%) were aortic dissections. Aortic diameters were minimally enlarged at the time of dissection in many cases. Time-to-aortic-event curves showed that missense pathogenic variant (PV) carriers have earlier-onset aortic events than null PV carriers. An MYLK missense variant segregated with aortic disease over five generations but decreases MYLK kinase acitivity marginally. Functional Assays fail to identify all pathogenic variants in MYLK.
CONCLUSION:
These data further define the aortic phenotype associated with MYLK pathogenic variants. Given minimal aortic enlargement before dissection, an alternative approach to guide the timing of aortic repair is proposed based on the probability of a dissection at a given age.
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Evolut R implantation via the brachial artery.
Eur J Cardiothorac Surg2018 Dec;54(6):1137-1139. doi: 10.1093/ejcts/ezy201.
Bruschi Giuseppe, Merlanti Bruno, Colombo Paola, Russo Claudio F
Abstract
Transfemoral transcatheter aortic valve implantation is an established therapy to treat elderly patients affected by severe aortic stenosis, who are considered to be at high or extreme risk for surgical aortic valve replacement. The transfemoral approach is contraindicated in patients with severe peripheral artery disease, small vessel size or severe tortuosity. In these patients, other vascular access routes such as transapical, subclavian or direct-aortic access may be considered. We describe the first case of a Medtronic Evolut R (Medtronic, Minneapolis, MN, USA) implantation made through the brachial artery in a 75-year-old patient affected by severe aortic stenosis.
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Pharmacological activation of autophagy favors the clearing of intracellular aggregates of misfolded prion protein peptide to prevent neuronal death.
Cell Death Dis2018 Feb;9(2):166. doi: 166.
Thellung Stefano, Scoti Beatrice, Corsaro Alessandro, Villa Valentina, Nizzari Mario, Gagliani Maria Cristina, Porcile Carola, Russo Claudio, Pagano Aldo, Tacchetti Carlo, Cortese Katia, Florio Tullio
Abstract
According to the "gain-of-toxicity mechanism", neuronal loss during cerebral proteinopathies is caused by accumulation of aggregation-prone conformers of misfolded cellular proteins, although it is still debated which aggregation state actually corresponds to the neurotoxic entity. Autophagy, originally described as a variant of programmed cell death, is now emerging as a crucial mechanism for cell survival in response to a variety of cell stressors, including nutrient deprivation, damage of cytoplasmic organelles, or accumulation of misfolded proteins. Impairment of autophagic flux in neurons often associates with neurodegeneration during cerebral amyloidosis, suggesting a role in clearing neurons from aggregation-prone misfolded proteins. Thus, autophagy may represent a target for innovative therapies. In this work, we show that alterations of autophagy progression occur in neurons following in vitro exposure to the amyloidogenic and neurotoxic prion protein-derived peptide PrP90-231. We report that the increase of autophagic flux represents a strategy adopted by neurons to survive the intracellular accumulation of misfolded PrP90-231. In particular, PrP90-231 internalization in A1 murine mesencephalic neurons occurs in acidic structures, showing electron microscopy hallmarks of autophagosomes and autophagolysosomes. However, these structures do not undergo resolution and accumulate in cytosol, suggesting that, in the presence of PrP90-231, autophagy is activated but its progression is impaired; the inability to clear PrP90-231 via autophagy induces cytotoxicity, causing impairment of lysosomal integrity and cytosolic diffusion of hydrolytic enzymes. Conversely, the induction of autophagy by pharmacological blockade of mTOR kinase or trophic factor deprivation restored autophagy resolution, reducing intracellular PrP90-231 accumulation and neuronal death. Taken together, these data indicate that PrP90-231 internalization induces an autophagic defensive response in A1 neurons, although incomplete and insufficient to grant survival; the pharmacological enhancement of this process exerts neuroprotection favoring the clearing of the internalized peptide and could represents a promising neuroprotective tool for neurodegenerative proteinopathies.
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Corrigendum to "A predictive model for early mortality after surgical treatment of heart valve or prosthesis infective endocarditis. The EndoSCORE". [Int. J. Cardiol. 241 (Aug 15 2017) 97-102].
Int J Cardiol2018 May;258():337. doi: 10.1016/j.ijcard.2018.01.019.
Di Mauro Michele, Dato Guglielmo Mario Actis, Barili Fabio, Gelsomino Sandro, Santè Pasquale, Corte Alessandro Della, Carrozza Antonio, Ratta Ester Della, Cugola Diego, Galletti Lorenzo, Devotini Roger, Casabona Riccardo, Santini Francesco, Salsano Antonio, Scrofani Roberto, Antona Carlo, Botta Luca, Russo Claudio, Mancuso Samuel, Rinaldi Mauro, De Vincentiis Carlo, Biondi Andrea, Beghi Cesare, Cappabianca Giangiuseppe, Tarzia Vincenzo, Gerosa Gino, De Bonis Michele, Pozzoli Alberto, Nicolini Francesco, Benassi Filippo, Rosato Francesco, Grasso Elena, Livi Ugolino, Sponga Sandro, Pacini Davide, Di Bartolomeo Roberto, DeMartino Andrea, Bortolotti Uberto, Onorati Francesco, Faggian Giuseppe, Lorusso Roberto, Vizzardi Enrico, Di Giammarco Gabriele, Marinelli Daniele, Villa Emmanuel, Troise Giovanni, Picichè Marco, Musumeci Francesco, Paparella Domenico, Margari Vito, Tritto Francesco, Damiani Girolamo, Scrascia Giuseppe, Zaccaria Salvatore, Renzulli Attilio, Serraino Giuseppe, Mariscalco Giovanni, Maselli Daniele, Foschi Massimiliano, Parolari Alessandro, Nappi Giannantonio,
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Imaging of metabolic bone disease.
Acta Biomed2018 Jan;89(1-S):197-207. doi: 10.23750/abm.v89i1-S.7023.
Mattera Maria, Reginelli Alfonso, Bartollino Silvia, Russo Claudio, Barile Antonio, Albano Domenico, Mauri Giovanni, Messina Carmelo, Cappabianca Salvatore, Guglielmi Giuseppe
Abstract
Osteoporosis is the most important metabolic bone disease, with a wide distribution among the elderly. It is characterized by low bone mass and micro architectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk. Identify bone weakening with an appropriate and accurate use of diagnostic imaging is of critical importance in the diagnosis and follow-up of osteoporotic patients. The aim of this review is to evaluate the detection rates of the different imaging modalities in the evaluation of bone strength, in the assessment of fracture risk and in the management of fragility fractures.
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Magnetic Resonance Imaging correlates of benign and malignant alterations of the spinal bone marrow.
Acta Biomed2018 Jan;89(1-S):18-33. doi: 10.23750/abm.v89i1-S.7008.
Caranci Ferdinando, Tedeschi Enrico, Ugga Lorenzo, D'Amico Alessandra, Schipani Serena, Bartollino Silvia, Russo Claudio, Splendiani Alessandra, Briganti Francesco, Zappia Marcello, Melone Mariarosa A B, Masciocchi Carlo, Brunese Luca
Abstract
BACKGROUND AND AIM OF THE WORK:
Bone marrow (BM) abnormalities in the spine are a common, sometimes unexpected, finding on Magnetic Resonance Imaging (MRI), which is the most sensitive imaging modality to evaluate the marrow, and their interpretation can be difficult for the unexperienced radiologist. In this review, the MRI appearance of normal age-related BM changes, as well as the imaging features of benign and malignant diseases, are presented.
DISCUSSION:
A large variety of BM signal alterations has been identified and described, including normal variants, BM reconversion, degenerative changes, infections, spondyloarthritis and osteonecrosis, trauma, neoplastic lesions (both primary or metastatic), post-radiation and chemotherapy sequelae.
CONCLUSIONS:
Knowledge of normal age-related BM appearance, normal variants and patterns of involvement in focal and diffuse bone diseases is essential, together with clinical and laboratory data, to narrow the list of the possible differential diagnoses. The radiologist should be familiar with these signal changes, as they can sometimes be discovered incidentally. In this context, it is equally important not to attribute pathological significance to benign alterations and to promptly detect signs of malignant diseases.
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Complexity and Selectivity of ?-Secretase Cleavage on Multiple Substrates: Consequences in Alzheimer's Disease and Cancer.
J Alzheimers Dis2018 ;61(1):1-15. doi: 10.3233/JAD-170628.
Medoro Alessandro, Bartollino Silvia, Mignogna Donatella, Passarella Daniela, Porcile Carola, Pagano Aldo, Florio Tullio, Nizzari Mario, Guerra Germano, Di Marco Roberto, Intrieri Mariano, Raimo Gennaro, Russo Claudio
Abstract
The processing of the amyloid-? protein precursor (A?PP) by ?- and ?-secretases is a pivotal event in the genesis of Alzheimer's disease (AD). Besides familial mutations on the A?PP gene, or upon its overexpression, familial forms of AD are often caused by mutations or deletions in presenilin 1 (PSEN1) and 2 (PSEN2) genes: the catalytic components of the proteolytic enzyme ?-secretase (GS). The "amyloid hypothesis", modified over time, states that the aberrant processing of A?PP by GS induces the formation of specific neurotoxic soluble amyloid-? (A?) peptides which, in turn, cause neurodegeneration. This theory, however, has recently evidenced significant limitations and, in particular, the following issues are debated: 1) the concept and significance of presenilin's "gain of function" versus "loss of function"; and 2) the presence of several and various GS substrates, which interact with A?PP and may influence A? formation. The latter consideration is suggestive: despite the increasing number of GS substrates so far identified, their reciprocal interaction with A?PP itself, even in the AD field, is significantly unexplored. On the other hand, GS is also an important pharmacological target in the cancer field; inhibitors or GS activity are investigated in clinical trials for treating different tumors. Furthermore, the function of A?PP and PSENs in brain development and in neuronal migration is well known. In this review, we focused on a specific subset of GS substrates that directly interact with A?PP and are involved in its proteolysis and signaling, by evaluating their role in neurodegeneration and in cell motility or proliferation, as a possible connection between AD and cancer.
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Survival and Left Ventricular Function Changes in Fulminant Versus Nonfulminant Acute Myocarditis.
Circulation2017 Aug;136(6):529-545. doi: 10.1161/CIRCULATIONAHA.117.026386.
Ammirati Enrico, Cipriani Manlio, Lilliu Marzia, Sormani Paola, Varrenti Marisa, Raineri Claudia, Petrella Duccio, Garascia Andrea, Pedrotti Patrizia, Roghi Alberto, Bonacina Edgardo, Moreo Antonella, Bottiroli Maurizio, Gagliardone Maria P, Mondino Michele, Ghio Stefano, Totaro Rossana, Turazza Fabio M, Russo Claudio F, Oliva Fabrizio, Camici Paolo G, Frigerio Maria
Abstract
BACKGROUND:
Previous reports have suggested that despite their dramatic presentation, patients with fulminant myocarditis (FM) might have better outcome than those with acute nonfulminant myocarditis (NFM). In this retrospective study, we report outcome and changes in left ventricular ejection fraction (LVEF) in a large cohort of patients with FM compared with patients with NFM.
METHODS:
The study population consists of 187 consecutive patients admitted between May 2001 and November 2016 with a diagnosis of acute myocarditis (onset of symptoms
RESULTS:
In the whole population (n=187), the rate of in-hospital death or heart transplantation was 25.5% versus 0% in FM versus NFM, respectively (
CONCLUSIONS:
Patients with FM have an increased mortality and need for heart transplantation compared with those with NFM. From a functional viewpoint, patients with FM have a more severely impaired LVEF at admission that, despite steep improvement during hospitalization, remains lower than that in patients with NFM at long-term follow-up. These findings also hold true when only the viral forms are considered and are different from previous studies showing better prognosis in FM.
© 2017 American Heart Association, Inc.
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HeartWare-HVAD for end-stage heart failure: a review of clinical experiences with ?50 patients.
Expert Rev Med Devices2017 Jun;14(6):423-437. doi: 10.1080/17434440.2017.1325318.
Botta Luca, De Chiara Benedetta, Macera Francesca, Cannata Aldo, Costetti Alessandro, Voltolini Alessandra, Moreo Antonella, Cipriani Manlio, Frigerio Maria, Russo Claudio Francesco
Abstract
Despite the improvements in medical and surgical treatments, the incidence of end-stage heart failure (ESHF) continues to increase. Different mechanical systems have been adopted to support failing left ventricles. Among continuous-flow devices, the HeartWare-HVAD was the first to use a centrifugal pump rather than an axial one. Areas covered: In this review article, we provide an overview of the HeartWare-HVAD as a ventricular assist device for ESHF, discussing indications, echocardiographic assessment, surgical techniques, outcomes, concerns and controversies. Scientific literature was reviewed with a MEDLINE search strategy combining 'HeartWare' or 'HVAD' with 'heart failure'. A total of 263 papers were found using the reported search. From these, 16 were identified to provide the best evidence on the subject reporting outcomes in ?50 patients. Expert commentary: HeartWare-HVAD is a minute device that provides full circulatory support in patients with ESHF. Its main indication remains bridge to heart transplantation (HTx). Median sternotomy is the preferred technique of implantation although less invasive procedures have been described. Early outcomes are satisfactory. Nevertheless, some fearing complications still occur during the mid- and long-term follow-up. Further technical developments and optimal medical management will guarantee better outcomes.
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Late Echocardiographic Study of Aortic Valve and Aortic Root after Surgery for Type A Acute Aortic Dissection.
J Cardiovasc Echogr2016 ;26(3):78-82. doi: 10.4103/2211-4122.187948.
Molteni Martina, De Chiara Benedetta, Casadei Francesca, Botta Luca, Merlanti Bruno, Russo Claudio Francesco, Giannattasio Cristina, Moreo Antonella
Abstract
OBJECTIVE:
In case of concomitant aortic regurgitation (AR) valve, sparing operation is considered the first choice in selected patients. The aim of this retrospective clinical and echocardiographic study was to evaluate the long-term survival results of conservative approach and the determinants of recurrent AR.
METHODS:
From 2000 to 2011, fifty patients (median: 63 years and interquartile range: 53-72) underwent an aortic valve-sparing procedure for acute aortic dissection, and discharged alive. The long-term clinical and echocardiographic outcome was analyzed.
RESULTS:
Late all-causes mortality was 18% (nine patients) at a median follow-up of 55.8 months. Ten patients (20%) underwent re-operations, five of them for aortic valve/root recurrent disease; freedom from proximal re-operation was 90%. Two-third of the patients had a preoperative AR grade
CONCLUSIONS:
Preoperative AR and late aortic root diameter were not the predictors of late AR. Late AR is higher in patients who underwent aortic commissures and cusps resuspension compared to the only replacement of the ascending aorta.
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Mitral periprosthetic leakage: contemporary results of surgical correction at a single centre.
Interact Cardiovasc Thorac Surg2017 Aug;25(2):185-190. doi: 10.1093/icvts/ivx101.
Botta Luca, De Chiara Benedetta, Quattrocchi Salvina, Casadei Francesca, Borgia Francesco, Giannattasio Cristina, Moreo Antonella, Russo Claudio Francesco
Abstract
OBJECTIVES:
Mitral periprosthetic leakage (PPL) is a serious complication following valve replacement. Conflicting outcomes of surgical treatment have been reported in the presence of multiple previous cardiac operations and associated co-pathological conditions.
METHODS:
Sixty-five symptomatic patients (37 women, mean age 64.8 years) underwent conventional operations at our hospital from 2006 to 2015. Mitral PPL was the leading surgical indication, although associated procedures were included. Previous transcatheter procedures and leaks involving multiple prostheses were excluded. The median number of past mitral operations was 2 (range 1-5). PPL recurrence was observed in 29% of cases. A previous operation on the aortic or tricuspid valve was performed in 31 patients.
RESULTS:
Mitral PPL involved one-, two- or three-quarters of the mitral perimeter in 46, 43 and 11% of cases. Prosthetic refixation or replacement was performed in 24 and 41 patients, respectively. Annular reconstruction was necessary in 17% of prosthetic replacements. Associated procedures were performed in 19 patients. The operation was executed through a right minithoracotomy (unclamped aorta) in 20% of patients. In-hospital deaths occurred in 3.1%. After a median follow-up of 60 months, freedom from all-cause mortality was 96.8, 91.5 and 88.8% at 1, 3 and 5 years. Lateral leaks [P?=?0.03; hazard ratio (HR)?=?4.57, 95% confidence interval (CI): 1.13-18.3] and PPL relapse (P?=?0.03; HR?=?4.33, 95% CI: 1.12-16.7) were independently associated with death. At follow-up, 4 patients had a?>2+ recurrent leak and 2 were reoperated.
CONCLUSIONS:
A customized conventional mitral reoperation still represents a satisfactory and effective treatment option for PPL and should be considered even in patients with very complex issues.
© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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A predictive model for early mortality after surgical treatment of heart valve or prosthesis infective endocarditis. The EndoSCORE.
Int J Cardiol2017 Aug;241():97-102. doi: 10.1016/j.ijcard.2017.03.148.
Di Mauro Michele, Dato Guglielmo Mario Actis, Barili Fabio, Gelsomino Sandro, Santè Pasquale, Corte Alessandro Della, Carrozza Antonio, Ratta Ester Della, Cugola Diego, Galletti Lorenzo, Devotini Roger, Casabona Riccardo, Santini Francesco, Salsano Antonio, Scrofani Roberto, Antona Carlo, Botta Luca, Russo Claudio, Mancuso Samuel, Rinaldi Mauro, De Vincentiis Carlo, Biondi Andrea, Beghi Cesare, Cappabianca Giangiuseppe, Tarzia Vincenzo, Gerosa Gino, De Bonis Michele, Pozzoli Alberto, Nicolini Francesco, Benassi Filippo, Rosato Francesco, Grasso Elena, Livi Ugolino, Sponga Sandro, Pacini Davide, Di Bartolomeo Roberto, De Martino Andrea, Bortolotti Uberto, Onorati Francesco, Faggian Giuseppe, Lorusso Roberto, Vizzardi Enrico, Di Giammarco Gabriele, Marinelli Daniele, Villa Emmanuel, Troise Giovanni, Picichè Marco, Musumeci Francesco, Paparella Domenico, Margari Vito, Tritto Francesco, Damiani Girolamo, Scrascia Giuseppe, Zaccaria Salvatore, Renzulli Attilio, Serraino Giuseppe, Mariscalco Giovanni, Maselli Daniele, Foschi Massimiliano, Parolari Alessandro, Nappi Giannantonio,
Abstract
BACKGROUND:
The aim of this large retrospective study was to provide a logistic risk model along an additive score to predict early mortality after surgical treatment of patients with heart valve or prosthesis infective endocarditis (IE).
METHODS:
From 2000 to 2015, 2715 patients with native valve endocarditis (NVE) or prosthesis valve endocarditis (PVE) were operated on in 26 Italian Cardiac Surgery Centers. The relationship between early mortality and covariates was evaluated with logistic mixed effect models. Fixed effects are parameters associated with the entire population or with certain repeatable levels of experimental factors, while random effects are associated with individual experimental units (centers).
RESULTS:
Early mortality was 11.0% (298/2715); At mixed effect logistic regression the following variables were found associated with early mortality: age class, female gender, LVEF, preoperative shock, COPD, creatinine value above 2mg/dl, presence of abscess, number of treated valve/prosthesis (with respect to one treated valve/prosthesis) and the isolation of Staphylococcus aureus, Fungus spp., Pseudomonas Aeruginosa and other micro-organisms, while Streptococcus spp., Enterococcus spp. and other Staphylococci did not affect early mortality, as well as no micro-organisms isolation. LVEF was found linearly associated with outcomes while non-linear association between mortality and age was tested and the best model was found with a categorization into four classes (AUC=0.851).
CONCLUSIONS:
The following study provides a logistic risk model to predict early mortality in patients with heart valve or prosthesis infective endocarditis undergoing surgical treatment, called "The EndoSCORE".
Copyright © 2017. Published by Elsevier B.V.
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Epoxy-Based Shape-Memory Actuators Obtained via Dual-Curing of Off-Stoichiometric "Thiol?Epoxy" Mixtures.
Polymers (Basel)2017 Mar;9(3):. doi: 113.
Belmonte Alberto, Russo Claudio, Ambrogi Veronica, Fernández-Francos Xavier, De la Flor Silvia
Abstract
In this work, epoxy-based shape-memory actuators have been developed by taking advantage of the sequential dual-curing of off-stoichiometric "thiol?epoxy" systems. Bent-shaped designs for flexural actuation were obtained thanks to the easy processing of these materials in the intermediate stage (after the first curing process), and successfully fixed through the second curing process. The samples were programmed into a flat temporary-shape and the recovery-process was analyzed in unconstrained, partially-constrained and fully-constrained conditions using a dynamic mechanical analyzer (DMA). Different "thiol?epoxy" systems and off-stoichiometric ratios were used to analyze the effect of the network structure on the actuation performance. The results evidenced the possibility to take advantage of the flexural recovery as a potential actuator, the operation of which can be modulated by changing the network structure and properties of the material. Under unconstrained-recovery conditions, faster and narrower recovery-processes (an average speed up to 80%/min) are attained by using materials with homogeneous network structure, while in partially- or fully-constrained conditions, a higher crosslinking density and the presence of crosslinks of higher functionality lead to a higher amount of energy released during the recovery-process, thus, increasing the work or the force released. Finally, an easy approach for the prediction of the work released by the shape-memory actuator has been proposed.
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Portico Sheathless Transcatheter Aortic Valve Implantation via Distal Axillary Artery.
Ann Thorac Surg2017 Feb;103(2):e175-e177. doi: 10.1016/j.athoracsur.2016.07.065.
Bruschi Giuseppe, Colombo Paola, Botta Luca, Nava Stefano, Merlanti Bruno, Belli Oriana, Musca Francesco, Soriano Francesco, Russo Claudio F, Oliva Fabrizio
Abstract
Transcatheter aortic valve implantation has been designed to treat older patients affected by severe aortic stenosis who are considered high-risk surgical candidates because of multiple comorbidities. The least invasive approach for transcatheter aortic valves implantation should be considered the transfemoral retrograde route, because it is minimally invasive and is feasible with local anesthesia and mild sedation. Despite significant technical improvements in recent years, the transfemoral approach is contraindicated in cases of severe peripheral artery disease. We describe the first case of a Portico transcatheter aortic valve implantation system (St. Jude Medical, Minneapolis, MN) made through the distal axillary artery in a 90-year-old patient affected by severe aortic stenosis.
Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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Arterial Stiffness in Aortic Stenosis: Relationship with Severity and Echocardiographic Procedures Response.
High Blood Press Cardiovasc Prev2017 Mar;24(1):19-27. doi: 10.1007/s40292-016-0176-x.
Bruschi Giuseppe, Maloberti Alessandro, Sormani Paola, Colombo Giulia, Nava Stefano, Vallerio Paola, Casadei Francesca, Bruno Jolie, Moreo Antonella, Merlanti Bruno, Russo Claudio, Oliva Fabrizio, Klugmann Silvio, Giannattasio Cristina
Abstract
INTRODUCTION:
Aortic stenosis (AS) is more than only a degenerative disease, it could be also an atherosclerotic-like process involving the valve instead of the vessels. Little is known about the relation of arterial stiffness and AS.
AIM:
We sought to determine wether pulse wave velocity (PWV), is related to AS severity and to the procedures response, both as surgical aortic-valve-replacement (AVR) and trascatheter-aortic-valve-implantation (TAVI).
METHODS:
30 patients with severe AS were treated (15 AVR, 15 TAVI). Before the procedures (t0) and after 1 week (t1) echocardiography and PWV were evaluated.
RESULTS:
On the whole population, subjects with higher PWV showed higher transvalvular pressure gradient at baseline (mean: 56.5 ± 15.1 vs 45.4 ± 9.5; peak: 93.3 ± 26.4 vs 73.3 ± 14.9, p = 0.02) and, a significantly greater response to the procedures (mean: -42.9 ± 17.2 vs -27.9 ± 10.1, peak: -68.7 ± 29.2 vs -42.8 ± 16.4, p = 0.02). When the two different procedures groups were separated, data were confirmed only in the TAVI subgroup.
CONCLUSIONS:
In patients undergoing procedures for AS, PWV is correlated with transvalvular gradient and, in TAVI subjects, is able to predict the echocardiographic response. Baseline evaluation of PWV in patients candidates to TAVI can help the selection of subjects, even if larger and longer studies are needed before definitive conclusion can be drawn.
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The inhibition of 45A ncRNA expression reduces tumor formation, affecting tumor nodules compactness and metastatic potential in neuroblastoma cells.
Oncotarget2017 Jan;8(5):8189-8205. doi: 10.18632/oncotarget.14138.
Penna Ilaria, Gigoni Arianna, Costa Delfina, Vella Serena, Russo Debora, Poggi Alessandro, Villa Federico, Brizzolara Antonella, Canale Claudio, Mescola Andrea, Daga Antonio, Russo Claudio, Nizzari Mario, Florio Tullio, Menichini Paola, Pagano Aldo
Abstract
We recently reported the in vitro over-expression of 45A, a RNA polymerase III-transcribed non-coding (nc)RNA, that perturbs the intracellular content of FE65L1 affecting cell proliferation rate, short-term response to genotoxic stress, substrate adhesion capacity and, ultimately, increasing the tumorigenic potential of human neuroblastoma cells. In this work, to deeply explore the mechanism by which 45A ncRNA contributes to cancer development, we targeted in vitro and in vivo 45A levels by the stable overexpression of antisense 45A RNA.45A downregulation leads to deep modifications of cytoskeleton organization, adhesion and migration of neuroblastoma cells. These effects are correlated with alterations in the expression of several genes including GTSE1 (G2 and S phase-expressed-1), a crucial regulator of tumor cell migration and metastatic potential. Interestingly, the downregulation of 45A ncRNA strongly affects the in vivo tumorigenic potential of SKNBE2 neuroblastoma cells, increasing tumor nodule compactness and reducing GTSE1 protein expression in a subcutaneous neuroblastoma mouse model. Moreover, intracardiac injection of neuroblastoma cells showed that downregulation of 45A ncRNA also influences tumor metastatic ability. In conclusion, our data highlight a key role of 45A ncRNA in cancer development and suggest that its modulation might represent a possible novel anticancer therapeutic approach.
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[Psychological evaluation and support in patients with left ventricular assist devices: preliminary data at 6-month follow-up].
G Ital Cardiol (Rome)2016 Nov;17(11):940-946. doi: 10.1714/2498.26204.
Voltolini Alessandra, Minotti Anna, Verde Alessandro, Cipriani Manlio, Garascia Andrea, Turazza Fabio, Macera Francesca, Perna Enrico, Russo Claudio F, Fumagalli Emilia, Frigerio Maria
Abstract
BACKGROUND:
Heart disease has an impact on patient's identity and self-perception. Taking into account the wide literature about psychological aspects before and after heart transplant, it clearly emerges that there is a lack of data and results for patients up to implantation of ventricular assist devices (VAD). The aim of the present study was to explore quality of life and factors correlated with psychological adjustment in patients supported with VAD.
METHODS:
From February 2013 to August 2014, 18 patients (17 male, mean age 57 years) under clinical evaluation before and after VAD implantation were enrolled. During interviews, patients were assessed with EuroQoL-5D questionnaire to monitor improvement of quality of life before implantation and at 3 and 6 months; critical issues, needs and point of views of patients have been described.
RESULTS:
A significant improvement in the quality of life score was observed at 3 (score 38 [interquartile range 30-40] vs 75 [60-80], p
CONCLUSIONS:
Successful treatment and efficient psychological care are closely related to assessment and continuous clinical support. This approach ensures a better selection of patients and improves their compliance. Further data are needed to support our preliminary observations and to explore long-term quality of life.
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[Acute aortic dissection type A: from the past to the present].
G Ital Cardiol (Rome)2016 Nov;17(11):908-914. doi: 10.1714/2498.26194.
Russo Claudio F, Mariscalco Giovanni, Santé Pasquale
Abstract
Acute aortic dissection type A (AADA) is a disease that has a catastrophic impact on a patient's life. Although refinements in perioperative and surgical care have translated into improved outcomes for patients affected by AADA, hospital mortality after surgery still remains very high, ranging from 15% to 30%. The management of AADA is complex and dictated by the modality of presentation, extent and location of the disease. Attempts to formulate consensus statements and relevant guidelines have identified significant gaps in the AADA knowledge with reference to pathogenesis, appropriate management and configuration for clinical services. Several international registries have been created to generate an evidence base that can address current and future management. In this context, the extensive use of surgical/hybrid approaches in treating AADA should be encouraged as well as more extensive interventions to replace the entire dissected aortic root and aortic arch tissues. In addition, the excellent outcome results recently achieved by high-volume surgical centers with focused expertise in AADA pointed out the need for regionalized super-centers offering specific multidisciplinary aortic surgery programs with dedicated high-specialized surgeons.
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Evolut R Implantation to Treat Severe Pure Aortic Regurgitation in a Patient With Mitral Bioprosthesis.
Ann Thorac Surg2016 Dec;102(6):e521-e524. doi: 10.1016/j.athoracsur.2016.05.054.
Bruschi Giuseppe, Colombo Paola, Nava Stefano, Musca Francesco, Merlanti Bruno, Belli Oriana, Soriano Francesco, Botta Luca, De Caria Danile, Giannattasio Cristina, Russo Claudio F
Abstract
Transcatheter aortic valves have been designed to treat high-risk surgical candidates affected by severe aortic stenosis, but little is known about the use of transcatheter valves in patients with severe pure aortic regurgitation. We describe the implantation of Medtronic CoreValve Evolut R (Medtronic, Minneapolis, MN) to treat an 82-year-old patient affected by severe pure aortic regurgitation who underwent prior mitral valve replacement with a biological valve protruding into the left ventricular outflow tract.
Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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A new access for transcatheter aortic valve implantation: Distal axillary artery.
Int J Cardiol2016 Nov;223():810-812. doi: 10.1016/j.ijcard.2016.08.290.
Bruschi Giuseppe, Colombo Paola, Merlanti Bruno, Nava Stefano, Belli Oriana, Musca Francesco, Soriano Francesco, Botta Luca, Calini Angelo, De Caria Daniele F, Oliva Fabrizio, Russo Claudio F
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Direct Transaortic TEVAR: An Alternative Option for Selected Patients With Unsuitable Peripheral Access.
Ann Thorac Surg2016 Aug;102(2):e117-9. doi: 10.1016/j.athoracsur.2016.01.010.
Botta Luca, Bruschi Giuseppe, Fratto Pasquale, Margari Vito, Solcia Marco, Borgia Francesco, Rampoldi Antonio, Russo Claudio Francesco
Abstract
Thoracic endovascular aortic repair (TEVAR) is effectively executed in patients with arch or descending aortic diseases. Peripheral access sites are preferably used as standard gates for TEVAR. Feasibility of a peripheral approach might need an intraoperative evaluation and alternative routes should have been carefully assessed. In this article, we report 2 successful cases of direct transaortic TEVAR, where stent grafts were directly introduced into the native ascending aorta without external conduits. A satisfactory result and the absence of aortic-related complications were observed at 2 and 5 years' follow-up, respectively.
Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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A prospective comparison of mid-term outcomes in patients treated with heart transplantation with advanced age donors versus left ventricular assist device implantation.
Interact Cardiovasc Thorac Surg2016 Oct;23(4):584-92. doi: 10.1093/icvts/ivw164.
Ammirati Enrico, Cipriani Manlio G, Varrenti Marisa, Colombo Tiziano, Garascia Andrea, Cannata Aldo, Pedrazzini Giovanna, Benazzi Elena, Milazzo Filippo, Oliva Fabrizio, Gagliardone Maria P, Russo Claudio F, Frigerio Maria
Abstract
OBJECTIVES:
In Europe, the age of heart donors is constantly increasing. Ageing of heart donors limits the probability of success of heart transplantation (HTx). The aim of this study is to compare the outcome of patients with advanced heart failure (HF) treated with a continuous-flow left ventricular assist device (CF-LVAD) with indication as bridge to transplantation (BTT) or bridge to candidacy (BTC) versus recipients of HTx with the donor's age above 55 years (HTx with donors >55 years).
METHODS:
we prospectively evaluated 301 consecutive patients with advanced HF treated with a CF-LVAD (n = 83) or HTx without prior bridging (n = 218) in our hospital from January 2006 to January 2015. We compared the outcome of CF-LVAD-BTT (n = 37) versus HTx with donors >55 years (n = 45) and the outcome of CF-LVAD-BTT plus BTC (n = 62) versus HTx with donors >55 years at the 1- and 2-year follow-up. Survival was evaluated according to the first operation.
RESULTS:
The perioperative (30-day) mortality rate was 0% in the LVAD-BTT group vs 20% (n = 9) in the HTx group with donors >55 years (P = 0.003). Perioperative mortality occurred in 5% of the LVAD-BTT/BTC patients (n = 3) and in 20% of the HTx with donors >55 year group (P = 0.026). Kaplan-Meier curves estimated a 2-year survival rate of 94.6% in CF-LVAD-BTT vs 68.9% in HTx with donors >55 years [age- and sex-adjusted hazard ratio (HR) 0.25; 95% confidence interval (CI) 0.08-0.81; P = 0.02 in favour of CF-LVAD]. Considering the post-HTx outcome, a trend in favour of CF-LVAD-BTT was also observed (age- and sex-adjusted HR 0.45; 95% CI 0.17-1.16; P = 0.09 in favour of CF-LVAD), whereas CF-LVAD-BTT/BTC showed a similar survival at 2 years compared with HTx with donors >55 years, both censoring the follow-up at the time of HTx and considering the post-HTx outcome.
CONCLUSIONS:
Early and mid-term outcomes of patients treated with a CF-LVAD with BTT indication seem better than HTx with old donors. It must be emphasized that up to 19% of patients in the CF-LVAD/BTT group underwent transplantation in an urgent condition due to complications related to the LVAD. At the 2-year follow-up, CF-LVAD with BTT and BTC indications have similar outcome than HTx using old heart donors. These results must be confirmed in a larger and multicentre population and extending the follow-up.
© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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Serum Levels of Acyl-Carnitines along the Continuum from Normal to Alzheimer's Dementia.
PLoS One2016 ;11(5):e0155694. doi: e0155694.
Cristofano Adriana, Sapere Nadia, La Marca Giancarlo, Angiolillo Antonella, Vitale Michela, Corbi Graziamaria, Scapagnini Giovanni, Intrieri Mariano, Russo Claudio, Corso Gaetano, Di Costanzo Alfonso
Abstract
This study aimed to determine the serum levels of free L-carnitine, acetyl-L-carnitine and 34 acyl-L-carnitine in healthy subjects and in patients with or at risk of Alzheimer's disease. Twenty-nine patients with probable Alzheimer's disease, 18 with mild cognitive impairment of the amnestic type, 24 with subjective memory complaint and 46 healthy subjects were enrolled in the study, and the levels of carnitine and acyl-carnitines were measured by tandem mass spectrometry. The concentrations of acetyl-L-carnitine progressively decreased passing from healthy subjects group (mean±SD, 5.6±1.3 ?mol/L) to subjective memory complaint (4.3±0.9 ?mol/L), mild cognitive impairment (4.0±0.53 ?mol/L), up to Alzheimer's disease (3.5±0.6 ?mol/L) group (p
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Antiplatelet versus oral anticoagulant therapy as antithrombotic prophylaxis after mitral valve repair.
J Thorac Cardiovasc Surg2016 May;151(5):1302-8.e1. doi: 10.1016/j.jtcvs.2015.12.036.
Paparella Domenico, Di Mauro Michele, Bitton Worms Keren, Bolotin Gil, Russo Claudio, Trunfio Salvatore, Scrofani Roberto, Antona Carlo, Actis Dato Guglielmo, Casabona Riccardo, Colli Andrea, Gerosa Gino, Renzulli Attilio, Serraino Filiberto, Scrascia Giuseppe, Zaccaria Salvatore, De Bonis Michele, Taramasso Maurizio, Delgado Luis, Tritto Francesco, Marmo Joseph, Parolari Alessandro, Myaseodova Veronika, Villa Emmanuel, Troise Giovanni, Nicolini Francesco, Gherli Tiziano, Whitlock Richard, Conte Manuela, Barili Fabio, Gelsomino Sandro, Lorusso Roberto, Sciatti Edoardo, Marinelli Daniele, Di Giammarco Gabriele, Calafiore Antonio Maria, Sheikh Azmat, Alfonso Juan Jaime, Glauber Mattia, Miceli Antonio,
Abstract
OBJECTIVE:
To verify the rate of thromboembolic and hemorrhagic complications during the first 6 months after mitral valve repair and to assess whether the type of antithrombotic therapy influenced clinical outcome.
METHODS:
Retrospective data were retrieved from 19 centers. Inclusion criteria were isolated mitral valve repair with ring implantation. Exclusion criteria were ongoing or past atrial fibrillation and any combined intraoperative surgical procedures. The study cohort consisted of 1882 patients (aged 58 ± 15 years; 36% women), and included 1517 treated with an oral anticoagulant (VKA group) and 365 with antiplatelet drugs (APLT group). Primary efficacy outcome was the incidence of arterial thromboembolic events within 6 months and primary safety outcome was the incidence of major bleeding within 6 months. Propensity matching was performed to obtain 2 comparable cohorts (858 vs 286).
RESULTS:
No differences were detected for arterial embolic complications in matched cohort (1.6% VKA vs 2.1% APLT; P = .50). Conversely, patients in the APLT group showed lower incidence of major bleeding complications (3.9% vs 0.7%; P = .01). Six-month mortality rate was significantly higher in the VKA group (2.7% vs 0.3%; P = .02). Multivariable analysis in the matched cohort found VKA as independent predictor of major bleeding complications and mortality at 6 months.
CONCLUSIONS:
Vitamin K antagonist therapy was not superior to antiplatelet therapy to prevent thromboembolic complications after mitral valve repair. Our data suggest that oral anticoagulation may carry a higher bleeding risk compared with antiplatelet therapy, although these results should be confirmed in an adequately powered randomized controlled trial.
Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
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Giant apparently not dissecting aneurysm and severe aortic valve insufficiency in an elite athlete.
Eur Heart J2016 Aug;37(32):2527. doi: 10.1093/eurheartj/ehv683.
Cereda Alberto, Sormani Paola, Russo Claudio F, Moreo Antonella, Giannattasio Cristina
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St. Jude Medical Trifecta aortic valve: results from a prospective regional multicentre registry.
J Cardiothorac Surg2015 Nov;10():169. doi: 169.
Mariscalco Giovanni, Mariani Silvia, Bichi Samuele, Biondi Andrea, Blasio Andrea, Borsani Paolo, Corti Fabrizio, De Chiara Benedetta, Gherli Riccardo, Leva Cristian, Russo Claudio Francesco, Tasca Giordano, Vanelli Paolo, Alfieri Ottavio, Antona Carlo, Di Credico Germano, Esposito Giampiero, Gamba Amando, Martinelli Luigi, Menicanti Lorenzo, Paolini Giovanni, Beghi Cesare
Abstract
BACKGROUND:
The Trifecta aortic bioprosthesis (St. Jude Medical, Inc., St. Paul, MN, USA) is a stented pericardial heart valve with excellent preliminary results. Aim of the study was to evaluate its early clinical and hemodynamic performances in a multicenter regional registry.
METHODS:
Between January 2011 and June 2012, 178 consecutive patients undergoing aortic valve replacement with the Trifecta bioprosthesis were prospectively enrolled at 9 Italian centers. Clinical and echocardiographic data were collectedat discharge, 6-months and at 1-year postoperatively.
RESULTS:
The average age was 75.4?±?7.7 years,and 95 (53 %) were men. Indication for valve replacement included stenosis in 123 patients (69 %), mixed lesions in 25 (14 %), and regurgitation in 30 (17 %). Ninety-three (52 %) patients were in NYHA functional class III/ IV. Hospital mortality accounted for 5 (2.8 %) patients. No valve-related perioperative complications were encountered. Median follow-up was 20.5 months (range: 1-34). Early (?6 months) complications included one thromboembolic event, one major bleeding, and 3 endocarditis (2 explants). Two late (>6 months) thromboembolic events and two endocarditis (1 explant) were registered. No valve thrombosis or structural deterioration were observed after discharge. At 30-months, freedom from all-cause mortality was 87 %, freedom from valve-related mortality 99.4 %, freedom from endocarditis 97.5 %, and freedom from valve explants 98 %. At 1-year, mean gradients ranged from 8 to 16 mmHg, and effective orifice area indexes from 1.0 to 1.2 cm(2)/m(2) for valve sizes from 19 to 27 mm, respectively. No patients had severe prosthesis-patient mismatch.
CONCLUSIONS:
Trifecta bioprosthesis provided favourable clinical and hemodynamic results over time.
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A life-threatening presentation of eosinophilic granulomatosis with polyangiitis.
J Cardiovasc Med (Hagerstown)2016 Dec;17 Suppl 2():e109-e111. doi: 10.2459/JCM.0000000000000330.
Ammirati Enrico, Cipriani Manlio, Musca Francesco, Bonacina Edgardo, Pedrotti Patrizia, Roghi Alberto, Astaneh Arash, Schroeder Jan W, Nonini Sandra, Russo Claudio F, Oliva Fabrizio, Frigerio Maria
Abstract
: Necrotizing eosinophilic myocarditis (NEM) is a life-threatening condition that needs rapid diagnosis by endomyocardial biopsy and hemodynamic support usually by mechanical circulatory systems. We present the case of a 25-year-old Caucasian man who developed a refractory cardiogenic shock due to a NEM that was supported with a peripheral veno-arterial extracorporeal membrane oxygenation associated with intravenous steroids and recovered after 2 weeks. Further instrumental investigations lead to the final diagnosis of NEM as first presentation of eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome), remarking the importance of identifying the systemic disorder that usually triggers the eosinophilic damage of the myocardium.
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Venoarterial Extracorporeal Membrane Oxygenation for Acute Fulminant Myocarditis in Adult Patients: A 5-Year Multi-Institutional Experience.
Ann Thorac Surg2016 Mar;101(3):919-26. doi: 10.1016/j.athoracsur.2015.08.014.
Lorusso Roberto, Centofanti Paolo, Gelsomino Sandro, Barili Fabio, Di Mauro Michele, Orlando Parise, Botta Luca, Milazzo Filippo, Actis Dato Guglielmo, Casabona Riccardo, Casali Giovanni, Musumeci Francesco, De Bonis Michele, Zangrillo Alberto, Alfieri Ottavio, Pellegrini Carlo, Mazzola Sandro, Coletti Giuseppe, Vizzardi Enrico, Bianco Roberto, Gerosa Gino, Massetti Massimo, Caldaroni Federica, Pilato Emanuele, Pacini Davide, Di Bartolomeo Roberto, Marinelli Giuseppe, Sponga Sandro, Livi Ugolino, Mauro Rinaldi, Mariscalco Giovanni, Beghi Cesare, Miceli Antonio, Glauber Mattia, Pappalardo Federico, Russo Claudio Francesco,
Abstract
BACKGROUND:
Acute fulminant myocarditis (AFM) may represent a life-threatening event, characterized by rapidly progressive cardiac compromise that ultimately leads to refractory cardiogenic shock or cardiac arrest. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides effective cardiocirculatory support in this circumstance, but few clinical series are available about early and long-term results. Data from a multicenter study group are reported which analyzed subjects affected by AFM and treated with VA-ECMO during a 5-year period.
METHOD:
From hospital databases, 57 patients with diagnoses of AFM treated with VA-ECMO in the past 5 years were found and analyzed. Mean age was 37.6 ± 11.8 years; 37 patients were women. At VA-ECMO implantation, cardiogenic shock was present in 38 patients, cardiac arrest in 12, and severe hemodynamic instability in 7. A peripheral approach was used with 47 patients, whereas 10 patients had a central implantation or other access.
RESULTS:
Mean VA-ECMO support was 9.9 ± 19 days (range, 2 to 24 days). Cardiac recovery with ECMO weaning was achieved in 43 patients (75.5%), major complications were observed in 40 patients (70.1%), and survival to hospital discharge occurred in 41 patients (71.9%). After hospital discharge (median follow-up, 15 months) there were 2 late deaths. The 5-year actual survival was 65.2% ± 7.9%, with recurrent self-recovering myocarditis observed in 2 patients (at 6 and 12 months from the first AFM event), and 1 heart transplantation.
CONCLUSIONS:
Cardiopulmonary support with VA-ECMO provides an invaluable tool in the treatment of AFM, although major complications may characterize the hospital course. Long-term outcome appears favorable with rare episodes of recurrent myocarditis or cardiac-related events.
Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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CoreValve Evolut R implantation as valve-in-valve in an Edwards SAPIEN 3 to treat paravalvular regurgitation.
EuroIntervention2015 Sep;11(5):e1. doi: 10.4244/EIJV11I5A116.
Bruschi Giuseppe, Soriano Francesco, Musca Francesco, Nava Stefano, Einaudi Arturo, Garascia Andrea, Belli Oriana, Barosi Alberto, Fratto Pasquale, Colombo Paola, Russo Claudio Francesco, Gagliardone Maria Pia, Klugmann Silvio
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Rationale and design of GISSI OUTLIERS VAR Study in bicuspid aortic valve patients: prospective longitudinal, multicenter study to investigate correlation between surgical, echo distinctive features, histologic and genetic findings in phenotypically homogeneous outlier cases.
Int J Cardiol2015 Nov;199():180-5. doi: 10.1016/j.ijcard.2015.06.182.
Merlanti Bruno, De Chiara Benedetta, Maggioni Aldo Pietro, Moreo Antonella, Pileggi Silvana, Romeo Gabriella, Russo Claudio Francesco, Rizzo Stefania, Martinelli Luigi, Maseri Attilio,
Abstract
BACKGROUND/OBJECTIVES:
Bicuspid aortic valve (BAV) is the most common congenital heart disorder, affecting up to 2% of the population. Involvement of aortic root and ascending aorta (aneurysm or, eventually, dissection) is frequent in patients with pathologic or normal functioning BAV. Unfortunately, there are no well-known correlations between valvular and vascular diseases. In VAR protocol, with a new strategy of research, we analysemultiple aspects of BAV disease through correlation between surgical, echo, histologic and genetic findings in phenotypically homogeneous outlier cases.
METHODS:
VAR protocol is a prospective, longitudinal, multicenter study. It observes 4 homogeneous small groups of BAV surgical patients (15 patients each): isolated aortic regurgitation, isolated ascending aortic aneurysm, aortic regurgitation associated with aortic aneurysm, isolated aortic stenosis in older patients (>60years). Echo analysis is extended to first-degree relatives and, in case of BAV, genetic test is performed. Patients and relatives are enrolled in 10 cardiac surgery/cardiologic centers throughout Italy.
CONCLUSIONS:
The aim of the study is to identify predictors of favorable or unfavorable evolution of BAV in terms of valvular dysfunction and/or aortic aneurysm. Correlations between different features could help in identification of various BAV risk groups, rationalizing follow-up and treatment.
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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Cardiogenic shock: How to overcome a clinical dilemma. Unmet needs in Emergency medicine.
Int J Cardiol2015 ;186():19-21. doi: 10.1016/j.ijcard.2015.02.111.
Morici Nuccia, Sacco Alice, Paino Roberto, Oreglia Jacopo Andrea, Bottiroli Maurizio, Senni Michele, Nichelatti Michele, Canova Paolo, Russo Claudio, Garascia Andrea, Kulgmann Silvio, Frigerio Maria, Oliva Fabrizio
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Mid-term survival after continuous-flow left ventricular assist device versus heart transplantation.
Heart Vessels2016 May;31(5):722-33. doi: 10.1007/s00380-015-0654-4.
Ammirati Enrico, Oliva Fabrizio G, Colombo Tiziano, Russo Claudio F, Cipriani Manlio G, Garascia Andrea, Guida Valentina, Colombo Giulia, Verde Alessandro, Perna Enrico, Cannata Aldo, Paino Roberto, Martinelli Luigi, Frigerio Maria
Abstract
There is a paucity of data about mid-term outcome of patients with advanced heart failure (HF) treated with left ventricular assist device (LVAD) in Europe, where donor shortage and their aging limit the availability and the probability of success of heart transplantation (HTx). The aim of this study is to compare Italian single-centre mid-term outcome in prospective patients treated with LVAD vs. HTx. We evaluated 213 consecutive patients with advanced HF who underwent continuous-flow LVAD implant or HTx from 1/2006 to 2/2012, with complete follow-up at 1 year (3/2013). We compared outcome in patients who received a LVAD (n = 49) with those who underwent HTx (n = 164) and in matched groups of 39 LVAD and 39 HTx patients. Patients that were treated with LVAD had a worse risk profile in comparison with HTx patients. Kaplan-Meier survival curves estimated a one-year survival of 75.5 % in LVAD vs. 82.3 % in HTx patients, a difference that was non-statistically significant [hazard ratio (HR) 1.46; 95 % confidence interval (CI) 0.74-2.86; p = 0.27 for LVAD vs. HTx]. After group matching 1-year survival was similar between LVAD (76.9 %) and HTx (79.5 %; HR 1.15; 95 % CI 0.44-2.98; p = 0.78). Concordant data was observed at 2-year follow-up. Patients treated with LVAD as bridge-to-transplant indication (n = 22) showed a non significant better outcome compared with HTx with a 95.5 and 90.9 % survival, at 1- and 2-year follow-up, respectively. Despite worse preoperative conditions, survival is not significantly lower after LVAD than after HTx at 2-year follow-up. Given the scarce number of donors for HTx, LVAD therapy represents a valid option, potentially affecting the current allocation strategy of heart donors also in Europe.
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Italian multicentre study on type A acute aortic dissection: a 33-year follow-up?.
Eur J Cardiothorac Surg2016 Jan;49(1):125-31. doi: 10.1093/ejcts/ezv048.
Russo Claudio F, Mariscalco Giovanni, Colli Andrea, Santè Pasquale, Nicolini Francesco, Miceli Antonio, De Chiara Benedetta, Beghi Cesare, Gerosa Gino, Glauber Mattia, Gherli Tiziano, Nappi Gianantonio, Murzi Michele, Molardi Alberto, Merlanti Bruno, Vizzardi Enrico, Bonadei Ivano, Coletti Giuseppe, Carrozzini Massimiliano, Gelsomino Sandro, Caiazzo Antonio, Lorusso Roberto
Abstract
OBJECTIVES:
Despite substantial progress in surgical techniques and perioperative management, the treatment and long-term follow-up of type A acute aortic dissection (AAD) still remain a major challenge. The objective of this retrospective, multicentre study was to assess in a large series of patients the early and long-term results after surgery for type A AAD.
METHODS:
We analysed the preoperative, intraoperative and postoperative conditions of 1.148 consecutive patients surgically treated in seven large referral centres from 1981 to 2013. We applied to each patient three different multi-parameter risk profiles (preadmission risk, admission risk and post-surgery risk) in order to compare risk factors and outcome. Long-term Kaplan-Meier survival was evaluated.
RESULTS:
The median age was 64 years and the male population was predominant (66%). Identified diagnosis of collagen disease was present in 9%, and Marfan syndrome in 5%. Bicuspid aortic valve was present in 69 patients (6%). Previous cardiac surgery was identified in 10% of the patients. During surgery, the native aortic valve was preserved in 72% of the cases, including leaflet resuspension in 23% and David operation in 1.2%. Considering aortic valve replacement (AVR: 28%), bioprosthesis implantation was performed in 14.7% of the subjects. Neurological impairment at discharge was shown in 23% of the cases among which 21% of patients had new neurological impairment versus preoperative conditions. The overall 30-day mortality rate was 25.7%. All risk profiles remained independently associated with in-hospital mortality. During the available follow-up of hospital survivors (median: 70 months, interquartile range: 34-113, maximum: 396), cardiac-related death occurred in 7.9% of the subjects. The cumulative survival rate for cardiac death was 95.3% at 5 years, 92.8% at 10 years and 52.8% at 20 years. Severe aortic regurgitation (AR) (grade 3-4) at the time of surgery showed to be a significant risk factor for reintervention during the follow-up (P
CONCLUSIONS:
Although surgery for type A has remained challenging over more than three decades, there is a positive trend in terms of hospital mortality and long-term follow-up. About 90% of patients were free from reoperation in the long term, although late AR remains a critical issue, suggesting that a thorough debate on surgical options, assessment and results of a conservative approach should be considered.
© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
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Phylogeography and systematics of the westernmost Italian Dolichopoda species (Orthoptera, Rhaphidophoridae).
Zookeys2014 ;(437):1-23. doi: 10.3897/zookeys.437.7917.
Allegrucci Giuliana, Rampini Mauro, Di Russo Claudio, Lana Enrico, Cocchi Sara, Sbordoni Valerio
Abstract
The genus Dolichopoda (Orthoptera; Rhaphidopohoridae) is present in Italy with 9 species distributed from northwestern Italy (Piedmont and Liguria) to the southernmost Apennines (Calabria), occurring also in the Tyrrhenian coastal areas and in Sardinia. Three morphologically very close taxa have been described in Piedmont and Liguria, i.e., D. ligustica ligustica, D. ligustica septentrionalis and D. azami azami. To investigate the delimitation of the northwestern species of Dolichopoda, we performed both morphological and molecular analyses. Morphological analysis was carried out by considering diagnostic characters generally used to distinguish different taxa, as the shape of epiphallus in males and the subgenital fig in females. Molecular analysis was performed by sequencing three mitochondrial genes, 12S rRNA, 16S rRNA, partially sequenced and the entire gene of COI. Results from both morphological and molecular analyses highlighted a very homogeneous group of populations, although genetically structured. Three haplogroups geographically distributed could be distinguished and based on these results we suggest a new taxonomic arrangement. All populations, due to the priority of description, should be assigned to D. azami azami Saulcy, 1893 and to preserve the names ligustica and septentrionalis, corresponding to different genetic haplogroups, we assign them to D. azami ligustica stat. n. Baccetti & Capra, 1959 and to D. azami septentrionalis stat. n. Baccetti & Capra, 1959.
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Functional and biochemical interaction between PPAR? receptors and TRPV1 channels: Potential role in PPAR? agonists-mediated analgesia.
Pharmacol Res2014 Sep;87():113-22. doi: 10.1016/j.phrs.2014.06.015.
Ambrosino Paolo, Soldovieri Maria Virginia, De Maria Michela, Russo Claudio, Taglialatela Maurizio
Abstract
Transient receptor potential vanilloid type-1 (TRPV1) channels expressed in primary afferent neurons play a critical role in nociception triggered by endogenous and exogenous compounds. In the present study, the functional and biochemical interaction between TRPV1 channels and type-? peroxisome proliferator-activated receptors (PPAR?) has been investigated. In TRPV1-expressing CHO cells, patch-clamp studies revealed that acute application of the PPAR? agonists clofibrate (CLO; 0.1-100 ?M), WY14643 (1-300 ?M), or GW7647 (0.1-100 nM) activated TRPV1 currents in a concentration-dependent manner, with EC50s of 5.3 ± 0.8 ?M, 13.0 ± 1.2 ?M, and 12.7 ± 0.3 nM, respectively. The role of PPAR? in these pharmacological responses was confirmed by the ability of the PPAR? antagonist GW6471 (10 ?M) to block CLO-, WY14643- and GW7647-induced TRPV1 activation, and by the observation that modulation of PPAR? levels via siRNA-mediated suppression or PPAR? over-expression affected TRPV1 channel activation by PPAR? agonists accordingly. In cells cotransfected with PPAR? and TRPV1, PPAR? receptors were detected in TRPV1-immunoprecipitated fractions. When compared to capsaicin (CAP), TRPV1 currents activated by PPAR? agonists showed a higher degree of acute desensitization and tachyphylaxis; moreover, GW7647, when pre-incubated at a concentration (1nM) unable to activate TRPV1 currents per se, desensitized CAP-induced TRPV1 currents. Finally, a sub-effective concentration of each PPAR? agonist inhibited TRPV1-dependent bradykinin-induced [Ca(2+)]i transients in sensory neurons. Collectively, these results provide evidence for a PPAR?-mediated pathway triggering TRPV1 channel activation and desensitization, and highlight a novel mechanism which might contribute to the analgesic effects shown by PPAR? agonists in vivo.
Copyright © 2014 Elsevier Ltd. All rights reserved.
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High resolution 3-T MR imaging in the evaluation of the facial nerve course.
G Chir2014 ;35(1-2):15-9.
Cassetta M, Barchetti F, Pranno N, Barchetti G, Fioravanti C, Stagnitti A, Rubini A, Fioravanti E, Saccoliti E, Elia D, Rossignuolo M, Russo Claudio, Cantisani V, D'Andrea V
Abstract
OBJECTIVES:
To assess the value of 3-Tesla (3-T) MR imaging (MRI) in the evaluation of the course of the intracranial and extra-cranial tracts of the facial nerve.
PATIENTS AND METHODS:
83 patients were studied by MRI in order to detect the course of facial nerve; a total of 166 facial nerves were examined. T2-weighted 3D Fast imaging employing steady-state acquisition (FIESTA) and T1-weighted Fast spoiled gradient recalled echo (fast SPRG) sequences were used. Two radiologists (reader A and B), independently, evaluated the course of the tracts of the facial nerve according to a qualitative scale (excellent, good, fair, poor). The Intraclass Correlation Coefficient (ICC) and Pearson correlation coefficient were used to assess the intra-observer and interobserver variability in the nerve course evaluation.
RESULTS:
Reader A evaluated 35 facial nerves as excellent, 94 as good, 33 as fair and 4 as poor. Reader B rated 31 facial nerves excellent, 89 good, 43 fair and 3 poor. The intraobserver variability was ICC = 0.919 in reader A and ICC = 0.842 in reader B. The interobserver variability (Pearson correlation coefficient) was 0.713 (p ? 0.01).
CONCLUSIONS:
According to the preliminary results of our study the use of 3-T MRI with FIESTA and fast SPGR sequences may allow the study of the course of the facial nerve and its branches. The knowledge of the course and of the anatomic relationships of these nerve bundles with surrounding structures, as well as of the anatomical variants, provide useful informations for a prompt neurosurgery and maxillofacial surgical planning.
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Comparative study of aCGH and Next Generation Sequencing (NGS) for chromosomal microdeletion and microduplication screening.
J Prenat Med2014 ;8(3-4):57-69.
Russo Claudio Dello, Di Giacomo Gianluca, Cignini Pietro, Padula Francesco, Mangiafico Lucia, Mesoraca Alvaro, D'Emidio Laura, McCluskey Megan R, Paganelli Arianna, Giorlandino Claudio
Abstract
BACKGROUND:
prenatal genetic diagnosis of rare disorders is undergoing in recent years a significant enhancement through the application of methods of massive parallel sequencing. Despite the quantity and quality of the data produced, just few analytical tools and software have been developed in order to identify structural and numerical chromosomal anomalies through NGS, mostly not compatible with benchtop NGS platform and routine clinical diagnosis.
METHODS:
we developed technical, bioinformatic, interpretive and validation pipelines for Next Generation Sequencing to identify SNPs, indels, aneuploidies, and CNVs (Copy Number Variations).
RESULTS:
we show a new targeted resequencing approach applied to prenatal diagnosis. For sample processing we used an enrichment method for 4,813 genes library preparation; after sequencing our bioinformatic pipelines allowed both SNPs analysis for approximately thirty diseases or diseases family involved in fetus development and numerical chromosomal anomalies screening.
CONCLUSIONS:
results obtained are compatible with those obtained through the gold standard technique, aCGH array, moreover allowing identification of genes involved in chromosome deletions or duplications and exclusion of point mutation on allele not affected by chromosome aberrations.
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Adiponectin as novel regulator of cell proliferation in human glioblastoma.
J Cell Physiol2014 Oct;229(10):1444-54. doi: 10.1002/jcp.24582.
Porcile Carola, Di Zazzo Erika, Monaco Maria Ludovica, D'Angelo Giorgia, Passarella Daniela, Russo Claudio, Di Costanzo Alfonso, Pattarozzi Alessandra, Gatti Monica, Bajetto Adriana, Zona Gianluigi, Barbieri Federica, Oriani Giovannangelo, Moncharmont Bruno, Florio Tullio, Daniele Aurora
Abstract
Adiponectin (Acrp30) is an adipocyte-secreted hormone with pleiotropic metabolic effects, whose reduced levels were related to development and progression of several malignancies. We looked at the presence of Acrp30 receptors in human glioblastomas (GBM), hypothesizing a role for Acrp30 also in this untreatable cancer. Here we demonstrate that human GBM express Acrp30 receptors (AdipoR1 and AdipoR2), which are often co-expressed in GBM samples (70% of the analyzed tumors). To investigate the effects of Acrp30 on GBM growth, we used human GBM cell lines U87-MG and U251, expressing both AdipoR1 and AdipoR2 receptors. In these cells, Acrp30 treatment inhibits DNA synthesis and cell proliferation rate, inducing arrest in G1 phase of the cell cycle. These effects were correlated to a sustained activation of ERK1/2 and Akt kinases, upon Acrp30 treatment. Our results suggest that Acrp30 may represent a novel endogenous negative regulator of GBM cell proliferation, to be evaluated for the possible development of novel pharmacological approaches.
© 2014 Wiley Periodicals, Inc.
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Minimally invasive approach for redo mitral valve surgery.
J Thorac Dis2013 Nov;5 Suppl 6(Suppl 6):S686-93. doi: 10.3978/j.issn.2072-1439.2013.10.12.
Botta Luca, Cannata Aldo, Bruschi Giuseppe, Fratto Pasquale, Taglieri Corrado, Russo Claudio Francesco, Martinelli Luigi
Abstract
Redo cardiac surgery represents a clinical challenge due to a higher rate of peri-operative morbidity and mortality. Mitral valve re-operations can be particularly demanding in patients with patent coronary artery bypass grafts, previous aortic valve replacement, calcified aorta or complications following a previous operation (abscesses, perivalvular leaks, or thrombosis). Risk of graft injuries, hemorrhage, the presence of dense adhesions and complex valve exposure can make redo valve operations challenging through a median sternotomy. In this review article we provide an overview of minimally invasive approaches for redo mitral valve surgery discussing indications, techniques, outcomes, concerns and controversies. Scientific literature about minimally invasive approach for redo mitral surgery was reviewed with a MEDLINE search strategy combining "mitral valve" with the following terms: 'minimally invasive', 'reoperation', and 'alternative approach'. The search was limited to the last ten years. A total of 168 papers were found using the reported search. From these, ten papers were identified to provide the best evidence on the subject. Mitral valve reoperations can be safely and effectively performed through a smaller right thoracotomy in the fourth intercostal space termed "mini" thoracotomy or "port access". The greatest potential benefit of a right mini-thoracotomy is the avoidance of sternal re-entry and limited dissection of adhesions, avoiding the risk of injury to cardiac structures or patent grafts. Good percentages of valve repair can be achieved. Mortality is low as well as major complications. Minimally invasive procedures with an unclamped aorta have the potential to combine the benefits of minimally invasive access and continuous myocardial perfusion. Less invasive trans-catheter techniques could be considered as the natural future evolution for management of structural heart disease and mitral reoperations. The safety and efficacy of these procedures has never been compared to open reoperations in a randomized trial, although published case series and comparisons to historical cohorts suggest that they are an effective and feasible alternative. Ongoing follow-up on current series will further define these procedures and provide valuable clinical outcome data.
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Molecular systematics of the genus Troglophilus (Rhaphidophoridae, Orthoptera) in Turkey: mitochondrial 16S rDNA evidences.
Zookeys2013 ;(257):33-46. doi: 10.3897/zookeys.257.4133.
Taylan Mehmet Sait, Russo Claudio Di, Rampini Mauro, Ketmaier Valerio
Abstract
This study focuses on the evolutionary relationships among Turkish species of the cave cricket genus Troglophilus.Fifteen populations were studied for sequence variation in a fragment (543 base pairs) of the mitochondrial DNA (mtDNA) 16S rDNA gene (16S) to reconstruct their phylogenetic relationships and biogeographic history. Genetic data retrieved three main clades and at least three divergent lineages that could not be attributed to any of the taxa known for the area. Molecular time estimates suggest that the diversification of the group took place between the Messinian and the Plio-Pleistocene.
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Emergency ECMO support for acute LVAD failure.
Int J Cardiol2013 Jul;167(2):e41-2. doi: 10.1016/j.ijcard.2013.03.072.
Russo Claudio Francesco, Botta Luca, Lanfranconi Marco, De Marco Federico, Frigerio Maria, Paino Roberto, Martinelli Luigi
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Postsurgical intrapericardial adhesions: mechanisms of formation and prevention.
Ann Thorac Surg2013 May;95(5):1818-26. doi: 10.1016/j.athoracsur.2012.11.020.
Cannata Aldo, Petrella Duccio, Russo Claudio Francesco, Bruschi Giuseppe, Fratto Pasquale, Gambacorta Marcello, Martinelli Luigi
Abstract
Postsurgical intrapericardial adhesions are still considered an unavoidable consequence of cardiothoracic operations. They increase the technical difficulty and the risk of reoperations. The pathogenesis of postsurgical adhesions is a multistep process, and the main key players are (1) loss of mesothelial cells, (2) accumulation of fibrin in areas devoid of mesothelial cells, (3) loss of normal pericardial fibrinolysis, and (4) local inflammation. Today, very promising methods to reduce adhesions are available for clinical use. This report reviews the process of formation of adhesions and the methods to prevent them, classified according to the mechanism of action.
Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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A novel snRNA-like transcript affects amyloidogenesis and cell cycle progression through perturbation of Fe65L1 (APBB2) alternative splicing.
Biochim Biophys Acta2013 Jun;1833(6):1511-26. doi: 10.1016/j.bbamcr.2013.02.020.
Penna Ilaria, Vassallo Irene, Nizzari Mario, Russo Debora, Costa Delfina, Menichini Paola, Poggi Alessandro, Russo Claudio, Dieci Giorgio, Florio Tullio, Cancedda Ranieri, Pagano Aldo
Abstract
FE65 proteins constitute a family of adaptors which modulates the processing of amyloid precursor protein and the consequent amyloid ? production. Thus, they have been involved in the complex and partially unknown cascade of reactions at the base of Alzheimer's disease etiology. However, FE65 and FE65-like proteins may be linked to neurodegeneration through the regulation of cell cycle in post-mitotic neurons. In this work we disclose novel molecular mechanisms by which APBB2 can modulate APP processing. We show that APBB2 mRNA splicing, driven by the over-expression of a novel non-coding RNA named 45A, allow the generation of alternative protein forms endowed with differential effects on A? production, cell cycle control, and DNA damage response. 45A overexpression also favors cell transformation and tumorigenesis leading to a marked increase of malignancy of neuroblastoma cells. Therefore, our results highlight a novel regulatory pathway of considerable interest linking APP processing with cell cycle regulation and DNA-surveillance systems, that may represent a molecular mechanism to induce neurodegeneration in post-mitotic neurons.
Copyright © 2013 Elsevier B.V. All rights reserved.
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Histological findings following use of CoSeal in a patient with a left ventricular assist device.
Surg Innov2013 Dec;20(6):NP35-7. doi: 10.1177/1553350612443899.
Cannata Aldo, Petrella Duccio, Gambacorta Marcello, Russo Claudio F, Bruschi Giuseppe, Martinelli Luigi
Abstract
Adhesions are a formidable challenge in patients undergoing reoperative cardiac surgery, particularly in those supported by an intracorporeal left ventricular assist device (LVAD) and undergoing heart transplantation. This report describes the pathological findings following the clinical use of a surgical sealant (CoSeal, Baxter Healthcare, Fremont, CA), in a patient who underwent LVAD implantation. On the treated surfaces, a minimal amount of adhesions were observed, whereas in untreated surfaces adhesions were present.
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[Proposal for updated listing criteria for heart transplantation and indications to implant of left ventricular assist devices].
G Ital Cardiol (Rome)2013 Feb;14(2):110-9. doi: 10.1714/1218.13523.
Ammirati Enrico, Oliva Fabrizio, Colombo Tiziano, Botta Luca, Cipriani Manlio, Cannata Aldo, Verde Alessandro, Turazza Fabio M, Russo Claudio F, Paino Roberto, Martinelli Luigi, Frigerio Maria
Abstract
Heart transplantation (HTx) is considered to be the gold standard treatment for advanced heart failure (HF) but it is available only for a minority of patients, due to paucity of donor hearts (278 HTx were performed in 2011 in Italy). Patients listed for HTx have a prolonged waiting time (that is about 2.3 years in the 2006-2010 time period in Italy) that is superior compared with patients who receive HTx (median time around 6 months), to underline the presence of an allocation system that prioritizes candidates in critical conditions. Patients listed for HTx have a poor quality of life and their annual mortality is around 8-10%. Another 10-15% of HTx candidates are removed from the waiting list each year because they are no longer suitable for transplantation. On the other hand, continuous-flow left ventricular assist devices (LVADs) have been demonstrated to improve survival and quality of life of patients with advanced/refractory HF. LVAD therapy can represent a valid alternative to HTx, and it is recommended for patients with advanced HF in the recent edition of the European Society of Cardiology guidelines on HF management. In the United States, a larger number of centers compared with European ones started to apply a strategy of LVAD implant for many patients who meet clinical criteria for listing for HTx. Data from our center concerning the last 6 years of LVAD implant (51 implants since 2006) reported a 75.5% survival rate at 1 year. In Italian series, as in our center, current HTx survival is only slightly superior (83% survival rate at 1 year), based on data from the Italian National Transplant Center. We report a proposal for updated listing criteria for HTx and indications for LVAD implant in patients with advanced acute and chronic HF. Criteria for identifying suitable patients for HTx and/or LVAD considering the shortage of donors are discussed.
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Activation and desensitization of TRPV1 channels in sensory neurons by the PPAR? agonist palmitoylethanolamide.
Br J Pharmacol2013 Mar;168(6):1430-44. doi: 10.1111/bph.12029.
Ambrosino Paolo, Soldovieri Maria Virginia, Russo Claudio, Taglialatela Maurizio
Abstract
BACKGROUND AND PURPOSE:
Palmitoylethanolamide (PEA) is an endogenous fatty acid amide displaying anti-inflammatory and analgesic actions. To investigate the molecular mechanism responsible for these effects, the ability of PEA and of pain-inducing stimuli such as capsaicin (CAP) or bradykinin (BK) to influence intracellular calcium concentrations ([Ca²?](i)) in peripheral sensory neurons, has been assessed in the present study. The potential involvement of the transcription factor PPAR? and of TRPV1 channels in PEA-induced effects was also studied.
EXPERIMENTAL APPROACH:
[Ca²?](i) was evaluated by single-cell microfluorimetry in differentiated F11 cells. Activation of TRPV1 channels was assessed by imaging and patch-clamp techniques in CHO cells transiently-transfected with rat TRPV1 cDNA.
KEY RESULTS:
In F11 cells, PEA (1-30 ?M) dose-dependently increased [Ca²?](i). The TRPV1 antagonists capsazepine (1 ?M) and SB-366791 (1 ?M), as well as the PPAR? antagonist GW-6471 (10 ?M), inhibited PEA-induced [Ca²?](i) increase; blockers of cannabinoid receptors were ineffective. PEA activated TRPV1 channels heterologously expressed in CHO cells; this effect appeared to be mediated at least in part by PPAR?. When compared with CAP, PEA showed similar potency and lower efficacy, and caused stronger TRPV1 currents desensitization. Sub-effective PEA concentrations, closer to those found in vivo, counteracted CAP- and BK-induced [Ca²?](i) transients, as well as CAP-induced TRPV1 activation.
CONCLUSIONS AND IMPLICATIONS:
Activation of PPAR? and TRPV1 channels, rather than of cannabinoid receptors, largely mediate PEA-induced [Ca²?](i) transients in sensory neurons. Differential TRPV1 activation and desensitization by CAP and PEA might contribute to their distinct pharmacological profile, possibly translating into potentially relevant clinical differences.
© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
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An intronic ncRNA-dependent regulation of SORL1 expression affecting A? formation is upregulated in post-mortem Alzheimer's disease brain samples.
Dis Model Mech2013 Mar;6(2):424-33. doi: 10.1242/dmm.009761.
Ciarlo Eleonora, Massone Sara, Penna Ilaria, Nizzari Mario, Gigoni Arianna, Dieci Giorgio, Russo Claudio, Florio Tullio, Cancedda Ranieri, Pagano Aldo
Abstract
Recent studies indicated that sortilin-related receptor 1 (SORL1) is a risk gene for late-onset Alzheimer's disease (AD), although its role in the aetiology and/or progression of this disorder is not fully understood. Here, we report the finding of a non-coding (nc) RNA (hereafter referred to as 51A) that maps in antisense configuration to intron 1 of the SORL1 gene. 51A expression drives a splicing shift of SORL1 from the synthesis of the canonical long protein variant A to an alternatively spliced protein form. This process, resulting in a decreased synthesis of SORL1 variant A, is associated with impaired processing of amyloid precursor protein (APP), leading to increased A? formation. Interestingly, we found that 51A is expressed in human brains, being frequently upregulated in cerebral cortices from individuals with Alzheimer's disease. Altogether, these findings document a novel ncRNA-dependent regulatory pathway that might have relevant implications in neurodegeneration.
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Four new species of Dolichopoda Bolivar, 1880 from Southern Sporades and Western Turkey (Orthoptera, Rhaphidophoridae, Dolichopodainae).
Zookeys2012 ;(201):43-58. doi: 10.3897/zookeys.201.2609.
Rampini Mauro, Russo Claudio Di, Taylan Mehmet Sait, Gelosa Arianna, Cobolli Marina
Abstract
A description of four new species of Dolichopoda Bolivar, 1880 (Orthoptera, Rhaphidophoridae) from Eastern Aegean region (Southern Sporades), including Western Turkey, is reported. This brings to a total of 11 the number of Dolichopoda species recorded for caves of the Aegean area. Overall, these species show a high degree of morphological homogeneity and they are very close to Dolichopoda paraskevi Boudou-Saltet, 1973 from Crete and Dolichopoda naxia Boudou-Saltet, 1972 from Cyclades (Naxos Island). The Western Turkish species are morphologically not closely related to the other Anatolian species; this suggests an independent origin for the taxa occurring in the Southern Taurus and Black Sea regions. These new data help to better define the already high level of diversity of the Hellenic Dolichopoda and strengthen the hypothesis that the central area of dispersal for the genus would correspond to the ancient Aegean plate.
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NDM29, a RNA polymerase III-dependent non coding RNA, promotes amyloidogenic processing of APP and amyloid ? secretion.
Biochim Biophys Acta2012 Jul;1823(7):1170-7. doi: 10.1016/j.bbamcr.2012.05.001.
Massone Sara, Ciarlo Eleonora, Vella Serena, Nizzari Mario, Florio Tullio, Russo Claudio, Cancedda Ranieri, Pagano Aldo
Abstract
Neuroblastoma Differentiation Marker 29 (NDM29) is a RNA polymerase (pol) III-transcribed non-coding (nc) RNA whose synthesis drives neuroblastoma (NB) cell differentiation to a nonmalignant neuron-like phenotype. Since in this process a complex pattern of molecular changes is associated to plasma membrane protein repertoire we hypothesized that the expression of NDM29 might influence also key players of neurodegenerative pathways. In this work we show that the NDM29-dependent cell maturation induces amyloid precursor protein (APP) synthesis, leading to the increase of amyloid ? peptide (A?) secretion and the concomitant increment of A? x-42/A? x-40 ratio. We also demonstrate that the expression of NDM29 RNA, and the consequent increase of A? formation, can be promoted by inflammatory stimuli (and repressed by anti-inflammatory drugs). Moreover, NDM29 expression was detected in normal human brains although an abnormal increased synthesis of this ncRNA is induced in patients affected by neurodegenerative diseases. Therefore, the complex of events triggered by NDM29 expression induces a condition that favors the formation of A? peptides in the extracellular space, as it may occur in Alzheimer's Disease (AD). In addition, these data unexpectedly show that a pol III-dependent small RNA can act as key regulator of brain physiology and/or pathology suggesting that a better knowledge of this portion of the human transcriptome might provide hints for neurodegeneration studies.
Copyright © 2012 Elsevier B.V. All rights reserved.
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Severity of oxidative stress and inflammatory activation in end-stage heart failure patients are unaltered after 1 month of left ventricular mechanical assistance.
Cytokine2012 Jul;59(1):138-44. doi: 10.1016/j.cyto.2012.04.018.
Caruso Raffaele, Verde Alessandro, Campolo Jonica, Milazzo Filippo, Russo Claudio, Boroni Chiara, Parolini Marina, Trunfio Salvatore, Paino Roberto, Martinelli Luigi, Frigerio Maria, Parodi Oberdan
Abstract
This study investigates the impact of early left ventricular (LV)-mechanical unloading on systemic oxidative stress and inflammation in terminal heart failure patients and their impact both on multi organ failure and on intensive care unit (ICU) stay. Circulating levels of urinary 15-isoprostane-F(2t) (8-epi-PGF2(?)) and pro-inflammatory markers [plasma interleukin (IL)-6, IL-8, and urinary neopterin, a monocyte activation index] were analyzed in 20 healthy subjects, 22 stable end-stage heart failure (ESHF) patients and in 23 LV assist device (LVAD) recipients at pre-implant and during first post-LVAD (PL) month. Multi-organ function was evaluated by total Sequential Organ Failure Assessment (tSOFA) score. In LVAD recipients the levels of oxidative-inflammatory markers and tSOFA score were higher compared to other groups. After device implantation 8-epi-PGF2(?) levels were unchanged, while IL-6, and IL-8 levels increased during first week, and at 1month returned to pre-implant values, while neopterin levels increased progressively during LVAD support. The tSOFA score worsened at 1 PL-week with respect to pre-implant value, but improved at 1 PL-month. The tSOFA score related with IL-6 and IL-8 levels, while length of ICU stay related with pre-implant IL-6 levels. These data suggest that hemodynamic instability in terminal HF is associated to worsening of systemic inflammatory and oxidative milieu that do not improve in the early phase of hemodynamic recovery and LV-unloading by LVAD, affecting multi-organ function and length of ICU stay. This data stimulate to evaluate the impact of inflammatory signals on long-term outcome of mechanical circulatory support.
Copyright © 2012 Elsevier Ltd. All rights reserved.
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Neurodegeneration in Alzheimer disease: role of amyloid precursor protein and presenilin 1 intracellular signaling.
J Toxicol2012 ;2012():187297. doi: 187297.
Nizzari Mario, Thellung Stefano, Corsaro Alessandro, Villa Valentina, Pagano Aldo, Porcile Carola, Russo Claudio, Florio Tullio
Abstract
Alzheimer disease (AD) is a heterogeneous neurodegenerative disorder characterized by (1) progressive loss of synapses and neurons, (2) intracellular neurofibrillary tangles, composed of hyperphosphorylated Tau protein, and (3) amyloid plaques. Genetically, AD is linked to mutations in few proteins amyloid precursor protein (APP) and presenilin 1 and 2 (PS1 and PS2). The molecular mechanisms underlying neurodegeneration in AD as well as the physiological function of APP are not yet known. A recent theory has proposed that APP and PS1 modulate intracellular signals to induce cell-cycle abnormalities responsible for neuronal death and possibly amyloid deposition. This hypothesis is supported by the presence of a complex network of proteins, clearly involved in the regulation of signal transduction mechanisms that interact with both APP and PS1. In this review we discuss the significance of novel finding related to cell-signaling events modulated by APP and PS1 in the development of neurodegeneration.
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Does the cardioplegic solution have an effect on early outcomes following heart transplantation?
Eur J Cardiothorac Surg2012 Apr;41(4):e48-52; discussion e52-3. doi: 10.1093/ejcts/ezr321.
Cannata Aldo, Botta Luca, Colombo Tiziano, Russo Claudio F, Taglieri Corrado, Bruschi Giuseppe, Merlanti Bruno, Frigerio Maria, Martinelli Luigi
Abstract
OBJECTIVE:
The choice of cardioplegic solution for myocardial preservation in heart transplantation (HT) remains debated. We analysed our experience with three different cardioplegic solutions in adult HT performed during past 5 years, in terms of non-immunological intraoperative biventricular graft failure (BVF) and in-hospital mortality.
METHODS:
A total of 133 patients underwent HT at our hospital from January 2006 to December 2010. Patients were divided into three groups, according to the solution adopted in the donor: HTK-Custodiol (n = 61), Celsior (n = 38) and St Thomas (n = 34). For each patient, solution was chosen according to surgeon's preference.
RESULTS:
Recipient and donor mean age was 48.2 ± 12.7 and 43.8 ± 13.6 years, respectively. Twenty-four patients (18.0%) were in Status 1 at the transplant. The mean ischaemic time was 187.9 ± 52.6 min. Intraoperative BVF was observed in 18 cases (13.5%). Patients with BVF, and their respective donors, were older than the other patients (patients: 53.3 vs 47.4 years, P = 0.06; donors: 49.4 vs 42.9 years, P 0.06), and experienced significantly higher in-hospital mortality (47.3 vs 7.8%, P = 0.0001). The combination of patients aged 60 years or older with donors aged 60 years or older carried a mortality of 66.6% (6 out of 9). The three groups of patients did not differ significantly in terms of preoperative and intraoperative features and outcomes, including biventricular graft failure and death. At multivariate analysis, predictors of in-hospital death were a combination of both a recipient and a donor aged ? 60 years (OR 27.9), intraoperative BVF (OR 14.8) and previous cardiac surgery (OR 13.0). Cardioplegic solution did not predict mortality.
CONCLUSIONS:
We did not observe a significant effect of the kind of cardioplegic solution on the early HT outcomes. The combination between both a recipient and a donor aged ? 60 years, reoperation and BVF are strong predictors of in-hospital death.
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Emergency surgery for native mitral valve endocarditis: the impact of septic and cardiogenic shock.
Ann Thorac Surg2012 May;93(5):1469-76. doi: 10.1016/j.athoracsur.2011.11.025.
Gelsomino Sandro, Maessen Jos G, van der Veen Frederik, Livi Ugolino, Renzulli Attilio, Lucà Fabiana, Carella Rocco, Crudeli Elena, Rubino Antonio, Rostagno Carlo, Russo Claudio, Borghetti Valentino, Beghi Cesare, De Bonis Michele, Gensini Gian Franco, Lorusso Roberto
Abstract
BACKGROUND:
Limited information exists about the real impact of the etiology of shock on early and late outcome after emergency surgery in acute native mitral valve endocarditis (ANMVE). This multicenter study analyzed the impact of the etiology of shock on early and late outcome in patients with ANMVE.
METHODS:
Data were collected in eight institutions. Three hundred-seventy-nine ANMVE patients undergoing surgery on an emergency basis between May 1991 and December 2009 were eligible for the study. According to current criteria used for the differential diagnosis of shock, patients were retrospectively assigned to one of three groups: group 1, no shock (n=154), group 2, cardiogenic shock (CS [n=118]), and group 3, septic shock (SS [n=107]). Median follow-up was 69.8 months.
RESULTS:
Early mortality was significantly higher in patients with SS (p
CONCLUSIONS:
Our study suggests that emergency surgery for ANMVE in patients with CS achieved satisfactory early and late results. In contrast, the presence of SS was linked to dismal early prognosis. Our findings need to be confirmed by further larger studies.
Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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Amyloid-? protein precursor regulates phosphorylation and cellular compartmentalization of microtubule associated protein tau.
J Alzheimers Dis2012 ;29(1):211-27. doi: 10.3233/JAD-2011-101590.
Nizzari Mario, Barbieri Federica, Gentile Maria Teresa, Passarella Daniela, Caorsi Calentina, Diaspro Alberto, Taglialatela Maurizio, Pagano Aldo, Colucci-D'Amato Luca, Florio Tullio, Russo Claudio
Abstract
Tau is a multifunctional protein detected in different cellular compartments in neuronal and non-neuronal cells. When hyperphosphorylated and aggregated in atrophic neurons, tau is considered the culprit for neuronal death in familial and sporadic tauopathies. With regards to Alzheimer's disease (AD) pathogenesis, it is not yet established whether entangled tau represents a cause or a consequence of neurodegeneration. In fact, it is unquestionably accepted that amyloid-? protein precursor (A?PP) plays a pivotal role in the genesis of the disease, and it is postulated that the formation of toxic amyloid-? peptides from A?PP is the primary event that subsequently induces abnormal tau phosphorylation. In this work, we show that in the brain of AD patients there is an imbalance between the nuclear and the cytoskeletal pools of phospho-tau. We observed that in non-AD subjects, there is a stable pool of phospho-tau which remains strictly confined to neuronal nuclei, while nuclear localization of phospho-tau is significantly underrepresented in neurons of AD patients bearing neurofibrillary tangles. A specific phosphorylation of tau is required during mitosis in vitro and in vivo, likely via a Grb2-ERK1/2 signaling cascade. In differentiated neuronal A1 cells, the overexpression of A?PP modulates tau phosphorylation, altering the ratio between cytoskeletal and nuclear pools, and correlates with cell death. Altogether our data provide evidence that A?PP, in addition to amyloid formation, modulates the phosphorylation of tau and its subcellular compartmentalization, an event that may lead to the formation of neurofibrillary tangles and to neurodegeneration when occurring in postmitotic neurons.
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Type 2 diabetes mellitus is associated with faster degeneration of bioprosthetic valve: results from a propensity score-matched Italian multicenter study.
Circulation2012 Jan;125(4):604-14. doi: 10.1161/CIRCULATIONAHA.111.025064.
Lorusso Roberto, Gelsomino Sandro, Lucà Fabiana, De Cicco Giuseppe, Billè Giuseppe, Carella Rocco, Villa Emmanuel, Troise Gianni, Viganò Mario, Banfi Carlo, Gazzaruso Carmine, Gagliardotto Pier, Menicanti Lorenzo, Formica Francesco, Paolini Giovanni, Benussi Stefano, Alfieri Ottavio, Pastore Matteo, Ferrarese Sandro, Mariscalco Giovanni, Di Credico Germano, Leva Cristian, Russo Claudio, Cannata Aldo, Trevisan Roberto, Livi Ugolino, Scrofani Roberto, Antona Carlo, Sala Andrea, Gensini Gian Franco, Maessen Jos, Giustina Andrea
Abstract
BACKGROUND:
The present study was aimed at determining the impact of type 2 diabetes mellitus (DM) on postoperative bioprosthetic structural valve degeneration.
METHODS AND RESULTS:
Twelve Italian centers participated in the study. Patient data refer to bioprosthetic implantations performed from November 1988 to December 2009, which resulted in 6184 patients (mean age 71.3±5.4 years, 60.1% male) being enrolled. Of these patients, 1731 (27.9%) had type 2 DM. The propensity score-matching algorithm successfully matched 1113 patients with type 2 DM with the same number of no-DM patients. The postmatching standard differences were less than 0.1 for each of the covariates, and 64.2% of DM patients were matched. The early (30 days) mortality rate was 7.8% (n=87) versus 2.9% (n=33) in patients with or without type 2 DM (P
CONCLUSIONS:
Patients with type 2 DM undergoing bioprosthetic valve implantation are at high risk of early and long-term mortality, as well as of structural valve degeneration.
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Selection of candidate housekeeping genes for normalization in human postmortem brain samples.
Int J Mol Sci2011 ;12(9):5461-70. doi: 10.3390/ijms12095461.
Penna Ilaria, Vella Serena, Gigoni Arianna, Russo Claudio, Cancedda Ranieri, Pagano Aldo
Abstract
The most frequently used technique to study the expression profile of genes involved in common neurological disorders is quantitative real-time RT-PCR, which allows the indirect detection of very low amounts of selected mRNAs in tissue samples. Expression analysis by RT-qPCR requires an appropriate normalization to the expression level of genes characterized by a stable, constitutive transcription. However, the identification of a gene transcribed at a very stable level is difficult if not impossible, since significant fluctuations of the level of mRNA synthesis often accompanies changes of cell behavior. The aim of this study is to identify the most stable genes in postmortem human brain samples of patients affected by Alzheimer's disease (AD) suitable as reference genes. The experiments analyzed 12 commonly used reference genes in brain samples from eight individuals with AD and seven controls. After a careful analysis of the results calculated by geNorm and NormFinder algorithms, we found that CYC1 and EIF4A2 are the best reference genes. We remark on the importance of the determination of the best reference genes for each sample to be analyzed and suggest a practical combination of reference genes to be used in the analysis of human postmortem samples.
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The "Alzheimer's disease signature": potential perspectives for novel biomarkers.
Immun Ageing2011 Sep;8():7. doi: 10.1186/1742-4933-8-7.
Davinelli Sergio, Intrieri Mariano, Russo Claudio, Di Costanzo Alfonso, Zella Davide, Bosco Paolo, Scapagnini Giovanni
Abstract
Alzheimer's disease is a progressive and neurodegenerative disorder which involves multiple molecular mechanisms. Intense research during the last years has accumulated a large body of data and the search for sensitive and specific biomarkers has undergone a rapid evolution. However, the diagnosis remains problematic and the current tests do not accurately detect the process leading to neurodegeneration. Biomarkers discovery and validation are considered the key aspects to support clinical diagnosis and provide discriminatory power between different stages of the disorder. A considerable challenge is to integrate different types of data from new potent approach to reach a common interpretation and replicate the findings across studies and populations. Furthermore, long-term clinical follow-up and combined analysis of several biomarkers are among the most promising perspectives to diagnose and manage the disease. The present review will focus on the recent published data providing an updated overview of the main achievements in the genetic and biochemical research of the Alzheimer's disease. We also discuss the latest and most significant results that will help to define a specific disease signature whose validity might be clinically relevant for future AD diagnosis.
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Relationship between myocardial redox state and matrix metalloproteinase activity in patients on left ventricular assist device support.
Circ J2011 ;75(10):2387-96.
Caruso Raffaele, Caselli Chiara, Boroni Chiara, Campolo Jonica, Milazzo Filippo, Cabiati Manuela, Russo Claudio, Parolini Marina, Giannessi Daniela, Frigerio Maria, Parodi Oberdan
Abstract
BACKGROUND:
Redox aminothiols have been reported to modulate the activity of recombinant metalloproteinases (MMP). The aim of the present study was to investigate the effects of myocardial redox state on the activities of MMP-2 and -9 implicated in cardiac remodeling in end-stage heart failure patients supported by left ventricular assist device (LVAD).
METHODS AND RESULTS:
During heart transplant (HT) surgery, myocardial specimens (MS) from right ventricular walls and LV walls were obtained from 7 LVAD recipients (LVAD group, MS n=35) and from 7 stable HT candidates on medical therapy (MT group, MS n=35). Myocardial MMP-2 and -9 activities and expression, tissue inhibitor of MMP (TIMP)-1 and -4, transforming growth factor (TGF)-?1 and aminothiol concentrations were measured. MMP-2 and -9 activities were evaluated also by incubating MS with different amounts of reduced and oxidized glutathione (GSH). MMP-2 and -9 activities and expression were lower in the LVAD group, whereas myocardial TIMP-1 and -4 concentrations were comparable to those of MT patients. Higher GSH and TGF-?1 concentrations were found in LVAD-recipients. Only GSH concentrations were inversely related to MMP-2 and -9 activities. In vitro, GSH had an inhibitory effect on MMP-2 and -9 activities.
CONCLUSIONS:
LVAD recipients show reduced myocardial MMP-2 and -9 activities and expression when compared to medically treated patients. Changes of myocardial redox state, predominantly GSH-dependent, appear to modulate MMP-2 and -9 activities by an inhibitory effect dependent on thiol content. These data support a role of GSH cycle in modulating the extracellular matrix in end-stage heart failure patients supported by LVAD.
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RNA polymerase III drives alternative splicing of the potassium channel-interacting protein contributing to brain complexity and neurodegeneration.
J Cell Biol2011 May;193(5):851-66. doi: 10.1083/jcb.201011053.
Massone Sara, Vassallo Irene, Castelnuovo Manuele, Fiorino Gloria, Gatta Elena, Robello Mauro, Borghi Roberta, Tabaton Massimo, Russo Claudio, Dieci Giorgio, Cancedda Ranieri, Pagano Aldo
Abstract
Alternative splicing generates protein isoforms that are conditionally or differentially expressed in specific tissues. The discovery of factors that control alternative splicing might clarify the molecular basis of biological and pathological processes. We found that IL1-?-dependent up-regulation of 38A, a small ribonucleic acid (RNA) polymerase III-transcribed RNA, drives the synthesis of an alternatively spliced form of the potassium channel-interacting protein (KCNIP4). The alternative KCNIP4 isoform cannot interact with the ?-secretase complex, resulting in modification of ?-secretase activity, amyloid precursor protein processing, and increased secretion of ?-amyloid enriched in the more toxic A? x-42 species. Notably, synthesis of the variant KCNIP4 isoform is also detrimental to brain physiology, as it results in the concomitant blockade of the fast kinetics of potassium channels. This alternative splicing shift is observed at high frequency in tissue samples from Alzheimer's disease patients, suggesting that RNA polymerase III cogenes may be upstream determinants of alternative splicing that significantly contribute to homeostasis and pathogenesis in the brain.
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Veno-arterial extracorporeal membrane oxygenation using Levitronix centrifugal pump as bridge to decision for refractory cardiogenic shock.
J Thorac Cardiovasc Surg2010 Dec;140(6):1416-21. doi: 10.1016/j.jtcvs.2010.07.083.
Russo Claudio F, Cannata Aldo, Lanfranconi Marco, Bruschi Giuseppe, Milazzo Filippo, Paino Roberto, Martinelli Luigi
Abstract
OBJECTIVES:
Cardiogenic shock still carries a very high mortality. We adopted veno-arterial extracorporeal membrane oxygenation using the Levitronix centrifugal pump (Levitronix LLC, Waltham, Massachusetts) as a first-line treatment of cardiogenic shock in a "bridge to decision" strategy. This article provides our experience of this clinical approach.
METHODS:
Since 1988, 160 ventricular assist devices have been implanted at our hospital for heart failure. Since 2005, 15 consecutive patients have been treated with veno-arterial extracorporeal membrane oxygenation for refractory cardiogenic shock. Veno-arterial extracorporeal membrane oxygenation has been implanted either centrally or peripherally.
RESULTS:
Mean age was 44.7 ± 20.0 years (2-78 years). There were 5 women. Veno-arterial extracorporeal membrane oxygenation was implanted peripherally in 8 cases (53.4%) and centrally in the remaining 7 (46.6%). Mean veno-arterial extracorporeal membrane oxygenation duration was 11.5 ± 8.1 days (range, 1-30). No patient experienced any neurologic event or vascular complication at the cannulation site. Twelve patients (80%) were weaned from veno-arterial extracorporeal membrane oxygenation or bridged to either a long-term left ventricular assist device or heart transplantation. Three patients died during veno-arterial extracorporeal membrane oxygenation support secondary to multi-organ failure. Seven patients (46.6%) were discharged from the hospital, with a 100% survival at follow-up. The survivors include 2 patients affected by fulminant myocarditis, who were bridged to recovery, and 5 patients who were bridged to heart transplantation. Survivors were younger than nonsurvivors (mean age, 28.5 vs 58.8 years, respectively).
CONCLUSIONS:
In our experience, the use of veno-arterial extracorporeal membrane oxygenation as bridge to decision has been effective to promptly restore adequate systemic perfusion, allowing further time to evaluate myocardial recovery or candidacy for ventricular assist device or heart transplantation. Younger patients, with no or mild end-organ injury, had the best outcomes. Peripheral cannulation decreases the surgical trauma and makes emergency implantation possible, even in the intensive care unit.
Copyright © 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
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17A, a novel non-coding RNA, regulates GABA B alternative splicing and signaling in response to inflammatory stimuli and in Alzheimer disease.
Neurobiol Dis2011 Feb;41(2):308-17. doi: 10.1016/j.nbd.2010.09.019.
Massone Sara, Vassallo Irene, Fiorino Gloria, Castelnuovo Manuele, Barbieri Federica, Borghi Roberta, Tabaton Massimo, Robello Mauro, Gatta Elena, Russo Claudio, Florio Tullio, Dieci Giorgio, Cancedda Ranieri, Pagano Aldo
Abstract
Alternative splicing is a central component of human brain complexity; nonetheless, its regulatory mechanisms are still largely unclear. In this work, we describe a novel non-coding (nc) RNA (named 17A) RNA polymerase (pol) III-dependent embedded in the human G-protein-coupled receptor 51 gene (GPR51, GABA B2 receptor). The stable expression of 17A in SHSY5Y neuroblastoma cells induces the synthesis of an alternative splicing isoform that abolish GABA B2 intracellular signaling (i.e., inhibition of cAMP accumulation and activation of K(+) channels). Indeed, 17A is expressed in human brain, and we report that it is upregulated in cerebral tissues derived from Alzheimer disease patients. We demonstrate that 17A expression in neuroblastoma cells enhances the secretion of amyloid ? peptide (A?) and the A? x-42/?? x-40 peptide ratio and that its synthesis is induced in response to inflammatory stimuli. These data correlate, for the first time, the activity of a novel pol III-dependent ncRNA to alternative splicing events and, possibly, to neurodegeneration induced by abnormal GABA B function. We anticipate that further analysis of pol III-dependent regulation of alternative splicing will disclose novel regulatory pathways associated to brain physiology and/or pathology.
Copyright © 2010 Elsevier Inc. All rights reserved.
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Relationship between bicuspid aortic valve morphology and aortic wall degeneration: further evidence is emerging.
Echocardiography2010 Sep;27(8):1028; author reply 1029. doi: 10.1111/j.1540-8175.2010.01265.x.
Cannata Aldo, Russo Claudio Francesco, Martinelli Luigi
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Destruction of the tricuspid septal leaflet: correction by bicuspidization.
Ann Thorac Surg2010 Sep;90(3):1028-9. doi: 10.1016/j.athoracsur.2009.10.075.
Russo Claudio F, Cannata Aldo, Lanfranconi Marco, Martinelli Luigi
Abstract
We describe a surgical technique to repair severe tricuspid valve regurgitation secondary to loss of the septal leaflet. Tricuspid valve competency is obtained by means of mobilization of the anterior and posterior leaflets.
2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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Cavernous hemangioma replacing the septal leaflet of the tricuspid valve.
J Card Surg2010 Sep;25(5):524-7. doi: 10.1111/j.1540-8191.2010.01064.x.
Cannata Aldo, Russo Claudio F, Merlanti Bruno, Pedrotti Patrizia, Moreo Antonella, Botta Luca, Martinelli Luigi
Abstract
Heart valve hemangioma is a rare finding. Here, we report a case of a hemangioma completely replacing the septal leaflet of the tricuspid valve. Preoperative imaging studies and operative anatomy are described.
© 2010 Wiley Periodicals, Inc.
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Early expression of pro- and anti-inflammatory cytokines in left ventricular assist device recipients with multiple organ failure syndrome.
ASAIO J2010 ;56(4):313-8. doi: 10.1097/MAT.0b013e3181de3049.
Caruso Raffaele, Trunfio Salvatore, Milazzo Filippo, Campolo Jonica, De Maria Renata, Colombo Tiziano, Parolini Marina, Cannata Aldo, Russo Claudio, Paino Roberto, Frigerio Maria, Martinelli Luigi, Parodi Oberdan
Abstract
To assess whether the combined evaluation of total Sequential Organ Failure Assessment (t-SOFA) score and pro- and anti-inflammatory cytokine profiles early after left ventricular assist device (LVAD) implant discriminates patients at high risk for multiple organ failure syndrome (MOFS) in the first month post-LVAD, we analyzed plasma interleukin (IL)-6, IL-8, IL-10, IL-1ra, IL-1beta, tumor necrosis factor-alpha (TNF-alpha), and urine neopterin levels before (day 0) and at 4 hours, 1, 3, 7, 14, and 30 days after LVAD implant in 23 recipients. Eight patients died of MOFS between days 7 and 30 (nonsurvivors). At preimplant, only blood urea nitrogen and age were higher in nonsurvivors than survivors. At 4 hours, IL-8, IL-10, and IL1-ra levels were higher in nonsurvivors than in survivors; t-SOFA was also higher and peaked on day 3 in nonsurvivors. Only IL-8 levels on day 1 were significantly associated with a t-SOFA > or =10 on day 3 (odds ratio 1.10, 95% confidence interval 1.01-1.21, p = 0.04). Neopterin, marker of monocyte activation, increased significantly only in nonsurvivors (p
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Efficacy of novel acridine derivatives in the inhibition of hPrP90-231 prion protein fragment toxicity.
Neurotox Res2011 May;19(4):556-74. doi: 10.1007/s12640-010-9189-8.
Villa Valentina, Tonelli Michele, Thellung Stefano, Corsaro Alessandro, Tasso Bruno, Novelli Federica, Canu Caterina, Pino Albiana, Chiovitti Katia, Paludi Domenico, Russo Claudio, Sparatore Anna, Aceto Antonio, Boido Vito, Sparatore Fabio, Florio Tullio
Abstract
Quinacrine is one of the few molecules tested to treat patients affected by prion diseases, although the clinical outcome is largely unsatisfactory. To identify novel derivatives with higher neuroprotective activity, we evaluated the effects of a small library of acridine derivatives. The 6-chloro-2-methoxyacridine derivatives bearing on position 9 a quinolizidin-1-ylamino (Q1, Q2) or a quinolizidin-1-ylalkylamino residue (Q3, Q4, Q6, Q7), the thio-bioisoster of Q3 (Q5), the 9-(N-lupinylthiopropyl)amino derivative (Q8) and simple acridines (Q9 and Q10) were considered. We compared the effects of quinacrine and these novel analogues in the inhibition of the cytotoxic activity and protease K (PK) resistance of the human prion protein fragment 90-231 (hPrP90-231). We demonstrate that quinacrine caused a significant reduction of hPrP90-231 toxicity due to its binding to the fragment and the prevention of its conversion in a toxic isoform. All acridine derivatives analyzed showed high affinity binding for hPrP90-231, but only Q3 and Q10, caused a significant reduction of hPrP90-231 cytotoxicity, with higher efficacy than quinacrine. We attempted to correlate the cytoprotective effects of the new compounds with some biochemical parameters (binding affinity to hPrP90-231, intrinsic fluorescence quenching, hydrophobic amino acid exposure), but a direct relationship occurred only with the reduction of PK resistance, likely due to the prevention of the acquisition of the ?-sheet-rich toxic conformation. These data represent interesting leads for further modifications of the basic side chain and the substituent pattern of the acridine nucleus to develop novel compounds with improved antiprion activity to be tested in in vivo experimental setting.
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Impact of prophylactic intra-aortic balloon counter-pulsation on postoperative outcome in high-risk cardiac surgery patients: a multicentre, propensity-score analysis.
Eur J Cardiothorac Surg2010 Nov;38(5):585-91. doi: 10.1016/j.ejcts.2010.03.017.
Lorusso Roberto, Gelsomino Sandro, Carella Rocco, Livi Ugolino, Mariscalco Giovanni, Onorati Francesco, Russo Claudio, Renzulli Attilio
Abstract
OBJECTIVE:
The aim of this multicentre study was to determine whether the prophylactic use of intra-aortic balloon pump (IABP) translates into better early and long-term results in high-risk patients undergoing cardiac surgery.
METHODS:
From January 2000 to March 2009, 6121 high-risk patients (EuroSCORE >8), at six different institutions, underwent cardiac surgery. Propensity-score computer matching was performed, based on 10 variables representing patients characteristics and preoperative risk factors to correct for and minimise selection bias (Hosmer-Lemeshow goodness of fit, p=0.3; c=0.94). A total of 956 patients were successfully matched and consisted of 478 pairs either undergoing preoperative IABP (group A) or not receiving IABP preoperatively (group B).
RESULTS:
Multivariate logistic regression (odds ratio) revealed that group B had a 64% higher risk of in-hospital mortality (p=0.001), 57% higher risk of 30-day mortality (p=0.003), 45% higher risk of perioperative myocardial infarction (p=0.01), 57% higher risk of postoperative low-output syndrome (p=0.003), 45% higher risk of intensive care unit (ICU) length of stay (p=0.001) and 44% higher risk of hospital length of stay (p=0.001). Patients in group A showed, at follow-up, significant improvements in left ventricular (LV) ejection fraction (p
CONCLUSIONS:
Prophylactic IABP support, in this multicentre experience, was showed to enhance perioperative management and outcome of high-risk cardiac surgery patients.
Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.
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Persistent increase of D-aspartate in D-aspartate oxidase mutant mice induces a precocious hippocampal age-dependent synaptic plasticity and spatial memory decay.
Neurobiol Aging2011 Nov;32(11):2061-74. doi: 10.1016/j.neurobiolaging.2009.12.007.
Errico Francesco, Nisticò Robert, Napolitano Francesco, Oliva Alessandra Bonito, Romano Rosaria, Barbieri Federica, Florio Tullio, Russo Claudio, Mercuri Nicola B, Usiello Alessandro
Abstract
The atypical amino acid d-aspartate (d-Asp) occurs at considerable amounts in the developing brain of mammals. However, during postnatal life, d-Asp levels diminish following the expression of d-aspartate oxidase (DDO) enzyme. The strict control of DDO over its substrate d-Asp is particularly evident in the hippocampus, a brain region crucially involved in memory, and highly vulnerable to age-related deterioration processes. Herein, we explored the influence of deregulated higher d-Asp brain content on hippocampus-related functions during aging of mice lacking DDO (Ddo(-/-)). Strikingly, we demonstrated that the enhancement of hippocampal synaptic plasticity and cognition in 4/5-month-old Ddo(-/-) mice is followed by an accelerated decay of basal glutamatergic transmission, NMDAR-dependent LTP and hippocampus-related reference memory at 13/14 months of age. Therefore, the precocious deterioration of hippocampal functions observed in mutants highlights for the first time a role for DDO enzyme in controlling the rate of brain aging process in mammals.
Copyright © 2009 Elsevier Inc. All rights reserved.
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Initial results of clinical trial with a new left ventricular assist device (LVAD) providing synchronous pulsatile flow.
Int J Artif Organs2009 Jun;32(6):344-53.
Gazzoli Fabrizio, Viganò Mario, Pagani Francesco, Alloni Alessia, Silvaggio Giuseppe, Panzavolta Marco, El Banayosy Aly, Koerfer Reiner, Morshuis Michiel, Pavie Alain, Leprince Pascal, Glauber Mattia, Del Sarto Paolo, Haxhademi Dorela, Vitali Ettore, Russo Claudio F, Scuri Silvia
Abstract
OBJECTIVES:
A multicentric European Clinical Study is ongoing to evaluate safety and efficacy of a new pulsatile implantable LVAD (BestBeat), smaller and lighter than similar devices, capable of providing synchronous and counterpulsating flow with respect to the LV of end-stage heart failure patients. Preliminary clinical results are reported.
METHODS:
The new BestBeat LVAD was used, consisting of an implantable pulsatile blood pump, electromechanically driven by a ball screw mechanism, and a wearable electronic controller and power sources. The clinical trial was conducted at 5 european centers. Adult patients affected by CHF in NYHA Class IV despite optimized medical treatment were enrolled. The primary study endpoint was survival at 90 days. Further study endpoints were maintenance of adequate LVAD pump flow and a minimum rate of adverse events during support.
RESULTS:
As of June 2008, 6 patients received the implant. Cumulative support time was 3.7 years, median support time 176 days. All patients who completed the study survived except for one, who died after 48 days, due to combined infection and cerebrovascular accident. Another two patients died: one from intracranial bleeding 113 days after implant, and one from septic shock after 123 days. Hemodynamic improvement with CI>2.0 l/min/m2 and recovery of end-organ function expressed by consistent improvement of BUN, creatinine and bilirubin were reached in all patients. No device failure was observed. There was no bleeding requiring re-exploration, no hemolysis and only two device-related infections (both in one patient). Neurologic events were reported, the most serious ones occurring in patients with pre-implant respiratory and kidney failure. Three patients were discharged home. Two patients were successfully transplanted, one after 6 months and one after 13 months on device.
CONCLUSIONS:
Good performance and efficacy of the device were observed; the endpoints of the study were achieved, and its safety was consistent with expectations. The ongoing study will allow further conclusions to be drawn.
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[Nutritional status of elderly institutionalized subjects in a health district in Frosinone (Italy)].
Ig Sanita Pubbl2009 ;65(1):17-28.
Langiano Elisa, Di Russo Claudio, Atrei Patrizia, Ferrara Maria, Allegretti Vincenzo, Verdicchio Immacolata, De Vito Elisabetta
Abstract
In recent years there has been a constant increase in the number of elderly people being admitted to nursing homes. Elderly nursing home residents seem to have a higher risk of malnutrition with respect to the community dwelling elderly population. A study was therefore performed to evaluate the nutritional status of elderly subjects living in 8 nursing homes in the "D" health district in Frosinone (Italy). Subjects aged over 65 years living in one of the selected nursing homes since at least two months were invited to participate. Nutritional status was evaluated by anthropometric measurements to calculate the Body Mass Index and by data collected through the Mini Nutritional Assessment. Additional data regarding the subject's educational level, social life, family ties, length of stay in the facility, physical activity, medical conditions, frequency of diarrhoeal episodes and eating habits, were collected through a questionnaire. Statistical analysis of data was performed with Epi Info software version 3.3 One hundred eighty four subjects participated in the study, 69.4% of which had been admitted to the nursing home following a request by their family, mainly for health reasons or because the family could no longer take care of them. Approximately 38% of subjects admitted having a moderate decrease in functional independence. The mean BMI was found to be 27.3 while the mean MNA was 20.6, with no sex- or age-related differences. The prevalence of underweight based on BMI threshold values was 6.3%; 30.8% of subjects were normal weight. On the other hand, MNA results revealed that 13% of study subjects were malnourished and 66.1% were at risk for malnutrition. These results indicate that assessment of nutritional status in elderly subjects should not be based on BMI alone and that MNA is a more appropriate tool in the elderly as it allows for a dynamic evaluation of the risk of malnutrition in this population. The results of this study also show a high risk of malnutrition in the study sample, and confirm the need for increased surveillance of nutritional status among residents of nursing homes.
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Use of CoSeal in a patient with a left ventricular assist device.
Ann Thorac Surg2009 Jun;87(6):1956-8. doi: 10.1016/j.athoracsur.2008.10.042.
Cannata Aldo, Taglieri Corrado, Russo Claudio F, Bruschi Giuseppe, Martinelli Luigi
Abstract
A 45-year-old man with end-stage idiopathic dilatated cardiomyopathy had previously undergone two left anterolateral thoracotomies for implantation and explantation of a left ventricular epicardial lead for biventricular pacing. Because of worsening heart failure and a predicted long delay to heart transplantation, a left-ventricular assist device was implanted, with application of CoSeal surgical sealant (Baxter Healthcare Corp, Fremont, CA) on the cardiac surface. At re-sternotomy for heart transplantation, surgical dissection of the left-ventricular assist device was greatly facilitated by the presence of avascular, very loose adhesions. CoSeal (Baxter Healthcare Corp) seems to be useful for the inhibition of adhesion formation after left-ventricular assist device implantation, although further clinical experience with this approach is required.
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Technique to prevent inadvertent paramedian sternotomy.
J Card Surg2009 ;24(3):290-1. doi: 10.1111/j.1540-8191.2009.00830.x.
Cannata Aldo, Russo Claudio Francesco, Vitali Ettore, Bruschi Giuseppe
Abstract
Previous reports documented the relationship between inadvertent paramedian sternotomy and postoperative sternal instability and dehiscence.We describe a modification of the technique of median sternotomy in order to prevent inadvertent paramedian sternotomy and related wound complications.
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Dual modulation of ERK1/2 and p38 MAP kinase activities induced by minocycline reverses the neurotoxic effects of the prion protein fragment 90-231.
Neurotox Res2009 Feb;15(2):138-54. doi: 10.1007/s12640-009-9015-3.
Corsaro Alessandro, Thellung Stefano, Chiovitti Katia, Villa Valentina, Simi Alessandro, Raggi Federica, Paludi Domenico, Russo Claudio, Aceto Antonio, Florio Tullio
Abstract
Several in vitro and in vivo studies addressed the identification of molecular determinants of the neuronal death induced by PrP(Sc) or related peptides. We developed an experimental model to assess PrP(Sc) neurotoxicity using a recombinant polypeptide encompassing amino acids 90-231 of human PrP (hPrP90-231) that corresponds to the protease-resistant core of PrP(Sc) identified in prion-infected brains. By means of mild thermal denaturation, we can convert hPrP90-231 from a PrP(C)-like conformation into a PrP(Sc)-like structure. In virtue of these structural changes, hPrP90-231 powerfully affected the survival of SH-SY5Y cells, inducing caspase 3 and p38-dependent apoptosis, while in the native alpha-helix-rich conformation, hPrP90-231 did not induce cell toxicity. The aim of this study was to identify drugs able to block hPrP90-231 neurotoxic effects, focusing on minocycline, a tetracycline with known neuroprotective activity. hPrP90-231 caused a caspase 3-dependent apoptosis via the blockade of ERK1/2 activation and the subsequent activation of p38 MAP kinase. We propose that hPrP90-231-induced apoptosis is dependent on the inhibition of ERK1/2 responsiveness to neurotrophic factors, removing a tonic inhibition of p38 activity and resulting in caspase 3 activation. Minocycline prevented hPrP90-231-induced toxicity interfering with this mechanism: the pretreatment with this tetracycline restored ERK1/2 activity and reverted p38 and caspase 3 activities. The effects of minocycline were not mediated by the prevention of hPrP90-231 structural changes or cell internalization (differently from Congo Red). In conclusion, minocycline elicits anti-apoptotic effects against the neurotoxic activity of hPrP90-231 and these effects are mediated by opposite modulation of ERK1/2 and p38 MAP kinase activities.
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Prevention of limb ischemia and edema during peripheral venoarterial extracorporeal membrane oxygenation in adults.
J Card Surg2009 ;24(2):185-7. doi: 10.1111/j.1540-8191.2009.00829.x.
Russo Claudio F, Cannata Aldo, Vitali Ettore, Lanfranconi Marco
Abstract
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a mechanical circulatory support indicated for the advanced treatment of refractory heart failure. The cannulation of the femoral vessels may be complicated by distal limb ischemia by arterial hypoperfusion and severe edema by venous obstruction. We describe a modified cannulation technique in order to prevent ischemia and edema of the inferior limb during VA-ECMO.
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Atorvastatin attenuates post-implant tissue degeneration of cardiac prosthetic valve bovine pericardial tissue in a subcutaneous animal model.
Int J Cardiol2010 May;141(1):68-74. doi: 10.1016/j.ijcard.2008.11.174.
Lorusso Roberto, Corradi Domenico, Maestri Roberta, Bosio Silvia, Curulli Alessandra, Beghi Cesare, Gerometta Piersilvio, Russo Claudio, Gelsomino Sandro, Moreo Antonella, De Cicco Giuseppe, Rosano Giuseppe, Volterrani Maurizio
Abstract
AIMS:
The aim of our study was to examine the effects of statin therapy (atorvastatin) on post-implant structural changes of bovine pericardial tissue in a subcutaneous animal model.
METHODS AND RESULTS:
Sixty male C57BL/6 mice underwent subcutaneous dorsal implantation of bovine pericardial fragments. Animals were randomized to treatment with atorvastatin (50 mg/kg) (statin group - SG) or to vehicle (control group - CG). After 1.5 months, all fragments were explanted and submitted to histopathological assessment (semi-quantitative analysis) to elucidate extent of inflammatory infiltrate, signs of tissue injury, or presence of microcalcification. Calcium determination of the implanted pericardial tissue was also performed by inductively coupled plasma mass spectrometry (ICP-MS) assessment. ICP-MS analysis showed that pericardial fragments in SG had significantly (p
CONCLUSIONS:
Our findings indicate that atorvastatin significantly attenuates the post-implant structural degeneration of artificial valve bovine pericardial tissue in a subcutaneous animal model. Further observations are mandatory to assess the effects of statins on the implanted bioprosthetic valve tissue in the blood circulation.
Copyright (c) 2008. Published by Elsevier Ireland Ltd.
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Aortic valve replacement dilemma: mechanical or biological prosthesis?
J Thorac Cardiovasc Surg2008 Oct;136(4):1101-2; author reply 1102. doi: 10.1016/j.jtcvs.2008.05.025.
Cannata Aldo, Russo Claudio Francesco, Taglieri Corrado
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Is aortic wall degeneration related to bicuspid aortic valve anatomy in patients with valvular disease?
J Thorac Cardiovasc Surg2008 Oct;136(4):937-42. doi: 10.1016/j.jtcvs.2007.11.072.
Russo Claudio F, Cannata Aldo, Lanfranconi Marco, Vitali Ettore, Garatti Andrea, Bonacina Edgardo
Abstract
OBJECTIVE:
Patients with bicuspid aortic valve are at increased risk for aortic complications.
METHODS:
A total of 115 consecutive patients with bicuspid aortic valve disease underwent surgery of the ascending aorta. We classified the cusp configuration by 3 types: fusion of left coronary and right coronary cusps (type A), fusion of right coronary and noncoronary cusps (type B), and fusion of left coronary and noncoronary cusps (type C). Histopathologic changes in the ascending aortic wall were graded (aortic wall score).
RESULTS:
We observed type A fusion in 85 patients (73.9%), type B fusion in 28 patients (24.3%), and type C fusion in 2 patients (1.8%). Patients with type A fusion were younger at operation than patients with type B fusion (51.3 +/- 15.5 years vs 58.7 +/- 7.6 years, respectively; P = .034). The mean ascending aorta diameter was 48.9 +/- 5.0 mm and 48.7 +/- 5.7 mm in type A and type B fusion groups, respectively (P = .34). The mean aortic root diameter was significantly larger in type A fusion (4.9 +/- 6.7 mm vs 32.7 +/- 2.8 mm; P
CONCLUSION:
In diseased bicuspid aortic valves, there was a statistically significant association between type A valve anatomy and a more severe degree of wall degeneration in the ascending aorta and dilatation of the aortic root at younger age compared with type B valve anatomy.
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Noncardiac surgical procedures in patient supported with long-term implantable left ventricular assist device.
Am J Surg2009 Jun;197(6):710-4. doi: 10.1016/j.amjsurg.2008.05.009.
Garatti Andrea, Bruschi Giuseppe, Colombo Tiziano, Russo Claudio, Milazzo Filippo, Catena Emanuele, Lanfranconi Marco, Vitali Ettore
Abstract
BACKGROUND:
Left ventricular assist devices (LVADs) are increasingly used as bridges to transplantation or as destination therapy. As sicker and older patients are more frequently considered for mechanical support, general surgical problems are expected to increase in these patients.
METHODS:
Anesthesia records and clinical charts were reviewed for 11 recipients of LVADs undergoing 12 general surgical procedures between January 1988 and March 2007.
RESULTS:
Eight patients underwent major surgical procedures: 1 intracranial hematoma drainage, 1 right hemicolectomy with ileocolostomy, 1 splenectomy, 1 surgical repair of an iliac-femoral artery pseudoaneurysm, 2 cholecystectomies, 1 pyelolithotomy, and 1 coil embolization of a femoral side-branch disruption. Four patients underwent minor surgical procedures. The mean duration of LVAD support before surgery was 58.7 +/- 45.6 days. All patients survived the procedures.
CONCLUSION:
Noncardiac surgery in LVAD recipients is feasible, without significant morbidity or mortality. Intraoperative coagulation management has a key role in safely performing these procedures.
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Mechanical circulatory support for patients with fulminant myocarditis: the role of echocardiography to address diagnosis, choice of device, management, and recovery.
J Cardiothorac Vasc Anesth2009 Feb;23(1):87-94. doi: 10.1053/j.jvca.2008.03.008.
Catena Emanuele, Paino Roberto, Milazzo Filippo, Colombo Tiziano, Marianeschi Stefano, Lanfranconi Marco, Aresta Francesca, Bruschi Giuseppe, Russo Claudio, Vitali Ettore
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Long-term results of lung cancer after heart transplantation: single center 20-year experience.
Lung Cancer2009 Jan;63(1):146-50. doi: 10.1016/j.lungcan.2008.04.018.
Bruschi Giuseppe, Conforti Serena, Torre Massimo, Colombo Tiziano, Russo Claudio F, Pedrazzini Giovanna, Frigerio Maria, Ravini Mario
Abstract
OBJECTIVE:
The present study analyses, long-term lung cancer survival rate in the Niguarda heart transplant population and the results of surgical treatments.
METHODS:
From November 1985 to December 2006, 786 heart transplants were performed in our Center; we underwent a retrospective review of patients developing primary lung cancer.
RESULTS:
Among 660 heart transplant recipients valuable in this study, 22 (3.3%) developed a primary lung cancer (20 male, 91%), their mean age at time of heart transplant was 54.5+/-5.2 years (range, 42-65). The mean time from transplantation to lung cancer diagnosis was 73.7+/-30 months. Eleven patients (50%) were in stage IIIB or higher at the time of presentation. The 5-year survival rate of the entire study population was 21.4%, with a median survival time (MST) of 10.1 months. Ten patients underwent surgical resection (9 lobectomies and 1 wedge resection) and demonstrated improved long-term survival with 5-year survival of 56% and MST 70.4 months, compared to patients who did not undergo any surgical procedure, all of whom died during follow-up, with 1-year survival of 33%.
CONCLUSIONS:
Long-term results following lung cancer surgery in heart transplant recipients are satisfactory when performed at the early stage of the disease. Preventive computed tomography screen should be considered as a routine method for early diagnosis in this group of high-risk patients.
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Clinical outcome and bridge to transplant rate of left ventricular assist device recipient patients: comparison between continuous-flow and pulsatile-flow devices.
Eur J Cardiothorac Surg2008 Aug;34(2):275-80; discussion 280. doi: 10.1016/j.ejcts.2008.02.019.
Garatti Andrea, Bruschi Giuseppe, Colombo Tiziano, Russo Claudio, Lanfranconi Marco, Milazzo Filippo, Frigerio Maria, Vitali Ettore
Abstract
BACKGROUND:
Long-term implantable continuous axial-flow pumps are increasingly used in bridging heart failure patients to heart transplant. Compared to pulsatile left ventricular assist devices (LVADs), they offer smaller dimensions, less surgical trauma and less thromboembolisms. However concerns still remain about the long-term effects of continuous-flow on patients' outcome. The aim of this study was to review our mechanical bridge to transplant experience to compare pre- and post-transplant outcomes between pulsatile and continuous-flow LVAD recipients.
METHODS:
Thirty-six patients with a continuous-flow device (Micromed DeBakey, Houston, TX or InCor Berlin Heart, Berlin, Germany--group A) were compared with 41 patients supported with a pulsatile device (Novacor, WorldHeart, Oakland, CA--group B).
RESULTS:
Mean age (48.6+/-12.4 vs 47.2+/-12.5) and LVAD duration (119.3+/-115.4 vs 128.3+/-198.3) were similar in the two groups. Group A recipients were smaller compared to group B (mean body surface area=1.77+/-0.18 vs 1.93+/-0.16; p
CONCLUSIONS:
In our experience, when compared to pulsatile LVAD, continuous-flow pumps are similarly effective in transplant rate and post-transplant outcome.
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Mitral valve surgery in emergency for severe acute regurgitation: analysis of postoperative results from a multicentre study.
Eur J Cardiothorac Surg2008 Apr;33(4):573-82. doi: 10.1016/j.ejcts.2007.12.050.
Lorusso Roberto, Gelsomino Sandro, De Cicco Giuseppe, Beghi Cesare, Russo Claudio, De Bonis Michele, Colli Andrea, Sala Andrea
Abstract
OBJECTIVE:
To evaluate postoperative outcome of emergency surgery for acute severe mitral regurgitation (ASMR) from a multicentre experience.
METHODS:
In six centres, 279 patients (mean age 62+/-14 years, 62% female) undergoing emergency surgery for ASMR from December 1986 to March 2007 were analysed and followed up. Aetiology included acute myocardial infarction (AMI) in 126 patients (group 1, 45%), degenerative mitral valve disease in 74 (group 2, 26%), and acute endocarditis (AE) in 79 (group 3, 28%). Preoperatively, all patients were in haemodynamic instability, with 185 patients in cardiogenic shock (66%), 184 (66%) intubated, and 61 (22%) on IABP, respectively. Valve repair was performed in 76 (27%), whereas 203 (73%) underwent valve replacement. Median follow-up (98% complete) was 70.8 months (inter-quartile range 59.8-86.66 months).
RESULTS:
Overall 30-day mortality was 22.5% (63/279). Early death was significantly lower in group 2 (p
CONCLUSIONS:
Emergency surgery for ASMR remains a surgical challenge for high incidence of early and late cardiac-related events, particularly in patients with associated coronary artery disease and acute endocarditis. Apparently, type of mitral valve surgical approaches (repair or replacement) did not provide any influence on postoperative outcome.
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Bicuspid aortic valve: about natural history of ascending aorta aneurysms.
Ann Thorac Surg -
Pre-operative redox state affects 1-month survival in patients with advanced heart failure undergoing left ventricular assist device implantation.
J Heart Lung Transplant2007 Nov;26(11):1177-81.
Caruso Raffaele, Garatti Andrea, Sedda Valentina, Milazzo Filippo, Campolo Jonica, Colombo Tiziano, Catena Emanuele, Cighetti Giuliana, Russo Claudio, Frigerio Maria, Vitali Ettore, Parodi Oberdan
Abstract
BACKGROUND:
Left ventricular assist device (LVAD) implantation has proven effective as a bridge to transplantation in end-stage heart failure patients (ESHFPs), although survival during device support is critical. Oxidative stress has been implicated in the development of heart failure, but the influence of redox state on in-hospital post-LVAD outcome has not been clarified.
METHODS AND RESULTS:
In this report we describe the oxidant/anti-oxidant profiles of 15 ESHFPs before LVAD placement, 5 of whom did not survive to 1 month, and in 30 subjects without cardiac disease, representing the control group.
CONCLUSIONS:
Preliminary findings suggest that adequate activity of the GPx-1-based anti-oxidant system before device placement is associated with patient survival up to 1 month, despite comparable baseline oxidative stress in patients who both survived and died (within 2 weeks post-LVAD).
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Intracellular accumulation of a mild-denatured monomer of the human PrP fragment 90-231, as possible mechanism of its neurotoxic effects.
J Neurochem2007 Dec;103(6):2597-609.
Chiovitti Katia, Corsaro Alessandro, Thellung Stefano, Villa Valentina, Paludi Domenico, D'Arrigo Cristina, Russo Claudio, Perico Angelo, Ianieri Adriana, Di Cola Domenico, Vergara Alberto, Aceto Antonio, Florio Tullio
Abstract
Because of high tendency of the prion protein (PrP) to aggregate, the exact PrP isoform responsible for prion diseases as well as the pathological mechanism that it activates remains still controversial. In this study, we show that a pre-fibrillar, monomeric or small oligomeric conformation of the human PrP fragment 90-231 (hPrP90-231), rather than soluble or fibrillar large aggregates, represents the neurotoxic species. In particular, we demonstrate that monomeric mild-denatured hPrP90-231 (incubated for 1 h at 53 degrees C) induces SH-SY5Y neuroblastoma cell death, while, when structured in large aggregates, it is ineffective. Using spectroscopic and cellular techniques we demonstrate that this toxic conformer is characterized by a high exposure of hydrophobic regions that favors the intracellular accumulation of the protein. Inside the cells hPrP90-231 is mainly compartmentalized into the lysosomes where it may trigger pro-apoptotic 'cell death' signals. The PrP toxic conformation, which we have obtained inducing a controlled in vitro conformational change of the protein, might mimic mild-unfolding events occurring in vivo, in the presence of specific mutations, oxidative reactions or proteolysis. Thus, in light of this model, we propose that novel therapeutic strategies, designed to inhibit the interaction of the toxic PrP with the plasmamembrane, could be beneficial to prevent the formation of intracellular neurotoxic aggregates and ultimately the neuronal death.
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Different structural stability and toxicity of PrP(ARR) and PrP(ARQ) sheep prion protein variants.
J Neurochem2007 Dec;103(6):2291-300.
Paludi Domenico, Thellung Stefano, Chiovitti Katia, Corsaro Alessandro, Villa Valentina, Russo Claudio, Ianieri Adriana, Bertsch Uwe, Kretzschmar Hans A, Aceto Antonio, Florio Tullio
Abstract
The polymorphisms at amino acid residues 136, 154, and 171 in ovine prion protein (PrP) have been associated with different susceptibility to scrapie: animals expressing PrP(ARQ) [PrP(Ala136/Arg154/Gln171)] show vulnerability, whereas those that express PrP(ARR) [PrP(Ala136/Arg154/Arg171)] are resistant to scrapie. The aim of this study was to evaluate the in vitro toxic effects of PrP(ARR) and PrP(ARQ) variants in relation with their structural characteristics. We show that both peptides cause cell death inducing apoptosis but, unexpectedly, the scrapie resistant PrP(ARR) form was more toxic than the scrapie susceptible PrP(ARQ) variant. Moreover, the alpha-helical conformation of PrP(ARR) was less stable than that of PrP(ARQ) and the structural determinants responsible of these different conformational stabilities were characterized by spectroscopic analysis. We observed that PrP toxicity was inversely related to protein structural stability, being the unfolded conformation more toxic than the native one. However, the PrP(ARQ) variant displays a higher propensity to form large aggregates than PrP(ARR). Interestingly, in the presence of small amounts of PrP(ARR), PrP(ARQ) aggregability was reduced to levels similar to that of PrP(ARR). Thus, in contrast to PrP(ARR) toxicity, scrapie transmissibility seems to reside in the more stable conformation of PrP(ARQ) that allows the formation of large amyloid fibrils.
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Drive-line exit-site infection in a patient with axial-flow pump support: successful management using vacuum-assisted therapy.
J Heart Lung Transplant2007 Sep;26(9):956-9.
Garatti Andrea, Giuseppe Bruschi, Russo Claudio Francesco, Marco Ordanini, Ettore Vitali
Abstract
Infection remains one of the most common causes of mortality during left ventricular assist device (LVAD) support, and poses major challenges to surgeons implanting these devices. We describe the case of a patient supported with an axial-flow pump for dilative cardiomyopathy, who experienced drive-line exit-site infection and was treated with extensive surgical debridement and reconstruction by applying vacuum-assisted therapy. He remained infection-free after wound healing and, after 7 months of mechanical support, had native heart function recovery and underwent LVAD removal.
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ERK1/2 and p38 MAP kinases control prion protein fragment 90-231-induced astrocyte proliferation and microglia activation.
Glia2007 Nov;55(14):1469-85.
Thellung Stefano, Villa Valentina, Corsaro Alessandro, Pellistri Francesca, Venezia Valentina, Russo Claudio, Aceto Antonio, Robello Mauro, Florio Tullio
Abstract
Astrogliosis and microglial activation are a common feature during prion diseases, causing the release of chemoattractant and proinflammatory factors as well as reactive free radicals, involved in neuronal degeneration. The recombinant protease-resistant domain of the prion protein (PrP90-231) displays in vitro neurotoxic properties when refolded in a beta-sheet-rich conformer. Here, we report that PrP90-231 induces the secretion of several cytokines, chemokines, and nitric oxide (NO) release, in both type I astrocytes and microglial cells. PrP90-231 elicited in both cell types the activation of ERK1/2 MAP kinase that displays, in astrocytes, a rapid kinetics and a proliferative response. Conversely, in microglia, PrP90-231-dependent MAP kinase activation was delayed and long lasting, inducing functional activation and growth arrest. In microglial cells, NO release, dependent on the expression of the inducible NO synthase (iNOS), and the secretion of the chemokine CCL5 were Ca(2+) dependent and under the control of the MAP kinases ERK1/2 and p38: ERK1/2 inhibition, using PD98059, reduced iNOS expression, while p38 blockade by PD169316 inhibited CCL5 release. In summary, we demonstrate that glial cells are activated by extracellular misfolded PrP90-231 resulting in a proliferative/secretive response of astrocytes and functional activation of microglia, both dependent on MAP kinase activation. In particular, in microglia, PrP90-231 activated a complex signalling cascade involved in the regulation of NO and chemokine release. These data argue in favor of a causal role for misfolded prion protein in sustaining glial activation and, possibly, glia-mediated neuronal death.
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Successful replacement of malfunctioning TCI HeartMate LVAD with DeBakey LVAD as a bridge to heart transplantation.
Interact Cardiovasc Thorac Surg2004 Dec;3(4):542-3.
Russo Claudio F, Fratto Pasquale A, Milazzo Filippo, Vitali Ettore
Abstract
Congestive heart failure is the leading cause of hospitalization and death in the developed world and affects about 0.4-2% of the adult population [Ann Thorac Surg 1999;68:637-40]. Heart transplantation remains the most effective therapy for end-stage heart disease, but the shortage of donors has led to increasing interest in other surgical options, especially ventricular assist devices (VAD). Several VADs are available to bridge patients to transplantation [N Engl J Med 2001;345:1435-43], including pulsatile devices like the HeartMate (HeartMate, Thoratec, Pleasanton, CA) and Novacor (World Heart, Netherlands), and the DeBakey VAD (MicroMed Technology, Inc., Houston, TX), which is an electromagnetically driven implantable titanium axial flow blood pump designed for left ventricular support. Despite technical improvements, VADs still are associated with serious complications. We reporte a successfull case where we replaced a TCI HeartMate with a DeBakey VAD because of a serious pocket infection, deterioration and failure of the inflow valve.
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Amyloid precursor protein and presenilin involvement in cell signaling.
Neurodegener Dis2007 ;4(2-3):101-11.
Venezia Valentina, Nizzari Mario, Carlo Pia, Corsaro Alessandro, Florio Tullio, Russo Claudio
Abstract
To date the most relevant role for the amyloid precursor protein (APP) and for the presenilins (PSs) on Alzheimer's disease (AD) genesis is linked to the 'amyloid hypothesis', which considers an aberrant formation of amyloid-beta peptides the cause of neurodegeneration. In this view, APP is merely a substrate, cleaved by the gamma-secretase complex to form toxic amyloid peptides, PSs are key players in gamma-secretase complex, and corollary or secondary events are Tau-linked pathology and gliosis. A second theory, complementary to the amyloid hypothesis, proposes that APP and PSs may modulate a yet unclear cell signal, the disruption of which may induce cell-cycle abnormalities, neuronal death, eventually amyloid formation and finally dementia. This hypothesis is supported by the presence of a complex network of proteins, with a clear relevance for signal transduction mechanisms, which interact with APP or PSs. In this scenario, the C-terminal domain of APP has a pivotal role due to the presence of the 682YENPTY687 motif that represents the docking site for multiple interacting proteins involved in cell signaling. In this review we discuss the significance of novel findings related to cell signaling events modulated by APP and PSs for AD development.
2007 S. Karger AG, Basel
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Mechanical circulatory support for cardiogenic shock complicating acute myocardial infarction: an experimental and clinical review.
ASAIO J2007 ;53(3):278-87.
Garatti Andrea, Russo Claudio, Lanfranconi Marco, Colombo Tiziano, Bruschi Giuseppe, Trunfio Salvatore, Milazzo Filippo, Catena Emanuele, Colombo Paola, Maria Frigerio, Vitali Ettore
Abstract
Cardiogenic shock (CS) occurs in 7% to 10% of cases after acute myocardial infarction and remains the most common cause of death in these patients. Despite aggressive treatment regimens such as fibrinolysis and percutaneous transluminal coronary angioplasty, mortality rates from CS remain extremely high. It has been shown that intra-aortic balloon pumping can result in initial hemodynamic stabilization. However, in the majority of studies, death was merely delayed. In recent years, efforts have been made to develop ventricular devices (LVAD) capable of providing complete short-term hemodynamic support. Seventeen major studies of LVAD support for CS complicating acute myocardial infarction are reported in the literature, with a mean weaning and survival rate of 58.5% and 40%, respectively. Patients considered in these studies are difficult to compare in terms of demographic and anatomic data, but taking these considerations into account, LVAD support seems to give no survival improvement in these patients compared with early reperfusion alone or associated with intra-aortic balloon pumping. Data emerging from experimental studies of acute myocardial infarction supported with LVAD are intriguing. In this review, we report the LVAD experience in the CS setting, starting from percutaneous extracorporeal support up to bridge therapy with implantable devices.
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Association of a presenilin 1 S170F mutation with a novel Alzheimer disease molecular phenotype.
Arch Neurol2007 May;64(5):738-45.
Piccini Alessandra, Zanusso Gianluigi, Borghi Roberta, Noviello Cristiana, Monaco Salvatore, Russo Roberta, Damonte Gianluca, Armirotti Andrea, Gelati Matteo, Giordano Renzo, Zambenedetti Pamela, Russo Claudio, Ghetti Bernardino, Tabaton Massimo
Abstract
OBJECTIVE:
To report an ataxic variant of Alzheimer disease expressing a novel molecular phenotype.
DESIGN:
Description of a novel phenotype associated with a presenilin 1 mutation.
SETTING:
The subject was an outpatient who was diagnosed at the local referral center.
PATIENT:
A 28-year-old man presented with psychiatric symptoms and cerebellar signs, followed by cognitive dysfunction. Severe beta-amyloid (Abeta) deposition was accompanied by neurofibrillary tangles and cell loss in the cerebral cortex and by Purkinje cell dendrite loss in the cerebellum. A presenilin 1 gene (PSEN1) S170F mutation was detected.
MAIN OUTCOME MEASURES:
We analyzed the processing of Abeta precursor protein in vitro as well as the Abeta species in brain tissue.
RESULTS:
The PSEN1 S170F mutation induced a 3-fold increase of both secreted Abeta(42) and Abeta(40) species and a 60% increase of secreted Abeta precursor protein in transfected cells. Soluble and insoluble fractions isolated from brain tissue showed a prevalence of N-terminally truncated Abeta species ending at both residues 40 and 42.
CONCLUSION:
These findings define a new Alzheimer disease molecular phenotype and support the concept that the phenotypic variability associated with PSEN1 mutations may be dictated by the Abeta aggregates' composition.
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Amino-terminally truncated prion protein PrP90-231 induces microglial activation in vitro.
Ann N Y Acad Sci2007 Jan;1096():258-70.
Thellung Stefano, Corsaro Alessandro, Villa Valentina, Venezia Valentina, Nizzari Mario, Bisaglia Michela, Russo Claudio, Schettini Gennaro, Aceto Antonio, Florio Tullio
Abstract
The conversion of the prion protein (PrP) into a protease-resistant isoform (PrP(Res)) is considered the pathogenic event responsible for prion encephalopathies. Microglia activation accompanies PrP(Res) deposition representing an early event in the progression of these diseases. It is now believed that microglial cells play a worsening, if not causative, role in prion-induced neuronal death, through the release of proinflammatory and neurotoxic molecules. Indeed, in vitro observations have demonstrated that PrP(Res) and the synthetic prion fragment PrP106-126 induce neuronal death by activating microglial to migrate in the lesion area and secrete cytokines. Recently, we and others have demonstrated that the recombinant peptide, corresponding to the protease-resistant portion of PrP encompassing the amino acids 90-231 (PrP90-231), when beta-structured, is toxic for neuronal cells, in vitro. Here we report that PrP90-231 induces activation of N9 microglial cells, characterized by cell proliferation arrest and increased secretion of different cytokines (RANTES, GCSF, and IL-12). Moreover, the treatment of N9 cells with PrP90-231 elicited inducible nitric oxide synthase (i-NOS) expression, nitric oxide release, and a delayed (15 min to 1 h of treatment) extracellular signal-regulated kinases 1/2 (ERK1/2) phosphorylation/activation. Although ERK1/2 is known to regulate proliferative and differentiative events, we show that its blockade, using the specific MEK inhibitor PD98059, did not prevent PrP90-231-induced inhibition of N9 cell proliferation. To our knowledge, this is the first evidence that a recombinant PrP(Res)-like peptide elicits microglial activation in vitro, thus representing a potentially important tool to develop possible therapeutic strategies to target prion-induced brain inflammation.
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Amyloid precursor protein and Presenilin 1 interaction studied by FRET in human H4 cells.
Ann N Y Acad Sci2007 Jan;1096():249-57.
Nizzari Mario, Venezia Valentina, Bianchini Paolo, Caorsi Valentina, Diaspro Alberto, Repetto Emanuela, Thellung Stefano, Corsaro Alessandro, Carlo Pia, Schettini Gennaro, Florio Tullio, Russo Claudio
Abstract
The mayor pathologic hallmarks of Alzheimer's disease (AD) are senile plaque and neurofibrillary tangles. Senile plaque are primarily made up of deposits of amyloid-beta protein, a proteolytic product derived from the amyloid precursor protein (APP). APP is a transmembrane protein detected into the endoplasmic reticulum, in the Golgi apparatus, at the cell surface, recycled by endocytosis to endosomes, whose physiological function is unclear. Presenilins (PS), are a component of gamma-secretase complex that cleave alpha-CTFs (carboxy-terminal fragment), or beta-CTFs, leaving 40 or 42 amino acids amyloid-beta peptides and 58 or 56 amino acids intracellular domains (AICD). Where the amyloid-beta peptides is generated is not clear. The study of APP-PS interaction in specific cell compartments provides a good opportunity to light upon the molecular mechanisms regulating the activity of the "gamma-secretase complex," and where beta-amyloid is generated. In our study we used a biophysical assay of protein proximity: fluorescence resonance energy transfer (FRET), that can provide information about molecular interactions when two proteins are in the close proximity (
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Amyloid precursor protein modulates ERK-1 and -2 signaling.
Ann N Y Acad Sci2006 Dec;1090():455-65.
Venezia Valentina, Nizzari Mario, Repetto Emanuela, Violani Elisabetta, Corsaro Alessandro, Thellung Stefano, Villa Valentina, Carlo Pia, Schettini Gennaro, Florio Tullio, Russo Claudio
Abstract
The amyloid precursor protein (APP) is a transmembrane protein with a short cytoplasmic tail whose physiological function is unclear, although it is well documented that the proteolytic processing of APP could influence the development of Alzheimer's disease (AD) through the formation of membrane-bound C-terminal fragments (CTFs) and of beta-amyloid peptides (Abeta). We have recently shown that tyrosine-phosphorylated APP and CTFs may interact with Grb2 and ShcA adaptor proteins and that this coupling occurs at a higher extent in AD subjects only. To study the interaction between APP or CTFs and ShcA/Grb2 and to investigate their molecular target we have used as experimental model two different cell lines: H4 human neuroglioma cells and APP/APLP null mouse embryonic fibroblast cells (MEFs). Here we show that in H4 cells APP interacts with Grb2; conversely in APP/APLP-null MEF cells this interaction is possible only after the reintroduction of human APP by transfection. We have also shown that in MEF cells the transfection of a plasmid encoding for human APP wild-type enhances the phosphorylation of ERK-1 and -2 as revealed by Western blotting and immunofluorescence experiments. Finally, also in H4 cells the overexpression of APP upregulates the levels of phospho-ERK-1 and -2. In summary our data suggest that APP may influence phospho-ERK-1 and -2 signaling through its binding with Grb2 and ShcA adaptors. The meaning of this event is not clear, but APP interaction with these adaptors could be relevant to regulate mitogenic pathway.
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Characterization of the proapoptotic intracellular mechanisms induced by a toxic conformer of the recombinant human prion protein fragment 90-231.
Ann N Y Acad Sci2006 Dec;1090():276-91.
Villa Valentina, Corsaro Alessandro, Thellung Stefano, Paludi Domenico, Chiovitti Katia, Venezia Valentina, Nizzari Mario, Russo Claudio, Schettini Gennaro, Aceto Antonio, Florio Tullio
Abstract
Prion diseases comprise a group of fatal neurodegenerative disorders that affect both animals and humans. The transition of the prion protein (PrP) from a mainly alpha-structured isoform (PrPC) to a prevalent beta-sheet-containing protein (PrPSc) is believed to represent a major pathogenetic mechanism in prion diseases. To investigate the linkage between PrP neurotoxicity and its conformation, we used a recombinant prion protein fragment corresponding to the amino acidic sequence 90-231 of human prion protein (hPrP90-231). Using thermal denaturation, we set up an experimental model to induce the process of conversion from PrPC to PrPSc. We report that partial thermal denaturation converts hPrP90-231 into a beta-sheet-rich isoform, displaying a temperature- and time-dependent conversion into oligomeric structures that share some physico-chemical characteristics with brain PrPSc. SH-SY5Y cells were chosen to characterize the potential neurotoxic effect of hPrP90-231 in its different structural conformations. We demonstrated that hPrP90-231 in beta-conformation, but not when alpha-structured, powerfully affected the survival of these cells. hPrP90-231 beta-structured caused DNA fragmentation and a significant increase in caspase-3 proteolytic activity (maximal effects+170%), suggesting the occurrence of apoptotic cell death. Finally, we investigated the involvement of MAP kinases in the regulation of beta-hPrP90-231-dependent apoptosis. We observed that the p38 MAP kinase blocker SB203580 prevented the apoptotic cell death evoked by hPrP90-231, and Western blot analysis revealed that the exposure of the cells to the peptide induced p38 phosphorylation. In conclusion, we demonstrate that the hPrP90-231 elicits proapoptotic activity when in beta-sheet-rich conformation and that this effect is mediated by p38 and caspase-3 activation.
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Amyloid precursor protein and Presenilin1 interact with the adaptor GRB2 and modulate ERK 1,2 signaling.
J Biol Chem2007 May;282(18):13833-44.
Nizzari Mario, Venezia Valentina, Repetto Emanuela, Caorsi Valentina, Magrassi Raffaella, Gagliani Maria Cristina, Carlo Pia, Florio Tullio, Schettini Gennaro, Tacchetti Carlo, Russo Tommaso, Diaspro Alberto, Russo Claudio
Abstract
The amyloid precursor protein (APP) and the presenilins 1 and 2 are genetically linked to the development of familial Alzheimer disease. APP is a single-pass transmembrane protein and precursor of fibrillar and toxic amyloid-beta peptides, which are considered responsible for Alzheimer disease neurodegeneration. Presenilins are multipass membrane proteins, involved in the enzymatic cleavage of APP and other signaling receptors and transducers. The role of APP and presenilins in Alzheimer disease development seems to be related to the formation of amyloid-beta peptides; however, their physiological function, reciprocal interaction, and molecular mechanisms leading to neurodegeneration are unclear. APP and presenilins are also involved in multiple interactions with intracellular proteins, the significance of which is under investigation. Among the different APP-interacting proteins, we focused our interest on the GRB2 adaptor protein, which connects cell surface receptors to intracellular signaling pathways. In this study we provide evidence by co-immunoprecipitation experiments, confocal and electron microscopy, and by fluorescence resonance energy transfer experiments that both APP and presenilin1 interact with GRB2 in vesicular structures at the centrosome of the cell. The final target for these interactions is ERK1,2, which is activated in mitotic centrosomes in a PS1- and APP-dependent manner. These data suggest that both APP and presenilin1 can be part of a common signaling pathway that regulates ERK1,2 and the cell cycle.
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About left atrial enlargement in dilated cardiomyopathy.
J Am Soc Echocardiogr -
Mitral valve periprosthetic leakage: Anatomical observations in 135 patients from a multicentre study.
Eur J Cardiothorac Surg2006 Dec;30(6):887-91.
De Cicco Giuseppe, Russo Claudio, Moreo Antonella, Beghi Cesare, Fucci Carlo, Gerometta Piersilvio, Lorusso Roberto
Abstract
OBJECTIVE:
Prosthetic valve dysfunction after mitral valve replacement (MVR) may be caused by several factors, which often lead to repeated surgery. One of the most frequent determinants of reoperation is periprosthetic leakage (PPL). A few published reports have analysed PPL incidence and postoperative results after MVR, but no specific attention has been paid towards the potential relation between anatomical factors and PPL occurrence, particularly not bacterial-related. The aim of this study was to evaluate the location of PPL after MVR through a multicentre retrospective study.
METHODS:
Between January 1985 and November 2005, 135 patients underwent reoperation at four institutions because of PPL after MVR and met the study inclusion criteria. The mitral valve annulus (MVA) was analysed in a clockwise format, indicating 12 o'clock as the mid-point of anterior annulus as viewed from the atrium.
RESULTS:
Overall hospital mortality was 3.7% (five patients). Repair of PPL was carried out in 83 cases whereas prosthetic valve replacement was necessary in 52 cases. The total number of sectors involved in PPL was 244. PPL occurred more frequently between hour 5 and hour 6, and hour 10 and hour 11, with the risk of leakage being, 2.8 and 2.0 times higher, respectively, than in any other portion of the MVA.
CONCLUSIONS:
Our study suggests that PPL occurs more frequently at antero-lateral and postero-medial segments of MVA. This finding might be linked to unusual anatomical and functional factors of the MVA and may call for adjunctive care to these sectors of MVA when performing suture placement during MVR.
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Traumatic right atrial disruption with hepatic and splenic injuries: treatment by CPB-assisted laparotomy and sternotomy.
Chir Ital2006 ;58(3):397-401.
Colombo Fabio, Sansonna Fabio, Russo Claudio Francesco, Ferrari Giovanni Carlo, De Carli Stefano, Cimbanassi Stefania, Magistro Carmelo, Costanzi Andrea, Pugliese Raffaele
Abstract
The Authors present a case of thoracoabdominal trauma from a road accident in a young woman who received care initially in a level II hospital. She was then transferred to a level I Trauma Centre with the onset of haemorrhagic shock due to haemopericardium and haemoperitoneum from liver injuries. A chest CT scan led to the suspicion of aortic dissection, hence a cardiopulmonary bypass (CPB) for life support was instituted just before laparotomy through the femoral vessels. Exploration of the peritoneal cavity was performed as a first step because haemoperitoneum was deemed to be the main cause of shock. One litre of blood was aspirated and hepatosplenic tears were sutured to obtain haemostasis. Subsequently, aortic dissection was ruled out by median sternotomy, while a right atrial disruption was identified and repaired by stitches and a pericardial homologous patch. Nevertheless, the ascending aorta was explored by transverse arteriotomy. The postoperative course was uneventful and the woman has never presented cardiac or abdominal symptoms as a result of trauma or surgery.
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Left ventricular mechanical support with the Impella Recover left direct microaxial blood pump: a single-center experience.
Artif Organs2006 Jul;30(7):523-8.
Garatti Andrea, Colombo Tiziano, Russo Claudio, Lanfranconi Marco, Milazzo Filippo, Catena Emanuele, Bruschi Giuseppe, Frigerio Maria, Vitali Ettore
Abstract
The Impella Recover left direct (LD) is a new intravascular microaxial blood pump, intended as a short-term mechanical support especially in case of acutely reduced left ventricular function. From September 2002 to October 2004, Impella was used to support 12 patients: six patients were supported as bridge-to-heart transplant (HTx); three patients were treated for fulminant acute myocarditis, and three patients for postcardiotomy low-output syndrome. Mean support time was 8.8 +/- 2.3 days. Overall mortality was 50%. Four patients were successfully HTxed; two patients supported as bridge-to-HTx died on left ventricular assist device. Two patients with myocarditis died of septic shock; two patients in the group of postcardiotomy died of multiorgan failure. The latter two patients were slowly weaned from the device, and at 3-months follow-up showed good improvement of the left ventricular function. Our initial experience with Impella Recover LD as mechanical support for patients in cardiogenic shock of various etiology is promising, yielding a good survival in a population of particularly compromised patients.
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Bridge to transplantation with the MicroMed DeBakey ventricular assist device axial pump: a single centre report.
J Cardiovasc Med (Hagerstown)2006 Feb;7(2):114-8.
Bruschi Giuseppe, Ribera Elena, Lanfranconi Marco, Russo Claudio, Colombo Tiziano, Garatti Andrea, Oliva Fabrizio, Milazzo Filippo, Frigerio Maria, Vitali Ettore
Abstract
OBJECTIVE:
Left ventricular assist devices (VADs) are an accepted therapy to bridge patients with end-stage heart failure to heart transplantation. The DeBakey VAD, a continuous axial flow pump weighing 93 g, has been introduced into clinical practice as a bridge to transplant.
METHODS:
Starting from April 2000,17 patients (12 males, five females, mean age 44.3 +/- 12.8 years; 11 dilated idiopathic cardiomyopathy, five ischaemic cardiomyopathy, one pulsatile device failure) with end-stage heart failure were implanted with a DeBakey VAD as a bridge to transplantation at our institution. Before implant, all patients suffered from severe heart failure (New York Heart Association functional class IV) despite optimal medical therapy and were put on the waiting list for heart transplantation. Mean cardiac index was 1.59 +/- 0.51 l/min/m2.
RESULTS:
Fourteen patients were successfully transplanted after 99 +/- 117 days of assistance (range 11-443 days). Two patients died during assistance of multiorgan failure, one patient is still on VAD. No patient needed additional right ventricular mechanical support. Left ventricular/left VAD thrombosis occurred in one patient who was successfully treated conservatively. No clinical elevation of plasma free haemoglobin was detected. Neither device, driveline, abdominal pocket infection nor device failure occurred.
CONCLUSIONS:
In our experience with the continuous axial flow DeBakey VAD, a high success rate was obtained associated with a low risk of complications. All the patients tolerated continuous blood flow for extended periods that makes this device a valuable alternative to pulsatile VADs as a bridge to transplantation.
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[Mechanical assist devices in advanced heart failure. Indications and perspectives].
G Ital Cardiol (Rome)2006 Feb;7(2):91-108.
Colombo Tiziano, Russo Claudio, Lanfranconi Marco, Bruschi Giuseppe, Garatti Andrea, Milazzo Filippo, Catena Emanuele, Oliva Fabrizio, Turazza Fabio, Frigerio Maria, Vitali Ettore
Abstract
Congestive heart failure is recognized as a major public health issue and is the leading cause of death in western countries. Heart transplantation currently remains the gold standard option for end-stage heart failure patients. Heart transplantation is also one of the most limited therapies, not only with regard to the lack of donor hearts but also because of the surgical limitations inherent to the clinical aspects of this severely ill patient population. Mechanical circulatory support systems have been developed as effective adjuvant therapeutic options in these terminally ill patients. Over the past two decades, mechanical circulatory support devices have steadily evolved in the clinical management of end-stage heart failure, and have emerged as a standard of care for the treatment of acute and chronic heart failure refractory to conventional medical therapy. Future blood pumps should be smaller and totally implantable, as well as more efficient, biocompatible, and reliable.
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Different clinical scenarios for circulatory mechanical support in acute and chronic heart failure.
Am J Cardiol2005 Dec;96(12A):34L-41L.
Vitali Ettore, Colombo Tiziano, Bruschi Giuseppe, Garatti Andrea, Russo Claudio, Lanfranconi Marco, Frigerio Maria
Abstract
Chronic heart failure (HF) is a leading cause of death in developed countries. Over the last 2 decades, mechanical circulatory support (MCS) devices have steadily evolved in the clinical management of end-stage HF and have emerged as a standard of care for the treatment of acute and chronic HF refractory to conventional medical therapy. Possible indications for using MCS are acute cardiogenic shock, as a bridge to transplantation, as a bridge to recovery, and more recently, as destination therapy in dilated cardiomyopathy, of either ischemic or idiopathic etiology. We reviewed the different clinical scenarios in which we think there are currently indications to implant different kinds of MCS systems.
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Left ventricular support by axial flow pump: the echocardiographic approach to device malfunction.
J Am Soc Echocardiogr2005 Dec;18(12):1422.
Catena Emanuele, Milazzo Filippo, Montorsi Emanuela, Bruschi Giuseppe, Cannata Aldo, Russo Claudio, Barosi Alberto, Tarelli Giuseppe, Tartara Paolo, Paino Roberto, Vitali Ettore
Abstract
Axial flow pumps have gained increased acceptance in recent years as a bridge to heart transplantation and, more recently, as destination therapy. As left ventricular (LV) assist device dysfunction will be increasingly prevalent, the aim of our work was to introduce an echocardiographic management protocol as a guide to recognize the causes of pump failure. In this article we describe the echocardiographic approach to 5 episodes of malfunction of an axial flow pump (DeBakey, MicroMed Technology Inc, Houston, Tex) in 4 patients: 4 episodes caused by thrombosis of LV assist device and one caused by abnormal increase of systemic vascular resistance. In our experience, echocardiography played a pivotal role in clinical management of LV assist device failure. It allowed us to: assess patency and position of inflow and outflow cannulae; research the source of thromboembolic material; assess adequate LV filling and unloading; and optimize right ventricular function, volume replacement therapy, and pharmacologic support.
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beta-amyloid is different in normal aging and in Alzheimer disease.
J Biol Chem2005 Oct;280(40):34186-92.
Piccini Alessandra, Russo Claudio, Gliozzi Alessandra, Relini Annalisa, Vitali Antonella, Borghi Roberta, Giliberto Luca, Armirotti Andrea, D'Arrigo Cristina, Bachi Angela, Cattaneo Angela, Canale Claudio, Torrassa Silvia, Saido Takaomi C, Markesbery William, Gambetti Pierluigi, Tabaton Massimo
Abstract
The mechanism of neurodegeneration caused by beta-amyloid in Alzheimer disease is controversial. Neuronal toxicity is exerted mostly by various species of soluble beta-amyloid oligomers that differ in their N- and C-terminal domains. However, abundant accumulation of beta-amyloid also occurs in the brains of cognitively normal elderly people, in the absence of obvious neuronal dysfunction. We postulated that neuronal toxicity depends on the molecular composition, rather than the amount, of the soluble beta-amyloid oligomers. Here we show that soluble beta-amyloid aggregates that accumulate in Alzheimer disease are different from those of normal aging in regard to the composition as well as the aggregation and toxicity properties.
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The amyloid precursor protein and its network of interacting proteins: physiological and pathological implications.
Brain Res Brain Res Rev2005 Apr;48(2):257-64.
Russo Claudio, Venezia Valentina, Repetto Emanuela, Nizzari Mario, Violani Elisabetta, Carlo Pia, Schettini Gennaro
Abstract
The amyloid precursor protein (APP) is an ubiquitous receptor-like molecule involved in the pathogenesis of Alzheimer's disease that generates beta-amyloid peptides and causes plaque formation. APP and some of its C-terminal proteolytic fragments (CTFs) have also been shown to be in the center of a complex protein-protein network, where selective phosphorylation of APP C-terminus may regulate the interaction with cytosolic phosphotyrosine binding (PTB) domain or Src homology 2 (SH2) domain containing proteins involved in cell signaling. We have recently described an interaction between tyrosine-phosphorylated CTFs and ShcA adaptor protein which is highly enhanced in AD brain, and a new interaction between APP and the adaptor protein Grb2 both in human brain and in neuroblastoma cultured cells. These data suggest a possible role in cell signaling for APP and its CTFs, in a manner similar to that previously reported for other receptors, through a tightly regulated coupling with intracellular adaptors to control the signaling of the cell. In this review, we discuss the significance of these novel findings for AD development.
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Different applications for left ventricular mechanical support with the Impella Recover 100 microaxial blood pump.
J Heart Lung Transplant2005 Apr;24(4):481-5.
Garatti Andrea, Colombo Tiziano, Russo Claudio, Lanfranconi Marco, Milazzo Filippo, Catena Emanuele, Bruschi Guiseppe, Frigerio Maria, Vitali Ettore
Abstract
The "Impella Recover 100" (IR100) is a new intravascular microaxial blood pump for use as short-term mechanical support for cases of acutely reduced left ventricular function. From September 2002 to April 2003, we used the IR100 to support 5 patients: 2 patients were bridged to heart transplant; 2 were being treated for fulminant acute myocarditis; and 1 for post-cardiotomy low-output syndrome. Only 1 patient with myocarditis died of septic shock, 2 had successful heart transplants; and the latter 2 were slowly weaned from the device and, at 3-month follow-up, showed moderate improvement of left ventricular (LV) function. Our initial experience with the IR100 as mechanical support for patients in cardiogenic shock of varying etiology has been positive, yielding good survival in a population of particularly compromised patients.
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One-year clinical experience with the Acorn CorCap cardiac support device: results of a limited market release safety study in Italy and Sweden.
Ital Heart J2005 Jan;6(1):59-65.
Livi Ugolino, Alfieri Ottavio, Vitali Ettore, Russo Claudio, Frigerio Maria, Tursi Vincenzo, Albanese Maria Cecilia, De Bonis Michele, Fragasso Gabriele, Franco-Cereceda Anders, Forssell Gunilla, Rorke Rebecca, Kubo Spencer H
Abstract
BACKGROUND:
The Acorn CorCap cardiac support device (CSD) is a mesh-like device intended to provide end-diastolic support and reduce ventricular wall stress. Animal studies with the CorCap CSD have demonstrated beneficial reverse remodeling, and preliminary safety studies in patients with heart failure have shown that the device is safe and associated with improved left ventricular (LV) structure and function. The objective of the current study was to further evaluate the safety and efficacy of the CorCap CSD in patients with advanced heart failure.
METHODS:
Twenty-four patients with dilated cardiomyopathy, severe LV dysfunction, and advanced heart failure (NYHA class II-IV) were enrolled at four centers in Italy and Sweden. All patients underwent CorCap CSD implantation either alone (n = 3) or in combination with mitral valve repair/replacement (n = 13), coronary artery bypass surgery (n = 6), combined mitral valve repair/coronary artery bypass surgery (n = 1) or aneurysmectomy (n = 1).
RESULTS:
The LV end-diastolic diameter decreased from 69.3 +/- 7.2 to 60.1 +/- 9.0 mm at 3 months, 60.9 +/- 9.6 mm at 6 months, and 58.9 +/- 8.0 mm at 12 months (all p
CONCLUSIONS:
In agreement with earlier safety studies, even the present investigation demonstrated improvements in cardiac structure and function as well as in patient functional status after Cor Cap CSD implantation. Randomized controlled trials are in progress.
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Apoptotic cell death and amyloid precursor protein signaling in neuroblastoma SH-SY5Y cells.
Ann N Y Acad Sci2004 Dec;1030():339-47.
Venezia Valentina, Russo Claudio, Repetto Emanuela, Nizzari Mario, Violani Elisabetta, Carlo Pia, Marchetti Bianca, Schettini Gennaro
Abstract
We have recently shown that the amyloid precursor protein (APP) and a subset of its C-terminal fragments (CTFs) are tyrosine phosphorylated in human brain and in cultured cells. Tyrosine phosphorylation generates a substrate that is sequentially bound by the adaptor proteins ShcA and Grb2, and this interaction is significantly enhanced in Alzheimer's disease brains. Here we have studied the APP/CTFs phosphorylation and ShcA activation in a human neuroblastoma cell line, SH-SY5Y, under basal and apoptotic conditions. To commit these cells to apoptosis, we used staurosporin, a well-known apoptotic inducer and protein kinase C blocker. Our data suggest the following: (1) in normally proliferating SH-SY5Y cells, full-length APP is complexed with Grb2[Q3], likely through its SH2 domain; (2) upon induction of apoptosis, APP is degraded and ShcA-Grb2 coimmunoprecipitates with CTFs recognized by anti-APP antibodies; and (3) caspase inhibitors partially block the degradation of APP and the coprecipitation of CTFs with ShcA-Grb2 adaptors. In summary, our data suggest that in SH-SY5Y cells, tyrosine-phosphorylated APP is involved in a complex with ShcA-Grb2 adaptors that is disrupted during apoptosis. The abnormal degradation of APP and consequent increased levels of CTFs (as has been observed in Alzheimer's disease and Down's syndrome) generate a complex between tyrosine-phosphorylated CTFs and intracellular adaptors. The signaling through APP and its CTFs may have significant relevance for apoptotic cell death in Alzheimer's disease.
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BACE1 overexpression regulates amyloid precursor protein cleavage and interaction with the ShcA adapter.
Ann N Y Acad Sci2004 Dec;1030():330-8.
Repetto Emanuela, Russo Claudio, Venezia Valentina, Nizzari Mario, Nitsch Roger M, Schettini Gennaro
Abstract
The amyloid precursor protein (APP) is a cell surface protein with a large extracellular N-terminal domain, a single transmembrane segment, and a short cytoplasmic tail. Its location and structural features are characteristic of a receptor for signal transduction. Yet, the physiological function of APP is unclear, although it is well documented that APP's proteolytic processing, through the formation of membrane-bound C-terminal fragments (CTFs) and of beta-amyloid peptides, likely influences the development of Alzheimer's disease (AD). There is evidence that BACE1 is the enzyme responsible for beta-site cleavage of the APP and for the generation of CTFs. BACE1 expression is upregulated in AD brain, and we have recently shown in human brain and in vitro that BACE product CTFs, when phosphorylated in tyrosine residues, interact with the adaptor proteins ShcA and Grb2, which usually are involved in signal transduction pathways. We investigated the interaction between ShcA, APP, and CTFs in the H4 human cell line that overexpresses BACE1 to clarify the significance of such interactions in vitro and for AD generation. Our result show that the APP, CTF, and ShcA interaction is induced only upon overexpression of BACE1 either transiently or in stable cell lines. In particular, although BACE1 drives the formation of C99 and C89 CTFs, only C99 interacts with the ShcA adaptor protein. Therefore, our data suggest that BACE1 activity influences APP processing and its intracellular signaling through the ShcA adaptor protein.
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Distal aortic arch aneurysm after endovascular stent graft repair for type B chronic aortic dissection.
J Thorac Cardiovasc Surg2004 Oct;128(4):634-6.
Russo Claudio F, Garatti Andrea, Puttini Maurizio, Vitali Ettore
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Apoptotic cell death influences the signaling activity of the amyloid precursor protein through ShcA and Grb2 adaptor proteins in neuroblastoma SH-SY5Y cells.
J Neurochem2004 Sep;90(6):1359-70.
Venezia Valentina, Russo Claudio, Repetto Emanuela, Salis Serena, Dolcini Virginia, Genova Francesca, Nizzari Mario, Mueller Ulrike, Schettini Gennaro
Abstract
The amyloid precursor protein (APP) is an ubiquitous receptor-like molecule involved in the pathogenesis of Alzheimer's disease (AD). APP and some of its C-terminal proteolytic fragments (CTFs) have been shown to be phosphorylated and to interact with cytosolic phosphotyrosine binding (PTB) domain containing proteins involved in cell signaling and vesicular transport. Among others, the interaction between tyrosine-phosphorylated CTFs and ShcA-Grb2 adaptors is highly enhanced in AD brain. Here we have identified in SH-SY5Y neuroblastoma cells an interaction between APP holoprotein and the adaptor Grb2. Upon activation of apoptotic cell death this interaction is rapidly degraded, APP is partially cleaved and the complex APP/Grb2 is replaced by a new complex between CTFs and ShcA that still involves Grb2. The formation of these complexes is regulated by beta-site APP-cleaving enzyme 1 and influences the phosphorylation of mitogen-activated protein kinase p44/42 extracellular signal-regulated kinase as well as the level of apoptotic death of the cells. These data suggest a dual role in cell signaling for APP and its CTFs in neuroblastoma cells, in a manner similar to that previously reported for other tyrosine kinase receptor, through a tightly regulated coupling with alternative intracellular adaptors to control the signaling of the cell.
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First successful bridge to recovery with the Impella Recover 100 left ventricular assist device for fulminant acute myocarditis.
Ital Heart J2003 Sep;4(9):642-5.
Colombo Tiziano, Garatti Andrea, Bruschi Giuseppe, Lanfranconi Marco, Russo Claudio, Milazzo Filippo, Catena Emanuele, Frigerio Maria, Vitali Ettore
Abstract
A patient with septic and cardiogenic shock secondary to acute fulminant myocarditis was successfully treated by mechanical offloading of the left ventricle using the Impella Recover 100, a new implantable micro-axial blood pump designed for short-term circulatory support (for a maximum of 7 days). The possibility of implanting this device without using cardiopulmonary bypass allowed as to manage the septic shock, to reverse cardiac and hepatorenal failure and to wean the patient off treatment after 18 days of support. At 3 months the left and right ventricular function was satisfactory. The widespread application of this kind of support depends on the availability of an inexpensive "mini-invasive" blood pump, appropriate weaning protocols and emerging strategies to promote sustainable myocardial recovery.
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Left ventricular assist devices as bridge to heart transplantation: The Niguarda Experience.
J Card Surg2003 ;18(2):107-13.
Vitali Ettore, Lanfranconi Marco, Bruschi Giuseppe, Russo Claudio, Colombo Tiziano, Ribera Elena
Abstract
BACKGROUND:
Congestive heart failure is the leading cause of death in Western countries. Heart transplantation currently is the only accepted therapy for patients with end-stage heart failure, but the supply of donor hearts is inadequate, and different mechanical circulatory support systems have been investigated as bridges to heart transplant.
METHODS:
Since April 1992, 53 patients (47 men, 6 women, aged 12 to 61 years) received left ventricle mechanical circulatory support as bridge to heart transplant. The two principal devices used were: the Novacor LVAS in 31 patients and the DeBakey VAD in 11 patients.
RESULTS:
All patients survived the operation. Mean duration of LVAD support was 2.8 +/- 5.6 months. Thirty-seven patients (71.1%) underwent heart transplantation. Twelve major bleeding episodes occurred in nine patients (16.9%). Globally, major and minor neurologic events occurred in 13 patients (24.5%). Ten patients (19.9%) assisted with the Novacor Wearable LVAS device were discharged at home while waiting for heart transplant (HTx). The mean follow-up of the 34 discharged transplanted patients was 45.3 +/- 37 months. Actuarial survival of transplanted patients while on LVAD was 91.0 +/- 4.9% and 83.4 +/- 8.5% at 1 and 5 years, respectively. No differences in post-transplant long-term survival and rejection and allograft vasculopathy occurred between patients transplanted with or without LVAD implanted.
CONCLUSIONS:
LVAD therapy proved to be effective in bridging patients with end-stage heart failure to HTx. While on LVAD support, patients assisted with implantable wearable devices could be discharged at home, ameliorating their quality of life. The excellent survival rate after HTx is concomitant with a low incidence of rejection and cardiac allograft vasculopathy.
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Surgical therapy in advanced heart failure.
Am J Cardiol2003 May;91(9A):88F-94F.
Vitali Ettore, Colombo Tiziano, Fratto Pasquale, Russo Claudio, Bruschi Giuseppe, Frigerio Maria
Abstract
Congestive heart failure (CHF) affects about 1% of adults in the United States and is a contributing factor in >250,000 deaths per year. In an increasingly elderly population, the surgical treatment of CHF made great progress during the past 3 decades, consuming enormous health care resources. Heart transplantation is still the most effective therapy for end-stage heart disease, with the 10-year survival rate after transplantation approaching 50%. Efforts to increase the supply of donor organs have failed to improve the shortage, underscoring the crucial need for alternatives to cardiac allotransplantation. Alternative surgical options to end-stage heart transplantation are rapidly evolving. Left ventricular assist devices have been used as a bridge to heart transplantation for patients who otherwise might die awaiting a new heart. There is also continued interest in the use of these devices either to bridge patients to full recovery or to destination therapy, without the need for heart replacement. Left ventricular reconstruction, including the Batista and Dor procedures, along with mitral valve repair, cardiomyoplasty, and extreme coronary artery bypass graft surgery, are now being increasingly performed as alternative options. The history, status, and personal experience of surgical treatment of end-stage heart disease are discussed.
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Successful experience in bridging patients to heart transplantation with the MicroMed DeBakey ventricular assist device.
Ann Thorac Surg2003 Apr;75(4):1200-4.
Vitali Ettore, Lanfranconi Marco, Ribera Elena, Bruschi Giuseppe, Colombo Tiziano, Frigerio Maria, Russo Claudio
Abstract
BACKGROUND:
Pulsatile left ventricular assist devices are used with increasing frequency to bridge patients with end-stage heart failure to heart transplantation (HTx). Implantation of pulsatile devices is a cumbersome surgical procedure that is associated with major complications, such as bleeding, thromboembolism, and infection. Recently, a continuous axial flow left ventricular assist device (DeBakey ventricular assist device) has been introduced with the goal of reducing the incidence of major complications.
METHODS:
We reviewed our experience with 11 patients who received a DeBakey ventricular assist device axial flow pump for bridge to HTx from April 2000 through November 2001.
RESULTS:
Two patients (18.2%) died of multiple-organ failure while on left ventricular assist device support. Bleeding requiring thoracotomy occurred in 2 patients (18.2%). One patient had a minor neurologic event, and one patient developed left ventricular assist device thrombosis, which was successfully treated without pump exchange. Renal failure developed in 1 patient and hepatic dysfunction in 2 patients. There were no instances of right heart failure. No device, pocket, or drive-line infections occurred. Nine patients (9 of 11, 81.8%) had HTx within 51 +/- 49 days (range, 11 to 141 days) after left ventricular assist device implant. One patient died 29 days after HTx because of acute rejection.
CONCLUSIONS:
The continuous axial flow DeBakey ventricular assist device had reliable features, including a high rate of bridge to HTx. This device had low complication and system failure rates. We consider the DeBakey ventricular assist device a favorable alternative to pulsatile heart assist devices as a bridge to HTx.
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Contribution of two conserved glycine residues to fibrillogenesis of the 106-126 prion protein fragment. Evidence that a soluble variant of the 106-126 peptide is neurotoxic.
J Neurochem2003 Apr;85(1):62-72.
Florio Tullio, Paludi Domenico, Villa Valentina, Principe Daniela Rossi, Corsaro Alessandro, Millo Enrico, Damonte Gianluca, D'Arrigo Cristina, Russo Claudio, Schettini Gennaro, Aceto Antonio
Abstract
The fibrillogenic peptide corresponding to the residues 106-126 of the prion protein sequence (PrP 106-126) is largely used to explore the neurotoxic mechanisms underlying the prion disease. However, whether the neuronal toxicity of PrP 106-126 is caused by a soluble or fibrillar form of this peptide is still unknown. The aim of this study was to correlate the structural state of this peptide with its neurotoxicity. Here we show that the two conserved Gly114 and Gly119 residues, in force of their intrinsic flexibility, prevent the peptide assuming a structured conformation, favouring its aggregation in amyloid fibrils. The substitution of both Gly114 and Gly119 with alanine residues (PrP 106-126 AA mutated peptide) reduces the flexibility of this prion fragment and results in a soluble, beta-structured peptide. Moreover, PrP 106-126 AA fragment was highly toxic when incubated with neuroblastoma cells, likely behaving as a neurotoxic protofibrillar intermediate of the wild-type PrP 106-126. These data further confirm that the fibrillar aggregation is not necessary for the induction of the toxic effects of PrP 106-126.
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Signal transduction through tyrosine-phosphorylated carboxy-terminal fragments of APP via an enhanced interaction with Shc/Grb2 adaptor proteins in reactive astrocytes of Alzheimer's disease brain.
Ann N Y Acad Sci2002 Nov;973():323-33.
Russo Claudio, Dolcini Virginia, Salis Serena, Venezia Valentina, Violani Elisabetta, Carlo Pia, Zambrano Nicola, Russo Tommaso, Schettini Gennro
Abstract
The processing of the amyloid precursor protein (APP) through the formation of C-terminal fragments (CTFs) and the production of beta-amyloid, are events likely to influence the development and the progression of Alzheimer's disease (AD). APP is a transmembrane protein similar to a cell-surface receptor with the intraluminal NPTY motif in the cytosolic C terminus. Although APP holoprotein can be bound to intracellular proteins like Fe65, X11, and mDab, the ultimate function and the mechanisms through which this putative receptor transfers its message are unclear. Here it is shown that in human brain, a subset of tyrosine-phosphorylated CTFs represent docking sites for the adaptor protein ShcA. ShcA immunoreactivity is greatly enhanced in Alzheimer's patients; it is mainly localized to glial cells and occurs at reactive astrocytes surrounding cerebral vessels and amyloid plaques. Grb2 also is involved in complexes with ShcA and tyrosine-phosphorylated CTFs, and in AD brain the interaction between Grb2-ShcA and CTFs is enhanced. Also, a higher amount of phospho-ERK1,2 is present in AD brain in comparison with control cases, likely as a result of the ShcA activation. In vitro experiments show that the ShcA-CTFs interaction is strictly confined to glial cells when treated with thrombin, which is a well-known ShcA and ERK1,2 activator, mitogen, and regulator of APP cleavage. In untreated cells ShcA does not interact with either APP or CTFs, although they are normally produced. Altogether these data suggest that CTFs are implicated in cell signaling via Shc transduction machinery, likely influencing MAPK activity and glial reaction in AD patients.
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Aortic complications after bicuspid aortic valve replacement: long-term results.
Ann Thorac Surg2002 Nov;74(5):S1773-6; discussion S1792-9.
Russo Claudio F, Mazzetti Simone, Garatti Andrea, Ribera Elena, Milazzo Angela, Bruschi Giuseppe, Lanfranconi Marco, Colombo Tiziano, Vitali Ettore
Abstract
BACKGROUND:
Bicuspid aortic valve (BAV) is a risk factor for aortic dissection and aneurysm. We studied patients with BAV and tricuspid aortic valve (TAV) to evaluate long-term changes in the ascending aorta after aortic valve replacement (AVR).
PATIENTS AND METHODS:
One hundred consecutive patients were allocated into two groups according to the presence of BAV (group A, 50 patients) or TAV (group B, 50 patients). Mean age was 51 +/- 12 years in group A, and 50 +/- years 12 in group B. No patients had hypertension or Marfan's syndrome. Until July 2001, mean follow-up was 234 +/- 47 months in group A and 241 +/- 43 months in group B.
RESULTS:
Five patients (10%, CL 5.7 to 13.9) in group A suffered late acute aortic dissection. Acute aortic dissection (5 vs 0, p = 0.0001) and sudden death (7 vs 0, p = 0.0001) occurred more frequently in patients with BAV. All survivors were assessed by echocardiogram. The mean diameter of the ascending aorta was 48.4 mm in group A and 36.8 mm in group B. Three patients in group A were operated on because of ascending aorta aneurysm more than 6 cm in diameter.
CONCLUSIONS:
As a result of our experience, we recommend a policy of prophylactic replacement of even a seemingly normal and definitely a mildly enlarged ascending aorta in cases of BAV at the moment of AVR, and consideration of a similar approach for any other cardiac surgical procedure in patients with BAV.
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Pyroglutamate-modified amyloid beta-peptides--AbetaN3(pE)--strongly affect cultured neuron and astrocyte survival.
J Neurochem2002 Sep;82(6):1480-9.
Russo Claudio, Violani Elisabetta, Salis Serena, Venezia Valentina, Dolcini Virginia, Damonte Gianluca, Benatti Umberto, D'Arrigo Cristina, Patrone Eligio, Carlo Pia, Schettini Gennaro
Abstract
N-terminally truncated amyloid-beta (Abeta) peptides are present in early and diffuse plaques of individuals with Alzheimer's disease (AD), are overproduced in early onset familial AD and their amount seems to be directly correlated to the severity and the progression of the disease in AD and Down's syndrome (DS). The pyroglutamate-containing isoforms at position 3 [AbetaN3(pE)-40/42] represent the prominent form among the N-truncated species, and may account for more than 50% of Abeta accumulated in plaques. In this study, we compared the toxic properties, fibrillogenic capabilities, and in vitro degradation profile of Abeta1-40, Abeta1-42, AbetaN3(pE)-40 and AbetaN3(pE)-42. Our data show that fibre morphology of Abeta peptides is greatly influenced by the C-terminus while toxicity, interaction with cell membranes and degradation are influenced by the N-terminus. AbetaN3(pE)-40 induced significantly more cell loss than the other species both in neuronal and glial cell cultures. Aggregated AbetaN3(pE) peptides were heavily distributed on plasma membrane and within the cytoplasm of treated cells. AbetaN3(pE)-40/42 peptides showed a significant resistance to degradation by cultured astrocytes, while full-length peptides resulted partially degraded. These findings suggest that formation of N-terminally modified peptides may enhance beta-amyloid aggregation and toxicity, likely worsening the onset and progression of the disease.
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Molecular aspects of neurodegeneration in Alzheimer's disease.
Funct Neurol2002 ;17(2):65-70.
Russo Claudio, Venezia Valentina, Salis Serena, Dolcini Virginia, Schettini Gennaro
Abstract
Alzheimer's disease (AD) is a degenerative disease of the brain, and the most common form of dementia. It is estimated that more than 22 million individuals worldwide will have AD by 2025. The causes of the disease are still unknown and recent hypotheses suggest that an aberrant protein processing initiates the neurodegeneration. Several lines of research are centered on the study of proteins that are genetically associated with this syndrome, such as amyloid precursor protein (APP) and presenilins. This review focuses on recent advances in the processing of APP and on the neuropathological role of its amyloidogenic fragments, which have been shown to be directly involved in neurodegeneration and glial inflammation and which likely influence the development of AD.
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Mechanisms of phenotypic heterogeneity in prion, Alzheimer and other conformational diseases.
J Alzheimers Dis2001 Feb;3(1):87-95.
Gambetti Pierluigi, Parchi Piero, Capellari Sabina, Russo Claudio, Tabaton Massimo, Teller Jan K., Chen Shu G.
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Signal transduction through tyrosine-phosphorylated C-terminal fragments of amyloid precursor protein via an enhanced interaction with Shc/Grb2 adaptor proteins in reactive astrocytes of Alzheimer's disease brain.
J Biol Chem2002 Sep;277(38):35282-8.
Russo Claudio, Dolcini Virginia, Salis Serena, Venezia Valentina, Zambrano Nicola, Russo Tommaso, Schettini Gennaro
Abstract
The proteolytic processing of amyloid precursor protein (APP) through the formation of membrane-bound C-terminal fragments (CTFs) and of soluble beta-amyloid peptides likely influences the development of Alzheimer's disease (AD). We show that in human brain a subset of CTFs are tyrosine-phosphorylated and form stable complexes with the adaptor protein ShcA. Grb2 is also part of these complexes, which are present in higher amounts in AD than in control brains. ShcA immunoreactivity is also greatly enhanced in patients with AD and occurs at reactive astrocytes surrounding cerebral vessels and amyloid plaques. A higher amount of phospho-ERK1,2, likely as result of the ShcA activation, is present in AD brains. In vitro experiments show that the ShcA-CTFs interaction is strictly confined to glial cells when treated with thrombin, which is a well known ShcA and ERK1,2 activator and a regulator of APP cleavage. In untreated cells ShcA does not interact with either APP or CTFs, although they are normally generated. Altogether these data suggest that CTFs are implicated in cell signaling via Shc transduction machinery, likely influencing MAPK activity and glial reaction in AD patients.
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Successful intraventricular thrombolysis during ventricular assist device support.
Ann Thorac Surg2002 May;73(5):1628-9.
Russo Claudio, De Biase Anna Maria, Bruschi Giuseppe, Agati Salvatore, Vitali Ettore
Abstract
Different types of mechanical ventricular assist devices are available for treating end stage congestive heart failure. Despite technical improvements, however, various complications are still reported for patients during mechanical support. We report our experience with intraventricular thrombolysis as a treatment for possible thrombosis of a continuous flow device that had been implanted as a bridge to heart transplantation. This approach has been demonstrated to be both effective and safe.
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