Protective effects of mesenchymal stem cells-derived extracellular vesicles against ischemia-reperfusion injury of hearts donated after circulatory death: Preliminary study in a pig model.

INTRODUCTION: Insufficient supply of cardiac grafts represents a severe obstacle in heart transplantation. Donation after Circulatory Death (DCD), in addition to conventional donation after brain death, is one promising option to overcome the organ shortage. However, DCD organs undergo an inevitable more extended period of warm unprotected ischemia between circulatory arrest and graft procurement. Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have shown remarkable protective effects against ischemia-reperfusion injury. Thus, we aimed to enhance grafts preservation from DCD donors, through treatment with MSC-EVs. METHODS: Female pigs were euthanized by barbiturate overdose and after 20 min of a flat EKG, the chest was opened, the heart harvested and subsequently connected to an extracorporeal perfusion machine. MSC-EVs, isolated by ion exchange chromatography, were added to the perfusion solution (1×1011 particles) and the heart was perfused for 2 h. Then, heart tissue biopsies were taken to assess histological changes, mitochondrial morphology, antioxidant enzyme activity and inflammation mediators' expression. Biochemical parameters of myocardial viability were assessed in the perfusate. RESULTS: The treatment with MSC-EVs significantly prevented mitochondria swelling, mitochondrial cristae loss and oxidative stress in cardiac tissue. The protective effect of MSC-EVs was confirmed by the delayed increase of the cardiac-specific enzymes CK and TnC in the perfusate and the reduction of caspase-3+ cells in tissue sections. CONCLUSION: MSC-EVs improve graft quality by preserving the mitochondrial ultrastructure protecting the myocardium against oxidative stress, reducing apoptosis of cardiac cells and preventing the increase of pro-inflammatory cytokines.

Overcoming the Boundaries of Heart Warm Ischemia in Donation After Circulatory Death: The Padua Case.

A 45 year old male obese patient with a previous history of repaired congenital heart disease developed worsening heart failure making heart transplantation listing mandatory. Unfortunately, due to his anthropometric measures, the search for a suitable brain-dead donor was unsuccessful. For this reason, he accepted to be enrolled in the controlled donation after circulatory death (cDCD) program. According to the Italian Law regulating death declaration after cardiac arrest (no-touch period of 20 minutes-one of the longest in the world), we faced a 34 minute cardiac asystole, after which the heart was recovered through a thoraco-abdominal normothermic regional perfusion excluding the epiaortic vessels. The heart was then preserved by means of cold static storage. Heart transplantation was performed successfully without any signs of primary graft failure. Postoperative endomyocardial biopsies were negative for acute cellular and antibody-mediated rejection. Furthermore, echocardiographic and cardiac magnetic resonance evaluation of the heart did not show any functional abnormalities. The patient was discharged on post-operative day (POD) #39 in good clinical conditions.

The AngioVac System in Childhood and Adolescence: A New Venovenous Extracorporeal Membrane Oxygenation-Like Configuration.

Intravascular and intracardiac clots, thrombi, and vegetative material can be safely and effectively treated with the AngioVac System (AngioDynamics, Latham, NY) as an alternative to open surgery. However, this technology is still not performed in children or adolescents as a rule. We aimed to present our experience with two cases (a 10 year old girl and a 17 year old male adolescent) with concurrent hypoxemia in whom this device was successfully used in combination with venovenous extracorporeal membrane oxygenation to remove caval thrombi and cavoatrial septic material, respectively. This extracorporeal circuit configuration allowed adequate respiratory support during the procedure. No endovascular recurrence of the pathologic material was found at 2 and 1 year of follow-up, respectively.

Proof of Concept: Trans-atrial AngioVac Aspiration of Mitral Valve Thrombosis in a COVID-19 Patient.

In patients with a prohibitive surgical risk, the AngioVac cannula can be used to remove left-sided cardiac masses, as an off-label adaptation of the device. We herein describe a novel micro-invasive approach to gain access to the left atrium for the aspiration of a mitral valve mass in a patient affected by severe coronavirus disease 2019. Through a right anterior mini-thoracotomy, the right superior pulmonary vein was accessed and used to insert the aspiration cannula. A parallel venous-arterial extracorporeal membrane oxygenation (ECMO)-like circuit provided circulatory and respiratory support to ensure proper intra- and postoperative hemodynamic stabilization.

Navigating the Heart. The Evolution of the AngioVac System in a Single-center Experience.

We investigated the efficacy, safety, and versatility of the AngioVac (AngioDynamics, Latham, NY) system for the treatment of intravascular and intracardiac masses of different origins. We prospectively enrolled all consecutive patients treated with the AngioVac system between July-2016 and November-2021 at our institution. Three configurations of the device were adopted in 44 patients: a venous-venous circuit in 21 cases (47.7%), a venous-arterial ECMO-like configuration in 20 (45.5%), and a venous-arterial-arterial circuit with 2 centrifugal pumps for left-sided cardiac masses in 3 (6.8%). Successful removal of the mass was achieved in 41 patients (93.2%), while in the other cases conversion to full sternotomy was necessary. Intraoperative complications occurred in 3 cases (6.8%), including 1 death, 1 pulmonary embolization, and 1 cardiac perforation. The AngioVac system is a valid, safe, and versatile option for the treatment of intravascular masses also in patients with prohibitive surgical risk.

Prognosticating Mortality of Primary Cardiogenic Shock Requiring Extracorporeal Life Support: The RESCUE Score.

We aimed to identify prognostic laboratory markers during extracorporeal life support (ECLS) in patients with primary refractory cardiogenic shock (RCS) and to create a preliminary specific mortality score. All 208 consecutive subjects admitted for primary RCS and treated with ECLS between January-2009 and December-2018 were retrospectively analyzed. Multivariate regression analysis on laboratory markers during the first nine days of ECLS was used to develop a "Refractory End-stage Shock CUred with Ecls" (RESCUE) score. Serum creatinine (OR = 3.72, 95%CI: 2.01-6.88), direct bilirubin (OR = 1.40, 95%CI: 1.05-1.8), and platelet count (OR = 0.62, 95%CI: 0.42-0.94) were independent predictors of in-hospital mortality and were included in the score. The mean AUC was 0.763 (95%CI: 0.698-0.828) in the development cohort and 0.729 (95%CI: 0.664-0.794) in the bootstrap internal validation cohort. The RESCUE score represents a novel promising instrument to predict early mortality during the first critical days of ECLS and to help in properly guiding the therapeutic decision-making process.

Mycobacterium chimaera Infections in a Unit of Cardio Surgery: Study at a General Hospital in Padua, Italy.

Mycobacterium chimaera is a slow-growing non-tuberculous mycobacterium already known for being able to colonize cardio surgery heater-cooler units (HCUs). This study aims to describe the real magnitude of the phenomenon, providing a methodological protocol and the results of a longitudinal survey. In the period 1 January 2017-23 May 2022, over 1191 samples were collected on 35 HCUs of two different manufacturers. Among them, we identified 118 (10.3%) positive results for M. chimaera. We propose our 4-year biosurveillance experience as a practical model to minimize microbiological patients' risk, suggesting the need for new procedures and interventions for a safer and more ecological cardio surgery.

Vacuum-Implemented Removal of Lead Vegetations in Cardiac Device-Related Infective Endocarditis.

When approaching infected lead removal in cardiac device-related infective endocarditis (CDRIE), a surgical consideration for large (>20 mm) vegetations is recommended. We report our experience with the removal of large CDRIE vegetations using the AngioVac system, as an alternative to conventional surgery. We retrospectively reviewed all infected lead extractions performed with a prior debulking using the AngioVac system, between October 2016 and April 2022 at our institution. A total of 13 patients presented a mean of 2(1) infected leads after a mean of 5.7(5.7) years from implantation (seven implantable cardioverter-defibrillators, four cardiac resynchronization therapy-defibrillators, and two pacemakers). The AngioVac system was used as a venous−venous bypass in six cases (46.2%), venous−venous ECMO-like circuit (with an oxygenator) in five (38.5%), and venous−arterial ECMO-like circuit in two cases (15.4%). Successful (>70%) aspiration of the vegetations was achieved in 12 patients (92.3%) and an intraoperative complication (cardiac perforation) only occurred in 1 case (7.7%). Subsequent lead extraction was successful in all cases, either manually (38.5%) or using mechanical tools (61.5%). The AngioVac system is a promising effective and safe option for large vegetation debulking in CDRIE. Planning the extracorporeal circuit design may represent the optimal strategy to enhance the tolerability of the procedure and minimize adverse events.

How to Optimize ECLS Results beyond Ventricular Unloading: From ECMO to CentriMag® eVAD.

CentriMag® extracorporeal VAD support could represent a more physiological choice than conventional ECMO in primary cardiogenic shock. We therefore evaluated the outcome of patients with primary cardiogenic shock who were supported with CentriMag® extracorporeal VAD implantation versus conventional ECMO. We retrospectively reviewed all extracorporeal life supports implanted for primary cardiogenic shock between January 2009 and December 2018 at our institution. Among 212 patients, 143 cases (67%) were treated exclusively with ECMO (Group 1) and 69 cases (33%) with extracorporeal VAD implantation (Group 2, 48 of whom as conversion of ECMO). ECLS mean duration was 8.37 ± 8.43 days in Group 1 and 14.25 ± 10.84 days in Group 2 (p = 0.001), while the mean rates of the highest predicted flow were 61.21 ± 16.01% and 79.49 ± 18.42% (p = 0.001), respectively. Increasing mechanical support flow was related to in-hospital mortality and overall mortality in Group 1 (HR 11.36, CI 95%: 2.19-44.20), but not in Group 2 (HR 1.48, CI 95%: 0.32-6.80). High-flow ECMO patients had lower survival with respect to high-flow extracorporeal VAD patients (p = 0.027). In the setting of high-flow mechanical circulatory support, CentriMag® extracorporeal VAD optimized patient survival, granting long-term assistance and physiological circulation patterns.

Temperature-Related Effects of Myocardial Protection Strategies in Swine Hearts after Prolonged Warm Ischemia.

Insufficient supply of cardiac grafts represents a severe obstacle in heart transplantation. Donation after circulatory death (DCD), in addition to conventional donation after brain death, is one promising option to overcome the organ shortage. However, DCD organs undergo an inevitably longer period of unprotected warm ischemia between circulatory arrest and graft procurement. In this scenario, we aim to improve heart preservation after a warm ischemic period of 20 min by testing different settings of myocardial protective strategies. Pig hearts were collected from a slaughterhouse and assigned to one of the five experimental groups: baseline (BL), cold cardioplegia (CC), cold cardioplegia + adenosine (CC-ADN), normothermic cardioplegia (NtC + CC) or normothermic cardioplegia + cold cardioplegia + adenosine (NtC-ADN + CC). After treatment, tissue biopsies were taken to assess mitochondrial morphology, antioxidant enzyme activity, lipid peroxidation and cytokine and chemokine expressions. NtC + CC treatment significantly prevented mitochondria swelling and mitochondrial cristae loss. Moreover, the antioxidant enzyme activity was lower in this group, as was lipid peroxidation, and the pro-inflammatory chemokine GM-CSF was diminished. Finally, we demonstrated that normothermic cardioplegia preserved mitochondria morphology, thus preventing oxidative stress and the subsequent inflammatory response. Therefore, normothermic cardioplegia is a better approach to preserve the heart after a warm ischemia period, with respect to cold cardioplegia, before transplantation.

Totally peripheral approach for ICD lead vegetation removal in a GUCH patient.

AngioVac system (AngioDynamics) has already proved to be a useful tool in the treatment of thrombotic and endocarditic formations concerning the venous district. Herein, the AngioVac aspiration system combined with the bidirectional rotational Evolution mechanical sheath lead extraction was used for an effective and safety cardiac-device-related-infective-endocarditis removal in a grown-up congenital heart disease patient through a totally peripheral approach.

Proof of Concept: Microinvasive AngioVac Approach in Renal Cell Carcinoma With Atrial Thrombosis.

The AngioVac system (AngioDynamics, Latham, NY) has already been described for treatment of thrombotic formations concerning the venous district and the tricuspid valve. We describe an innovative application of the AngioVac system to treat the inferior vena cava thrombosis associated with renal cell carcinoma. In a high surgical risk patient, we utilized a microinvasive and a modified venoarterial AngioVac circuit to remove the atrial thrombus, ensure temporary circulatory support during abdominal surgery, and prevent pulmonary embolism.

RegenHeart: A Time-Effective, Low-Concentration, Detergent-Based Method Aiming for Conservative Decellularization of the Whole Heart Organ.

Heart failure is the worst outcome of all cardiovascular diseases and still represents nowadays the leading cause of mortality with no effective clinical treatments, apart from organ transplantation with allogeneic or artificial substitutes. Although applied as the gold standard, allogeneic heart transplantation cannot be considered a permanent clinical answer because of several drawbacks, as the side effects of administered immunosuppressive therapies. For the increasing number of heart failure patients, a biological cardiac substitute based on a decellularized organ and autologous cells might be the lifelong, biocompatible solution free from the need for immunosuppression regimen. A novel decellularization method is here proposed and tested on rat hearts in order to reduce the concentration and incubation time with cytotoxic detergents needed to render acellular these organs. By protease inhibition, antioxidation, and excitation-contraction uncoupling in simultaneous perfusion/submersion modality, a strongly limited exposure to detergents was sufficient to generate very well-preserved acellular hearts with unaltered extracellular matrix macro- and microarchitecture, as well as bioactivity.

Transapical Aspiration of a Mitral Mass With the AngioVac System on a Beating Heart.

The AngioVac System has already proved to be effective and safe in the treatment of thrombotic and endocarditic formations concerning the venous district and the tricuspid valve. We describe an innovative use of the AngioVac System to treat a left-sided heart mass. In a high-surgical-risk patient, we used a micro-invasive transapical access and a modified extracorporeal membrane oxygenation circuit to remove the mass from the mitral bioprosthesis without having to replace it. Further experiences are required to confirm the safety of this technique in high-risk patients.

Minimally invasive surgery for atrial septal defects: a 20-year experience at a single centre.

OBJECTIVES: Our goal was to evaluate the results of our 20-year experience with minimally invasive surgical approaches for closing ostium secundum atrial septal defects, focusing on clinical results, patient satisfaction and cost-effectiveness. METHODS: We included 538 patients who underwent surgical ostium secundum atrial septal defects closure with minimally invasive approaches. RESULTS: The minimally invasive approaches included right anterior minithoracotomy (n = 335, 62%), midline lower ministernotomy (135, 25%) and right lateral minithoracotomy (n = 68, 13%). Central cannulation was used in 374 patients (69%), whereas, more recently, a remote cardiopulmonary bypass with peripheral cannulation was used in 164 selected patients (31%). Median intensive care unit and postoperative hospitalization stays were 1 day [interquartile range (IQR) 1-1 day] and 5 days (IQR 5-6 days), respectively. Thirty-one patients had postoperative complications (5.8%); postcardiotomy syndrome was the most frequent complication (n = 20/538, 3.7%). Decreases in the length of postoperative hospitalization (P < 0.001) and in hospital costs (P = 0.009) were achieved over time. At a median follow-up of 12.1 years (IQR 0.6-14 years), all patients are in good clinical condition with no limitations to physical activity. The vast majority of patients (524/538 patients, 97%) were very satisfied with the result of the minimally invasive approaches (99/100 patients, 99% in the last 5 years). CONCLUSIONS: Minimally invasive approaches for closing ostium secundum atrial septal defects proved safe and effective both in children and in adults with a very high satisfaction rate for the cosmetic result. A continuous evolution of our minimally invasive approaches, with a constant quest for less invasive procedures, led us to a miniaturization of the surgical accesses, reducing hospitalization time and hospital costs.

HandS ECMO: Preliminary Experience With "Hub and Spoke" Model in Neonates With Meconium Aspiration Syndrome.

We aim to evaluate clinical outcomes of emergent extracorporeal membrane oxygenation (ECMO) implantation in newborns with life-threatening meconium aspiration syndrome (MAS) in peripheral hospitals with Hub and Spoke (HandS) setting. We retrospectively reviewed all neonates presenting with MAS, with no other comorbidities, treated with HandS ECMO, in peripheral hospitals. Team activation time (TAT) was described as the time from first alerting call to ECMO support initiation. From May 2014 to December 2016, 4 patients met our inclusion criteria. In addition, 2 cases occurred on the same day, requiring a second simultaneous HandS ECMO team activation. All patients were younger than 8 days of life (1, 1, 4, and 7), with a mean BSA 0.21 ± 0.03m2 , and TAT of 203, 265, 320, and 340 min. One patient presented ventricular fibrillation after priming administration. Veno-arterial ECMO was established in all patients after uneventful surgical neck vessels cannulation (right carotid artery and jugular vein). Mean time from skin incision to ECMO initiation was 19 ± 1.4 min. Mean length of ECMO support was 2.75 ± 1.3 days. All patients were weaned off support without complications. At a mean follow up of 20.5 ± 7.8 months, all patients are alive, with no medications, normal somatic growth, and neuropsychological development. MAS is a life-threatening condition that can be successfully managed with ECMO support. A highly trained multidisciplinary HandS ECMO team is crucial for the successful management of these severely ill newborns in peripheral hospitals.

Impacto na qualidade de vida em pacientes usuários de medicação retroviral e submetidos à gluteoplastia: estudo de coorte histórica / Gluteal contour restoration in antiretroviral users and its quality-of-life related impacts: a historical cohort study

INTRODUÇÃO: Desde a introdução do tratamento do HIV com uso da terapia antirretroviral altamente ativa, a mortalidade por essa doença foi reduzida drasticamente em todo o mundo. Um dos parefeitos relacionados à utilização desses fármacos é a lipodistrofia glútea. O objetivo deste trabalho é verificar o impacto da correção dessa deformidade na qualidade de vida de pacientes com HIV. MÉTODOS: Foi conduzido um estudo de coorte histórica com 23 pacientes submetidos à gluteoplastia com implante intramuscular, entre janeiro de 2010 e dezembro de 2014, avaliando a qualidade de vida por meio do em Nottingham Health Profile em. As informações foram coletadas de julho a agosto de 2015. A análise estatística foi feita utilizando-se o em Related-Samples McNemar Test em. RESULTADOS: strong Houve diferença significativa entre o pré-operatório e pós-operatório em 19 das 38 perguntas. CONCLUSÃO: É possível afirmar que a reconstrução glútea melhora a qualidade de vida de pacientes HIV positivos acometidos por lipodistrofia glútea relacionada a antirretrovirais.

INTRODUCTION: Since the introduction of highly active antiretroviral therapy for the treatment of human immunodeficiency virus (HIV), disease mortality has been dramatically reduced worldwide. One related side effect from the use of these drugs is gluteal lipodystrophy. The aim of this study is to assess the quality-of-life impact of correcting this deformity in HIV patients. METHODS: A historical cohort study was conducted between January 2010 and December 2014 with 23 patients, assessing the quality of their lives using the Nottingham Health Profile. A statistical analysis was performed using the McNemar test for related samples. RESULTS: There was a significant difference between preoperative and postoperative response in 19 of the 38 questions. CONCLUSION: We may say that gluteal reconstruction plays a role in improving quality of life for HIV patients who have been affected by antiretroviral related gluteal lipodystrophy.

The Vietnamese pig as a translational animal model to evaluate tissue engineered heart valves: promising early experience.

Several animal models are currently used for the surgical implantation of either biologic or biopolymeric scaffolds in order to provide in vivo assessment of tissue-engineered heart valves. The Vietnamese pig (VP) is herein proposed as a suitable recipient to test the function of novel bioengineered valve substitutes, in the reconstruction of the right ventricular outflow tract (RVOT). This review aims to provide a complete and exhaustive panel of physiological parameters and methodological information for preclinical studies of tissue-engineered heart valves in the VP animal model.

The "basic" approach: a single-centre experience with a cost-reducing model for paediatric cardiac extracorporeal membrane oxygenation.

Objectives: Extracorporeal membrane oxygenation (ECMO) is a lifesaving but expensive therapy in terms of financial, technical and human resources. We report our experience with a 'basic' ECMO support model, consisting of ECMO initiated and managed without the constant presence of a bedside specialist, to assess safety, clinical outcomes and financial impact on our health system. Methods: We did a retrospective single-centre study of paediatric cardiac ECMO between January 2001 and March 2014. Outcomes included postimplant complications and survival at weaning and at discharge. We used activity based costing to compare the costs of current basic ECMO with those of a 'full optional' dedicated ECMO team (hypothesis 1); ECMO with a bedside nurse and perfusionist (hypothesis 2), and ECMO with a bedside perfusionist (hypothesis 3). Results: Basic cardiac ECMO was required for 121 patients (median age 75 days, median weight 4.4 kg). A total of 107 patients (88%) had congenital heart disease; 37 had univentricular physiology. The median duration of ECMO was 7 days (interquartile range [IQR], 4-15 days). Overall survival at weaning and at 30 days in the neonatal and paediatric age groups was 58.6% and 30.6%, respectively; these results were not significantly different from Extracorporeal Life Support Organization data. Cost analysis revealed a saving of €30 366, €22 144 and €13 837 for each patient on basic ECMO for hypotheses 1, 2 and 3, respectively. Conclusions: Despite reduced human, technical and economical resources, a basic ECMO model without a bedside specialist was associated with satisfactory survival and lower costs.

O impacto de ações assistenciais na percepção da qualidade do Sistema Único de Saúde (SUS), Brasil: um estudo transversal / The impact of care actions on the perception of the quality of the Single Health System (SUS), Brazil: a cross-sectional study

INTRODUÇÃO: O tumor de pele não melanoma é o câncer mais frequente no Brasil. A ressecção cirúrgica é um dos pilares do manejo e ações assistenciais como mutirões de cirurgias são formas de reduzir o tempo de espera por tratamento. MÉTODOS: Nesse trabalho, conduziu-se um estudo transversal com 40 pacientes, 20 deles participantes de mutirão e 20 controles. Coletaram-se dados epidemiológicos, além de nove perguntas relacionadas à qualidade do Sistema Único de Saúde (SUS). RESULTADOS: Observou-se diferença significativa entre as respostas relacionadas ao tempo de espera por cirurgias no SUS (p < 0,05). CONCLUSÃO: Pode-se verificar melhora na impressão dos pacientes em relação ao SUS quando incluídos em ações assistenciais.

INTRODUCTION: Non-melanoma skin cancer is the most prevalent cancer in Brazil. Surgical resection is one of the pillars of management, and care actions, such as surgical task forces, are one way to reduce treatment waiting time. METHODS: In this research, we conducted a cross-sectional study with 40 patients; 20 of whom were treated by a surgical task force and 20 were controls. Epidemiological data were collected in addition to answers to nine questions related to the quality of the Single Health System (SUS in Portuguese). RESULTS: A significant difference was observed in responses related to the waiting time for surgery in the SUS (p < 0.05). CONCLUSION: One can observe an improvement in the perception of patients, with regard to the SUS, when included in care actions.