Trasplante cardíaco

Kyobu Geka. 2022 Apr;75(4):259-264.

ABSTRACT

In order to overcome challenges of serious short supply of donor organs, a unique partnership between transplant consultant doctors and local physicians, named medical consultant( MC) system, started in 2002 to maximize the organ utilization rate. As the first step of this system, skillfull heart transplant surgeons were sent to procurement hospitals as MCs to assess donor organ function and provide intensive care to donors. Since 2006, the MC doctors have requested the donors' attending physicians to perform aggressive bronchial suctioning using bronchoscopy, leading to an improved lung utilization rate and better graft survival. Since 2011, more than 25 lung MCs have been registered to assess donor lungs and provide advices on intensive respiratory care to donors. The effects of this system on lung transplantation opportunities and outcomes were retrospectively reviewed in 187 brain-dead lung donor candidates, which were chronologically divided into 3 phases:Ⅰ( May 1998 to November 2006, n=44) and Ⅱ( December 2006 to January 2011, n=64), before and after MCs requested local attending physicians to perform aggressive bronchial suctioning using bronchoscopy, respectively;and phase Ⅲ (February 2011 to January 2013, n=79), after the emergence of lung MCs( Hoshikawa Y, et al. Transplant Proc 47( 3):746-750, 2015). The lung utilization rates in phases Ⅰ, Ⅱ, and Ⅲ, were 61, 72, and 75%( per donor);51, 65, and 68% (per lung, p=0.03). Graft death due to primary graft dysfunction was significantly more frequent in phase Ⅰ (13.3%) than in phases Ⅱ (3.6%) and Ⅲ (3.7%, per lung, p=0.04). The lung utilization rate of 63 brain-dead lung donor candidates for a period of one year from June 2020 to May 2021, which was analyzed anew for this article, was 83%( per donor) and 72%( per lung). We discussed current status and tasks of the lung MC system which has been operated for 10 years.

PMID:35342155

Curr Probl Cardiol. 2022 Mar 24:101176. doi: 10.1016/j.cpcardiol.2022.101176. Online ahead of print.

ABSTRACT

BACKGROUND: As the rapidly aging population and the rising incidence of end-stage heart failure (HF), extensive research has been conducted on heart transplantation (HTx). Bibliometrics harbors the function for describing the relationships of knowledge structures in different research fields and predicting the growth trend .

METHODS: The publications were searched and filtered based on the WOS core database. The target literature was visualized and analyzed by CiteSpace or VOSviewer .

RESULTS: In total, 19,998 published papers were obtained. There is a wave-like growth in HTx development. Most advanced research results are concentrated in a few developed countries, while the interactions with developing countries are still in infancy. The United States occupies a strong dominant position among active countries on HTx. Early research hotpots mostly focused on primary disease, survival risk factors, and complications. In recent years, the research frontiers have shifted steadily to clinical evaluation of immunosuppressants and diagnosis of acute rejection, cardiac re-injury with COVID-19, innovations in ventricular assist devices(VAD), and donation allocation strategies. The research directions of HTx are gradually shifting from observational studies to intervention research.

PMID:35341797 | DOI:10.1016/j.cpcardiol.2022.101176

J Heart Lung Transplant. 2022 Feb 26:S1053-2498(22)01831-9. doi: 10.1016/j.healun.2022.02.012. Online ahead of print.

ABSTRACT

BACKGROUND: The lung allocation score prioritizes candidates for a lung transplant in the United States. As the country adopts the continuous distribution framework for organ allocation, we must reevaluate lung allocation score assumptions to maximize transplant benefit.

METHODS: We used Scientific Registry of Transplant Recipients data to study the impact of these changes: (1) updating cohorts; (2) transitioning from 1- to 5-year posttransplant survival; (3) using time-varying effects for non-proportional hazards; and (4) weighting waitlist and posttransplant area under the curve differently. Models were compared using Spearman correlations and C-statistics. The thoracic simulation allocation model characterized transplant rates and proportions of recipient subgroups under the current and new systems.

RESULTS: Posttransplant areas under the curve models were estimated with recipients aged ≥12 from January 1, 2014, to December 31, 2018. All models had similar C-statistics and Spearman correlations, indicating similar predictive performance and posttransplant area under the curve rankings. Five-year posttransplant area under the curve across age and diagnosis groups varied more than 1-year groups. Using the thoracic simulation allocation model, 1- and 5-year posttransplant model under the curve models showed similar transplant rates and recipient characteristics under the current system, but under continuous distribution, 5-year posttransplant area under the curve resulted in increased transplant rates with more recipients younger and in diagnosis groups B and C.

CONCLUSION: Incorporating equally weighted waitlist and posttransplant models using 5-year posttransplant survival detected the largest variability in survival under the continuous distribution system, which could improve long-term survival in the United States.

PMID:35341678 | DOI:10.1016/j.healun.2022.02.012

Ann Thorac Surg. 2022 Mar 18:S0003-4975(22)00154-0. doi: 10.1016/j.athoracsur.2021.11.078. Online ahead of print.

ABSTRACT

The HeartWare HVAD System (Medtronic) is a durable implantable left ventricular assist device that has been implanted in approximately 20,000 patients worldwide for bridge to transplant and destination therapy indications. In December 2020, Medtronic issued an Urgent Medical Device Communication informing clinicians of a critical device malfunction in which the HVAD may experience a delay or failure to restart after elective or accidental discontinuation of pump operation. Moreover, evolving retrospective comparative effectiveness studies of patients supported with the HVAD demonstrated a significantly higher risk of stroke and all-cause mortality when compared with a newer generation of a commercially available durable left ventricular assist device. Considering the totality of this new information on HVAD performance and the availability of an alternate commercially available device, Medtronic halted the sale and distribution of the HVAD System in June 2021. The decision to remove the HVAD from commercial distribution now requires the use of the HeartMate 3 left ventricular assist system (Abbott, Inc) if a patient previously implanted with an HVAD requires a pump exchange. The goal of this document is to review important differences in the design of the HVAD and HeartMate 3 that are relevant to the medical management of patients supported with these devices, and to assess the technical aspects of an HVAD-to-HeartMate 3 exchange. This document provides the best available evidence that supports best practices.

PMID:35341592 | DOI:10.1016/j.athoracsur.2021.11.078

J Thorac Cardiovasc Surg. 2022 Mar 15:S0022-5223(21)01738-4. doi: 10.1016/j.jtcvs.2021.11.085. Online ahead of print.

ABSTRACT

The HeartWare HVAD System (Medtronic) is a durable implantable left ventricular assist device that has been implanted in approximately 20,000 patients worldwide for bridge to transplant and destination therapy indications. In December 2020, Medtronic issued an Urgent Medical Device Communication informing clinicians of a critical device malfunction in which the HVAD may experience a delay or failure to restart after elective or accidental discontinuation of pump operation. Moreover, evolving retrospective comparative effectiveness studies of patients supported with the HVAD demonstrated a significantly higher risk of stroke and all-cause mortality when compared with a newer generation of a commercially available durable left ventricular assist device. Considering the totality of this new information on HVAD performance and the availability of an alternate commercially available device, Medtronic halted the sale and distribution of the HVAD System in June 2021. The decision to remove the HVAD from commercial distribution now requires the use of the HeartMate 3 left ventricular assist system (Abbott, Inc) if a patient previously implanted with an HVAD requires a pump exchange. The goal of this document is to review important differences in the design of the HVAD and HeartMate 3 that are relevant to the medical management of patients supported with these devices, and to assess the technical aspects of an HVAD-to-HeartMate 3 exchange. This document provides the best available evidence that supports best practices.

PMID:35341579 | DOI:10.1016/j.jtcvs.2021.11.085

Am J Cardiol. 2022 Mar 24:S0002-9149(22)00183-7. doi: 10.1016/j.amjcard.2022.02.018. Online ahead of print.

ABSTRACT

New-onset heart failure is a frequent complication after orthotopic liver transplantation (OLT). Left atrial enlargement (LAE) may be a sign of occult left heart disease. Our primary objective was to determine invasive hemodynamic and clinical predictors of LAE and then investigate its effect on post-transplant outcomes. Of 609 subjects who received OLT between January 1, 2010, and October 1, 2018, 145 who underwent preoperative right-sided cardiac catheterization and transthoracic echocardiography were included. Seventy-eight subjects (54%) had pretransplant LAE. Those with LAE had significantly lower systemic vascular resistance with higher cardiac and stroke volume index (61.0 vs 51.7 ml/m2; p <0.001), but there was no difference in pulmonary artery wedge pressure. There was a linear relation between left atrial volume index and stroke volume index (R2 = 0.490, p<0.001), but not pulmonary artery wedge pressure. The presence of severe LAE was associated with a reduced likelihood (hazard ratio = 0.26, p = 0.033) of reaching the composite end point of new-onset systolic heart failure, heart failure hospitalization, or heart failure death within 12 months post-transplant. There was also a significant reduction in LAE after transplantation (p = 0.013). In conclusion, LAE was common in OLT recipients and was more closely associated with stroke volume than left heart filling pressures. The presence of LAE was associated with a reduced likelihood of reaching composite outcomes and tended to regress after transplant.

PMID:35341576 | DOI:10.1016/j.amjcard.2022.02.018

Transpl Int. 2022 Mar 10;35:10176. doi: 10.3389/ti.2022.10176. eCollection 2022.

ABSTRACT

Severe primary graft dysfunction (PGD) is the leading cause of early postoperative mortality following orthotopic heart transplantation (OHT). Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been used as salvage therapy. This study aimed to evaluate the outcomes in adult OHT recipients who underwent VA-ECMO for severe PGD. We retrospectively reviewed 899 adult (≥18 years) patients who underwent primary OHT at our institution between 1997 and 2017. Recipients treated with VA-ECMO (19, 2.1%) exhibited a higher incidence of previous cardiac surgery (p = .0220), chronic obstructive pulmonary disease (p = .0352), and treatment with a calcium channel blocker (p = .0018) and amiodarone (p = .0148). Cardiopulmonary bypass (p = .0410) and aortic cross-clamp times (p = .0477) were longer in the VA-ECMO cohort and they were more likely to have received postoperative transfusion (p = .0013); intra-aortic balloon pump (IABP, p < .0001), and reoperation for bleeding or tamponade (p < .0001). The 30-day, 1-year, and overall survival after transplantation of non-ECMO patients were 95.9, 88.8, and 67.4%, respectively, compared to 73.7, 57.9, and 47.4%, respectively in the ECMO cohort. Fourteen (73.7%) of the ECMO patients were weaned after a median of 7 days following OHT (range: 1-12 days). Following OHT, VA-ECMO may be a useful salvage therapy for severe PGD and can potentially support the usage of marginal donor hearts.

PMID:35340846 | PMC:PMC8943911 | DOI:10.3389/ti.2022.10176

Pediatr Transplant. 2022 Mar 27:e14276. doi: 10.1111/petr.14276. Online ahead of print.

ABSTRACT

INTRODUCTION: Brugada syndrome is an inherited channelopathy characterized by arrhythmia and an increased risk of sudden cardiac death (SCD). Implantation of a defibrillator for primary or secondary prevention is the only effective strategy to decrease the risk of SCD in Brugada syndrome. We present a case in which a cardiac donor had a pathogenic variant for Brugada syndrome, discovered on genetic testing after transplantation.

CASE REPORT: A young child with dilated cardiomyopathy underwent orthotopic heart transplantation from a donor with in-hospital cardiac arrest in the context of fever and a normal ECG. Approximately 1 month after transplant, the donor's post mortem genetic testing revealed a pathogenic loss-of-function SCN5A variant associated with Brugada syndrome, which was confirmed on genetic testing on a post-transplant endomyocardial biopsy from the recipient. The recipient's post-transplant electrocardiographic monitoring revealed persistent right bundle branch block and progressive, asymptomatic sinus node dysfunction. The recipient was managed with precautionary measures including aggressive fever management, avoidance of drugs that increase arrhythmia risk in Brugada syndrome, and increased frequency of arrhythmia surveillance. The recipient remains asymptomatic at over 3 years post-transplant with preserved graft function and no documented ventricular arrhythmias.

CONCLUSION: We describe the clinical course of "acquired" Brugada syndrome in a cardiac allograft recipient, which has not been previously reported. The time-sensitive nature of donor organ selection, especially in critically ill recipients, combined with the growing use of molecular autopsies in patients with unexplained etiologies for death may increasingly result in important donor genetic information being made available after transplantation.

PMID:35340105 | DOI:10.1111/petr.14276

Pediatr Transplant. 2022 Mar 27:e14272. doi: 10.1111/petr.14272. Online ahead of print.

ABSTRACT

BACKGROUND: Third-dose mRNA COVID-19 vaccine is currently recommended in the United States for SOT recipients based in part on data showing diminished immune response, including Ab production, after a two-dose regimen. Data on vaccine response in adolescent and young adult SOT recipients are limited, including no data reported on third-dose responsiveness.

METHODS: Results of serologic testing in a convenience sample of 28 vaccinated adolescent and young adult HT recipients at a single institution were collected from the medical record and summarized.

RESULTS: At a median of 98.5 days (IQR 59-150) after second dose, 17 (61%) had an Ab response. Among 12 who had serology before and after third-dose vaccination, four of seven who were negative prior to third dose became positive at a median of 34 days (IQR 31-39.5) following third dose. No myocarditis, acute rejection, graft dysfunction, graft loss, or deaths were observed.

CONCLUSIONS: These findings support recommendations for the routine administration of three doses of mRNA vaccines in adolescent and young adult HT recipients and show a potential subpopulation in whom the fourth dose should be contemplated.

PMID:35340096 | DOI:10.1111/petr.14272

Ann Thorac Surg. 2022 Mar 23:S0003-4975(22)00366-6. doi: 10.1016/j.athoracsur.2022.02.073. Online ahead of print.

ABSTRACT

BACKGROUND: Some patients with hypertrophic cardiomyopathy (HCM) present with reduced left ventricular (LV) stroke volume and elongated systolic cavity obliteration due to symmetric LV hypertrophy. In the present report, we detail our experience with transapical septal myectomy to enlarge the LV volume and relieve cavity obliteration in this unique subgroup of HCM patients.

METHODS: We analyzed 38 patients with HCM who had extended symmetrical LV hypertrophy and underwent transapical septal myectomy to enlarge LV cavity from February 2001 to May 2021.

RESULTS: At the time of evaluation for surgery, 84.2% (n=32) of the patients were in New York Heart Association class III/IV. The peak oxygen consumption was 51.5 (44.0-58.0)% of the normal predicted values on the preoperative exercise stress test (n=16). Preoperative left atrial sizes in this cohort were enlarged (left atrial volume index, 39.0 (33.5-51.5) mL/m2), despite only 4 patients with moderate or greater mitral valve regurgitation (MR). All patients underwent transapical septal myectomy to enlarge the LV cavity size. There was no postoperative (within 30 days) mortality. During a median (IQR) follow-up of 3.4 (0.7-6.9) years, the estimated survival rates were 100%, 92%, and 87% at 1-, 3-, and 5-year respectively. Follow-up surveys suggested that 16 of the 17 contacted patients experienced improvement in their heart function post procedure.

CONCLUSIONS: Transapical myectomy to enlarge LV cavity volume can be performed safely with good early survival and functional results. This procedure is an important alternative to cardiac transplantation for HCM patients with systolic cavity obliteration and progressive heart failure.

PMID:35339438 | DOI:10.1016/j.athoracsur.2022.02.073

J Cardiovasc Comput Tomogr. 2022 Mar 16:S1934-5925(22)00040-5. doi: 10.1016/j.jcct.2022.03.003. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiac screening using coronary computed tomography angiography (CCTA) in kidney transplant candidates before transplantation yields both diagnostic and prognostic information. Whether CT-derived fractional flow reserve (FFRCT) analysis provides prognostic information is unknown. This study aimed to assess the prognostic value of FFRCT for predicting major adverse cardiac events (MACE) and all-cause mortality in kidney transplant candidates.

METHODS: Among 553 consecutive kidney transplant candidates, 340 CCTA scans (61%) were evaluated with FFRCT analysis. Patients were categorized into groups based on lowest distal FFRCT; normal >0.80, intermediate 0.80-0.76, and low ≤0.75. In patients with ≥50% stenosis, a lesion-specific FFRCT was defined as; normal >0.80 and abnormal ≤0.80. The primary endpoint was MACE (cardiac death, resuscitated cardiac arrest, myocardial infarction or revascularization). The secondary endpoint was all-cause mortality.

RESULTS: Median follow-up was 3.3 years [2.0-5.1]. MACE occurred in 28 patients (8.2%), 29 patients (8.5%) died. When adjusting for risk factors and transplantation during follow-up, MACE occurred more frequently in patients with distal FFRCT ≤0.75 compared to patients with distal FFRCT >0.80: Hazard Ratio (HR): 3.8 (95%CI: 1.5-9.7), p ​< ​0.01. In the lesion-specific analysis with <50% stenosis as reference, patients with lesion-specific FFRCT >0.80 had a HR for MACE of 1.5 (95%CI: 0.4-4.8), p ​= ​0.55 while patients with lesion-specific FFRCT ≤0.80 had a HR of 6.0 (95%CI: 2.5-14.4), p ​< ​0.01. Abnormal FFRCT values were not associated with increased mortality.

CONCLUSION: In kidney transplant candidates, abnormal FFRCT values were associated with increased MACE but not mortality. Use of FFRCT may improve cardiac evaluation prior to transplantation.

PMID:35339408 | DOI:10.1016/j.jcct.2022.03.003

Biochem Biophys Res Commun. 2022 Mar 19;606:10-16. doi: 10.1016/j.bbrc.2022.03.043. Online ahead of print.

ABSTRACT

BACKGROUND: There is compelling evidence implicating dysregulated inflammation in the mechanism of ventricular remodeling and heart failure (HF) after MI. The transcription factor nuclear factor erythroid-derived 2-like 2 (Nrf2, encoded by Nfe2l2) is a promising target in this context since it impedes transcriptional upregulation of pro-inflammatory cytokines and is anti-inflammatory in various murine models.

OBJECTIVES: We aimed to investigate the contribution of Nrf2 to the inflammatory response after experimental myocardial infarction (MI).

METHODS: We subjected Nrf2-/- mice and wild type (WT) controls to permanent left coronary artery (LCA) ligation. The inflammatory response was investigated with fluorescence-activated cell sorting (FACS) analysis of peripheral blood and heart cell suspensions, together with qRT-PCR of infarcted tissue for chemokines and their receptors. To investigate whether Nrf2-mediated transcription is a dedicated function of leukocytes, we interrogated publicly available RNA-sequencing (RNA-seq) data from mouse hearts after permanent LCA ligation for Nrf2-regulated gene (NRG) expression.

RESULTS: FACS analysis demonstrated a profoundly inflamed phenotype in the hearts of global Nrf2-/- mice as compared to WT mice after MI. Moreover, infarcted tissue from Nrf2-/- mice displayed higher expression of mRNA coding for inflammatory cytokines, chemokines, and their receptors, including IL-6, Ccl2, and Cxcr4. RNA-seq analysis showed upregulated NRG expression in WT mice after MI compared to naive mice, which was significantly higher in bioinformatically isolated CCR2+ cells.

CONCLUSIONS: Taken together, the results suggest that Nrf2 signalling in leukocytes, and possibly CCR2+ monocytes and monocyte-derived cardiac resident macrophages, may be potential targets to prevent post-MI ventricular remodeling.

PMID:35338853 | DOI:10.1016/j.bbrc.2022.03.043

ESC Heart Fail. 2022 Mar 26. doi: 10.1002/ehf2.13899. Online ahead of print.

ABSTRACT

AIMS: Left ventricular assist devices (LVADs) have reduced the mortality of patients with advanced heart failure both as bridge-to-transplant and as destination therapy. However, LVADs are associated with various complications, including bleedings, which affect the prognosis. The aim of the study was to explore the prevalence, management, and outcomes of haemorrhagic adverse events in LVAD recipients.

METHODS AND RESULTS: We conducted a retrospective, single-centre, cohort study including all patients who received an LVAD from January 2008 to December 2019 in our tertiary centre (Rangueil University Hospital, Toulouse, France). Bleeding events, death, and heart transplantation were collected from electronic medical files. Eighty-eight patients were included, and 43 (49%) presented at least one bleeding event. Gastrointestinal (GI) bleeding was the most frequent (n = 21, 24%), followed by epistaxis (n = 12, 14%) and intracranial haemorrhage (n = 9, 10%). Bleeding events were associated with increased mortality [hazard ratio (HR) 3.8, 95% confidence interval (CI) 1.5-9.3, P < 0.01], particularly in case of intracranial haemorrhage (HR 14.6, 95% CI 4.2-51.1, P < 0.0001). GI bleedings were associated with a trend towards increased mortality (HR 3.0, 95% CI 0.9-9.3, P = 0.05). Each bleeding episode multiplied the risk of death by 1.8 (95% CI 1.2-2.7, P < 0.01). Finally, only early bleedings (<9 months post-implantation) had an impact on mortality (HR 4.2, 95% CI 1.6-11.1, P < 0.01). Therapeutic management was mainly based on temporary interruption of anticoagulation and permanent interruption of antiplatelet therapy. Invasive management was rarely performed.

CONCLUSIONS: Haemorrhagic events in LVAD recipients are frequent and associated with increased mortality. GI bleedings are the most frequent, and intracranial haemorrhages the most associated with mortality. Management remains empirical requiring more research.

PMID:35338605 | DOI:10.1002/ehf2.13899

Mod Pathol. 2022 Mar 25. doi: 10.1038/s41379-022-01070-2. Online ahead of print.

ABSTRACT

The ability of thymic histopathology to predict the long-term impact of thymectomy in non-thymomatous myasthenia gravis (NTMG) is mainly uncharted. We applied digital pathology to quantitatively characterize differences of thymic histology between early-onset (EOMG) and late-onset MG (LOMG) and to investigate the role of thymic changes for thymectomy outcomes in MG. We analyzed 83 thymic H&E slides from thymectomized NTMG patients, of which 69 had EOMG and 14 LOMG, using digital pathology open-access software QuPath. We compared the results to the retrospectively assessed clinical outcome at two years after thymectomy and at the last follow-up visit where complete stable remission and minimal use of medication were primary outcomes. The automated annotation pipeline was an effective and reliable way to analyze thymic H&E samples compared to manual annotation with mean intraclass correlation of 0.80. The ratio of thymic tissue to stroma and fat was increased in EOMG compared to LOMG (p = 8.7e-07), whereas no difference was observed in the ratio of medulla to cortex between these subtypes. AChRAb seropositivity correlated with the number of ectopic germinal centers (eGC; p = 0.00067) but not with other histological areas. Patients with an increased number of eGCs had better post-thymectomy outcomes at two years after thymectomy (p = 0.0035) and at the last follow-up (p = 0.0267). ROC analysis showed that eGC area predicts thymectomy outcome in EOMG with an AUC of 0.79. Digital pathology can thus help in providing a predictive tool to the clinician, the eGC number, to guide the post-thymectomy treatment decisions in EOMG patients.

PMID:35338262 | DOI:10.1038/s41379-022-01070-2

Int J Cardiol. 2022 Mar 22:S0167-5273(22)00403-X. doi: 10.1016/j.ijcard.2022.03.044. Online ahead of print.

ABSTRACT

BACKGROUND: Under the revised heart allocation system in the United States, bridge to transplant (BTT) patients with left ventricular assist device (LVAD) have a longer waitlist period, as they are now lowly prioritized. However, little is known regarding the long-term trajectory of functional capacity (FC) and health-related quality of life (HR-QOL) among BTT-LVAD patients.

METHODS: We retrospectively analyzed 442 consecutive patients with BTT-LVAD between April 2013 and May 2019 from a Japanese nationwide registry. FC (New York Heart Association [NYHA] functional class, peak oxygen uptake [VO2], and 6-min walk test [6MWT]) and HR-QOL (European Quality of Life [EQ-5D index] and Visual Analogue Scale [EQ-VAS]) were assessed at baseline and for up to 60 months after LVAD implantation.

RESULTS: During the follow-up period of 30 months (IQR 18-42 months), 100 (22.6%) patients underwent transplantation, 37 (8.3%) died, and 14 (3.1%) underwent explantation for recovery. Mean peak VO2, 6MWT distance, EQ-5D index, and EQ-VAS significantly improved 3 months after LVAD implantation (p = 0.0012, p = 0.0037, p < 0.001, p < 0.001, respectively). Furthermore, these improvements were sustained for up to 60 months following LVAD implantation. Major adverse events including device failure, infection, stroke, and bleeding, which occurred within the first 3 months after LVAD implantation may have not affected FC or HR-QOL for up to 60 months (p = 0.15, p = 0.22, respectively).

CONCLUSIONS: BTT patients showed long-term preservation of FC and HR-QOL, suggesting that BTT remains an option despite the long waiting time to HTx.

PMID:35337935 | DOI:10.1016/j.ijcard.2022.03.044

Kidney Int. 2022 Mar 22:S0085-2538(22)00209-5. doi: 10.1016/j.kint.2022.02.027. Online ahead of print.

ABSTRACT

Kidney mass and function are sexually determined, but the cellular events and the molecular mechanisms involved in this dimorphism are poorly characterized. By combining female and male mice with castration/replacement experiments, we showed that male mice exhibited kidney overgrowth from five weeks of age. This effect was organ specific, since liver and heart weight were comparable between males and females, regardless of age. Consistently, the androgen receptor was found to be expressed in the kidneys of males, but not in the liver. In growing mice, androgens led to kidney overgrowth by first inducing a burst of cell proliferation and then an increase of cell size. Remarkably, androgens were also required to maintain cell size in adults. In fact, orchiectomy resulted in smaller kidneys in a matter of few weeks. These changes paralleled the changes of the expression of ornithine decarboxylase and cyclin D1, two known mediators of kidney growth, whereas, unexpectedly, mTORC1 and Hippo pathways did not seem to be involved. Androgens also enhanced kidney autophagy, very likely by increasing transcription factor EB nuclear translocation. Functionally, the increase of tubular mass resulted in increased sodium/phosphate transport. These findings were relevant to humans. Remarkably, by studying living gender-paired kidney donors-recipients, we showed that tubular cell size increased three months after transplantation in men as compared to women, regardless of the donor gender. Thus, our results identify novel signaling pathways that may be involved in androgen-induced kidney growth and homeostasis, and suggest that androgens determine kidney size after transplantation.

PMID:35337891 | DOI:10.1016/j.kint.2022.02.027

J Cardiothorac Vasc Anesth. 2022 Feb 12:S1053-0770(22)00121-5. doi: 10.1053/j.jvca.2022.02.014. Online ahead of print.

NO ABSTRACT

PMID:35337745 | DOI:10.1053/j.jvca.2022.02.014

Transplant Proc. 2022 Feb 10:S0041-1345(22)00132-4. doi: 10.1016/j.transproceed.2022.02.009. Online ahead of print.

ABSTRACT

BACKGROUND: COVID-19 has drastically affected transplant services, but there is limited understanding of the discrepancy of COVID-19 effects on various regions of the world.

METHODS: We have explored the Global Observatory for Organ Donation and Transplantation data for assessing the transplant number changes between the calendar year 2019 (n = 157,301) and 2020 (129,681).

RESULTS: There was a disproportionate impact of COVID-19 on different areas of the world. Globally, there was a decline of 17.5%, in which deceased donation, kidney (20.9%), pancreas (16.2%), lung (12.7%), liver (11.3%), and heart (8%) transplant declined disproportionally in different regions of the world. The pandemic affected almost all geographic regions and nations, but China and the United States were mostly able to recover from the initial halt of the transplant practices by the pandemic so that there was a cumulative increase in transplant numbers.

CONCLUSIONS: Our data show that developing nations lagged behind, whereas developed nations have been able to recover their transplantation programs during the pandemic. Further policy making and preparedness is required to safeguard the most vulnerable areas of the world to minimize the impact of any future pandemic on transplantation practices.

PMID:35337665 | PMC:PMC8828418 | DOI:10.1016/j.transproceed.2022.02.009

Viruses. 2022 Mar 17;14(3):628. doi: 10.3390/v14030628.

ABSTRACT

Background: Since the outbreak of the COVID-19 pandemic, a growing number of evidence suggests that COVID-19 presents sex-dependent differences in clinical course and outcomes. Nevertheless, there is still an unmet need to stratify the risk for poor outcome at the beginning of hospitalization. Since individual C2HEST components are similar COVID-19 mortality risk factors, we evaluated sex-related predictive value of the score. Material and Methods: A total of 2183 medical records of consecutive patients hospitalized due to confirmed SARS-CoV-2 infections were analyzed. Subjects were assigned to one of two of the study arms (male vs. female) and afterward allocated to different stratum based on the C2HEST score result. The measured outcomes included: in-hospital-mortality, three-month- and six-month-all-cause-mortality and in-hospital non-fatal adverse clinical events. Results: The C2HEST score predicted the mortality with better sensitivity in female population regarding the short- and mid-term. Among secondary outcomes, C2HEST-score revealed predictive value in both genders for pneumonia, myocardial injury, myocardial infarction, acute heart failure, cardiogenic shock, and acute kidney injury. Additionally in the male cohort, the C2HEST value predicted acute liver dysfunction and all-cause bleeding, whereas in the female arm-stroke/TIA and SIRS. Conclusion: In the present study, we demonstrated the better C2HEST-score predictive value for mortality in women and illustrated sex-dependent differences predicting non-fatal secondary outcomes.

PMID:35337035 | PMC:PMC8950798 | DOI:10.3390/v14030628

Medicina (Kaunas). 2022 Mar 20;58(3):449. doi: 10.3390/medicina58030449.

ABSTRACT

A 48-year-old female patient underwent a heart transplantation for acute fulminant myocarditis, following heterologous vaccination with the ChAdOx1 nCoV-19 and Pfizer-BioNTech COVID-19. She had no history of severe acute respiratory syndrome coronavirus-2 infection. She did not exhibit clinical signs or have laboratory findings of concomitant infection before or after vaccination. Heart transplantation was performed because her heart failed to recover with venoarterial extracorporeal oxygenation support. Organ autopsy revealed giant cell myocarditis, possibly related to the vaccines. Clinicians may have to consider the possibility of the development of giant cell myocarditis, especially in patients with rapidly deteriorating cardiac function and myocarditis symptoms after COVID-19 vaccination.

PMID:35334625 | PMC:PMC8950462 | DOI:10.3390/medicina58030449