Potential Association of Blood Transfusion in Deceased Donors With Outcomes of Liver Transplantation in the United States.

BACKGROUND: Donor blood transfusion may potentially affect transplant outcomes through an inflammatory response, recipient sensitization, or transmission of infection. The aim of this study was to evaluate the association of donor blood transfusion with outcomes of liver transplantation (LT). METHODS: From January 2004 to December 2022, donor blood transfusion information was available for 113,017 adult recipients of LT in the United Network for Organ Sharing database and was classified into 4 levels of transfusion: no-transfusion (N = 68,130), transfusion of 1-5 units (N = 33,629), 6-10 units (N = 8067), and >10 units (N = 5329). Recipient survival analysis was performed by Kaplan-Meier method and multivariable Cox-hazard model. RESULTS: Among this cohort, 40.8% of donors (N = 46,261) received blood transfusion during the index hospitalization. Compared to no-blood transfusion donors, blood transfusion donors were younger (median age 37 versus 46 y P < 0.001) and were more brain death donors (94.5% versus 92.1%, P < 0.001). An increased risk of rejection at 6-mo (transfusion 10.3% versus no-transfusion 9.9%, P = 0.055) and 1 y (transfusion 12.5% versus no-transfusion 11.9%, P = 0.0036) post-LT was noted in this cohort. Multivariable Cox-hazard model showed blood transfusion was associated with increased 1-y mortality (transfusion 1.07; 95% CI 1.02-1.12, P = 0.007) and graft failure (transfusion 1.09; 95% CI 1.04-1.13, P < 0.001). CONCLUSIONS: Donor blood transfusion was associated with an increased risk of rejection at 6 mo and 1 y among LT recipients and worse post-transplant graft and overall survival. Additional information regarding donor blood transfusion, along with other known factors, may be considered when deciding the optimization of overall immune suppression in LT recipients to decrease the risk of delayed rejection.

1-Year Outcomes of Lung Transplantation for Coronavirus Disease 2019-Associated End-Stage Lung Disease in the United States.

BACKGROUND: Lung transplantation can provide quality of life and survival benefits for patients with coronavirus disease 2019 (COVID-19)-associated end-stage lung disease. Characteristics and outcomes of these lung transplant recipients are limited to mostly single-center experiences or provide a short-term follow-up. METHODS: Characteristics of deceased donors and adult lung transplant recipients for COVID-19-associated end-stage lung disease between August-2020 and June-2022 were analyzed using deidentified United Network for Organ Sharing database. Post-transplant patient survival of COVID-19 recipients was analyzed and compared with non-COVID-19 recipients. Secondary outcomes were length of hospitalization, post-transplant complications, and rates of organ rejection. RESULTS: During the study period, 400 lung transplants for COVID-associated end-stage lung disease comprised 8.7% of all lung transplants performed in United States. In the COVID-19 group, Hispanic males received lung transplants at significantly higher rates. The COVID-19 group was younger and had greater need for intensive care unit stay, mechanical ventilation, hemodialysis, extracorporeal membrane oxygenation support, and receipt of antibiotics pre-lung transplant. They had higher lung allocation score, with a shorter wait-list time and received more double lung transplants compared with non-COVID-19 recipients. Post-transplant, the COVID-19 cohort had longer hospital stays, with similar 1-year patient survival (COVID, 86.6% vs non-COVID, 86.3%). Post-transplant, COVID-19-associated deaths were 9.2% of all deaths among lung transplant recipients. CONCLUSIONS: Lung transplantation offers a effective option for carefully selected patients with end-stage lung disease from prior COVID-19, with short-term and long-term outcomes similar to those for lung transplant recipients of non-COVID-19 etiology.

Utilization of hepatitis C virus infected donors in heart transplant recipients with elevated MELD-XI score.

BACKGROUND: The advent of direct-acting antivirals has helped to increase the safe utilization of organs from hepatitis C virus positive (HCV+) donors. However, the outcomes of heart transplantation (HT) using an HCV+ donor are unclear in recipients with underlying liver disease represented by an elevated model for end-stage liver disease excluding international normalized ratio (MELD-XI). METHODS: The United Network of Organ Sharing database was queried from Jan 2016 to Dec 2021. Post-transplant outcomes stratified by recipient MELD-XI score (low <10.37, medium, 10.38-13.39, and high >13.4) was compared between patients with HT from HCV+ (N = 792) and patients with HT from HCV-negative donors (N = 15,266). RESULTS: The median MELD-XI score was comparable (HCV+, 12.1, vs. HCV-negative, 11.8, p = .37). In the HCV+ group, donors were older (33 vs. 31 years, p < .001). Ischemic time of donor hearts (3.48 vs. 3.28 h, p < .001) and travel distance (250 vs. 157 miles, p < .001) were longer in HCV+ group. In the Kaplan Meier analysis with a median follow-up of 750 days, survival was comparable between the two groups (2-year survival, MELD-XI Low: HCV+, 92.4 ± 3.6% vs. HCV-negative, 91.1 ±.8%, p = .83, Medium: HCV+ 89.2 ± 4.3% vs. HCV-negative, 88.2 ± 1.0%, p = .68, and High: HCV+, 84.9 ± 4.5% vs. HCV-negative, 84.6 ± 1.1%, p = .75) In multivariate Cox hazard models, HCV donors were not associated with mortality in each MELD-XI subgroup (Low: adjusted hazard ratio (aHR), 1.02, p = .94; Medium: aHR, .95, p = .81; and High: aHR, .93, p = .68). CONCLUSION: Utilization of HCV+ hearts was not associated with an increased risk of adverse outcomes in recipients with an elevated MELD- XI score.

Groin wound management after decannulation of veno-arterial extracorporeal membrane oxygenation in heart transplantation: Role of sartorius muscle flap.

BACKGROUND: The management of complex groin wounds following VA-ECMO after heart transplant (HT) is uncertain due to limited experience. Sartorius muscle flaps (SMF) have been used in vascular surgery for groin wound complications. However, their use in HT recipients with perioperative VA-ECMO is unclear. This study aims to describe characteristics and outcomes of HT patients with groin complications after arterial decannulation for femoral VA-ECMO. METHODS: We retrospectively reviewed HT patients who underwent peri-transplant femoral VA-ECMO at our institution from April 2011 to February 2023. Patients were categorized into two groups based on the presence of cannulation-related wound complications. RESULTS: Among the 34 patients requiring VA-ECMO peri-transplant, 17 (50%) experienced complications at the cannulation site. Baseline characteristics including duration of VA-ECMO support were comparable in both groups. Patients with complications presented mostly with open wounds (41.1%) after a median duration of 22 days post-transplant. Concurrent groin infections were observed in 52.3% of patients, all caused by gram-negative bacteria. Wound complications were managed with 12 (70.6%) undergoing SMF treatment and 5 (31.2%) receiving conventional therapy. Four SMF recipients had preemptive procedures for wound dehiscence, while eight underwent SMF for groin infections. Among the SMF group, 11 patients had favorable outcomes without recurrent complications, except for one patient who developed a groin infection with pseudoaneurysm formation. Conventional therapy with vacuum assisted closure (VAC) and antibiotics were utilized in four patients without infection and one patient with infection. Three patients required additional surgeries with favorable healing of the wound. CONCLUSION: Complications related to femoral VA-ECMO are common in HT patients, with infection being the most frequent complication. SMFs can be a useful tool to prevent progression of infection and improve local healing.

Cannulation-related adverse events of peripheral veno-arterial extracorporeal membrane oxygenation support in heart transplantation: Axillary versus femoral artery cannulation.

BACKGROUND: In heart transplantation (HT), peripheral veno-arterial extracorporeal membranous oxygenation (VA-ECMO) is utilized preoperatively as a direct bridge to HT or postoperatively for primary graft dysfunction (PGD). Little is known about wound complications of an arterial VA-ECMO cannulation site which can be fatal. METHODS: From 2009 to 2021, outcomes of 80 HT recipients who were supported with peripheral VA-ECMO either preoperatively or postoperatively were compared based on the site of arterial cannulation: axillary (AX: N = 49) versus femoral artery (FA: N = 31). RESULTS: Patients in the AX group were older (AX: 59 years vs. 52 years, p = .006), and less likely to have extracorporeal cardiopulmonary resuscitation (0% vs. 12.9%, p = .040). Survival to discharge (AX, 81.6% vs. FA. 90.3%, p = .460), incidence of stroke (10.2% vs. 6.5%, p = .863), VA-ECMO cannulation-related bleeding (6.1% vs. 12.9%, p = .522), and arm or limb ischemia (0% vs. 3.2%, p = .816) were comparable. ECMO cannulation-related wound complications were lower in the AX group (AX, 4.1% vs. FA, 45.2%, p < .001) including the wound infections (2.0% vs. 32.3%, p < .001). In FA group, all organisms were gram-negative species. In univariate logistic regression analysis, AX cannulation was associated with less ECMO cannulation-related wound complications (Odds ratio, .23, p < .001). There was no difference between cutdown and percutaneous FA insertion regarding cannulation-related complications. CONCLUSIONS: Given the lower rate of wound complications and comparable hospital outcomes with femoral cannulation, axillary VA-ECMO may be an excellent option in HT candidates or recipients when possible.

Solid organ transplantation from COVID positive donors in the United States: Analysis of United Network for Organ Sharing database.

BACKGROUND: Significant uncertainties remain regarding the utilization of organs for solid organ transplantation (SOT) from donors with coronavirus disease 2019 (COVID-19). The aim of this study was to assess the trends in utilization of organs from donors with COVID-19 and their short-term outcomes. METHODS: Deceased donors between March 2020 and December 2021 with a positive COVID nucleic acid test from respiratory tract within 14 days of transplantation were analyzed using the de-identified United Network for Organ Sharing (UNOS) database. Donor and recipient characteristics of COVID-19 positive (COVID+) organs were compared to COVID-19 negative (COVID-) organs during this period. We analyzed the trends in the utilization of SOT from COVID+ donors across the United States, donor characteristics, and the quality of donor organ and recipient outcomes (length of hospitalization, rates of organ rejection, delayed graft function, 30-day graft/patient survival). RESULTS: During the study period, 193 COVID+ donors led to the transplantation of 281-kidneys, 106-livers, and 36-hearts in 414 adult recipients. COVID+ patients donated a median of two organs. These donors were younger and had a lower median Kidney Donor Profile Index (0.37 vs. 0.50, p < .001), lower median serum creatinine (0.8 vs. 1.0 mg/dl, p = .003), similar median serum total bilirubin (0.6 mg/dl, p = .46), and similar left ventricular ejection fraction (60%, p = .84) when compared to COVID- donors. Short-term outcomes, including 30-day graft/patient survival, were similar in both groups. CONCLUSIONS: Analysis of short-term outcomes from the UNOS database indicates that a positive COVID test in an otherwise medically suitable donor should not preclude consideration of non-lung solid organ transplantation.

Does utilization of heart machine perfusion for donation after cardiac death transplantation affect outcomes of other abdominal transplanted organs?

INTRODUCTION: Machine perfusion of heart for donation after circulatory death (DCD) is being increasingly utilized. Current protocols for utilizing heart DCD's machine perfusion might prolong donor warm ischemic time for nonheart organs. The aim of this study was to analyze the effects of utilizing heart machine perfusion on liver and kidney transplants from the same donor. METHODS: We analyzed data of DCD donors from the United Network for Organ Sharing (UNOS) from January-2020 to September-2021 among two groups: donors with heart machine perfusion (HM) and without heart machine perfusion (NHM). Propensity score (PS) matching was performed to compare the short-term outcomes of liver and kidney transplants between two groups. RESULTS: Total of 102 liver and 319 kidney transplants were performed using organs from donors with HM. After PS matching, no statistically significant difference was seen in 1-year graft survival (GS) for both liver and kidney transplants between two groups (liver HM 90.6% vs. NHM 90.2%, p = .47; kidney HM 95.2% vs. NHM 92.9%, p = .40). There was no difference in the delayed graft function (DGF) rates in kidney transplantation (KT) (HM 42% vs. NHM 35%, p = .062). CONCLUSION: Utilization of heart machine perfusion in DCD donors had no significant impact on 1-year outcomes of liver and kidney transplantation.

Successful liver transplantation in a patient recovered from COVID-19.

Transplantation in potential candidates who have recently recovered from COVID-19 is a challenge with uncertainties regarding the diagnosis, multi-organ systemic involvement, prolonged viral shedding in immunocompromised patients, and optimal immunosuppression. A 42 year male with alcoholic hepatitis underwent a successful deceased donor liver transplantation 71 days after the initial diagnosis of COVID-19. At the time of transplant, he was SARS-CoV-2 PCR negative for 24 days and had a MELD score of 33. His post-operative course was complicated by acute rejection which responded to intense immune-suppression using T-cell depletion and steroids. He was discharged with normal end-organ function and no evidence of any active infection including COVID-19. Prospective organ transplant recipients who have recovered from COVID-19 can be considered for transplantation after careful pre-transplant evaluation, donor selection, and individualized risk-benefit analysis.

The Impact on Medical Students of the 9/11 Attacks on New York's World Trade Center.

Phenomenon: Little is known about how participation in disaster relief impacts medical students. During the terror attacks of September 11, 2001, New York Medical College School of Medicine students witnessed the attacks and then became members of emergency treatment teams at St. Vincent's Hospital, the trauma center nearest to the World Trade Center. To date, only two reports describe how 9/11 influenced the lives of medical students. This study was designed to characterize the short- and long-term effects on NYMC students and to compare those effects between students assigned to St Vincent's Hospital and classmates assigned to rotations at facilities more remote from the attack site. We hypothesized that participation in direct relief efforts by students assigned to the St. Vincent's site might have long-lasting effects on their lives and these effects might vary when compared to classmates assigned elsewhere. Approach: This was a retrospective, survey-based, unmatched cohort study. Participants included all school of medicine graduates who were St. Vincent's rotators on 9/11 (N = 22) and classmates (N = 24) assigned to other sites who could be contacted and agreed to participate. Our primary measure was whether the 9/11 experience affected the participant's life, defined as an affirmative response to the item which asked whether the 9/11 experience affected the participant's "life thereafter, career choice, attitudes toward life or attitudes toward practice." Secondary measures included self-reported effects on career, life, attitudes, health, resilience, personal growth, personality features, and the temporal relationship between the attack and stress symptoms. Findings: Completed surveys were received from 16/22 (73%) St. Vincent's and 18/24 (75%) non-Saint Vincent's participants: 62% male, 82% had children, 74% identified as Caucasian/white and 76% employed full-time. Overall, slightly more than half (58%) of respondents reported an effect of 9/11 on their life, with a greater but non-significant proportion of St. Vincent's rotators reporting life impact (67% versus 50% for St. Vincent's versus other locations, respectively). High post-9/11 stress levels, current marriage, and ability to make and keep family and social relationships were associated with an effect on life which approached statistical significance. Participants reported positive or no post 9/11 effects on empathy and altruism (50%), resilience (47%), attitudes toward medical practice and career (32%), and charitable giving (24%), while positive, negative, or no effects were reported for attitude toward life, family and social relations, physical health, and conscientiousness. Mental health was the only domain in which all participants reported unchanged or negative effects. Two St. Vincent's rotators but no students assigned elsewhere believed they experienced 9/11-related post-traumatic stress disorder. Insights: Just over half of New York Medical College School of Medicine students rotating at St. Vincent's Hospital on 9/11 or elsewhere reported significant life-effects as a result of direct/indirect experiences related to the attack. Perceived stress may have been a more important driver of this life-change than other factors such as geographic proximity to the disaster site and/or direct participation in relief efforts. Further study of medical school interventions focused on stress reduction among students who participate in disaster relief is warranted.

Biennial Upsurge and Molecular Epidemiology of Enterovirus D68 Infection in New York, USA, 2014 to 2018.

Enterovirus D68 (EV-D68) infection has been associated with outbreaks of severe respiratory illness and increased cases of nonpolio acute flaccid myelitis. The patterns of EV-D68 circulation and molecular epidemiology are not fully understood. In this study, nasopharyngeal (NP) specimens collected from patients in the Lower Hudson Valley, New York, from 2014 to 2018 were examined for rhinovirus/enterovirus (RhV/EV) by the FilmArray respiratory panel. Selected RhV/EV-positive NP specimens were analyzed using two EV-D68-specific real-time RT-PCR assays, Sanger sequencing and metatranscriptomic next-generation sequencing. A total of 2,398 NP specimens were examined. EV-D68 was detected in 348 patients with NP specimens collected in 2014 (n = 94), 2015 (n = 0), 2016 (n = 160), 2017 (n = 5), and 2018 (n = 89), demonstrating a biennial upsurge of EV-D68 infection in the study area. Ninety-one complete or nearly complete EV-D68 genome sequences were obtained. Genomic analysis of these EV-D68 strains revealed dynamics and evolution of circulating EV-D68 strains since 2014. The dominant EV-D68 strains causing the 2014 outbreak belonged to subclade B1, with a few belonging to subclade B2. New EV-D68 subclade B3 strains emerged in 2016 and continued in circulation in 2018. Clade D strains that are rarely detected in the United States also arose and spread in 2018. The establishment of distinct viral strains and their variable circulation patterns provide essential information for future surveillance, diagnosis, vaccine development, and prediction of EV-D68-associated disease prevalence and potential outbreaks.

Integrated Genome-Wide Analysis of an Isogenic Pair of Pseudomonas aeruginosa Clinical Isolates with Differential Antimicrobial Resistance to Ceftolozane/Tazobactam, Ceftazidime/Avibactam, and Piperacillin/Tazobactam.

Multidrug-resistant (MDR) Pseudomonas aeruginosa is one of the main causes of morbidity and mortality in hospitalized patients and the leading cause of nosocomial infections. We investigated, here, two MDR P. aeruginosa clinical isolates from a hospitalized patient with differential antimicrobial resistance to ceftazidime/avibactam (CZA), ceftolozane/tazobactam (C/T), and piperacillin/tazobactam (P/T). Their assembled complete genomes revealed they belonged to ST235, a widespread MDR clone; and were isogenic with only a single nucleotide variant, causing G183D mutation in AmpC ß-lactamase, responsible for a phenotypic change from susceptible to resistant to CZA and C/T. Further epigenomic profiling uncovered two conserved DNA methylation motifs targeted by two distinct putative methyltransferase-containing restriction-modification systems, respectively; more intriguingly, there was a significant difference between the paired isolates in the pattern of genomic DNA methylation and modifications. Moreover, genome-wide gene expression profiling demonstrated the inheritable genomic methylation and modification induced 14 genes being differentially regulated, of which only toxR (downregulated), a regulatory transcription factor, had its promoter region differentially methylate and modified. Since highly expressed opdQ encodes an OprD porin family protein, therefore, we proposed an epigenetic regulation of opdQ expression pertinent to the phenotypic change of P. aeruginosa from resistant to susceptible to P/T. The disclosed epigenetic mechanism controlling phenotypic antimicrobial resistance deserves further experimental investigation.

Anaplasma phagocytophilum presenting with orchitis in a renal transplant recipient.

Human granulocytic anaplasmosis (HGA), caused by Anaplasma phagocytophilum, is an emerging tick-borne disease. It is spread by the black-legged deer tick Ixodes scapularis that serves as the vector for six human pathogens. HGA is still rarely reported in solid organ transplant recipients. In solid organ transplant recipients, orchitis has been reported secondary to chickenpox, tuberculosis and infections due to Listeria monocytogenes and Nocardia asteroides. Orchitis as a presenting feature of HGA infection has only been reported in animals. We present a unique case of a renal transplant recipient with HGA that presented as orchitis. We also compare the clinical presentation and laboratory findings of our patient with other cases of HGA in transplant recipients. To the best of our knowledge, our patient is one of the first cases of A phagocytophilum mono-infection causing a classical presentation of orchitis in a transplant patient.