Faculty Bibliography

Background/UNASSIGNED:Few reports have focused on newer coronavirus disease 2019 (COVID-19) therapies (remdesivir, dexamethasone, and convalescent plasma) in solid organ transplant recipients; concerns had been raised regarding possible adverse impact on allograft function or secondary infections. Methods/UNASSIGNED:We studied 77 solid organ transplant inpatients with COVID-19 during 2 therapeutic eras (Era 1: March-May 2020, 21 patients; and Era 2: June-November 2020, 56 patients) and 52 solid organ transplant outpatients. Results/UNASSIGNED:In Era 1, no patients received remdesivir or dexamethasone, and 4 of 21 (19.4%) received convalescent plasma, whereas in Era 2, remdesivir (24/56, 42.9%), dexamethasone (24/56, 42.9%), and convalescent plasma (40/56, 71.4%) were commonly used. Mortality was low across both eras, 4 of 77 (5.6%), and rejection occurred in only 2 of 77 (2.8%) inpatients; infections were similar in hypoxemic patients with or without dexamethasone. Preexisting graft dysfunction was associated with greater need for hospitalization, higher severity score, and lower survival. Acute kidney injury was present in 37.3% of inpatients; renal function improved more rapidly in patients who received remdesivir and convalescent plasma. Post-COVID-19 renal and liver function were comparable between eras, out to 90 d. Conclusions/UNASSIGNED:Newer COVID-19 therapies did not appear to have a deleterious effect on allograft function, and infectious complications were comparable.

BACKGROUND:Historically, donation after circulatory death (DCD) livers were frequently discarded due to higher mortality and graft loss after liver transplantation (LT). However, the demand for liver transplantation continues to outstrip the supply of "acceptable" organs. Additionally, changes in the donor pool, organ allocation, clinical management of donors and recipients, and improved clinical protocols might have altered post-DCD-LT outcomes. METHODS:We studied 5,975 recovered DCD livers using U.S. SRTR data from 2005-2017, with a comparison group of 78,235 adult DBD livers recovered during the same time period. We quantified temporal trends in discard using adjusted multilevel logistic regression and temporal trends in post-LT mortality and graft loss for DCD LT recipients using adjusted Cox regression. RESULTS:DCD livers were more likely to be discarded than DBD livers across the entire study period, and the relative likelihood of discard increased over time (adjusted odds ratio [aOR] of discard DCD vs. DBD 3.854.455.14 2005-2007, 5.225.876.59 2015-2017) despite improving outcomes after DCD LT. Mortality risk for DCD LTs decreased in each time period (compared to 2005-2007, aHR 2008-2011 0.720.840.97, aHR 2012-2014 0.480.580.70, aHR 2015-2017 0.340.430.55), as did risk of graft loss (compared to 2005-2007, aHR 2008-2011 0.690.810.94, aHR 2012-2014 0.450.550.67, aHR 2015-2017 0.360.450.56). CONCLUSIONS:Despite dramatic improvements in outcomes of DCD LT recipients, DCD livers remain substantially more likely to be discarded than DBD livers, and this discrepancy has actually increased over time. DCD livers are underutilized and have the potential to expand the donor pool.

Patient and graft survival are similar following whole versus split liver transplants (SLT) among pediatric and adult recipients, yet SLTs are rarely used. We sought to determine the survival benefit associated with accepting a splittable offer for SLT versus declining and waiting for a subsequent offer using 2010-2018 SRTR data on 928 pediatric and 1814 adult LT candidates who were ever offered a splittable graft. We compared eventual mortality, regardless of subsequent transplants, between those who accepted versus declined a splittable liver offer with adjustment for PELD/MELD, diagnosis, and weight among pediatric candidates, and matching for MELD, height, and offer among adult candidates. Among pediatric candidates ≤7kg, splittable offer acceptance versus decline was associated with a 63% reduction in mortality (aHR _0.17 0.37_0.80 , p=0.01; 93.1% versus 84.0% one-year survival post-decision). Within one year of decline for those ≤7kg, 6.4% died and 31.1% received a whole liver transplant. Among pediatric candidates >7kg, there was no significant difference associated with acceptance of a splittable offer (aHR _0.63 1.07_1.82 , p=0.81; 91.7% vs 94.4% one-year survival post-decision). Within one year of decline for those >7kg, 1.8% died and 45.8% received a whole liver. Among adult candidates, splittable offer acceptance was associated with a 43% reduction in mortality (aHR _0.39 0.57_0.83, p=0.005; 92.2% vs 84.4% one-year survival post-decision). Within one year of decline for adult candidates, 7.9% died and 39.3% received a whole liver. Conclusion: Accepting splittable offers for SLT could significantly improve survival for small children and adults on the waitlist.

BACKGROUND:Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) occurs in critically ill patients with COVID-19. Risks and outcomes remain poorly understood. METHODS:A retrospective cohort study of mechanically ventilated adult patients with COVID-19 admitted to 5 Johns Hopkins hospitals was conducted between March and August 2020. CAPA was defined using composite clinical criteria. Fine and Gray competing risks regression was used to analyze clinical outcomes and, multilevel mixed-effects ordinal logistic regression was used to compare longitudinal disease severity scores. RESULTS:In the cohort of 396 people, 39 met criteria for CAPA. Patients with CAPA were more likely than those without CAPA to have underlying pulmonary vascular disease (41% vs 21.6%, respectively; P = .01), liver disease (35.9% vs 18.2%; P = .02), coagulopathy (51.3% vs 33.1%; P = .03), solid tumors (25.6% vs 10.9%; P = .02), multiple myeloma (5.1% vs 0.3%; P = .03), and corticosteroid exposure during the index admission (66.7% vs 42.6%; P = .005), and had lower body mass indexes (median, 26.6 vs 29.9 [calculated as weight in kilograms divided by height in meters squared]; P = .04). Patients with CAPA had worse outcomes, as measured by ordinal severity of disease scores, requiring longer time to improvement (adjusted odds ratio, 1.081.091.1; P < .001), and advancing in severity almost twice as quickly (subhazard ratio, 1.31.82.5; P < .001). They were intubated twice as long as those without CAPA (subhazard ratio, 0.40.50.6; P < .001) and had longer hospital stays (median [interquartile range], 41.1 [20.5-72.4) vs 18.5 [10.7-31.8] days; P < .001). CONCLUSION:CAPA is associated with poor outcomes. Attention to preventive measures (screening and/or prophylaxis) is warranted in people with high risk of CAPA.

Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016-July 2019, there were 45 LTs (8 simultaneous liver-kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D-/R+ (10 D- were false-positive). The median follow-up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)-seropositive, 13% HCV-viremic. Weighted 1-year survival was 83.3% versus 100.0% in D+ versus D- groups (p = .04). There were no differences in one-year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p > .05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.

UNLABELLED:Kidney transplantation (KT) is controversial in patients with pretransplant pulmonary hypertension (PtPH). We aimed to quantify post-KT graft and patient survival as well as survival benefit in recipients with PtPH. METHODS/UNASSIGNED:Using UR Renal Data System (2000-2018), we studied 90 819 adult KT recipients. Delayed graft function, death-censored graft failure, and mortality were compared between recipients with and without PtPH using inverse probability weighted logistic and Cox regression. Survival benefit of KT was determined using stochastic matching and stabilized inverse probability treatment Cox regression. RESULTS/UNASSIGNED: < 0.01) compared with those who remained on the waitlist. CONCLUSIONS/UNASSIGNED:Although PtPH is associated with inferior post-KT outcomes, KT is associated with better survival compared with remaining on the waitlist. Therefore, KT is a viable treatment modality for appropriately selected patients with PtPH.

With a later onset of diabetes complications and thus increasing age of transplant candidates, many centers have extended upper age limits for pancreas transplantation. This study investigates the effect of recipient and donor age on outcomes after pancreas transplantation.We retrospectively analyzed 565 pancreas transplants performed at two Eurotransplant centers. The cohort was split at a recipient and donor age of 50 and 40 years, respectively. Median recipient age in old patients (≥50 years; 27.2%) was 54 years and 40 years in young patients (<50 years). Compared to young recipients, old recipients had an inferior patient survival rate (≥50: 5yr, 82.8%; 10yr, 65.6%; <50: 5yr, 93.3%; 10yr, 82.0%; P < 0.0001). Old recipients demonstrated comparable death-censored pancreas (≥50: 1yr, 80.6%; 5yr, 70.2%; <50: 1yr, 87.3%; 5yr, 77.8%; P = 0.35) and kidney graft survival (≥50: 1yr, 97.4%; 5yr, 90.6%; <50: 1yr, 97.8%; 5yr, 90.2%; P = 0.53) compared to young recipients. Besides a lower rate of kidney rejection, similar relative risks for postoperative complications were detected in old and young patients. This study shows that despite an increased mortality in old recipients, excellent graft survival can be achieved similar to that of young patients. Age alone should not exclude patients from receiving a pancreas transplant.