Influence of induction therapy and antiretroviral regimen on outcomes in kidney transplant recipients living with human immunodeficiency.

PURPOSE: Kidney transplantation has a survival benefit for people with human immunodeficiency virus (HIV) and end-stage kidney disease, however increased rates of rejection remain an issue. Questions remain regarding the impact of induction immunosuppression therapy and antiretroviral (ARV) choice on long-term outcomes. METHODS: We performed a multicenter retrospective analysis of outcomes in recipients with HIV who received kidneys from donors without HIV transplanted between 2004 and 2019. The association between induction and ARV regimens and long-term outcomes including rejection, graft, and recipient survival over 5 years was investigated using Cox regression modeling. RESULTS: Seventy-eight kidney transplants (KT) performed in 77 recipients at five US transplant centers were included, with median follow up of 7.1 (4.3-10.7) years. Overall recipient and graft survival were 83% and 67%, respectively. Rejection occurred in 37% (29/78). Recipients with rejection were more likely to be younger, recipients of deceased donor organs, and Black. Receipt of rabbit anti-thymocyte globulin (rATG) induction without protease-inhibitor (PI)-based ARVs was associated with 83% lower risk of rejection (adjusted hazard ratio (aHR) 0.17 (95% CI 0.05-0.63), p =.007) and a non-statistically significantly lower risk of graft failure (aHR 0.18 (0.03-1.16), p =.07) when compared to those who received other induction and ARV combinations. CONCLUSIONS: In this multicenter retrospective study, we found a trend toward lower rejection and improved graft survival among those who received both rATG for induction and PI-sparing ARVs.

Deceased Donors With HIV in the Era of the HOPE Act: Referrals and Procurement.

Background: The HIV Organ Policy Equity Act legalizes organ procurement from donors with HIV (HIV D+). A prior survey of Organ Procurement Organizations (OPOs) estimated >2000 HIV D+ referrals/year; however, only 30-35 HIV D+/year have had organs procured. Given this gap, we sought to understand HIV D+ referrals and procurements in practice. Methods: We prospectively collected data on all OPO-reported HIV D+ referrals, including reasons for nonprocurement. We evaluated trends and compared HIV D+ characteristics by procurement status using regression, chi-squared tests, and Wilcoxon rank-sum tests. Results: From December 23, 2015 to May 31, 2021, there were 710 HIV D+ referrals from 49 OPOs, of which 171 (24%) had organs procured. HIV D+ referrals increased from 7 to 15 per month (P < 0.001), and the procurement rate increased from 10% to 39% (P < 0.001). Compared with HIV D+ without procurement, HIV D+ with procurement were younger (median age 36 versus 50 y), more commonly White (46% versus 36%), and more often had trauma-related deaths (29% versus 8%) (all P < 0.001). Nonprocurement was attributed to medical reasons in 63% of cases, of which 36% were AIDS-defining infections and 64% were HIV-unrelated, commonly due to organ failure (36%), high neurologic function (31%), and cancer (14%). Nonprocurement was attributed to nonmedical reasons in 26% of cases, commonly due to no authorization (42%), no waitlist candidates (21%), or no transplant center interest (20%). Conclusions: In the early years of the HIV Organ Policy Equity Act, actual HIV D+ referrals were much lower than prior estimates; however, the numbers and procurement rates increased over time. Nonprocurement was attributed to both medical and nonmedical issues, and addressing these issues could increase organ availability.

Similar Risk of Kidney Failure among Patients with Blinding Diseases Who Receive Ranibizumab, Aflibercept, and Bevacizumab: An Observational Health Data Sciences and Informatics Network Study.

PURPOSE: To characterize the incidence of kidney failure associated with intravitreal anti-VEGF exposure; and compare the risk of kidney failure in patients treated with ranibizumab, aflibercept, or bevacizumab. DESIGN: Retrospective cohort study across 12 databases in the Observational Health Data Sciences and Informatics (OHDSI) network. SUBJECTS: Subjects aged ≥ 18 years with ≥ 3 monthly intravitreal anti-VEGF medications for a blinding disease (diabetic retinopathy, diabetic macular edema, exudative age-related macular degeneration, or retinal vein occlusion). METHODS: The standardized incidence proportions and rates of kidney failure while on treatment with anti-VEGF were calculated. For each comparison (e.g., aflibercept versus ranibizumab), patients from each group were matched 1:1 using propensity scores. Cox proportional hazards models were used to estimate the risk of kidney failure while on treatment. A random effects meta-analysis was performed to combine each database's hazard ratio (HR) estimate into a single network-wide estimate. MAIN OUTCOME MEASURES: Incidence of kidney failure while on anti-VEGF treatment, and time from cohort entry to kidney failure. RESULTS: Of the 6.1 million patients with blinding diseases, 37 189 who received ranibizumab, 39 447 aflibercept, and 163 611 bevacizumab were included; the total treatment exposure time was 161 724 person-years. The average standardized incidence proportion of kidney failure was 678 per 100 000 persons (range, 0-2389), and incidence rate 742 per 100 000 person-years (range, 0-2661). The meta-analysis HR of kidney failure comparing aflibercept with ranibizumab was 1.01 (95% confidence interval [CI], 0.70-1.47; P = 0.45), ranibizumab with bevacizumab 0.95 (95% CI, 0.68-1.32; P = 0.62), and aflibercept with bevacizumab 0.95 (95% CI, 0.65-1.39; P = 0.60). CONCLUSIONS: There was no substantially different relative risk of kidney failure between those who received ranibizumab, bevacizumab, or aflibercept. Practicing ophthalmologists and nephrologists should be aware of the risk of kidney failure among patients receiving intravitreal anti-VEGF medications and that there is little empirical evidence to preferentially choose among the specific intravitreal anti-VEGF agents. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Wait Time Advantage for Transplant Candidates With HIV Who Accept Kidneys From Donors With HIV Under the HOPE Act.

BACKGROUND: Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D + ), it is crucial to understand whether this has impacted transplant rates for this population. METHODS: Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D + kidneys (HOPE) compared with 46 025 candidates not listed for D + kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D + , false-positive [FP; donor with false-positive HIV testing], D - [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. RESULTS: HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D + , 34% D - , 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D - , 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates ( P < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P < 0.001). CONCLUSIONS: Listing for D + kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV.

Multinational patterns of second line antihyperglycaemic drug initiation across cardiovascular risk groups: federated pharmacoepidemiological evaluation in LEGEND-T2DM.

Objective: To assess the uptake of second line antihyperglycaemic drugs among patients with type 2 diabetes mellitus who are receiving metformin. Design: Federated pharmacoepidemiological evaluation in LEGEND-T2DM. Setting: 10 US and seven non-US electronic health record and administrative claims databases in the Observational Health Data Sciences and Informatics network in eight countries from 2011 to the end of 2021. Participants: 4.8 million patients (≥18 years) across US and non-US based databases with type 2 diabetes mellitus who had received metformin monotherapy and had initiated second line treatments. Exposure: The exposure used to evaluate each database was calendar year trends, with the years in the study that were specific to each cohort. Main outcomes measures: The outcome was the incidence of second line antihyperglycaemic drug use (ie, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, and sulfonylureas) among individuals who were already receiving treatment with metformin. The relative drug class level uptake across cardiovascular risk groups was also evaluated. Results: 4.6 million patients were identified in US databases, 61 382 from Spain, 32 442 from Germany, 25 173 from the UK, 13 270 from France, 5580 from Scotland, 4614 from Hong Kong, and 2322 from Australia. During 2011-21, the combined proportional initiation of the cardioprotective antihyperglycaemic drugs (glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors) increased across all data sources, with the combined initiation of these drugs as second line drugs in 2021 ranging from 35.2% to 68.2% in the US databases, 15.4% in France, 34.7% in Spain, 50.1% in Germany, and 54.8% in Scotland. From 2016 to 2021, in some US and non-US databases, uptake of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors increased more significantly among populations with no cardiovascular disease compared with patients with established cardiovascular disease. No data source provided evidence of a greater increase in the uptake of these two drug classes in populations with cardiovascular disease compared with no cardiovascular disease. Conclusions: Despite the increase in overall uptake of cardioprotective antihyperglycaemic drugs as second line treatments for type 2 diabetes mellitus, their uptake was lower in patients with cardiovascular disease than in people with no cardiovascular disease over the past decade. A strategy is needed to ensure that medication use is concordant with guideline recommendations to improve outcomes of patients with type 2 diabetes mellitus.

To decline or not to decline: Consequences of decision-making regarding lung offers from donors with hepatitis C.

OBJECTIVE: Lung transplants from donors with hepatitis C (HCV D+) have excellent outcomes, but these organs continue to be declined. We evaluated whether (1) being listed to consider and (2) accepting versus declining HCV D+ offers provided a survival benefit to lung transplant candidates. METHODS: Using the Scientific Registry of Transplant Recipients, we identified all adult (≥18 years) lung transplant candidates 2016-2021 and compared waitlist mortality between those willing versus not willing to consider HCV D+ offers using competing risk regression. We identified all candidates offered an HCV D+ lung that was later accepted and followed them from offer decision until death or end-of-study. We estimated adjusted mortality risk of accepting versus declining an HCV D+ lung offer using propensity-weighted Cox regression. RESULTS: From 2016 to 2021, we identified 21,007 lung transplant candidates, 33.8% of whom were willing to consider HCV D+ offers. Candidates willing to consider HCV D+ offers had a 17% lower risk of waitlist mortality (subhazard ratio, 0.83; 95% confidence interval, 0.75-0.91, P < .001). Over the same period, 665 HCV D+ lung offers were accepted after being declined a total of 2562 times. HCV D+ offer acceptance versus decline was associated with a 20% lower risk of mortality (adjusted hazard ratio, 0.80; 95% confidence interval, 0.66-0.96, P = .02). CONCLUSIONS: Considering HCV D+ lung offers was associated with a 17% lower risk of waitlist mortality, whereas accepting versus declining an HCV D+ lung offer was associated with a 20% lower risk of mortality. Centers and candidates should consider accepting suitable HCV D+ lung offers to optimize outcomes.

Transplant Candidate Outcomes After Declining a DCD Liver in the United States.

BACKGROUND: In the context of the organ shortage, donation after circulatory death (DCD) provides an opportunity to expand the donor pool. Although deceased-donor liver transplantation from DCD donors has expanded, DCD livers continue to be discarded at elevated rates; the use of DCD livers from older donors, or donors with comorbidities, is controversial. METHODS: Using US registry data from 2009 to 2020, we identified 1564 candidates on whose behalf a DCD liver offer was accepted ("acceptors") and 16 981 candidates on whose behalf the same DCD offers were declined ("decliners"). We characterized outcomes of decliners using a competing risk framework and estimated the survival benefit (adjusted hazard ratio [95% confidence interval]) of accepting DCD livers using Cox regression. RESULTS: Within 10 y of DCD offer decline, 50.9% of candidates died or were removed from the waitlist before transplantation with any type of allograft. DCD acceptors had lower mortality compared with decliners at 10 y postoffer (35.4% versus 48.9%, P < 0.001). After adjustment for candidate covariates, DCD offer acceptance was associated with a 46% reduction in mortality (0.54 [0.49-0.61]). Acceptors of older (age ≥50), obese (body mass index ≥30), hypertensive, nonlocal, diabetic, and increased risk DCD livers had 44% (0.56 [0.42-0.73]), 40% (0.60 [0.49-0.74]), 48% (0.52 [0.41-0.66]), 46% (0.54 [0.45-0.65]), 32% (0.68 [0.43-1.05]), and 45% (0.55 [0.42-0.72]) lower mortality risk compared with DCD decliners, respectively. CONCLUSIONS: DCD offer acceptance is associated with considerable long-term survival benefits for liver transplant candidates, even with older DCD donors or donors with comorbidities. Increased recovery and utilization of DCD livers should be encouraged.

Proximal vs. Total Gastrectomy: Is There a Difference in Quality of Life for Patients?

BACKGROUND: Proximal gastrectomy (PG) has been excluded from the arsenal of western surgical oncologists for fear of bile reflux and diet intolerance. However, it is often an appropriate, less morbid operation for patients requiring resection of a proximal gastric cancer. METHODS: Between 2013 and 2017, we performed 19 PG and 37 total gastrectomies (TGs), of whom 15 and 25 were alive at the time of data collection. In this single-center series, we present findings of a 10-question interview of patients who underwent proximal (n = 8) or TG (n = 16) regarding postgastrectomy food-related symptoms, based on a modified version of the validated Postgastrectomy Syndrome Assessment Scale. RESULTS: Out of 7 Likert scale questions, there were no statistically significant differences between the groups regarding bile reflux, early satiety, appetite, energy level, physical activity limitations, pain, or general dissatisfaction with their surgery. Patients from both groups reported eating similar amounts of their preoperative volume per meal and overall food volume for the day. Both groups reported eating a similar number of snacks and meals throughout the day. Food satisfaction scores, calculated by summation of the Likert scores, were not different. CONCLUSION: Although limited by the small population, we did not find a clinically relevant difference in food-related symptoms comparing PG and TG patients. This pilot study suggests that PG is an appropriate alternative to TG in certain populations. Anecdotal beliefs regarding potential bile reflux or diet intolerance should be reconsidered.

Offer Acceptance Patterns for Liver Donors Aged 70 and Older.

Despite a documented survival benefit, older liver donor (OLD, age ≥70) graft offers are frequently declined, with utilization worsening over the last decade. To understand how offer acceptance varies by center, we studied 1113 eventually transplanted OLD grafts from 2009 to 2017 using Scientific Registry of Transplant Recipients (SRTR) data and random-intercept multilevel logistic regression. To understand how center-level acceptance of OLD graft offers might be associated with waitlist and posttransplant outcomes, we studied all adult, actively listed, liver-only candidates and recipients during the study period using Poisson regression (transplant rate), competing risks regression (waitlist mortality), and Cox regression (posttransplant mortality). Among 117 centers, OLD offer acceptance ranged from 0 (23 centers) to 95 acceptances, with a median odds ratio of 2.88. Thus, a candidate may be three times as likely to receive an OLD graft simply by listing at a different center. Centers in the highest quartile (Q4) of OLD acceptance (accepted 39% of OLD offers) accepted more nationally shared organs (Q4 versus Q1: 14.1% versus 0.0%, P < 0.001) and had higher annual liver transplant volume (Q4 versus Q1: 80 versus 21, P < 0.001). After adjustment, nationally shared OLD offers (adjusted odds ratio [aOR]: 0.16, 95% confidence interval [CI]: 0.13-0.20) and offers to centers with higher median Model for End-Stage Liver Disease (MELD) at transplant (aOR: 0.74, 95% CI: 0.62-0.87) were less likely to be accepted. OLD offers to centers with higher annual transplant volume were more likely to be accepted (aOR: 1.21, 95% CI: 1.14-1.30). Additionally, candidates listed at centers within the highest quartile of OLD graft offer acceptance had higher deceased donor liver transplantation (DDLT) rates (adjusted incidence rate ratio: 1.45, 95% CI: 1.41-1.50), lower waitlist mortality (adjusted subhazard ratio: 0.76, 95% CI: 0.72-0.76), and similar posttransplant survival (adjusted hazard ratio: 0.93, 95% CI: 0.86-1.01) when compared with those listed at centers in the lowest quartile of OLD graft offer acceptance. The wide variation in OLD offer acceptance supports the need for optimizing the organ offer process and efficiently directing OLD offers to centers more likely to use them.

Learning and Predicting from Dynamic Models for COVID-19 Patient Monitoring.

COVID-19 has challenged health systems to learn how to learn. This paper describes the context, methods and challenges for learning to improve COVID-19 care at one academic health center. Challenges to learning include: (1) choosing a right clinical target; (2) designing methods for accurate predictions by borrowing strength from prior patients' experiences; (3) communicating the methodology to clinicians so they understand and trust it; (4) communicating the predictions to the patient at the moment of clinical decision; and (5) continuously evaluating and revising the methods so they adapt to changing patients and clinical demands. To illustrate these challenges, this paper contrasts two statistical modeling approaches - prospective longitudinal models in common use and retrospective analogues complementary in the COVID-19 context - for predicting future biomarker trajectories and major clinical events. The methods are applied to and validated on a cohort of 1,678 patients who were hospitalized with COVID-19 during the early months of the pandemic. We emphasize graphical tools to promote physician learning and inform clinical decision making.

HOPE in action: A prospective multicenter pilot study of liver transplantation from donors with HIV to recipients with HIV.

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.

Survival Benefit of Split-Liver Transplantation for Pediatric and Adult Candidates.

Patient and graft survival are similar following whole-liver transplantations (WLTs) versus split-liver transplantations (SLTs) among pediatric and adult recipients, yet SLTs are rarely used. We sought to determine the survival benefit associated with accepting a splittable graft offer for SLT versus declining and waiting for a subsequent offer using 2010 to 2018 Scientific Registry of Transplant Recipients (SRTR) data on 928 pediatric and 1814 adult liver transplantation candidates who were ever offered a splittable graft. We compared eventual mortality, regardless of subsequent transplants, between those patients who accepted versus declined a split liver offer with adjustments for Pediatric End-Stage Liver Disease/Model for End-Stage Liver Disease (MELD) scores, diagnosis, and weight among pediatric candidates and matching for MELD score, height, and offer among adult candidates. Among pediatric candidates ≤7 kg, split liver offer acceptance versus decline was associated with a 63% reduction in mortality (adjusted hazard ratio [aHR], 0.17 0.370.80 [P = 0.01]; 93.1% versus 84.0% 1-year survival after decision). Within 1 year of decline for those ≤7 kg, 6.4% died and 31.1% received a WLT. Among pediatric candidates >7 kg, there was no significant difference associated with acceptance of a split liver offer (aHR, 0.63 1.071.82 [P = 0.81]; 91.7% versus 94.4% 1-year survival after decision). Within 1 year of decline for those >7 kg, 1.8% died and 45.8% received a WLT. Among adult candidates, split liver offer acceptance was associated with a 43% reduction in mortality (aHR, 0.39 0.570.83 [P = 0.005]; 92.2% versus 84.4% 1-year survival after decision). Within 1 year of decline for adult candidates, 7.9% died and 39.3% received a WLT. Accepting split liver offers for SLT could significantly improve survival for small children and adults on the waiting list.

Outcome-Stratified Analysis of Biomarker Trajectories for Patients Infected With Severe Acute Respiratory Syndrome Coronavirus 2.

Longitudinal trajectories of vital signs and biomarkers during hospital admission of patients with COVID-19 remain poorly characterized despite their potential to provide critical insights about disease progression. We studied 1884 patients with severe acute respiratory syndrome coronavirus 2 infection from April 3, 2020, to June 25, 2020, within 1 Maryland hospital system and used a retrospective longitudinal framework with linear mixed-effects models to investigate relevant biomarker trajectories leading up to 3 critical outcomes: mechanical ventilation, discharge, and death. Trajectories of 4 vital signs (respiratory rate, ratio of oxygen saturation (Spo2) to fraction of inspired oxygen (Fio2), pulse, and temperature) and 4 laboratory values (C-reactive protein (CRP), absolute lymphocyte count (ALC), estimated glomerular filtration rate, and D-dimer) clearly distinguished the trajectories of patients with COVID-19. Before any ventilation, log(CRP), log(ALC), respiratory rate, and Spo2-to-Fio2 ratio trajectories diverge approximately 8-10 days before discharge or death. After ventilation, log(CRP), log(ALC), respiratory rate, Spo2-to-Fio2 ratio, and estimated glomerular filtration rate trajectories again diverge 10-20 days before death or discharge. Trajectories improved until discharge and remained unchanged or worsened until death. Our approach characterizes the distribution of biomarker trajectories leading up to competing outcomes of discharge versus death. Moving forward, this model can contribute to quantifying the joint probability of biomarkers and outcomes when provided clinical data up to a given moment.

Better Understanding the Disparity Associated With Black Race in Heart Transplant Outcomes: A National Registry Analysis.

BACKGROUND: Black heart transplant recipients have higher risk of mortality than White recipients. Better understanding of this disparity, including subgroups most affected and timing of the highest risk, is necessary to improve care of Black recipients. We hypothesize that this disparity may be most pronounced among young recipients, as barriers to care like socioeconomic factors may be particularly salient in a younger population and lead to higher early risk of mortality. METHODS: We studied 22 997 adult heart transplant recipients using the Scientific Registry of Transplant Recipients data from January 2005 to 2017 using Cox regression models adjusted for recipient, donor, and transplant characteristics. RESULTS: Among recipients aged 18 to 30 years, Black recipients had 2.05-fold (95% CI, 1.67-2.51) higher risk of mortality compared with non-Black recipients (P<0.001, interaction P<0.001); however, the risk was significant only in the first year post-transplant (first year: adjusted hazard ratio, 2.30 [95% CI, 1.60-3.31], P<0.001; after first year: adjusted hazard ratio, 0.84 [95% CI, 0.54-1.29]; P=0.4). This association was attenuated among recipients aged 31 to 40 and 41 to 60 years, in whom Black recipients had 1.53-fold ([95% CI, 1.25-1.89] P<0.001) and 1.20-fold ([95% CI, 1.09-1.33] P<0.001) higher risk of mortality. Among recipients aged 61 to 80 years, no significant association was seen with Black race (adjusted hazard ratio, 1.12 [95% CI, 0.97-1.29]; P=0.1). CONCLUSIONS: Young Black recipients have a high risk of mortality in the first year after heart transplant, which has been masked in decades of research looking at disparities in aggregate. To reduce overall racial disparities, clinical research moving forward should focus on targeted interventions for young Black recipients during this period.

Decreased incidence of acute rejection without increased incidence of cytomegalovirus (CMV) infection in kidney transplant recipients receiving rabbit anti-thymocyte globulin without CMV prophylaxis - a cohort single-center study.

Induction therapy with rabbit anti-thymocyte globulin (rATG) in low-risk kidney transplant recipients (KTR) remains controversial, given the associated increased risk of cytomegalovirus (CMV) infection. This natural experiment compared 12-month clinical outcomes in low-risk KTR without CMV prophylaxis (January/3/13-September/16/15) receiving no induction or a single 3 mg/kg dose of rATG. We used logistic regression to characterize delayed graft function (DGF), negative binomial to characterize length of hospital stay (LOS), and Cox regression to characterize acute rejection (AR), CMV infection, graft loss, death, and hospital readmissions. Recipients receiving 3 mg/kg rATG had an 81% lower risk of AR (aHR 0.14 0.190.25 , P < 0.001) but no increased rate of hospital readmissions because of infections (0.68 0.911.21 , P = 0.5). There was no association between 3 mg/kg rATG and CMV infection/disease (aHR 0.86 1.101.40 , P = 0.5), even when the analysis was stratified according to recipient CMV serostatus positive (aHR 0.94 1.251.65 , P = 0.1) and negative (aHR 0.28 0.571.16 , P = 0.1). There was no association between 3 mg/kg rATG and mortality (aHR 0.51 1.253.08 , P = 0.6), and graft loss (aHR 0.34 0.731.55 , P = 0.4). Among low-risk KTR receiving no CMV pharmacological prophylaxis, 3 mg/kg rATG induction was associated with a significant reduction in the incidence of AR without an increased risk of CMV infection, regardless of recipient pretransplant CMV serostatus.

Center-level Variation in HLA-incompatible Living Donor Kidney Transplantation Outcomes.

BACKGROUND: Desensitization protocols for HLA-incompatible living donor kidney transplantation (ILDKT) vary across centers. The impact of these, as well as other practice variations, on ILDKT outcomes remains unknown. METHODS: We sought to quantify center-level variation in mortality and graft loss following ILDKT using a 25-center cohort of 1358 ILDKT recipients with linkage to Scientific Registry of Transplant Recipients for accurate outcome ascertainment. We used multilevel Cox regression with shared frailty to determine the variation in post-ILDKT outcomes attributable to between-center differences and to identify any center-level characteristics associated with improved post-ILDKT outcomes. RESULTS: After adjusting for patient-level characteristics, only 6 centers (24%) had lower mortality and 1 (4%) had higher mortality than average. Similarly, only 5 centers (20%) had higher graft loss and 2 had lower graft loss than average. Only 4.7% of the differences in mortality (P < 0.01) and 4.4% of the differences in graft loss (P < 0.01) were attributable to between-center variation. These translated to a median hazard ratio of 1.36 for mortality and 1.34 of graft loss for similar candidates at different centers. Post-ILDKT outcomes were not associated with the following center-level characteristics: ILDKT volume and transplanting a higher proportion of highly sensitized, prior transplant, preemptive, or minority candidates. CONCLUSIONS: Unlike most aspects of transplantation in which center-level variation and volume impact outcomes, we did not find substantial evidence for this in ILDKT. Our findings support the continued practice of ILDKT across these diverse centers.

Patient Trajectories Among Persons Hospitalized for COVID-19 : A Cohort Study.

BACKGROUND: Risk factors for progression of coronavirus disease 2019 (COVID-19) to severe disease or death are underexplored in U.S. cohorts. OBJECTIVE: To determine the factors on hospital admission that are predictive of severe disease or death from COVID-19. DESIGN: Retrospective cohort analysis. SETTING: Five hospitals in the Maryland and Washington, DC, area. PATIENTS: 832 consecutive COVID-19 admissions from 4 March to 24 April 2020, with follow-up through 27 June 2020. MEASUREMENTS: Patient trajectories and outcomes, categorized by using the World Health Organization COVID-19 disease severity scale. Primary outcomes were death and a composite of severe disease or death. RESULTS: Median patient age was 64 years (range, 1 to 108 years); 47% were women, 40% were Black, 16% were Latinx, and 21% were nursing home residents. Among all patients, 131 (16%) died and 694 (83%) were discharged (523 [63%] had mild to moderate disease and 171 [20%] had severe disease). Of deaths, 66 (50%) were nursing home residents. Of 787 patients admitted with mild to moderate disease, 302 (38%) progressed to severe disease or death: 181 (60%) by day 2 and 238 (79%) by day 4. Patients had markedly different probabilities of disease progression on the basis of age, nursing home residence, comorbid conditions, obesity, respiratory symptoms, respiratory rate, fever, absolute lymphocyte count, hypoalbuminemia, troponin level, and C-reactive protein level and the interactions among these factors. Using only factors present on admission, a model to predict in-hospital disease progression had an area under the curve of 0.85, 0.79, and 0.79 at days 2, 4, and 7, respectively. LIMITATION: The study was done in a single health care system. CONCLUSION: A combination of demographic and clinical variables is strongly associated with severe COVID-19 disease or death and their early onset. The COVID-19 Inpatient Risk Calculator (CIRC), using factors present on admission, can inform clinical and resource allocation decisions. PRIMARY FUNDING SOURCE: Hopkins inHealth and COVID-19 Administrative Supplement for the HHS Region 3 Treatment Center from the Office of the Assistant Secretary for Preparedness and Response.

A prospective multicenter pilot study of HIV-positive deceased donor to HIV-positive recipient kidney transplantation: HOPE in action.

HIV-positive donor to HIV-positive recipient (HIV D+/R+) transplantation is permitted in the United States under the HIV Organ Policy Equity Act. To explore safety and the risk attributable to an HIV+ donor, we performed a prospective multicenter pilot study comparing HIV D+/R+ vs HIV-negative donor to HIV+ recipient (HIV D-/R+) kidney transplantation (KT). From 3/2016 to 7/2019 at 14 centers, there were 75 HIV+ KTs: 25 D+ and 50 D- (22 recipients from D- with false positive HIV tests). Median follow-up was 1.7 years. There were no deaths nor differences in 1-year graft survival (91% D+ vs 92% D-, P = .9), 1-year mean estimated glomerular filtration rate (63 mL/min D+ vs 57 mL/min D-, P = .31), HIV breakthrough (4% D+ vs 6% D-, P > .99), infectious hospitalizations (28% vs 26%, P = .85), or opportunistic infections (16% vs 12%, P = .72). One-year rejection was higher for D+ recipients (50% vs 29%, HR: 1.83, 95% CI 0.84-3.95, P = .13) but did not reach statistical significance; rejection was lower with lymphocyte-depleting induction (21% vs 44%, HR: 0.33, 95% CI 0.21-0.87, P = .03). In this multicenter pilot study directly comparing HIV D+/R+ with HIV D-/R+ KT, overall transplant and HIV outcomes were excellent; a trend toward higher rejection with D+ raises concerns that merit further investigation.

Survival benefit of accepting kidneys from older donation after cardiac death donors.

Kidneys from older (age ≥50 years) donation after cardiac death (DCD50) donors are less likely to be transplanted due to inferior posttransplant outcomes. However, candidates who decline a DCD50 offer must wait for an uncertain future offer. To characterize the survival benefit of accepting DCD50 kidneys, we used 2010-2018 Scientific Registry for Transplant Recipients (SRTR) data to identify 92 081 adult kidney transplantation candidates who were offered a DCD50 kidney that was eventually accepted for transplantation. DCD50 kidneys offered to candidates increased from 590 in 2010 to 1441 in 2018. However, 34.6% of DCD50 kidneys were discarded. Candidates who accepted DCD50 offers had 49% decreased mortality risk (adjusted hazard ratio [aHR] 0.46 0.510.55 , cumulative mortality at 6-year 23.3% vs 34.0%, P < .001) compared with those who declined the same offer (decliners). Six years after their initial DCD50 offer decline, 43.0% of decliners received a deceased donor kidney transplant (DDKT), 6.3% received living donor kidney transplant (LDKT), 22.6% died, 22.0% were removed for other reasons, and 6.0% were still on the waitlist. Comparable survival benefit was observed even with DCD donors age ≥60 (aHR: 0.42 0.520.65 , P < .001). Accepting DCD50 kidneys was associated with a substantial survival benefit; providers and patients should consider these benefits when evaluating offers.