Faculty Bibliography

BACKGROUND:Transplant surgery fellowship has evolved over the years and today there are 66 accredited training programs in the US and Canada. There is growing concern, however, about the number of US-trained general surgery residents pursuing transplant surgery. In this study, we examined the transplant surgery pipeline, comparing it with other surgical subspecialty fellowships, and characterized the resident transplantation experience. METHODS:Datasets were compiled and analyzed from surgical fellowship match data obtained from the National Resident Matching Program and ACGME reports and relative fellowship competitiveness was assessed. The surgical resident training experience in transplantation was evaluated. RESULTS:From 2006 to 2018, a total of 1,094 applicants have applied for 946 transplant surgery fellowship positions; 299 (27.3%) were US graduates. During this period, there was a 0.8% decrease per year in US-trained surgical residents matching into transplant surgery (p = 0.042). In addition, transplant surgery was one of the least competitive fellowships compared with other National Resident Matching Program surgical subspeciality fellowships, as measured by the number of US applicants per available fellowship position, average number of fellowship programs listed on each applicant's rank list, and proportion of unfilled fellowship positions (each, p < 0.05). Finally, from 2015 to 2017, there were 57 general surgery residency programs that produced 77 transplant surgery fellows, but nearly one-half of the fellows (n = 36 [46.8%]) came from 16 (28.1%) programs. CONCLUSIONS:Transplant surgery is one of the least competitive and sought after surgical fellowships for US-trained residents. These findings highlight the need for dedicated efforts to increase exposure, mentorship, and interest in transplantation to recruit strong US graduates.

Allografts from living kidney donors with hypertension may carry subclinical kidney disease from the donor to the recipient and, thus, lead to adverse recipient outcomes. We examined eGFR trajectories and all-cause allograft failure in recipients from donors with versus without hypertension, using mixed-linear and Cox regression models stratified by donor age. We studied a US cohort from 1/1/2005 to 6/30/2017; 49 990 recipients of allografts from younger (<50 years old) donors including 597 with donor hypertension and 21 130 recipients of allografts from older (≥50 years old) donors including 1441 with donor hypertension. Donor hypertension was defined as documented predonation use of antihypertensive therapy. Among recipients from younger donors with versus without hypertension, the annual eGFR decline was -1.03 versus -0.53 ml/min/m² (P = 0.002); 13-year allograft survival was 49.7% vs. 59.0% (adjusted allograft failure hazard ratio [aHR] 1.23; 95% CI 1.05-1.43; P = 0.009). Among recipients from older donors with versus without hypertension, the annual eGFR decline was -0.67 versus -0.66 ml/min/m² (P = 0.9); 13-year allograft survival was 48.6% versus 52.6% (aHR 1.05; 95% CI 0.94-1.17; P = 0.4). In secondary analyses, our inferences remained similar for risk of death-censored allograft failure and mortality. Hypertension in younger, but not older, living kidney donors is associated with worse recipient outcomes.

During the COVID-19 pandemic, there has been wide heterogeneity in the medical management of transplant recipients. We aimed to pragmatically capture immunosuppression practices globally following the early months of the pandemic. From June to September 2020, we surveyed 1267 physicians; 40.5% from 71 countries participated. Management decisions were made on a case-by-case basis by the majority (69.6%) of the programs. Overall, 76.8% performed ≥1 transplantation and many commented on avoiding high-risk transplantations. For induction, 26.5% were less likely to give T-cell depletion and 14.8% were more likely to give non-depleting agents. These practices varied by program-level factors more so than the COVID-19 burden. In patients with mild, moderate and severe COVID-19 symptoms 59.7%, 76.0%, and 79.5% decreased/stopped anti-metabolites, 23.2%, 45.4%, and 68.2% decreased/stopped calcineurin inhibitors, and 25.7%, 43.9%, and 57.7% decreased/stopped mTOR inhibitors, respectively. Also, 2.1%, 30.6%, and 46.0% increased steroids in patients with mild, moderate, and severe COVID-19 symptoms. For prevalent transplant recipients, some programs also reported decreasing/stopping steroids (1.8%), anti-metabolites (10.3%), calcineurin inhibitors (4.1%), and mTOR inhibitors (5.5%). Transplant programs changed immunosuppression practices but also avoided high-risk transplants and increased maintenance steroids. The long-term ramifications of these practices remain to be seen as programs face the aftermath of the pandemic.

Transplant recipients were excluded from the initial clinical trials determining safety and efficacy of the landmark COVID-19 vaccines. Further, there is increasing evidence that immunosuppressed transplant recipients have a blunted antibody response to COVID-19 vaccination. In a concerning report by Sattler et al. in this issue of the JCI, kidney transplant recipients not only lacked a humoral response following two doses of Pfizer BNT162b2, but also displayed substantial impairment of the cellular response to SARS-CoV-2 antigens. This Commentary addresses potential strategies for transplant providers to evaluate and augment vaccine immunogenicity given the likelihood that COVID-19 will remain a world-wide threat to the health of transplant recipients.

BACKGROUND:The human immunodeficiency virus (HIV)-1 latent reservoir (LR) in resting CD4+ T cells is a barrier to cure. LR measurements are commonly performed on blood samples and therefore may miss latently infected cells residing in tissues, including lymph nodes. METHODS:We determined the frequency of intact HIV-1 proviruses and proviral inducibility in matched peripheral blood (PB) and lymph node (LN) samples from 10 HIV-1-infected patients on antiretroviral therapy (ART) using the intact proviral DNA assay and a novel quantitative viral induction assay. Prominent viral sequences from induced viral RNA were characterized using a next-generation sequencing assay. RESULTS:The frequencies of CD4+ T cells with intact proviruses were not significantly different in PB versus LN (61/106 vs 104/106 CD4+ cells), and they were substantially lower than frequencies of CD4+ T cells with defective proviruses. The frequencies of CD4+ T cells induced to produce high levels of viral RNA were not significantly different in PB versus LN (4.3/106 vs 7.9/106), but they were 14-fold lower than the frequencies of cells with intact proviruses. Sequencing of HIV-1 RNA from induced proviruses revealed comparable sequences in paired PB and LN samples. CONCLUSIONS:These results further support the use of PB as an appropriate proxy for the HIV-1 LR in secondary lymphoid organs.

Organ transplant patients have poor immune responses to COVID-19 vaccines; thus designing vaccine strategies to protect this vulnerable population from SARS-CoV-2 infection is crucial.

A widely accepted severe acute respiratory syndrome 2 (SARS-CoV-2) vaccine could protect vulnerable populations, but the willingness of solid organ transplant recipients (SOTRs) to accept a potential vaccine remains unknown.

BACKGROUND AND OBJECTIVES:Patients with kidney failure report a high symptom burden, which likely increases while on dialysis due to physical and mental stressors and decreases after kidney transplantation due to restoration of kidney function. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:=190), and post-transplantation symptom score trajectories (mixed effects models). RESULTS:At evaluation, candidates reported being moderately to extremely bothered by fatigue (32%), xeroderma (27%), muscle soreness (26%), and pruritus (25%); 16% reported high and 21% reported very high symptom burden. Candidates with very high symptom burden were at greater waitlist mortality risk (adjusted subdistribution hazard ratio, 1.67; 95% confidence interval, 1.06 to 2.62). By transplantation, 34% experienced an increased symptom burden, whereas 42% remained unchanged. The estimated overall symptom score was 82.3 points at transplantation and 90.6 points at 3 months (10% improvement); the score increased 2.75 points per month (95% confidence interval, 2.38 to 3.13) from 0 to 3 months, and plateaued (-0.06 points per month; 95% confidence interval, -0.30 to 0.18) from 3 to 12 months post-transplantation. There were early (first 3 months) improvements in nine of 11 symptoms; pruritus (23% improvement) and fatigue (21% improvement) had the greatest improvements. CONCLUSIONS:Among candidates, very high symptom burden was associated with waitlist mortality, but for those surviving and undergoing kidney transplantation, symptoms improved.

Background/UNASSIGNED:Among adult kidney transplant (KT) recipients, the risk of post-KT adverse outcomes differs by type of induction immunosuppression. Immune response to induction differs as recipients age; yet, choice of induction is barely tailored by age likely due to a lack of evidence of the risks and benefits. Methods/UNASSIGNED:Using Scientific Registry of Transplant Recipients data, we identified 39336 first-time KT recipients (2010-2016). We estimated the length of stay (LOS), acute rejection (AR), graft failure, and death by induction type using logistic and Cox regression weighted by propensity score to adjust for confounders. We tested whether these estimates differed by age (65+ versus 18-64 y) using a Wald test. Results/UNASSIGNED: = 0.03 and 0.003) differed by recipient age. Discharge was on average 11% shorter in rATG among younger recipients (relative time = 0.89; 95% confidence interval [CI], 0.81-0.99) but not among older recipients (relative time = 1.01; 95% CI, 0.95-1.08). rATG was not associated with mortality among older (hazard ratio = 1.05; 95% CI, 0.96-1.15), but among younger recipients (hazard ratio = 0.87; 95% CI, 0.80-0.95), it was associated with reduced mortality risk. Conclusions/UNASSIGNED:rATG should be considered to prevent AR, especially among recipients with high-immunologic risk regardless of age; however, choice of induction should be tailored to reduce LOS and risk of mortality, particularly among younger recipients.