Faculty Bibliography

In this study of 12 people with HIV (PWH) who received the first dose of SARS-CoV-2 mRNA vaccination, anti-SARS-CoV-2 receptor-binding domain antibodies were detectable in all participants; lower antibody levels were seen in those with lower CD4+ counts, and vaccine reactions were generally mild.

BACKGROUND:Belatacept may impair humoral immunity, impacting the effectiveness of SARS-CoV-2 mRNA vaccines in transplant recipients. We investigated immunogenicity after SARS-CoV-2 mRNA vaccines in kidney transplant recipients who are and are not taking belatacept. METHODS:Participants were recruited between December 9, 2020, and April 1, 2021. Blood samples were collected after dose 1 and dose 2 (D1, D2) and analyzed using either an anti-SARS-CoV-2 enzyme immunoassay against the S1 domain of the SARS-CoV-2 spike protein or immunoassay against the receptor-binding domain of the SARS-CoV-2 spike protein. Stabilized inverse probability of treatment weights was used to compare immunogenicity, and a weighted logistics regression was used to calculate fold change of positive response. RESULTS:Among the 609 participants studied, 24 (4%) were taking belatacept. After dose 1, 0/24 (0%) belatacept patients had detectable antibodies, compared with 77 of 568 (14%) among the equivalent nonbelatacept population (P = 0.06). After dose 2, 1/19 (5%) belatacept patients had detectable antibodies, compared with 190/381 (50%) among the equivalent nonbelatacept population (P < 0.001). Belatacept use was associated with 16.7-fold lower odds of having a positive post-D2 titer result (P < 0.01). CONCLUSIONS:Additional measures need to be explored to protect kidney transplant recipients taking belatacept. Best safety practices should be continued despite vaccination among this population.

Frailty is a multidimensional condition and is the result of the body's age-associated decline in physical, cognitive, physiological, and immune reserves. The aim of this systematic review is to assess the quality of evidence of the included studies, determine the prevalence of frailty among kidney transplant candidates, and evaluate the relationship between frailty and associated patient characteristics and outcomes after kidney transplantation.

BACKGROUND AND OBJECTIVES:Patients with sickle cell disease-associated kidney failure have high mortality, which might be lowered by kidney transplantation. However, because they show higher post-transplant mortality compared with patients with other kidney failure etiologies, kidney transplantation remains controversial in this population, potentially limiting their chance of receiving transplantation. We aimed to quantify the decrease in mortality associated with transplantation in this population and determine the chance of receiving transplantation with sickle cell disease as the cause of kidney failure as compared with other etiologies of kidney failure. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Using a national registry, we studied all adults with kidney failure who began maintenance dialysis or were added to the kidney transplant waiting list in 1998-2017. To quantify the decrease in mortality associated with transplantation, we measured the absolute risk difference and hazard ratio for mortality in matched pairs of transplant recipients versus waitlisted candidates in the sickle cell and control groups. To compare the chance of receiving transplantation, we estimated hazard ratios for receiving transplantation in the sickle cell and control groups, treating death as a competing risk. RESULTS:=0.8). Nonetheless, the sickle cell group was less likely to receive transplantation than the controls (subdistribution hazard ratio, 0.73; 95% confidence interval, 0.61 to 0.87). Similar disparities were found among waitlisted candidates (subdistribution hazard ratio, 0.62; 95% confidence interval, 0.53 to 0.72). CONCLUSIONS:Patients with sickle cell disease-associated kidney failure exhibited similar decreases in mortality associated with kidney transplantation as compared with those with other kidney failure etiologies. Nonetheless, the sickle cell population was less likely to receive transplantation, even after waitlist registration.

BACKGROUND:Kidney allograft failure is a common cause of end-stage renal disease. We aimed to develop a dynamic artificial intelligence approach to enhance risk stratification for kidney transplant recipients by generating continuously refined predictions of survival using updates of clinical data. METHODS:In this observational study, we used data from adult recipients of kidney transplants from 18 academic transplant centres in Europe, the USA, and South America, and a cohort of patients from six randomised controlled trials. The development cohort comprised patients from four centres in France, with all other patients included in external validation cohorts. To build deeply phenotyped cohorts of transplant recipients, the following data were collected in the development cohort: clinical, histological, immunological variables, and repeated measurements of estimated glomerular filtration rate (eGFR) and proteinuria (measured using the proteinuria to creatininuria ratio). To develop a dynamic prediction system based on these clinical assessments and repeated measurements, we used a Bayesian joint models-an artificial intelligence approach. The prediction performances of the model were assessed via discrimination, through calculation of the area under the receiver operator curve (AUC), and calibration. This study is registered with ClinicalTrials.gov, NCT04258891. FINDINGS/RESULTS:13 608 patients were included (3774 in the development cohort and 9834 in the external validation cohorts) and contributed 89 328 patient-years of data, and 416 510 eGFR and proteinuria measurements. Bayesian joint models showed that recipient immunological profile, allograft interstitial fibrosis and tubular atrophy, allograft inflammation, and repeated measurements of eGFR and proteinuria were independent risk factors for allograft survival. The final model showed accurate calibration and very high discrimination in the development cohort (overall dynamic AUC 0·857 [95% CI 0·847-0·866]) with a persistent improvement in AUCs for each new repeated measurement (from 0·780 [0·768-0·794] to 0·926 [0·917-0·932]; p<0·0001). The predictive performance was confirmed in the external validation cohorts from Europe (overall AUC 0·845 [0·837-0·854]), the USA (overall AUC 0·820 [0·808-0·831]), South America (overall AUC 0·868 [0·856-0·880]), and the cohort of patients from randomised controlled trials (overall AUC 0·857 [0·840-0·875]). INTERPRETATION/CONCLUSIONS:Because of its dynamic design, this model can be continuously updated and holds value as a bedside tool that could refine the prognostic judgements of clinicians in everyday practice, hence enhancing precision medicine in the transplant setting. FUNDING/BACKGROUND:MSD Avenir, French National Institute for Health and Medical Research, and Bettencourt Schueller Foundation.

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.