Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection among Kidney Transplant Recipients: A Large Single-Center Experience.

Background: Kidney transplant recipients (KTRs) are a vulnerable immunocompromised population at risk of severe COVID-19 disease and mortality after SARS-CoV-2 infection. We sought to characterize the post-infection sequelae in KTRs at our center. Methods: We studied all adult KTRs (with a functioning allograft) who had their first episode of SARS-CoV-2 infection between 04/2020 and 04/2022. Outcomes of interest included risk factors for hospitalization, all-cause mortality, COVID-19-related mortality, and allograft failure. Results: Of 979 KTRs with SARS-CoV-2 infection, 381 (39%) were hospitalized. In the multivariate analysis, risk factors for hospitalization included advanced age/year (HR: 1.03, 95% CI: 1.02-1.04), male sex (HR: 1.29, 95% CI: 1.04-1.60), non-white race (HR: 1.48, 95% CI: 1.17-1.88), and diabetes as a cause of ESKD (HR: 1.77, 95% CI: 1.41-2.21). SARS-CoV-2 Vaccination was associated with decreased risk of hospitalization (HR: 0.73, 95% CI: 0.59-0.90), all-cause mortality (HR: 0.52, 95% CI: 0.37-0.74), and COVID-19-related mortality (HR: 0.47, 95% CI: 0.31-0.71) in the univariate and multivariate analyses. Risk factors for both all-cause and COVID-19-related mortality in the multivariate analyses included advanced age, hospitalization, and respiratory symptoms for hospital admission. Furthermore, additional risk factors for all-cause mortality in the multivariate analysis included being a non-white recipient and diabetes as a cause of ESKD, with being a recipient of a living donor as protective. Conclusions: Hospitalization due to COVID-19-associated symptoms is associated with increased mortality. Vaccination is a protective factor against hospitalization and mortality.

Avascular Necrosis in Kidney Transplant Recipients is Associated With an Increased Risk of Patient Death.

Introduction: Avascular necrosis is a debilitating osseous complication in transplant recipients. Project Aim: This program evaluation sought to describe risk factors and adverse outcomes of avascular necrosis in kidney transplant recipients. Design: This was a retrospective evaluation of all recipients of kidneys and simultaneous pancreas and kidneys between 2001 and 2018 from a single center. Controls were selected based on the incidence density, sampling at a 1:3 ratio based on the post-transplant interval. Outcomes of interest were acute rejection, death-censored graft failure, and patient mortality. Results: A total of 88 kidney recipients had avascular necrosis and were compared with 257 controls. Most of the recipient's and donors' baseline characteristics were similar between the groups, except calcineurin inhibitor-based immunosuppression was more prevalent, and non-white donors were less prevalent in the control group. Looking for risk factors for avascular necrosis, calcineurin inhibitor-based immunosuppression was associated with a lower risk for avascular necrosis in the univariate analysis, but this was not found after adjustment of multiple variables. In multivariate analysis, avascular necrosis was associated with an increased risk for patient death (hazard ratio: 1.68; 95% confidence interval: 1.16-2.44; P = .008) but not for acute rejection or death censored graft failure. Conclusion: Although limited by small sample size, this evaluation found avascular necrosis to be associated with an increased risk of patient death. This finding may be useful for the provider taking care of the patients and discussing the various outcomes after the transplant.

Higher and Sustained Cell-Mediated Immune Responses After 3 Doses of mRNA COVID-19 Vaccine in Patients With Inflammatory Bowel Disease on Anti-Tumor Necrosis Factor Therapy.

INTRODUCTION: Studies suggest that the generation of durable T-cell immunity following coronavirus disease 2019 (COVID-19) vaccination protects against severe disease. The aim of this study was to measure cell-mediated immune response (CMIR) 1-2 months and 6 months after a third dose of a COVID-19 mRNA vaccine. METHODS: This prospective study (HumoRal and CellULar initial and Sustained immunogenicity in patients with inflammatory bowel disease [IBD]) evaluated CMIR at 28-65 days (t 1 ) after dose 2, 28-65 days (t 2 ) (n = 183) and 6 months (±45 days) (t 3 ) (n = 167) after a third dose of an mRNA COVID-19 vaccine. A small cohort had blood sample available 28-65 days (t 4 ) (n = 55) after a fourth dose. Primary outcomes were CMIR at (t 2 ) and (t 3 ). Secondary outcomes included the effect of immunosuppressing IBD medications on CMIR and response at (t 4 ). RESULTS: All patients had measurable CMIR at all time points. CMIR increased at t 2 compared with that at t 1 (median 1,467 responding cells per million (interquartile range [IQR] 410-5,971) vs 313 (94-960) P < 0.001). There was no significant waning in t 2 vs t 3 or significant boosting at t 4 . Those on anti-tumor necrosis factor monotherapy had a higher CMIR compared with those not on this therapy at t 2 (4,132 [IQR 1,136-8,795] vs 869 [IQR 343-3,221] P < 0.001) and t 3 (2,843 [IQR 596-6,459] vs 654 [IQR 143-2,067] P < 0.001). In univariable analysis, anti-tumor necrosis factor monotherapy was associated with a higher CMIR at t 2 ( P < 0.001) and t 3 ( P < 0.001) and confirmed in a multivariable model ( P < 0.001). DISCUSSION: A third dose of a COVID-19 vaccine boosts CMIR, and the response is sustained in patients with IBD.

Analysis of Individual Components of Frailty in Simultaneous Pancreas and Kidney, and Solitary Pancreas Transplant Recipients.

Backgrounds: It is not known which of the 5 components of the Fried frailty score have the most predictive value for outcomes in simultaneous pancreas-kidney transplant (SPK) and solitary pancreas transplant (SPT) recipients. Methods: In this study, we sought to investigate the association between pretransplant overall frailty and individual frailty components, with posttransplant outcomes among SPK and SPT recipients. Outcomes of interest were length of stay, kidney delayed graft function (K-DGF), readmission within 30 d after discharge, cardiovascular events, acute rejection, pancreas death-censored graft failure (DCGF), kidney DCGF, and death. Results: Of the individual frailty components among SPK (n = 113), only slow walk time was associated with an increased risk of mortality (adjusted odds ratio [aOR]: 4.99; P = 0.03). Among SPT (n = 49), higher sum frailty scores (coefficient correlation 0.29; P = 0.04) and weight loss (coefficient correlation = 0.30; P = 0.03) were associated with prolonged length of stay. Similarly, weight loss among SPT was associated with an increased risk of DCGF (aOR: 4.34; P = 0.049). Low grip strength was strongly associated with an increased risk of early readmission (aOR: 13.08; P = 0.008). Conclusions: We found that not all components of frailty contribute equally to predicting outcomes. Objective measurements of slow walk time, unintentional weight loss, and low grip strength were found to be associated with less optimal outcomes in pancreas transplant recipients. Targeted interventions may improve posttransplant outcomes.

Discordance in cytomegalovirus viremia in kidney recipients from the same donor is associated with the worst outcomes.

BACKGROUND: Cytomegalovirus (CMV) is a common viral infection in kidney transplant recipients (KTR) that has been associated with negative outcomes. The effect on outcomes of concordance versus discordance in CMV between two different recipients of kidneys from the same donor is largely unknown. METHODS: We reviewed all adult deceased donor kidney transplant recipients (DDKTs) for which both kidneys were transplanted to two different recipients at our center between 2014 and 2019. Recipient pairs from each donor were divided into groups based on concordance or discordance for the development of CMV viremia between the pair; concordant no CMV (cc-no-CMV) if neither KTR developed CMV, concordant CMV (cc-CMV) if both KTRs developed CMV. The discordant group was then further divided based on the individual development of CMV (dc-CMV) or lack of development of CMV (dc-no-CMV). Patient mortality and death-censored graft failure (DCGF) were outcomes of interest. RESULTS: Of 578 KTRs, 67% were cc-no-CMV, 5% were cc-CMV, 14% were dc-no-CMV, and 14% dc-CMV. Some of the baseline characteristics differ among the groups including a higher prevalence of high-risk serostatus (D+/R-) in cc-CMV (32%) and dc-CMV (32%). In multivariate analysis, with reference to cc-no-CMV, dc-CMV was associated with increased risk for DCGF (HR 3.13, 95% CI 1.58-6.19), and so was delayed graft function. Factors associated with increased risk of mortality were advanced recipient age and DGF. cc-CMV was neither associated with mortality nor DCGF. CONCLUSIONS: These findings support that in certain contexts, CMV viremia has adverse allograft outcomes, and this is highlighted when illustrated via discordance in CMV between pair kidneys from the same deceased donor.

Neural correlates of safety learning.

Accurate discrimination between safe and dangerous stimuli is essential for survival. Prior research has begun to uncover the neural structures that are necessary for learning this discrimination, but exploration of brain regions involved in this learning process has been mostly limited to males. Recent findings show sex differences in discrimination learning, with reduced fear expression to safe cues in females compared to males. Here, we used male and female Sprague Dawley rats to explore neural activation, as measured by Fos expression, in fear and safety learning related brain regions. Neural activation after fear discrimination (Discrimination) was compared between males and females, as well as with fear conditioned (Fear Only) and stimulus presented (Control) conditions. Correlations of discrimination ability and neural activation were also calculated. We uncovered a correlation between central amygdala (CeA) activation and discrimination abilities in males and females. Anterior medial bed nucleus of the stria terminalis (BNST) was the only region where sex differences in Fos counts were observed in the Discrimination condition, and the only region where neural activation significantly differed between Fear Only and Discrimination conditions. Together, these findings indicate the importance of fear expression circuitry in mediating discrimination responses and generate important questions for future investigation.

Responding to a medical crisis: Lessons from the Halifax disaster 100 years ago.

One hundred years ago, a massive explosion occurred in the harbor of Halifax, Nova Scotia, destroying the city and killing more than 2,000 and injuring more than 9,000. It was the worst manmade explosion the world had ever seen, not exceeded until the atomic bomb blast over Hiroshima in 1945. An urgent appeal for assistance came from the survivors, and many volunteers responded. This report describes the prompt and remarkable medical relief effort of the citizens of Massachusetts to help their Canadian neighbors.