Faculty Bibliography

INTRODUCTION:We developed the strength training intervention (STRIVE), a home-based exercise program targeting physical function in patients with cirrhosis. In this pilot study, we aimed to evaluate the safety and efficacy of STRIVE. METHODS:Eligible were adult patients with cirrhosis at 3 sites. Patients were randomized 2:1-12 weeks of STRIVE, a 30-minute strength training video plus a health coach or standard of care (SOC). Physical function and quality of life were assessed using the Liver Frailty Index (LFI) and Chronic Liver Disease Questionnaire (CLDQ), respectively. RESULTS:Fifty-eight and 25 were randomized to STRIVE and SOC arms, respectively: 43% women, median age was 61 years, MELDNa, Model for End-Stage Liver Disease Sodium was 14, and 54% were Child-Pugh B/C. Baseline characteristics were similar in the STRIVE vs SOC arms except for rates of hepatic encephalopathy (19 vs 36%). LFI @ 12 weeks was available in 43 STRIVE and 20 SOC participants. After 12 weeks, the median LFI improved from 3.8 to 3.6 (ΔLFI -0.1) in the STRIVE arm and 3.7 to 3.6 (ΔLFI -0.1) in the SOC arm (P = 0.65 for ΔLFI difference). CLDQ scores improved from 4.6 to 5.2 in STRIVE participants (ΔCLDQ 0.38) and did not change in SOC participants (4.2-4.2; ΔCLDQ -0.03) (P = 0.09 for ΔCLDQ difference). One patient died (SOC arm) of bleeding. Only 14% of STRIVE participants adhered to the strength training video for 10-12 weeks. No adverse events were reported by STRIVE participants. DISCUSSION:STRIVE, a home-based structured exercise program for patients with cirrhosis, was safely administered at 3 sites, but adherence was low. Although all participants showed minimal improvement in the LFI, STRIVE was associated with a substantial improvement in quality of life.

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.

OBJECTIVES/OBJECTIVE:The creation and maintenance of durable hemodialysis access is critically important for reducing patient morbidity and controlling overall costs within health systems. Our objective was to quantify the costs associated with hemodialysis access creation and its maintenance over time within a rate-controlled health system where charges equate to payments. METHODS:The Maryland Health Services Cost Review Commission administrative claims database was used to identify patients who underwent first-time access creation from 2012-2020. Patients were identified using CPT codes for access creation, and costs were accrued for the initial encounter and all subsequent outpatient access-related encounters. T-tests and Wilcoxon tests were used to compare reinterventions and access-related costs ($USD) between arteriovenous fistulae (AVF) and arteriovenous grafts (AVG). Multivariable modeling was used to quantify the association of access type with charge variation. RESULTS:Overall, 12,716 patients underwent first-time access creation (69.3% AVF vs. 30.7% AVG). There was no difference in freedom from reintervention between the two access types at any point following creation (HR: 1.03, 95%CI: 0.97-1.10); however, AVF were associated with a lower number of cumulative reinterventions (1.50 vs. 2.24) compared to AVG (P<0.0001). AVF was associated with lower overall costs in the year of creation ($9,388 vs. $13,539, P<0.0001), a difference that remained significant over the subsequent 3 years. The lower costs associated with AVF were present both in the costs associated with creation and subsequent maintenance. On multivariable analysis, AVF was associated with a $3,557 reduction in total access-related costs versus AVG (95%CI -$3828, -3287). CONCLUSION/CONCLUSIONS:AVF require fewer interventions and are associated with lower costs at placement and over the first three years of maintenance compared to AVG. The use of AVF for first-time hemodialysis access represents an opportunity for healthcare savings in appropriately selected patients with a high preoperative likelihood of AVF maturation.

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.

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.

In the seven years since the HIV Organ Policy Equity (HOPE) Act made HIV-positive organ donation to HIV-positive recipients legally permissible in the United States, there have been fewer HIV-positive organ donations than expected. Organ procurement organizations (OPOs) play a key role in the transplant system and barriers at OPOs may be partly responsible for the relatively low number of HIV-positive donors. To understand potential OPO barriers, we conducted semi-structured interviews with 20 OPO staff members. Interviews were recorded, transcribed, and analyzed using a conventional content analytic approach with two coders. OPO staff had high levels of knowledge about HOPE. Many had evaluated referrals of HIV-positive donors and approached families for authorization. Barriers to HIV-positive organ recovery identified included obtaining authorization for donation, potentially disclosing HIV status to next-of-kin, and fear of HIV infection among those engaged in organ recovery. Strategies to overcome these barriers include providing continuing education about the specific tasks required to procure organs from HIV-positive donors, implementing targeted interventions to reduce fear of infection, and developing partnerships with HIV advocacy and care organizations. Given the central role OPOs play, HIV-positive donations are unlikely to occur in significant numbers unless these barriers can be overcome.

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.

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.