Faculty Bibliography

Genetically modified xenografts are one of the most promising solutions to the discrepancy between the numbers of available human organs for transplantation and potential recipients. To date, a porcine heart has been implanted into only one human recipient. Here, using 10-gene-edited pigs, we transplanted porcine hearts into two brain-dead human recipients and monitored xenograft function, hemodynamics and systemic responses over the course of 66 hours. Although both xenografts demonstrated excellent cardiac function immediately after transplantation and continued to function for the duration of the study, cardiac function declined postoperatively in one case, attributed to a size mismatch between the donor pig and the recipient. For both hearts, we confirmed transgene expression and found no evidence of cellular or antibody-mediated rejection, as assessed using histology, flow cytometry and a cytotoxic crossmatch assay. Moreover, we found no evidence of zoonotic transmission from the donor pigs to the human recipients. While substantial additional work will be needed to advance this technology to human trials, these results indicate that pig-to-human heart xenotransplantation can be performed successfully without hyperacute rejection or zoonosis.

BACKGROUND/UNASSIGNED:Living kidney donation is possible for people living with HIV (PLWH) in the United States within research studies under the HIV Organ Policy Equity (HOPE) Act. There are concerns that donor nephrectomy may have an increased risk of end-stage renal disease (ESRD) in PLWH due to HIV-associated kidney disease and antiretroviral therapy (ART) nephrotoxicity. Here we report the first 3 cases of living kidney donors with HIV under the HOPE Act in the United States. METHODS/UNASSIGNED:Within the HOPE in Action Multicenter Consortium, we conducted a prospective study of living kidney donors with HIV. Pre-donation, we estimated the 9-year cumulative incidence of ESRD, performed genetic testing of apolipoprotein L1 (APOL1), excluding individuals with high-risk variants, and performed pre-donation kidney biopsies (HOPE Act requirement). The primary endpoint was ≥grade 3 nephrectomy-related adverse events (AEs) in year one. Post-donation, we monitored glomerular filtration rate (measured by iohexol/Tc-99m DTPA [mGFR] or estimated with serum creatinine [eGFR]), HIV RNA, CD4 count, and ART. FINDINGS/UNASSIGNED: at two years (eGFR) in donor 3. HIV RNA remained <20 copies/mL and CD4 count remained stable in all donors. INTERPRETATION/UNASSIGNED:The first three living kidney donors with HIV under the HOPE Act in the United States have had promising outcomes at two-four years, providing proof-of-concept to support living donation from PLWH to recipients with HIV. FUNDING/UNASSIGNED:National Institute of Allergy and Infectious Diseases, National Institutes of Health.

IntroductionOlder adults with IBD are at higher risk for postoperative complications as compared to their younger counterparts, however factors contributing to this are unknown. We assessed risk factors associated with adverse IBD-related surgical outcomes, evaluated trends in emergency surgery, and explored differential risks by age.MethodsUsing the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, we identified adults ≥18 years of age who underwent an IBD-related intestinal resection from 2005-2019. Our primary outcome included a 30-day composite of mortality, readmission, reoperation, and/or major postoperative complication.ResultsOverall, 49,746 intestinal resections were performed with 9,390 (18.8%) occurring among older adults with IBD. Nearly 37% of older adults experienced an adverse outcome as compared to 28.1% among younger adults with IBD (p<0.01). Among all adults with IBD, the presence of preoperative sepsis (aOR, 2.08; 95%CI 1.94-2.24), malnutrition (aOR, 1.22; 95%CI 1.14-1.31), dependent functional status (aOR, 6.92; 95%CI 4.36-11.57), and requiring emergency surgery (aOR, 1.50; 95%CI 1.38-1.64) increased the odds of an adverse postoperative outcome, with similar results observed when stratifying by age. Further, 8.8% of surgeries among older adults were emergent, with no change observed over time (p=0.16).DiscussionPreoperative factors contributing to the risk of an adverse surgical outcome are similar between younger and older individuals with IBD, and include elements such as malnutrition and functional status. Incorporating these measures into surgical decision-making can reduce surgical delays in older individuals at low-risk and help target interventions in those at high risk, transforming care for thousands of older adults with IBD.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Older adults initiating dialysis have a high risk of mortality and that risk may be related to potentially inappropriate medications (PIMs). Our objective was to identify and validate mortality risk associated with American Geriatrics Society Beers Criteria PIM classes and concomitant PIM use. METHODS:We used US Renal Data System data to establish a cohort of adults aged ≥ 65 years initiating dialysis (2013-2014) and had no PIM prescriptions in the 6 months prior to dialysis initiation. In a development cohort (40% sample), adjusted Cox proportional hazards models were performed to determine which of 30 PIM classes were associated with mortality (or "high-risk" PIMs). Adjusted Cox models were performed to assess the association of the number of "high-risk" PIM fills/month with mortality. All models were repeated in the validation cohort (60% sample). RESULTS:In the development cohort (n = 15,570), only 13 of 30 PIM classes were associated with a higher mortality risk. Compared with those with no "high-risk" PIM fills/month, patients having one "high-risk" PIM fill/month had a 1.29-fold (95% confidence interval 1.21-1.38) increased risk of death; those with two or more "high-risk" PIM fills/month had a 1.40-fold (95% confidence interval 1.24-1.58) increased risk. These findings were similar in the validation cohort (n = 23,569). CONCLUSIONS:Only a minority of Beers Criteria PIM classes may be associated with mortality in the older dialysis population; however, mortality risk increases with concomitant use of "high-risk" PIMs. Additional studies are needed to confirm these associations and their underlying mechanisms.

SIGNIFICANCE STATEMENT:Cardiovascular diseases account for 32% of deaths among kidney transplant recipients. Statin therapy is common in this population. However, its effect on mortality prevention remains unclear among kidney transplant recipients, whose clinical risk profile might be unique because of concomitant immunosuppressive therapy. In this national study of 58,264 single-kidney transplant recipients, statin use was associated with a 5% decrease in mortality. More importantly, this protective association was stronger among those who used a mammalian target of rapamycin (mTOR) inhibitor for immunosuppression (27% decrease in mTOR inhibitor users versus 5% in nonusers). Our results suggest that statin therapy may reduce mortality in kidney transplant recipients and that the strength of this protective association may vary by immunosuppression regimen. BACKGROUND:Cardiovascular diseases are the leading cause of mortality in kidney transplant (KT) recipients, accounting for 32% of deaths. Statins are widely used in KT recipients, but effectiveness for preventing mortality remains unclear in this population, especially because of interaction between statins and immunosuppressive agents. We analyzed a national cohort to assess the real-world effectiveness of statins for reducing all-cause mortality in KT recipients. METHODS:We studied statin use and mortality among 58,264 adults (18 years or older) who received single kidneys between 2006 and 2016 and had Medicare part A/B/D. Statin use was ascertained from Medicare prescription drug claims and deaths from Center for Medicare and Medicaid Services records. We estimated the association of statin use with mortality using multivariable Cox models, with statin use as a time-varying exposure and immunosuppression regimen as effect modifiers. RESULTS:Statin use increased from 45.5% at KT to 58.2% at 1-year post-KT to 70.9% at 5-year post-KT. We observed 9785 deaths over 236,944 person-years. Overall, statin use was significantly associated with lower mortality (adjusted hazard ratio [aHR], 0.95; 95% confidence interval [CI], 0.90 to 0.99). The strength of this protective association varied by calcineurin inhibitor use (among tacrolimus users, aHR, 0.97; 95% CI, 0.92 to 1.03 versus among calcineurin nonusers, aHR, 0.72; 95% CI, 0.60 to 0.87; interaction P =0.002), mammalian target of rapamycin (mTOR) inhibitor use (among mTOR inhibitor users, aHR, 0.73; 95% CI, 0.57 to 0.92 versus among nonusers, aHR, 0.95; 95% CI, 0.91 to 1.00; interaction P =0.03), and mycophenolate use (among mycophenolate users, aHR, 0.96; 95% CI, 0.91 to 1.02 versus among nonusers, aHR, 0.76; 95% CI, 0.64 to 0.89; interaction P =0.002). CONCLUSION:Real-world evidence supports statin therapy for reducing all-cause mortality in KT recipients. Effectiveness might be greater when combined with mTOR inhibitor-based immunosuppression.

BACKGROUND/UNASSIGNED:The COVID-19 pandemic led to the urgent implementation of telehealth visits in inflammatory bowel disease (IBD) care; however, data assessing feasibility remain limited. OBJECTIVES/UNASSIGNED:We looked to determine the completion rate of telehealth appointments for adults with IBD, as well as to evaluate demographic, clinical, and social predictors of incomplete appointments. DESIGN/UNASSIGNED:We conducted a retrospective analysis of all patients with IBD who had at least one scheduled telehealth visit at the NYU IBD Center between 1 March 2020 and 31 August 2021, with only the first scheduled telehealth appointment considered. METHODS/UNASSIGNED:Medical records were parsed for relevant covariables, and multivariable logistic regression was used to estimate the adjusted association between demographic factors and an incomplete telehealth appointment. RESULTS/UNASSIGNED: = 0.22). After adjustment, patients with CD had higher odds of an incomplete appointment as compared to patients with UC [adjusted odds ratio (adjOR): 1.37, 95% confidence interval (CI): 1.10-1.69], as did females (adjOR: 1.26, 95% CI: 1.04-1.54), and patients who had a non-first-degree relative listed as an emergency contact (adjOR: 1.69, 95% CI: 1.16-2.44). While age ⩾60 years was not associated with appointment completion status, we did find that age >80 years was an independent predictor of missed telehealth appointments (adjOR: 2.92, 95% CI: 1.12-7.63) when compared to individuals aged 60-70 years. CONCLUSION/UNASSIGNED:telehealth, particularly those aged 60-80 years, may therefore provide an additional venue to complement in-person care.