Faculty Bibliography

COVID-19 has profoundly affected the American health care system; its effect on the liver transplant (LT) waitlist based on COVID-19 incidence has not been characterized. Using SRTR data, we compared observed LT waitlist registrations, waitlist mortality, deceased donor LTs (DDLT), and living donor LTs (LDLT) 3/15/2020-8/31/2020 to expected values based on historical trends 1/2016-1/2020, stratified by statewide COVID-19 incidence. Overall, from 3/15 to 4/30, new listings were 11% fewer than expected (IRR = _0.84 0.89_0.93 ), LDLTs were 49% fewer (IRR = _0.37 0.51_0.72 ), and DDLTs were 9% fewer (IRR = _0.85 0.91_0.97 ). In May, new listings were 21% fewer (IRR = _0.74 0.79_0.84 ), LDLTs were 42% fewer (IRR = _0.39 0.58_0.85 ) and DDLTs were 13% more (IRR = _1.07 1.15_1.23 ). Centers in states with the highest incidence 3/15-4/30 had 59% more waitlist deaths (IRR = _1.09 1.59_2.32 ) and 34% fewer DDLTs (IRR = _0.50 0.66_0.86 ). By August, waitlist outcomes were occurring at expected rates, except for DDLT (13% more across all incidences). While the early COVID-affected states endured major transplant practice changes, later in the pandemic the newly COVID-affected areas were not impacted to the same extent. These results speak to the adaptability of the transplant community in addressing the pandemic and applying new knowledge to patient care.

HIV-positive donor to HIV-positive recipient (HIV D+/R+) transplantation is permitted in the United States under the HIV Organ Policy Equity Act. To explore safety and the risk attributable to an HIV+ donor, we performed a prospective multicenter pilot study comparing HIV D+/R+ vs HIV-negative donor to HIV+ recipient (HIV D-/R+) kidney transplantation (KT). From 3/2016 to 7/2019 at 14 centers, there were 75 HIV+ KTs: 25 D+ and 50 D- (22 recipients from D- with false positive HIV tests). Median follow-up was 1.7 years. There were no deaths nor differences in 1-year graft survival (91% D+ vs 92% D-, P = .9), 1-year mean estimated glomerular filtration rate (63 mL/min D+ vs 57 mL/min D-, P = .31), HIV breakthrough (4% D+ vs 6% D-, P > .99), infectious hospitalizations (28% vs 26%, P = .85), or opportunistic infections (16% vs 12%, P = .72). One-year rejection was higher for D+ recipients (50% vs 29%, HR: 1.83, 95% CI 0.84-3.95, P = .13) but did not reach statistical significance; rejection was lower with lymphocyte-depleting induction (21% vs 44%, HR: 0.33, 95% CI 0.21-0.87, P = .03). In this multicenter pilot study directly comparing HIV D+/R+ with HIV D-/R+ KT, overall transplant and HIV outcomes were excellent; a trend toward higher rejection with D+ raises concerns that merit further investigation.

Importance:Historically, deceased organ donation was lower among Black compared with White populations, motivating efforts to reduce racial disparities. The overarching effect of these efforts in Black and other racial/ethnic groups remains unclear. Objective:To examine changes in deceased organ donation over time. Design, Setting, and Participants:This population-based cohort study used data from January 1, 1999, through December 31, 2017, from the Scientific Registry of Transplant Recipients to quantify the number of actual deceased organ donors, and from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Detailed Mortality File to quantify the number of potential donors (individuals who died under conditions consistent with organ donation). Data were analyzed from December 2, 2019, to May 14, 2020. Exposures:Race and ethnicity of deceased and potential donors. Main Outcomes and Measures:For each racial/ethnic group and year, a donation ratio was calculated as the number of actual deceased donors divided by the number of potential donors. Direct age and sex standardization was used to allow for group comparisons, and Poisson regression was used to quantify changes in donation ratio over time. Results:A total of 141 534 deceased donors and 5 268 200 potential donors were included in the analysis. Among Black individuals, the donation ratio increased 2.58-fold from 1999 to 2017 (yearly change in adjusted incidence rate ratio [aIRR], 1.05; 95% CI, 1.05-1.05; P < .001). This increase was significantly greater than the 1.60-fold increase seen in White individuals. Nevertheless, substantial racial differences remained, with Black individuals still donating at only 69% the rate of White individuals in 2017 (P < .001). Among other racial minority populations, changes were less drastic. Deceased organ donation increased 1.80-fold among American Indian/Alaska Native and 1.40-fold among Asian or Pacific Islander populations, with substantial racial differences remaining in 2017 (American Indian/Alaska Native population donation at 28% and Asian/Pacific Islander population donation at 85% the rate of the White population). Deceased organ donation differences between Hispanic/Latino and non-Hispanic/Latino populations increased over time (4% lower in 2017). Conclusions and Relevance:The findings of this cohort study suggest that differences in deceased organ donation between White and some racial minority populations have attenuated over time. The greatest gains were observed among Black individuals, who have been the primary targets of study and intervention. Despite improvements, substantial differences remain, suggesting that novel approaches are needed to understand and address relatively lower rates of deceased organ donation among all racial minorities.

BACKGROUND:The aim of this study is to describe the economic trends in adults who underwent elective thyroidectomy. METHODS:We performed a population-based study utilizing the Premier Healthcare Database to examine adult patients who underwent elective thyroidectomy between January 2006 and December 2014. Time was divided into three equal time periods (2006-2008, 2009-2011, and 2012-2014). To examine trend in patient charges, we modeled patient charges using generalized linear regressions adjusting for key covariates with standard errors clustered at the hospital level. RESULTS:Our study cohort consisted of 52,012 adult patients who underwent a thyroid operation. During the study period, the most common procedure changed from a thyroid lobectomy to bilateral thyroidectomy. Over the study period, there was an increase in the proportion of completion thyroidectomies from 1.1% to 1.6% (P < 0.001), malignant diagnoses from 21.7% to 26.8% (P < 0.001), procedures performed at teaching hospitals from 27.7% to 32.9% (P < 0.001), and procedures performed on an outpatient basis from 93.85% to 97.55% (P < 0.001). The annual increase in median patient charge adjusted for inflation was $895 or 4.3% resulting in an increase of 38.8% over 9 y. Higher thyroidectomy charges were associated with male patients, malignant surgical pathology, patients undergoing limited or radical neck dissection, experiencing complications, those with managed health care insurance, and a prolonged length of stay. CONCLUSIONS:Despite recent changes in thyroid surgery practices to decrease the economic burden of hospitals, costs continue to rise 4.3% annually. Additional prospective studies are needed to identify factors associated with this increasing cost.

Desensitization has enabled incompatible living donor kidney transplantation (ILDKT) across HLA/ABO barriers, but added immunomodulation might put patients at increased risk of infections. We studied 475 recipients from our center from 2010 to 2015, categorized by desensitization intensity: none/compatible (n = 260), low (0-4 plasmaphereses, n = 47), moderate (5-9, n = 74), and high (≥10, n = 94). The 1-year cumulative incidence of infection was 50.1%, 49.8%, 66.0%, and 73.5% for recipients who received none, low, moderate, and high-intensity desensitization (P < .001). The most common infections were UTI (33.5% of ILDKT vs. 21.5% compatible), opportunistic (21.9% vs. 10.8%), and bloodstream (19.1% vs. 5.4%) (P < .001). In weighted models, a trend toward increased risk was seen in low (wIRR = _0.77 1.40_2.56 ,P = .3) and moderately (wIRR = _0.88 1.35_2.06 ,P = .2) desensitized recipients, with a statistically significant 2.22-fold (wIRR = _1.33 2.22_3.72 ,P = .002) increased risk in highly desensitized recipients. Recipients with ≥4 infections were at higher risk of prolonged hospitalization (wIRR = _2.62 3.57_4.88 , P < .001) and death-censored graft loss (wHR = _1.15 4.01_13.95 ,P = .03). Post-KT infections are more common in desensitized ILDKT recipients. A subset of highly desensitized patients is at ultra-high risk for infections. Strategies should be designed to protect patients from the morbidity of recurrent infections, and to extend the survival benefit of ILDKT across the spectrum of recipients.

Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR = _1.03 1.68_2.72 ). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction > .1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF = _1.45 2.09_3.02 ; PFNC = _1.67 2.40_3.46 ; PCC = _1.48 2.24_3.37 ). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction = .1), its impact on DCGF risk was less consequential for ILDKT (aHR = _1.34 1.62_1.95 ) than CLDKT (aHR = _1.96 2.29_2.67 ) (p interaction = .004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.

Background/UNASSIGNED:Despite the revolutionary role of direct-acting antivirals for hepatitis C virus (HCV), the treatment timing for liver transplant candidates remains controversial. We hypothesize that deferring treatment until after liver transplantation improves access to a larger and higher-quality donor pool without a detrimental impact on post-liver transplantation outcomes. Methods/UNASSIGNED:This single-center study includes recipients that underwent deceased-donor liver transplant with HCV as the primary indication January 1, 2014, to December 31, 2018. For recipients that were untreated (n = 87) versus treated (n = 42) pre-LT, we compared post-LT mortality using Cox regression with inverse probability of treatment-weighted data. Results/UNASSIGNED: = 0.06). Conclusions/UNASSIGNED:Deferring HCV treatment improves access to higher-quality donors and may improve post-LT survival.

With a later onset of diabetes complications and thus increasing age of transplant candidates, many centers have extended upper age limits for pancreas transplantation. This study investigates the effect of recipient and donor age on outcomes after pancreas transplantation.We retrospectively analyzed 565 pancreas transplants performed at two Eurotransplant centers. The cohort was split at a recipient and donor age of 50 and 40 years, respectively. Median recipient age in old patients (≥50 years; 27.2%) was 54 years and 40 years in young patients (<50 years). Compared to young recipients, old recipients had an inferior patient survival rate (≥50: 5yr, 82.8%; 10yr, 65.6%; <50: 5yr, 93.3%; 10yr, 82.0%; P < 0.0001). Old recipients demonstrated comparable death-censored pancreas (≥50: 1yr, 80.6%; 5yr, 70.2%; <50: 1yr, 87.3%; 5yr, 77.8%; P = 0.35) and kidney graft survival (≥50: 1yr, 97.4%; 5yr, 90.6%; <50: 1yr, 97.8%; 5yr, 90.2%; P = 0.53) compared to young recipients. Besides a lower rate of kidney rejection, similar relative risks for postoperative complications were detected in old and young patients. This study shows that despite an increased mortality in old recipients, excellent graft survival can be achieved similar to that of young patients. Age alone should not exclude patients from receiving a pancreas transplant.

BACKGROUND:Transplantation of HIV-positive (HIV+) donor organs for HIV+ recipients (HIV D+/R+) is now being performed as research in the United States, but raises ethical concerns. While patient-reported outcome measures are increasingly used to evaluate clinical interventions, there is no published measure to aptly capture patients' experiences in the unique context of experimental HIV D+/R+ transplantation. Therefore, we developed PROMETHEUS (patient-reported measure of experimental transplants with HIV and ethics in the United States). To do so, we created a conceptual framework, drafted a pilot battery using existing and new measures related to this context, and refined it based on cognitive and pilot testing. PROMETHEUS was administered 6-months post-transplant in a clinical trial evaluating these transplants. We analyzed data from the first 20 patient-participants for reliability and validity by calculating Cronbach's alpha and reviewing item performance characteristics. RESULTS:PROMETHEUS 1.0 consisted of 29 items with 5 putative subscales: Emotions; Trust; Decision Making; Transplant; and Decision Satisfaction. Overall, responses were positive. Cronbach's alpha was > 0.8 for all subscales except Transplant, which was 0.38. Two Transplant subscale items were removed due to poor reliability and construct validity. CONCLUSIONS:We developed PROMETHEUS to systematically capture patient-reported experiences with this novel experimental transplantation program, nested it in an actual clinical trial, and obtained preliminary data regarding its performance.

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.