Faculty Bibliography

OBJECTIVES:The COVID-19 pandemic significantly affected the provisions of health services to necessary but deprioritised fields, such as transplantation. Many programmes had to ramp-down their activity, which may significantly affect transplant volumes. We aimed to pragmatically analyse measures of transplant activity and compare them by a country's income level and cumulative COVID-19 incidence (CCI). DESIGN, SETTING AND PARTICIPANTS:From June to September 2020, we surveyed transplant physicians identified as key informants in their programmes. Of the 1267 eligible physicians, 40.5% from 71 countries participated. OUTCOME:Four pragmatic measures of transplant activity. RESULTS:Overall, 46.5% of the programmes from high-income countries anticipate being able to maintain >75% of their transplant volume compared with 31.6% of the programmes from upper-middle-income countries, and with 21.7% from low/lower-middle-income countries (p<0.001). This could be because more programmes in high-income countries reported being able to perform transplantation/s (86.8%%-58.5%-67.9%, p<0.001), maintain prepandemic deceased donor offers (31.0%%-14.2%-26.4%, p<0.01) and avoid a ramp down phase (30.9%%-19.7%-8.3%, p<0.001), respectively. In a multivariable analysis that adjusted for CCI, programmes in upper-middle-income countries (adjusted OR, aOR=0.47, 95% CI 0.27 to 0.81) and low/lower-middle-income countries (aOR 0.33, 95% CI 0.16 to 0.67) had lower odds of being able to maintain >75% of their transplant volume, compared with programmes in high-income countries. Again, this could be attributed to lower-income being associated with 3.3-3.9 higher odds of performing no transplantation/s, 66%-68% lower odds of maintaining prepandemic donor offers and 37%-76% lower odds of avoiding ramp-down of transplantation. Overall, CCI was not associated with these measures. CONCLUSIONS:The impact of the pandemic on transplantation was more in lower-income countries, independent of the COVID-19 burden. Given the lag of 1-2 years in objective data being reported by global registries, our findings may inform practice and policy. Transplant programmes in lower-income countries may need more effort to rebuild disrupted services and recuperate from the pandemic even if their COVID-19 burden was low.

BACKGROUND:Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) occurs in critically ill patients with COVID-19. Risks and outcomes remain poorly understood. METHODS:A retrospective cohort study of mechanically ventilated adult patients with COVID-19 admitted to 5 Johns Hopkins hospitals was conducted between March and August 2020. CAPA was defined using composite clinical criteria. Fine and Gray competing risks regression was used to analyze clinical outcomes and, multilevel mixed-effects ordinal logistic regression was used to compare longitudinal disease severity scores. RESULTS:In the cohort of 396 people, 39 met criteria for CAPA. Patients with CAPA were more likely than those without CAPA to have underlying pulmonary vascular disease (41% vs 21.6%, respectively; P = .01), liver disease (35.9% vs 18.2%; P = .02), coagulopathy (51.3% vs 33.1%; P = .03), solid tumors (25.6% vs 10.9%; P = .02), multiple myeloma (5.1% vs 0.3%; P = .03), and corticosteroid exposure during the index admission (66.7% vs 42.6%; P = .005), and had lower body mass indexes (median, 26.6 vs 29.9 [calculated as weight in kilograms divided by height in meters squared]; P = .04). Patients with CAPA had worse outcomes, as measured by ordinal severity of disease scores, requiring longer time to improvement (adjusted odds ratio, 1.081.091.1; P < .001), and advancing in severity almost twice as quickly (subhazard ratio, 1.31.82.5; P < .001). They were intubated twice as long as those without CAPA (subhazard ratio, 0.40.50.6; P < .001) and had longer hospital stays (median [interquartile range], 41.1 [20.5-72.4) vs 18.5 [10.7-31.8] days; P < .001). CONCLUSION:CAPA is associated with poor outcomes. Attention to preventive measures (screening and/or prophylaxis) is warranted in people with high risk of CAPA.

Status 1A liver transplant candidates are given the highest medical priority for the allocation of deceased donor livers. Organ Procurement and Transplantation Network (OPTN) policy requires physicians to certify that a candidate has a life expectancy without a transplant of less than 7 days for that candidate to be given status 1A. Additionally, candidates receiving status 1A must have one of six medical conditions listed in policy. Using Scientific Registry of Transplant Recipients data from all prevalent liver transplant candidates from 2010 to 2020, we used a bias-corrected Kaplan-Meier model to calculate the survival of status 1A candidates and to determine their life expectancy without a transplant. We found that status 1A candidates have a life expectancy without a transplant of 24 (95% CI 20-46) days-over three times longer than what policy requires for status 1A designation. We repeated the analysis for subgroups of status 1A candidates based on the medical conditions that grant status 1A. We found that none of these subgroups met the life expectancy requirement. Harmonizing OPTN policy with observed data would sustain the integrity of the allocation process.

Background/UNASSIGNED:Few reports have focused on newer coronavirus disease 2019 (COVID-19) therapies (remdesivir, dexamethasone, and convalescent plasma) in solid organ transplant recipients; concerns had been raised regarding possible adverse impact on allograft function or secondary infections. Methods/UNASSIGNED:We studied 77 solid organ transplant inpatients with COVID-19 during 2 therapeutic eras (Era 1: March-May 2020, 21 patients; and Era 2: June-November 2020, 56 patients) and 52 solid organ transplant outpatients. Results/UNASSIGNED:In Era 1, no patients received remdesivir or dexamethasone, and 4 of 21 (19.4%) received convalescent plasma, whereas in Era 2, remdesivir (24/56, 42.9%), dexamethasone (24/56, 42.9%), and convalescent plasma (40/56, 71.4%) were commonly used. Mortality was low across both eras, 4 of 77 (5.6%), and rejection occurred in only 2 of 77 (2.8%) inpatients; infections were similar in hypoxemic patients with or without dexamethasone. Preexisting graft dysfunction was associated with greater need for hospitalization, higher severity score, and lower survival. Acute kidney injury was present in 37.3% of inpatients; renal function improved more rapidly in patients who received remdesivir and convalescent plasma. Post-COVID-19 renal and liver function were comparable between eras, out to 90 d. Conclusions/UNASSIGNED:Newer COVID-19 therapies did not appear to have a deleterious effect on allograft function, and infectious complications were comparable.

Rationale & Objective/UNASSIGNED:Posttransplant diabetes mellitus (DM) after kidney transplantation increases morbidity and mortality, particularly in older and obese recipients. We aimed to examine the impact of immunosuppression selection on the risk of posttransplant DM among both older and obese kidney transplant recipients. Study Design/UNASSIGNED:Retrospective database study. Setting & Participants/UNASSIGNED:Kidney-only transplant recipients aged ≥18 years from 2005 to 2016 in the United States from US Renal Data System records, which integrate Organ Procurement and Transplantation Network/United Network for Organ Sharing records with Medicare billing claims. Exposures/UNASSIGNED:Various immunosuppression regimens in the first 3 months after transplant. Outcomes/UNASSIGNED:Development of DM >3 months-to-1 year posttransplant. Analytical Approach/UNASSIGNED:We used multivariable Cox regression to compare the incidence of posttransplant DM by immunosuppression regimen with the reference regimen of thymoglobulin (TMG) or alemtuzumab (ALEM) with tacrolimus + mycophenolic acid + prednisone using inverse propensity weighting. Results/UNASSIGNED:(aHR, 0.63; 95% CI, 0.46-0.87). Limitations/UNASSIGNED:Retrospective study and lacked data on immunosuppression levels. Conclusions/UNASSIGNED:The beneficial impact of steroid avoidance using tacrolimus on posttransplant DM appears to differ by patient age and induction regimen.

Increasing numbers of compatible pairs are choosing to enter paired exchange programs, but motivations, outcomes, and system-level effects of participation are not well described. Using a linkage of the Scientific Registry of Transplant Recipients and National Kidney Registry, we compared outcomes of traditional (originally incompatible) recipients to originally compatible recipients using the Kaplan-Meier method. We identified 154 compatible pairs. Most pairs sought to improve HLA matching. Compared to the original donor, actual donors were younger (39 vs. 50 years, p < .001), less often female (52% vs. 68%, p < .01), higher BMI (27 vs. 25 kg/m², p = .03), less frequently blood type O (36% vs. 80%, p < .001), and had higher eGFR (99 vs. 94 ml/min/1.73 m², p = .02), with a better LKDPI (median 7 vs. 22, p < .001). We observed no differences in graft failure or mortality. Compatible pairs made 280 additional transplants possible, many in highly sensitized recipients with long wait times. Compatible pair recipients derived several benefits from paired exchange, including better donor quality. Living donor pairs should receive counseling regarding all options available, including kidney paired donation. As more compatible pairs choose to enter exchange programs, consideration should be given to optimizing compatible pair and hard-to-transplant recipient outcomes.

BACKGROUND:The association between exposure to air pollution and papillary thyroid carcinoma is unknown. We sought to estimate the relationship between long-term exposure to the fine (diameter ≤ 2.5 μm) particulate matter component of air pollution and the risk of papillary thyroid cancer. METHODS:Adult (age ≥18) patients with newly diagnosed papillary thyroid carcinoma between January 1, 2013 and December 31, 2016 across a single health system were identified using electronic medical records. Data from 1,990 patients with papillary thyroid carcinoma were compared with 3,980 age- and sex-matched control subjects without any evidence of thyroid disease. Cumulative fine (diameter <2.5 μm) particulate matter exposure was estimated by incorporating patients' residential zip codes into a deep learning neural networks model, which uses both meteorological and satellite-based measurements. Conditional logistic regression was performed to assess for association between papillary thyroid carcinoma and increasing fine (diameter ≤2.5 μm) particulate matter concentrations over 1, 2, and 3 years of cumulative exposure preceding papillary thyroid carcinoma diagnosis. RESULTS:n = 0.04). Among current smokers (n = 623), the risk of developing papillary thyroid carcinoma was highest (adjusted odds ratio = 1.35, 95% confidence interval: 1.12-1.63). CONCLUSION/CONCLUSIONS:Increasing concentration of fine (diameter ≤2.5 μm) particulate matter in air pollution is significantly associated with the incidence of papillary thyroid carcinoma with 2 and 3 years of exposure. Our novel findings provide additional insight into the potential associations between risk factors and papillary thyroid carcinoma and warrant further investigation, specifically in areas with high levels of air pollution both nationally and internationally.

Physical frailty and impaired cognition are common in patients with cirrhosis. Physical frailty can be assessed using performance-based tests, but the extent to which impaired cognition may impact performance is not well characterized. We assessed the relationship between impaired cognition and physical frailty in patients with cirrhosis. We enrolled 1,623 ambulatory adult patients with cirrhosis waiting for liver transplantation at 10 sites. Frailty was assessed with the liver frailty index (LFI; "frail," LFI ≥ 4.4). Cognition was assessed at the same visit with the number connection test (NCT); continuous "impaired cognition" was examined in primary analysis, with longer NCT (more seconds) indicating worse impaired cognition. For descriptive statistics, "impaired cognition" was NCT ≥ 45 seconds. Linear regression associated frailty and impaired cognition; competing risk regression estimated subhazard ratios (sHRs) of wait-list mortality (i.e., death/delisting for sickness). Median NCT was 41 seconds, and 42% had impaired cognition. Median LFI (4.2 vs. 3.8) and rates of frailty (38% vs. 20%) differed between those with and without impaired cognition. In adjusted analysis, every 10-second NCT increase associated with a 0.08-LFI increase (95% confidence interval [CI], 0.07-0.10). In univariable analysis, both frailty (sHR, 1.63; 95% CI, 1.43-1.87) and impaired cognition (sHR, 1.07; 95% CI, 1.04-1.10) associated with wait-list mortality. After adjustment, frailty but not impaired cognition remained significantly associated with wait-list mortality (sHR, 1.55; 95% CI, 1.33-1.79). Impaired cognition mediated 7.4% (95% CI, 2.0%-16.4%) of the total effect of frailty on 1-year wait-list mortality. Conclusion: Patients with cirrhosis with higher impaired cognition displayed higher rates of physical frailty, yet frailty independently associated with wait-list mortality while impaired cognition did not. Our data provide evidence for using the LFI to understand mortality risk in patients with cirrhosis, even when concurrent impaired cognition varies.