Faculty Bibliography

BACKGROUND:Air pollution is associated with cardiopulmonary disease and death in the general population. Fine particulate matter (PM2.5) is particularly harmful due to its ability to penetrate into areas of gas exchange within the lungs. Persons with advanced lung disease are believed to be particularly susceptible to PM2.5 exposure but few studies have examined the effect of exposure on this population. Here we investigate the association between PM2.5 exposure and adverse waitlist events among lung transplant (LT) candidates. METHODS:US registry data were used to identify LT candidates listed between 1/1/2010-12/31/2016. Annual PM2.5 concentration at year of listing was estimated for each candidate's ZIP Code using NASA's SEDAC Global Annual PM2.5 Grids. We estimated crude and adjusted hazard ratios for adverse waitlist events, defined as death or removal, using Cox proportional hazards regression. RESULTS:Of the 15,075 included candidates, median age at listing was 60, 43.8% were female and 81.7% were non-Hispanic white. Median ZIP Code PM2.5 concentration was 9.06µg/m3. When compared to those living in ZIP Codes with lower PM2.5 exposure (PM2.5 <10.53µg/m3), candidates in ZIP Codes in the highest quartile of PM2.5 exposure (≥10.53µg/m3) had 1.14-fold (95%CI 1.04-1.25) risk of adverse waitlist events. The result remained significant after adjusting for demographics, education, insurance, smoking, lung allocation score, BMI, and blood type (HR=1.17; 95%CI 1.07-1.29). CONCLUSIONS:Elevated ambient PM2.5 concentration was associated with adverse waitlist events among LT candidates. These findings highlight the impact of air pollution on clinical outcomes in this critically ill population.

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.

Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016-July 2019, there were 45 LTs (8 simultaneous liver-kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D-/R+ (10 D- were false-positive). The median follow-up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)-seropositive, 13% HCV-viremic. Weighted 1-year survival was 83.3% versus 100.0% in D+ versus D- groups (p = .04). There were no differences in one-year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p > .05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.

BACKGROUND:Frailty, a phenotype characterized by decreased physiologic reserve and the inability to recover following confrontation with a stressor like hemodialysis, may help identify which patients on incident hemodialysis will experience longer postdialysis recovery times. Recovery time is associated with downstream outcomes, including quality of life and mortality. We characterized postdialysis recovery times among patients new to hemodialysis and quantified the association between frailty and hemodialysis recovery time. METHODS:Among 285 patients on hemodialysis enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) study, frailty was measured using the Fried phenotype. Self-reported recovery time was obtained by telephone interview. We estimated the association of frailty (intermediately frail and frail versus nonfrail) and postdialysis recovery time using adjusted negative binomial regression. RESULTS:Median time between dialysis initiation and study enrollment was 3.4 months (IQR, 2.7-4.9), and that between initiation and recovery time assessment was 11 months (IQR, 9.3-15). Mean age was 55 years, 24% were >65 years, and 73% were Black; 72% of individuals recovered in ≤1 hour, 20% recovered in 1-6 hours, 5% required 6-12 hours to recover, and <5% required >12 hours to recover. Those with intermediate frailty, frailty, and age ≤65 years had 2.56-fold (95% CI, 1.45 to 4.52), 1.72-fold (95% CI, 1.03 to 2.89), and 2.35-fold (95% CI, 1.44 to 3.85) risks, respectively, of longer recovery time independent of demographic characteristics, comorbidity, and dialysis-related factors. CONCLUSIONS:In adults new to hemodialysis, frailty was independently associated with prolonged postdialysis recovery. Future studies should assess the effect of frailty-targeted interventions on recovery time to improve clinical outcomes.

UNLABELLED:Kidney transplantation (KT) is controversial in patients with pretransplant pulmonary hypertension (PtPH). We aimed to quantify post-KT graft and patient survival as well as survival benefit in recipients with PtPH. METHODS/UNASSIGNED:Using UR Renal Data System (2000-2018), we studied 90 819 adult KT recipients. Delayed graft function, death-censored graft failure, and mortality were compared between recipients with and without PtPH using inverse probability weighted logistic and Cox regression. Survival benefit of KT was determined using stochastic matching and stabilized inverse probability treatment Cox regression. RESULTS/UNASSIGNED: < 0.01) compared with those who remained on the waitlist. CONCLUSIONS/UNASSIGNED:Although PtPH is associated with inferior post-KT outcomes, KT is associated with better survival compared with remaining on the waitlist. Therefore, KT is a viable treatment modality for appropriately selected patients with PtPH.

Purpose of Review/UNASSIGNED:To summarize the research on post-operative delirium among patients undergoing solid organ transplantation in efforts to improve recognition, evaluation, and management, as well as highlight areas for future research. Recent Findings/UNASSIGNED:Delirium is a common complication in patients with organ failure before and after undergoing solid organ transplant (range: 4.7-47%). However, it is frequently unrecognized and underdiagnosed-even among those closely monitored after major surgery-given that its manifestation is often variable and inconsistent. Delirium has multifactorial etiologies comprising of a complex mix of predisposing recipient, donor, and transplant factors, as well as intraoperative and perioperative factors. Evidence suggests that delirium risk increases with presence of a greater number of such risk factors, and can lead to adverse outcomes such as increased hospital length of stay, time in the ICU, time on mechanical ventilators, graft dysfunction, graft loss, and mortality. Though no trials have been conducted among transplant populations specifically, delirium has been shown to be preventable among hospitalized older adults generally. Multicomponent, primary prevention strategies designed to target multiple risk factors of delirium, such as cognitive impairment, sleep deprivation, immobility, visual impairment, hearing impairment, and dehydration, have been identified as most effective. Whether these approaches translate to improvements in quality of life and long-term health outcomes among patients with organ failure before and after transplantation is yet to be determined. Summary/UNASSIGNED:Delirium is an important, common, yet potentially preventable complication among patients with organ failure. Future studies are needed to test the efficacy of multicomponent, primary prevention strategies on long-term health outcomes among these vulnerable populations.