Association of Race and Ethnicity With High Longevity Deceased Donor Kidney Transplantation Under the US Kidney Allocation System.

RATIONALE & OBJECTIVE: The US Kidney Allocation System (KAS) prioritizes candidates with ≤20% Estimated Post-Transplant Survival (EPTS) for high longevity kidneys defined by a ≤20% Kidney Donor Profile Index (KDPI). Use of EPTS in the KAS deprioritizes candidates with older age, diabetes, and longer dialysis durations. We assessed whether this use also disadvantages racial-ethnic minority candidates, who are younger but more likely to have diabetes and longer durations of kidney failure requiring dialysis. STUDY DESIGN: Observational cohort study. SETTING: & Participants: Adult candidates for and recipients of kidney transplantation represented in the Scientific Registry of Transplant Recipients from January 2015 through December 2020. EXPOSURE: Race and ethnicity. OUTCOMES: Age-adjusted assignment to ≤20% EPTS, transplantation of a ≤20% KDPI kidney, and post-transplant survival in longevity matched recipients by racial-ethnicity. ANALYTIC APPROACH: Multivariable logistic regression, Fine-Gray competing risks survival analysis, and Kaplan-Meier and Cox Proportional Hazards methods. RESULTS: The cohort included 199,444 candidates (7% Asian, 29% Black, 19% Hispanic/Latino, 43% White) listed for deceased donor kidney transplantation. Non-White candidates had significantly higher rates of diabetes, longer dialysis duration, and were younger than White candidates. Adjusted for age, Asian, Black, and Hispanic/Latino candidates had significantly lower odds of having a ETPS score ≤20% (OR 0.86, [0.81, 0.91], 0.52 [0.50, 0.54], and 0.49, [0.47, 0.51]), and were less likely to receive a ≤20% KDPI kidney (subHR 0.70 [0.66, 0.75], 0.89 [0.87, 0.92], and 0.73 [0.71, 0.76]), compared to White candidates. Among recipients with ≤20% EPTS scores transplanted with a ≤20% KDPI deceased donor kidney, Asian and Hispanic recipients had lower post-transplant mortality (HR 0.45 [0.27, 0.77], and 0.63 [0.47, 0.86]) and Black recipients had higher but not statistically significant post-transplant mortality (HR 1.22 [0.99, 1.52]) compared to White recipients. LIMITATIONS: Provider reported race-ethnicity data and 5-year post transplant follow-up period. CONCLUSIONS: The US kidney allocation system is less likely to identify racial-ethnic minority candidates as having a ≤20% EPTS score which triggers allocation of high longevity deceased donor kidneys. These findings should inform the OPTN about how to remedy racial/ethnic disparities introduced through KAS's current approach of allocating allografts with longer predicted longevity to recipients with longer estimated post-transplant survival.

Post-transplant survival after normothermic regional perfusion versus direct procurement and perfusion in donation after circulatory determination of death in heart transplantation.

BACKGROUND: Since 2019, the annual transplantation rate of hearts donated following circulatory death (DCD) has increased significantly in the United States. The 2 major heart procurement techniques following circulatory death are direct procurement and perfusion (DPP) and normothermic regional perfusion (NRP). Post-transplant survival for heart recipients has not been compared between these 2 techniques. METHODS: This observational study uses data on adult heart transplants from donors after circulatory death from January 1, 2019 to December 31, 2021 in the Scientific Registry of Transplant Recipients. We identified comparable transplant cases across procurement types using propensity-score matching and measured the association between procurement technique and 1-year post-transplant survival using Kaplan-Meier and Cox proportional hazards model stratefied by matching pairs. RESULTS: Among 318 DCD heart transplants, 216 (68%) were procured via DPP, and 102 (32%) via NRP. Among 22 transplant centers that accepted circulatory-death donors, 3 used NRP exclusively, and 5 used both procurement techniques. After propensity-score matching on recipient and donor factors, there was no significant difference in 1-year post-transplant survival (93.1% for NRP vs 91.1% for DPP, p = 0.79) between procurement techniques. CONCLUSIONS: NRP and DPP procurements are associated with similar 1-year post-transplant survival. If NRP is ethically permissible and improves outcomes for abdominal organs, it should be the preferred procurement technique for DCD hearts.

Development and Validation of a Risk Score Predicting Death Without Transplant in Adult Heart Transplant Candidates.

Importance: The US heart allocation system prioritizes medically urgent candidates with a high risk of dying without transplant. The current therapy-based 6-status system is susceptible to manipulation and has limited rank ordering ability. Objective: To develop and validate a candidate risk score that incorporates current clinical, laboratory, and hemodynamic data. Design, Setting, and Participants: A registry-based observational study of adult heart transplant candidates (aged ≥18 years) from the US heart allocation system listed between January 1, 2019, and December 31, 2022, split by center into training (70%) and test (30%) datasets. Adult candidates were listed between January 1, 2019, and December 31, 2022. Main Outcomes and Measures: A US candidate risk score (US-CRS) model was developed by adding a predefined set of predictors to the current French Candidate Risk Score (French-CRS) model. Sensitivity analyses were performed, which included intra-aortic balloon pumps (IABP) and percutaneous ventricular assist devices (VAD) in the definition of short-term mechanical circulatory support (MCS) for the US-CRS. Performance of the US-CRS model, French-CRS model, and 6-status model in the test dataset was evaluated by time-dependent area under the receiver operating characteristic curve (AUC) for death without transplant within 6 weeks and overall survival concordance (c-index) with integrated AUC. Results: A total of 16 905 adult heart transplant candidates were listed (mean [SD] age, 53 [13] years; 73% male; 58% White); 796 patients (4.7%) died without a transplant. The final US-CRS contained time-varying short-term MCS (ventricular assist-extracorporeal membrane oxygenation or temporary surgical VAD), the log of bilirubin, estimated glomerular filtration rate, the log of B-type natriuretic peptide, albumin, sodium, and durable left ventricular assist device. In the test dataset, the AUC for death within 6 weeks of listing for the US-CRS model was 0.79 (95% CI, 0.75-0.83), for the French-CRS model was 0.72 (95% CI, 0.67-0.76), and 6-status model was 0.68 (95% CI, 0.62-0.73). Overall c-index for the US-CRS model was 0.76 (95% CI, 0.73-0.80), for the French-CRS model was 0.69 (95% CI, 0.65-0.73), and 6-status model was 0.67 (95% CI, 0.63-0.71). Classifying IABP and percutaneous VAD as short-term MCS reduced the effect size by 54%. Conclusions and Relevance: In this registry-based study of US heart transplant candidates, a continuous multivariable allocation score outperformed the 6-status system in rank ordering heart transplant candidates by medical urgency and may be useful for the medical urgency component of heart allocation.

The Accuracy of Initial U.S. Heart Transplant Candidate Rankings.

BACKGROUND: The U.S. heart allocation system ranks candidates with only 6 treatment-based categorical "statuses" and ignores many objective patient characteristics. OBJECTIVES: This study sought to determine the effectiveness of the standard 6-status ranking system and several novel prediction models in identifying the most urgent heart transplant candidates. METHODS: The primary outcome was death before receipt of a heart transplant. The accuracy of the 6-status system was evaluated using Harrell's C-index and log-rank tests of Kaplan-Meier estimated survival by status for candidates listed postpolicy (November 2018 to March 2020) in the Scientific Registry of Transplant Recipients data set. The authors then developed Cox proportional hazards models and random survival forest models using prepolicy data (2010-2017). The predictor variables included age, diagnosis, laboratory measurements, hemodynamics, and supportive treatment at the time of listing. The performance of these models was compared with the candidate's 6-status ranking in the postpolicy data. RESULTS: Since policy implementation, the 6-status ranking at listing has had moderate ability to rank-order candidates (C-index: 0.67). Statuses 4 and 6 had no significant difference in survival (P = 0.80), and status 5 had lower survival than status 4 (P < 0.001). Novel multivariable prediction models derived with prepolicy data ranked candidates correctly more often than the 6-status rankings (Cox proportional hazards model C-index: 0.76; random survival forest model C-index: 0.74). Objective physiologic measurements, such as glomerular filtration rate, had high variable importance. CONCLUSIONS: The treatment-based 6-status heart allocation system has only moderate ability to rank-order candidates by medical urgency. Predictive models that incorporate physiologic measurements can more effectively rank-order heart transplant candidates by urgency.

Quantitative EEG signatures of delirium and coma in mechanically ventilated ICU patients.

OBJECTIVE: To identify quantitative electroencephalography (EEG)-based indicators of delirium or coma in mechanically ventilated patients. METHODS: We prospectively enrolled 28 mechanically ventilated intensive care unit (ICU) patients to undergo 24-hour continuous EEG, 25 of whom completed the study. We assessed patients twice daily using the Richmond Agitation-Sedation Scale (RASS) and Confusion Assessment Method for the ICU (CAM-ICU). We evaluated the spectral profile, regional connectivity and complexity of 5-minute EEG segments after each assessment. We used penalized regression to select EEG metrics associated with delirium or coma, and compared mixed-effects models predicting delirium with and without the selected EEG metrics. RESULTS: Delta variability, high-beta variability, relative theta power, and relative alpha power contributed independently to EEG-based identification of delirium or coma. A model with these metrics achieved better prediction of delirium or coma than a model with clinical variables alone (Akaike Information Criterion: 36 vs 43, p = 0.006 by likelihood ratio test). The area under the receiver operating characteristic curve for an ad hoc hypothetical delirium score using these metrics was 0.94 (95%CI 0.83-0.99). CONCLUSIONS: We identified four EEG metrics that, in combination, provided excellent discrimination between delirious/comatose and non-delirious mechanically ventilated ICU patients. SIGNIFICANCE: Our findings give insight to neurophysiologic changes underlying delirium and provide a basis for pragmatic, EEG-based delirium monitoring technology.

Proteomic changes associated with racial background and sepsis survival outcomes.

Intra-abdominal infection is a common cause of sepsis, and intra-abdominal sepsis leads to ∼156 000 U.S. deaths annually. African American/Black adults have higher incidence and mortality rates from sepsis compared to Non-Hispanic White adults. A limited number of studies have traced survival outcomes to molecular changes; however, these studies primarily only included Non-Hispanic White adults. Our goal is to better understand molecular changes that may contribute to differences in sepsis survival in African American/Black and Non-Hispanic White adults with primary intra-abdominal infection. We employed discovery-based plasma proteomics of patient samples from the Protocolized Care for Early Septic Shock (ProCESS) cohort (N = 107). We identified 49 proteins involved in the acute phase response and complement system whose expression levels are associated with both survival outcome and racial background. Additionally, 82 proteins differentially-expressed in survivors were specific to African American/Black or Non-Hispanic White patients, suggesting molecular-level heterogeneity in sepsis patients in key inflammatory pathways. A smaller, robust set of 19 proteins were in common in African American/Black and Non-Hispanic White survivors and may represent potential universal molecular changes in sepsis. Overall, this study identifies molecular factors that may contribute to differences in survival outcomes in African American/Black patients that are not fully explained by socioeconomic or other non-biological factors.

Long-term bowel dysfunction and decision regret in diverticulitis: A mixed methods study.

BACKGROUND: This study had aimed to describe long-term decision regret, bowel dysfunction, and the overall quality of life in patients with diverticulitis, and to determine if elective colectomy was associated with these patient-reported outcome measures. METHODS: This mixed-methods, survey-based study was administered to a national cohort of patients in the United States with diverticulitis. We measured decision regret (Brehaut Decision Regret), bowel dysfunction (Low Anterior Resection Syndrome score), and the overall quality of life (EuroQol 5 Dimension) in this population. We asked open-ended questions to elucidate factors that influenced patients' choices between elective colectomy and observation. RESULTS: Among the 614 respondents, 294 (48%) chose between colectomy and observational management, 94 (15%) had surgery, and 157 (26%) had major Low Anterior Resection Syndrome. Of the 294 that chose between colectomy and observational management, 51 (17%) experienced decision regret. Colectomy was associated with an average decrease in the Brehaut Decision Regret score by 6 points but was not associated with a categorical measure of decision regret (Brehaut Score ≥50). Bowel dysfunction and overall quality of life were not significantly associated with colectomy. Disease-related factors, psychosocial factors, and interactions with physicians were commonly cited as reasons for pursuing colectomy or observational management. CONCLUSION: Patients with self-reported diverticulitis describe high levels of decision regret and bowel dysfunction regardless of chosen management strategy. Physicians should be aware that psychosocial factors can strongly influence a patient's choice between colectomy and observational management. We advocated for future prospective studies using patient reported outcome metrics to improve outcomes in diverticulitis.

Proton pump inhibitors use and risk of incident nephrolithiasis.

Proton pump inhibitors (PPIs) are widely prescribed medications that have effects on both enteric and urinary solute handling with an unknown effect on risk of nephrolithiasis. Our objectives were to examine the association between PPI exposure and incident nephrolithiasis and to determine its effect on 24H urine chemistry. We performed a single-center retrospective study on patients diagnosed with gastroesophageal reflux disease (GERD) without a history of kidney stones. Exposure to PPIs was abstracted, and then subsequent kidney stone diagnoses were identified. Multivariable Cox models with time-varying covariates were used to estimate the hazard of PPI use on incident nephrolithiasis. We used multivariable linear regression to analyze a subset of patients who went through 24-h urine analysis. We identified n = 55,765 PPI-naïve GERD patients without prior kidney stone diagnoses of whom 40,866 (73.2%) were exposed to PPI over a median of 3 year follow up. On multivariable analysis, PPI use was associated with higher risk of incident kidney stone diagnoses (HR 1.19, 95% CI 1.06-1.34). Among 593 patients with GERD with 24-H urine data, the PPI-exposed group (n = 307) had significantly lower mean urinary citrate (mean 3.0 vs 3.4 mmol, p = 0.029) and urinary magnesium (mean 3.6 vs 4.3 mmol, p < 0.001) on multivariable analyses. Exposure to PPIs is associated with an increased risk of kidney stones among patients with GERD. Hypomagnesemia and hypocitraturia associated with PPI exposure may contribute to kidney stone risk.

Weight Loss Outcomes following Roux-en-Y Gastric Bypass and Sleeve Gastrectomy in an Ethnically Diverse Bariatric Population: Which Is More Effective?

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) have comparable weight loss outcomes in a general bariatric population. OBJECTIVES: This study aimed to investigate whether similar outcomes can be observed in Hispanic and African American population. Settings. Community Hospital in New York, New York, United States. METHODS: The 5-year prospective data of patients who underwent LRYGB and LSG at a single center were retrospectively reviewed. The long-term weight loss outcomes between patients who had LRYGB and LSG were compared after adjusting for age, sex, race, diabetes mellitus, and hypertension with the linear mixed-effects or logistic regression model. RESULTS: Most patients were Hispanic (59.2%) and African American (22.7%). The mean% total weight loss (%TWL) values of patients with BMI <45 kg/m2 who underwent LRYGB and LSG were 73% and 62% after 1 year, 69% and 56% after 2 years, and 71% and 54% after 5 years, respectively. In patients with a BMI of 45-50 kg/m2 who underwent LRYGB and LSG, the mean %TWL values were 69% and 56% after 1 year, 75% and 58% after 2 years, and 57% and 45% after 5 years, respectively. Meanwhile, the %TWL values of patients with BMI >50 kg/m2 who had LRYGB and LSG were 53% and 42% after 1 year, 53% and 45% after 2 years, and 49% and 36% after 5 years, respectively. All results were statistically significant (p < 0.0001) and remained valid after adjusting for cofactors. CONCLUSION: Thus, LRYGB had consistent and sustained long-term weight loss outcomes compared with LSG in a predominantly ethnically diverse patient population with different BMI. Our study had several limitations in that it is retrospective in nature and some patients were lost to follow-up during the study period.

Improvement in glycated hemoglobin A1C after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy in an ethnically diverse population with diabetes.

BACKGROUND: Obesity is a well-known risk factor for the development of type 2 diabetes. The efficacy of bariatric surgery in reducing weight with resulting improvement in type 2 diabetes has been reliably demonstrated. OBJECTIVES: We investigated and compared the effects of laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) on glycated hemoglobin (HbA1C) levels in a predominantly Hispanic and black population. SETTINGS: Community Hospital in New York, New York, United States. METHODS: This is a retrospective review of a 5-year data from a single center where patients with diabetes who underwent LRYGB or LSG were included. HbA1C levels and body mass index were analyzed preoperatively and then annually postoperatively for up to 5 years. Improvements in HbA1C were compared between the 2 groups after adjusting for age, sex, race, and hypertension with linear mixed-effects or logistic regression models. RESULTS: Of the 676 included patients, 84.8% were females and the mean age was 47 years. HbA1C levels decreased significantly (P < .05) in the entire group at 1 (21%), 2 (20%), 3 (20%), 4 (18%), and 5 (14%) years. Compared with LSG, LRYGB patients displayed greater improvement in HbA1C levels at 1 year (25% versus 17%, P = .001). The differences in the reduction of HbA1C between LRYGB and LSG for the other time intervals were not significant (P > .05), 24% versus 17% (2 yr), 22% versus 16% (3 yr), 22% versus 13% (4 yr), and 17% versus 10% (5 yr). Changes in body mass index were not correlated to changes in HbA1C at various study points. CONCLUSION: Both LRYGB and LSG resulted in significant decreases in HbA1C levels and are correlated with changes in body mass index. LRYGB had the greatest effect at 1 year postoperatively. There was no significant difference in HbA1C reduction for LRYGB and LSG after 1 year postoperatively in this predominantly Hispanic and black cohort.