Outpatient mean arterial pressure: A potentially modifiable risk for acute kidney injury and death among patients with cirrhosis.

Mean arterial blood pressure (MAP), which decreases as portal hypertension progresses, may be a modifiable risk factor among patients with cirrhosis. We included adults enrolled in the Functional Assessment in Liver Transplantation study. We completed latent class trajectory analyses to define MAP trajectories. We completed time-dependent Cox-regression analyses to test the association between outpatient MAP and 3 cirrhosis-related outcomes: (1) stage 2 acute kidney injury (AKI), defined as a ≥200% increase in serum creatinine from baseline; (2) a 5-point increase in the MELD-Na score, defined as the incidence of increase from initial MELD-Na; (3) waitlist mortality, defined as death on the waitlist. For each outcome, we defined MAP cut points by determining the maximally selected Log-rank statistic after univariable Cox-regression analyses. Among the 1786 patients included in this analysis, our latent class trajectory analyses identified 3 specific outpatient MAP trajectories: "stable-low," "stable-high," and "increasing-to-decreasing." However, >80% of patients were in a "stable-low" trajectory. We found in adjusted analyses that outpatient MAP was associated with each of our outcomes: Stage 2 AKI (adjusted hazard ratio 0.88 per 10 mm Hg increase in MAP [95% CI: 0.79-0.99]); 5-point increase in MELD-Na (adjusted hazard ratio: 0.91 [95% CI: 0.86-0.96]; waitlist mortality (adjusted hazard ratio: 0.89 [95% CI: 0.81-0.96]). For each outcome, we found that an outpatient MAP of 82 mm Hg was most associated with outcomes ( p <0.05 for all). Our study informs the association between outpatient MAP and cirrhosis-related outcomes. These findings, coupled with the identification of specific thresholds, lay the foundation for the trial of targeted outpatient MAP modulation in patients with cirrhosis.

Surgeon Intersectionality and Academic Promotion and Retention in the US.

Introduction: Efforts have been made to increase the number of women and physicians who are underrepresented in medicine (UIM). However, surgery has been slow to diversify, and there are limited data surrounding the impact of intersectionality. Objective: To assess the combined association of race and ethnicity and sex with rates of promotion and attrition among US academic medical department of surgery faculty. Design, Setting, and Participants: This was a retrospective cohort study using faculty roster data from the Association of American Medical Colleges. All full-time academic department of surgery faculty with an appointment any time from January 1, 2005, to December 31, 2020, were included. Study data were analyzed from September 2022 to February 2023. Exposures: Full-time academic faculty in a department of surgery with a documented self-reported race, ethnicity, and sex within the designated categories of the faculty roster of Association of American Medical Colleges. Main Outcomes and Measures: Trends in race and ethnicity and sex, rates of promotion, and rates attrition from 2010 to 2020 were assessed with Kaplan-Meier and Cox time-to-event analyses. Results: A total of 31 045 faculty members (23 092 male [74%]; 7953 female [26%]) from 138 institutions were included. The mean (SD) program percentage of UIM male faculty increased from 8.4% (5.5%) in 2010 to 8.5% (6.2%) in 2020 (P < .001), whereas UIM female faculty members increased from 2.3% (2.6%) to 3.3% (2.5%) over the 10-year period (P < .001). The mean program percentage of non-UIM females increased at every rank (percentage point increase per year from 2010 to 2020 in instructor: 1.1; 95% CI, 0.73-1.5; assistant professor: 1.1; 95% CI, 0.93-1.3; associate professor: 0.55; 95% CI, 0.49-0.61; professor: 0.50; 95% CI, 0.41-0.60; all P < .001). There was no change in the mean program percentage of UIM female instructors or full professors. The mean (SD) percentage of UIM female assistant and associate professors increased from 3.0% (4.1%) to 5.0% (4.0%) and 1.6% (3.2%) to 2.2% (3.4%), respectively (P =.002). There was no change in the mean program percentage of UIM male instructors, associate, or full professors. Compared with non-Hispanic White males, Hispanic females were 32% less likely to be promoted within 10 years (hazard ratio [HR], 0.68; 95% CI, 0.54-0.86; P <.001), non-Hispanic White females were 25% less likely (HR, 0.75; 95% CI, 0.71-0.78; P <.001), Hispanic males were 15% less likely (HR, 0.85; 95% CI, 0.76-0.96; P =.007), and Asian females were 12% less likely (HR, 0.88; 95% CI, 0.80-0.96; P =.03). Non-UIM males had the shortest median (IQR) time to promotion, whereas non-UIM females had the longest (6.9 [6.8-7.0] years vs 7.2 [7.0-7.6] years, respectively; P < .001). After 10 years, 79% of non-UIM males (13 202 of 16 299), 71% of non-UIM females (3784 of 5330), 68% of UIM males (1738 of 2538), and 63% of UIM females (625 of 999) remained on the faculty. UIM females had a higher risk of attrition compared with non-UIM females (HR, 1.3; 95% CI, 1.1-1.5; P = .001) and UIM males (HR, 1.2; 95% CI, 1.0-1.4; P = .05). The mean (SE) time to attrition was shortest for UIM females and longest for non-UIM males (8.2 [0.14] years vs 9.0 [0.02] years, respectively; P < .001). Conclusion and Relevance: Results of this cohort study suggest that intersectionality was associated with promotion and attrition, with UIM females least likely to be promoted and at highest risk for attrition. Further efforts to understand these vulnerabilities are essential.

Adaptation of a health literacy screener for computerized, self-administered use by U.S. adults.

Objective: Health literacy is a critical health determinant, for which few computerized, self-administered assessments exist. This study adapted and tested the reliability of the Newest Vital Sign© (NVS) as a computerized, self-administered health literacy screener. Methods: Phase one involved 33 participants to create response options for a computerized, self-administered NVS (C-NVS). Phase two was a randomized crossover trial to test the consistency of C-NVS and original, interviewer-administered NVS (I-NVS) scores in 89 participants. Results: Linear mixed-effects regression model results showed a significant carryover effect (p < .001). Crossover trial data from time 1 showed that participants who initially received the C-NVS had significantly higher average scores (M = 5.7, SD = 0.6) than participants who received the I-NVS (M = 4.5, SD = 1.5; t(87) = 5.25, p < .001). Exploratory analysis results showed that when the washout period was longer than 33 days (75th percentile) the carryover effect was not statistically significant (p = .077). Conclusion and innovation: Findings suggest learning can occur when health literacy screeners are administered more than once in less than a month's time and computerized, self-administered health literacy screeners may produce ceiling effects. A universal precautions approach to health literacy therefore remains germane.

Problematic alcohol use and its impact on liver disease quality of life in a multicenter study of patients with cirrhosis.

BACKGROUND: Management of cirrhosis is challenging and has been complicated by the COVID-19 pandemic due to decreased access to care, increased psychological distress, and alcohol misuse. Recently, The National Institute on Alcohol Abuse and Alcoholism has broadened the definition of recovery from alcohol use disorder to include quality of life (QoL) as an indicator of recovery. This study examined the associations of alcohol-associated cirrhosis etiology and problematic drinking with liver disease QoL (LDQoL). METHODS: Patients with cirrhosis (N=329) were recruited from 3 sites (63% from 2 Veterans Affairs Health Care Systems and 37% from 1 safety net hospital) serving populations that are economically or socially marginalized. Cirrhosis etiology was ascertained by chart review of medical records. Problematic drinking was defined by ≥8 on the Alcohol Use Disorders Identification Test. Multivariable general linear modeling adjusting for age, sex, race/ethnicity, site, pandemic-related stress, and history of anxiety/depressive disorder were conducted. Sensitivity analyses further adjusted for indicators of liver disease severity. RESULTS: Participants were on average 64.6 years old, 17% female, 58% non-White, 44% with alcohol-associated cirrhosis, and 17% with problematic drinking. Problematic drinking was significantly associated with worse LDQoL scores in the overall scale and in the memory/concentration and health distress subscales. These associations remained significant after adjusting for indicators of liver disease severity, including Model for End-Stage Liver Disease-Sodium score and decompensated cirrhosis status. CONCLUSIONS: Among patients with cirrhosis, problematic drinking was associated with worse LDQoL, especially in the domains of memory/concentration and health distress. Assessment and awareness of cognitive deficits and negative emotionality within the context of cirrhosis and problematic drinking may help clinicians provide better integrated care for this population.

Factors associated with trauma recidivism in young children.

BACKGROUND: Trauma recidivism is associated with future trauma-associated morbidity and mortality. Previous evidence suggests that socioeconomic factors predict trauma recidivism in older children (10-18 years); however, risk factors in US children ≤10 have not been studied. We sought to determine the factors associated with trauma recidivism in young children ≤10. METHODS: We conducted a retrospective cohort study of pediatric trauma patients ≤10 years who presented to a single ACS-verified level I Pediatric Trauma Center from 7/1/2017 - 6/30/2021. All patients were evaluated for prior injury during trauma registry entry. Characteristics at the index injury were collected via chart review. Patients were geocoded to assess social vulnerability index (SVI). Logistic regression examined factors associated with recidivism. Best subset selection was used to compare multivariable models and identify the most predictive and parsimonious model. Statistical significance was set at p < 0.05. RESULTS: Of the 3,518 patients who presented in the study period, 169 (4.8%) experienced a prior injury. 76% (n = 128) had one prior injury presentation, 18% (n = 31) had 2 prior presentations, and 5.9% (n = 10) had ≥3. Falls were the most common mechanism in recidivists (63% vs. 52%, p = 0.009). Child physical abuse occurred in 6.5% of patients and 0.9% experienced penetrating injury. The majority (83%, n = 137) were discharged home from the ED. There was no significant difference in the frequency of penetrating injury and child physical abuse between recidivists and non-recidivists. Following logistic regression, the most parsimonious model demonstrated that recidivism was associated with comorbidities, age, falls, injury location, non-transfer, and racialization. No significant associations were found with SVI and insurance status. CONCLUSIONS: Medical comorbidities, young age, injury location, and falls were primarily associated with trauma recidivism. Support for parents of young children and those with special healthcare needs through injury prevention programs could reduce trauma recidivism in this population.Level of Evidence: III, Prognostic & Epidemiological.

The liver frailty index is a predictor of healthcare utilization after liver transplantation in older adults.

BACKGROUND: Older adults have higher healthcare utilization after liver transplantation (LT), yet objective risk stratification tools in this population are lacking. We evaluated the Liver Frailty Index (LFI) as one potential tool. METHODS: Ambulatory LT candidates ≥65 years without hepatocellular carcinoma (HCC) who underwent LT from 1/2012 to 6/2022 at 8 U.S. centers were included. Estimates of the difference in median using quantile regression were used to assess the adjusted association between LFI and hospitalized days within 90 days post-LT. RESULTS: Of 131 LT recipients, median (interquartile range [IQR]) (1st -3rd quartiles) age was 68 years (66-70); median pre-LT MELD-Na was 19 (15-24). Median LFI was 4.1 (3.6-4.7); 27% were frail (LFI≥4.5). Median hospitalized days within 90 days post-LT was 11 (7-20). Compared with non-frail patients, frail patients were hospitalized for a median of 5 days longer post-LT (95% CI .30-9.7, p = .04). Each .5 unit increase in pre-LT LFI was associated with an increase of 1.16 days (95%CI .42-2.69, p = .02) in hospitalized days post-LT. CONCLUSION: Among older adults undergoing LT, frailty was associated with more hospitalized days within 90 days after LT. The LFI can identify older adults who might benefit from pre-LT or early post-LT programs which may reduce post-LT healthcare utilization, such as early rehabilitation or post-hospital discharge programs.

The impact of histologic subtype on primary site surgery in the management of metastatic lobular versus ductal breast cancer: a population based study from the National Cancer Database (NCDB).

PURPOSE: Primary site surgery for metastatic breast cancer improves local control but does not impact overall survival. Whether histologic subtype influences patient selection for surgery is unknown. Given differences in surgical management between early-stage lobular versus ductal disease, we evaluated the impact of histology on primary site surgery in patients with metastatic breast cancer. METHODS: The National Cancer Database (NCDB, 2010-2016) was queried for patients with stage IV HR-positive, HER2-negative invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). We compared clinicopathologic features, primary site surgery rates, and outcomes by histologic subtype. Multivariable Cox proportional hazard models with and without propensity score matching were used for overall survival (OS) analyses. RESULTS: In 25,294 patients, primary site surgery was slightly but significantly less common in the 6,123 patients with ILC compared to the 19,171 patients with IDC (26.9% versus 28.8%, p = 0.004). Those with ILC were less likely to receive chemotherapy (41.3% versus 47.4%, p < 0.0001) or radiotherapy (29.1% versus 37.9%, p < 0.0001), and had shorter OS. While mastectomy rates were similar, those with ILC who underwent lumpectomy had significantly higher positive margin rates (ILC 15.7% versus IDC 11.2%, p = 0.025). In both groups, the odds of undergoing surgery decreased over time, and were higher in younger patients with T2/T3 tumors and higher nodal burden. CONCLUSION: Lobular histology is associated with less primary site surgery, higher positive margin rates, less radiotherapy and chemotherapy, and shorter OS compared to those with HR-positive HER2-negative IDC. These findings support the need for ILC-specific data and treatment approaches in the setting of metastatic disease.

Clinical Characteristics Associated With Posttransplant Survival Among Adults 70 Years Old or Older Undergoing Liver Transplantation.

GOALS: We sought to identify pre-liver transplantation (LT) characteristics among older adults associated with post-LT survival. BACKGROUND: The proportion of older patients undergoing deceased-donor liver transplantation (DDLT) has increased over time. STUDY: We analyzed adult DDLT recipients in the United Network for Organ Sharing registry from 2016 through 2020, excluding patients listed as status 1 or with a model of end-stage liver disease exceptions for hepatocellular carcinoma. Kaplan-Meier methods were used to estimate post-LT survival probabilities among older recipients (age ≥70 y). Associations between clinical covariates and post-LT mortality were assessed using Cox regressions. RESULTS: Of 22,862 DDLT recipients, 897 (4%) were 70 years old or older. Compared with younger recipients, older recipients had worse overall survival ( P < 0.01) (1 y: 88% vs 92%, 3 y: 77% vs 86%, and 5 y: 67% vs 78%). Among older adults, in univariate Cox regressions, dialysis [hazards ratio (HR): 1.96, 95% CI: 1.38-2.77] and poor functional status [defined as Karnofsky Performance Score (KPS) <40] (HR: 1.82, 95% CI: 1.31-2.53) were each associated with mortality, remaining significant on multivariable Cox regressions. The effect of dialysis and KPS <40 at LT on post-LT survival (HR: 2.67, 95% CI: 1.77-4.01) was worse than the effects of either KPS <40 (HR: 1.52, 95% CI: 1.03-2.23) or dialysis alone (HR: 1.44, 95% CI: 0.62-3.36). Older recipients with KPS >40 without dialysis had comparable survival rates compared with younger recipients ( P = 0.30). CONCLUSIONS: While older DDLT recipients had worse overall post-LT survival compared with younger recipients, favorable survival rates were observed among older adults who did not require dialysis and had poor functional status. Poor functional status and dialysis at LT may be useful to stratify older adults at higher risk for poor post-LT outcomes.

Association of body mass index with post-liver transplant outcomes.

BACKGROUND: Patients with obesity have inferior outcomes after general surgery procedures, but studies evaluating post-liver transplant (LT) outcomes have been limited by small sample sizes or lack of granularity of outcomes. We evaluated the relationship between obesity and post-LT outcomes, including those observed in other populations to be obesity-related. METHODS: Included were 1357 LT recipients prospectively enrolled in the ambulatory pre-LT setting at 8 U.S. CENTERS: Recipient were categorized by body mass index (BMI, kg/m2 ): non-obese (BMI < 30), class 1 obesity (BMI 30-<35), and classes 2-3 obesity (BMI ≥ 35). Post-transplant complications were compared by BMI using Chi-square and rank-sum testing, logistic regression, Kaplan-Meier curves, and Cox regression. RESULTS: Classes 2-3 obesity was associated with higher adjusted odds than non-obesity of venous thrombosis [adjusted odds ratio (aOR) 2.06, 95% CI 1.01-4.23, p = .047] and wound dehiscence (aOR 2.45, 95% CI 1.19-5.06, p = .02). Compared with non-obese recipients, post-LT hospital stay was significantly longer for recipients with classes 2-3 obesity [p = .01; median (Q1-Q3) 9 (6-14) vs. 8 (6-12) days) or class 1 obesity [p = .002; 9 (6-14) vs. 8 (6-11) days].  Likelihood of ICU readmission, infection, discharge to a non-home facility, rejection, 30-day readmission, and 1-year readmission were similar across BMI categories (all p > .05). CONCLUSION: Compared to non-obese recipients, obese recipients had similar post-LT survival but longer hospital stay and higher likelihood of wound dehiscence and venous thrombosis. These findings underscore that obesity alone should not preclude LT, but recipients with obesity should be monitored for obesity-related complications such as wound dehiscence and venous thrombosis.

Prevalence of cognitive impairment in liver transplant recipients.

Liver transplant (LT) recipients have a high burden of cognitive impairment risk factors identified in other populations, yet little work has explored cognition in the United States LT population. We characterized prevalence of cognitive impairment (CI) in LT recipients pre-LT and ≥3 months post-LT. Adult LT recipients with cirrhosis but without active pre-LT hepatic encephalopathy (HE) were screened for CI using the Montreal Cognitive Assessment (MoCA) for CI (MoCA <24) both pre-LT and ≥3 months post-LT. The association between cognitive performance and recipient characteristics was assessed using logistic regression. Of 107 LT recipients, 36% had pre-LT CI and 27% had post-LT CI [median (Q1-Q3) MoCA 26 (23-28)]. Each 1-point increase in pre-LT MoCA was associated with 26% lower odds of post-LT cognitive impairment (aOR .74, 95% CI .63-.87, p < .001), after adjusting for recipient age, history of HE, and time since LT. In this study of cirrhosis recipients without active pre-LT HE, cognitive impairment was prevalent before LT and remained prevalent ≥3 months after LT (27%), long after effects of portal hypertension on cognition would be expected to have resolved. Our data expose an urgent need for more comprehensive neurologic examination of LT recipients to better identify, characterize, and address predictors of post-LT cognitive impairment.

Variation in skeletal muscle mass among patients with cirrhosis of different self-identified race/ethnicity.

Skeletal muscle index (SMI) remains a strong predictor of mortality in cirrhosis patients. However, the extent to which SMI varies by race/ethnicity has not been fully evaluated. Among 317 patients, 55% identified themselves as non-Hispanic White (NHW), 26% Hispanic White (HW), 13% Asian, and 6% Black. There was significant variation in SMI by race/ethnicity; median SMI was lowest in Asian and highest in Black patients. There were significant differences of sarcopenia by race/ethnicity using established SMI cutpoints: 48% NHW, 33% HW, 67% Asian, and 37% Black (P = 0.003). Using these cutpoints, SMI was significantly associated with waitlist mortality only in NHW patients but not in other racial/ethnic groups.

AFP-L3 and DCP strongly predict early hepatocellular carcinoma recurrence after liver transplantation.

BACKGROUND & AIMS: Alpha-fetoprotein (AFP) predicts hepatocellular carcinoma (HCC) recurrence after liver transplant (LT) but remains an imperfect biomarker. The role of DCP (des-gamma-carboxyprothrombin) and AFP-L3 (AFP bound to Lens culinaris agglutinin) in predicting HCC recurrence remains incompletely characterized. AFP-L3 and DCP could identify patients at high risk of post-transplant HCC recurrence and serve as liver transplant exclusion criteria to defer transplant until patients receive additional risk-reducing pre-transplant locoregional therapy. METHODS: This prospective cohort study included consecutive patients with HCC who underwent LT (within or down-staged to Milan criteria) between 2017 and 2022. Pre-transplant AFP, AFP-L3, and DCP measurements were obtained. The primary endpoint was the ability of biomarkers to predict HCC recurrence-free survival. RESULTS: This cohort included 285 patients with a median age of 67 (IQR 63-71). At LT, median biomarker values were AFP 5.0 ng/ml (IQR 3.0-12.1), AFP-L3 6.7% (0.5-13.2), and DCP 1.0 ng/ml (0.3-2.8). Most (94.7%) patients received pre-LT locoregional therapy. After a median post-LT follow-up of 3.1 years, HCC recurrence was observed in 18 (6.3%) patients. AFP-L3 and DCP outperformed AFP with C-statistics of 0.81 and 0.86 respectively, compared with 0.74 for AFP. A dual-biomarker combination of AFP-L3 ≥15% and DCP ≥7.5 predicted 61.1% of HCC recurrences, whereas HCC only recurred in 7 of 265 (2.6%) patients not meeting this threshold. The Kaplan-Meier recurrence-free survival rate at 3 years post-LT was 43.7% for patients with dual-positive biomarkers compared to 97.0% for all others (p <0.001). CONCLUSIONS: Dual-positivity for AFP-L3 ≥15% and DCP ≥7.5 strongly predicted post-LT HCC recurrence. This model could refine LT selection criteria and identify high-risk patients who require additional locoregional therapy prior to LT. IMPACT AND IMPLICATIONS: Alpha-fetoprotein (AFP) is used to predict hepatocellular carcinoma (HCC) recurrence after liver transplant, but it remains an imperfect biomarker. In this prospective study, the biomarkers DCP (des-gamma-carboxyprothrombin) and AFP-L3 (AFP bound to Lens culinaris agglutinin) strongly predicted early HCC recurrence and outperformed AFP. A dual-biomarker combination of AFP-L3 ≥15% and DCP ≥7.5 predicted the majority of recurrences and could be used to further refine liver transplant eligibility criteria.

The impact of histologic subtype on primary site surgery in the management of metastatic lobular versus ductal breast cancer: a population based study from the National Cancer Database.

Purpose: Primary site surgery for metastatic breast cancer improves local control but does not impact overall survival. Whether histologic subtype influences patient selection for surgery is unknown. Given differences in surgical management between early-stage lobular versus ductal disease, we evaluated the impact of histology on primary site surgery in patients with metastatic breast cancer. Methods: The National Cancer Database (NCDB, 2010-2016) was queried for patients with stage IV HR-positive, HER2-negative invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). We compared clinicopathologic features, primary site surgery rates, and outcomes by histologic subtype. Multivariable Cox proportional hazard models with and without propensity score matching were used for overall survival (OS) analyses. Results: In 25,294 patients, primary site surgery was slightly but significantly less common in the 6,123 patients with ILC compared to the 19,171 patients with IDC (26.9% versus 28.8%, p = 0.004). Those with ILC were less likely to receive chemotherapy (41.3% versus 47.4%, p < 0.0001) or radiotherapy (29.1% versus 37.9%, p < 0.0001), and had shorter OS. While mastectomy rates were similar, those with ILC had more positive margins (10.6% versus 8.3%, p = 0.005). In both groups, the odds of undergoing surgery decreased over time, and were higher in younger patients with T2/T3 tumors and higher nodal burden. Conclusion: Lobular histology is associated with less primary site surgery, higher positive margin rates, less radiotherapy and chemotherapy, and shorter OS compared to those with HR-positive HER2-negative IDC. These findings support the need for ILC-specific data and treatment approaches in the setting of metastatic disease.

Factors Associated With Liver Transplant Referral Among Patients With Cirrhosis at Multiple Safety-Net Hospitals.

Importance: A high proportion of underserved patients with cirrhosis receive care at safety-net hospitals (SNHs). While liver transplant (LT) can be a life-saving treatment for cirrhosis, data on referral patterns from SNHs to LT centers are lacking. Objective: To identify factors associated with LT referral within the SNH context. Design, Setting, and Participants: This retrospective cohort study included 521 adult patients with cirrhosis and model for end-stage liver disease-sodium (MELD-Na) scores of 15 or greater. Participants received outpatient hepatology care at 3 SNHs between January 1, 2016, and December 31, 2017, with end of follow-up on May 1, 2022. Exposures: Patient demographic characteristics, socioeconomic status, and liver disease factors. Main Outcomes and Measures: Primary outcome was referral for LT. Descriptive statistics were used to describe patient characteristics. Multivariable logistic regression was performed to evaluate factors associated with LT referral. Multiple chained imputation was used to address missing values. Results: Of 521 patients, 365 (70.1%) were men, the median age was 60 (IQR, 52-66) years, most (311 [59.7%]) were Hispanic or Latinx, 338 (64.9%) had Medicaid insurance, and 427 (82.0%) had a history of alcohol use (127 [24.4%] current vs 300 [57.6%] prior). The most common liver disease etiology was alcohol associated liver disease (280 [53.7%]), followed by hepatitis C virus infection (141 [27.1%]). Median MELD-Na score was 19 (IQR, 16-22). One hundred forty-five patients (27.8%) were referred for LT. Of these, 51 (35.2%) were wait-listed, and 28 (19.3%) underwent LT. In a multivariable model, male sex (adjusted odds ratio [AOR], 0.50 [95% CI, 0.31-0.81]), Black race vs Hispanic or Latinx ethnicity (AOR, 0.19 [95% CI, 0.04-0.89]), uninsured status (AOR, 0.40 [95% CI, 0.18-0.89]), and hospital site (AOR, 0.40 [95% CI, 0.18-0.87]) were associated with lower odds of being referred. Reasons for not being referred (n = 376) included active alcohol use and/or limited sobriety (123 [32.7%]), insurance issues (80 [21.3%]), lack of social support (15 [4.0%]), undocumented status (7 [1.9%]), and unstable housing (6 [1.6%]). Conclusions: In this cohort study of SNHs, less than one-third of patients with cirrhosis and MELD-Na scores of 15 or greater were referred for LT. The identified sociodemographic factors negatively associated with LT referral highlight potential intervention targets and opportunities to standardize LT referral practices to increase access to life-saving transplant among underserved patients.

Community-level social vulnerability and individual socioeconomic status on liver transplant referral outcome.

BACKGROUND: Recent endeavors emphasize the importance of understanding early barriers to liver transplantation (LT) by consistently collecting data on patient demographics, socioeconomic factors, and geographic social deprivation indices. METHODS: In this retrospective single-center cohort study of 1657 adults referred for LT evaluation, we assessed the association between community-level vulnerability and individual socioeconomic status measures on the rate of waitlisting and transplantation. Patients' addresses were linked to Social Vulnerability Index (SVI) at the census tract-level to characterize community-level vulnerability. Descriptive statistics were used to describe patient characteristics. Multivariable cause-specific HRs were used to assess the association between community-level vulnerability, individual measures of the socioeconomic status, and LT evaluation outcomes (waitlist and transplantation). RESULTS: Among the 1657 patients referred for LT during the study period, 54% were waitlisted and 26% underwent LT. A 0.1 increase in overall SVI correlated with an 8% lower rate of waitlisting (HR 0.92, 95% CI 0.87-0.96, p < 0.001), with socioeconomic status, household characteristics, housing type and transportation, and racial and ethnic minority status domains contributing significantly to this association. Patients residing in more vulnerable communities experienced a 6% lower rate of transplantation (HR 0.94, 95% CI 0.91- 0.98, p = 0.007), with socioeconomic status and household characteristic domain of SVI significantly contributing to this association. At the individual level, both government insurance and employment status were associated with lower rates of waitlisting and transplantation. There was no association with mortality prior to waitlisting or mortality while on the waitlist. CONCLUSION: Our findings indicate that both individual and community measures of the socioeconomic status (overall SVI) are associated with LT evaluation outcomes. Furthermore, we identified individual measures of neighborhood deprivation associated with both waitlisting and transplantation.

The tele-liver frailty index (TeLeFI): development of a novel frailty tool in patients with cirrhosis via telemedicine.

Frailty is a critical determinant of outcomes in cirrhosis patients. The increasing use of telemedicine has created an unmet need for virtual frailty assessment. We aimed to develop a telemedicine-enabled frailty tool (tele-liver frailty index). Adults with cirrhosis in the liver transplant setting underwent ambulatory frailty testing with the liver frailty index (LFI) in-person, then virtual administration of (1) validated surveys (eg, SARC-F and Duke Activity Status Index [DASI]), (2) chair stands, and (3) balance. Two models were selected and internally validated for predicting LFI ≥4.4 using: (1) Bayesian information criterion (BIC), (2) C-statistics, and (3) ease of use. Of 145 patients, the median (interquartile range) LFI was 3.7 (3.3-4.2); 15% were frail. Frail (vs not frail) patients reported significantly greater impairment on all virtually assessed instruments. We selected 2 parsimonious models: (1) DASI + chair/bed transfer (SARC-F) (BIC 255, C-statistics 0.78), and (2) DASI + chair/bed transfer (SARC-F) + virtually assessed chair stands (BIC 244, C-statistics 0.79). Both models had high C-statistics (0.76-0.78) for predicting frailty. In conclusion, the tele-liver frailty index is a novel tool to screen frailty in liver transplant patients via telemedicine pragmatically and may be used to identify patients who require in-person frailty assessment, more frequent follow-up, or frailty intervention.

Interrater reliability of chart-based assessment of functional impairment after pediatric injury using the functional status scale.

BACKGROUND: Functional impairment has been proposed as an alternative outcome for quality improvement in pediatric trauma. The functional status scale (FSS) has been used in studies of injured children, but has only been validated with resource-intensive in-person assessment. Implementation with retrospective chart-based FSS assessment would offer a simplified and scalable alternative. The purpose of this study was to evaluate interrater reliability of retrospective FSS assessment and to identify factors associated with unreliable assessment. METHODS: A retrospective cohort of admissions to a Level I pediatric trauma center between July 2020 and June 2021 was analyzed. Two physicians and two nurse registrars reviewed charts to obtain measures of six FSS domains (mental status, sensory functioning, communication, motor functioning, feeding, and respiratory status) at discharge. Functional impairment was categorized by total FSS scores as good (6,7), mild impairment (8,9), moderate impairment (10-15), severe impairment (16-21), or very severe impairment (>21). Interrater reliability was assessed using intraclass correlation (ICC). Predictors of rater disagreement were evaluated using multivariable logistic regression. RESULTS: The cohort included 443 children with a mean age of 7.4 years (standard deviation, 5.4 years) and median Injury Severity Score of 9 (interquartile range, 5-12). The median time per chart to assess FSS was 2 minutes (interquartile range, 1-2). Thirty-seven patients (8%) had functional impairment at discharge. Interrater reliability was excellent for total FSS score (ICC = 0.87) and good for FSS impairment categorization (ICC = 0.80). Rater disagreement of functional impairment categorization occurred in 14% of cases overall. Higher level of functional impairment and use of therapies (occupational and speech language therapy) were independently associated with more frequent rater disagreement. CONCLUSION: Chart-based FSS assessment is feasible and reliable, but may require more detailed review for patients with higher level of impairment that require allied health therapy. Validation of chart-based assessment is needed before widespread implementation. LEVEL OF EVIDENCE: Prognostic/Epidemiological, Level III.

Serum and plasma protein biomarkers associated with frailty in patients with cirrhosis.

Frailty, a clinical phenotype of decreased physiological reserve, is a strong determinant of adverse health outcomes in patients with cirrhosis. The only cirrhosis-specific frailty metric is the Liver Frailty Index (LFI), which must be administered in person and may not be feasible for every clinical scenario. We sought to discover candidate serum/plasma protein biomarkers that could differentiate frail from robust patients with cirrhosis. A total of 140 adults with cirrhosis awaiting liver transplantation in the ambulatory setting with LFI assessments and available serum/plasma samples were included. We selected 70 pairs of patients on opposite ends of the frailty spectrum (LFI>4.4 for frail and LFI<3.2 for robust) who were matched by age, sex, etiology, HCC, and Model for End-Stage Liver Disease-Sodium. Twenty-five biomarkers with biologically plausible associations with frailty were analyzed using ELISA by a single laboratory. Conditional logistic regression was used to examine their association with frailty. Of the 25 biomarkers analyzed, we identified 7 proteins that were differentially expressed between frail and robust patients. We observed differences in 6 of the 7 proteins in the expected direction: (a) higher median values in frail versus robust with growth differentiation factor-15 (3682 vs. 2249 pg/mL), IL-6 (17.4 vs. 6.4 pg/mL), TNF-alpha receptor 1 (2062 vs. 1627 pg/mL), leucine-rich alpha-2 glycoprotein (44.0 vs. 38.6 µg/mL), and myostatin (4066 vs. 6006 ng/mL) and (b) lower median values in frail versus robust with alpha-2-Heremans-Schmid glycoprotein (0.11 vs. 0.13 mg/mL) and free total testosterone (1.2 vs. 2.4 ng/mL). These biomarkers represent inflammatory, musculoskeletal, and endocrine/metabolic systems, reflecting the multiple physiological derangements observed in frailty. These data lay the foundation for confirmatory work and development of a laboratory frailty index for patients with cirrhosis to improve diagnosis and prognostication.

Number of Local Regional Therapies for Hepatocellular Carcinoma and Peri-Operative Outcomes after Liver Transplantation.

The wait times for patients with hepatocellular carcinoma (HCC) listed for liver transplant are longer than ever, which has led to an increased reliance on the use of pre-operative LRTs. The impact that multiple rounds of LRTs have on peri-operative outcomes following transplant is unknown. This was a retrospective single center analysis of 298 consecutive patients with HCC who underwent liver transplant (January 2017 to May 2021). The data was obtained from two institution-specific databases and the TransQIP database. Of the 298 patients, 27 (9.1%) underwent no LRTs, 156 (52.4%) underwent 1-2 LRTs, and 115 (38.6%) underwent ≥3 LRTs prior to LT. The patients with ≥3 LRTs had a significantly higher rate of bile leak compared to patients who received 1-2 LRTs (7.0 vs. 1.3%, p = 0.014). Unadjusted and adjusted regression analyses demonstrated a significant association between the total number of LRTs administered and bile leak, but not rates of overall biliary complications. The total number of LRTs was not significantly associated with any other peri-operative or post-operative outcome measure. These findings support the aggressive use of LRTs to control HCC in patients awaiting liver transplant, with further evaluation needed to confirm the biliary leak findings.

Predicting future sleep problems in young autistic children.

LAY ABSTRACT: Sleep problems are common in autistic children and negatively impact daytime functioning. A method for predicting sleep problems could help with treatment and prevention of such problems. This study aimed to determine predictors of sleep problems among young autistic children. Study participants consisted of autistic children aged 2-5 years who did not have sleep problems at a first visit (Autism Treatment Network Registry) and had sleep data available at a subsequent visit (Registry Call-Back Assessment study). Sleep problems for five study cohorts of children were defined by different methods, including parent questionnaires and parent- or clinician-report of sleep problems. We found that self-injurious behavior, sensory issues, dental problems, and lower primary caregiver education level were significant risk factors of future sleep problems. These predictors may help clinicians provide prevention or earlier treatment for children who are at risk of developing sleep problems.