The Effect of Intersectionality on Attrition among US General Surgery Trainees.

OBJECTIVE: To examine the association between intersectionality of race, ethnicity, and sex on retention of U.S. general surgery residents. SUMMARY BACKGROUND DATA: There are limited data on the role that intersectionality plays on the US general surgery resident experience. METHODS: Analysis was performed using Association of American Medical Colleges (AAMC) data for general surgery residents who started their training between 2005-2015 (followed through completion). Regression analyses were used to assess demographic associations with time to attrition or successful completion of residency training. Associations between faculty and resident demographics were assessed. RESULTS: 25,029 residents were included. Over the decade-long study period, the number of underrepresented in medicine (UIM) residents as a percentage of all residents remained similar from 17% to 19% (P=0.24). The percent of UIM males starting training in 2005 was 11% and 12% in 2015 (P-value=0.38). UIM females comprised 5.5% of trainees in 2005 and increased to 6.9% (P-value=0.003) in 2015; and female non-UIM residents increased from 23 to 28% (P-value<0.001). The overall rate of resident attrition was 15%. UIM females had the highest yearly attrition rate at 21% compared to non-UIM males at 13% (HR 1.7, P<0.001). UIM females were more likely to leave residency compared to UIM males (HR: 1.5; P<0.001). The percent of UIM faculty was positively correlated with percent of UIM residents (r=0.64, P<0.001). CONCLUSIONS: Increasing intersectionality is positively associated with attrition during surgery residency. The diversity of faculty appears to be associated with resident diversity.

Clinically relevant cut-points for changes in the Liver Frailty Index are associated with waitlist mortality in patients with cirrhosis.

BACKGROUND & AIMS: Physical frailty is a critical determinant of mortality in patients with cirrhosis and can be objectively measured using the Liver Frailty Index (LFI) that is potentially modifiable.. We aimed to LFI cut-points associated with waitlist mortality. APPROACH & RESULTS: Ambulatory adults with cirrhosis without HCC awaiting liver transplantation (LT) from 9 centers from 2012-2021 for ≥3 months with ≥2 pre-LT LFI assessments were included. The primary explanatory variable was change in LFI from first to second assessments per 3 months (∆LFI); we evaluated clinically-relevant ∆LFI cut-points at 0.1, 0.2, 0.3, and 0.5. The primary outcome was waitlist mortality (death or delisting for being too sick) with transplant considered as a competing event. Among 1029 patients, median (IQR) age was 58 (51-63) years; 42% were female; and median lab MELDNa at first assessment was 18 (15-22). For each 0.1 improvement in ∆LFI, risk of overall mortality decreased by 6% (cause-specific hazard ratio [cHR] 0.94, 95%CI 0.92-0.97, p < 0.001). ∆LFI was associated with waitlist mortality at cut-points as low as 0.1 (cHR 0.63, 95%CI 0.46-0.87) and 0.2 (HR 0.61, 95%CI 0.42-0.87). CONCLUSIONS: An improvement in LFI per 3 months as small as 0.1 in the pre-LT period is associated with a clinically meaningful reduction in waitlist mortality. These data provide estimates of the reduction in mortality risk associated with improvements in LFI that can be used to assess effectiveness of interventions targeting physical frailty in cirrhosis patients.

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.

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.

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.

Assessing Adherence to US LI-RADS Follow-up Recommendations in Vulnerable Patients Undergoing Hepatocellular Carcinoma Surveillance.

Purpose To assess adherence to the US Liver Imaging Reporting and Data System (LI-RADS) recommendations for hepatocellular carcinoma (HCC) surveillance and associated patient-level factors in a vulnerable, diverse patient sample. Materials and Methods The radiology report database was queried retrospectively for patients who underwent US LI-RADS-based surveillance examinations at a single institution between June 1, 2020, and February 28, 2021. Initial US and follow-up liver imaging were included. Sociodemographic and clinical data were captured from electronic medical records. Adherence to radiologist recommendation was defined as imaging (US, CT, or MRI) follow-up in 5-7 months for US-1, imaging follow-up in 3-6 months for US-2, and CT or MRI follow-up in 2 months for US-3. Descriptive analysis and multivariable modeling that adjusted for age, sex, race, and time since COVID-19 pandemic onset were performed. Results Among 936 patients, the mean age was 59.1 years; 531 patients (56.7%) were male and 544 (58.1%) were Asian or Pacific Islander, 91 (9.7%) were Black, 129 (13.8%) were Hispanic, 147 (15.7%) were White, and 25 (2.7%) self-reported as other race. The overall adherence rate was 38.8% (95% CI: 35.7, 41.9). The most common liver disease etiology was hepatitis B (60.6% [657 of 936 patients]); 19.7% of patients (183 of 936) had current or past substance use disorder, and 44.8% (416 of 936) smoked. At adjusted multivariable analysis, older age (odds ratio [OR], 1.20; P = .02), male sex (OR, 1.62; P = .003), hepatology clinic attendance (OR, 3.81; P < .001), and recent prior US examination (OR, 2.44; P < .001) were associated with full adherence, while current smoking (OR, 0.39; P < .001) was negatively associated. Conclusion Adherence to HCC imaging surveillance was suboptimal, despite US LI-RADS implementation. Keywords: Liver, Ultrasound, Screening, Abdomen/GI, Cirrhosis, Metabolic Disorders, Socioeconomic Issues Supplemental material is available for this article. © RSNA, 2024.

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.

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.

Pathologic Exploration of the Axillary Soft Tissue Microenvironment and Its Impact on Axillary Management and Breast Cancer Outcomes.

PURPOSE: Axillary soft tissue (AXT) involvement with tumor cells extending beyond the positive lymph node (LN+) and extracapsular extension (ECE) has been overlooked in breast pathology specimen analysis. MATERIALS AND METHODS: We analyzed 2,162 LN+ patients, dividing them into four groups on the basis of axillary pathology: (1) LN+ only, (2) LN+ and ECE only, (3) LN+ and AXT without ECE, and (4) LN+ with both AXT and ECE. The primary end points were 10-year locoregional failure (LRF), the 10-year axillary failure, and 10-year distant metastasis rates. Multivariable Cox models, accounting for clinical factors, were fitted using the entire cohort, and subgroups analyses were conducted. RESULTS: The median follow-up was 9.4 years. The 10-year distant metastasis incidence was 42% for LN + AXT + ECE, 23% for both LN + AXT and LN + ECE only, and 13% for LN+ only. The 10-year axillary failure rates were 4.5% for LN + AXT + ECE, 4.6% for LN + AXT, 0.8% for LN + ECE only, and 1.6% for LN+ only. The 10-year LRF rates were 14% for LN + AXT + ECE, 10% for LN + AXT, 5.7% for LN + ECE only, and 6.2% for LN+ only. Multivariable analysis revealed that AXT was significantly associated with distant metastasis (hazard ratio [HR], 1.6; P < .001), locoregional failure (HR, 2.3; P < .001), and axillary failure (HR, 3.3; P = .003). Subgroup analyses showed that regional LN radiation (RLNR) improved locoregional tumor outcomes with AXT, ECE, or both (HR, 0.5; P = .03). Delivering ≤50 Gy to the axilla in the presence of AXT/ECE increased axillary failure (HR, 3.0; P = .04). Moreover, when delivering RLNR, axillary LN dissection could be de-escalated to sentinel node biopsy even in the presence of features such as AXT or ECE without significantly increasing any failure outcome: (HR, 1.0; P = .92) for LRF, (HR, 1.1; P = .94) axillary failure, and (HR, 0.4; P = .01) distant metastasis. CONCLUSION: Routine reporting of axillary tissue involvement, beyond LNs and ECE, is crucial in predicting breast cancer outcomes. Ruling out the presence of AXT is imperative before any form of axillary de-escalation, especially RLNR omission.

Neighborhood Income Is Associated with Health Care Use in Pediatric Short Bowel Syndrome.

OBJECTIVE: To evaluate associations between neighborhood income and burden of hospitalizations for children with short bowel syndrome (SBS). STUDY DESIGN: We used the Pediatric Health Information System (PHIS) database to evaluate associations between neighborhood income and hospital readmissions, readmissions for central line-associated bloodstream infections (CLABSI), and hospital length of stay (LOS) for patients <18 years with SBS hospitalized between January 1, 2006, and October 1, 2015. We analyzed readmissions with recurrent event analysis and analyzed LOS with linear mixed effects modeling. We used a conceptual model to guide our multivariable analyses, adjusting for race, ethnicity, and insurance status. RESULTS: We included 4289 children with 16 347 hospitalizations from 43 institutions. Fifty-seven percent of the children were male, 21% were Black, 19% were Hispanic, and 67% had public insurance. In univariable analysis, children from low-income neighborhoods had a 38% increased risk for all-cause hospitalizations (rate ratio [RR] 1.38, 95% CI 1.10-1.72, P = .01), an 83% increased risk for CLABSI hospitalizations (RR 1.83, 95% CI 1.37-2.44, P < .001), and increased hospital LOS (ß 0.15, 95% CI 0.01-0.29, P = .04). In multivariable analysis, the association between low-income neighborhoods and elevated risk for CLABSI hospitalizations persisted (RR 1.70, 95% CI 1.23-2.35, P < .01, respectively). CONCLUSIONS: Children with SBS from low-income neighborhoods are at increased risk for hospitalizations due to CLABSI. Examination of specific household- and neighborhood-level factors contributing to this disparity may inform equity-based interventions.

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.

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.

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.

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.

Downstaging hepatocellular carcinoma before liver transplantation: A multicenter analysis of the "all-comers" protocol in the Multicenter Evaluation of Reduction in Tumor Size before Liver Transplantation (MERITS-LT) consortium.

Patients with hepatocellular carcinoma meeting united network for organ sharing (UNOS)-downstaging (DS) criteria have excellent liver transplantation (LT) outcomes after DS. However, outcomes for "all-comers" (AC) patients with tumors initially exceeding UNOS-DS are poorly understood. Patients meeting AC (n = 82) or UNOS-DS (n = 229) at 7 LT centers in 4 UNOS regions were prospectively followed from 2015-2020. AC patients had a lower probability of successful DS (67% vs 83% within 12 months; P < .001). The 3-year survival was 69% for UNOS-DS vs 58% for AC (P = .05) and reduced to 30% in patients with Child-Pugh B/C cirrhosis or alpha-fetoprotein (AFP) ≥ 500. Five-year LT probability was 42% for AC vs 74% in UNOS-DS (P = .10). Thirty-eight percent were understaged on explant, with the increasing sum of the largest tumor diameter plus the number of lesions before LT (odds ratio 1.3; P = .01) and AFP ≥ 20 (odds ratio 5.9; P = .005) associated with understaging. Post-LT 3-year survival was 91% for AC vs 81% for UNOS-DS (P = .67). In this first prospective multiregional study of AC patients from the multicenter evaluation of reduction in tumor size before liver transplantation (MERITS-LT) consortium, we observed a 65% probability of successful DS. Three-year survival in AC was nearly 60%, though AC with Child-Pugh B/C or AFP ≥ 500 had poor survival. Explant pathology and 3-year post-LT outcomes were similar between cohorts, suggesting that LT is a reasonable goal in selected AC patients.

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.

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.