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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

CT-quantified sarcopenic visceral obesity is associated with poor transplant waitlist mortality in patients with cirrhosis.

Sarcopenic obesity is associated with higher rates of morbidity and mortality than seen with either sarcopenia or obesity alone. We aimed to define sarcopenic visceral obesity (SVO) using CT-quantified skeletal muscle index and visceral-to-subcutaneous adipose tissue ratio and to examine its association with waitlist mortality in patients with cirrhosis. Included were 326 adults with cirrhosis awaiting liver transplantation in the ambulatory setting with available abdominal CT within 6 months from enrollment between February 2015 and January 2018. SVO was defined as patients with sarcopenia (skeletal muscle index <50 cm 2 /m 2 in men and <39 cm 2 /m 2 in women) and visceral obesity (visceral-to-subcutaneous adipose tissue ratio ≥1.21 in men and ≥0.48 in women). The percentage who met criteria for sarcopenia, visceral obesity, and SVO were 44%, 29%, and 13%, respectively. Cumulative incidence of waitlist mortality was higher in patients with SVO compared to patients with sarcopenia without visceral obesity or visceral obesity without sarcopenia at 12 months (40% vs. 21% vs. 12%) (overall logrank p =0.003). In univariable Cox regression, SVO was associated with waitlist mortality (HR: 3.42, 95% CI: 1.58-7.39), which remained significant after adjusting for age, sex, diabetes, ascites, encephalopathy, MELDNa, liver frailty index, and different body compositions (HR: 2.64, 95% CI: 1.11-6.30). SVO was associated with increase waitlist mortality in patients with cirrhosis in the ambulatory setting awaiting liver transplantation. Concurrent loss of skeletal muscle and gain of adipose tissue seen in SVO quantified by CT may be a useful and objective measurement to identify patients at risk for suboptimal pretransplant outcomes.

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.

Frailty, mortality, and health care utilization after liver transplantation: From the Multicenter Functional Assessment in Liver Transplantation (FrAILT) Study.

BACKGROUND AND AIMS: Frailty is a well-established risk factor for poor outcomes in patients with cirrhosis awaiting liver transplantation (LT), but whether it predicts outcomes among those who have undergone LT is unknown. APPROACH AND RESULTS: Adult LT recipients from 8 US centers (2012-2019) were included. Pre-LT frailty was assessed in the ambulatory setting using the Liver Frailty Index (LFI). "Frail" was defined by an optimal cut point of LFI ≥ 4.5. We used the 75th percentile to define "prolonged" post-LT length of stay (LOS; ≥12 days), intensive care unit (ICU) days (≥4 days), and inpatient days within 90 post-LT days (≥17 days). Of 1166 LT recipients, 21% were frail pre-LT. Cumulative incidence of death at 1 and 5 years was 6% and 16% for frail and 4% and 10% for nonfrail patients (overall log-rank p = 0.02). Pre-LT frailty was associated with an unadjusted 62% increased risk of post-LT mortality (95% CI, 1.08-2.44); after adjustment for body mass index, HCC, donor age, and donation after cardiac death status, the HR was 2.13 (95% CI, 1.39-3.26). Patients who were frail versus nonfrail experienced a higher adjusted odds of prolonged LT LOS (OR, 2.00; 95% CI, 1.47-2.73), ICU stay (OR, 1.56; 95% CI, 1.12-2.14), inpatient days within 90 post-LT days (OR, 1.72; 95% CI, 1.25-2.37), and nonhome discharge (OR, 2.50; 95% CI, 1.58-3.97). CONCLUSIONS: Compared with nonfrail patients, frail LT recipients had a higher risk of post-LT death and greater post-LT health care utilization, although overall post-LT survival was acceptable. These data lay the foundation to investigate whether targeting pre-LT frailty will improve post-LT outcomes and reduce resource utilization.

Cirrhosis Inpatients Receive More Opioids and Fewer Nonopioid Analgesics Than Patients Without Cirrhosis.

GOALS/BACKGROUND: Pain is common among cirrhosis patients, particularly those hospitalized with acute illness. Managing pain in this population is challenging due to concern for adverse events and lack of guidelines for analgesic use. We sought to characterize analgesic use among inpatients with cirrhosis compared with matched noncirrhosis controls, as well as hospital-level variation in prescribing patterns. METHODS: We utilized the Vizient Clinical Database, which includes clinical and billing data from hospitalizations at >500 US academic medical centers. We identified cirrhosis patients hospitalized in 2017-2018, and a matched cohort of noncirrhosis patients. Types of analgesic given-acetaminophen (APAP), nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and adjuvants (eg, gabapentinoids, antidepressants) were defined from inpatient prescription records. Conditional logistic regression was used to associate cirrhosis diagnosis with analgesic use. RESULTS: Of 116,363 cirrhosis inpatients, 83% received at least 1 dose of an analgesic and 58% had regular inpatient analgesic use, rates that were clinically similar to noncirrhosis controls. Cirrhosis inpatients were half as likely to receive APAP (26% vs. 42%, P <0.01) or NSAIDs (3% vs. 7%, P <0.01), but were more likely to receive opioids (59% vs. 54%, P <0.01), particularly decompensated patients (60%). There was notable variation in analgesic prescribing patterns between hospitals, especially among cirrhosis patients. CONCLUSIONS: Analgesic use was common among inpatients, with similar rates among patients with and without cirrhosis. Cirrhosis patients-particularly decompensated patients-were less likely to receive APAP and NSAIDs and more likely to receive opioid analgesics. Because of lack of evidence-based guidance for management of cirrhosis patients with pain, providers may avoid nonopioid analgesics due to perceived risks and consequently may overutilize opioids in this high-risk population.

Sarcopenic visceral obesity is associated with increased post-liver transplant mortality in acutely ill patients with cirrhosis.

"Sarcopenic obesity" refers to a condition of low muscle mass in the context of obesity, though may be difficult to assess in patients with cirrhosis who are acutely ill. We aimed to define sarcopenic visceral obesity (SVO) using CT-based skeletal muscle index (SMI) and visceral-to-subcutaneous adipose tissue ratio (VSR) to examine its association with post-transplant mortality. We analyzed 116 adult inpatients with cirrhosis who were urgently listed and transplanted between 1/2005 and 12/2017 at 4 North American transplant centers. SVO was defined as patients with sarcopenia (SMI <50 cm2 /m2 in men and <39 cm2 /m2 in women) and visceral obesity (VSR ≥ 1.54 in men and ≥1.37 in women). The percentage who met criteria for sarcopenia, visceral obesity, and SVO were 45%, 42%, and 20%, respectively. Cumulative rates of post-transplant mortality were higher in patients with SVO compared to patients with sarcopenia or visceral obesity alone at 36 months (39% vs. 14% vs. 8%) [logrank p = .01]. In univariable regression, SVO was associated with post-transplant mortality (HR 2.92, 95%CI 1.04-8.23) and remained significant after adjusting for age, sex, diabetes, encephalopathy, hepatocellular carcinoma, and MELD-Na (HR 3.50, 95%CI 1.10-11.15). In conclusion, SVO is associated with increased post-transplant mortality in acutely ill patients with cirrhosis.

The 21-Gene Recurrence Score in Clinically High-Risk Lobular and Ductal Breast Cancer: A National Cancer Database Study.

OBJECTIVE: The aim of this study was to evaluate whether patients with invasive lobular carcinoma (ILC) are more likely to have discordant clinical and genomic risk than those with invasive ductal carcinoma (IDC) when using the 21-gene recurrence score (RS), and to assess overall survival outcomes of patients with 1-3 positive nodes and RS ≤25 with and without chemotherapy, stratified by histology. METHODS: We performed a cohort study using the National Cancer Database and included patients with hormone receptor-positive, HER2-negative, stage I-III invasive breast cancer who underwent 21-gene RS testing. Our primary outcome was rate of discordant clinical and genomic risk status by histologic subtype. Propensity score matching was used to compare 60-month overall survival in individuals with 1-3 positive nodes and RS ≤25 who did and did not receive chemotherapy. RESULTS: Overall, 186,867 patients were included in our analysis, including 37,685 (20.2%) patients with ILC. There was a significantly higher rate of discordant clinical and genomic risk in patients with ILC compared with IDC. Among patients with 1-3 positive nodes and RS ≤25, there was no significant difference in survival between those who did and did not receive chemotherapy in the IDC or ILC cohorts. Unadjusted exploratory analyses of patients under age 50 years with 1-3 positive nodes and RS ≤25 showed improved overall survival in IDC patients who received chemotherapy, but not among those with ILC. CONCLUSION: Our findings highlight the importance of lobular-specific tools for stratifying clinical and genomic risk, as well as the need for histologic subtype-specific analyses in randomized trials.

Consent to organ offers from public health service "Increased Risk" donors decreases time to transplant and waitlist mortality.

BACKGROUND: The Public Health Service Increased Risk designation identified organ donors at increased risk of transmitting hepatitis B, hepatitis C, and human immunodeficiency virus. Despite clear data demonstrating a low absolute risk of disease transmission from these donors, patients are hesitant to consent to receiving organs from these donors. We hypothesize that patients who consent to receiving offers from these donors have decreased time to transplant and decreased waitlist mortality. METHODS: We performed a single-center retrospective review of all-comers waitlisted for liver transplant from 2013 to 2019. The three competing risk events (transplant, death, and removal from transplant list) were analyzed. 1603 patients were included, of which 1244 (77.6%) consented to offers from increased risk donors. RESULTS: Compared to those who did not consent, those who did had 2.3 times the rate of transplant (SHR 2.29, 95% CI 1.88-2.79, p < 0.0001), with a median time to transplant of 11 months versus 14 months (p < 0.0001), as well as a 44% decrease in the rate of death on the waitlist (SHR 0.56, 95% CI 0.42-0.74, p < 0.0001). All findings remained significant after controlling for the recipient age, race, gender, blood type, and MELD. Of those who did not consent, 63/359 (17.5%) received a transplant, all of which were from standard criteria donors, and of those who did consent, 615/1244 (49.4%) received a transplant, of which 183/615 (29.8%) were from increased risk donors. CONCLUSIONS: The findings of decreased rates of transplantation and increased risk of death on the waiting list by patients who were unwilling to accept risks of viral transmission of 1/300-1/1000 in the worst case scenarios suggests that this consent process may be harmful especially when involving "trigger" words such as HIV. The rigor of the consent process for the use of these organs was recently changed but a broader discussion about informed consent in similar situations is important.

Weight loss does not decrease risk of breast cancer-related arm lymphedema.

BACKGROUND: The goal of this study was to determine the relationship between postoperative weight change and breast cancer-related lymphedema (BCRL). METHODS: In this cohort study, 1161 women underwent unilateral breast surgery for breast cancer from 2005 to 2020 and were prospectively screened for BCRL. Arm volume measurements were obtained via an optoelectronic perometer preoperatively, postoperatively, and in the follow-up setting every 6 to 12 months. Mean follow-up from preoperative baseline was 49.1 months. The main outcome was BCRL, defined as a relative volume change of the ipsilateral arm of ≥10% at least 3 months after surgery. RESULTS: A total of 92 patients (7.9%) developed BCRL. Net weight loss versus net weight gain from baseline to last follow-up was not protective against developing BCRL (hazard ratio, 1.38; 95% confidence interval, 0.89-2.13; P = .152). CONCLUSIONS: Although weight loss may be recommended as part of an individualized lifestyle management program for overall health, weight loss alone may not decrease the risk of developing BCRL.

Subclinical Lymphedema After Treatment for Breast Cancer: Risk of Progression and Considerations for Early Intervention.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a devastating complication of breast cancer (BC) treatment. The authors hypothesized that identifying subclinical lymphedema (SCL) presents an opportunity to prevent BCRL development. They aimed to assess rates of SCL progression (relative volume change [RVC], 5-10%) to BCRL (RVC, ≥10%) in women undergoing axillary surgery for BC via axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB). METHODS: Patients treated for BC were prospectively screened at preoperative baseline and throughout the follow-up period using the perometer. The cohort was stratified according to nodal surgery (ALND or SLNB) to analyze rates of progression to BCRL. RESULTS: The study cohort included 1790 patients. Of the 1359 patients who underwent SLNB, 331 (24.4%) experienced SCL, with 38 (11.5%) of these patients progressing to BCRL. Of the 431 patients who underwent ALND, 171 (39.7%) experienced SCL, with 67 (39.2%) of these patients progressing to BCRL. Relative to the patients without SCL, those more likely to experience BCRL were the ALND patients with early SCL (< 3 months postoperatively; hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.58-4.27; p = 0.0002) or late SCL (≥3 months postoperatively; HR, 3.14; 95% CI, 1.95-5.05; p < 0.0001) and the SLNB patients with early SCL (HR, 6.75; 95% CI, 3.8-11.98; p < 0.0001 or late SCL (HR, 3.02; 95% CI, 1.65-5.50; p = 0.0003). CONCLUSION: The study suggests that patients with SCL after axillary nodal surgery for BC are more likely to progress to BCRL than those who do not experience SCL. This presents a tremendous opportunity for early intervention to prevent BCRL and improve the quality of life for women treated for BC.

Sex differences in scores on standardized measures of autism symptoms: a multisite integrative data analysis.

BACKGROUND: Concerns have been raised that scores on standard measures of autism spectrum disorder (ASD) symptoms may differ as a function of sex. However, these findings are hindered by small female samples studied thus far. The current study evaluated if, after accounting for age, IQ, and language level, sex affects ASD severity estimates from diagnostic measures among children with ASD. METHODS: Data were obtained from eight sources comprising 27 sites. Linear mixed-effects models, including a random effect for site, were fit for 10 outcomes (Autism Diagnostic Observation Schedule [ADOS] domain-level calibrated severity scores, Autism Diagnostic Interview-Revised [ADI-R] raw scores by age-based algorithm, and raw scores from the two indices on the Social Responsiveness Scale [SRS]). Sex was added to the models after controlling for age, NVIQ, and an indicator for language level. RESULTS: Sex significantly improved model fit for half of the outcomes, but least square mean differences were generally negligible (effect sizes [ES] < 0.20), increasing to small to moderate in adolescence (ES < 0.40). Boys received more severe RRB scores than girls on both the ADOS and ADI-R (age 4 + algorithm), and girls received more severe scores than boys on both SRS indices, which emerged in adolescence. CONCLUSIONS: This study combined several available databases to create the largest sample of girls with ASD diagnoses. We found minimal differences due to sex beyond other known influences on ASD severity indicators. This may suggest that, among children who ultimately receive a clinical ASD diagnosis, severity estimates do not systematically differ to such an extent that sex-specific scoring procedures would be necessary. However, given the limitations inherent in clinically ascertained samples, future research must address questions about systematic sex differences among children or adults who do not receive clinical diagnoses of ASD. Moreover, while the current study helps resolve questions about widely used diagnostic instruments, we could not address sex differences in phenotypic aspects outside of these scores.