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Background. Cardiovascular disease and physical decline are prevalent and associated with morbidity/mortality in liver transplant (LT) patients. Cardiopulmonary exercise testing (CPX) provides comprehensive cardiopulmonary and exercise response assessments. We investigated cardiorespiratory fitness (CRF) and cardiac stress generated during CPX in LT candidates. Methods. LT candidates at 2 centers underwent CPX. Standard-of-care cardiac stress testing (dobutamine stress echocardiography, DSE) results were recorded. Physical function was assessed with liver frailty index and 6-min walk test. CPX/DSE double products were calculated to quantify cardiac stress. To better study the association of CPX-derived metrics with physical function, the cohort was divided into 2 groups based on 6-min walk test median (372 m). Results. Fifty-four participants (62 ± 8 y; 65% men, Model for End-Stage Liver Disease-Na 14 [10–18]) underwent CPX. Peak oxygen consumption was 14.1 mL/kg/min for an anerobic threshold of 10.2 mL/kg/min, with further CRF decline in the lower 6MWT cohort despite lack of liver frailty index-frailty in 90%. DSE was nondiagnostic in 18% versus 4% of CPX (P = 0.058). All CPX were negative for ischemia. A double product of ≥25 000 was observed in 32% of CPX and 11% of DSE (P = 0.020). Respiratory function testing was normal. No patient presented major cardiovascular events at 30 d post-LT. Conclusions. CPX provided efficient and effective combined cardiopulmonary risk and frailty assessments of LT candidates in a 1-stop test. The CRF was found to be very low despite preserved physical function or lack of frailty.

Abstract INTRODUCTION Poorer baseline functioning is associated with long‐term cognitive decline among Hispanic older adults, but little is known about associations of these factors with Alzheimer's disease (AD) neuroimaging biomarkers. METHODS A total of 461 Hispanic and White non‐Hispanic (NHW) older adults who are cognitively normal (n = 76), had impaired cognition without mild cognitive impairment (MCI) (n = 41), or carried a diagnosis of MCI (n = 253) or dementia (n = 91) completed neuropsychological and functional assessment, genetic testing, and brain magnetic resonance imaging (MRI). Structural equation modeling (SEM) was used to examine predictive associations between functional and cognitive measures of AD neuroimaging biomarkers. RESULTS MRI volumes significantly predicted functional limitations in both groups. Sex and amyloid load significantly predicted functional limitations among the Hispanic group only. Years of education and MRI regional volume were the strongest predictors of cognition among both groups. DISCUSSION Results indicate that functional performance is associated with early AD biomarkers among Hispanic older adults. Clinical implications are discussed. Highlights The current study addresses health disparities in Alzheimer's disease (AD) and related dementia assessment among Hispanics by identifying measures sensitive to early AD biomarkers. Associations of functional measures with AD genetic and neuroimaging biomarkers revealed that similarities in these associations exist between Hispanic and White non‐Hispanic individuals, but biological sex and amyloid load significantly predicted functional limitations among the Hispanic group only. These results have clinical implications for physicians who treat Hispanic AD patients and indicate that when compared to traditional diagnostic assessments, functional assessments may better aid in AD diagnostic precision among Hispanics.

Introduction and Objectives: Sarcopenia is a common complication of end-stage liver disease (ESLD), but its exact relationship to myosteatosis and frailty remains unclear. In this pilot study, we tested the feasibility of a specialized MRI protocol and automated image analysis in patients with ESLD. Materials and Methods: In a single-center prospective study, adult liver transplant candidates with ESLD underwent assessment of muscle composition between 3/2022 and 6/2022 using the AMRA® MAsS Scan. The primary outcome of interest was feasibility of the novel MRI technique in patients with ESLD. We also tested if thigh muscle composition correlated with validated measures of frailty and sarcopenia. Results: Eighteen subjects (71 % male, mean age 59 years) were enrolled. The most common etiologies of cirrhosis were alcohol-related liver disease (44 %) and non-alcohol-associated fatty liver disease (33 %), with a mean MELD-Na of 13 (± 4). The mean time needed to complete the MRI protocol was 14.9 min and only one patient could not complete it due to metal hardware in both knees. Forty-one percent of patients had adverse muscle composition (high thigh fat infiltration and low-fat free muscle volume) and these patients were more likely to have undergone a recent large volume paracentesis (43 % vs. 0 %, p < 0.02). The adverse muscle composition group performed significantly worse on the 6-minute walk test compared to the remainder of the cohort (379 vs 470 m, p < 0.01). Conclusions: The AMRA® MAsS Scan is feasible to perform in patients with ESLD and can be used to quantify myosteatosis, a marker of muscle quality and potentially muscle functionality in ESLD.

Abstract Although liver transplantation (LT) is an effective therapy for cirrhosis, the risk of post-LT NASH is alarmingly high and is associated with accelerated progression to fibrosis/cirrhosis, cardiovascular disease and decreased survival. Lack of risk stratification strategies hampers early intervention against development of post-LT NASH fibrosis. The liver undergoes significant remodeling during inflammatory injury. During such remodeling, degraded peptide fragments (i.e., ‘degradome’) of the ECM and other proteins increase in plasma, making it a useful diagnostic/prognostic tool in chronic liver disease. To investigate whether liver injury caused by post-LT NASH would yield a unique degradome profile that is predictive of severe post-LT NASH fibrosis, a retrospective analysis of 22 biobanked samples from the Starzl Transplantation Institute (12 with post-LT NASH after 5 years and 10 without) was performed. Total plasma peptides were isolated and analyzed by 1D-LC–MS/MS analysis using a Proxeon EASY-nLC 1000 UHPLC and nanoelectrospray ionization into an Orbitrap Elite mass spectrometer. Qualitative and quantitative peptide features data were developed from MSn datasets using PEAKS Studio X (v10). LC–MS/MS yielded ~ 2700 identifiable peptide features based on the results from Peaks Studio analysis. Several peptides were significantly altered in patients that later developed fibrosis and heatmap analysis of the top 25 most significantly changed peptides, most of which were ECM-derived, clustered the 2 patient groups well. Supervised modeling of the dataset indicated that a fraction of the total peptide signal (~ 15%) could explain the differences between the groups, indicating a strong potential for representative biomarker selection. A similar degradome profile was observed when the plasma degradome patterns were compared being obesity sensitive (C57Bl6/J) and insensitive (AJ) mouse strains. The plasma degradome profile of post-LT patients yielded stark difference based on later development of post-LT NASH fibrosis. This approach could yield new “fingerprints” that can serve as minimally-invasive biomarkers of negative outcomes post-LT.

Summary: Background: The prevalence and impact of alcohol withdrawal syndrome (AWS) in patients with alcohol-associated hepatitis (AH) are unknown. In this study, we aimed to investigate the prevalence, predictors, management, and clinical impact of AWS in patients hospitalized with AH. Methods: A multinational, retrospective cohort study enrolling patients hospitalized with AH at 5 medical centres in Spain and in the USA was performed between January 1st, 2016 to January 31st, 2021. Data were retrospectively retrieved from electronic health records. Diagnosis of AWS was based on clinical criteria and use of sedatives to control AWS symptoms. The primary outcome was mortality. Multivariable models controlling for demographic variables and disease severity were performed to determine predictors of AWS (adjusted odds ratio [OR]) and the impact of AWS condition and management on clinical outcomes (adjusted hazard ratio [HR]). Findings: In total, 432 patients were included. The median MELD score at admission was 21.9 (18.3–27.3). The overall prevalence of AWS was 32%. Lower platelet levels (OR = 1.61, 95% CI 1.05–2.48) and previous history of AWS (OR = 2.09, 95% CI 1.31–3.33) were associated with a higher rate of incident AWS, whereas the use of prophylaxis decreased the risk (OR = 0.58, 95% CI 0.36–0.93). The use of intravenous benzodiazepines (HR = 2.18, 95% CI 1.02–4.64) and phenobarbital (HR = 2.99, 95% CI 1.07–8.37) for AWS treatment were independently associated with a higher mortality. The development of AWS increased the rate of infections (OR = 2.24, 95% CI 1.44–3.49), the need for mechanical ventilation (OR = 2.49, 95% CI 1.38–4.49), and ICU admission (OR = 1.96, 95% CI 1.19–3.23). Finally, AWS was associated with higher 28-day (HR = 2.31, 95% CI 1.40–3.82), 90-day (HR = 1.78, 95% CI 1.18–2.69), and 180-day mortality (HR = 1.54, 95% CI 1.06–2.24). Interpretation: AWS commonly occurs in patients hospitalized with AH and complicates the hospitalization course. Routine prophylaxis is associated with a lower prevalence of AWS. Prospective studies should determine diagnostic criteria and prophylaxis regimens for AWS management in patients with AH. Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Acute kidney injury (AKI) and frailty are major drivers of outcomes among patients with cirrhosis. What is unknown is the impact of physical frailty on the development of AKI. We included adults with cirrhosis without hepatocellular carcinoma listed for liver transplantation at nine US centers (n = 1,033). Frailty was assessed using the Liver Frailty Index (LFI); “frail” was defined by LFI ≥ 4.2. Chronic kidney disease as a baseline estimated glomerular filtration rate

Physical frailty and impaired cognition are common in patients with cirrhosis. Physical frailty can be assessed using performance‐based tests, but the extent to which impaired cognition may impact performance is not well characterized. We assessed the relationship between impaired cognition and physical frailty in patients with cirrhosis. We enrolled 1,623 ambulatory adult patients with cirrhosis waiting for liver transplantation at 10 sites. Frailty was assessed with the liver frailty index (LFI; “frail,” LFI ≥ 4.4). Cognition was assessed at the same visit with the number connection test (NCT); continuous “impaired cognition” was examined in primary analysis, with longer NCT (more seconds) indicating worse impaired cognition. For descriptive statistics, “impaired cognition” was NCT ≥ 45 seconds. Linear regression associated frailty and impaired cognition; competing risk regression estimated subhazard ratios (sHRs) of wait‐list mortality (i.e., death/delisting for sickness). Median NCT was 41 seconds, and 42% had impaired cognition. Median LFI (4.2 vs. 3.8) and rates of frailty (38% vs. 20%) differed between those with and without impaired cognition. In adjusted analysis, every 10‐second NCT increase associated with a 0.08‐LFI increase (95% confidence interval [CI], 0.07‐0.10). In univariable analysis, both frailty (sHR, 1.63; 95% CI, 1.43‐1.87) and impaired cognition (sHR, 1.07; 95% CI, 1.04‐1.10) associated with wait‐list mortality. After adjustment, frailty but not impaired cognition remained significantly associated with wait‐list mortality (sHR, 1.55; 95% CI, 1.33‐1.79). Impaired cognition mediated 7.4% (95% CI, 2.0%‐16.4%) of the total effect of frailty on 1‐year wait‐list mortality. Conclusion: Patients with cirrhosis with higher impaired cognition displayed higher rates of physical frailty, yet frailty independently associated with wait‐list mortality while impaired cognition did not. Our data provide evidence for using the LFI to understand mortality risk in patients with cirrhosis, even when concurrent impaired cognition varies.

Introduction: Loneliness, “a subjective feeling of being isolated”, is a strong predictor of adverse health. We characterized loneliness in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT). Methods: We surveyed loneliness in ambulatory ESLD adults awaiting LT at 7 U.S. sites using the validated UCLA Three-Item Loneliness Scale, May2020-Jan2021; “lonely”=total ≥5. Liver Frailty Index (LFI) assessed frailty; “frail”=LFI≥4.4. Logistic regression associated loneliness and co-variables. Results: Of 454 participants, median MELDNa was 14 (IQR 10-19) and 26% met criteria for “lonely”. Compared to those not lonely, those lonely were younger (57 v. 61y), more likely to be female (48% v. 31%) or frail (21 v. 11%), and less likely to be working (15% v. 26%) or in a committed partnership (52% v. 71%). After multivariable adjustment, frailty (OR=2.24, 95%CI=1.23-4.08), younger age (OR=1.19, 95%CI=1.07-1.34), female sex (OR=1.83, 95%CI=1.14-2.92), not working (OR=2.16, 95%CI=1.16-4.03), and not in a committed partnership (OR=2.07, 95%CI=1.29-3.32) remained significantly associated with higher odds of loneliness. Conclusion: Loneliness is prevalent in adults awaiting LT, and independently associated with younger age, female sex and physical frailty. These data lay the foundation to investigate the extent to which loneliness impacts health outcomes in LT, as in the general population.Clinical Trial Registry Website: https://clinicaltrials.gov Trial Number: NCT03228290

Background. The COVID-19 pandemic has limited liver transplant (LT) candidates access to clinics. Telehealth methods to assess frailty are needed. We developed a method to estimate the step length of LT candidates, which would permit remotely obtaining the 6-min walk test (6MWT) distance with a personal activity tracker (PAT). Methods. 6MWT was performed while candidates wore a PAT. On first 21 subjects (stride cohort), the step length was measured and compared with calculated one (6MWT-distance/6MWT steps). On a second cohort (PAT-6MWT; n = 116), we collected the 6MWT step count and used multivariable models to generate formulas estimating step length. We multiplied the estimated step length times 6MWT steps to estimate the distance and compared it to the measured distance. The liver frailty index (LFI) and 6MWT were used as frailty metrics. Results. Measured/calculated step length were highly correlated (ρ = 0.85; P

Abstract Objectives In the 2016 Peace Accord with the Fuerzas Armadas Revolucionarias de Colombia (FARC), Colombia promised to reincorporate 14,000 ex‐combatants into the healthcare system. However, FARC ex‐combatants have faced significant challenges in receiving healthcare, and little is known about physicians’ abilities to address this population's healthcare needs. Methods An electronic questionnaire sent to the Colombian Emergency Medicine professional society and teaching hospitals assessed physicians’ knowledge, attitudes, and experiences with the FARC ex‐combatant reincorporation process. Results Among 53 participants, most were male (60.4%), and ∼25% were affected by the FARC conflict (22.6%). Overall knowledge of FARC reincorporation was low, with nearly two‐thirds of participants (61.6%) scoring in the lowest category. Attitudes around ex‐combatants showed low bias. Few physicians received training about reincorporation (7.5%), but 83% indicated they would like such training. Twenty‐two participants (41.5%) had identified a patient as an ex‐combatant in the healthcare setting. Higher knowledge scores were significantly correlated with training about reincorporation (r = 0.354, n = 53, P = 0.015), and experience identifying patients as ex‐combatants (r = 0.356, n = 47, P = 0.014). Conclusion Findings suggested high interest in training and low knowledge of the reincorporation process. Most physicians had low bias, frequent experiences with ex‐combatants, and cared for these patients when they self‐identify. The emergency department (ED) serves as an entrance into healthcare for this population and a potential setting for interventions to improve care delivery, especially those related to mental healthcare. Future studies could evaluate effects of care delivery following training on ex‐combatant healthcare reintegration.

Introduction Globally, medical students have demonstrated knowledge gaps in emergency care and acute stabilization. In Colombia, new graduates provide care for vulnerable populations. The World Health Organization (WHO) Basic Emergency Care (BEC) course trains frontline providers with limited resources in the management of acute illness and injury. While this course may serve medical students as adjunct to current curriculum, its utility in this learner group has not been investigated. This study performs a baseline assessment of knowledge and confidence in emergency management taught in the BEC amongst medical students in Colombia. Methods A validated, cross-sectional survey assessing knowledge and confidence of emergency care congruent with BEC content was electronically administered to graduating medical students across Colombia. Knowledge was evaluated via 15 multiple choice questions and confidence via 13 questions using 100 mm visual analog scales. Mean knowledge and confidence scores were compared across demographics, geography and prior training using Chi-Squared or one-way ANOVA analyses. Results Data were gathered from 468 graduating medical students at 36 institutions. The mean knowledge score was 59.9% ± 23% (95% CI 57.8–62.0%); the mean confidence score was 59.6 mm ±16.7 mm (95% CI 58.1–61.2). Increasing knowledge and confidence scores were associated with prior completion of emergency management training courses (pConclusion Knowledge and confidence levels of emergency care management for graduating medical students across Colombia demonstrated room for additional, specialized training. Higher scores were seen in groups that had completed emergency care courses. Implementation of the BEC as an adjunct to current curriculum may serve a valuable addition.

Alcoholic hepatitis is the severest clinical presentation of alcoholic liver disease. Lacking an effective pharmacologic treatment, alcoholic hepatitis is associated with a poor prognosis and its recovery relies mostly on abstinence. With alcohol use disorder being universally on the rise, the impact of alcoholic hepatitis on society and health-care costs is expected to increase significantly. Prognostic factors and liver biopsy can help with timely diagnosis, to determine eligibility and response to corticosteroids, and for prognostication and transplant referral. Although recent discoveries in the pathophysiology of alcoholic hepatitis are encouraging and could pave the way for novel treatment modalities, a multidisciplinary approach considering timely identification and treatment of liver-related complications, infectious and metabolic disease, malnutrition, and addiction counseling should be emphasized. Apart from proper selection of candidates, transplant programs should provide adequate post-transplant addiction support in order to make of early liver transplantation for alcoholic hepatitis the ultimate sobering experience in the next decade.

Background and aims. Practitioners treating hepatitis C (HCV) provide healthcare to a special population with high rates of substance abuse and psychiatric disorders. We investigated the psychosocial profile in HCV patients and tested what variables affect commencement of antiviral therapy.Material and methods. Recreational drug use (RDU), marijuana (THC), alcohol use, and psychiatric history were initially investigated with a questionnaire prior to history and physical. Following an educational intervention, we reinterrogated patients for RDU and THC use, and revision of initial statement was documented. Variables affecting commencement of antiviral therapy were analysed with logistic regression.Results. Out of 153 patients, 140 (92%) answered the questionnaire. Intervention increased total yield by 6%, however, 39% (11/28) of those initially denying use revised their statement. Drug screening identified 9 more patients with RDU/THC use. Half of patients consuming alcohol were heavy drinkers, and psychiatric disease was identified in 54%. Only 73 (48%) of 139 patients eligible for antivirals received treatment. Multivariable analysis revealed that younger patients (OR = 1.04, 95% CI 1.01-1.08), and those testing positive on drug screen (OR = 0.41, 95% CI 0.19-0.92) were less likely to be treated. Denial by insurance and loss to follow-up were the most common reasons for not starting antiviral treatment.Conclusion. Substance abuse is highly prevalent among HCV patients, and it is difficult to tell prior from current users. Integral care of HCV patients should include a diligent screen for substance abuse and rehabilitation referral, aiming to increase the pool of patients eligible for antiviral therapy. This can only be achieved through a multidisciplinary approach.

Hepatitis B virus (HBV) reactivation is a well-established complication of severe immunosuppression in patients with hematologic malignancy and positive hepatitis B surface antigen (HBsAg). Patients who receive high-dose chemotherapy, corticosteroids, rituximab, or have a bone marrow transplant are particularly at increased risk for HBV reactivation. However, limited information is available in the literature regarding HBV reactivation in patients with isolated anti-HBc, particularly in the setting of multiple myeloma (MM). We report two cases of HBV reactivation in MM patients with isolated anti-HBc positive with a rather atypical presentation. In conclusion, our cases highlight that clinicians need to be cognizant about this potentially fatal but preventable complication of chemotherapy and immunosuppression.

Liver disease and portal hypertension can be associated with pulmonary vascular complications, including portopulmonary hypertension (POPH), characterised by an elevated mean pulmonary artery pressure secondary to an increased pulmonary vascular resistance, and hepatopulmonary syndrome (HPS), characterised by hypoxaemia due to pulmonary vasodilatation and shunting. Although clear diagnostic guidelines exist for both conditions on the basis of echocardiography, right heart catheterisation and arterial blood gases, there is considerable variation between centres regarding diagnosis and management of these conditions. Awareness of evaluation and management algorithms for POPH and HPS are critical for optimisation of outcomes in patients with these conditions. Key aspects of management of POPH and HPS include identification of patients likely to benefit from liver transplantation (LTx) and management before and after LTx. Although both disorders may improve after LTx, severe forms of POPH represent a contraindication to LTx. Novel approaches to the treatment of POPH and HPS offer new management options that may expand the pool of transplantable patients and improve overall outcomes.