IL-1R1 and IL-18 Signals Regulate Mesenchymal Stromal Cells in an Aged Murine Model of Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) are age-related diseases characterized by bone marrow (BM) dysfunction and an increased risk of developing acute leukemia. While there is growing evidence highlighting the crucial role of the BM microenvironment (BMME) in MDS, the specific influence of inflammation on BMME changes, as well as the potential benefits of targeting cytokines therapeutically, remain to be elucidated. We previously found interleukin-1 (IL-1) to be a driver of aging phenotypes of BMME and hematopoietic stem and progenitor cells (HSPCs).

ENHANCEMENT OF CIRRHOSIS MORTALITY PREDICTION BY INCLUDING HEPATIC ENCEPHALOPATHY TO MELD3.0 IN A NATIONAL VETERAN COHORT.

Despite negative outcomes, hepatic encephalopathy (HE) is not included in model-for-end-stage liver disease (MELD) scores, including MELD3.0. In a national Veterans affairs (VA) database, we studied the additive mortality predictive impact of a documented inpatient overt HE diagnosis on MELD3.

Microbiota transplant for hepatic encephalopathy in cirrhosis: The THEMATIC trial.

Background: Preventing hepatic encephalopathy (HE) recurrence in cirrhosis, which is associated with an altered gut-liver-brain axis, is an unmet need. Fecal microbiota transplantation (FMT) is beneficial in phase-1 studies, but route and dose-related questions remain.

Methods: We performed a phase-2 randomized, placebo-controlled, double-blind, clinical trial of capsule and enema FMT in cirrhosis and HE on lactulose and rifaximin.

Identifying and treating metabolic dysfunction-associated steatotic liver disease among at-risk Veterans.

Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD), an increasing public health concern, remains challenging to diagnose and risk-stratify. We assessed the 1) prevalence of MASLD risk factors among Veterans in Veterans Health Administration (VA) care, 2) factors associated with MASLD diagnosis; and 3) associations between MASLD diagnosis and receipt of care.

Methods: Veterans with MASLD risk factors, including obesity, pre-diabetes, diabetes, or dyslipidemia, were identified using International Classification of Diseases-10 codes and followed in 2019-2022.

Interaction of the Gut-Liver-Brain Axis and the sterolbiome with sexual dysfunction in patients with cirrhosis.

There is a complex interplay between the gut microbes, liver, and central nervous system, a gut-liver-brain axis, where the brain impacts intestinal and hepatic function while the gut and liver can impact cognition and mental status. Dysregulation of this axis can be seen in numerous diseases. Hepatic encephalopathy, a consequence of cirrhosis, is perhaps the best studied perturbation of this system.

A novel sweat sensor detects inflammatory differential rhythmicity patterns in inpatients and outpatients with cirrhosis.

Patients with cirrhosis have high systemic inflammation (TNFα, CRP, and IL-6) that is associated with poor outcomes. These biomarkers need continuous non-invasive monitoring, which is difficult with blood. We studied the AWARE sweat-sensor to measure these in passively expressed sweat in healthy people (N = 12) and cirrhosis (N = 32, 10 outpatients/22 inpatients) for 3 days.

International consensus statement on microbiome testing in clinical practice.

There is growing interest in the potential exploitation of the gut microbiome as a diagnostic tool in medicine, but evidence supporting its clinical usefulness is scarce. An increasing number of commercial providers offer direct-to-consumer microbiome diagnostic tests without any consensus on their regulation or any proven value in clinical practice, which could result in considerable waste of individual and health-care resources and potential drawbacks in the clinical management of patients. We convened an international multidisciplinary expert panel to standardise best practices of microbiome testing for clinical implementation, including recommendations on general principles and minimum requirements for their provision, indications, pre-testing protocols, method of analyses, reporting of results, and potential clinical value.

The burden of hepatic encephalopathy and the use of albumin as a potential treatment.

As a potential sequela of cirrhosis, hepatic encephalopathy (HE) significantly impacts the lives of patients and caregivers and places a substantial burden on the healthcare system. With an increasing incidence over time and a cumulative effect on cognition, HE adversely effects quality of life, morbidity and mortality in patients with cirrhosis. HE can range from minimal or covert (MHE/CHE) to overt and symptomatic (OHE).

Microbiome-Centered Therapies for the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant global health issue, affecting over 30% of the population worldwide due to the rising prevalence of metabolic risk factors such as obesity and type 2 diabetes mellitus (T2DM). This spectrum of liver disease ranges from isolated steatosis to more severe forms such as steatohepatitis, fibrosis, and cirrhosis. Recent studies highlight the role of gut microbiota in MASLD pathogenesis, showing that dysbiosis significantly impacts metabolic health and the progression of liver disease.

Sex Differences in Patient-Reported Outcomes and Perception of Ascites Burden Among Outpatients With Decompensated Cirrhosis and Ascites.

Introduction: Perception of the ascites burden and its effects on quality of life may be different between sexes. This study assessed sex differences in perception of ascites burden and its impact on health-related quality of life (HRQoL) in patients with recurrent or refractory ascites.

Methods: The North American Consortium for the Study of End-stage Liver Disease prospectively enrolled outpatients with cirrhosis and large ascites requiring repeat large volume paracenteses.

Present and future of fecal microbiome transplantation in cirrhosis.

Over the last few decades, there have been tremendous advances in our understanding of the role of the gut microbiome in cirrhosis and the clinical sequelae that follow. Progressive dysbiosis and immune dysregulation occur in patients with cirrhosis. In fact, alterations in the gut microbiome occur long before a diagnosis of cirrhosis is made.

Tobacco use, cirrhosis, and age are predictors of readiness to change and continued drinking following brief alcohol intervention in veterans.

Alcohol use disorder is prevalent within the Veterans Health System, especially in patients being seen in hepatology clinics, and needs a point-of-care strategy. A brief alcohol intervention based on AUDIT-C (Alcohol Use Disorders Identification Test) may be needed for the management of hazardous alcohol intake, but feasibility is unclear. We aimed to define predictors of readiness to cease alcohol intake (0-10, 10 being ready to quit now) and continued drinking after using a brief alcohol intervention in veterans seen in hepatology clinics cross-sectionally and longitudinally over 6 months.

Stereotactic radiofrequency lesioning of caudal zona incerta for parkinsonian tremor.

This video showcases stereotactic radiofrequency lesioning of the caudal zona incerta (CZi) for parkinsonian tremor in a 70-year-old patient. The preoperative evaluation, including imaging and frame placement, is detailed. The surgical procedure involves meticulous targeting and trajectory planning.

Referral to hepatology is lower in patients with excessive alcohol use who have mental health disorders despite a high fibrosis-4 index.

Background: Alcohol use disorder (AUD) is a multifaceted disease, and integration of AUD treatment between mental health and hepatology is necessary to improve outcomes. We aimed to ascertain whether patients with excessive alcohol use (EAU) and high FIB-4, which is a non-invasive method to identify advanced liver disease, are appropriately referred to hepatology and detect which clinical barriers, if any, might pertain.

Methods: Records of patients with excessive alcohol use between 2013 and 2023 were extracted from a large public system.

Beyond the Incision: A Comparative Study of Suprainguinal and Inguinal Varicocele Surgeries.

Background Varicocele, characterised by the abnormal dilation of the pampiniform plexus of scrotal veins, is a prevalent and treatable cause contributing to male infertility, affecting 40% of men experiencing primary infertility and 80% of those with secondary infertility. Often asymptomatic, it can lead to chronic scrotal pain or a feeling of heaviness. Surgical interventions such as open, laparoscopic, or microsurgical varicocelectomy aim to eliminate venous reflux into the scrotum.

Global prevalence and characteristics of infections and clinical outcomes in hospitalised patients with cirrhosis: a prospective cohort study for the CLEARED Consortium.

Background: Infections have a poor prognosis in inpatients with cirrhosis. We aimed to determine regional variations in infections and their association with clinical outcomes in a global cohort of inpatients with cirrhosis.

Methods: In this prospective cohort study initiated by the CLEARED Consortium, we enrolled adults (aged >18 years) with cirrhosis who were non-electively admitted to 98 hospitals from 26 countries or regions across six continents between Nov 5, 2021, and Dec 10, 2022.

Ultralow-dose irradiation enables engraftment and intravital tracking of disease initiating niches in clonal hematopoiesis.

Recent advances in imaging suggested that spatial organization of hematopoietic cells in their bone marrow microenvironment (niche) regulates cell expansion, governing progression, and leukemic transformation of hematological clonal disorders. However, our ability to interrogate the niche in pre-malignant conditions has been limited, as standard murine models of these diseases rely largely on transplantation of the mutant clones into conditioned mice where the marrow microenvironment is compromised. Here, we leveraged live-animal microscopy and ultralow dose whole body or focal irradiation to capture single cells and early expansion of benign/pre-malignant clones in the functionally preserved microenvironment.

Gut microbiome profiles to exclude the diagnosis of hepatic encephalopathy in patients with cirrhosis.

Patients with cirrhosis who have cognitive complaints are presumed to have hepatic encephalopathy (HE), which leads to unwarranted medications while ignoring the underlying disease process causing these complaints. Since neuropsychological testing, the current gold standard for HE diagnosis, is not readily available, an orderable test is needed. We aimed to develop and validate a rapid gut microbiota test to exclude HE and determine stakeholder input on this approach.