Diagnostic Yield of Endoscopic Ultrasound-Guided Liver Biopsy in Comparison to Percutaneous Liver Biopsy: A Meta-Analysis of Randomized Controlled Trials and Trial Sequential Analysis.

BACKGROUND: The efficacy of endoscopic ultrasound-guided liver biopsy (EUS-LB) compared to percutaneous liver biopsy (PC-LB) remains uncertain. METHODS: Our data consist of randomized controlled trials (RCTs) comparing EUS-LB to PC-LB, found through a literature search via PubMed/Medline and Embase. The primary outcome was sample adequacy, whereas secondary outcomes were longest and total lengths of tissue specimens, diagnostic accuracy, and number of complete portal tracts (CPTs). RESULTS: Sample adequacy did not significantly differ between EUS-LB and PC-LB (risk ratio [RR] 1.18; 95% confidence interval [CI] 0.58-2.38; p = 0.65), with very low evidence quality and inadequate sample size as per trial sequential analysis (TSA). The two techniques were equivalent with respect to diagnostic accuracy (RR: 1; CI: 0.95-1.05; p = 0.88), mean number of complete portal tracts (mean difference: 2.29, -4.08 to 8.66; p = 0.48), and total specimen length (mean difference: -0.51, -20.92 to 19.9; p = 0.96). The mean maximum specimen length was significantly longer in the PC-LB group (mean difference: -3.11, -5.51 to -0.71; p = 0.01), and TSA showed that the required information size was reached. CONCLUSION: EUS-LB and PC-LB are comparable in terms of diagnostic performance although PC-LB provides longer non-fragmented specimens.

Evaluation of ChatGPT as a Counselling Tool for Italian-Speaking MASLD Patients: Assessment of Accuracy, Completeness and Comprehensibility.

BACKGROUND: Artificial intelligence (AI)-based chatbots have shown promise in providing counseling to patients with metabolic dysfunction-associated steatotic liver disease (MASLD). While ChatGPT3.5 has demonstrated the ability to comprehensively answer MASLD-related questions in English, its accuracy remains suboptimal. Whether language influences these results is unclear. This study aims to assess ChatGPT's performance as a counseling tool for Italian MASLD patients. METHODS: Thirteen Italian experts rated the accuracy, completeness and comprehensibility of ChatGPT3.5 in answering 15 MASLD-related questions in Italian using a six-point accuracy, three-point completeness and three-point comprehensibility Likert's scale. RESULTS: Mean scores for accuracy, completeness and comprehensibility were 4.57 ± 0.42, 2.14 ± 0.31 and 2.91 ± 0.07, respectively. The physical activity domain achieved the highest mean scores for accuracy and completeness, whereas the specialist referral domain achieved the lowest. Overall, Fleiss's coefficient of concordance for accuracy, completeness and comprehensibility across all 15 questions was 0.016, 0.075 and -0.010, respectively. Age and academic role of the evaluators did not influence the scores. The results were not significantly different from our previous study focusing on English. CONCLUSION: Language does not appear to affect ChatGPT's ability to provide comprehensible and complete counseling to MASLD patients, but accuracy remains suboptimal in certain domains.

Myosteatosis is closely associated with sarcopenia and significantly worse outcomes in patients with cirrhosis.

BACKGROUND & AIMS: Sarcopenia and myosteatosis are common in patients with cirrhosis. This study aimed to determine the prevalence of these muscle changes, their interrelations and their prognostic impact over a 12-month period. METHODS: We conducted a prospective multicentre study involving 433 patients. Sarcopenia and myosteatosis were evaluated using computed tomography scans. The 1-year cumulative incidence of relevant events was assessed by competing risk analysis. We used a Fine-Gray model adjusted for known prognostic factors to evaluate the impact of sarcopenia and myosteatosis on mortality, hospitalization, and liver decompensation. RESULTS: At enrolment, 166 patients presented with isolated myosteatosis, 36 with isolated sarcopenia, 135 with combined sarcopenia and myosteatosis and 96 patients showed no muscle changes. The 1-year cumulative incidence of death in patients with either sarcopenia and myosteatosis (13.8%) or isolated myosteatosis (13.4%) was over twice that of patients without muscle changes (5.2%) or with isolated sarcopenia (5.6%). The adjusted sub-hazard ratio for death in patients with muscle changes was 1.36 (95% CI 0.99-1.86, p = 0.058). The cumulative incidence of hospitalization was significantly higher in patients with combined sarcopenia and myosteatosis than in patients without muscle changes (adjusted sub-hazard ratio 1.18, 95% CI 1.04-1.35). The cumulative incidence of liver decompensation was greater in patients with combined sarcopenia and myosteatosis (p = 0.018) and those with isolated sarcopenia (p = 0.046) than in patients without muscle changes. Lastly, we found a strong correlation of function tests and frailty scores with the presence of muscle changes. CONCLUSIONS: Myosteatosis, whether alone or combined with sarcopenia, is highly prevalent in patients with cirrhosis and is associated with significantly worse outcomes. The prognostic role of sarcopenia should always be evaluated in relation to the presence of myosteatosis. IMPACT AND IMPLICATIONS: This study investigates the prognostic role of muscle changes in patients with cirrhosis. The novelty of this study is its multicentre, prospective nature and the fact that it distinguishes between the impact of individual muscle changes and their combination on prognosis in cirrhosis. This study highlights the prognostic role of myosteatosis, especially when combined with sarcopenia. On the other hand, the relevance of sarcopenia could be mitigated when considered together with myosteatosis. The implication from these findings is that sarcopenia should never be evaluated individually and that myosteatosis may play a dominant role in the prognosis of patients with cirrhosis.

The autoimmune landscape of Porto-sinusoidal vascular disorder: What the rheumatologist needs to know.

Porto-sinusoidal vascular disorder (PSVD) encompasses a group of vascular disorders characterized by lesions of the portal venules and sinusoids with clinical manifestations ranging from non-specific abnormalities in serum liver enzymes to clinically overt portal hypertension and related complications. Several reports have documented cases of PSVD in patients with systemic autoimmune conditions, such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. It is of note that these diseases share specific pathophysiological features with PSVD, including endothelial dysfunction, vascular inflammation, and molecular signatures. This narrative review aims to summarize the current knowledge on the association between PSVD and systemic autoimmune diseases, emphasizing the importance of promptly recognizing this condition in the rheumatological practice, and highlighting the key aspects where further research is necessary from both pathogenic and clinical perspectives.

Prevalence of HCV infection in Europe in the DAA era: Review.

In 2016, the Global Health Sector Strategy, ratified by the 69th World Health Assembly, set the ambitious goal of eliminating hepatitis C virus (HCV) and hepatitis B virus infections by 2030, emphasizing the importance of national screening programmes. Achieving this goal depends on each country's ability to identify and treat 80% of chronic hepatitis C cases, a critical threshold set by the World Health Organization. Traditionally, estimates of HCV prevalence have been based on interferon era studies that focused on high-risk subgroups rather than the general population. In addition, the incomplete data available from national registries also limited the understanding of HCV prevalence. The 2016 report from the European Centre for Disease Prevention and Control highlighted that HCV rates varied across European counties, ranging from .1% to 5.9%. However, data were only available for 13 countries, making the overall picture less clear. Additionally, the epidemiological data may have underestimated the true burden of HCV due to lack of awareness among those with chronic infection. The main objective of this review is to provide a comprehensive summary of HCV epidemiology in Europe in the current era of direct-acting antivirals (DAAs). The data included in the analysis range from the end of 2013 to December 2023 and have been categorised according to the United Nations Geoscheme. The resulting synthesis underscores the noteworthy impact of DAA treatment on the epidemiological situation.

Optimizing large language models in digestive disease: strategies and challenges to improve clinical outcomes.

Large Language Models (LLMs) are transformer-based neural networks with billions of parameters trained on very large text corpora from diverse sources. LLMs have the potential to improve healthcare due to their capability to parse complex concepts and generate context-based responses. The interest in LLMs has not spared digestive disease academics, who have mainly investigated foundational LLM accuracy, which ranges from 25% to 90% and is influenced by the lack of standardized rules to report methodologies and results for LLM-oriented research. In addition, a critical issue is the absence of a universally accepted definition of accuracy, varying from binary to scalar interpretations, often tied to grader expertise without reference to clinical guidelines. We address strategies and challenges to increase accuracy. In particular, LLMs can be infused with domain knowledge using Retrieval Augmented Generation (RAG) or Supervised Fine-Tuning (SFT) with reinforcement learning from human feedback (RLHF). RAG faces challenges with in-context window limits and accurate information retrieval from the provided context. SFT, a deeper adaptation method, is computationally demanding and requires specialized knowledge. LLMs may increase patient quality of care across the field of digestive diseases, where physicians are often engaged in screening, treatment and surveillance for a broad range of pathologies for which in-context learning or SFT with RLHF could improve clinical decision-making and patient outcomes. However, despite their potential, the safe deployment of LLMs in healthcare still needs to overcome hurdles in accuracy, suggesting a need for strategies that integrate human feedback with advanced model training.

Novel Techniques, Biomarkers and Molecular Targets to Address Cardiometabolic Diseases.

Cardiometabolic diseases (CMDs) are interrelated and multifactorial conditions, including arterial hypertension, type 2 diabetes, heart failure, coronary artery disease, and stroke. Due to the burden of cardiovascular morbidity and mortality associated with CMDs' increasing prevalence, there is a critical need for novel diagnostic and therapeutic strategies in their management. In clinical practice, innovative methods such as epicardial adipose tissue evaluation, ventricular-arterial coupling, and exercise tolerance studies could help to elucidate the multifaceted mechanisms associated with CMDs. Similarly, epigenetic changes involving noncoding RNAs, chromatin modulation, and cellular senescence could represent both novel biomarkers and targets for CMDs. Despite the promising data available, significant challenges remain in translating basic research findings into clinical practice, highlighting the need for further investigation into the complex pathophysiology underlying CMDs.

Lean body mass and the cardiorespiratory phenotype: An ethnic-specific relationship in Hans Chinese women and men.

BACKGROUND: Lean body mass (LBM) and the functional capacity of cardiovascular (CV) and respiratory systems constitute a female-specific relationship in European-American individuals. Whether this recent finding be extrapolated to the world's largest ethnic group, that is, Hans Chinese (HC, a population characterized by low LBM), is unknown. METHODS: Healthy HC adults (n = 144, 50% ♀) closely matched by sex, age and physical activity were included. Total and regional (leg, arm and trunk) LBM and body composition were measured via dual-energy X-ray absorptiometry. Cardiac structure, stiffness, central/peripheral haemodynamics and peak O2 consumption (VO2peak) were assessed via transthoracic echocardiography and pulmonary gas analyses at rest and during exercise up to peak effort. Regression analyses determined the sex-specific relationship of LBM with cardiac and aerobic phenotypes. RESULTS: Total and regional LBM were lower and body fat percentage higher in women compared with men (P < 0.001). In both sexes, total LBM positively associated with left ventricular (LV) mass and peak volumes (r ≥ 0.33, P ≤ 0.005) and negatively with LV end-systolic and central arterial stiffness (r ≥ -0.34, P ≤ 0.004). Total LBM strongly associated with VO2peak (r ≥ 0.60, P < 0.001) and peak cardiac output (r ≥ 0.40, P < 0.001) in women and men. Among regional LBM, leg LBM prominently associated with the arterio-venous O2 difference at peak exercise in both sexes (r ≥ 0.43, P < 0.001). Adjustment by adiposity or CV risk factors did not modify the results. CONCLUSIONS: LBM independently determines internal cardiac dimensions, ventricular mass, distensibility and the capacity to deliver and consume O2 in HC adults irrespective of sex.

Risk of hepatitis B virus reactivation in oncological patients treated with tyrosine kinase inhibitors: A case report and literature analysis.

Hepatitis B virus (HBV) reactivation (HBVr) represents a severe and potentially life-threatening condition, and preventive measures are available through blood test screening or prophylactic therapy administration. The assessment of HBVr traditionally considers factors such as HBV profile, including hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen, along with type of medication (chemotherapy; immunomodulants). Nevertheless, consideration of possible patient's underlying tumor and the specific malignancy type (solid or hematologic) plays a crucial role and needs to be assessed for decision-making process.

Development of a high-throughput liquid chromatography-tandem mass spectrometry platform for the determination of intact natriuretic peptides in human plasma.

We present an innovative, reliable, and antibody-free analytical method to determine multiple intact natriuretic peptides in human plasma. These biomolecules are routinely used to confirm the diagnosis and monitor the evolution of heart failure, so that their determination is essential to improve diagnosis and monitor the efficacy of treatment. However, common immunoassay kits suffer from main limitations due to high cross-reactivity with structurally similar species. In our method, we pre-treated the sample by combining salting-out with ammonium sulfate with microextraction by packed sorbent technique. Analyses were then carried out by ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometry. The use of 3-nitrobenzyl alcohol as a supercharger reagent enhanced the ESI ionization and improved the signal-to-noise ratio. The analytical protocol showed good linearity over one order of magnitude, recovery in the range of 94-105 %, and good intra- and inter-day reproducibility (RSD<20 %), and the presence of a matrix effect. Limits of detection were in the range of pg/mL for all peptides (0.2-20 pg/mL). Stability study in plasma samples demonstrated that proper protease inhibitors need to be included in blood collection tubes to avoid peptide degradation. Preliminary analyses on plasma samples from heart failure patients allow the quantification of ANP 1-28 as the most abundant species and the detection of ANP 5-28, BNP 1-32, and BNP 5-32. The method could be used to investigate how cross-reactivity issues among structurally similar species impact determinations by ELISA kits.

Psychrobacter raelei sp. nov., isolated from a dog with peritonitis.

A strain belonging to the genus Psychrobacter, named PraFG1T, was isolated from the peritoneal effusion of a stray dog during necropsy procedures. The strain was characterized by the phylogenetic analyses based on the nucleotide sequences of 16S and 23S rRNA genes and of gyrB, which placed the strain in the genus Psychrobacter. The nucleotide sequence of the chromosome confirmed the placement, showing an average nucleotide identity of 72.1, 77.7, and 77.5 % with the closest related species, namely Psychrobacter sanguinis, Psychrobacter piechaudii, and Psychrobacter phenylpyruvicus, respectively, thus indicating a novel species. The polyphasic characterization by biochemical and fatty acid profiling as well as MALDI-TOF supported those findings. The strain was halotolerant, capable of growing within a temperature range between 4 and 37 °C, it was positive for catalase and oxidase, indole producing, nitrate reducing, and not able to use 5-keto-d-gluconic acid as a carbon source. Taken together, the data suggest that strain PraFG1T could be considered as representing a novel species, with the name Psychrobacter raelei sp. nov. (type strain PraFG1T=CIP 111873T=LMG 32233T).

Prognostic implication of lung ultrasound in heart failure: pooled analysis of international cohorts.

BACKGROUND: Lung ultrasound (LUS) is often used to assess congestion in heart failure (HF). In this study, we assessed the prognostic role of LUS in HF patients at admission and hospital discharge, and in an out-patient setting and explored whether clinical factors (age, sex, left ventricular ejection fraction (LVEF) and atrial fibrillation) impact the prognostic value of LUS findings. Further, we assessed the incremental prognostic value of LUS on top of AHEAD and MAGGIC clinical risk scores. METHODS AND RESULTS: We pooled data of patients hospitalized for HF or followed-up in out-patient clinics from international cohorts. We enrolled 1,947 patients, at admission (n=578), discharge (n=389) and in out-patient clinic (n=980). Total LUS B-line count was calculated for the 8-zone scanning protocol. The primary outcome was a composite of re-hospitalization for HF and all-cause death. Compared to those in the lower tertiles of B-lines, patients in the highest tertile were older, more likely to have signs of HF and higher NT-proBNP levels. A higher number of B-lines was associated with increased risk of primary outcome at discharge (Tertile3 vs Tertile1: adjustedHR= 5.74 (3.26- 10.12), p<0.0001) and in out-patients (Tertile3 vs Tertile1: adjustedHR= 2.66 (1.08- 6.54), p=0.033). Age and LVEF did not influence the prognostic capacity of LUS in different clinical settings. Adding B-line count to MAGGIC and AHEAD scores improved net reclassification significantly in all three clinical settings. CONCLUSION: A higher number of B-lines in patients with HF was associated with increased risk of morbidity and mortality, regardless of the clinical setting.

Poisoning by Nerium oleander L. in Franconia Geese.

This study describes the acute poisoning of four 3-month-old Franconia geese (Anser anser) by oleander plants (Nerium oleander). After the accidental ingestion of oleander clippings, the geese exhibited a rapid onset of severe symptoms, leading to mortality within 15-90 min. Necropsy revealed cardiac and renal lesions. Specifically, interstitial edema, red blood cell infiltration, and myofibril loss were observed in the cardiac muscle, and tubular epithelial degeneration, interstitial edema, and hemorrhages were evident in the kidneys. Oleandrin, a glycoside with cardiac effects, was detected in the liver, kidneys, heart, brain, and muscles. The clinical implications underscore the urgency of veterinary intervention upon oleander ingestion, and the specific findings contribute valuable insights into the pathological effects of acute oleander poisoning in geese, aiding veterinarians in prompt diagnosis and treatment.

mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis.

BACKGROUND: Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L-1·min-1. A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown. METHODS: In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm2 underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141). RESULTS: One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48; P=0.036), indexed left atrial volume (OR per SD, 2.15; P=0.001), E/e' at rest (OR per SD, 1.61; P=0.012), mPAP/CO slope (OR per SD, 2.01; P=0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59; P=0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28; P=0.219). Peak Vo2 (percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area (P<0.001). These results were confirmed in the validation cohort. CONCLUSIONS: In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak Vo2 were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak Vo2 and mPAP/CO slope cumulatively improved risk stratification.

Accuracy, Reliability, and Comprehensibility of ChatGPT-Generated Medical Responses for Patients With Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is an increasing global health problem and is expected to become the leading indication for liver transplantation.1 There are no approved NAFLD-specific pharmacotherapies, and lifestyle modification is the primary recommended therapy.2 Innovative approaches to facilitate the implementation and long-term maintenance of lifestyle changes are needed to address the challenging and complex nature of the management of NAFLD, which recently was renamed as metabolic dysfunction-associated steatotic liver disease, to overcome the limitations and stigma of the previous name.3,4 Artificial intelligence (AI)-powered chatbots have been shown to provide effective personalized support and education to patients, with the potential to complement health care resources. The OpenAI Foundation's AI chatbot, Chat Generative Pretrained Transformer (ChatGPT), has attracted worldwide attention for its remarkable performance in question-answer tasks.5-7 This study evaluated the accuracy, completeness, and comprehensiveness of chatGPT's responses to NAFLD-related questions, with the aim of assessing its performance in addressing patients' queries about the disease and lifestyle behaviors.

Patient phenotype profiling using echocardiography and natriuretic peptides to personalise heart failure therapy.

Heart failure (HF) is a progressive condition with a clinical picture resulting from reduced cardiac output (CO) and/or elevated left ventricular (LV) filling pressures (LVFP). The original Diamond-Forrester classification, based on haemodynamic data reflecting CO and pulmonary congestion, was introduced to grade severity, manage, and risk stratify advanced HF patients, providing evidence that survival progressively worsened for those classified as warm/dry, cold/dry, warm/wet, and cold/wet. Invasive haemodynamic evaluation in critically ill patients has been replaced by non-invasive haemodynamic phenotype profiling using echocardiography. Decreased CO is not infrequent among ambulatory HF patients with reduced ejection fraction, ranging from 23 to 45%. The Diamond-Forrester classification may be used in combination with the evaluation of natriuretic peptides (NPs) in ambulatory HF patients to pursue the goal of early identification of those at high risk of adverse events and personalise therapy to antagonise neurohormonal systems, reduce congestion, and preserve tissue/renal perfusion. The most benefit of the Guideline-directed medical treatment is to be expected in stable patients with the warm/dry profile, who more often respond with LV reverse remodelling, while more selective individualised treatments guided by echocardiography and NPs are necessary for patients with persisting congestion and/or tissue/renal hypoperfusion (cold/dry, warm/wet, and cold/wet phenotypes) to achieve stabilization and to avoid further neurohormonal activation, as a result of inappropriate use of vasodilating or negative chronotropic drugs, thus pursuing the therapeutic objectives. Therefore, tracking the haemodynamic status over time by clinical, imaging, and laboratory indicators helps implement therapy by individualising drug regimens and interventions according to patients' phenotypes even in an ambulatory setting.