Circadian heart rate fluctuations predict cardiovascular and all-cause mortality in type 2 and type 1 diabetes: a 21-year retrospective longitudinal study.

BACKGROUND: Circadian heart rate (HR) fluctuations are associated with cardiovascular health. We examined their relationship with microvascular disease and long-term survival in patients with diabetes. METHODS: In this secondary analysis from the CHAMP1ON cohort of 497 adults with metabolic disease, 349 participants who had type 1 or type 2 diabetes, baseline 24h ambulatory blood pressure and HR monitoring (ABPM), and survival data over a 21-year observational follow-up were included. Clinical features, microvascular complications, and mortality rates were examined in participants with low circadian HR fluctuations (24h-HR SD below the median of 30.4) and blunted nocturnal HR dip (<10%). RESULTS: Low 24h-HR SD and blunted nocturnal HR dip were associated with an adverse cardiometabolic risk profile and 12-23% higher prevalence of cardiac autonomic neuropathy and nephropathy. After 6,251 person-years follow-up (21.0 [14.0-21.0] years), a total of 136 (39%) deaths occurred, of which 100 (68%) of cardiovascular cause. The low 24h-HR SD group had a higher risk for both cardiovascular (adjusted hazard ratio [aHR] 2.00, 95%CI 1.30-3.08, p=0.002) and all-cause mortality (aHR 1.61, 95%CI 1.13-2.29, p=0.009), compared with high 24h-HR SD. Similarly, patients with blunted nocturnal HR dip had a higher risk for cardiovascular (aHR 1.63, 95%CI 1.08-2.46, p=0.019) and all-cause mortality (aHR 1.69, 95%CI 1.20-2.38, p=0.003), compared with those with preserved nocturnal HR dip. CONCLUSIONS: Impaired circadian HR fluctuations are associated with microvascular disease and long-term cardiovascular and all-cause mortality in diabetes. ABPM-derived HR measures may provide a widely available and inexpensive risk stratification tool in this high-risk population.

Circadian heart rate (HR) fluctuations are associated with cardiovascular health. We examined their relationship with microvascular disease and long-term survival in patients with diabetes. Impaired HR fluctuations measured by 24h ambulatory blood pressure and HR monitoring (ABPM) were associated with an adverse cardiometabolic risk profile, higher prevalence of cardiac autonomic neuropathy and nephropathy, and higher risk for cardiovascular and all-cause mortality over a 21-year follow-up. ABPM-derived HR measures may provide a cost-effective risk stratification tool in this high-risk population.

Link between persistent, unexplained gamma-glutamyltransferase elevation and porto-sinusoidal vascular disorder.

Background & Aims: Porto-sinusoidal vascular disorder (PSVD) is a group of vascular disorders characterized by lesions involving portal venules and sinusoids, irrespective of the presence of portal hypertension. Liver biopsy is essential for diagnosis. In a single-center study, we demonstrated high rates of PSVD in patients with persistently elevated gamma-glutamyltransferase (GGT). This multicenter study aims to establish PSVD prevalence in a larger dataset of individuals with persistent and unexplained GGT elevation, and to identify associated risk factors. Methods: The study included all patients who underwent liver biopsy for persistent and unexplained GGT elevation in five Italian hepatology units between March 2015 and December 2021. Results: A total of 144 patients met the inclusion criteria. The majority were males (76/144, 52.8%) and mean age was 51.9 years (range 19-74). Only 12 (8.3%) had liver stiffness measurements (LSM) >10 kPa, while 7 (4.8%) had ultrasound evidence of portal hypertension. Histological findings were consistent with PSVD in 96 patients (67%). Alternative diagnoses were steatohepatitis in 13 (9%), sarcoidosis in 3 (2%) and congenital hepatic fibrosis in 3 (2%) patients. Histological findings were non-specific in 29 (20%) patients. PSVD was associated with male sex (odds ratio [OR] 2.60, 95% CI 1.13-5.99), LSM <10 kPa (OR 11.05, 95% CI 2.16-56.66) and GGT <200 U/L (OR 2.69, 95% CI 1.22-5.98). Conclusions: PSVD was the main cause of persistent and unexplained elevation of GGT3. Male sex, LSM <10 kPa and GGT <200 U/L were associated with PSVD. These findings highlight the role of liver biopsy in elucidating the underlying pathology and aiding in the diagnosis of patients with persistent and unexplained GGT elevation. Impact and implications: In outpatient settings, it is common to encounter individuals with persistent and unexplained gamma-glutamyltransferase elevations. This study reveals, for the first time, a non-negligible prevalence of porto-sinusoidal vascular disorder among these individuals when they undergo liver biopsy. Male sex, liver stiffness measurement <10 kPa, and gamma-glutamyltransferase <200 IU/L predict this histological finding. These results may raise awareness of clinically relevant conditions that may be present in patients with persistent liver enzyme changes, even in the absence of signs of advanced chronic liver disease or portal hypertension. Additionally, the data may encourage further studies in the field of porto-sinusoidal vascular disorder, particularly to define its clinical evolution in patients without signs of portal hypertension at diagnosis.

Glucagon-like peptide-1 receptor agonists and risk of gastrointestinal cancers: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used for glucose lowering and weight-loss. However, their association with gastrointestinal cancer remains uncertain. This meta-analysis assesses the risk of gastrointestinal cancer in patients treated with GLP-1 RAs. METHODS: We searched Medline/PubMed, Embase, and Scopus databases from inception to November 15, 2023, for randomized controlled trials (RCTs) with at least 24 weeks of safety follow-up. Pooled risk ratios (RRs) were calculated using fixed- and random-effect models. Risk of bias was assessed using the revised Cochrane risk-of-bias tool, and certainty of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. RESULTS: We included 90 RCTs with 124,791 participants, with an average follow-up of 3.1 years per participant. No significant association was found between GLP-1 RAs and the risk of any gastrointestinal cancer (RRrandom=0.99, 95 % CI: 0.86-1.13), or site-specific gastrointestinal cancers including biliary tract (RR=0.98, 0.54-1.78), colorectal (RR=1.13, 0.92-1.39), gallbladder (RR=1.32, 0.43-4.00), gastric (RR=0.88, 0.58-1.33), hepatic (RR=0.79, 0.51-1.21), oesophageal (RR=0.70, 0.38-1.28), pancreatic (RR=1.05, 0.77-1.43), and small intestine cancer (RR=0.78, 0.20-3.04). The corresponding absolute risk differences excluded important impacts on risk. Additional analyses, limited to placebo-controlled trials, high-dose studies, or those with a follow-up duration of ≥5 years, confirmed these findings. Risk of bias was generally low and the certainty of evidence was high for all outcomes. CONCLUSIONS: This meta-analysis found no significant impact of GLP-1 RAs on gastrointestinal cancer risk. Long-term safety monitoring of these agents remains important. SYSTEMATIC REVIEW REGISTRATION: CRD42023476762.

Integrative assessment of congestion in heart failure using ultrasound imaging.

In heart failure (HF), congestion is a key pathophysiologic hallmark and a major contributor to morbidity and mortality. However, the presence of congestion is often overlooked in both acute and chronic settings, particularly when it is not clinically evident, which can have important clinical consequences. Ultrasound (US) is a widely available, non-invasive, sensitive tool that might enable clinicians to detect and quantify the presence of (subclinical) congestion in different organs and tissues and guide therapeutic strategies. In particular, left ventricular filling pressures and pulmonary pressures can be estimated using transthoracic echocardiography; extravascular lung water accumulation can be evaluated by lung US; finally, systemic venous congestion can be assessed at the level of the inferior vena cava or internal jugular vein. The Doppler evaluation of renal, hepatic and portal venous flow can provide additional valuable information. This review aims to describe US techniques allowing multi-organ evaluation of congestion, underlining their role in detecting, monitoring, and treating volume overload more objectively.

Molecular detection of avian pathogens in poultry red mite (Dermanyssus gallinae) in Algerian layer farms as a potential predictive tool.

The poultry red mite Dermanyssus gallinae is a hematophagous ectoparasite of layer hens. Infestations with poultry red mites pose an increasing threat to the egg production industry, causing serious problems to animal health and welfare, directly or indirectly as a vector of several infectious agents. In this study, we aimed to investigate common avian pathogens in mites. The mite samples were collected from 58 poultry farms in 7 regions accounting for more than 70 % of the national egg production in Algeria. The presence of 13 avian pathogens was detected using DNA and RNA samples from mites collected. Results revealed significant associations between PRM and potential pathogens such as Escherichia coli, Salmonella enterica, fowlpox virus, and gallid herpesvirus 1. Pathogen detection in Dermanyssus gallinae could serve as an early diagnostic or a risk analysis tool for infectious diseases in poultry farms, facilitating effective disease management strategies. Despite further research being necessary to address uncertainties, such a strategy could be used to enhance the integrated management of poultry health.

Transthoracic and transoesophageal echocardiography for tricuspid transcatheter edge-to-edge repair: a step-by-step protocol.

Tricuspid regurgitation (TR) carries an unfavourable prognosis and often leads to progressive right ventricular (RV) failure. Secondary TR accounts for over 90% of cases and is caused by RV and/or tricuspid annulus dilation, in the setting of left heart disease or pulmonary hypertension. Surgical treatment for isolated TR entails a high operative risk and is seldom performed. Recently, transcatheter edge-to-edge repair (TEER) has emerged as a low-risk alternative treatment in selected patients. Although the experience gained from mitral TEER has paved the way for the technique's adaptation to the tricuspid valve (TV), its anatomical complexity necessitates precise imaging. To this end, a comprehensive protocol integrating 2D and 3D imaging from both transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE) plays a crucial role. TTE allows for an initial morphological assessment of the TV, quantification of TR severity, evaluation of biventricular function, and non-invasive haemodynamic evaluation of pulmonary circulation. TOE, conversely, provides a detailed evaluation of TV morphology, enabling precise assessment of TR mechanism and severity, and represents the primary method for determining eligibility for TEER. Once a patient is considered eligible for TEER, TOE, alongside fluoroscopy, will guide the procedure in the catheterization lab. High-quality TOE imaging is crucial for patient selection and to achieve procedural success. The present review examines the roles of TTE and TOE in managing patients with severe TR eligible for TEER, proposing the step-by-step protocol successfully adopted in our centre.

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.

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.

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.

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.

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

AIMS: Lung ultrasound (LUS) is often used to assess congestion in heart failure (HF). In this study, we assessed the prognostic role of LUS in patients with HF at admission and hospital discharge, and in an outpatient 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 the following two clinical risk scores: (i) the atrial fibrillation, haemoglobin, elderly, abnormal renal parameters, diabetes mellitus (AHEAD) and (ii) the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) clinical risk scores. METHODS AND RESULTS: We pooled data on patients hospitalized for HF or followed up in outpatient clinics from international cohorts. We enrolled 1947 patients at admission (n = 578), discharge (n = 389), and in outpatient clinics (n = 980). The total LUS B-line count was calculated for the eight-zone scanning protocol. The primary outcome was a composite of rehospitalization for HF and all-cause death. Compared with those in the lower tertiles of B lines, patients in the highest tertiles were older, more likely to have signs of HF and had higher N-terminal pro b-type natriuretic peptide (NT-proBNP) levels. A higher number of B lines was associated with increased risk of primary outcome at discharge [Tertile 3 vs. Tertile 1: adjusted hazard ratio (HR): 5.74 (3.26-10.12), P < 0.0001] and in outpatients [Tertile 3 vs. Tertile 1: adjusted HR: 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 the 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 an increased risk of morbidity and mortality, regardless of the clinical setting.

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.