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These guidelines on transjugular intrahepatic portosystemic stent-shunt (TIPSS) in the management of portal hypertension have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the Liver Section of the BSG. The guidelines are new and have been produced in collaboration with the British Society of Interventional Radiology (BSIR) and British Association of the Study of the Liver (BASL). The guidelines development group comprises elected members of the BSG Liver Section, representation from BASL, a nursing representative and two patient representatives. The quality of evidence and grading of recommendations was appraised using the GRADE system. These guidelines are aimed at healthcare professionals considering referring a patient for a TIPSS. They comprise the following subheadings: indications; patient selection; procedural details; complications; and research agenda. They are not designed to address: the management of the underlying liver disease; the role of TIPSS in children; or complex technical and procedural aspects of TIPSS.

Malnutrition is a common condition encountered in patients with inflammatory bowel disease (IBD) and is often associated with sarcopenia (the reduction of muscle mass and strength) which is an ever-growing consideration in chronic diseases. Recent data suggest the prevalence of sarcopenia is 52% and 37% in Crohn’s disease and ulcerative colitis, respectively, however it is challenging to fully appreciate the prevalence of sarcopenia in IBD. Sarcopenia is an important consideration in the management of IBD, including the impact on quality of life, prognostication, and treatment such as surgical interventions, biologics and immunomodulators. There is evolving research in many chronic inflammatory states, such as chronic liver disease and rheumatoid arthritis, whereby interventions have begun to be developed to counteract sarcopenia. The purpose of this review is to evaluate the current literature regarding the impact of sarcopenia in the management of IBD, from mechanistic drivers through to assessment and management.

Background Patients with end‐stage liver disease (ESLD) often present with sarcopenia, defined as loss of skeletal muscle mass and quality, which is associated with reduced quality of life and increased mortality. However, the molecular mechanisms driving sarcopenia in ESLD are not fully understood and there are currently no therapeutic interventions. This study aimed to identify potential circulating factors contributing to sarcopenia progression in ESLD by assessing their role in driving transcriptomic alterations in skeletal muscle. Methods Quadriceps muscle tissue, plasma and serum were obtained from ESLD patients (n = 24) and age/sex‐matched healthy controls (HC; n = 18) (Clinical Trial ID: NCT04734496, Ethical Approval 18/WM/0167). Total RNA from snap‐frozen vastus lateralis muscle biopsies underwent RNA sequencing (Illumina). Serum concentrations of 60 cytokines were profiled by Luminex and ELISA, with comparisons made both between ESLD and HC, and across ESLD aetiologies (alcohol‐related, NAFLD, viral hepatitis, other). In vitro, primary human myotubes (from non‐ESLD aged donors, NRES #16/SS/0172) were treated with 10% ESLD or HC plasma (24 h, n = 6 per group) followed by RNA sequencing (BGI Genomics). Differentially expressed genes (p < 0.05, fold‐change > 1.5) were identified via Qlucore and DESeq2, and pathway analysis performed using Ingenuity (Qiagen). The impact of physiological concentrations of candidate cytokines (IL‐1α, GDF‐15 and HGF) on myotube thickness, differentiation and mitochondrial function was assessed by immunofluorescence microscopy, RT‐qPCR and metabolic flux assays. Results In ESLD muscle, 387 and 225 genes were significantly up‐ and downregulated compared to HC, respectively, with cellular senescence identified as a top dysregulated function. Upstream regulator analysis predicted activation of hepatocyte growth factor (HGF) and interleukin‐1 signalling. Subgroup analysis revealed distinct transcriptomic profiles based on disease aetiology. Serum profiling identified 15 cytokines significantly elevated (p < 0.05) and five reduced (p < 0.05) in ESLD, including increased HGF and reduced interleukin‐1 receptor antagonist. Stratified analysis also revealed aetiology specific cytokine profiles, with only GDF‐15 significantly (p < 0.0001) elevated in all groupsTwenty‐four‐hour ESLD plasma treatment induced 423 differentially expressed genes in human myotubes, which were again associated with significant activation of senescence pathways, with IL‐1 identified as a key upstream driver. In vitro, IL‐1α, GDF‐15, and HGF significantly reduced myotube thickness, nuclear fusion index and perturbed metabolism (increased glycolysis, impaired oxidative phosphorylation). Conclusions Collectively, these findings suggest that sarcopenia in ESLD is driven by aetiology‐specific mechanisms, highlighting the potential for targeted therapies to improve muscle mass and function.

Differences between automated cuff oscillometric blood pressure (BP) and invasive measurements are well described, but the causes are not fully understood. Automated BP devices record cuff oscillometric mean arterial pressure (MAP) as a key measurement step that is presumed to be accurate, but if not, could create error in cuff systolic (SBP) and diastolic BP (DBP) estimations. This has never been determined and was the aim of the study. Data from five studies with similar protocols were analysed ( N  = 262 patients undergoing coronary angiography, 61 ± 11 years, 65% male). Cuff oscillometric MAP was measured using five different models of automated cuff BP devices simultaneous to invasively measured MAP (fluid-filled or solid-state catheters). Cuff SBP and DBP were estimated by device-specific algorithms. Differences (∆) were calculated as cuff–invasive aortic BP. There were significant associations between ∆MAP and ∆SBP in four out of five devices (unstandardised β range = 0.42–1.04). The ∆MAP explained 6–52% of the variance in ∆SBP. In the same four devices, there were significant associations between ∆MAP and ∆DBP (unstandardised β range = 0.57–0.97) and ∆MAP explained 35–52% of the variance in ∆DBP. In conclusion, there are differences between cuff oscillometric MAP and invasive MAP which are associated with ∆SBP and ∆DBP. Further research is required to improve cuff oscillometric BP and greater transparency needed to understand algorithms used in these devices.

Patients with chronic liver disease (CLD) often present with significant frailty, sarcopenia, and impaired immune function. However, the mechanisms driving the development of these age-related phenotypes are not fully understood. To determine whether accelerated biological aging may play a role in CLD, epigenetic, transcriptomic, and phenotypic assessments were performed on the skeletal muscle tissue and immune cells of CLD patients and age-matched healthy controls. Accelerated biological aging of the skeletal muscle tissue of CLD patients was detected, as evidenced by an increase in epigenetic age compared with chronological age (mean +2.2 ± 4.8 years compared with healthy controls at −3.0 ± 3.2 years, p  = 0.0001). Considering disease etiology, age acceleration was significantly greater in both the alcohol-related (ArLD) ( p  = 0.01) and nonalcoholic fatty liver disease (NAFLD) ( p  = 0.0026) subgroups than in the healthy control subgroup, with no age acceleration observed in the immune-mediated subgroup or healthy control subgroup ( p  = 0.3). The skeletal muscle transcriptome was also enriched for genes associated with cellular senescence. Similarly, blood cell epigenetic age was significantly greater than that in control individuals, as calculated using the PhenoAge ( p  < 0.0001), DunedinPACE ( p  < 0.0001), or Hannum ( p  = 0.01) epigenetic clocks, with no difference using the Horvath clock. Analysis of the IMM-Age score indicated a prematurely aged immune phenotype in CLD patients that was 2-fold greater than that observed in age-matched healthy controls ( p  < 0.0001). These findings suggested that accelerated cellular aging may contribute to a phenotype associated with advanced age in CLD patients. Therefore, therapeutic interventions to reduce biological aging in CLD patients may improve health outcomes. Skeletal Muscle Ageing in CLD: Implications for Therapeutic Interventions Chronic liver disease, a long-term condition damaging the liver, is causing more deaths worldwide. Patients often develop immune dysfunction and sarcopenia. This study aimed to see if CLD patients show signs of fast biological ageing, particularly in muscles and the immune system. The research compared CLD patients to healthy people, looking at muscle samples, blood samples, and immune cells to check for ageing signs. Results showed that CLD patients have faster biological ageing in muscles and immune cells, with increased epigenetic age and more senescence-associated genes. This suggests that CLD speeds up the ageing process, which could explain the common occurrence of sarcopenia and immune dysfunction in these patients. Future implications include the possibility of developing treatments targeting the ageing process in CLD patients, offering hope for better health and quality of life This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

Alzheimer’s disease (AD) is influenced by both genetic and environmental factors; thus, brain epigenomic alterations may provide insights into AD pathogenesis. Multiple array-based Epigenome-Wide Association Studies (EWASs) have identified robust brain methylation changes in AD; however, array-based assays only test about 2% of all CpG sites in the genome. Here, we develop EWASplus, a computational method that uses a supervised machine learning strategy to extend EWAS coverage to the entire genome. Application to six AD-related traits predicts hundreds of new significant brain CpGs associated with AD, some of which are further validated experimentally. EWASplus also performs well on data collected from independent cohorts and different brain regions. Genes found near top EWASplus loci are enriched for kinases and for genes with evidence for physical interactions with known AD genes. In this work, we show that EWASplus implicates additional epigenetic loci for AD that are not found using array-based AD EWASs. Array-based epigenome-wide association studies only test about 2% of the CpG sites in the genome. Here, the authors describe EWASplus, a supervised machine learning strategy that extends EWAS coverage to the entire genome, and use it to identify novel brain CpGs associated with Alzheimer’s disease.

Clinic blood pressure (BP) is recommended for absolute cardiovascular disease (CVD) risk assessment. However, in ‘real-world’ settings, clinic BP measurement is unstandardised and less reliable compared to more rigorous methods but the impact for absolute CVD risk assessment is unknown. This study aimed to determine the difference in absolute CVD risk assessment using real-world clinic BP compared to standardised BP methods. Participants were patients ( n  = 226, 59 ± 15 years; 58% female) with hypertension referred to a BP clinic for assessment. ‘Real-world’ clinic BP was provided by the referring doctor. All participants had unobserved automated office BP (AOBP) and 24-h ambulatory BP monitoring (ABPM) measured at the clinic. Absolute CVD risk was calculated (Framingham) using systolic BP from the referring doctor (clinic BP), AOBP and ABPM, with agreement assessed by Kappa statistic. Clinic systolic BP was 18 mmHg than AOBP and daytime ABPM and 22 mmHg higher than 24-h ABPM ( p  < 0.001). Subsequently, absolute CVD risk scores using clinic BP were higher compared to AOBP, daytime ABPM and 24-h ABPM (10.4 ± 8.1%, 7.8 ± 6.4%, 7.8 ± 6.3%, and 7.3 ± 6.1%, respectively, P  < 0.001). As a result, more participants were classified as high CVD risk using clinic BP ( n  = 89, 40%) compared with AOBP (n = 44, 20%) daytime ABPM ( n  = 38, 17%) and 24-h ABPM ( n  = 38, 17%) ( p  < 0.001) with weak agreement in risk classification (κ = 0.57[0.45–0.69], κ = 0.52[0.41–0.64] and κ = 0.55[0.43–0.66], respectively). Real-world clinic BP was higher and classified twice as many participants at high CVD risk compared to AOBP or ABPM. Given the challenges to high-quality BP measurement in clinic, more rigorous BP measurement methods are needed for absolute CVD risk assessment.

Alström Syndrome (ALMS) is an ultra-rare multisystem genetic disorder caused by autosomal recessive variants in the ALMS1 gene, which is located on chromosome 2p13. ALMS is a multisystem, progressive disease characterised by visual disturbance, hearing impairment, cardiomyopathy, childhood obesity, extreme insulin resistance, accelerated non-alcoholic fatty liver disease (NAFLD), renal dysfunction, respiratory disease, endocrine and urologic disorders. Clinical symptoms first appear in infancy with great variability in age of onset and severity. ALMS has an estimated incidence of 1 case per 1,000,000 live births and ethnically or geographically isolated populations have a higher-than-average frequency. The rarity and complexity of the syndrome and the lack of expertise can lead to delayed diagnosis, misdiagnosis and inadequate care. Multidisciplinary and multiprofessional teams of experts are essential for the management of patients with ALMS, as early diagnosis and intervention can slow the progression of multi-organ dysfunctions and improve patient quality of life. These guidelines are intended to define standard of care for patients suspected or diagnosed with ALMS of any age. All information contained in this document has originated from a systematic review of the literature and the experiences of the authors in their care of patients with ALMS. The Appraisal of Guidelines for Research & Evaluation (AGREE II) system was adopted for the development of the guidelines and for defining the related levels of evidence and strengths of recommendations. These guidelines are addressed to: a) specialist centres, other hospital-based medical teams and staffs involved with the care of ALMS patients, b) family physicians and other primary caregivers and c) patients and their families.