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Mashup Score: 2Inappropriate use of proton pump inhibitors in clinical practice globally: a systematic review and meta-analysis - 22 hour(s) ago
We read with interest the population-based cohort studies by Abrahami et al on proton pump inhibitors (PPI) and the risk of gastric and colon cancers.1 2 PPI are used at all levels of healthcare and across different subspecialties for various indications.3 4 A recent systematic review on the global trends and practices of PPI recognised 28 million PPI users from 23 countries, suggesting that 23.4% of the adults were using PPI.5 Inappropriate use of PPI appears to be frequent, although there is a lack of compiled information on the prevalence of inappropriate overuse of PPI. Hence, we conducted a systematic review and meta-analysis on the inappropriate overuse of PPI globally. The details of the methodology are described in the online supplemental file. The literature was searched from inception until 19 July 2023 (PubMed, Embase and Scopus) for studies that reported on the inappropriate overuse of PPI. Two investigators independently performed each step, from screening to study selecti
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Mashup Score: 2
Objective The dysregulation of the axon guidance pathway is common in pancreatic ductal adenocarcinoma (PDAC), yet our understanding of its biological relevance is limited. Here, we investigated the functional role of the axon guidance cue SEMA3A in supporting PDAC progression. Design We integrated bulk and single-cell transcriptomic datasets of human PDAC with in situ hybridisation analyses of patients’ tissues to evaluate SEMA3A expression in molecular subtypes of PDAC. Gain and loss of function experiments in PDAC cell lines and organoids were performed to dissect how SEMA3A contributes to define a biologically aggressive phenotype. Results In PDAC tissues, SEMA3A is expressed by stromal elements and selectively enriched in basal-like/squamous epithelial cells. Accordingly, expression of SEMA3A in PDAC cells is induced by both cell-intrinsic and cell-extrinsic determinants of the basal-like phenotype. In vitro , SEMA3A promotes cell migration as well as anoikis resistance. At the mo
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Mashup Score: 6Fluorescently labelled vedolizumab to visualise drug distribution and mucosal target cells in inflammatory bowel disease - 1 day(s) ago
Objective Improving patient selection and development of biological therapies such as vedolizumab in IBD requires a thorough understanding of the mechanism of action and target binding, thereby providing individualised treatment strategies. We aimed to visualise the macroscopic and microscopic distribution of intravenous injected fluorescently labelled vedolizumab, vedo-800CW, and identify its target cells using fluorescence molecular imaging (FMI). Design Forty three FMI procedures were performed, which consisted of macroscopic in vivo assessment during endoscopy, followed by macroscopic and microscopic ex vivo imaging. In phase A, patients received an intravenous dose of 4.5 mg, 15 mg vedo-800CW or no tracer prior to endoscopy. In phase B, patients received 15 mg vedo-800CW preceded by an unlabelled (sub)therapeutic dose of vedolizumab. Results FMI quantification showed a dose-dependent increase in vedo-800CW fluorescence intensity in inflamed tissues, with 15 mg (153.7 au (132.3–163
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Mashup Score: 29Fibrosis in IBD: from pathogenesis to therapeutic targets - 1 day(s) ago
Background Intestinal fibrosis resulting in stricture formation and obstruction in Crohn’s disease (CD) and increased wall stiffness leading to symptoms in ulcerative colitis (UC) is among the largest unmet needs in inflammatory bowel disease (IBD). Fibrosis is caused by a multifactorial and complex process involving immune and non-immune cells, their soluble mediators and exposure to luminal contents, such as microbiota and environmental factors. To date, no antifibrotic therapy is available. Some progress has been made in creating consensus definitions and measurements to quantify stricture morphology for clinical practice and trials, but approaches to determine the degree of fibrosis within a stricture are still lacking. Objective We herein describe the current state of stricture pathogenesis, measuring tools and clinical trial endpoints development. Design Data presented and discussed in this review derive from the past and recent literature and the authors’ own research and experi
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Mashup Score: 14British Society of Gastroenterology guidelines for the management of hepatocellular carcinoma in adults - 2 day(s) ago
Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Servi
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Mashup Score: 10Histone methyltransferase Suv39h1 regulates hepatic stellate cell activation and is targetable in liver fibrosis - 2 day(s) ago
Objective Liver fibrosis is a prelude to a host of end-stage liver diseases. Hepatic stellate cells (HSCs), switching from a quiescent state to myofibroblasts, are the major source for excessive production of extracellular matrix proteins. In the present study, we investigated the role of Suv39h1, a lysine methyltransferase, in HSC-myofibroblast transition and the implication in liver fibrosis. Design HSC-specific or myofibroblast-specific Suv39h1 deletion was achieved by crossbreeding the Suv39h1 f/f mice to the Lrat -Cre mice or the Postn -CreERT2 mice. Liver fibrosis was induced by CCl4 injection or bile duct ligation. Results We report that Suv39h1 expression was universally upregulated during HSC-myofibroblast transition in different cell and animal models of liver fibrosis and in human cirrhotic liver tissues. Consistently, Suv39h1 knockdown blocked HSC-myofibroblast transition in vitro. HSC-specific or myofibroblast-specific deletion of Suv39h1 ameliorated liver fibrosis in mice
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Mashup Score: 16Coeliac disease: the paradox of diagnosing a food hypersensitivity disorder with autoantibodies - 3 day(s) ago
Serum antibodies to the autoantigen transglutaminase 2 (TG2) are increasingly harnessed to diagnose coeliac disease. Diagnostic guidelines for children give recommendation for a no-biopsy-based diagnosis through detection of high amounts of IgA anti-TG2 antibodies in serum with confirmation of positivity in a separate blood sample by characteristic autoantibody-staining of tissue. While measurement of IgA anti-TG2 also is important in the diagnostic workup of adults, the adult guidelines still mandate examination of gut biopsies. This requirement might well change in the future, as might the necessity for confirming autoantibody positivity by tissue staining. The key role of autoantibody serology for diagnosis of coeliac disease is paradoxical. Coeliac disease was considered, and still can be considered, a food intolerance disorder where autoantibodies at face value are out of place. The immunological mechanisms underlying the formation of autoantibodies in response to gluten exposure
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Mashup Score: 8Predicting treatment response in ASUC: do we measure systemic severity, organ response or both? - 3 day(s) ago
We would like to congratulate Adams et al on the paper addressing the important issue regarding the development of prognostic clinical indexes for patients with acute severe ulcerative colitis (ASUC) leading to the development of the ADMIT-ASC score.1 Although we acknowledge the initiative, the development of a static prognostic index might be reconsidered with the increased availability and use of noninvasive and real-time cross-sectional imaging. Recently, we investigated the use of intestinal ultrasound (IUS) to measure early changes in the sigmoid bowel wall thickness (BWT) as an indicator of intravenous corticosteroid (CS) response in patients admitted with ASUC. A >20% reduction in BWT after 48 hours predicted CS response within 7 days (p<0.0001 for pMayo response, p=0.006 for no need of rescue therapy) and was superior to CRP, albumin or pMayo response at 48 hours in multivariate analysis.2 With C-reactive protein (CRP), albumin and endoscopic severity scores being major compone
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Mashup Score: 33Serum ferritin levels can predict long-term outcomes in patients with metabolic dysfunction-associated steatotic liver disease - 4 day(s) ago
Objective Hyperferritinaemia is associated with liver fibrosis severity in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), but the longitudinal implications have not been thoroughly investigated. We assessed the role of serum ferritin in predicting long-term outcomes or death. Design We evaluated the relationship between baseline serum ferritin and longitudinal events in a multicentre cohort of 1342 patients. Four survival models considering ferritin with confounders or non-invasive scoring systems were applied with repeated five-fold cross-validation schema. Prediction performance was evaluated in terms of Harrell’s C-index and its improvement by including ferritin as a covariate. Results Median follow-up time was 96 months. Liver-related events occurred in 7.7%, hepatocellular carcinoma in 1.9%, cardiovascular events in 10.9%, extrahepatic cancers in 8.3% and all-cause mortality in 5.8%. Hyperferritinaemia was associated with a 50% increased risk of li
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#GUTImages from the paper by @AngeloArmandi et al on "Serum ferritin levels can predict long-term outcomes in patients with metabolic dysfunction-associated steatotic liver disease" via https://t.co/oap3sTWjmt @DinaTiniakos @lucavalenti75 @lmiele74 @hanneshagstrom @mromerogomez https://t.co/6KG8WdxzSU
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Mashup Score: 0Gut: 73 (5) - 4 day(s) ago
(21 November, 2023) Emily L Black, Emma Ococks, Ginny Devonshire, Alvin Wei Tian Ng, Maria O’Donovan, Shalini Malhotra, Monika Tripathi, Ahmad Miremadi, Adam Freeman, Hannah Coles, Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium, Rebecca C Fitzgerald (8 February, 2024) Free Kurtis F Budden, Shakti D Shukla, Kate L Bowerman, Annalicia Vaughan, Shaan L Gellatly, David L A Wood, Nancy Lachner, Sobia Idrees, Saima Firdous Rehman, Alen Faiz, Vyoma K Patel, Chantal Donovan, Charlotte
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