Assessing Generative Pretrained Transformers (GPT) in Clinical Decision-Making: Comparative Analysis of GPT-3.5 and GPT-4.

BACKGROUND: Artificial intelligence, particularly chatbot systems, is becoming an instrumental tool in health care, aiding clinical decision-making and patient engagement. OBJECTIVE: This study aims to analyze the performance of ChatGPT-3.5 and ChatGPT-4 in addressing complex clinical and ethical dilemmas, and to illustrate their potential role in health care decision-making while comparing seniors' and residents' ratings, and specific question types. METHODS: A total of 4 specialized physicians formulated 176 real-world clinical questions. A total of 8 senior physicians and residents assessed responses from GPT-3.5 and GPT-4 on a 1-5 scale across 5 categories: accuracy, relevance, clarity, utility, and comprehensiveness. Evaluations were conducted within internal medicine, emergency medicine, and ethics. Comparisons were made globally, between seniors and residents, and across classifications. RESULTS: Both GPT models received high mean scores (4.4, SD 0.8 for GPT-4 and 4.1, SD 1.0 for GPT-3.5). GPT-4 outperformed GPT-3.5 across all rating dimensions, with seniors consistently rating responses higher than residents for both models. Specifically, seniors rated GPT-4 as more beneficial and complete (mean 4.6 vs 4.0 and 4.6 vs 4.1, respectively; P<.001), and GPT-3.5 similarly (mean 4.1 vs 3.7 and 3.9 vs 3.5, respectively; P<.001). Ethical queries received the highest ratings for both models, with mean scores reflecting consistency across accuracy and completeness criteria. Distinctions among question types were significant, particularly for the GPT-4 mean scores in completeness across emergency, internal, and ethical questions (4.2, SD 1.0; 4.3, SD 0.8; and 4.5, SD 0.7, respectively; P<.001), and for GPT-3.5's accuracy, beneficial, and completeness dimensions. CONCLUSIONS: ChatGPT's potential to assist physicians with medical issues is promising, with prospects to enhance diagnostics, treatments, and ethics. While integration into clinical workflows may be valuable, it must complement, not replace, human expertise. Continued research is essential to ensure safe and effective implementation in clinical environments.

Adverse cardiovascular events in rheumatoid arthritis patients treated with JAK inhibitors: An analysis of postmarketing spontaneous safety reports.

OBJECTIVES: The ORAL Surveillance trial, a postmarketing safety clinical trial, found an increased risk of adverse cardiovascular events and venous thromboembolism (VTE) in patients treated with Janus Kinase (JAK) inhibitors compared to tumor necrosis factor (TNF) inhibitors. However, additional studies yielded mixed results and data on other JAK inhibitors are limited. METHODS: A retrospective, pharmacovigilance study using the FDA adverse event reporting system (FAERS) to assess reporting of adverse cardiovascular events following treatment with JAK inhibitors in rheumatoid arthritis (RA) patients between January 2015 and June 2023. To identify disproportionately increased reporting, an adjusted reporting odds ratio (adj.ROR) was calculated with a multivariable logistic regression model. RESULTS: We identified safety reports of 75,407 RA patients treated with JAK inhibitors (tofacitinib, n = 52,181; upadacitinib, n = 21,006; baricitinib, n = 2,220) and 303,278 patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs; TNF inhibitors, rituximab, and tocilizumab). The mean age was 61.2(±12) and 59.0(±13), respectively; 82 % and 81 % were women. Compared to bDMARDs, JAK inhibitors were associated with an increased reporting of VTE [n = 1,393, adj.ROR=2.11 (1.97-2.25)], stroke [n = 973, adj.ROR=1.25 (1.16-1.34)], ischemic heart disease [IHD, n = 999, adj.ROR=1.23 (1.13-1.33)], peripheral edema [n = 2699, adj.ROR=1.22 (1.17-1.28)], and tachyarrhythmias [n = 370, adj.ROR=1.15 (1.00-1.33)]. Most of the events occurred in the first year after treatment initiation. When different JAK inhibitors were compared, VTE, stroke, and IHD were more frequently reported with upadacitinib and baricitinib than tofacitinib. When stratified by age category, all safety signals were statistically significant in patients aged≤65 years. CONCLUSION: In this global postmarketing study, JAK inhibitors are associated with increased reporting of VTE, stroke, IHD, and tachyarrhythmias. These adverse events were reported following all JAK inhibitors that were studied, suggesting a class effect.

Exploring the Link Between Ankylosing Spondylitis and Inflammatory Bowel Disease: A Retrospective Cohort Study.

BACKGROUND: Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are chronic conditions with overlapping pathogenic mechanisms. The genetic predisposition and inflammatory pathways common to both diseases suggest a syndemic relationship. While some evidence points to a connection between the two conditions, other reports do not support this link. OBJECTIVES: To investigate the association between AS and the subsequent incidence of IBD. To identify potential risk factors and effect modifiers that contribute to this relationship. METHODS: Utilizing the Chronic Disease Registry of Clalit Health Services, we conducted a retrospective cohort study of individuals diagnosed with AS between January 2002 and December 2018. We compared these patients with age- and sex-matched controls, excluding those with a prior diagnosis of IBD. Statistical analyses included chi-square and t-tests for demographic comparisons, and Cox proportional hazards models for evaluating the risk of IBD development, with adjustments for various co-morbidities and demographic factors. RESULTS: The study included 5825 AS patients and 28,356 controls. AS patients demonstrated a significantly higher incidence of IBD with hazard ratios of 6.09 for Crohn's disease and 2.31 for ulcerative colitis, after multivariate adjustment. The overall incidence of IBD in the AS cohort was significantly higher compared to controls. CONCLUSIONS: AS patients exhibit a markedly increased risk of developing IBD. These findings advocate for heightened clinical vigilance for IBD symptoms in AS patients and suggest the need for a multidisciplinary approach to patient care. Further research into the shared pathogenic pathways is needed to develop personalized treatment strategies and improve patient management.

Ecogastroenterology: cultivating sustainable clinical excellence in an environmentally conscious landscape.

Gastrointestinal practices, especially endoscopy, have a substantial environmental impact, marked by notable greenhouse gas emissions and waste generation. As the world struggles with climate change, there emerges a pressing need to re-evaluate and reform the environmental footprint within gastrointestinal medicine. The challenge lies in finding a harmonious balance between ensuring clinical effectiveness and upholding environmental responsibility. This task involves recognising that the most significant reduction in the carbon footprint of endoscopy is achieved by avoiding unnecessary procedures; addressing the use of single-use endoscopes and accessories; and extending beyond the procedural suites to include clinics, virtual care, and conferences, among other aspects of gastrointestinal practice. The emerging digital realm in health care is crucial, given the potential environmental advantages of virtual gastroenterological care. Through an in-depth analysis, this review presents a path towards sustainable gastrointestinal practices, emphasising integrated strategies that prioritise both patient care and environmental stewardship.

The association between psoriasis, psoriasis severity, and inflammatory bowel disease: a population-based analysis.

Background: The skin-gut axis, characterized by bidirectional communication between the skin and gut, plays a crucial role in the pathogenesis of psoriasis and inflammatory bowel diseases (IBD). Objectives: We aimed to explore the association between psoriasis and IBD and identify predictors associated with IBD development among patients with psoriasis. Design: Retrospective cohort study. Methods: A retrospective study which utilized an electronic database from the Meuhedet Health Maintenance Organization (MHMO) in Israel. Psoriasis was categorized as severe if any systemic agent or phototherapy was administered. Univariate and multivariate logistic regressions were used to identify specific predictors for IBD, with adjustments made for potential confounders. The study received approval from the Ethical Committee of the MHMO. Results: In total, 61,003 adult patients who were diagnosed with psoriasis between 2000 and 2022 were included. Among them, 1495/61,003 patients (2.4%) were diagnosed with IBD, as compared to 3834/244,012 patients (1.6%) in the non-psoriasis group [adjusted odds ratio (OR): 1.47; 95% confidence interval (CI): 1.37-1.56; p < 0.001]. Increased age (OR: 1.01; 95% CI: 1.01-1.02; p < 0.001), male gender (OR: 1.22; 95% CI: 1.03-1.45; p = 0.024), and Jewish ethnicity (OR: 2.5; 95% CI: 1.2-4.1; p < 0.001) were identified as significant risk factors for IBD. Spondyloarthropathies, including psoriatic arthritis (OR: 2.27; 95% CI: 1.86-2.77; p < 0.001) and ankylosing spondylitis (OR: 2.82; 95% CI: 1.5-5.32; p < 0.05), were associated with a higher prevalence of IBD. Furthermore, severe psoriasis was significantly associated with a higher likelihood of IBD, compared to mild psoriasis (OR: 16.03; 95% CI: 11.02-23.34; p < 0.001). Conclusion: A significant association between psoriasis and IBD was demonstrated, including its subtypes: Crohn's disease and ulcerative colitis. Moreover, such association may depend on psoriasis severity as determined by the treatment used. This association warrants further investigation and implies a potential need for closer monitoring of patients with severe psoriasis.

Association between psoriatic disease severity and risk of inflammatory bowel diseases 1- Gut and skin barrier play an integral role in psoriasis and inflammatory bowel disease (IBD) development. 2- Shared genetic and environmental factors could explain the association between both diseases. 3- We report increased association between psoriasis and IBD, a relationship that is more pronounced in patients with severe psoriasis. 4- Patients with spondyloarthritis related diseases have a stronger association with IBD.

Unraveling the connection: Uveitis prevalence and risk factors in psoriasis patients - a population-based study.

The association between uveitis and spondyloarthropathy (SpA)-related conditions is well-established. However, evidence describing the link between uveitis and psoriasis, and psoriasis without concomitant SpA-related conditions is scarce and conflicting. This large-scale population-based study sought to describe the prevalence and features of uveitis among psoriasis patients in Israel as well as investigating the risk for uveitis in different subgroups of psoriasis patients compared to the general population. We conducted a retrospective study utilizing the electronic database of the Meuhedet Health Maintenance Organization. The study included all patients diagnosed with psoriasis between 2000 and 2020, each patient was matched with four controls based on age, sex, place of residence, and index date. Logistic regression models were employed to assess the association between psoriasis and uveitis while adjusting for the presence of SpA-related conditions. A total of 61 003 psoriasis patients and 244 012 matched controls were included. The prevalence of uveitis was 1.3% versus 1.1% respectively (OR 1.12; 95% CI 1.10-1.30; p < 0.001). When adjusting to psoriasis severity, concurrent SpA, and psoriasis treatment no significant association was found. The rates of uveitis among psoriasis patients with concurrent SpA-related conditions was 3.2% compared to 1.4% in controls without psoriasis or SpA (OR 2.38; 95% CI 2.00-2.83; p < 0.001), while in psoriasis patients without SpA, the rate of uveitis was 1.0% and was similar to controls. Although crude rates of uveitis were higher in patients with severe psoriasis compared to mild psoriasis (2.1% vs. 1.1%), after adjustment, no significant association compared to controls was found in either group. Our findings suggest that the positive association between psoriasis and uveitis is primarily mediated by the coexistence of other SpA-related conditions. These findings imply the presence of a shared pathogenetic mechanism and set the direction for a phenotypic-targeted screening strategy.

Allergic manifestations in women with silicone breast implants.

INTRODUCTION: Silicone breast implants (SBI) result in immune dysregulation and are associated with autoimmune diseases. Recently, we reported dysregulated levels of IgG autoantibodies directed against G protein-coupled receptors (GPCRs) of the autonomic nervous system which were linked to the autoimmune dysautonomia in silicone breast implant illness (SBII). AIMS: We aimed to explore the possible association between allergy with dysregulated IgE autoantibodies directed against GPCRs of the autonomic nervous system in women with SBI. METHODS: Circulating levels of IgE autoantibodies against GPCRs of the autonomic nervous system (adrenergic, muscarinic, endothelin and angiotensin receptors) have been evaluated in women with SBIs who complained of allergic symptoms, and compared to subjects with SBI without allergic manifestations and to age-matched healthy women without SBI. RESULTS: We report a significant dysregulation in three circulating autoantibodies: IgE-beta1 adrenergic receptor (B1AR), IgE-alpha 1 adrenergic receptor (A1AR) and IgE-muscarinic acetylcholine receptor type 1 (M1R) autoantibodies in women with SBI who complained of allergic symptoms. CONCLUSIONS: Allergic reactions associated with SBI are not uncommon. Imbalance of circulating levels of IgE autoantibodies against GPCRs of the autonomic nervous system might play a role not only in allergic reactions, but also in other enigmatic aspects of SBII such as autoimmune dysautonomia.

Deep Learning in Coeliac Disease: A Systematic Review on Novel Diagnostic Approaches to Disease Diagnosis.

BACKGROUND: Coeliac disease affects approximately 1% of the global population with the diagnosis often relying on invasive and time-demanding methods. Deep learning, a powerful tool in medical science, shows potential for non-invasive, accurate coeliac disease diagnosis, though challenges remain. OBJECTIVE: This systematic review aimed to evaluate the current state of deep-learning applications in coeliac disease diagnosis and identify potential areas for future research that could enhance diagnostic accuracy, sensitivity, and specificity. METHODS: A systematic review was conducted using the following databases: PubMed, Embase, Web of Science, and Scopus. PRISMA guidelines were applied. Two independent reviewers identified research articles using deep learning for coeliac disease diagnosis and severity assessment. Only original research articles with performance metrics data were included. The quality of the diagnostic accuracy studies was assessed using the QUADAS-2 tool, categorizing studies based on risk of bias and concerns about applicability. Due to heterogeneity, a narrative synthesis was conducted to describe the applications and efficacy of the deep-learning techniques (DLT) in coeliac disease diagnosis. RESULTS: The initial search across four databases yielded 417 studies with 195 being removed due to duplicity. Finally, eight studies were found to be suitable for inclusion after rigorous evaluation. They were all published between 2017 and 2023 and focused on using DLT for coeliac disease diagnosis or assessing disease severity. Different deep-learning architectures were applied. Accuracy levels ranged from 84% to 95.94% with the GoogLeNet model achieving 100% sensitivity and specificity for video capsule endoscopy images. CONCLUSIONS: DLT hold substantial potential in coeliac disease diagnosis. They offer improved accuracy and the prospect of mitigating clinician bias. However, key challenges persist, notably the requirement for more extensive and diverse datasets, especially to detect milder forms of coeliac disease. These methods are in their nascent stages, underscoring the need of integrating multiple data sources to achieve comprehensive coeliac disease diagnosis.

A comparative systematic review and meta-analysis on the diagnostic accuracy of non-invasive tests for Helicobacter pylori detection in elderly patients.

Background: Helicobacter pylori (H. pylori) infection, a type I carcinogen, affects approximately 50% of the global population, correlating with various gastric pathologies. Notably, diagnostic sensitivities of non-invasive methods, such as the stool antigen test (HpSA), Serology, and Urea Breath Test (UBT), have been suggested to be less effective in older age groups. This study systematically reviews and meta-analyzes the diagnostic accuracy of these tests within the elderly population. Methods: A comprehensive literature search was performed across multiple databases, including PubMed, Medline, and Web of Science, up to July 2023. Data were pooled and analyzed using random-effects models. Sensitivity, specificity, and Diagnostic Odds Ratios (DOR) were computed for the tests. Heterogeneity and risk of bias were assessed. Results: Eight studies involving diverse geographic locations and totaling between 46 and 1,441 participants per study were included. The pooled sensitivity and specificity for HpSA were 72.5 and 94.7%, for Serology 83.7 and 73.3%, and for UBT 96.4 and 88.3%, respectively. DOR for UBT, HpSA, and Serology were 94.5, 47.9, and 14.2, respectively. High levels of heterogeneity were observed across the studies. Conclusion: UBT and HpSA proved effective for diagnosing H. pylori in those over 60, while serology showed lower specificity. Despite methodological variations in available studies, these non-invasive tests offer reliable alternatives, especially for older patients who recently undergone endoscopy or without an indication for it, warranting consideration by healthcare practitioners.

Evaluating the role of ChatGPT in gastroenterology: a comprehensive systematic review of applications, benefits, and limitations.

Background: The integration of artificial intelligence (AI) into healthcare has opened new avenues for enhancing patient care and clinical research. In gastroenterology, the potential of AI tools, specifically large language models like ChatGPT, is being explored to understand their utility and effectiveness. Objectives: The primary goal of this systematic review is to assess the various applications, ascertain the benefits, and identify the limitations of utilizing ChatGPT within the realm of gastroenterology. Design: Through a systematic approach, this review aggregates findings from multiple studies to evaluate the impact of ChatGPT on the field. Data sources and methods: The review was based on a detailed literature search of the PubMed database, targeting research that delves into the use of ChatGPT for gastroenterological purposes. It incorporated six selected studies, which were meticulously evaluated for quality using the Joanna Briggs Institute critical appraisal instruments. The data were then synthesized narratively to encapsulate the roles, advantages, and drawbacks of ChatGPT in gastroenterology. Results: The investigation unearthed various roles of ChatGPT, including its use in patient education, diagnostic self-assessment, disease management, and the formulation of research queries. Notable benefits were its capability to provide pertinent recommendations, enhance communication between patients and physicians, and prompt valuable research inquiries. Nonetheless, it encountered obstacles in decoding intricate medical questions, yielded inconsistent responses at times, and exhibited limitations in generating novel content. The review also considered ethical implications. Conclusion: ChatGPT has demonstrated significant potential in the field of gastroenterology, especially in facilitating patient-physician interactions and managing diseases. Despite these advancements, the review underscores the necessity for ongoing refinement, customization, and ethical regulation of AI tools. These findings serve to enrich the dialog concerning AI's role in healthcare, with a specific focus on ChatGPT's application in gastroenterology.

Checking how ChatGPT works in gastroenterology: a detailed look at its uses, advantages, and challenges Goal We looked at how ChatGPT, a computer program, is used in the study Gastroenterology. We wanted to understand what's good about it, what's challenging, and how it can help doctors and patients. How We Did It We searched for articles about ChatGPT in Gastroenterology on PubMed. We found six suitable articles and checked their quality using the Joanna Briggs Institute (JBI) critical appraisal tools. Then, we put all the information together to get a clear picture. What We Found Doctors and researchers use ChatGPT in many ways. Some use it to teach patients about their health, while others use it to help patients check their symptoms or manage their conditions. It can even help come up with research questions. The good things about ChatGPT are that it gives helpful advice, makes talking between doctors and patients easier, and helps come up with research topics. But, sometimes it doesn't understand hard medical questions, gives different answers for the same question, or lacks new ideas. There are also concerns about using it the right way. What This Means ChatGPT can be a helpful tool in Gastroenterology, especially when talking with patients and managing their health. But, there are challenges that need to be fixed. Our review helps people understand how ChatGPT can be used in health care, especially in the field of Gastroenterology.

Deep Learning and Gastric Cancer: Systematic Review of AI-Assisted Endoscopy.

BACKGROUND: Gastric cancer (GC), a significant health burden worldwide, is typically diagnosed in the advanced stages due to its non-specific symptoms and complex morphological features. Deep learning (DL) has shown potential for improving and standardizing early GC detection. This systematic review aims to evaluate the current status of DL in pre-malignant, early-stage, and gastric neoplasia analysis. METHODS: A comprehensive literature search was conducted in PubMed/MEDLINE for original studies implementing DL algorithms for gastric neoplasia detection using endoscopic images. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The focus was on studies providing quantitative diagnostic performance measures and those comparing AI performance with human endoscopists. RESULTS: Our review encompasses 42 studies that utilize a variety of DL techniques. The findings demonstrate the utility of DL in GC classification, detection, tumor invasion depth assessment, cancer margin delineation, lesion segmentation, and detection of early-stage and pre-malignant lesions. Notably, DL models frequently matched or outperformed human endoscopists in diagnostic accuracy. However, heterogeneity in DL algorithms, imaging techniques, and study designs precluded a definitive conclusion about the best algorithmic approach. CONCLUSIONS: The promise of artificial intelligence in improving and standardizing gastric neoplasia detection, diagnosis, and segmentation is significant. This review is limited by predominantly single-center studies and undisclosed datasets used in AI training, impacting generalizability and demographic representation. Further, retrospective algorithm training may not reflect actual clinical performance, and a lack of model details hinders replication efforts. More research is needed to substantiate these findings, including larger-scale multi-center studies, prospective clinical trials, and comprehensive technical reporting of DL algorithms and datasets, particularly regarding the heterogeneity in DL algorithms and study designs.

Big data- and machine learning-based analysis of a global pharmacovigilance database enables the discovery of sex-specific differences in the safety profile of dual IL4/IL13 blockade.

Background: Due to its apparent efficacy and safety, dupilumab, a monoclonal antibody that blocks Interleukin 4 (IL-4) and Interleukin 13 (IL-13), has been approved for treating T-helper 2 (Th2) disorders. However, adverse effects like local injection site reactions, conjunctivitis, headaches, and nasopharyngitis have been reported. Sex differences are known to influence both adaptive and innate immune responses and, thus, may have a bearing on the occurrence of these adverse effects. Nevertheless, the literature lacks a comprehensive exploration of this influence, a gap this study aims to bridge. Materials and Methods: A comprehensive data mining of VigiBase, the World Health Organization (WHO) global pharmacovigilance database which contains case safety reports of adverse drug reactions (ADRs) was performed to test for sex -specific safety response to dual IL4/IL13 blockade by dupilumab. The information component (IC), a measure of the disproportionality of ADR occurrence, was evaluated and compared between males and females to identify potential sexual dimorphism. Results: Of the 94,065 ADRs recorded in the WHO global pharmacovigilance database, 2,001 (57.4%) were reported among female dupilumab users, and 1,768 (50.7%) were among males. Immune/autoimmune T-helper 1 (Th1)-, innate- and T-helper 17 (Th17)-driven diseases and degenerative ones were consistently reported with a stronger association with Dupilumab in males than females. Some adverse events were more robustly associated with Dupilumab in females. Conclusion: Dupilumab has an excellent safety profile, even though some ADRs may occur. The risk is higher among male patients, further studies, including ad hoc studies, are needed to establish causality.

Biologic Treatment Modification Efficacy in Concurrent Inflammatory Bowel Disease and Ankylosing Spondylitis: A Retrospective Cohort Study at a Single Tertiary Center.

BACKGROUND: The link between ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) is well-established, with concurrent prevalence estimates ranging from 5-10%. However, there are still significant gaps in our understanding, and a comprehensive treatment guideline for these co-diagnosed patients has yet to be established. Our objective was to explore patterns of treatment alterations following the diagnosis of AS in patients previously diagnosed with IBD, and vice versa. Additionally, we sought to determine how these modifications influence clinical outcomes in both conditions. METHODS: This retrospective data-based cohort study included patients with coexisting IBD and AS that were diagnosed between the years 2009-2022 and were followed by the gastroenterology and the rheumatology units of the Sheba Medical Center, Israel. The data were extracted from the electronic health record and included demographic information, medication history, treatment modification at the time of second diagnosis, and the characteristics and activity of both IBD and AS at the index time and at the 3-month mark. RESULTS: The study included a total of 68 patients, with a male predominance (40 patients, 59%). The median age was 43 years (IQR 31-55) and 78% had Crohn's disease (CD). The median duration between the diagnosis of the first disease to the second one was 4 years (IQR 1-9.5). A significant proportion of patients (85%) underwent treatment modification at their second diagnosis. Out of the total cohort, 28% initiated biological therapy, 17.6% switched their biologic regimen, and 16.2% discontinued NSAIDS. Patients who underwent biologic modifications at time of the second diagnosis (the initiation/switch/augmentation of a concurrent regimen) experienced significantly higher rates of clinical improvement in either IBD or AS at the 90-day follow-up compared to patients who did not (68% vs. 32%, p = 0.004), and biologic modification was found to be an independent predictor for clinical improvement (OR 3.69, CI 1.08-12.58, p = 0.037). CONCLUSIONS: Our findings suggest that biologic therapy modification at the time of the second diagnosis was associated with a higher rate of improvement in AS/IBD at the 90-day follow-up.

Unraveling the Immunopathological Landscape of Celiac Disease: A Comprehensive Review.

Celiac disease (CD) presents a complex interplay of both innate and adaptive immune responses that drive a variety of pathological manifestations. Recent studies highlight the role of immune-mediated pathogenesis, pinpointing the involvement of antibodies against tissue transglutaminases (TG2, TG3, TG6), specific HLA molecules (DQ2/8), and the regulatory role of interleukin-15, among other cellular and molecular pathways. These aspects illuminate the systemic nature of CD, reflecting its wide-reaching impact that extends beyond gastrointestinal symptoms to affect other physiological systems and giving rise to a range of pathological landscapes, including refractory CD (RCD) and, in severe cases, enteropathy-associated T cell lymphoma. The existing primary therapeutic strategy, a gluten-free diet (GFD), poses significant challenges, such as low adherence rates, necessitating alternative treatments. Emerging therapies target various stages of the disease pathology, from preventing immunogenic gluten peptide absorption to enhancing intestinal epithelial integrity and modulating the immune response, heralding potential breakthroughs in CD management. As the understanding of CD deepens, novel therapeutic avenues are emerging, paving the way for more effective and sophisticated treatment strategies with the aim of enhancing the quality of life of CD patients. This review aims to delineate the immunopathology of CD and exploring its implications on other systems, its complications and the development of novel treatments.

Increased risk of osteoporosis and femoral neck fractures in patients with familial Mediterranean fever-a large retrospective cohort study.

OBJECTIVES: The direct impact of inflammatory conditions and their therapy with corticosteroids both contribute to an increased risk of osteoporosis with associated fractures. Familial-Mediterranean-Fever (FMF) is an autoinflammatory disorder not commonly treated with corticosteroids. Evidence regarding FMF association with osteoporosis and femur fractures is anecdotal. We aimed to evaluate the incidence and risk of osteoporosis and femoral neck fracture in FMF patients compared with the general population. METHODS: A retrospective cohort study using the electronic database of Clalit Health Services of all FMF patients first diagnosed between 2000-2016 and controls was evaluated including age and sex matched controls in 1:1 ratio. Follow-up continued until the first diagnosis of osteoporosis or fracture. Risk for these conditions was compared using univariate and multivariate cox-regression models. RESULTS: 9,769 FMF patients were followed for a median period of 12.5 years. 304 FMF patients were diagnosed with osteoporosis compared with 191 controls, resulting in an incidence rate (per 10 000 persons-years) of 28.8 and 17.8 respectively, and a crude HR of 1.62 (95%CI 1.35-1.93; p< 0.001). Patients were diagnosed with osteoporosis at a considerably younger age than controls (60.1 ± 12.4 vs 62.5 ± 11.0 years; p= 0.028). 56 FMF patients were diagnosed with femoral neck fracture compared with 35 controls, resulting in an incidence rate of 5.3 and 3.3 respectively, and a crude HR of 1.60 (95%CI 1.05-2.44; p< 0.05). CONCLUSION: FMF patients are at increased risk for osteoporosis and consequently femur fracture. Our findings emphasize the importance of considering bone health in the management of FMF patients.

The Prevalence of Dementia among Dermatomyositis and Polymyositis Patients: A Retrospective Cohort Study.

BACKGROUND: Polymyositis (PM) and dermatomyositis (DM) are inflammatory mediated myopathies characterized by progressive symmetric proximal muscle weakness and associated with extra-muscular involvement. Central nervous system complications are rarely reported with these diseases. OBJECTIVES: To investigate the association between dementia and PM/DM. METHODS: A retrospective cohort study was conducted using a database from Clalit Health Care, the largest health maintenance organization in Israel. Patients with a first recorded diagnosis of PM/DM were included and were compared with age- and sex-matched controls by a ratio of 1:5. The prevalence of dementia among PM/DM patients compared to controls was assessed using a univariate and a multivariable model. Binary logistic regression analysis was conducted to assess the association of different factors with dementia within the PM/DM cohort. RESULTS: The study included 2085 PM/DM cases (17.0%) and 10,193 age- and sex-matched controls (83.0%). During the follow-up time, 36 PM/DM patients were diagnosed with dementia compared to 160 controls, with a univariate hazard ratio (HR) of 1.10 (95% confidence interval [95%CI] 0.77-1.58). Within the PM/DM cohort, significant predictors for the development of dementia included increased age at diagnosis (5 years increment; OR 1.86, 95%CI 1.57-2.21, P < 0.001) and treatment with glucocorticoids (OR 5.40, 95%CI 1.67-17.67, P = 0.005). CONCLUSIONS: In our cohort, inflammatory myopathies were not associated with dementia. Age and treatment with glucocorticoids were associated with dementia. If dementia is diagnosed in patients with inflammatory myopathies, other systemic causes should be investigated.

Gastric Perforation After Microwave Ablation to Adjacent Hepatocellular Lesion.

Locoregional treatment modalities for hepatocellular carcinoma are generally effective and safe and benefit the subset of patients who are not eligible for surgery or have marginal hepatic function. This case report discusses a 77-year-old patient with cirrhosis who underwent microwave lesion ablation for 3 hepatocellular carcinoma nodules. On the 12th day after ablation, the patient was diagnosed with a perforation of the anterior wall of the stomach near one of the target ablation sites on the left side of the liver. The patient underwent surgical therapy with clinical improvement. This report highlights the potential risks associated with microwave ablation for hepatocellular carcinoma.

Ankylosing spondylitis is associated with increased prevalence of valvular heart diseases: a cross-sectional population-based study.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory arthritis primarily affecting the sacroiliac joint and axial skeleton with associated extra-articular involvement including cardiovascular system disease including aortic valve disease with variable reported prevalence. The aim of this study is to determine the prevalence of heart valve disorders in AS patients. METHODS: This was a retrospective, population-based, cross-sectional study that retrieved data from the Clalit Health Services registry. Cases were defined as having AS, whereas controls were frequency matched by age and sex in a ratio of 5:1. The prevalence of valvular heart diseases was compared between the two groups; a multivariate logistic regression model was applied to estimate the association after controlling for potential confounders. RESULTS: We included 4082 AS patients and 20 397 controls frequency matched by age and sex. AS patients had a significantly higher prevalence of cardiovascular risk factors (P < .001) and a higher prevalence of valvular heart disease. In the multivariate logistic regression model, adjusting for multiple confounding factors, AS was independently associated with aortic stenosis [odds ratio (OR): 2.25, 95% confidence interval (CI): 1.57-3.23, P < 0.001], aortic insufficiency (OR: 2.44, 95% CI: 1.50-3.94, P < 0.001), and mitral insufficiency (OR: 1.75, 95% CI: 1.17-2.61, P < 0.001) but not mitral stenosis (OR: 1.31, 95% CI: 0.60-2.70, P = 0.47). CONCLUSIONS: Our study reports the increased risk of valvular heart diseases in patients with AS, possibly due to the inflammatory milieu associated with the disease process and the result of biomechanical stress affecting the enthesis-like valvular structures.

The risk of osteoporosis in patients with ankylosing spondylitis—A large retrospective matched cohort study / El riesgo de osteoporosis en pacientes con espondilitis anquilosante: un estudio retrospectivo de cohortes emparejadas

Background Ankylosing spondylitis (AS) is associated with increased bone turnover and systemic inflammation. Osteoporosis is common but frequently underappreciated in AS, studies regarding the incidence of osteoporosis in AS are limited and based on small cohorts. The aim of this study is to assess the risk of osteoporosis in patients with AS compared to matched controls. Methods A population based retrospective cohort study using data retrieved from a large electronic medical record in Israel, the Clalit health services. Included patients that were diagnosed with AS from January 2002 to December 2018 were followed for development of osteoporosis. The incidence of osteoporosis was compared between AS and controls and a logistic regression model was used to assess the interaction between AS and osteoporosis. Results The study included 5476 AS patients, and 27,657 age- and sex-frequency matched controls. The incidence of osteoporosis in AS patients was significantly higher than controls (4.7% vs 2.8%, p < 0.001) in the whole cohort as well as when stratified by sex. Osteoporosis developed earlier in patients with AS versus controls (4.1 vs 5.2 years, p < 0.001). In multivariate analysis and after adjustment to several potential confounders, AS was found to independently associated with osteoporosis (HR 1.83, 95%CI 1.58–2.11, p < 0.0001). Conclusions Our study confirms the higher incidence and earlier development of osteoporosis in patients with AS. Such finding highlights the increased need of awareness and earlier detection of such comorbidity allowing prompt treatment to prevent undesired sequalae including increased risk of fractures (AU)

Antecedentes La espondilitis anquilosante (EA) se asocia a un aumento del recambio óseo y de la inflamación sistémica. La osteoporosis es común pero frecuentemente subestimada en la EA: los estudios sobre la incidencia de la osteoporosis en la EA son limitados y se basan en cohortes pequeñas. El objetivo de este estudio es evaluar el riesgo de osteoporosis en pacientes con EA en comparación con controles emparejados. Métodos Estudio de cohorte retrospectivo basado en la población utilizando datos recuperados de un gran registro médico electrónico en Israel, los servicios de salud Clalit. Se incluyeron pacientes a los que se les diagnosticó EA desde enero de 2002 hasta diciembre de 2018 y se les hizo un seguimiento para el desarrollo de osteoporosis. Se comparó la incidencia de osteoporosis entre los pacientes con EA y los controles y se utilizó un modelo de regresión logística para evaluar la interacción entre la EA y la osteoporosis. Resultados El estudio incluyó a 5.476 pacientes con EA y a 2.7657 controles emparejados por edad y sexo. La incidencia de osteoporosis en los pacientes con EA fue significativamente mayor que en los controles (4,7% frente a 2,8%; p < 0,001) en toda la cohorte, así como cuando se estratificó por sexo. La osteoporosis se desarrolló antes en los pacientes con EA frente a los controles (4,1 frente a 5,2 años; p < 0,001). En el análisis multivariado y tras ajustar varios posibles factores de confusión, se observó que la EA se asociaba de forma independiente con la osteoporosis (HR: 1,83; IC 95%: 1,58-2,11; p < 0,0001). Conclusiones Nuestro estudio confirma la existencia de mayor incidencia y el desarrollo más temprano de la osteoporosis en pacientes con EA. Este hallazgo pone de manifiesto la necesidad de una mayor concienciación y una detección más temprana de esta comorbilidad, lo que permitirá un tratamiento rápido para evitar secuelas no deseadas, como el aumento del riesgo de fracturas (AU)