A Hidden Cause of Hypertransaminasemia: Liver Toxicity Caused by Chelidonium Majus L. : Report of Two Cases of Herb-Induced Liver Injury and Literature Review.

BACKGROUND: In instances where individuals manifest elevated transaminase levels without a clearly discernible cause, a comprehensive patient history proves invaluable in unveiling latent triggers. In this report, we present 2 cases of herb-induced liver injury (HILI) characterized by severe hypertransaminasemia attributed to the consumption of Chelidonium majus L . (also known as greater celandine [GC]), an agent considered an alternative therapeutic remedy. AREAS OF UNCERTAINTY: Exploring the occurrence and range of clinical manifestations in HILI linked to Chelidonium majus L ., while also investigating the potential triggers and predisposing factors for hepatotoxic reactions post Chelidonium majus L. usage, remains challenging due to the absence of definitive laboratory tests to identify the causative agent. DATA SOURCES: Two case reports were detailed, and a systematic literature review using PubMed was conducted including published literature till March 2023. Moreover, a manual search of reference lists of pertinent articles was performed to identify any additional relevant missed publications. RESULTS: In the first case, a 64-year-old woman presented with jaundice, revealing a 1-month history of using GC capsules to manage gallstones. Diagnostic assessment identified HILI, gallstones, and choledocolithiasis, with transaminase levels exceeding 1000 IU/L. After discontinuing GC and receiving intravenous therapy with amino acids and phospholipids, the patient's condition significantly improved. Subsequently, she underwent endoscopic common bile duct stone removal and cholecystectomy. In the second case, a 66-year-old woman presented with elevated liver function test results discovered incidentally during musculoskeletal pain evaluation. Upon further questioning, the patient disclosed regular consumption of GC tea for "health promotion." Following intravenous therapy using amino acids and phospholipids, her transaminase levels returned to normal. The literature review identified 38 cases of HILI associated with GC preparations, primarily in adult women aged 27-77 years, with a predominant reporting location in Germany. Various forms of GC were used, with treatment durations ranging from 1 week to a year. Discontinuation of GC generally led to recovery in these cases. CONCLUSION: Chelidonium majus L ., a potent herb often used in alternative medicine, has significant hepatotoxic potential, requiring physicians to be vigilant in cases of unexplained liver injury.

Prevalence and Natural History of Segmental Colitis Associated With Diverticulosis.

INTRODUCTION: We assessed the prevalence and clinical outcomes of segmental colitis associated with diverticulosis (SCAD) in patients with newly diagnosed diverticulosis. METHODS: A 3-year international, multicenter, prospective cohort study was conducted involving 2,215 patients. RESULTS: SCAD diagnosis was posed in 44 patients (30 male patients; median age: 64.5 years; prevalence of 1.99%, 95% confidence interval, 1.45%-2.66%). Patients with SCAD types D and B showed worse symptoms, higher fecal calprotectin values, needed more steroids, and reached less likely complete remission. DISCUSSION: Although SCAD generally had a benign outcome, types B and D were associated with more severe symptoms and worse clinical course.

Adiponectin Levels in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Adipose tissue plays an important role in the pathogenesis of inflammatory conditions. The role of adipokines in inflammatory bowel disease (IBD) has been evaluated in the current literature with conflicting results. The aim of this study was to evaluate adiponectin levels in IBD patients, including Crohn's disease (CD) and ulcerative colitis (UC), compared to controls, as well as further subgroup analyses. Hence, assessing the potential role of adiponectin as a surrogate marker. METHODS: We performed a systematic electronic search on PubMed, Embase, Scopus, and Cochrane Library, including observational or interventional studies evaluating serum or plasma adiponectin levels in IBD patients in humans. The primary summary outcome was the mean difference (MD) in serum or plasma adiponectin levels between IBD patients versus controls. Subgroup analyses were conducted involving adiponectin levels in CD and UC compared to controls, as well as CD compared to UC. RESULTS: A total of 20 studies were included in our qualitative synthesis and 14 studies in our quantitative synthesis, with a total population sample of 2,085 subjects. No significant MD in serum adiponectin levels was observed between IBD patients versus controls {-1.331 (95% confidence interval [CI]: -3.135-0.472)}, UC patients versus controls (-0.213 [95% CI: -1.898-1.472]), and CD patients versus controls (-0.851 [95% CI: -2.263-0.561]). Nevertheless, a significant MD was found between UC patients versus CD patients (0.859 [95% CI: 0.097-1.622]). CONCLUSIONS: Serum adiponectin levels were not able to differentiate between IBD, UC, and CD patients compared to controls. However, significantly higher serum adiponectin levels were observed in UC compared to CD patients.

How to Reduce Cardiovascular Risk in Nonalcoholic Fatty Liver Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a rapidly growing multisystem disease with extrahepatic manifestations, including effects on the cardiovascular (CV) system. The leading cause of death in NAFLD is of cardiac etiology being ischemic heart disease. AREAS OF UNCERTAINTY: NAFLD is associated with several CV complications including cardiac structural and functional alterations. However, there are no current approved pharmacotherapies for treating NAFLD, leading to increased CV risk with an increasing morbidity and mortality. DATA SOURCES: We summarize the currently available therapeutic strategies in managing NAFLD and their cardioprotective effects according to recently published data, guidelines, and practice guidance recommendations. THERAPEUTIC ADVANCES: Several therapeutic modalities evaluated in NAFLD include nonpharmacological strategies, pharmacotherapies and surgical management. Nonpharmacological strategies are recommended in early stages of NAFLD and include weight loss, physical activity, and dietary changes. Personalized management strategies with nonpharmacological lifestyle modifications are associated with reduced CV risk, improved liver enzyme levels, in addition to liver fat content, injury, and fibrosis. Several pharmacotherapies including lipid-lowering agents and antidiabetic drugs such as insulin sensitizers and incretin mimetics, in addition to antioxidants, ursodeoxycholic acid, semi-synthetic bile acid analogue, acetylsalicylic acid, and renin-angiotensin system inhibitors have been evaluated in the current literature. Despite promising results of several drugs in NAFLD with cardioprotective effects, we currently remain with no approved medical drugs for treating NAFLD. Although bariatric surgery was demonstrated to be associated with CV risk reduction and improvements in hepatic steatosis, inflammation, and fibrosis, it remains of limited use because of its invasiveness. CONCLUSIONS: Management of NAFLD necessitates a multidisciplinary team with a patient-centered and individualized medicine approach. Early lifestyle modifications are essential in NAFLD to reduce CV risk. Experimental studies are required to confirm hepatic and cardioprotective effects associated with several drugs. Bariatric surgery remains of limited use.

Do Colonic Mucosal Tumor Necrosis Factor Alpha Levels Play a Role in Diverticular Disease? A Systematic Review and Meta-Analysis.

Diverticular disease (DD) is the most frequent condition in the Western world that affects the colon. Although chronic mild inflammatory processes have recently been proposed as a central factor in DD, limited information is currently available regarding the role of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α). Therefore, we conducted a systematic review and meta-analysis aiming to assess the mucosal TNF-α levels in DD. We conducted a systematic literature search using PubMed, Embase, and Scopus to identify observational studies assessing the TNF-α levels in DD. Full-text articles that satisfied our inclusion and exclusion criteria were included, and a quality assessment was performed using the Newcastle-Ottawa Scale (NOS). The principal summary outcome was the mean difference (MD). The results were reported as MD (95% confidence interval (CI)). A total of 12 articles involving 883 subjects were included in the qualitative synthesis, out of which 6 studies were included in our quantitative synthesis. We did not observe statistical significance related to the mucosal TNF-α levels in symptomatic uncomplicated diverticular disease (SUDD) vs. the controls (0.517 (95% CI -1.148-2.182)), and symptomatic vs. asymptomatic DD patients (0.657 (95% CI -0.883-2.196)). However, the TNF-α levels were found to be significantly increased in DD compared to irritable bowel disease (IBS) patients (27.368 (95% CI 23.744-30.992)), and segmental colitis associated with diverticulosis (SCAD) vs. IBS patients (25.303 (95% CI 19.823-30.784)). Between SUDD and the controls, as well as symptomatic and asymptomatic DD, there were no significant differences in the mucosal TNF-α levels. However, the TNF-α levels were considerably higher in DD and SCAD patients than IBS patients. Our findings suggest that TNF-α may play a key role in the pathogenesis of DD in specific subgroups and could potentially be a target for future therapies.

Hemogram-Derived Ratios in the Prognosis of Acute Diverticulitis.

Background and Objectives: It is crucial to quickly identify those patients who need immediate treatment in order to avoid the various complications related to acute diverticulitis (AD). Although several studies evaluated the neutrophil-to-lymphocyte ratio (NLR) suggesting its predictive value in assessing the severity of AD, results have been inconclusive. Therefore, we aimed to assess the relationship between the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the monocyte-to-lymphocyte ratio (MLR), and systemic immune inflammation (SII) with the severity of AD, the ability to predict the presence or absence of complications, and the recurrence rate, based on the values of inflammatory markers. Materials and Methods: We retrospectively reviewed 147 patients diagnosed with AD between January 2012 to February 2023. Patients were divided into 2 groups, uncomplicated and complicated AD. The characteristics and full blood count between both groups were compared. Results: A total of 65 (44.22%) patients were classified as having complicated AD. The area under the ROC curve (AUROC) defining a Hinchey score ≥ 1b was as follows: SII, 0.812 (95% confidence interval (CI), 0.73 -0.888); NLR, 0.773 (95% CI, 0.676-0.857); PLR, 0.725 (95% CI, 0.63-0.813); MLR: 0.665 (95% CI, 0.542 -0.777). An SII cutoff value of > 1200 marked the highest yield for diagnosing complicated AD, with a sensitivity of 82% and a specificity of 76%. The cumulative recurrence rate was not significantly different in the groups of SII ≥ median vs. SII < median (p = 0.35), NLR ≥ median vs. NLR < median (p = 0.347), PLR ≥ median vs. PLR < median (p = 0.597), and MLR ≥ median vs. MLR < median (p = 0.651). Conclusions: Our study indicates that SII, NLR, and PLR are statistically significant and clinically useful classifying ratios to predict higher Hinchey scores. However, they cannot predict recurrences.

Prognostic performance of the 'DICA' endoscopic classification and the 'CODA' score in predicting clinical outcomes of diverticular disease: an international, multicentre, prospective cohort study.

OBJECTIVE: To investigate the predictive value of the Diverticular Inflammation and Complication Assessment (DICA) classification and to develop and validate a combined endoscopic-clinical score predicting clinical outcomes of diverticulosis, named Combined Overview on Diverticular Assessment (CODA). DESIGN: A multicentre, prospective, international cohort study. SETTING: 43 gastroenterology and endoscopy centres located in Europe and South America. PARTICIPANTS: 2215 patients (2198 completing the study) at the first diagnosis of diverticulosis/diverticular disease were enrolled. Patients were scored according to DICA classifications. INTERVENTIONS: A 3-year follow-up was performed. MAIN OUTCOME MEASURES: To predict the acute diverticulitis and the surgery according to DICA classification. Survival methods for censored observation were used to develop and validate a novel combined endoscopic-clinical score for predicting diverticulitis and surgery (CODA score). RESULTS: The 3-year cumulative probability of diverticulitis and surgery was of 3.3% (95% CI 2.5% to 4.5%) in DICA 1, 11.6% (95% CI 9.2% to 14.5%) in DICA 2 and 22.0% (95% CI 17.2% to 28.0%) in DICA 3 (p<0.001), and 0.15% (95% CI 0.04% to 0.59%) in DICA 1, 3.0% (95% CI 1.9% to 4.7%) in DICA 2 and 11.0% (95% CI 7.5% to 16.0%) in DICA 3 (p<0.001), respectively. The 3-year cumulative probability of diverticulitis and surgery was ≤4%, and ≤0.7% in CODA A; <10% and <2.5% in CODA B; >10% and >2.5% in CODA C, respectively. The CODA score showed optimal discrimination capacity in predicting the risk of surgery in the development (c-statistic: 0.829; 95% CI 0.811 to 0.846) and validation cohort (c-statistic: 0.943; 95% CI 0.905 to 0.981). CONCLUSIONS: DICA classification has a significant role in predicting the risk of diverticulitis and surgery in patients with diverticulosis, which is significantly enhanced by the CODA score. TRIAL REGISTRATION NUMBER: NCT02758860.

Post COVID-19 irritable bowel syndrome.

OBJECTIVES: The long-term consequences of COVID-19 infection on the gastrointestinal tract remain unclear. Here, we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut-brain interaction after hospitalisation for SARS-CoV-2 infection. DESIGN: GI-COVID-19 is a prospective, multicentre, controlled study. Patients with and without COVID-19 diagnosis were evaluated on hospital admission and after 1, 6 and 12 months post hospitalisation. Gastrointestinal symptoms, anxiety and depression were assessed using validated questionnaires. RESULTS: The study included 2183 hospitalised patients. The primary analysis included a total of 883 patients (614 patients with COVID-19 and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrolment, gastrointestinal symptoms were more frequent among patients with COVID-19 than in the control group (59.3% vs 39.7%, p<0.001). At the 12-month follow-up, constipation and hard stools were significantly more prevalent in controls than in patients with COVID-19 (16% vs 9.6%, p=0.019 and 17.7% vs 10.9%, p=0.011, respectively). Compared with controls, patients with COVID-19 reported higher rates of irritable bowel syndrome (IBS) according to Rome IV criteria: 0.5% versus 3.2%, p=0.045. Factors significantly associated with IBS diagnosis included history of allergies, chronic intake of proton pump inhibitors and presence of dyspnoea. At the 6-month follow-up, the rate of patients with COVID-19 fulfilling the criteria for depression was higher than among controls. CONCLUSION: Compared with controls, hospitalised patients with COVID-19 had fewer problems of constipation and hard stools at 12 months after acute infection. Patients with COVID-19 had significantly higher rates of IBS than controls. TRIAL REGISTRATION NUMBER: NCT04691895.

Greater Overlap of Rome IV Disorders of Gut-Brain Interactions Leads to Increased Disease Severity and Poorer Quality of Life.

BACKGROUND AND AIMS: Conditions such as irritable bowel syndrome (IBS), functional dyspepsia, and functional constipation are among the prevalent gastrointestinal (GI) disorders classified as disorders of gut-brain interaction (DGBI), which can adversely affect the lives of sufferers. This study aimed to assess the degree and consequences of overlapping DGBI in a large population-based global scale. METHODS: Internet survey data from 54,127 adults (49.1% women) in 26 countries were analyzed by 4 GI anatomic regions (esophageal, gastroduodenal, bowel, and anorectal). The number of DGBI-affected GI regions was assessed, including associations with sex, age, disease severity, quality of life, psychosocial variables, and health care utilization. RESULTS: A total of 40.3% of surveyed individuals met Rome IV criteria for a DGBI. The percentages with 1-4 DGBI-affected GI regions were 68.3%, 22.3%, 7.1%, and 2.3%, respectively. The IBS symptom severity score increased significantly from 1 (207.6) to 4 (291.6) regions, as did non-GI symptom reporting (somatization), anxiety and depression, concerns and embarrassment about bowel function, doctor visits, medications, and abdominal surgeries (all P < .0001). Quality of life decreased with increasing number of DGBI regions (P < .0001). In a logistic mixed model, non-GI symptoms (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.08-1.10), being very vs not concerned (OR, 2.55; 95% CI, 2.27-2.90), being very vs not embarrassed about bowel function (OR, 1.20; 95% CI, 1.08-1.33), and mean number of doctor visits (OR, 1.23; 95% CI, 1.115-1.32) were most strongly associated with number of DGBI regions. CONCLUSIONS: DGBI in multiple anatomic GI regions is associated with increased psychological comorbidity, health care utilization, and IBS severity. Physician awareness of overlap could improve quality of care, prevent unnecessary interventions, and yield more positive health outcomes.

Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study.

BACKGROUND & AIMS: Although functional gastrointestinal disorders (FGIDs), now called disorders of gut-brain interaction, have major economic effects on health care systems and adversely affect quality of life, little is known about their global prevalence and distribution. We investigated the prevalence of and factors associated with 22 FGIDs, in 33 countries on 6 continents. METHODS: Data were collected via the Internet in 24 countries, personal interviews in 7 countries, and both in 2 countries, using the Rome IV diagnostic questionnaire, Rome III irritable bowel syndrome questions, and 80 items to identify variables associated with FGIDs. Data collection methods differed for Internet and household groups, so data analyses were conducted and reported separately. RESULTS: Among the 73,076 adult respondents (49.5% women), diagnostic criteria were met for at least 1 FGID by 40.3% persons who completed the Internet surveys (95% confidence interval [CI], 39.9-40.7) and 20.7% of persons who completed the household surveys (95% CI, 20.2-21.3). FGIDs were more prevalent among women than men, based on responses to the Internet survey (odds ratio, 1.7; 95% CI, 1.6-1.7) and household survey (odds ratio, 1.3; 95% CI, 1.3-1.4). FGIDs were associated with lower quality of life and more frequent doctor visits. Proportions of subjects with irritable bowel syndrome were lower when the Rome IV criteria were used, compared with the Rome III criteria, in the Internet survey (4.1% vs 10.1%) and household survey (1.5% vs 3.5%). CONCLUSIONS: In a large-scale multinational study, we found that more than 40% of persons worldwide have FGIDs, which affect quality of life and health care use. Although the absolute prevalence was higher among Internet respondents, similar trends and relative distributions were found in people who completed Internet vs personal interviews.

Prevalence of Gastrointestinal Symptoms in Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Results of the Prospective Controlled Multinational GI-COVID-19 Study.

INTRODUCTION: Gastrointestinal (GI) symptoms in coronavirus-19 disease (COVID-19) have been reported with great variability and without standardization. In hospitalized patients, we aimed to evaluate the prevalence of GI symptoms, factors associated with their occurrence, and variation at 1 month. METHODS: The GI-COVID-19 is a prospective, multicenter, controlled study. Patients with and without COVID-19 diagnosis were recruited at hospital admission and asked for GI symptoms at admission and after 1 month, using the validated Gastrointestinal Symptom Rating Scale questionnaire. RESULTS: The study included 2036 hospitalized patients. A total of 871 patients (575 COVID+ and 296 COVID-) were included for the primary analysis. GI symptoms occurred more frequently in patients with COVID-19 (59.7%; 343/575 patients) than in the control group (43.2%; 128/296 patients) (P < 0.001). Patients with COVID-19 complained of higher presence or intensity of nausea, diarrhea, loose stools, and urgency as compared with controls. At a 1-month follow-up, a reduction in the presence or intensity of GI symptoms was found in COVID-19 patients with GI symptoms at hospital admission. Nausea remained increased over controls. Factors significantly associated with nausea persistence in COVID-19 were female sex, high body mass index, the presence of dyspnea, and increased C-reactive protein levels. DISCUSSION: The prevalence of GI symptoms in hospitalized patients with COVID-19 is higher than previously reported. Systemic and respiratory symptoms are often associated with GI complaints. Nausea may persist after the resolution of COVID-19 infection.

Pharmacological Management of Inflammatory Bowel Disease: a Century of Expert Opinions in Cecil Textbook of Medicine.

BACKGROUND: Advances in drug therapy for inflammatory bowel disease (IBD) [Crohn disease and ulcerative colitis (UC)] have contributed to a decrease in the severity of these chronic and disabling conditions. STUDY QUESTION: What are the milestones of the changes in the expert approach to the pharmacological management of IBD in the past century? STUDY DESIGN: To determine the changes in the experts' approach to the management of regional ileitis and UC, as presented in a widely used textbook in the United States. DATA SOURCES: The chapters presenting the management of IBD in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020. RESULTS: No specific interventions existed from 1927 through 1942. The pharmacological management of IBD has had 3 slightly overlapping eras starting in 1943. During the first period (1943-1951), the medical management relied on antibiotics, primarily sulfonamides and chloramphenicol. In the second (1955-75), experts recommended the use of adrenocorticotropic hormone or corticosteroids and 5-aminosalicylate. In the third era, which commenced in 1979 and is continuing to date, the pharmacological interventions have been expanded and refined to include 5 main drug classes, 5-aminosalicylates (sulfasalazine, mesalamine, and olsalazine), corticosteroids (prednisone and budesonide), immunomodulators (azathioprine, 6-mercaptopurine, cyclosporine, and tofacitinib), biologics (infliximab adalimumab certolizumab pegol, and natalizumab), and antibiotics (metronidazole and ciprofloxacin). A consensus exists that the monoclonal antibodies again tumor necrosis factor alpha are cost-effective for induction and maintenance of clinical remission in both UC (golimumab) and Crohn disease (certolizumab pegol). The newer agents ustekinumab (a monoclonal antibody to the interleukin p40 subunit) and vedolizumab (a monoclonal antibody to the homing receptor integrin complex) have also performed well. CONCLUSIONS: The pharmacological management of IBD has been the focus of intense research and development in the past 60 years. The pillars of drug treatment have been 5-aminosalicylates and corticosteroids. Recent pharmacological innovations (immunomodulators and biologicals) constitute an encouraging paradigm shift in the treatment of UC and Crohn disease.

Automated Chicago Classification for Esophageal Motility Disorder Diagnosis Using Machine Learning.

The goal of this paper is to provide a Machine Learning-based solution that can be utilized to automate the Chicago Classification algorithm, the state-of-the-art scheme for esophageal motility disease identification. First, the photos were preprocessed by locating the area of interest-the precise instant of swallowing. After resizing and rescaling the photos, they were utilized as input for the Deep Learning models. The InceptionV3 Deep Learning model was used to identify the precise class of the IRP. We used the DenseNet201 CNN architecture to classify the images into 5 different classes of swallowing disorders. Finally, we combined the results of the two trained ML models to automate the Chicago Classification algorithm. With this solution we obtained a top-1 accuracy and f1-score of 86% with no human intervention, automating the whole flow, from image preprocessing until Chicago classification and diagnosis.

Dietary interventions and irritable bowel syndrome - what really works?

PURPOSE OF REVIEW: The review examines the latest research on the use of dietary interventions in the management of irritable bowel syndrome (IBS) in order to understand what is the evidence supporting the efficacy of a dietary approach in this disorder. RECENT FINDINGS: A general dietary advice should be offered to all IBS patients. Psyllium supplementation is recommended in IBS with both constipation and diarrhea predominance. There is increasing evidence showing the beneficial effects of a low fermentable oligo-, di-, monosaccharides, and polyols (FODMAP) diet (LFD) on IBS symptoms. FODMAPs that are well tolerated should be reintroduced in daily diet, to increase acceptability of the diet, and limit potentially harmful effects. The benefits observed with the gluten-free diet seem determined by the reduction of FODMAPs rather than gluten. Modulation of gut microbiota using probiotics shows promising results, but there are unanswered questions regarding the optimal strains, dose and duration of treatment. Additional evidence is also needed for the role of prebiotics and synbiotics in IBS. SUMMARY: Food is both trigger of IBS symptoms and therapeutic tool. Recent studies demonstrated the beneficial effects of LFD on symptom control, as well as the role of probiotics, which seem to contribute to gut health and function.

B cell-activating factor (BAFF) in children with inflammatory bowel disease.

BACKGROUND: Assessing the inflammation is important in the follow-up of paediatric patients with inflammatory bowel disease (IBD). We aim to evaluate the value of B cell-activating factor (BAFF) in paediatric IBD as a potential biomarker for follow-up. METHOD: We determined BAFF in serum and faeces and faecal calprotectin (CP) in 32 IBD children-16 Crohn's disease (CD) and 16 ulcerative colitis (UC). Twenty-six healthy children and 10 children with irritable bowel syndrome (IBS) were included as controls. RESULTS: No differences were found in serum BAFF between IBD, IBS, and healthy group: 1037.35, 990.9 and 979.8 pg/ml, respectively, all p > 0.05, but faecal BAFF was higher in the IBD group: 15.1, 8.5 and 8.2 pg/ml, respectively, p < 0.05, and higher in the UC group (55.975 pg/ml) compared to the CD group (10.95 pg/ml), p = 0.015. Splitting the IBD group in relation to the CP level, the serum BAFF had no significantly different values between the subgroups, but the faecal BAFF was significantly higher in the >250 µg/g subgroup. Cut-off values of BAFF were calculated. CONCLUSION: Faecal BAFF is a promising marker for monitoring the children with IBD, higher levels of BAFF being correlated with high CP. IMPACT: Faecal BAFF is a promising marker in monitoring the children with IBD, higher levels of BAFF being correlated with high faecal calprotectin. To our knowledge, this is the first paediatric study concerning BAFF evaluation in IBD. Faecal BAFF levels could be considered a potential non-invasive marker in monitoring IBD activity in paediatric population with clinically mild or inactive disease.

Chronic Abdominal Pain in General Practice.

Background and Summary: Chronic abdominal pain is a challenging complaint for both primary care providers and gastroenterologists alike, due to a broad differential diagnosis and sometimes extensive and negative workup. In the absence of red flag features that herald more acute conditions, the majority of patients with chronic abdominal pain have a benign cause or a functional disorder (e.g., irritable bowel syndrome). The costs associated with a diagnostic workup are an expensive burden to health care. A systematic approach for evaluating patients and initiating a management plan are recommended in the primary care setting. Undiagnosed abdominal pain should be investigated starting with a detailed history and physical examination. Diagnostic investigations should be limited and adapted according to the clinical features, the alarm symptoms, and the symptom severity. This review will focus on the diagnostic tools which general practitioners utilize in the evaluation of chronic abdominal pain. Key Messages: The primary role of the general practitioner is to differentiate an organic disease from a functional one, to refer to a specialist, or to provide treatment for the underlying cause of pain. The functional disorders should be considered after the organic pathology has been confidently excluded. Once a diagnosis of functional pain is established, repetitive testing is not recommended and the patient should be referred to receive psychological support (e.g., cognitive therapy) associated with available pharmacological therapeutic options.

Albendazole-Induced Liver Injury.

BACKGROUND: Albendazole is an anthelmintic drug used worldwide for prophylactic or curative treatment. Side effects include diarrhea, abdominal pain, elevated levels of hepatic transaminases, dizziness, neutropenia, and alopecia. AREAS OF UNCERTAINTY: The main question of the systematic review is if albendazole administration can cause liver injury or liver failure. DATA SOURCES: Two researchers conducted the search on PubMed and the key words used were: "albendazole," "anthelmintic," "drug-induced liver injury," and "acute hepatitis." Two new case reports were included in the systematic review. RESULTS: Literature search concluded in 10 cases listed on PubMed. Another 2 new case reports from our experience are included in the systematic review. Most common symptoms presented are jaundice, anorexia, and vomiting after the single-use of albendazole or long-term usage. All cases presented high levels of transaminases, with remission after stopping the administration of albendazole. The treatment with albendazole was mostly given for liver hydatid cysts or empirically. CONCLUSIONS: Albendazole is a prescription-based drug used by most patients without medical advice, without knowing the risk of side effects. The anthelmintic drug may induce liver injury, even in small doses; in result, practitioners and patients should take this information in consideration.

Pharmacological Management of Peptic Ulcer: A Century of Expert Opinions in Cecil Textbook of Medicine.

BACKGROUND: Advances in drug therapy for peptic ulcer have had a significant impact on quality of life and work potential of many millions of affected persons and have contributed to a remarkable decrease in the prevalence of the disease, frequency and severity of complications, hospitalizations, and mortality. STUDY QUESTION: What are the milestones of the changes in the expert approach to the pharmacological management of peptic ulcer in the past century? STUDY DESIGN: To determine the changes in the experts' approach to the management of peptic ulcer, as presented in a widely used textbook in the United States. DATA SOURCES: The chapters presenting the management of peptic ulcer in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020. RESULTS: Acid neutralization with alkalies was the only pharmacological intervention recommended in the textbooks published from 1927 to 1975. Atropine and other antimuscarinic agents were mainly used to relieve pain and acid secretion according to the paradigm "no acid no ulcer." The shift to the acid suppression paradigm started with the introduction of the histamine-2 receptor antagonist cimetidine in 1979, the proton-pump inhibitor omeprazole in 1988, and the prostaglandin agonist misoprostol in 1992. Finally, the eradication of Helicobacter pylori was codified in 1996. CONCLUSIONS: The pharmacological management of peptic ulcer has remained archaic well into the 20th century. Fundamental progress occurred in a very short period (1979-1996) and was due to paradigm shifts from acid neutralization to acid suppression and later the recognition of the role of H. pylori infection.

Integrated Relaxation Pressure Classification and Probe Positioning Failure Detection in High-Resolution Esophageal Manometry Using Machine Learning.

High-resolution esophageal manometry is used for the study of esophageal motility disorders, with the help of catheters with up to 36 sensors. Color pressure topography plots are generated and analyzed and using the Chicago algorithm a final diagnosis is established. One of the main parameters in this algorithm is integrated relaxation pressure (IRP). The procedure is time consuming. Our aim was to firstly develop a machine learning based solution to detect probe positioning failure and to create a classifier to automatically determine whether the IRP is in the normal range or higher than the cut-off, based solely on the raw images. The first step was the preprocessing of the images, by finding the region of interest-the exact moment of swallowing. Afterwards, the images were resized and rescaled, so they could be used as input for deep learning models. We used the InceptionV3 deep learning model to classify the images as correct or failure in catheter positioning and to determine the exact class of the IRP. The accuracy of the trained convolutional neural networks was above 90% for both problems. This work is just the first step in fully automating the Chicago Classification, reducing human intervention.

Genetic predisposition in metabolic-dysfunction-associated fatty liver disease and cardiovascular outcomes-Systematic review.

BACKGROUND: Despite the demonstrated increased cardiovascular (CV) risk associated with metabolic-dysfunction-associated fatty liver disease (MAFLD), genetic variants predisposing to MAFLD were not constantly associated with CV events. Recently, rs641738C > T near membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) has been studied in MAFLD and CV outcomes. Therefore, we aimed to evaluate the association between rs641738C > T in the presence and severity of hepatic steatosis, fibrosis, biochemical markers and progression to hepatocellular carcinoma (HCC), in addition to CV outcomes in MAFLD. MATERIALS AND METHODS: An electronic search on PubMed, Embase and Cochrane Library for articles published till 23 March 2020 was systematically performed. Articles were screened, and data extracted from eligible studies by two reviewers independently. RESULTS: Studies conducted on adults with MAFLD involving European, Hispanic and African American populations evaluating rs641738 reported reduced hepatic expression of MBOAT7, increased hepatic fat content, severity of MAFLD, susceptibility to develop NASH, advanced fibrosis and HCC in adults. However, most articles involving Asian individuals contradicted these findings. Studies involving obese children associated rs641738 with increased plasma alanine aminotransferase (ALT) levels, while its association with MAFLD remains inconsistent. The rs641738 variant was assessed as a MAFLD susceptibility gene in coronary artery disease (CAD) reporting neutral effects. CONCLUSIONS: Despite inconclusive results in Asian populations, rs641738C > T near MBOAT7 is associated with increased hepatic fat, MAFLD severity, susceptibility to develop NASH, advanced fibrosis and HCC in adults from Caucasian, Hispanic and African American ethnicities with MAFLD, as well as elevated ALT levels in children, while exerting neutral effects in CAD.