Muscular Hyperplasia in Crohn's disease Strictures: Through Thick and Thin.

Fibrostenosing Crohn's disease (CD) represents a challenging clinical condition characterized by the development of symptomatic strictures within the gastrointestinal tract. Despite therapeutic advancements in managing inflammation, the progression of fibrostenotic complications remains a significant concern, often necessitating surgical intervention. Recent investigations have unveiled the pivotal role of smooth muscle cell hyperplasia in driving luminal narrowing and clinical symptomatology. Drawing parallels to analogous inflammatory conditions affecting other organs, such as the airways and blood vessels, sheds light on common underlying mechanisms of muscular hyperplasia. This review synthesizes current evidence to elucidate the mechanisms underlying smooth muscle cell proliferation in CD-associated strictures, offering insights into potential therapeutic targets. By highlighting the emerging significance of muscle thickening as a novel therapeutic target, this review aims to inform future research endeavors and clinical strategies with the goal to mitigate the burden of fibrostenotic complications in CD and other conditions.

Cardiovascular Risk Factors and Physical Fitness Among Subjects with Asymptomatic Colonic Diverticulosis.

BACKGROUND: The association between diverticular disease and atherosclerotic cardiovascular disease (ASCVD) has been demonstrated previously, mainly in symptomatic subjects. AIMS: To evaluate 10 years cardiovascular risk, exercise performance and association to ASCVD among subjects with asymptomatic diverticulosis. METHODS: A retrospective cross-sectional cohort of self-referred participants in a medical screening program, who underwent a screening colonoscopy. Demographics, clinical and laboratory variables, ASCVD score, and metabolic equivalents (METs) during treadmill stress test were compared between subjects with and without diverticulosis as diagnosed on screening colonoscopy. RESULTS: 4586 participants underwent screening colonoscopy; 799 (17.4%) had diverticulosis. Among 50-69 yo participants, diverticulosis subjects had a higher ASCVD score compared to non-diverticulosis subjects. Exercise performance was comparable between the groups, across all age groups. Using logistic regression analysis, advanced age group (50-59 yo Adjusted odds ratio (AOR) [95% confidence interval (CI)] 2.57 (1.52-4.34), p < 0.001; 60-69 yo, AOR 2.87 (2.09-3.95), p < 0.001; ≥ 70 yo AOR 4.81 (3.23-7.15), p < 0.001; compared to < 50 yo age group), smoking [AOR 1.27 (1.05-1.55), p = 0.016], HTN [AOR 1.27 (1.03-1.56), p = 0.022], obesity [AOR 1.36 (1.06-1.74), p = 0.014] and male sex [AOR 1.29 (1.02-1.64), p = 0.036] were associated with diverticular detection during screening colonoscopy. Among males, achieving METs score ≥ 10 was inversely associated with diverticular detection during screening colonoscopy [AOR 0.64 (0.43-0.95), p = 0.027]. CONCLUSIONS: Ten years probability for ASCVD estimated by the ASCVD score is higher among subjects with asymptomatic diverticulosis compared to subjects without diverticulosis. Improved exercise performance is demonstrated for the first time to correlate with decreased probability for diverticular disease in screening colonoscopy.

Disproportionately Low Albumin and High Neutrophil-to-Lymphocyte Ratio in Small Bowel Adenocarcinoma Patients With Long-Duration Crohn's Disease.

INTRODUCTION: Although Crohn's disease (CD) is a known risk factor of small bowel adenocarcinoma (SBA), early diagnosis remains a significant clinical challenge. Identification of biomarkers for SBA may lead to early detection. METHODS: This is a retrospective study comparing albumin levels and neutrophil-to-lymphocyte ratio (NLR) of patients with long-standing CD who underwent small bowel resection with and without malignancy. RESULTS: Forty-two patients with CD were included in this study (11 with SBA). Median NLR before surgery was 8.5 (interquartile range 6.2-31.3) in patients with SBA and 3.8 (interquartile range 2.8-5.3) for patients without SBA ( P < 0.05). Mean albumin levels before surgery were significantly lower among patients with SBA compared with patients without SBA (2.6 ± 0.6 g/dL vs 3.5 ± 0.6 g/dL, respectively, P < 0.05), despite patients with SBA being under longer total parenteral nutrition treatment duration. DISCUSSION: CD patients with SBA diagnosis have increased NLR and lower albumin before surgery compared with CD patients without detection of SBA.

A Novel Prediction Tool for Endoscopic Intervention in Patients with Acute Upper Gastro-Intestinal Bleeding.

(1) Background: Predicting which patients with upper gastro-intestinal bleeding (UGIB) will receive intervention during urgent endoscopy can allow for better triaging and resource utilization but remains sub-optimal. Using machine learning modelling we aimed to devise an improved endoscopic intervention predicting tool. (2) Methods: A retrospective cohort study of adult patients diagnosed with UGIB between 2012−2018 who underwent esophagogastroduodenoscopy (EGD) during hospitalization. We assessed the correlation between various parameters with endoscopic intervention and examined the prediction performance of the Glasgow-Blatchford score (GBS) and the pre-endoscopic Rockall score for endoscopic intervention. We also trained and tested a new machine learning-based model for the prediction of endoscopic intervention. (3) Results: A total of 883 patients were included. Risk factors for endoscopic intervention included cirrhosis (9.0% vs. 3.8%, p = 0.01), syncope at presentation (19.3% vs. 5.4%, p < 0.01), early EGD (6.8 h vs. 17.0 h, p < 0.01), pre-endoscopic administration of tranexamic acid (TXA) (43.4% vs. 31.0%, p < 0.01) and erythromycin (17.2% vs. 5.6%, p < 0.01). Higher GBS (11 vs. 9, p < 0.01) and pre-endoscopy Rockall score (4.7 vs. 4.1, p < 0.01) were significantly associated with endoscopic intervention; however, the predictive performance of the scores was low (AUC of 0.54, and 0.56, respectively). A combined machine learning-developed model demonstrated improved predictive ability (AUC 0.68) using parameters not included in standard GBS. (4) Conclusions: The GBS and pre-endoscopic Rockall score performed poorly in endoscopic intervention prediction. An improved predictive tool has been proposed here. Further studies are needed to examine if predicting this important triaging decision can be further optimized.

Top 25 cited articles on Covid-19 and IBD: A bibliometric analysis.

OBJECTIVES: The use of citation analysis to identify the most cited Covid-19 and inflammatory bowel disease (IBD) manuscripts to provide an insight into the advances and knowledge accumulated regarding the pandemic in this subgroup of patients. METHODS: We've used a public application programming interface (API) U.S. National Center for Biotechnology Information (NCBI) to access the PubMed database. Data lock was performed on April 19, 2022. The API was used to retrieve all available IBD AND Covid-19 -related entries. For each retrieved entry, we've also obtained its citation count. RESULTS: The top 25 manuscripts were published between 2020 and 2021. The total citation count is 2051. The citation count of articles ranged from 41 to 313. The top 25 manuscripts were published in eight journals, while 16 were published in Gastroenterology and Gut. 36% of the most cited manuscripts reported clinical characteristics and patient outcomes, and 32% dealt with patient management. The most impactful manuscripts provided evidence that IBD patients are not at increased risk for severe morbidity or mortality from Covid-19 and that it is not advisable to discontinue the anti-inflammatory treatment for IBD during the pandemic. Two basic science studies demonstrated mechanistic insights for these observations. Studies that examined the immunogenic response of IBD patients treated with biologics were also part of the top-cited list. CONCLUSIONS: Impactful scientific publications on Covid-19 in IBD patients provided reassurance and directed treatment at the time of this newly recognized severe disease.

Adverse Clinical Outcomes among Inflammatory Bowel Disease Patients Treated for Urinary Tract Infection.

Background: Urinary tract infection (UTI) is the most common urologic complication among patients with inflammatory bowel disease (IBD). However, data regarding UTI outcomes in this population are scarce. We aimed to evaluate adverse outcomes of UTI among patients with IBD. Methods: This was a retrospective cohort study of consecutive adult patients who visited the emergency room (ER) at Sheba Medical Center due to a UTI between 2012 and 2018. Data included demographic and clinical variables. UTI cases were extracted using ICD-10 coding. Results: Of 21,808 (ER) visits with a UTI, 122 were IBD patients (Crohn's disease­52, ulcerative colitis­70). Contrary to non-IBD subjects, patients with IBD had higher rates of hospitalization, acute kidney injury (AKI) and 30 day-recurrent hospitalization (59.3% vs. 68.9%, p = 0.032; 4.6% vs. 13.9%, p < 0.001; 7.3% vs. 15.6%, p = 0.001, respectively). Among patients with IBD, advanced age (p = 0.005) and recent hospitalization (p = 0.037) were associated with increased risk for hospitalization, while hydronephrosis (p = 0.005), recent hospitalization (p = 0.011) and AKI (p = 0.017) were associated with increased 30-day recurrent hospitalization. Neither immunosuppressants nor biologics were associated with UTI outcomes among patients with IBD. Conclusions: Patients with IBD treated for a UTI had higher rates of hospitalization, AKI and 30-day recurrent hospitalization than non-IBD patients. No association was observed between immunosuppressants or biologics and UTI outcomes.

Predictors of Immunogenicity to Infliximab among Patients with Inflammatory Bowel Disease: Does Ethnicity Matter?

BACKGROUND: Up to 60% of inflammatory bowel disease (IBD) patients treated with infliximab develop antibodies to infliximab (ATI), which are associated with low drug levels and loss of response (LOR). Hence, mapping out predictors of immunogenicity toward infliximab is essential for tailoring patient-specific therapy. Jewish Sephardi ethnicity, in addition to monotherapy, has been previously identified as a potential risk factor for ATI formation and infliximab failure. OBJECTIVES: To explore the association between Jewish sub-group ethnicity among patients with IBD and the risk of infliximab immunogenicity and therapy failure. To confirm findings of a previous cohort that addressed the same question. METHODS: This retrospective cohort study included all infliximab-treated patients of Jewish ethnicity with regular prospective measurements of infliximab trough levels and ATI. Drug and ATI levels were prospectively measured, clinical data was retrieved from medical charts. RESULTS: The study comprised 109 Jewish patients (54 Ashkenazi, 55 Sephardi) treated with infliximab. There was no statistically significant difference in proportion of ATI between Sephardi and Ashkenazi patients with IBD (32% Ashkenazi and 33% Sephardi patients developed ATI, odds ratio [OR] 0.944, P = 0.9). Of all variables explored, monotherapy and older age were the only factors associated with ATI formation (OR 0.336, 95% confidence interval 0.145-0.778, P = 0.01, median 34 vs. 28, interquartile range 28-48, 23-35 years, P = 0.02, respectively). CONCLUSIONS: Contrary to previous findings, Sephardi Jewish ethnicity was not identified as a risk factor for ATI formation compared with Ashkenazi Jewish ethnicity. Other risk factors remained unchanged.

Capsule Endoscopy in Crohn's Disease-From a Relative Contraindication to Habitual Monitoring Tool.

Crohn's disease (CD) is a chronic inflammatory disorder that may involve the gastrointestinal tract from the mouth to the anus. Habitual disease monitoring is highly important during disease management, aiming to identify and treat disease exacerbations, in order to avoid immediate and future complications. Currently, ilio-clonoscopy is the gold standard for mucosal assessment. However, the procedure is invasive, involves sedation and allows for visualization of the colon and only a small part of the terminal ileum, while most of the small bowel is not visualized. Since CD may involve the whole length of the small bowel, the disease extent might be underestimated. Capsule endoscopy (CE) provides a technology that can screen the entire bowel in a non-invasive procedure, with minimal side effects. In recent years, this technique has gained in popularity for CD evaluation and monitoring. When CE was first introduced, two decades ago, the fear of possible capsule retention in the narrowed inflamed bowel lumen limited its use in CD patients, and a known CD located at the small bowel was even regarded as a relative contraindication for capsule examination. However, at present, as experience using CE in CD patients has accumulated, this procedure has become one of the accepted tools for disease diagnosis and monitoring. In our current review, we summarize the historic change in the indications and contraindications for the usage of capsule endoscopy for the evaluation of CD, and discuss international recommendations regarding CE's role in CD diagnosis and monitoring.

Association of Infliximab and Vedolizumab Trough Levels with Reported Rates of Adverse Events: A Cross-Sectional Study.

Infliximab and vedolizumab are effective treatments for inflammatory bowel disease (IBD), although associated with adverse events (AE). While low or non-existent drug levels and positive antidrug antibodies have been associated with therapeutic failure, there is no clear association between higher drug levels and AE. A cross-sectional study consisting of Crohn's disease (CD) and ulcerative colitis (UC) patients receiving infliximab or vedolizumab at the Sheba Medical Center was performed. Patients completed a questionnaire regarding AEs related to biological therapy. Serum trough levels obtained on the same day were analyzed. Objective measures of outcomes were retrieved from medical records. Questionnaires were completed by infliximab (n = 169) and vedolizumab (n = 88)-treated therapy patients. Higher infliximab levels were only numerically associated with the occurrence of at least one AE (p = 0.08). When excluding fatigue and abdominal pain, higher infliximab levels were statistically associated with the occurrence of at least one AE (p = 0.03). Vedolizumab drug levels > 18 µg/mL were also linked with the occurrence of more AEs. No specific association was observed between the increased levels of either infliximab or vedolizumab and specific AEs (neurological symptoms, upper GI symptoms, infectious complications, and musculoskeletal symptoms). As significant AEs are very rare, additional multi-center studies are required.

Assays used to assess biosimilarity of therapies for inflammatory bowel disease.

Introduction: Biological drugs have revolutionized the treatment of various medical conditions. Recently, upon expiration of patents of a few biological agents, biosimilars are being rapidly developed as an affordable substitute for more expensive biologic drugs, which may serve as a therapeutic alternative for biologics reference medical product (RMP). Prior to approval for use of the biosimilar drug for treatment of RMP indications, a process involving several different assays is required, in which the biosimilar must prove to posses no meaningful differences from an existing approved RMP in terms of purity, safety and potency.Areas covered: This report describes the different assays which are used to assess biosimilar drugs using CT-P13 infliximab biosimilar as a case-in-point. It covers the assays of physicochemical characterization, biological activity, and immunogenicity and examines their rational along with methodological and conceptual caveats clinicians should be cognizant of.Expert opinion: The approval of a biosimilar is a complex process that requires several assays, specifically tailored to the characteristics of the RMP. Determining the required assays and the allowable margin of confidence are of great importance but are not sufficient in order to prove that the biosimilar is indeed not inferior in its clinical potency and safety to the RMP.

[HANTAVIRUS PULMONARY SYNDROME DIAGNOSED IN A RETURNED TRAVELER FROM THE USA].

INTRODUCTION: Hantavirus pulmonary syndrome (HPS) is a rare and sometimes fatal respiratory disease in humans. The infection is acquired mainly through inhalation of aerosolized rodent secretions which serves as the reservoir for the virus. HPS cases are mostly reported from the American continent. In this article we describe a case of fulminant HPS in a 47 years old man who had traveled with his family on vacation to the southwestern region of the United States. The patient was hospitalized one month after his return to Israel and the diagnosis of hantavirus infection (species Sin Nombre Virus), was performed on samples sent to the CDC's Viral Special Pathogens Branch. Clinicians should be aware of this special entity and consider HPS in the differential diagnosis of patients with respiratory failure and fever, when there is a history of travel to the endemic area.