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Objective: Drug sustainability (DS), a surrogate marker for drug efficacy, is important, especially when aiming for precision medicine. However, it lacks reliable prediction methods., Aims: To develop and externally validate a web-based artificial intelligence(AI)-derived tool for predicting DS of infliximab and vedolizumab in patients with moderate-to-severe Ulcerative Colitis (UC)., Methods: Data from three Israeli centers included infliximab or vedolizumab patients treated for >54 weeks. Sustainability meant no corticosteroids, hospitalizations or surgeries. Machine learning techniques predicted >54-week and overall DS using baseline clinical data., Results: The model was developed using data from 246 patients from Rabin Medical Center and externally validated on 67 patients from Rambam Health Care Campus and Sheba Medical Center. No significant difference in DS was observed across the datasets. Most patients were biologic-naïve and primarily treated with vedolizumab. The model performed well, with an area under the ROC curve of 0.86, and showed good accuracy (65.5 %-76.9 %) across the test sets., Conclusions: The study introduces a novel, AI-based tool for predicting >54-week DS of infliximab and vedolizumab in moderate-to-severe UC, using baseline parameters. This can aid clinical decision-making in the framework of precision medicine, promising to optimize disease management while maintaining physician autonomy., Competing Interests: Conflicts of interest HY- Has received research grants from Pfizer; consulting fees from Abbvie, Janssen, Pfizer, Takeda, and BMS; Speaker fees from Abbvie, Janssen, Pfizer, Takeda, and Bristol Myers Squibb; Data Safety Monitoring Board or Advisory Board fees from Abbvie, Pfizer Takeda and Bristol Myers Squibb. JEO- Has received grant support from Pfizer, consulting fees from Takeda, and speaker fees from Abbvie, Janssen, Pfizer, Takeda, Novartis, and Bristol Myers Squibb. IAB- Has received speaker fees from Abbvie, Janssen, Pfizer, Takeda, and Neopharm. ID- consultation fee or honorarium from: Abbott, Abbvie, Athos, Arena, Altman Research, Cambridge Healthcare, Celltrion, Celgene/BMS, Eli-Lilly, Ferring, Falk Pharma, Food Industries Organization, Gilead, Galapagos, Iterative Scopes, Integra Holdings, Janssen, Neopharm, Pfizer, Rafa laboratories, Roche/Genentech, Sangamo, Sublimity, Sandoz, Takeda, Wildbio. Grants: Altman Research, BMS, Pfizer UK- Research support- Jannsen, Takeda, Medtronic, speaker/advisory fees- Abbvie BMS Celtrion Jannsen Pfizer Takeda Medtronic Roche No specific funding has been received for this study., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: We examined corticosteroid use among Israeli patients with Inflammatory Bowel Disease (IBD), focusing on demographic, disease-related, and psychosocial factors. The objective was to contribute to the development of strategies minimizing corticosteroid dependence and improving patient outcomes, given the adverse effects associated with prolonged corticosteroid use., Methods: A comprehensive analysis was conducted on data collected from adult IBD patients attending six gastroenterological outpatient clinics in Israel. The data collected encompassed disease characteristics, demographic information, service level characteristics, social data, and steroid use. Statistical analyses were performed to associate these variables with steroid use., Results: Out of 402 patients, 26 % had been treated with corticosteroids in the previous year, with a majority of these having only one treatment course. Of patients treated with steroids, 57% (n-44) met steroid dependent/excess criteria. Steroid use was more common in patients diagnosed with ulcerative colitis (UC) compared to those with Crohn's disease. Factors such as a diagnosis of UC, male gender, elevated C-reactive protein and fecal calprotectin, and decreased albumin and hemoglobin were associated with steroid use., Conclusion: Corticosteroid use among Israeli IBD patients was associated with disease-related factors and some demographic characteristics. The results highlight the need for continued research to inform strategies aimed at reducing corticosteroid dependence in managing IBD, thereby improving patient outcomes., Competing Interests: Conflict of interest None., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Surveillance colonoscopies are crucial for high-risk patients with inflammatory bowel diseases (IBD) to detect colorectal carcinoma (CRC). However, there is no established quality metric for dysplasia detection rate (DDR) in IBD surveillance. This study assessed the DDR in a dedicated surveillance program at a tertiary referral center for IBD., Methods: Consecutive patients with quiescent colitis were enrolled in a cross-sectional study evaluating DDR. High-definition colonoscopy with dye chromoendoscopy (DCE) was performed by a specialized operator. Advanced dysplasia (AD) was defined as low-grade dysplasia ≥ 10 mm, high-grade dysplasia, or colorectal cancer. Risk factors for dysplasia detection were analyzed., Results: In total, 119 patients underwent 151 procedures, identifying 206 lesions, of which 40 dysplastic with seven AD . Per-lesion and per-procedure DDR were 19.4 % and 20.5 %, respectively. The per-procedure AD detection rate (ADDR) was 4.6 %. A Kudo pit pattern of II-V had a sensitivity of 92.5 % for dysplasia detection but a false positive rate of 64.8 % (p < 0.001). Age at diagnosis and at index colonoscopy and past or indefinite dysplasia were associated with per-procedure dysplasia detection., Conclusions: In a real-world setting, a dedicated surveillance program achieved a high DDR. We suggest that optimal DDR in high-risk IBD patients be defined and implemented as a standardized quality measure for surveillance programs., Competing Interests: Conflict of interest H.Y.- reports institutional research grants from Pfizer and the ISF; consulting fees from Abbvie, Janssen, Pfizer, and Takeda; honoraria for lectures from Abbvie, Janssen, Pfizer, Takeda, and BMS; participation in a Data Safety Monitoring Board or Advisory Board from Abbvie, Pfizer, Takeda, and BMS. I.D.: Advisory boards, consultation, speaking and teaching: Abbvie, Abbott, Arena, Athos, BMS/Celgene, Cambridge Healthcare, Celltrion, Genentech/Roche, Gilead, Galapagos, Eli-Lilly, Ferring, Falk Pharma, Food industries organization, Integra Holdings, Iterative Scopes, Janssen, Neopharm, Wild bio, Pfizer, Rafa Laboratories, Sangamo, Sublimity, Takeda J.E.O.: consultation fees from Pfizer, Abbvie, and Takeda; honoraria for lectures from Pfizer, Abbvie, and Takeda I.A.B.: consultation fees from Pfizer, Abbvie, and Takeda; honoraria for lectures from Pfizer, Abbvie, and Takeda, (Copyright © 2023. Published by Elsevier Ltd.)

Background: We sought to define the effectiveness and safety of tofacitinib in a real-world (RW) cohort of Israeli patients with moderate to severe ulcerative colitis (UC)., Methods: This was a multi-center retrospective observational cohort study (2019-2020) to assess the effectiveness and safety of tofacitinib induction and maintenance therapy up to 26 weeks. Clinical response and remission were defined as a reduction in Simple Clinical Colitis Activity Index (SCCAI) or partial Mayo score (PMS) of ≥3 points, and SCCAI ≤2 or a PMS ≤1, respectively., Results: We included 73 patients, 47% male; median age 26 years [IQR: 19.5-39.5], disease duration 7 years [IQR: 2.5-14.5], follow-up 7.1 months [IQR: 3-12], 91% biologics-experienced, and 74% ≥ 2-biologics. Half of patients used concomitant corticosteroids (CS). Overall, 56.1% discontinued therapy due to either lack of response and/or adverse events (AEs), median time to discontinuation - 9.7 months [IQR 3.4-16]. Overall, response, remission, and CS-free-remission were achieved in 47.6%, 20.6%, and 17.5% of patients, respectively. At early maintenance (week 26), response, remission, and CS-free-remission were achieved in 65%, 22.5%, and 20% of patients, respectively. At week 26, tofacitinib 10 mg BID was still used in 43%. Seventeen patients (23.2%) had an adverse event including herpes zoster- 2.7%, hospitalization- 12.3%, and colectomy- 2.7%., Conclusions: Tofacitinib was effective in achieving CS-free-remission in about 1/5 of highly biologics -experienced patients with UC. Despite a considerable proportion of patients maintained on tofacitinib 10 mg bid, it was well tolerated and safe. Earlier positioning of tofacitinib in the therapeutic algorithm may result in improved outcomes., Competing Interests: Conflict of interest H. Yanai: reports institutional research grants from Pfizer; consulting fees from Abbvie, Ferring, Janssen, Neopharm Ltd., Pfizer, Takeda; honoraria for lectures from Abbvie, Janssen, Pfizer, Takeda; participation on a Data Safety Monitoring Board or Advisory Board from Abbvie, Neopharm Ltd., Pfizer, Takeda. I. Avni Biron: Consulting fees from Takeda; honoraria for lectures from Abbvie, Janssen, Pfizer, Takeda, Neopharm Ltd; Clinical R&D team employee, Medtronic. I.Dotan: Consultation: Arena, Athos therapeutics, Gilead, Cambridge Healthcare, Wild bio, Food industries organization, Integra Holdings, Iterative Scopes. Speakers Bureau/lectures: Janssen, Abbvie, Takeda, Pfizer, Genentech/Roche, Arena, Neopharm, Celltrion, Rafa Laboratories, Ferring, Falk Pharma, Nestle, Celgene/BMS, Abbott. DSMB/advisory boards: SPARE consortium Janssen, Abbvie, Takeda, Pfizer, Genentech/Roche, Arena, Neopharm, Gilead, Galapagos, Celltrion, Sublimity, Wild bio, Athos therapeutics, Food industries organization, Celgene/BMS, Abbott, Sublimity, Sandoz. A. Bar-Gil Shitrit: Research grants from Takeda and Janssen, Consulting and honoraria for lectures from Takeda, Janssen' Abbvie, Pfizer and Neopharm. U. Kopylov: Research grants from Janssen, Takeda Medtronic, Consulting and honoraria- Abbvie, BMS, Janssen, MSD Medtronic, Takeda, Pfizer R. Weisshof: Consulting and honoraria for lectures from Takeda, Janssen, Abbvie. Advisory board fees from Janssen and AMAG Pharmaceuticals N. Maharshak: speaking and/ or consulting fees from Pfizer, Takeda, Janssen, Ferring, BiomX, BMS, Nestle and grant support from Takeda, Janssen, Abbott, Pfizer, BMS, Corundum Innovation Ltd E. Israeli: Research grants from Abbvie; Consulting and honoraria for lectures from Takeda, Janssen, Abbvie, Pfizer, Ferring Teva and BMS. I. Goren: Institutional research grant from Pfizer JE Ollech: Institutional research grant from Pfizer B. Koslowsky, A. Levartovsky, N. Aviv Cohen, D. Hovel, T. Naftali, Y. Snir, H. Banai-Eran, Y. Broitman, T. Sharar-Fischler -None., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Patients with Crohn's disease (CD) frequently undergo abdominopelvic computed tomography (APCT) in the emergency department (ED). It's essential to diagnose clinically actionable findings (CAF) as they may need immediate intervention, frequently surgical. However, repeated APCT's includes increased ionizing radiation exposure. Guidance regarding APCT performance is mostly clinical and empiric., Aims: We used a machine learning (ML) approach for predicting CAF on APCT in the ED., Methods: We performed a retrospective cohort study of patients with CD who presented to the ED and underwent APCT. CAF were defined as bowel obstruction, perforation, intra-abdominal abscess or complicated fistula. ML was used to predict the probability of having CAF on APCT, using routine clinical variables., Results: Of 101 admissions included, 44 (43.5%) had CAF on APCT. ML successfully identified patients at low (NPV 91.6%, CI-95% 90.6-92.5) and high (PPV 92.8%, CI-95%, 92.3-93.2) risk for CAF (AUROC = 0.774), using beats-per-minute, mean arterial pressure, neutrophil-to-lymphocyte ratio and sex. This allowed the construction of a risk stratification scheme according to patients' probability for CAF on APCT., Conclusion: We present a novel artificial intelligence-based approach, utilizing readily available clinical variables to better select patients with CD in the ED for APCT. This might reduce the number of APCTs performed, avoiding related hazards while ensuring high-risk patients undergo APCT., (Copyright © 2021. Published by Elsevier Ltd.)

Clostridium difficile is an anaerobic, gram positive, sporulating, toxin-producing bacillus which causes a spectrum of clinical disease ranging from an asymptomatic carrier state to toxic megacolon and fulminant disease. Infection with C. difficile is an expensive and pervasive health care burden. The current theory regarding the development of C. difficile infection (CDI) suggests that disruption of the structure and/or function of an individual's normal intestinal microbiota enables colonization by C. difficile, and in the absence of an effective immune response, the bacteria causes illness. In this article we discuss the role of the colonic microbiota in the development of CDI and the potential role of probiotics in preventing and treating CDI. We review the evidence from in vitro laboratory and pre-clinical studies, as well as evidence from clinical studies and discuss the current recommendations for the use of probiotics for CDI in clinical practice., (Copyright © 2016. Published by Elsevier Ltd.)

We prospectively assessed the diagnostic value of pleural fluid complement levels (total, C3, C4) in 135 patients with pleural effusion of five main etiologies, using novel markers. Complement levels correlated with pleural levels of protein, amylase, and transuded fluids. On univariate analysis, CHF-related pleural effusions were associated with significantly lower C4 levels than postsurgery or parapneumonic effusions. On multivariate analysis, pleural fluid C4 level was a significant predictor of CHF. Although the specificity, positive predictive value, and accuracy of the parameters were low in all diagnostic groups, their negative predictive value as well as the AUC ROC was high for CHF and post-LTX. We conclude that pleural fluid C4 levels can differentiate CHF-related pleural effusion from other etiologies and that normal level of C3 or C4 rule out CHF or LTX as causes of pleural effusion. Complement should be included in the assessment of pleural effusion when traditional diagnostic methods fail.

Background: Itraconazole is often given for fungal prophylaxis to lung transplant recipients after transplantation. The aim of this study was to determine the extent of interaction between tacrolimus and itraconazole in lung transplant recipients and the efficacy of itraconazole prophylaxis., Methods: The study group included 40 lung transplant recipients followed for at least 12 months. All received prophylactic itraconazole, 200 mg twice a day, for the first 6 months after transplantation. Tacrolimus levels and dosage requirements were compared during and after itraconazole therapy. Rejection rate, fungal infection rate, and renal function were assessed. The mean cost per daily treatment of the itraconazole/tacrolimus combination and tacrolimus alone was calculated., Results: The mean tacrolimus dose during itraconazole treatment was 3.26 +/- 2.1 mg/day compared with 5.74 +/- 2.9 mg/day after itraconazole was stopped (p < 0.0001) for a mean total daily dose elevation of tacrolimus of 76%. When the cost of itraconazole was taken into account, the average total daily cost of the combined treatment was US5.86 dollars less than the treatment with tacrolimus alone. No differences in the rejection or fungal infection rate, or in renal toxicity, were observed between the periods with and without itraconazole treatment, although less positive fungal isolates were identified during itraconazole therapy., Conclusion: Prophylaxis therapy with itraconazole is highly effective. Itraconazole reduces the dose of tacrolimus and therefore lowers the cost of therapy without causing an increase in rejection rate and with renal function preservation.