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Adi Lahat,1,2 Uri Kopylov,1,2 Marianne M Amitai,3 Sandra Neuman,1,2 Nina Levhar,1,2 Doron Yablecovitch,1,2 Benjamin Avidan,1,2 Henit Yanai,2,4 Iris Dotan,2,4 Yehuda Chowers,5,6 Batya Weiss,7 Shomron Ben-Horin,1,2,* Rami Eliakim1,2,* On behalf of the Israeli IBD Research Network (IIRN) 1Department of Gastroenterology, Chaim Sheba Medical Center, Tel Hashomer, Israel; 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Department of Diagnostic Imaging, Chaim Sheba Medical Center, Tel Hashomer, Israel; 4IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv Medical Center, Tel Aviv, Isarel; 5Rambam Health Care Campus, Haifa, Israel; 6Bruce Rappaport School of Medicine, Technion Israel Institute of Technology, Haifa, Israel; 7Edmond and Lily Safra Children’s Hospital, Tel Hashomer, Israel *These authors contributed equally to this work Background: Despite differences in the information obtained by capsule endoscopy (CE) and magnetic resonance enterography (MRE), one of these modalities is usually needed when evaluating disease activity. There are no data on patients’ preference that would help guide the choice between these two modalities in these instances.Aim: To compare patients’ tolerance and preference to MRE versus CE.Patients and methods: Patients with known small bowel Crohn’s disease (CD) in clinical remission (Crohn’s disease activity index [CDAI]

Abstract Background and aims--The pulmonary symptoms of patients with lung disease may be ascribed to gastro-oesophageal reflux although a causal relationship between acid reflux and coughing or wheezing has not [...]

Background and Aims: Patients frequently have concerns about their disease and find it challenging to obtain accurate Information. OpenAI's ChatGPT chatbot (ChatGPT) is a new large language model developed to provide answers to a wide range of questions in various fields. Our aim is to evaluate the performance of ChatGPT in answering patients' questions regarding gastrointestinal health., Methods: To evaluate the performance of ChatGPT in answering patients' questions, we used a representative sample of 110 real-life questions. The answers provided by ChatGPT were rated in consensus by three experienced gastroenterologists. The accuracy, clarity, and efficacy of the answers provided by ChatGPT were assessed., Results: ChatGPT was able to provide accurate and clear answers to patients' questions in some cases, but not in others. For questions about treatments, the average accuracy, clarity, and efficacy scores (1 to 5) were 3.9 ± 0.8, 3.9 ± 0.9, and 3.3 ± 0.9, respectively. For symptoms questions, the average accuracy, clarity, and efficacy scores were 3.4 ± 0.8, 3.7 ± 0.7, and 3.2 ± 0.7, respectively. For diagnostic test questions, the average accuracy, clarity, and efficacy scores were 3.7 ± 1.7, 3.7 ± 1.8, and 3.5 ± 1.7, respectively., Conclusions: While ChatGPT has potential as a source of information, further development is needed. The quality of information is contingent upon the quality of the online information provided. These findings may be useful for healthcare providers and patients alike in understanding the capabilities and limitations of ChatGPT.

The field of gastroenterology (GI) is constantly evolving. It is essential to pinpoint the most pressing and important research questions. To evaluate the potential of chatGPT for identifying research priorities in GI and provide a starting point for further investigation. We queried chatGPT on four key topics in GI: inflammatory bowel disease, microbiome, Artificial Intelligence in GI, and advanced endoscopy in GI. A panel of experienced gastroenterologists separately reviewed and rated the generated research questions on a scale of 1-5, with 5 being the most important and relevant to current research in GI. chatGPT generated relevant and clear research questions. Yet, the questions were not considered original by the panel of gastroenterologists. On average, the questions were rated 3.6 ± 1.4, with inter-rater reliability ranging from 0.80 to 0.98 (p < 0.001). The mean grades for relevance, clarity, specificity, and originality were 4.9 ± 0.1, 4.6 ± 0.4, 3.1 ± 0.2, 1.5 ± 0.4, respectively. Our study suggests that Large Language Models (LLMs) may be a useful tool for identifying research priorities in the field of GI, but more work is needed to improve the novelty of the generated research questions., (© 2023. The Author(s).)

Background: Early colonoscopy (within 8-24 h) is recommended in different guidelines for acute lower gastrointestinal bleeding (LGIB). Despite this recommendation, evidence for its effectiveness are conflicting, and early colonoscopy is often not performed., Objectives: We aimed to evaluate the utility of early colonoscopy by examining the findings during the procedure, and by comparing in-hospital and long-term outcomes between patients who did and did not undergo early colonoscopy., Design: This is a retrospective cohort study based on the electronic medical records of a large tertiary hospital in Israel., Methods: All patients hospitalized with acute LGIB to acute wards between 2012 and 2022 were included. First, structured and free-text procedure notes from patients who did undergo early colonoscopy were examined. Second, we compared in-hospital and long-term outcomes between patients who did and did not undergo early colonoscopy while adjusting for possible confounders using multivariable regression of the type appropriate for each outcome., Results: Overall, 953 patients were included, of which 90 underwent early colonoscopy. The majority (54%) were found insufficiently prepared. Common findings were diverticulosis (38%) and colon polyps (20%). The procedure was effective for hemostasis in only 13% of the cases. Early colonoscopy was not significantly associated with increased survival (exponentiated coefficient = 1.19, 95% CI: 0.76, 1.87), decreased length of hospitalization (exponentiated coefficient = 1.08, 95% CI: 0.97, 1.21), or increased blood hemoglobin at discharge (coefficient =-0.27, 95% CI: -0.58, 0.03)., Conclusions: Early colonoscopy was often not effective and was not associated with significantly improved outcomes., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Background: Crohn's disease (CD) and ulcerative colitis (UC) are chronic, immune-mediated inflammatory bowel diseases (IBD) affecting millions of people worldwide. IBD therapies, designed for continuous immune suppression, often render patients more susceptible to infections. The effect of the immune suppression on the risk of coronavirus disease-19 (COVID-19) is not fully determined yet., Objective: To describe COVID-19 characteristics and outcomes and to evaluate the association between IBD phenotypes, infection outcomes and immunomodulatory therapies., Methods: In this multi-center study, we prospectively followed IBD patients with proven COVID-19. De-identified data from medical charts were collected including age, gender, IBD type, IBD clinical activity, IBD treatments, comorbidities, symptoms and outcomes of COVID-19. A multivariable regression model was used to examine the effect of immunosuppressant drugs on the risk of infection by COVID-19 and the outcomes., Results: Of 144 IBD patients, 104 (72%) were CD and 40 (28%) were UC. Mean age was 32.2 ± 12.6 years. No mortalities were reported. In total, 94 patients (65.3%) received biologic therapy. Of them, 51 (54%) at escalated doses, 10 (11%) in combination with immunomodulators and 9 (10%) with concomitant corticosteroids. Disease location, behavior and activity did not correlate with the severity of COVID-19. Biologics as monotherapy or with immunomodulators or corticosteroids were not associated with more severe infection. On the contrary, patients receiving biologics had significantly milder infection course ( p = 0.001) and were less likely to be hospitalized ( p = 0.001). Treatment was postponed in 34.7% of patients until recovery from COVID-19, without consequent exacerbation., Conclusion: We did not witness aggravated COVID-19 outcomes in patients with IBD. Patients treated with biologics had a favorable outcome.

Climate change has been shown to have a substantial impact on agriculture and high temperatures and heat stress are known to have many negative effects on the vegetative and reproductive phases of plants. In a previous study, we addressed the effects of high temperature environments on olive oil yield and quality, by comparing the fruit development and oil accumulation and quality of five olive cultivars placed in high temperature and moderate temperature environments. The aim of the current study was to explore the molecular mechanism resulting in the negative effect of a high temperature environment on oil quantity and quality. We analyzed the transcriptome of two extreme cultivars, 'Barnea', which is tolerant to high temperatures in regard to quantity of oil production, but sensitive regarding its quality, and 'Souri', which is heat sensitive regarding quantity of oil produced, but relatively tolerant regarding its quality. Transcriptome analyses have been carried out at three different time points during fruit development, focusing on the genes involved in the oil biosynthesis pathway. We found that heat-shock protein expression was induced by the high temperature environment, but the degree of induction was cultivar dependent. The 'Barnea' cultivar, whose oil production showed greater tolerance to high temperatures, exhibited a larger degree of induction than the heat sensitive 'Souri'. On the other hand, many genes involved in olive oil biosynthesis were found to be repressed as a response to high temperatures. OePDCT as well as OeFAD2 genes showed cultivar dependent expression patterns according to their heat tolerance characteristics. The transcription factors OeDof4.3 , OeWRI1.1 , OeDof4.4 and OeWRI1.2 were identified as key factors in regulating the oil biosynthesis pathway in response to heat stress, based on their co-expression characteristics with other genes involved in this pathway. Our results may contribute to identifying or developing a more heat tolerant cultivar, which will be able to produce high yield and quality oil in a future characterized by global warming.

Global warming is predicted to have a negative effect on plant growth due to the damaging effect of high temperatures. In order to address the effect of high temperature environments on olive oil yield and quality, we compared its effect on the fruit development of five olive cultivars placed in a region noted for its high summer temperatures, with trees of the same cultivars placed in a region of relatively mild summers. We found that the effects of a high temperature environment are genotype dependent and in general, high temperatures during fruit development affected three important traits: fruit weight, oil concentration and oil quality. None of the tested cultivars exhibited complete heat stress tolerance. Final dry fruit weight at harvest of the 'Barnea' cultivar was not affected by the high temperature environment, whereas the 'Koroneiki', 'Coratina', 'Souri' and 'Picholine' cultivars exhibited decreased dry fruit weight at harvest in response to higher temperatures by 0.2, 1, 0.4 and 0.2 g respectively. The pattern of final oil concentration was also cultivar dependent, 'Barnea', 'Coratina' and 'Picholine' not being affected by the high temperature environment, whereas the 'Koroneiki' and 'Souri' cultivars showed a decreased dry fruit oil concentration at harvest under the same conditions by 15 and 8% respectively. Regarding the quality of oil produced, the 'Souri' cultivar proved more tolerant to a high temperature environment than any other of the cultivars analyzed in this study. These results suggest that different olive cultivars have developed a variety of mechanisms in dealing with high temperatures. Elucidation of the mechanism of each of these responses may open the way to development of a variety of olives broadly adapted to conditions of high temperatures., Competing Interests: The authors have declared that no competing interests exist.

Background: Matrix metalloproteinase-9 (MMP-9) is a novel marker of intestinal inflammation. The aim of this study was to assess if serum MMP-9 levels predict clinical flare in patients with quiescent Crohn's disease (CD)., Methods: This study was a post hoc analysis of a prospective observational study in which quiescent CD patients were included and followed until clinical relapse or the end of a 2-year follow-up period. Serial C-reactive protein (CRP) and fecal calprotectin (FC) levels were measured, and the patients underwent repeated capsule endoscopies (CEs) every 6 months. Small bowel inflammation was quantified by Lewis score (LS) for CE. A baseline magnetic resonance enterography was also performed, and MaRIA score was calculated. Serum MMP-9 levels in baseline blood samples were quantified by ELISA., Results: Out of 58 eligible enrolled patients, 16 had a flare. Higher levels of baseline MMP-9 were found in patients who developed subsequent symptomatic flare compared with patients who did not [median 661 ng/ml, 25-75 interquartile range (IQR; 478.2-1441.3) versus 525.5 ng/ ml (339-662.7), respectively, p  = 0.01]. Patients with serum MMP-9 levels of 945 ng/ ml or higher were at increased risk for relapse within 24 months [area under the curve (AUC) of 0.72 [95% confidence interval (CI): 0.56-0.88]; hazard ratio 8.1 (95% CI 3.0-21.9, p  < 0.001)]. Serum MMP-9 concentrations showed weak and moderate correlation to baseline LS and FC, respectively ( r  = 0.31, p  = 0.02; r  = 0.46, p  < 0.001). No correlation was found between serum MMP-9 to CRP and MaRIA score., Conclusions: Serum MMP-9 may be a promising biomarker for prediction of clinical flare in CD patients with quiescent disease., Competing Interests: Conflict of interest statement: Doron Yablecovitch, none to declare; Uri Kopylov, Speaker fees/advisory Janssen Medtronic Abvvie Takeda MSD; Research support, Janssen Takeda Medtronic; Adi Lahat, none to declare; Michal M. Amitai, none to declare; Eyal Klang, none to declare; Dana Ben-Ami Shor, none to declare; Sandra Neuman, none to declare; Nina Levhar, none to declare; Ella Fudim, none to declare; Benjamin Avidan, none to declare; Limor Selinger, none to declare; Noam Zingboim-Orbach, none to declare; Orit Picard, none to declare; Miri Yavzori, none to declare; Rami Eliakim, Consultation/lecture fee Medtronic/Given Imaging, consultant fee from Abbvie and Takeda; Shomron Ben Horin, Research support or consultancy/Advisory board fees from MSD, AbbVie, Janssen, CellTrion, Pfizer, GSK, and Takeda, (© The Author(s), 2019.)

Currently, table olives, unlike oil olives, are harvested manually. Shortage of manpower and increasing labor costs are the main incentives to mechanizing the harvesting of table olives. One of the major limiting factors in adopting mechanical harvest of table olives is the injury to fruit during mechanical harvest, which lowers the quality of the final product. In this study, we used the Israeli germplasm collection of olive cultivars at the Volcani Institute to screen the sensitivity of many olive cultivars to browning in response to injury. The browning process after induced mechanical injury was characterized in 106 olive cultivars. The proportional area of brown coloring after injury, compared to the total fruit surface area, ranged from 0 to 83.61%. Fourteen cultivars were found to be resistant to browning and did not show any brown spot 3 h after application of pressure. Among them, there are some cultivars that can serve as table olives. The different response to mechanical damage shown by the cultivars could be mainly due to genetic differences. Mesocarp cells in the fruits of the sensitive cultivars were damaged and missing the cell wall as a result of the applied pressure. The cuticles of resistant cultivars were thicker compared to those of susceptible cultivars. Finally, we showed that the browning process is enzymatic. We suggest cuticle thickness as an indicator of table olive cultivars suitable for mechanical harvest. A shift to browning-resistant cultivars in place of the popular cultivars currently in use will enable the mechanical harvest of table olive without affecting fruit quality., (Copyright © 2019 Goldental-Cohen, Biton, Many, Ben-Sason, Zemach, Avidan and Ben-Ari.)

Background: Small-bowel capsule endoscopy (CE) is a prime modality for evaluation of the small bowel. The Lewis score (LS) and the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI) are validated endoscopic indices for quantification of small-bowel inflammation on CE. It is unclear whether these indexes are interchangeable for the evaluation of mucosal inflammation in established Crohn's disease (CD). The aim of this study was to compare the quantitative evaluation of small- bowel inflammation by LS and CECDAI., Methods: Patients with known quiescent small-bowel CD for at least 3 months (Crohn's disease activity index < 150) were prospectively recruited and underwent CE. The LS was calculated using RAPID 8 capsule-reading software and the CECDAI was calculated manually. Cumulative LS (C-LS) was calculated by summation of individual tertile LS. Fecal calprotectin (FCP) and C-reactive protein (CRP) levels were measured and correlated with the scores., Results: A total of 50 patients were included in the study. There was a moderate correlation between the worst segment LS and CECDAI (Pearson's r = 0.66, p = 0.001), and a strong correlation between C-LS and CECDAI ( r = 0.81, p = 0.0001). CECDAI < 5.4 corresponded to mucosal healing (LS < 135), while CECDAI > 9.2 corresponded to moderate-to-severe inflammation (LS ⩾ 790). There was a moderate correlation between capsule scores and FCP levels ( r = 0.39, p = 0.002 for LS, r = 0.48, p = 0.001 for C-LS, and r = 0.53, p = 0.001 for CECDAI, respectively). CRP levels were not significantly correlated with either score., Conclusions: CECDAI and C-LS are strongly correlated and perform similarly for quantitative assessment of mucosal inflammation in established CD., Competing Interests: Conflict of interest statement: UK received research support from Takeda Pharmaceutical Company and Janssen Pharmaceutica, speaker fees from Jannsen Pharmaceutica, AbbVie, and Takeda Pharmaceutical Company, and consultancy fees from Jannsen Pharmaceutica, Takeda Pharmaceutical Company, and CTS Pharma. SB-H received research support and/or consultancy fees from MSD, AbbVie, Janssen Pharmaceutica, CellTrion Healthcare, and Takeda Pharmaceutical Company. RE received advisory board/lecture fee from Medtronic/Given Imaging. All the other authors declare no conflicts of interest in preparing this article.

Background: Helicobacter pylori (HP) infection is present in about 50% of the global population, and is associated with chronic gastritis, peptic disease and gastric malignancies. HP prevalence in Crohn's disease (CD) patients was shown to be low compared to the general population, and its influence on disease activity is yet to be determined. Our aims were to determine the prevalence of HP in a selected group of CD patients with quiescent disease, and to assess the influence of its eradication on disease activity and endoscopic and laboratory activity measures., Methods: Consecutive CD patients with quiescent disease underwent meticulous disease evaluation with MR enterography (MRE), video capsule endoscopy (VCE), CRP, fecal calprotectin and CDAI. All patients were tested for the presence of HP using stool antigen detection kit. Patients infected with HP were offered eradication treatment with sequential therapy. HP eradication was confirmed using urease breath test and stool antigen test. The influence of HP eradication on disease activity was assessed., Results: Out of 56 patients enrolled, six patients (10.7%) had HP infection. Of them, five patients had gastro- duodenitis per VCE. All HP positive patients were offered eradication treatment and underwent successful eradication. Notably, 23 (50%) of patients had proximal disease per VCE, most of them (78%) were HP negative. CDAI, CRP, fecal calprotectin and VCE Lewis inflammatory score did not change significantly following HP eradication, Gastric findings on VCE were not impacted by HP eradication., Conclusions: The prevalence of HP infection in patients with quiescent CD is relatively low. Eradication of the bacteria did not significantly change neither disease activity measures nor the presence of gastro- duodenitis per VCE, suggesting it might be part of proximal CD. The influence of HP on CD activity merits further investigation.

Background and Aims: Histopathology is the most accurate test to detect H. pylori when performed correctly with unknown validity in daily practice clinic settings. We aimed to determine the rate of potentially false-negative H. pylori results that might be due to continued use of proton pump inhibitors (PPIs) in routine endoscopy practice. We also aimed to establish whether gastroenterologists recommend routine cessation of PPIs before esophagogastroduodenoscopy (EGD) and whether they regularly document that biopsies for H. pylori testing have been taken while the patients are on PPI treatment., Methods: Detailed information about three known factors (PPIs, antibiotics and prior H. pylori eradication treatment), which may cause histology or rapid urease test (RUT) to be unreliable, had been prospectively collected through interviews using a questionnaire before each test. Gastric biopsies were stained with H&E for histological analysis., Results: A total of 409 individuals at three academic gastroenterology institutions were tested 200 times with histology. Fifty-six per cent (68 of 122) of all negative tests fell in the category of continuing PPI use, which had the potential to make the histology and RUT results unreliable., Conclusions: These data demonstrate a clear and important gap between current guidelines and real-world practice with regards to the diagnosis of H. pylori during EGD. A negative histology or RUT should be considered false negative until potential protocol violations are excluded. Documentation of PPI use during the EGD should be an integral part of the EGD report. The current practice of taking biopsies for H. pylori testing in patients under PPIs should be reevaluated.

Background: Video capsule endoscopy (VCE) and magnetic resonance enterography (MRE) are the prime modalities for the evaluation of small bowel (SB) Crohn's disease (CD). Mucosal inflammation on VCE is quantified using the Lewis score (LS). Diffusion-weighted (DW) magnetic resonance imaging (MRI) allows for accurate assessment of SB inflammation without administration of intravenous contrast material. The Magnetic Resonance Index of Activity (MaRiA) and the Clermont index are quantitative activity indices validated for contrast-enhanced MRE and DW-MRE, respectively. The aim of this study was to compare the quantification of distal SB inflammation by VCE and MR-related activity indices., Methods: Patients with known quiescent SB CD were prospectively recruited and underwent MRE and VCE. LS, MaRIA and Clermont scores were calculated for the distal SB., Results: Both MRI-based indices significantly correlated with the LS and the Clermont index (r = 0.50, p = 0.001 and r = 0.53, p = 0.001, respectively). Both MaRIA and Clermont scores were significantly lower in patients with mucosal healing (LS < 135). The area under the curve (AUC) with both MR scores was moderate for prediction of any mucosal inflammation (LS ⩾ 135) and excellent for prediction of moderate-to-severe inflammation (LS ⩾ 790) (0.71 and 0.74 versus 0.93 and 0.91 for MaRIA and Clermont score, respectively)., Conclusions: Modest correlation between VCE- and MRE-based quantitative indices of inflammation in patients with quiescent SB CD was observed. Between-modality correlation was higher in patients with endoscopically severe disease. DW-MRE gauged by Clermont score was at least as accurate as contrast-enhanced MRE for quantification of SB inflammation.

Background & Aims: The phytochemical compound curcumin was reported to be effective in maintaining remission in patients with ulcerative colitis (UC). We investigated curcumin's efficacy in inducing remission in patients with active mild-to-moderate UC., Methods: We performed a multicenter randomized, placebo-controlled, double-blind study of 50 mesalamine-treated patients with active mild-to-moderate UC (defined by the Simple Clinical Colitis Activity Index [SCCAI]) who did not respond to an additional 2 weeks of the maximum dose of mesalamine oral and topical therapy. Patients were randomly assigned to groups who were given curcumin capsules (3 g/day, n = 26) or an identical placebo (n = 24) for 1 month, with continued mesalamine. The primary outcome was the rate of clinical remission (SCCAI ≤2) at week 4. Clinical and endoscopic responses were also recorded., Results: In the intention-to-treat analysis, 14 patients (53.8%) receiving curcumin achieved clinical remission at week 4, compared with none of the patients receiving placebo (P = .01; odds ratio [OR], 42; 95% confidence interval [CI], 2.3-760). Clinical response (reduction of ≥3 points in SCCAI) was achieved by 17 patients (65.3%) in the curcumin group vs. 3 patients (12.5%) in the placebo group (P < .001; OR, 13.2; 95% CI, 3.1-56.6). Endoscopic remission (partial Mayo score ≤1) was observed in 8 of the 22 patients evaluated in the curcumin group (38%), compared with none of 16 patients evaluated in the placebo group (P = .043; OR, 20.7; 95% CI, 1.1-393). Adverse events were rare and comparable between the 2 groups., Conclusions: Addition of curcumin to mesalamine therapy was superior to the combination of placebo and mesalamine in inducing clinical and endoscopic remission in patients with mild-to-moderate active UC, producing no apparent adverse effects. Curcumin may be a safe and promising agent for treatment of UC. Clinicaltrials.gov number: NCT01320436., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Infliximab is an anti-tumor necrosis factor (TNF) used for treatment of inflammatory bowel disease (IBD) as well as rheumatoid arthritis, psoriasis, and other inflammatory conditions. Antibodies to infliximab (ATI) develop in approximately 45% of infliximab-treated IBD patients and are correlated with loss of clinical response. Scarce data exist as to factors which predict infliximab immunogenicity.To investigate factors that may predict formation of antibodies to infliximab (ATI) and infliximab therapy failure an observational study of consecutive IBD patients treated with infliximab between 2009 and 2013 was performed. Trough levels of ATI were measured. Patients were monitored for disease activity using clinical activity indexes and were classified according to ATI formation and clinical response. All clinical and demographic parameters were analyzed for association with the designated outcomes.One hundred fifty-nine patients were included and 1505 sera were tested. On multivariate analysis, Jewish Ashkenazi ethnicity was protective against both development of ATI (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.17-0.7, P = 0.005) and treatment failure (OR 0.29, 95% CI 0.13-0.66, P = 0.003). Concomitant immunomodulator therapy was also negatively associated with immunogenicity and infliximab therapy failure (OR 0.31, 95% CI 0.15-0.65, P = 0.002; OR 0.42 95% CI 0.18-0.99, p = 0.04, respectively), whereas episodic therapy was positively associated with both outcomes (OR 4.2 95% CI 1.07-16.1, p = 0.04, OR 4.45 95% CI 1.2-16.6, p = 0.026 respectively). All other variables, including IBD type, gender, weight, age, smoking status and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn's disease patients, a non-stricturing non-penetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14-0.96, p = 0.04). P = 0.04, respectively), whereas episodic/interrupted therapy was positively associated with both outcomes (OR 4.2, 95% CI 1.07-16.1, P = 0.04; OR 4.45, 95% CI 1.2-16.6, P = 0.026, respectively). All other variables, including IBD type, sex, weight, age, smoking status, and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn disease patients, a nonstricturing nonpenetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14-0.96, P = 0.04).Jewish Ashkenazi ethnicity is protective of ATI formation and infliximab therapy failure. These findings suggest a role for ethnicity, and implicitly for genetic predisposition, in modulating the risk of anti-TNF immunogenicity and treatment unresponsiveness.

Objective: To examine the prevalence, etiology, risk factors, and outcomes of liver abnormality in pregnancy, in a tertiary medical center, and to study the potential impact of artificial reproduction techniques (ART) on the incidence and the outcome of pregnancy-related liver abnormality., Design: A retrospective case-control study using an electronic database and patients' files., Setting: Tertiary referral center., Patient(s): Women in the third trimester of pregnancy who were hospitalized for delivery., Intervention(s): None., Main Outcome Measure(s): Development of significant elevation of alanine aminotransferase (ALT ≥ 100 IU/L). Secondary outcomes included development of maternal and fetal complications., Result(s): The upper limit of normal of ALT was ≥ 1.5 times and it occurred in 440 (1.6%) pregnancies; of those, 228 (0.8%) had ALT ≥ 100 IU/L. The etiology of significant liver test abnormality was idiopathic in 47% of patients. Compared with spontaneous pregnancies (295/23,793), ART was significantly associated with liver test abnormality (145/4, 520). The presence of ALT ≥ 100 IU/L in the third trimester was associated with higher rates of cesarean sections, prematurity, low birthweight, and fetal complications., Conclusion(s): A definite etiology was not determined in about half of pregnancy-associated liver test abnormality. The ART was significantly associated with liver test elevation. Significant liver test abnormality in the third trimester may have an impact on maternal and fetal/neonatal outcomes., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Polypectomy techniques have been implicated as factors in the effectiveness of polyp resection. The range of polypectomy practices among gastroenterologists in Israel is unknown., Methods: A structured survey was sent to all Israeli gastroenterology departments in all 15 major academic hospitals and to 3 central outpatient clinics., Results: The survey was completed by 100 clinicians (45% contacted) derived from 13 of 15 academic centers (85%) and from all 3 outpatient clinics. Significant differences were noted in the preferred polypectomy for the resection of polyps 1-3 mm and 7-9 mm in diameter whereas for those polyps 4-6 mm in diameter, both the hot forceps and hot snare were most commonly used technique. Coagulation was employed in 42% of cases, pure cutting in 20% and blend current in 38% of cases. Narrow band imaging was used by 54% of practitioners, and only 33% of gastroenterologists regularly used dye spraying techniques. When removing pedunculated polyps >1 cm in diameter, 75% did not use any specific measures designed to prevent perforation or hemorrhage. Performance of >300 colonoscopies per year was associated with a greater use of dye spraying techniques and working in a hospital was more likely to be accompanied by clip deployment to larger polypectomy stalks as part of the procedure., Conclusion: Our results demonstrate considerable heterogeneity in the techniques used for removal of polyps <1 cm. Most practitioners do not regularly use advanced techniques for polyp detection or for the prevention of post-polypectomy bleeding.

Background & Aims: There are few data on risk of travel for patients with inflammatory bowel disease (IBD). We assessed rates of illness while traveling among patients with IBD., Methods: We performed a retrospective, case-controlled study of illnesses among 222 patients with IBD and 224 healthy individuals (controls) during 1099 total trips. Data were retrieved by structured questionnaires, personal interviews, and chart review., Results: Participants had 142 episodes of illness during the trips; 92% were enteric disease. An episode of illness occurred during 79/523 (15.1%) trips made by patients with IBD compared with 63/576 (10.9%) trips made by controls (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.01-2.0; P = .04). However, this difference was mostly attributable to the increased incidence of illness among IBD patients traveling in industrialized countries. In contrast, the rate of illness among travelers to developing countries was similar among patients with IBD and controls (34/200, 17% vs 52/243, 21% of trips, respectively; P = .24). Moreover, numerically more controls that traveled to the tropics developed illness than travelers with IBD (43/135 vs 23/97, respectively; P = .18). In multivariate analysis, factors that increased risk for travel illness included frequent flares of IBD (OR, 1.9; 95% CI, 1.1-3.4; P = .02) and prior IBD-related hospitalizations (OR, 3.5; 95% CI, 1.3-9.3; P = .01); remission within 3 months before traveling reduced the risk for illness (OR, 0.3; 95% CI, 0.16-0.5; P < .001). Use of immunomodulatory drugs was not independently associated with risk of illness during travel., Conclusions: Patients with IBD have a higher rate of illness compared with controls during trips to industrialized countries, but not to developing or tropical regions. These findings indicate that most travel-associated illnesses stem from sporadic IBD flares rather than increased susceptibility to enteric infections., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: A family history of inflammatory bowel disease (IBD) is present in some ulcerative colitis (UC) patients. We aimed to investigate the familial occurrence of UC and its impact on disease severity., Methods: A structured questionnaire was distributed to patients with UC. Parameters pertaining to disease severity were compared for patients with or without positive family history of IBD., Results: The study group consisted of 168 UC patients with a total of 952 first degree relatives. Positive family history for IBD in a first degree relative was reported in 24 patients (14%). Six of the 336 parents (1.8%) had IBD (all with UC). There were 13 siblings with IBD (4 CD, 9 UC) out of 249 (5.4%). Seven of 376 (1.9%) offsprings had IBD (4 CD, 3 UC). Familial patients were more commonly females and have reported significantly more disease exacerbations than the sporadic group (17.7±15 versus 6.8±11, respectively, p=0.006). On multivariate analysis, familial disease was significantly and independently associated with both female sex (OR 4.1, 95% CI 1.1-14.9, p=0.04) and more exacerbations per year (annual OR 1.05, 95% CI 1.01-1.1, p=0.02). However, similar proportions of sporadic and familial patients wherever hospitalized, underwent colectomy or were treated by immune-suppressors., Conclusions: Familial occurrence of UC is not uncommon among Jewish patients in Israel. The familial-genetic component may preferentially influence disease occurrence among females, and is possibly associated with more disease flares although other parameters of disease severity do not seem to be impacted.

Background & Aims: Cystic lesions of the pancreas are detected more often nowadays. Many are considered premalignant and pancreatic resection is recommended. This study was undertaken to assess the natural course of asymptomatic pancreatic cysts and their malignant potential., Methods: All patients referred for endoscopic ultrasound (EUS) between 1994 and 2003 because of pancreatic cystic lesions were included., Results: A total of 135 patients underwent EUS because of pancreatic cysts. Twenty-three patients were excluded because they were symptomatic or had pancreatic pseudocysts. The other 112 patients were diagnosed as having true pancreatic cysts. Fourteen of the 112 patients were referred for surgery based on either unfavorable EUS morphology or fine-needle aspiration results. In 4 (29%) of 14 surgical specimens, the histology was that of malignancy. An additional 8 patients with serous cystadenoma and pseudocysts were excluded from the analysis. The remaining 90 patients were defined as having indeterminate or mucinous cysts and were managed conservatively. The follow-up period lasted between 12 and 180 months (mean, 48 +/- 33 mo). Malignancy was diagnosed in only 1 patient after 7 years of follow-up evaluation. None of the 57 patients available for clinical follow-up evaluation became symptomatic. The size of the cyst remained unchanged in 45 patients, increased in 2, and resolved in 9. Thirty-three patients were followed up through the Israel Registry: 31 were alive and 2 died from unrelated causes., Conclusions: Our data suggest that a considerable number of asymptomatic pancreatic cystic lesions can be managed conservatively, at least for a mean period of 4 years. Malignant transformation in pancreatic cystic lesions probably is less frequent than previously reported.

Aim: To prospectively study the incidence and the natural history of acute diverticulitis in young patients., Methods: A total of 207 patients hospitalized at our hospital between January 2000 to February 2005 with the diagnosis of acute diverticulitis were included. Their demographic characteristics, medical history, physical, radiographic and endoscopic findings as well as therapy were recorded. Patients were followed every 6 mo for the first year and later annually., Results: The mean patients' age was 61 (range 27-92) years. Twenty-five patients (12%) were younger than 45 years. Acute diverticulitis was significantly more prevalent among male in the young age group as compared to the older age group (19/25, 76% vs 61/182, 33%, respectively, P = 0.0001). Complications occurred more often in the young age group; 32% vs 13%, (P = 0.002). During follow-up, 6 patients (28%) remained asymptomatic in the young age group as compared to 87 patients (55%) in the older age group (P = 0.024). As a result, sigmoidectomies were performed twice as often in the young age group (38% vs 13%, P = 0.002)., Conclusion: Diverticulitis in young patients has a male predominance, a more aggressive course with a higher rate of complications and a higher recurrence rate. An earlier surgical approach might be considered in young patients with acute diverticulitis.

Tumour necrosis factor (TNF)-alpha is an important pro-inflammatory cytokine that has been implicated in the pathogenesis of inflammatory bowel disease (IBD). The promoter TNF-857 C-->T single nucleotide polymorphism (SNP) is functional through the binding to the transcription factor octamer transcription factor-1 (OCT-1). In order to investigate the frequency of this SNP in Israeli Jewish IBD patients, we analysed a cohort of well-characterized patients, 153 with Crohn's disease (CD) and 78 with ulcerative colitis (UC) and 188 healthy controls individually matched for age, sex and ethnicity. Forty-one per cent of the patients were of Ashkenazi and 48% were of non-Ashkenazi background. The remaining 11% were of mixed Ashkenazi-non-Ashkenazi background. Patients and controls were genotyped for the TNF-857 SNP by Taqman technology. Stratification for the CARD15 Arg702Trp, Gly908Arg and Leu1007fsinsC mutations took place in 136 CD patients. Carrier frequency of TNF-857T between CD and controls (36% vs. 40%; P = 0.556; OR: 1.18, 95% CI 0.74-1.88), or between UC and controls (41% vs. 37%; P = 0.743; OR: 0.85, 95% CI 0.45-1.62) did not differ significantly. Neither did stratifying for the presence of at least one of the common CARD15 mutations result in a significant difference between CD and controls. No associations were found between TNF-857T and CD phenotype as defined by the Vienna classification, perianal disease or extra-intestinal disease irrespective of CARD15 carrier status. In conclusion, it appears that TNF-857 SNP does not contribute to susceptibility of IBD, neither does it define the phenotype of CD in Israeli Jewish IBD patients.

Background: Screening for celiac disease is based on the sequential evaluation of serologic tests and intestinal biopsy; an optimal screening protocol is still under investigation. The screening policy of one of the main healthcare providers in Israel (Maccabi) consists of measuring total immunoglobulin A and tissue transglutaminase IgA antibodies and confirming positive results by endomysial antibodies. For IgA-deficient patients antigliadin IgG is measured., Objectives: To evaluate the use of tTGA as a first-level screening test in patients suspected of having celiac disease, Methods: The results of tTGA and EMA tests over a 3 month period were obtained from the laboratory computer. Letters were sent to the referring physicians of patients with positive tests, requesting clinical information and small intestinal biopsy results. tTGA was performed using an anti-guinea pig tTG-IgA enzyme-linked immunosorbent assay kit., Results: Overall, 2,505 tTGA tests were performed: 216 (8.6%) were tTGA-positive of which 162 (75%) were EMA-negative (group 1) and 54 (25%) EMA-positive (group 2.) Clinical information was obtained for 91 patients in group 1 and 32 in group 2. Small intestinal biopsy was performed in 33 (36%) and 27 patients (84%) in groups 1 and 2, respectively. Celiac disease was diagnosed in 4 biopsies (12%) in group 1 and 23 (85%) in group 2 (P < 0.0001). The positive predictive value was 45% for tTGA and 85% for EMA., Conclusions: Symptomatic patients with positive tTGA and negative EMA have a low rate of celiac disease compared to those who are tTGA-positive and EMA-positive. Confirmation with EMA is advised when tTGA is performed as a first-level screening for suspected celiac disease.

Background: Current treatment for the eradication of Helicobacter pylori in patients with peptic disease is based on the combination of antibiotic and anti-acid regimens. Multiple combinations have been investigated, however no consensus has been reached regarding the optimal duration and medications., Objectives: To assess the efficacy of two treatment regimens in patients with peptic ulcer disease and non-ulcer dyspepsia, and to determine the need for gastric mucosal culture in patients failing previous treatment., Methods: Ninety patients with established peptic ulcer and NUD (with previously proven ulcer) were randomly assigned to receive either bismuth-subcitrate, amoxycillin and metrnidazole (BAM) or lansoprasole, clarithromycine and metronidazole (LCM) for 7 days. Patients with active peptic disease were treated with ranitidine 300 mg/day for an additional month., Results: Eradication failed in 8 of the 42 patients in the BAM group and in 2 of the 43 patients in the LCM group, as determined by the 13C urea breath test or rapid urease test (19% vs. 5%, respectively, P = 0.05). Five of these 10 patients were randomly assigned to treatment with lansoprazole, amoxycillin and clarithromycin (LAC) regardless of the culture obtained, and the other 5 patients were assigned to treatment with lansoprazole and two antibacterial agents chosen according to a susceptibility test. Eradication of H. pylori was confirmed by the 13C urea breath test. The same protocol (LAC) was used in all patients in the first group and in four of the five patients in the second group. The culture results did not influence the treatment protocol employed., Conclusions: Combination therapy based on proton pump inhibitor and two antibiotics is superior to bismuth-based therapy for one week. Gastric-mucosal culture testing for sensitivity of H. pylori to antibiotics is probably unnecessary before the initiation of therapy for patients with eradication failure.

Background: About one-third of patients with severe ulcerative colitis do not respond to conventional therapy and require urgent colectomy. It was recently shown that cyclosporin is effective in some of these patients., Objectives: To review the current experience of six hospitals in central Israel that used cyclosporin in patients with severe ulcerative colitis., Methods: The files of all 32 patients treated with cyclosporin for corticosteroid-resistant ulcerative colitis were reviewed. Activity of disease was measured by a clinical activity, index colonoscopy and laboratory tests., Results: The average duration of treatment with intravenous cyclosporin was 12.7 days (range 9-28) after which the disease activity index dropped from an average of 14.22 to 4.74. The mean time for response was 7.5 days (4-14). Twelve patients (40%) required surgery within 6 months and another 6 patients (18.8%) were operated on after more than 6 months. Twelve patients (37%) maintained remission for at least 6 months and did not require surgery. In one patient treatment was stopped because of non-compliance and one was lost to follow-up. There were numerous side effects, but in only one case with neurotoxicity was treatment withdrawn., Conclusions: Cyclosporin is a relatively safe and effective treatment for severe ulcerative colitis. It induced long-term remission in 37% of the patients, and in those who required surgery the treatment resulted in an improved clinical condition before the operation.