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עמוד בית
Wed, 29.05.24

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April 2024
Kassem Sharif MD, Adi Lahat MD, Yonatan Shneor Patt MD, Niv Ben-Shabat MD, Mahmud Omar MD, Abdulla Watad MD, Howard Amital MD MHA, Omer Gendelman MD

Background: Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are chronic conditions with overlapping pathogenic mechanisms. The genetic predisposition and inflammatory pathways common to both diseases suggest a syndemic relationship. While some evidence points to a connection between the two conditions, other reports do not support this link.

Objectives: To investigate the association between AS and the subsequent incidence of IBD. To identify potential risk factors and effect modifiers that contribute to this relationship.

Methods: Utilizing the Chronic Disease Registry of Clalit Health Services, we conducted a retrospective cohort study of individuals diagnosed with AS between January 2002 and December 2018. We compared these patients with age- and sex-matched controls, excluding those with a prior diagnosis of IBD. Statistical analyses included chi-square and t-tests for demographic comparisons, and Cox proportional hazards models for evaluating the risk of IBD development, with adjustments for various co-morbidities and demographic factors.

Results: The study included 5825 AS patients and 28,356 controls. AS patients demonstrated a significantly higher incidence of IBD with hazard ratios of 6.09 for Crohn's disease and 2.31 for ulcerative colitis, after multivariate adjustment. The overall incidence of IBD in the AS cohort was significantly higher compared to controls.

Conclusions: AS patients exhibit a markedly increased risk of developing IBD. These findings advocate for heightened clinical vigilance for IBD symptoms in AS patients and suggest the need for a multidisciplinary approach to patient care. Further research into the shared pathogenic pathways is needed to develop personalized treatment strategies and improve patient management.

March 2024
Jill Savren Lotker MD, Ariel Roguin MD PhD, Arthur Kerner MD, Erez Marcusohn MD, Ofer Kobo MD PhD

Background: Patients with inflammatory bowel disease (IBD) are at increased risk after percutaneous coronary intervention (PCI).

Objectives: To compare the clinical outcomes within 30 days, one year, and five years of undergoing PCI.

Methods: We conducted a retrospective cohort study of adult patients with IBD who underwent PCI in a tertiary care center from January 2009 to December 2019.

Results: We included 44 patients, 26 with Crohn’s disease (CD) and 18 with ulcerative colitis (UC), who underwent PCI. Patients with CD underwent PCI at a younger age compared to UC (57.8 vs. 68.9 years, P < 0.001) and were more likely to be male (88.46% of CD vs. 61.1% of UC, P < 0.03). CD patients had a higher rate of non-steroidal treatment compared to UC patients (50% vs. 5.56%, P < 0.001). Acute coronary syndromes (ACS) and/or the need for revascularization (e.g., PCI) were the most common clinical events to occur following PCI, in both groups. Of patients who experienced ACS and/or unplanned revascularization within 5 years, 25% of UC vs. 40% of CD had target lesion failure (TLF) due to in-stent restenosis and 10% of CD had TLF due to stent thrombosis.

Conclusions: We observed higher rates of TLF in IBD patients compared to the general population as well as differences in clinical outcomes between UC and CD patients. A better understanding of the prognostic factors and pathophysiology of these differences may have clinical importance in tailoring the appropriate treatment or type of revascularization for this high-risk group.

December 2023
Yael Weintraub MD, Raffi Lev-Tzion MD, Jacob Ollech MD, Hagar Olshaker MD, Irit Rosen MD, Shlomi Cohen MD, David Varssano MD, Dror S. Shouval MD, Manar Matar MD

Anti-tumor necrosis factor-alpha (anti-TNFα) medications are the most frequently used biologicals to treat inflammatory bowel disease (IBD). Little is known about the ocular side effects of this drug category. We present a case series of six young patients with Crohn disease (CD) and no previous ophthalmologic manifestations who developed blepharitis after commencing treatment with anti-TNFα therapy. Six otherwise healthy patients with CD, with no history of allergies or prior ocular complaints, developed blepharitis at a median of 7.5 months after the initiation of anti-TNFα therapy. All ophthalmic findings were treated topically. The ocular symptoms of two of the patients resolved shortly after discontinuation of the anti-TNFα treatment. The other four presented with relapsing-remitting symptoms. Blepharitis is a common ocular disease in the general population and an extra-intestinal manifestation in patients with IBD. It may be an adverse effect of anti-TNFα therapy in this patient population.

December 2021
Ido Veisman MD, Doron Yablecovitch MD, Uri Kopylov MD, Rami Eliakim MD, Shomron Ben-Horin MD, and Bella Ungar MD

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.

March 2021
Yaron Niv MD AGAF FACG

Hospitalization of ulcerative colitis patients is needed in severe exacerbation of the disease or for managing complications. In this systematic review and meta-analysis the prevalence of hospitalization in ulcerative colitis and possible predictive factors are discussed. A systematic literature search of English language publications that were published before 31 December 2019 was conducted. Retrospective cohort studies describing hospitalizations of UC patients were included. Meta-analysis was performed by using comprehensive meta-analysis software. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated for the number of patients hospitalized. Seven studies and 15 datasets were found that fulfilled the inclusion criteria. In total, the studies included 2067 patients from six countries. The event rates for the number of patients hospitalized in a follow-up duration of 42,320 patient-years and for the number of patients underwent operation in a follow-up of 24,650 patient-years were 0.065 (95%CI 0.063–0.068) and 0.019 (95%CI 0.017–0.021), respectively. More studies during the era of biologics need to be performed to identify the factors predictive of hospitalization and surgery with UC. Prevention of inflammation and UC complications may prevent hospitalization and the need for surgical treatment

November 2020
Amir Mari MD, Tawfik Khoury MD, Mahmud Mahamid MD, Shorbaji Akram MD, Yael Kopelman MD, and Fadi Abu Baker MD

Background: While the routine performance of terminal ileum (TI) intubation during colonoscopy procedures is perceived to have a low yield, its utility during colonoscopies performed for specific indications have not been well studied.

Objectives: To assess the diagnostic yield of an indication-based ileoscopy in real-life practice.

Methods: The authors reviewed endoscopic reports of patients who underwent colonoscopies over an 8-year period (2011–2018) and had routine ileoscopy during these procedures. Demographic data, indications for colonoscopy, and endoscopic findings were documented. Diagnostic yield and odds ratio for TI findings were calculated.

Results: Over 30,000 colonoscopy reports performed during the study period were reviewed. Ilesocopy was performed in 1800 patients, 216 patients had findings in the TI (ileitis or ulcers). TI findings were more prevalent in younger ages (38.3 ± 17.6 vs. 43.6 ± 20, P < 0.05). The greatest yield of ileoscopy was evident when performed for the evaluation of chronic abdominal pain and diarrhea (14.4% vs. 9.3%, odds ratio [OR] 1.62, P < 0.05). Positive fecal occult blood test (FOBT) (OR 0.1, 95% confidence interval [95%CI] 0.02–0.5, P = 0.005) and constipation (OR 0.44, 95%CI 0.2–0.9, P = 0.04) were negatively associated with TI findings.

Conclusions: Ileoscopy may have the greatest utility in evaluating suspected inflammatory bowel disease (IBD) patients, but may not add value to the evaluation of constipation and positive FOBT

February 2020
Yaron Niv MD AGAF FACG

Despite advances in therapeutic modalities, especially with biologic treatments, the number of hospitalizations due to complications for Crohn's disease did not decrease. We examined the prevalence and possible predictive factors of hospitalizations in Crohn's disease. A systematic literature search was conducted until 31 October 2018. Relevant studies were screened according to established protocol. Retrospective cohort studies describing hospitalizations of Crohn's disease patients were included. Meta-analysis was performed by using comprehensive meta-analysis software. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated for the number of patients hospitalized. Twelve studies published before 31 March 2018 fulfilled the inclusion criteria and were comprised of 23 data-sets and included 4421 patients from six countries. A funnel plot demonstrates a moderate publication bias. We reported the event rates for the number of patients hospitalized, in a follow-up survey of 20,987 patient-years, and for the patients who underwent surgery in a follow-up of 5061 patient-years, with ORs of 0.233 with 95%CI 0.227–0.239, and 0.124 with 95%CI 0.114–0.135 (P < 0.001), respectively. Thus, when collecting the data from 12 cohort studies we found that hospitalization takes place in 23.3% of the patients, and operation in 12.4% along their disease duration. Patients with Crohn's disease may be hospitalized due to exacerbation of their inflammatory disease, because of non-inflammatory disease (such as fistula or stricture), or due to medical complications. The goal of therapy should be to keep the Crohn's disease patients in their natural environment and out of the hospital and to prevent surgery as much as possible.

March 2019
Ibrahim Zvidi MD, Doron Boltin MBBS, Yaron Niv MD, Ram Dickman MD, Gerald Fraser MD and Shlomo Birkenfeld MD

Background: Temporal trends in the incidence of inflammatory bowel disease (IBD) in the Arab and Jewish populations in Israel have been poorly described.

Objectives: To compare the annual incidence and prevalence rates of Crohn's disease (CD) and ulcerative colitis (UC) in the Arab and Jewish populations in Israel between the years 2003 and 2008.

Methods: We applied a common case identification algorithm to the Clalit Health Services database to both determine trends in age-adjusted incidence and prevalence rates for IBD in both populations during this period and estimate the burden of IBD in Israel.

Results: The incidence of CD in the Arab population increased from 3.1/100,000 in 2003 to 10.6/100,000 person-years in 2008, compared with a decrease in the Jewish population from 14.3/100,000 to 11.7/100,000 person-years for the same period. The incidence of UC in the Arab population increased from 4.1/100,000 in 2003 to 5.0/100,000 person-years in 2008, a low but stable rate, compared with a decrease from 16.4/100,000 to 9.5/100,000 person-years for the same time period in the Jewish population. The prevalence of both diseases increased due to the accumulation of incident cases but remained much lower among Arabs.

Conclusions: Understanding the factors underlying the differences in incidence and prevalence of IBD in the Jewish and Arab populations may shed light on the genetic and environmental factors associated with these diseases.

November 2018
Naim Abu Freha MD MHA, Wafi Badarna MD, Muhammad Abu Tailakh RN MPH PhD, Heba Abu Kaf MD, Alex Fich MD, Doron Schwartz MD, Arik Segal, Jabir Elkrinawi and Amir Karban MD

Background: Inflammatory bowel disease (IBD) prevalence is increasing among Bedouin Arabs in Israel. This population is known to have a high rate of consanguinity. NOD2/CARD15 mutations are well-studied in IBD.

Objectives: To investigate the frequency of NOD2/CARD15 mutations in IBD Bedouin patients and their relevance to disease phenotype.

Methods: The IBD-Arab cohort in southern Israel included 68 patients, of which 25 Crohn's disease (CD) patients and 25 ulcerative colitis (UC) patients consented to participate (72%). Blood samples were obtained from all participants who were genotyped for NOD2/CARD15 variants Arg702Trp, Gly908Arg, and Leu1007fsinsC.

Results: The NOD2/CARD15 mutation frequency was higher in Crohn's disease than in ulcerative colitis patients. Carrier frequency for the Gly908Arg mutation in CD and UC patients was 8/25 (32%) and 3/25 (12%), respectively (P = 0.08). Neither the Arg702Trp nor Leu1007fsinsC mutation was found in our cohort. No homozygous/compound heterozygote mutations were found. Genotype-phenotype analysis revealed that CD patients carrying the Gly908Arg mutation were younger at diagnosis, 22.8 ± 4.5 vs. 28.82 ± 9.1 years (P = 0.04). All carriers were males, compared with 41.2% in non-carriers (P = 0.005). NOD2/CARD15 mutation carriers with UC were older, 67.0 ± 24.5 years compared with 41.2 ± 12.3 years (P = 0.006). No other associations regarding disease localization or other clinical parameter were found.

Conclusions: The frequency of NOD2/CARD15 gene mutations is high in CD and UC among Bedouin Arab IBD patients and is associated with younger age at onset in CD and male gender.

Igor Snast MD, Iris Ostfeld MD, Lev Pavlovsky MD PhD, Emmilia Hodak MD and Anat Gafter-Gvili MD
October 2016
Naseem Shadafny MD, Samuel N. Heyman MD, Michael Bursztyn MD, Anna Dinaburg MD, Ran Nir-Paz MD and Zvi Ackerman MD
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