The association between sonographic common bile duct dilatation and outcomes in emergency department patients with cholangitis.

BACKGROUND: The presentation of the patient with acute cholangitis (AC) ranges from mild illness to life-threatening shock. Therefore, prompt diagnosis and treatment are critical. Abdominal ultrasound (US) is the imaging of choice to locate bile duct dilatation. Other modalities include abdominal computed tomography (CT) or endoscopic retrograde cholangiopancreatography (ERCP). OBJECTIVES: To determine whether sonographic common bile duct dilatation in emergency department (ED) patients with AC predicts outcomes including sepsis, hospital length of stay (LOS), admission to the intensive care unit (ICU), time to ERCP, and mortality. METHODS: Electronic medical records of all patients hospitalized in a tertiary care medical center between July 2012-February 2021 with a discharge diagnosis of cholangitis were assessed. Patients were dichotomously classified as CBD dilated or CBD non-dilated based on ultrasound. Dilation was defined as CBD larger than 6 mm in patients younger than 60 or larger than 6 mm + 1 mm per decade in patients over 60. RESULTS: The study included 271 patients- 172 with CBD dilation versus 99 without. Mean LOS was 9.92 days for those with a dilated CBD versus 13.4 days without. The mean time to ERCP was 4.26 days for those with a dilated CBD versus 6.56 days without. Sepsis, mortality, and ICU admission were scarce and there was no statistically significant difference between the cohorts. CONCLUSION: Patients with a dilated CBD per the abdominal US performed during the patient's ED stay, underwent ERCP earlier, and were hospitalized fewer days than patients without CBD dilation.

Real-world experience with Curcumin-QingDai combination for patients with active ulcerative colitis: A retrospective multicentre cohort study.

BACKGROUND: Curcumin and QingDai (QD, Indigo) have been shown to be effective for treating active ulcerative colitis (UC). AIM: To evaluate the real-world experience with the Curcumin-QingDai (CurQD) herbal combination to induce remission in active UC. METHODS: A retrospec-tive multicentre adult cohort study from five tertiary academic centres (2018-2022). Active UC was defined as a Simple Clinical Colitis Activity Index (SCCAI) ≥ 3. Patients were induced by CurQD. The primary outcome was clinical remission at weeks 8-12, defined as SCCAI ≤2 and a decrease ≥3 points from baseline. Secondary outcomes were clinical response (SCCAI decrease ≥3 points), corticosteroid-free remission, faecal calprotectin (FC) response (reduction ≥50%), FC normalisation (FC ≤100 µg/g for patients with FC ≥300 µg/g at baseline), and safety. All outcomes were analysed for patients who were maintaining stable treatment. RESULTS: Eighty-eight patients were included; 50% were biologics/small molecules experienced, and 36.5% received ≥2 biologics/small molecules. Clinical remission was achieved in 41 (46.5%), and clinical response in 53 (60.2%). Median SCCAI decreased from 7 (IQR:5-9) to 2 (IQR:1-3); p < 0.0001. Of the 26 patients on corticosteroids at baseline, seven achieved corticosteroid-free remission. Among 43 biologics/small molecules experienced patients, clinical remission was achieved in 39.5% and clinical response in 58.1%. FC normalisation and response were achieved in 17/29 and 27/33, respectively. Median FC decreased from 1000 µg/g (IQR:392-2772) at baseline to 75 µg/g (IQR:12-136) at the end of inductions (n = 30 patients with paired samples); p < 0.0001. No overt safety signals emerged. CONCLUSION: In this real-world cohort, CurQD effectively induced clinical and biomarker remission in patients with active UC, including patients who were biologics/small molecules experienced.

High Failure Rate Following Restorative Surgery for Rectal Prolapse in Systemic Sclerosis Patients.

INTRODUCTION: Systemic sclerosis (SSc) is a rare autoimmune connective tissue disorder. Colonic disorders are reported in 70% of patients. Only a few cases of rectal prolapse surgical repair in SSc patients were published, demonstrating high recurrence rate following any restorative surgery. The aim of this study is to present our surgical experience combined with the reported cases of SSc patients who underwent surgical interventions for rectal prolapse. METHODS: We reviewed our data and the published reports in the English literature of patients with SSc who underwent surgery for rectal prolapse. We located 6 case reports, in addition to 3 patients who were operated in our center. RESULTS: A total of 19 procedures (9 patients) were included, among them 17 restorative surgeries and 2 low anterior resections (LAR) with end-colostomy. All patients were female (mean age 70.3). Index surgery was perineal rectosigmoidectomy in 5, abdominal resection rectopexy in 3, and LAR with colostomy in 1 patient. All patients following restorative surgery suffered from fecal incontinence. 5 patients (62.5%) who underwent restorative surgery required at least 1 re-operation. The 2 patients who underwent LAR and colostomy reported a complete resolution of anorectal symptoms with a major improvement in their quality of life. CONCLUSION: High recurrence rate is expected in SSc patients with rectal prolapse who undergo a restorative procedure. Low anterior resection and permanent colostomy provide an alternative surgical option to patients with SSc and prolapse in contrast to restorative surgery. We believe that this surgical approach should be offered for these patients.

Inflammatory bowel disease in families with four or more affected first-degree relatives.

BACKGROUND: Family history increases the risk for inflammatory bowel diseases (IBDs). However, data on differences in phenotypic characteristics among patients with a strong family history of IBD are scarce and controversial. The aim of the study was to compare the phenotypic features of IBD patients with four or more affected first-degree relatives with sporadic cases of IBD. METHODS: Patients with familial and sporadic IBD were identified from the institutional IBD database. IBD patients from families with at least four first-degree affected relatives were selected for analysis and were compared to non-matched sporadic cases with IBD chosen randomly. Comparison for type of IBD (Crohn's disease (CD) vs. ulcerative colitis (UC)), age at onset as well as for disease extent, behavior, extraintestinal manifestations and indicators of severe disease were analyzed. RESULTS: Thirty-five patients with familial IBD (28 CD, seven UC) were compared to 88 sporadic IBD patients (61 CD, 24 UC and three IBDU). Disease duration was 10.3 ± 8.2 in the familial and 8.0 ± 7.2 years in the sporadic cases, p=.13. The familial cases were younger at diagnosis (19.3 ± 8.6 vs. 25.7 ± 11.8, p=.004). Patients with familial compared to sporadic IBD were significantly more likely to require steroid treatment (80% vs. 54.5%, p=.009), biological treatment (94.3%, vs. 63.6%, p<.001) or surgery (25.7%, vs. 11.4%, p=.048). CONCLUSIONS: IBD with a very strong positive family history is associated with younger age at onset and a more adverse IBD phenotype compared to sporadic IBD.

COVID-19 in Patients with Inflammatory Bowel Disease: The Israeli Experience.

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.

External kinesiology tape for improvement in fecal incontinence symptom bother in women: a pilot study.

INTRODUCTION AND HYPOTHESIS: Fecal incontinence is a debilitating condition with a devastating impact on quality of life. Using a commercially available kinesiology band we developed an anal tape to be applied to the anus with the aim to determine its impact on symptom bother and quality of life. METHODS: Four-week prospective, self-controlled, pilot study of patients with FI. The primary outcome was improvement in any of the four domains (lifestyle, coping/behavior, depression/self-perception, embarrassment) evaluated by the "Fecal Incontinence Quality of Life Scale." Secondary outcomes included improvement in frequency of incontinence events and safety. Days 0-14 served as control period and days 15-28 as study period. Patients were asked to rate their satisfaction and willingness to use the device in the future using a 10-cm continuous visual analog scale. RESULTS: Twenty patients completed the study. Median age was 64 years; all patients were females. Significant improvements were observed in all domains of the Fecal Incontinence Quality of Life Scale from baseline to day 28 (p < 0.001 for all) and in three of four domains between day 15 and 28 (p < 0.04) but not between days 1 and 14. Five patients (25%) had a ≥ 50% improvement in incontinence events. Patients reported satisfaction and willingness to use the anal tape in the future. Other than mild difficulty to remove the anal tape, no adverse events were reported. CONCLUSIONS: In this small pilot study, the use of the anal tape was safe and effective. The primary outcome of significant improvement in quality of life was achieved ( ClinicalTrials.gov ID:NCT02989545). PUBLIC TRIAL REGISTRY: ClinicalTrials.gov identifier NCT02989545. https://clinicaltrials.gov/ct2/show/NCT02989545.

Short-term effectiveness and safety of tofacitinib in ulcerative colitis - real world data from tertiary medical centers in Israel.

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.

Anemia can predict the prognosis of colorectal cancer in the pre-operative stage: a retrospective analysis.

BACKGROUND: Early detection of colorectal cancer (CRC) improves prognosis, yet many CRCs are diagnosed following symptoms. The aim of this study was to determine which CRC-related symptoms or signs can predict an advanced CRC in the pre-operative stage. METHODS: Retrospective analysis of 300 patients who underwent surgery for CRC between the years 2008 and 2019. Patients' symptoms prior to CRC diagnosis were documented. Primary endpoint was the association of signs or/and symptoms with CRC diagnosis at TNM stages of 2-4 (i.e., highly advanced), compared to TNM score of 0-1 (i.e., locally advanced). RESULTS: Three hundred patients, 91 with locally advanced and 209 with highly advanced CRC, were enrolled. There was a significant correlation between highly advanced CRC, compared to locally advanced, regarding tumor size (4.8 vs. 2.6 cm, p<0.001), presentation of any symptom prior to diagnosis (77% vs. 54%, p<0.001), anemia (46% vs. 29%, p=0.004), and severe anemia (17% vs. 4%, p=0.002). Mean hemoglobin was 12.2 ± 2.2 and 13.1 ± 1.8 in the highly advanced compared to locally advanced CRC, respectively, p<0.001. Anemia correlated with the T stage of the tumor: 21% of patients diagnosed at stages 0-1 had anemia, 39% at stage 2, 44% at stage 3, and 66% at stage 4 (p=0.001). CONCLUSIONS: Anemia is the only finding that correlates with highly advanced CRC, in the pre-operative stage. When CRC has been diagnosed, the presence of anemia, at any level, may be considered in determining prognosis at the pre-operative stage. Physicians should be aware that when anemia is present, the risk for highly advanced CRC increases, and therefore should pursue with CRC detection.

Military Aviators with Inflammatory Bowel Diseases Continued Flying.

INTRODUCTION: Military aviators are likely to be first diagnosed with inflammatory bowel diseases (IBD) during military service. Current recommendations support continuing flying with restrictions, but risks may be significant. The aim of the study was to document the long-term results of aviators newly diagnosed with IBD. METHODS: A prospective observational study over a 23-yr period included all Israeli Air Force (IAF) aviators with IBD. Primary end point was the qualification and safety to continue operational flying following IBD diagnosis. RESULTS: Subjects were 16 male aviators with an average follow-up of 130 mo. Average age was 27 (2045) and average time from symptoms onset to final diagnosis was 7.3 mo. Eight (50%) patients had Crohns disease (CD), and the other eight had ulcerative colitis (UC). Eight (50%) were high performance platform aviators. Two patients received biologic treatment, two were treated with repeated corticosteroid courses, and four with immunosuppressive therapy. Two patients underwent surgery and four needed different lengths of hospitalizations. Eight (50%) aviators (3 CD, 5 UC) were grounded for a mean of 177 d (5590). Altogether grounding for IBD aviators was 46/2087 mo (2.2%). Most grounding periods were short term and reversible. All aviators continued flying under annual monitoring or as needed and no compromise of their abilities was documented. CONCLUSIONS: All aviators were able to continue flying and no events of sudden incapacitation or severe disabling flares have been seen among patients. Our study findings support the current recommendation to continue flying when IBD is in stable remission. Tehori O, Koslowsky B, Gabbai D, Shapira S, Ben-Ari O. Military aviators with inflammatory bowel diseases continued flying. Aerosp Med Hum Perform. 2021; 92(10):831834.

The pediatric ulcerative colitis activity index (PUCAI) predicts steroid-failure in adults with acute severe colitis.

BACKGROUND: One-third of patients with acute severe ulcerative colitis (ASC) fail to respond to intravenous corticosteroids (IVCS) and require second-line therapy or colectomy. We aimed to explore the performance of the Pediatric Ulcerative Colitis Activity Index (PUCAI), for predicting response to IVCS in adults with ASC, and to base a two-step decision-making process for guiding the introduction of second-line therapy. METHODS: This was a retrospective multicenter cohort study of adult patients with ASC. PUCAI score, Oxford criteria, and Swedish index were determined at baseline, day three and five of hospitalization, and discharge when outcomes were ascertained. RESULTS: 153 patients were included (mean age 34.7 ± 14.6, median disease duration 7.8 years [IQR 0-17.4]), of whom 51 (33%) required second-line therapy, and 23 (15%) eventually underwent colectomy by discharge. At days three and five, the median PUCAI scores were higher in non-responders compared with responders (55 [45-69] vs. 38 [25-55] at day 3, and 55 [36-65] vs. 20 [5-30] at day 5; both p < .001). The negative and positive predictive values (NPV and PPV) of IVCS failure were 76/63% for the Oxford criteria, 83/52% for the Swedish index as determined on day 3, and 73/100% for PUCAI ≥ 65 points on day five. The corresponding figures for PUCAI ≥ 45 at day 3 were 83/54%. CONCLUSION: The PUCAI is a highly predictive tool for IVCS failure. PUCAI ≥ 45 on day 3 has an excellent NPV for IVCS failure indicating preparation for second-line therapy, and PUCAI ≥ 65 on day 5 has a high PPV to initiate the therapy.

Safety of oesophagogastroduodenoscopy in a nonagenarian population.

BACKGROUND: invasive gastrointestinal (GI) procedures are increasingly performed on much older patients but data regarding oesophagogastroduodenoscopy (OGD) in this population are limited. We compared the indications, safety and benefits of OGD for nonagenarians compared to octogenarians. METHODS: an observational retrospective review of patients who underwent OGD between 2013 and 2018 at a gastroenterology institute in one large hospital. Patients aged 90 and above 'nonagenarians' were compared to those aged 80-89 'octogenarians'. RESULTS: 472 patients (231 nonagenarians and 241 octogenarians), median age of 91 for nonagenarians (201 aged 90-94, 30 aged 95 and older) and 82 (174 aged 80-84, 67 aged 85-89) for octogenarians. GI bleeding was a more common and dyspepsia, a less common, indication for nonagenarians compared to octogenarians (55 and 7%, versus 43 and 18%). Significant findings and need for endoscopic treatments were both more commonly found in nonagenarians compared to octogenarians (25 and 24% versus 15 and 8%, respectively). General anaesthesia was more commonly given to nonagenarians (35 versus 10%). Immediate complications and 30-day mortality rate were similar between the groups: (2.6% of nonagenarians versus 1.6% of octogenarians). Of 30 patients aged 95 and older, 13% had late adverse events, compared to 1% of the overall cohort. CONCLUSIONS: OGD appears safe in nonagenarians. Pathological findings and endoscopic interventions are more common. Decisions regarding OGD should not be based on age alone.

Gastroenterologists' Attitude Regarding Medical Cannabis for Inflammatory Bowel Diseases in Israel.

BACKGROUND: The use of medical cannabis (MC) for inflammatory bowel diseases (IBDs) is expanding. Current evidence does not support the efficacy of MC for reducing inflammation in IBD patients. Even so, many gastroenterologists encounter the issue of recommending use of MC to IBD patients. METHODS: A Web-based survey was completed by 84 (34%) gastroenterologists in Israel. RESULTS: Out of 84 physicians whom completed the questionnaire, 59 (70%) were male, 34 (40%) were under age 50 years, 71 (85%) were adult gastroenterologists, and 53 (63%) work mainly in a hospital. Of them, 15, 41, and 44% of physicians think that MC is very effective, mildly effective, and not effective at all, respectively. Physicians will commonly, rarely, and never recommend MC in 31, 47, and 22%, respectively. Older physicians (above age 50 years) were significantly more likely to have a positive attitude towards MC in both questions. When presented with a clinical scenario of a patient in deep remission, requesting to increase the dose, 32% would increase, 49% would maintain, and only 18% would stop prescribing MC altogether; 48% of physicians did not know the recommended initial dose for MC. Only 2 (2.5%) physicians initiated the use of MC to all patients. Female gastroenterologists were significantly more likely to initiate MC, p = 0.048. CONCLUSION: The use of MC for IBD patients is commonly encountered. Completely different attitudes regarding this treatment were seen. Age above 50 years and female physicians generally had a more positive attitude towards the use of MC. Guidelines and clear recommendations are needed.

Peri-myocarditis caused by topical rectal mesalamine.

Peri-myocarditis has been associated to mesalamine use. The definite association and use of topical rectal mesalamine to peri-myocarditis is not commonly known. In this case, we present a 46-year-old male exposed repeatedly to mesalamine with repeated peri-myocarditis. The relation to the medication was definite. Although an uncommon side effect of mesalamine, the possibility of peri or myocarditis should be considered. Awareness and early recognition may avoid potentially severe complications.

Factors Associated with Inflammatory Bowel Disease Flare During Pregnancy Among Women with Preconception Remission.

BACKGROUND: The factors associated with inflammatory bowel diseases (IBD) relapse throughout gestation in those with preconception remission remain unknown. AIMS: We aimed to investigate disease and pregnancy course among IBD women with quiescent disease at conception. METHODS: Women with IBD attending a multidisciplinary clinic for preconception, antenatal and postnatal treatment were prospectively recruited during 2011-2018. RESULTS: Overall, 298 women with IBD with quiescent disease at the time of conception constituted the study cohort. Of these, 112 (37.6%) women experienced disease flare during pregnancy. The risk of disease relapse was higher in those with ulcerative colitis (UC) as compared to those with Crohn's disease (CD) (48.1% vs. 31.8%, P = 0.005). The proportion of women with prior IBD-related gastrointestinal surgery was lower in those who experienced disease flare up (13.4% vs. 26.3%, P = 0.009). The use of biologic therapy at the time of conception was associated with lower rates of disease relapse (25.0% vs. 43.9%, P = 0.001). In multivariate analysis, use of conventional medications or no treatment (aOR [95% CI]: 2.0 (1.12, 3.57), P = 0.02) and lack of prior history of IBD-related surgery (aOR [95% CI]: 3.13 (1.37, 7.14), P = 0.007) were independently positively associated with disease relapse. Rates of hospitalization during pregnancy (21.4% vs. 2.2%, P < 0.001) and preterm delivery (22.3% vs. 9.1%, P = 0.002) were higher, and birthweight was lower (median 2987 vs. 3153 grams, P = 0.05) in those with disease flare as compared to those who maintained remission. CONCLUSION: Prior IBD-related surgery and biologic therapy were found as independent protective factors against relapse during pregnancy among women with quiescent disease at conception.

The severity of anemia does not correlate with the risk of gastrointestinal cancer in subsequent evaluation.

Introduction: Iron deficiency anemia (IDA) is a risk factor for gastrointestinal (GI) malignancies. Little is known regarding the correlation between the depth of anemia and the risk for GI malignancy. The aim of this study was to test the hypothesis that very low hemoglobin levels pose an additional risk compared to low hemoglobin levels.Methods: Patients 40-70 years old, presenting to the ER with IDA during years 2016-2017 were retrospectively analyzed. Comparison was performed between two groups, one with a very low hemoglobin level (below 8 g/dL) and the other a low hemoglobin level (between 8-10 g/dL).Results: 1020 patients were analyzed, and 107 fulfilled the inclusion criteria. Seventy-five patients (70%) were in the very low hemoglobin group and 21 patients (19.6%) were diagnosed with a new GI malignancy. Mean age was 56, 49 (45%) were females, and 68 (63%) underwent esophagogastroduodenoscopy (EGD) or/and colonoscopy during the index hospitalization. The median hemoglobin and MCV were 7.3 G/dL, and 73 fL, respectively. New malignancies were found in 15/75 (20%) and 6/32 (19%) of patients with very low and low hemoglobin levels, respectively (p = .88). GI malignancies were more commonly found in females compared to males, 14 (29%) vs. 7 (12%), p = .032, respectively. The right colon was the most common site for malignancy. Active GI bleeding was not a risk factor for GI malignancy.Conclusions: Very low hemoglobin levels and overt GI bleeding do not pose an additional risk factor for GI malignancy, compared to low hemoglobin levels and no overt GI bleeding.

Disease flare at prior pregnancy and disease activity at conception are important determinants of disease relapse at subsequent pregnancy in women with inflammatory bowel diseases.

PURPOSE: Disease flare throughout gestation are not uncommon among women with inflammatory bowel diseases (IBD), and can substantially affect pregnancy outcomes. We aimed to evaluate the effect of prior pregnancy outcome on the risk of disease flare at subsequent pregnancy in women with IBD. METHODS: Women with IBD attending a multidisciplinary clinic for the preconception, antenatal and postnatal treatment were prospectively recruited during 2011-2018. RESULTS: Overall, 476 IBD women were followed during the study period. Of them, 69 (14.5%) had two pregnancies throughout follow-up period and constituted the study cohort. Among these 69 women, 48 (69.6%) had Crohn's disease and 21 (30.4%) ulcerative colitis. The median interpregnancy interval was 20 [11-32] months. Overall, 34 (49.3%) women experienced disease flare at the subsequent pregnancy. In multivariate analysis, active disease at conception (odds ratio [95% CI]: 25.65 (3.05, 25.52), P < 0.001) and history of disease flare at the previous pregnancy (odds ratio [95% CI]: 4.21 (1.10, 16.58), P < 0.001) were the only independent predictors of disease relapse in current gestation. Rates of hospitalization during pregnancy (14.7% vs. 0, P = 0.02) and preterm delivery (32.4% vs. 5.7%, P = 0.006) were higher, and neonatal birth weight was lower (median 3039 vs. 3300 g, P = 0.03), in those with disease flare as compared to those with maintained remission. CONCLUSION: History of disease relapse at previous gestation and periconception disease activity were found as important predictors of disease flare among IBD women. These data would facilitate adequate counseling and informed management decisions among reproductive-aged IBD women and their treating physicians.

Safety and effectiveness of ustekinumab for induction of remission in patients with Crohn's disease: A multicenter Israeli study.

INTRODUCTION: Ustekinumab is an effective treatment of Crohn's disease (CD). Real-world data addressing the efficacy and safety of ustekinumab are scarce. AIM: Our aim was to assess the safety and efficacy of ustekinumab in a large national patient cohort. METHODS: A prospective multicenter study, in which we followed patients with active CD treated with ustekinumab for 24 weeks. Induction dose was intravenous ranging from 260 to 520 mg, according to body weight, followed by 90 mg doses given subcutaneously every 8 weeks. Clinical response was defined as a reduction of at least 1 severity category, as defined by Harvey-Bradshaw index (HBI). Patients with HBI < 5 were considered to be in clinical remission. Patients who stopped needing steroids at week 24 were defined as being in steroid-free clinical remission. RESULTS: A total of 106 CD patients from eight Israeli centers were included. All patients were previously exposed to at least one biological agent. Our cohort consisted of 65 (61.3%) females. Mean age was 41 ± 14 years with an average disease duration of 12.2 ± 8 years. A total of 96 (90.5%) patients continued treatment throughout week 24. Clinical response was observed in 52% of these patients with mean HBI reduction from 8.34 ± 3.8 to 6.8 ± 4.4 at week 24 (p = 0.001). Clinical remission was achieved in 33 patients (31.1%). Moreover, the number of patients requiring steroid treatment was reduced by 66% at week 24. Out of 106 patients, 11 patients (10.4%) discontinued treatment: 3 due to adverse events (2.8%), 7 due to a lack of response, and 1 who was lost to follow-up. Following 24 weeks of treatment, 15 patients reported minor adverse events. CONCLUSIONS: In a large real-world Israeli cohort of non-naïve-to-biological-treatment CD patients, ustekinumab was effective and safe in induction of clinical remission with a significant reduction in the number of patients requiring steroid treatment.

Clinical utility of fecal calprotectin in monitoring disease activity and predicting relapse in pregnant patients with inflammatory bowel diseases.

OBJECTIVES: Inflammatory bowel diseases (IBDs) are commonly diagnosed in reproductive-aged women and can substantially affect pregnancy outcomes. Non-invasive monitoring of IBD during the prenatal course is particularly challenging as traditional laboratory biomarkers are often affected by pregnancy-related physiologic changes. We aimed to evaluate the role of fecal calprotectin (FC) in monitoring disease activity and predicting relapse among IBD women throughout gestation. METHODS: Women with IBD attending a multidisciplinary clinic for the preconception, antenatal and postnatal treatment were prospectively recruited during 2014-2018. FC levels were determined with an enzyme-linked immunoassay. RESULTS: A total of 265 FC (preconception, n = 41; 1st trimester, n = 48; 2nd trimester, n = 84; 3rd trimester, n = 76; postpartum, n = 16) measurements were obtained in 157 pregnancies. Higher FC concentrations were found in all time points in those with active disease than those in remission as assessed by either physician global assessment or disease clinical scores. FC levels were significantly correlated with physician global assessment and disease activity indices in all 5 periods of investigation. Excluding those with disease flare at the time of conception, disease relapse was encountered during the prenatal course in 40 (31.5%) of the remaining 127 pregnancies. FC levels were significantly higher in those who experienced a disease flare later in the course of gestation as compared to those who maintained clinical remission (median 341 vs. 224 µg/g, P = 0.04). CONCLUSION: FC appears to be a reliable marker of ongoing disease activity throughout the prenatal course as well as a predictor of imminent disease flare among IBD pregnant patients.

Development and Validation of the IBD-REFER Criteria: Early Referral for Suspected Inflammatory Bowel Diseases in Adults and Children.

Background: Early treatment of inflammatory bowel disease (IBD) is associated with positive outcomes but a significant diagnostic delay has been reported in most countries. Aim: We aimed to develop and validate IBD-REFER criteria, intended for primary care physicians, to screen patients at risk for IBD. Methods: A Delphi group of 10 experts generated a list of symptoms associated with the onset of IBD, supplemented by a review of the literature. The list was reduced in an iterative process and graded based on importance. For data-driven statistical formatting, the charts of 200 IBD (100 children, 100 adults) and 100 non-IBD controls but with gastrointestinal symptoms were reviewed. The IBD-REFER items were scored for each subject, as well as the contending Red Flag criteria from the International Organization for the Study of IBD. External validation was performed on additionally enrolled cohorts of 100 IBD patients and 50 controls. Results: The Delphi process retained 5 items as major criteria (≥1 item required for early referral) and 11 as minor (≥2 items required). Following the removal of uninformative items and further formatting in the data-driven stage, 10 core items were retained: 3 as major and 7 as minor. In the external validation, the final IBD-REFER criteria had a sensitivity/specificity of 98%/96% in adults and 96%/96% in children, significantly higher than achieved by the Red Flag criteria (71%/84% and 60%/88%, respectively; P < 0.001). Conclusion: The IBD-REFER criteria may guide the selection of patients for expedited gastrointestinal investigation.

Ethnic Variations in Inflammatory Bowel Diseases Among Israel's Populations.

BACKGROUND: Crohn's disease and ulcerative colitis are the two major classic presentations of inflammatory bowel diseases (IBD). Studies have shown a wide variation in the incidence and prevalence attributed to different geographic and ethnic populations. OBJECTIVES: To assess the clinical characteristics of IBD among Arabs in Israel and to compare them to characteristics of IBD among Ashkenazi Jews. METHODS: This retrospective, comparative study compared the clinical characteristics of IBD among 150 Arabs from the Holy Family Hospital and the Nazareth Hospital EMMS, both located in Nazareth, Israel, to those of 97 age- and sex-matched Ashkenazi Jewish patients from Shaare Zedek Medical Center, Jerusalem, Israel. RESULTS: The Arab cohort, which included 106 patients (70%) with Crohn's disease and 44 (29%) with ulcerative colitis, was compared to 97 Ashkenazi patients (81% with Crohn's disease and 17% with ulcerative colitis) (P < 0.05). Alcohol consumption was found in both groups, but Arabs smoked more (46% vs. 12%, respectively, P < 0.05). Obstructive phenotype was lower in Arabs (10% vs. 32%, P < 0.05). 5-aminosalicylic acid and anti-tumor necrosis factor alpha were prescribed for the Arab and Ashkenazi groups (89% and 21%, respectively). The need for surgical intervention due to disease severity and/or complications was not significant (22% vs. 24%). CONCLUSIONS: Despite similar reports of NOD2/CARD15 mutations, Crohn's disease is more common than ulcerative colitis within the Arab-Israeli population. Increased smoking rates may explain milder disease severities in Arabs, as reflected by lower obstructive pattern and frequent use of milder therapeutic modalities.