Hypermobility spectrum disorders and irritable bowel syndrome: A nationwide study of 1.6 million adolescents.

BACKGROUND AND AIM: The association between hypermobility spectrum disorders/hypermobile type Ehlers-Danlos syndrome (HDS/hEDS) and irritable bowel syndrome (IBS) is yet to be clarified. We aimed to assess this association in a national sample of adolescents. METHODS: A population-based cross-sectional study included 1 627 345 Israeli adolescents (58% male; mean age 17 years) who were medically assessed before compulsory military service during 1998-2020. Diagnoses of HSD/hEDS and IBS were confirmed by board-certified specialists. The prevalence and odds ratios (ORs) for IBS in adolescents with and without HSD/hEDS were computed. RESULTS: A total of 4686 adolescents (2553 male) with HSD/hEDS were identified, of whom 71 were diagnosed with IBS (prevalence = 1.5%). Of the 1 621 721 adolescents in the control group, 8751 were diagnosed with IBS (prevalence = 0.5%). Unadjusted logistic regression revealed a significant association between HSD/hEDS and IBS (OR = 2.16 [95% confidence interval, CI, 1.90-2.45]), which persisted in multivariable adjusted models (OR = 2.58 [95% CI, 2.02-3.24]), and in several sensitivity analyses. The association was evident in both male and female adolescents with ORs of 2.60 (95% CI, 1.87-3.49), and 2.46 (95% CI, 1.66-3.49), respectively. The association was accentuated in a sensitivity analysis accounting for other medical and psychiatric comorbidities. CONCLUSIONS: We found a significant association between HSD/hEDS and IBS in both male and female adolescents. Clinical awareness of the association can promote early diagnosis of IBS and appropriate multidisciplinary treatment. Further research is required to identify the common pathological pathways of the conditions and to develop new IBS treatment strategies for people with HSD/hEDS.

Thiopurines Have Longer Treatment Durability than Methotrexate in Adults and Children with Crohn's Disease: A Nationwide Analysis from the epi-IIRN Cohort.

BACKGROUND: Thiopurines and methotrexate have long been used to maintain remission in Crohn's disease [CD]. In this nationwide study, we aimed to compare the effectiveness and safety of these drugs in CD. METHODS: We used data from the epi-IIRN cohort, including all patients with CD diagnosed in Israel. Outcomes were compared by propensity-score matching and included therapeutic failure, hospitalisations, surgeries, steroid dependency, and adverse events. RESULTS: Of the 19264 patients diagnosed with CD since 2005, 3885 [20%] ever received thiopurines as monotherapy and 553 [2.9%] received methotrexate. Whereas the use of thiopurines declined from 22% in 2012-2015 to 12% in 2017-2020, the use of methotrexate remained stable. The probability of sustaining therapy at 1, 3, and 5 years was 64%, 51%, and 44% for thiopurines and 56%, 30%, and 23% for methotrexate, respectively [p <0.001]. Propensity-score matching, including 303 patients [202 with thiopurines, 101 with methotrexate], demonstrated a higher rate of 5-year durability for thiopurines [40%] than methotrexate [18%; p <0.001]. Time to steroid dependency [p = 0.9], hospitalisation [p = 0.8], and surgery [p = 0.1] were comparable between groups. These outcomes reflect also shorter median time to biologics with methotrexate (2.2 [IQR 1.6-3.1 years) versus thiopurines (6.6 [2.4-8.5]; p = 0.02). The overall adverse events rate was higher with thiopurines [20%] than methotrexate [12%; p <0.001], including three lymphoma cases in males, although the difference was not significant [4.8 vs 0 cases/10 000 treatment-years, respectively; p = 0.6]. CONCLUSION: Thiopurines demonstrated higher treatment durability than methotrexate but more frequent adverse events. However, disease outcomes were similar, partly due to more frequent escalation to biologics with methotrexate.

Improved Outcomes of Paediatric and Adult Crohn's Disease and Association With Emerging Use of Biologics-A Nationwide Study From the Epi-IIRN.

BACKGROUND: The effectiveness of biologics for improving long-term outcomes in patients with Crohn's disease [CD] is still controversial. In this nationwide study, we aimed to evaluate trends of long-term outcomes in all CD patients in Israel during the biologics era. METHODS: Trends of outcomes were analysed using data from the four Israeli health maintenance organisations, covering 98% of the population; joinpoint regression models were used to explore changes of these trends over 2005 to 2019. RESULTS: A total of 16 936 patients were diagnosed with CD in Israel since 2005 (2932 [17%] paediatric onset, 14 004 [83%] adult onset) with 114 947 person-years of follow-up. The cumulative rate of any CD related surgery was 5%, 9%, 11%, and 14% at 1, 3, 5, and 10 years from diagnosis. The increase in use of biologics was sharp (from 8.9% to 36%; average annual percent change [AAPC], 14.3%), and the time to biologics was shorter in recent years (median time of 4.8 [1.9-8.1] years in those diagnosed in 2005-2008 compared with 0.5 [0.2-1.1] years in those diagnosed in 2015-2018; p < 0.001). A significant decrease was noted in the hazard of hospitalisations (1.3 [0.1-4.6] years compared with 0.2 [0.02-0.9] years; p < 0.001), steroid dependency (1.5 [0.2-5.4] years compared with 0.1 [0.02-0.4] years; p < 0.001), and intestinal surgeries [4.7 [1.6-8.2] years compared with 0.6 [0.2-1.4] years; p < 0.001), but not of perianal surgery (4.2 [1.1-7.7] years compared with 0.6 [0.2-1.4] years; p = 0.2). Outcomes were consistently worse in paediatric onset compared with adults. CONCLUSIONS: The rates of hospitalisations, steroid dependency, and intestinal resections decreased in association with increased use of biologics both in children and in adults, but not the rate of perianal surgeries.

Colectomy Rates did not Decrease in Paediatric- and Adult-Onset Ulcerative Colitis During the Biologics Era: A Nationwide Study From the epi-IIRN.

BACKGROUND: It is still of debate whether the advent of biologics has been associated with a change in the natural history of ulcerative colitis [UC]. In this nationwide study we evaluated trends of long-term outcomes in all patients diagnosed with UC in Israel during the biologic era. METHODS: Data in the epi-IIRN cohort were retrieved from the four Israeli Health Maintenance Organizations covering 98% of the population, and linked to the Ministry of Health prospective registry on surgeries and hospitalizations. Joinpoint Regression and Kaplan-Meier survival analyses were used, reporting annual average percentage change [AAPC] for each outcome. RESULTS: A total of 13 231 patients were diagnosed with UC since 2005 (1426 [11%] paediatric-onset, 10 310 [78%] adults, 1495 [11%] elderly) with 93 675 person-years of follow-up. The probabilities of surgery after 1, 3 and 5 years from diagnosis were 1.1, 2.3 and 4.1%, respectively, and the corresponding rates of hospitalizations were 22, 33 and 41%. The overall utilization of biologics in UC increased from 0.1% in 2005 to 9.6% in 2019 [AAPC 22.1%] and they were prescribed earlier during the disease course (median of 5.6 years [interquartile range 2.8-9.1] in 2005-2008 vs 0.8 years [0.4-1.5] in 2015-2018; p < 0.001]. Annual rates of surgeries [AAPC -1.3; p = 0.6] and steroid-dependency [AAPC -1.2; p = 0.3] remained unchanged, while rates of hospitalizations slightly decreased [AAPC -1.2; p < 0.001]. Outcomes were consistently worse in paediatric-onset disease than in adults, despite higher utilization of biologics [28% vs 12%, respectively; p < 0.001]. CONCLUSION: During the biologic era rates of surgeries and steroid-dependency have remained unchanged in patients with UC, while rates of hospitalizations have slightly decreased.

Genetic analysis of four consanguineous multiplex families with inflammatory bowel disease.

BACKGROUND: Family studies support a genetic predisposition to inflammatory bowel diseases (IBD), but known genetic variants only partially explain the disease heritability. Families with multiple affected individuals potentially harbour rare and high-impact causal variants. Long regions of homozygosity due to recent inbreeding may increase the risk of individuals bearing homozygous loss-of-function variants. This study aimed to identify rare and homozygous genetic variants contributing to IBD. METHODS: Four families with known consanguinity and multiple cases of IBD were recruited. In a family-specific analysis, we utilised homozygosity mapping complemented by whole-exome sequencing. RESULTS: We detected a single region of homozygosity shared by Crohn's disease cases from a family of Druze ancestry, spanning 2.6 Mb containing the NOD2 gene. Whole-exome sequencing did not identify any potentially damaging variants within the region, suggesting that non-coding variation may be involved. In addition, affected individuals in the families harboured several rare and potentially damaging homozygous variants in genes with a role in autophagy and innate immunity including LRRK1, WHAMM, DENND3, and C5. CONCLUSION: This study examined the potential contribution of rare, high-impact homozygous variants in consanguineous families with IBD. While the analysis was not designed to achieve statistical significance, our findings highlight genes or loci that warrant further research. Non-coding variants affecting NOD2 may be of importance in Druze patients with Crohn's disease.

Predictors of endoscopic intervention in upper gastrointestinal bleeding patients hospitalized for another illness: a multi-center retrospective study.

BACKGROUND: To characterize variables that may predict the need for endoscopic intervention in inpatients admitted for several causes who during the hospitalization developed acute non-variceal upper gastrointestinal bleeding (NVUGIB). METHODS: A retrospective analysis of inpatients who underwent upper gastro-intestinal endoscopy for acute NVUGIB while hospitalized for other causes from 1 January 2016 to 1 December 2017, was performed. In the primary outcome analysis, patients (N.=14) who underwent endoscopic intervention (group A) were compared to those (N.=87) who did not need for endoscopic intervention (group B). Secondary outcome analysis included patients who had significant endoscopic findings compared to those who did not have them. RESULTS: Multivariate regression analysis showed that in the primary outcome analysis, two parameters were significant: the number of packed red blood cells (PRBC) units transfused (odds ratio [OR]: 1.5, P=0.01) and Rockall Score (RS) (OR: 1.4, P=0.06) with receiver operator characteristic (ROC) curve of 0.7844. In the secondary outcome analysis, only the use of proton pump inhibitor drugs at admission was associated with protective effect for the development of significant endoscopic findings (odds ratio [OR]: 0.42, P=0.05) with ROC curve of 0.7342. CONCLUSIONS: In hospitalized patients, in case of de novo NVUGIB, the number of PRBC units transfused and RS are predictive of significant endoscopic findings.

Cardiovascular risk factors are not present in adolescents with inflammatory bowel disease.

AIM: Due to conflicting data, we aimed to investigate the association of inflammatory bowel disease (IBD) with cardiovascular disease (CVD) risk factors at late adolescence in a cross-sectional population-based study. METHODS: A total of 1 144 213 Jewish Israeli adolescents who underwent a general health examination prior to enlistment at median age of 17.1 years from 1988 to 2016 were included. Covariate data included demographics, blood pressure, resting heart rate and risk factors associated with CVD. RESULTS: Overall, 2372 cases of IBD were identified, including 1612 cases of Crohn's disease (68%). Univariate analysis showed marginally lower systolic and diastolic blood pressure in patients with IBD with no difference following multivariate analysis. Diagnosis of Crohn's disease in males was associated with lower rates of overweight (15.8% vs 21.2%, P < .001) and obesity (3.7% vs 6.1% P = .003), whereas females with Crohn's disease had a lower rate of overweight (14.0% vs 17.9% P = .04) but not obesity. Patients with ulcerative colitis did not differ from controls in terms of overweight or obesity. Patients with Crohn's disease had an increased prevalence of hereditary hypercoagulability (odds ratio 16.9, 95% confidence interval 8.0-35.7, P < .001). CONCLUSION: Significant risk factors for CVD were not present in adolescents with IBD.

Comorbidities in adolescents with inflammatory bowel disease: findings from a population-based cohort study.

BACKGROUND: Inflammatory bowel diseases are associated with various immune- and non-immune-mediated conditions. We aimed to assess the association of inflammatory bowel diseases with comorbidities at late adolescence. METHODS: Jewish Israeli adolescents who underwent a general health evaluation prior to enlistment to the Israeli Defense Forces from 2002 to 2016 were included. RESULTS: Overall, 891 subjects (595 Crohn's disease, 296 ulcerative colitis, median age 17.1 years) and 1,141,841 controls were analyzed. Crohn's disease was associated with arthritis (odds ratio (OR) 4.7, 95% confidence interval (CI) 2.4-9.1), thyroid disease (OR 2.6, 95% CI 1.2-5.5), atopic dermatitis (OR 2, 95% CI 1.1-3.6), autoimmune hepatitis (OR 4.4, 95% CI 2.3-8.6), nephrolithiasis (OR 3.6, 95% CI 1.2-11.4), and pancreatitis (OR 41.8, 95% CI 17.2-101.9). Ulcerative colitis was associated with arthritis (OR 3.6, 95% CI 1.0-9.8), thyroid disease (OR 4.8, 95% CI 1.2-19.4), autoimmune hepatitis (OR 8, 95% CI 4-16.2), and pancreatitis (OR 51, 95% CI 16.1-158.9). Primary sclerosing cholangitis was associated with both diseases. Asthma, celiac, type 1 diabetes, psoriasis, and bone fractures were not more common in both diseases. Male predominance was noted for most associations. CONCLUSIONS: At adolescence, both Crohn's disease and ulcerative colitis are associated with multiple comorbidities, not limited to autoimmune disorders.

Inflammatory bowel disease patient profiles are related to specific information needs: A nationwide survey.

BACKGROUND: Inflammatory bowel diseases (IBD) is a heterogenous, lifelong disease, with an unpredictable and potentially progressive course, that may impose negative psychosocial impact on patients. While informed patients with chronic illness have improved adherence and outcomes, previous research showed that the majority of IBD patients receive insufficient information regarding their disease. The large heterogeneity of IBD and the wide range of information topics makes a one-size fits all knowledge resource overwhelming and cumbersome. We hypothesized that different patient profiles may have different and specific information needs, the identification of which will allow building personalized computer-based information resources in the future. AIM: To evaluate the scope of disease-related knowledge among IBD patients and determine whether different patient profiles drive unique information needs. METHODS: We conducted a nationwide survey addressing hospital-based IBD clinics. A Total of 571 patients completed a 28-item questionnaire, rating the amount of information received at time of diagnosis and the importance of information, as perceived by participants, for a newly diagnosed patient, and for the participants themselves, at current time. We performed an exploratory factor analysis of the crude responses aiming to create a number of representative knowledge domains (factors), and analyzed the responses of a set of 15 real-life patient profiles generated by the study team. RESULTS: Participants gave low ratings for the amount of information received at disease onset (averaging 0.9/5) and high ratings for importance, both for the newly diagnosed patients (mean 4.2/5) and for the participants themselves at current time (mean 3.5/5). Factor analysis grouped responses into six information-domains. The responses of selected profiles, compared with the rest of the participants, yielded significant associations (defined as a difference in rating of > 0.5 points with a P < 0.05). Patients with active disease showed a higher interest in work-disability, stress-coping, and therapy-complications. Patients newly diagnosed at age > 50, and patients with long-standing disease (> 10 years) showed less interest in work-disability. Patients in remission with mesalamine or no therapy showed less interest in all domains except for nutrition and long-term complications. CONCLUSION: We demonstrate unmet patient information needs. Analysis of various patient profiles revealed associations with specific information topics, paving the way for building patient-tailored information resources.

Endoscopic Ultrasound-Guided Angiotherapy for Gastric Varices: A Single Center Experience.

There are limited efficacious therapeutic options for management of gastric variceal bleeding. Treatment modalities include transjugular intrahepatic portosystemic shunt, surgical shunts, and endoscopic interventions, including the recent advancement of endoscopic ultrasound (EUS)-guided coiling. We present a case series of 10 patients with portal hypertension (7 with liver cirrhosis and 3 without cirrhosis), complicated by gastric varices (GV) with bleeding. All cases were treated successfully with EUS-guided coiling leading to variceal eradication. There were 10 occurrences of minimal self-limited bleeding at the puncture site during the procedure, and only one occurrence of major bleeding that necessitated cyanoacrylate glue injection for homeostasis. There were no other adverse events within a mean follow-up time of 9.7 months (range, 1-28 months). Conclusion: In our series, EUS-guided angiotherapy was effective for GV eradication with a high safety profile.

A Validated Score Assessing the Risk of an Intra-Abdominal Abscess in Patients with Crohn's Disease Presenting at the Emergency Department.

BACKGROUND AND AIMS: A majority of acutely ill Crohn's disease [CD] patients who present to Emergency Department [ED] will undergo an abdominal CT to rule out disease complications. We aimed to generate a simple non-invasive scoring model to predict the presence of an intra-abdominal abscess in CD patients in the ED. METHODS: We performed a retrospective case-control study at four Israeli hospitals from January 1, 2010 to May 30, 2018. Inclusion criteria included patients with an established diagnosis of CD that had cross-sectional abdominal imaging performed. A total of 322 patients were included, and 81 [25%] were diagnosed with an intra-abdominal abscess. RESULTS: In univariate analysis, ileo-colonic location (odds ratio [OR] 1.88, p = 0.0148), perianal CD [OR 7.01, p = 0.0004], fever [OR 1.88, p = 0.0247], neutrophil-to-lymphocyte ratio [OR 1.12, p < 0.0001], and C-reactive protein [OR 1.10, p < 0.0001] were significantly associated with abscess formation, whereas current use of corticosteroids was negatively associated with abscess formation [OR 0.46, 95% CI, 0.2-0.88, p = 0.0192]. We developed a diagnostic score that included five parameters that were significant on multivariate regression analysis, with assignment of weights for each variable according to the coefficient estimate. A low cut-off score of ≤7 was associated with a negative predictive value [NPV] of 93% for abscess formation, whereas a high cut-off score of >9 was associated with a positive predictive value of 65%. We validated this score with an independent cohort [area under the curve of 0.881 and NPV of 98.5%]. CONCLUSION: We recommend incorporating this score as an aid for stratifying acutely ill CD patients in the ED with low or high probability of the presence of an intra-abdominal abscess.

Trends in the epidemiology of inflammatory bowel disease among Jewish Israeli adolescents: a population-based study.

BACKGROUND: The incidence and prevalence trends of inflammatory bowel disease (IBD) vary between developed and developing countries. AIM: To investigate the prevalence and associated sociodemographic factors of IBD in Israeli Jewish adolescents METHODS: The files of the army medical corps were reviewed for adolescents recruited in 2002-2016 with confirmed IBD. Covariate data included birth date, patient and parental country of birth, number of children in the household, age at diagnosis, and socioeconomic status. Findings were compared with the remaining recruits without IBD. RESULTS: Of the 1,144,213 adolescents recruited, 2372 (0.2%) had IBD (Crohn's disease, 68%). Median age of the cohort was 17.1 years (interquartile range, 16.9-17.3). Over the study period, the annual point prevalence per 100,000 examinees significantly increased: total IBD, 58 to 373; Crohn's disease, 42 to 425; ulcerative colitis, 16 to 128. Mean age at IBD diagnosis decreased from 15.0 ± 2.8 years in 2002-2008 to 14.3 ± 3.1 years in 2009-2016 (P < 0.0001). Significance was maintained on separate analyses of Crohn's disease and ulcerative colitis. Both diseases were significantly less prevalent in subjects from families with at least one parent born in a developing country and ≥3 children. There was a significant association of lower socioeconomic status with lower prevalence of Crohn's disease (odds ratio 0.41, 95% confidence interval, 0.31-0.54) and ulcerative colitis (odds ratio 0.25, 95% confidence interval, 0.15-0.42). CONCLUSIONS: The point prevalence of Crohn's disease and ulcerative colitis in Israeli Jewish adolescents increased six-fold and eight-fold, respectively, over 15 years along with a decrease in age at diagnosis.

To Pull or to Scope: A Prospective Safety and Cost-effectiveness of Percutaneous Endoscopic Gastrostomy Tube Replacement Methods.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tubes are routinely used as an effective method for providing enteral nutrition. The need for their exchange is common. GOALS: We aimed to examine the comparative safety and cost-effectiveness of PEG percutaneous counter-traction "pulling" approach or by endoscopically guided retrieval. STUDY: A prospective 215 consecutive patients undergoing PEG tube insertion were included. Fifty patients in total were excluded. The patients were examined for demographics, indications for PEG replacement, as well as procedure-related complications and procedural costs. RESULTS: Group A included 70 patients (42%) with PEG tubes replaced endoscopically, whereas group B included 95 patients (58%) with PEG tubes replaced percutaneously. Baselines characteristics were similar between the 2 groups (P=NS). Group A and group B had similar immediate complication rates including 4 patients in group B (4.2%), and 2 patients in group A (2.8%) (P=0.24). Complications included a conservatively managed esophageal perforation, and self-limited mild bleeding groups A and group B, respectively. The mean procedure cost was significantly higher in the endoscopic PEG replacement group compared with the percutaneous PEG replacement group ($650 vs. $350, respectively). CONCLUSION: Percutaneous PEG replacement appears as safe as endoscopic PEG replacement, however, percutaneous tube exchange is less costly.

Effectiveness and safety of vedolizumab for maintenance treatment in inflammatory bowel disease-The Israeli real world experience.

INTRODUCTION: Several real-world experience (RWE) studies with vedolizumab (VDZ) for induction of remission in inflammatory bowel diseases (IBD) have been published; however, long-term RWE data is scarce. AIMS: To describe the effectiveness and safety of VDZ in maintenance treatment of IBD. METHODS: A multicenter retrospective national study. The primary outcome of was clinical response at week 52; main secondary aims included clinical remission at week 52, rates of secondary loss of response and treatment discontinuation. RESULTS: We included 193 (133-CD; 60-UC) patients from 9 Israeli IBD centers. At week 52, response was observed in 62/133 (46.7%) CD patients, including 28 (21%) in clinical remission; 71 (53.3%) discontinued treatment or did not respond. For UC, response at week 52 was observed in 27/60 (45%), including 20 (33%) in clinical remission; 33 (55%) discontinued treatment or did not respond. Secondary non-response by week 52 occurred in 19.4% and 23.5% of week 14 responders in CD and UC, respectively. Week 14 response was associated with treatment continuation at week 52: no predictors of secondary loss of response were identified. SUMMARY: VDZ is safe and effective for maintenance of response and remission in IBD; week 14 response is positively associated with long-term response in both UC and CD.

Acute Portal Vein Thrombosis Predicts Concomitant Diagnosis of Hepatocellular Carcinoma in Cirrhotic Patients.

PURPOSE: Portal vein thrombosis (PVT) is a common condition in cirrhotic patients and mostly attributed to portal hypertension. The objective of our study was to examine the association of PVT with hepatocellular carcinoma (HCC) in cirrhotic patients. METHODS: A retrospective study was performed to identify cirrhotic patients with thrombosis of the portal system. Clinical and laboratory characteristics were collected and analyzed. RESULTS: Thirty-nine patients were identified. Twenty-four out of 39 patients with PVT did not develop HCC (group A) after follow-up time of 38.5 months from the diagnosis of PVT. Eight patients (20.5%) were diagnosed with HCC within two weeks following diagnosis of PVT (group B). Seven patients (17.9%) were diagnosed with tumor thrombus (group C) at time of PVT diagnosis. The average age was 53.5, 66.5, and 69 years for groups A, B, and C respectively. Most patients (75 and 87.5% for groups B and C respectively) diagnosed with PVT and HCC were males. The most common cause of cirrhosis in groups B and C was chronic hepatitis B virus infection (HBV) in 62.5% and 50% respectively. The most common clinical presentation of PVT in group A was abdominal pain in 55.5% compared to new/worsening ascites in 43% and 37.5% for groups B and C respectively. The platelet count in groups B and C was higher as compared to that in group A (126 and 125 vs. 107 thousand, P = NS). CONCLUSION: In 38.4% of cases, new diagnosis of PVT was associated with concomitant diagnosis of HCC. Identifiable risk factors were chronic HBV infection and higher platelet count.

Anthropometric Measures in Adolescents With Inflammatory Bowel Disease: A Population-Based Study.

BACKGROUND: Growth impairment is common in pediatric inflammatory bowel disease (IBD) patients. Nevertheless, a controversy exists regarding disease impact on anthropometric measures in the long term. Thus, we aimed to investigate the impact of IBD on anthropometric measures, including weight, height, and body mass index (BMI), during late adolescence in a cross-sectional, population-based study. METHODS: A total of 1,144,213 Jewish Israeli adolescents who underwent a general health examination from 2002 to 2016 at a median age (interquartile range) of 17.1 (16.9-17.3) years were included. Inflammatory bowel disease cases were stratified into Crohn's disease (CD) and ulcerative colitis (UC). Patients were also subgrouped based on age at IBD diagnosis. RESULTS: Overall, 2372 cases of IBD were identified out of 1,144,213 persons examined (0.2%). Crohn's disease accounted for 68% of IBD cases. Males and females with CD (but not with UC) had significantly lower weight and BMI compared with controls. Differences in height at late adolescence were not statistically significant for either disease compared with controls (females: 162 cm vs 161.7 cm vs 161.5 cm; males: 174 cm vs 173.7 cm vs 173.6 cm for controls, UC, and CD, respectively). In a subgroup analysis, patients with CD diagnosed at age <14 years were significantly shorter than controls (males: 172.7 cm vs 174 cm; P = 0.001; females: 160.6 cm vs 162; P = 0.008). This pattern was not noted in UC patients. CONCLUSIONS: Adolescents with CD were leaner compared with the general population. No overall difference was noted in height at late adolescence. Younger age at diagnosis was associated with reduced height in CD patients.

Portal lymphadenopathy predicts non-alcoholic steatohepatitis and advanced fibrosis in non-alcoholic fatty liver disease.

BACKGROUND AND AIM: The progression of non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) is believed to be the driver for future development of fibrosis and cirrhosis. Nevertheless, there remains a clear deficit in non-invasive methods for the diagnosis of NASH. The aim of the present study was to evaluate the prevalence of portal lymphadenopathy (PL) in biopsy- proven NAFLD patients and to determine whether PL correlates with NAFLD stage and severity. METHODS: A retrospective study included biopsy-proven NAFLD patients with up to date (within one year) abdominal imaging by computed tomography (CT) and/or magnetic resonance imaging (MRI). Patients were clustered into three groups based on their NAFLD Activity Score (NAS): NAS1-2 (mild), NAS3-4 (moderate) and NAS≥5 (advanced). We Assessed for association between PL and other clinical and laboratory findings with NAS, NAS components and fibrosis. RESULTS: Seventy-five patients with NAFLD and no other competing etiologies for liver diseases or PL were included. The mean age was 50.7±14.84 years with male predominance (N = 47, 62.7%). Twenty-five (33.3%), 37 (49.3%) and 13 (17.3%) patients had mild, moderate and advanced NAS, respectively. PL significantly correlated with advanced NAS ≥ 5 (Fisher's (F) 9.5, P = 0.009). Correlation was driven mainly by a link to hepatocytes ballooning (F of 5.9, P = 0.043). In addition, PL significantly correlated with portal inflammation (F 4.29, P = 0.038). As for hepatic fibrosis, the F test wasn't significant, though spearman's coefficient (SC) was significant (0.277, P = 0.012). On multivariate analysis, PL was identified as a sole predictor of advanced NAS score (Odds ratio of 2.68, P = 0.002). Incorporation of PL into noninvasive fibrosis scores improved their diagnostic yield. CONCLUSION: PL predicts severity of NAFLD. Its presence may serve as a novel radiological marker for NAFLD/NASH differentiation and disease progression.

State of the art review with literature summary on gastric peroral endoscopic pyloromyotomy for gastroparesis.

Gastroparesis is a debilitating progressive disease that significantly impacts a patient's life with limited and challenging treatments available. Although the pathogenesis is multifactorial, pylorospasm is believed to have a major underlying role. Several therapeutic interventions directed to the pylorus have been developed over the last decade, including intra-pyloric injections of botulinum toxin, transpyloric stenting, and surgical pyloroplasty. All of these treatment options had limited and disappointing results. More recently, gastric peroral endoscopic myotomy (G-POEM) has been reported as a treatment for refractory gastroparesis. In this review article, we provide an overview on gastroparesis with a focus on the therapeutic interventions. In addition, we provide a literature summary and pool analysis of the clinical efficacy, scintigraphic efficacy, and safety profile of all studies that evaluated G-POEM in gastroparesis. Overall, seven studies have reported on the use of G-POEM in gastroparesis, and the pooled analysis of these studies showed a technical success of 100%, with clinical efficacy as assessed by the Gastroparesis Cardinal Symptoms Index of 81.5%, gastric emptying scintigraphy normalization in approximately 55.5% of the cases, perioperative complications in 7.6%, and intraoperative complications in 6.6%. This suggests that G-POEM is a new promising therapeutic intervention for the treatment of gastroparesis with durable effect and limited potential adverse events.

Current and Future Treatment of Hepatocellular Carcinoma: An Updated Comprehensive Review.

Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related mortality. The principal treatment is surgical resection or liver transplantation, depending on whether the patient is a suitable transplant candidate. However, in most patients with HCC the diagnosis is often late, thereby excluding the patients from definitive surgical resection. Medical treatment includes sorafenib, which is the most commonly used systemic therapy; although, it has been shown to only minimally impact patient survival by several months. Chemotherapy and radiotherapy are generally ineffective. Due to the poor prognosis of patients with HCC, newer treatments are needed with several being in development, either in pre-clinical or clinical studies. In this review article, we provide an update on the current and future medical and surgical management of HCC.

Birth Month as a Risk Factor for the Diagnosis of Celiac Disease Later in Life: A Population-based Study.

Various perinatal factors have been implicated in association with the risk of developing celiac disease (CD) in genetically susceptible individuals. Our aim was to investigate the association of month and season of birth with the development of CD later in life in a large National cohort in Israel. Data were retrieved from a National database of more than 2 million Israeli Jewish adolescents born between 1971 and 1998. Overall, 10,566 CD cases out of 2,001,353 subjects (0.53%) were identified and analyzed. CD risk was significantly higher for subjects born in May (odds ratio [OR] 1.07, P = 0.04) and June (OR 1.09, P = 0.008). Birth during the winter season (December to February) showed a marginal significance toward reduced risk (OR 0.97, P = 0.05). In conclusion, children born in May and June are at increased risk for CD. This increased risk provides further evidence that perinatal environmental factors increase the risk of developing CD.