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Background: Sex-based differences are common among diseases. We aimed to investigate the differences in colonoscopy indications and its findings between males and females. Methods: A large, multi-center, cross-sectional, retrospective study included all colonoscopies performed between 2016 and 2021 in seven endoscopy departments. The indications and findings of the procedures were compared between males and females. Results: A total of 151,411 (52.6%) women and 136,519 (47.4%) men were included, aged 56.54 ± 12.9 years and 56.59 ± 12.7. Cecal intubation was similar (95.6% vs 95.5%, p = 0.251). More females had excellent or good bowel preparation compared to males (71.4% vs 65.6%). Colonoscopy due to abdominal pain, constipation, diarrhea, and anemia was higher in females compared to males (15% vs 9.9%, 3.9% vs 2.2%, and 7.6% vs 4.9%, p < 0.001, respectively), while positive FOBT, rectal bleeding and post-polypectomy surveillance and screening were more common indications among males (9.5% vs 7.8%, 10.7% vs 7.8%, and 10.8% vs 7.1%, respectively). On colonoscopy, males were found to have significantly higher colorectal cancer and polyps (0.5% vs 0.4% and 35.1% vs 24.6%). Polyp detection rates were lower in females across all indications, whereas diverticulosis rates were higher in males. However, a clinically significant difference regarding diverticulosis was observed only in patients with anemia as the indication. Conclusions: Notable differences exist between males and females in terms of the indications and findings on colonoscopy. This highlights the need for identifying the factors contributing to these differences and the developing sex-specific approaches for the diagnosis and management of gastrointestinal diseases.

Aim: We aimed to investigate the association between Glucagon-like-peptide-1 receptors agonists (GLP1-RA) use and gastric residue on esophagogastroduodenoscopy (EGD)., Methods: A multicenter, retrospective study included all EGDs conducted across seven gastroenterology departments. EGDs with the diagnosis of "poor preparation" or described as a poor preparation in the endoscopist's report were considered as gastric residue., Results: 120,879 EGDs were included in the analysis. Of these, 1671 patients treated with GLP1-RA were compared to 119,208 without GLP1-RA treatment. Of the GLP1-RA group, 93 (5.6 %) had gastric residue compared to 2327 (2.0 %) among the non-GLP1-RA group (p < 0.001). Sup-group analysis: 71 (6.2 %) of the 1141 DM patients treated with GLP1-RA compared to 307 (3.0 %) of the 10,152 DM patients without GLP1-RA treatment (p < 0.001). Additionally, 22 (4.2 %) of 503 non-DM patients treated with GLP1-RA had gastric residue compared to 2065 (2.0 %) of the non-DM non-GLP1-RA group (n = 109,056) (p < 0.001). In multivariate analysis, DM and GLP1-RA were both found to be independent risk factors for excess gastric residue., Conclusion: Our results may have important clinical relevance for EGD preparation among GLP1-RA treated patients, either requiring a longer fasting time prior to EGD or holding the medication prior to EGD according to the half-life of the drug., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Early onset colorectal cancer (EO-CRC) is increasing. We investigated the risk factors for ER-CRC compared to late onset CRC (LO-CRC). CRC patients between the years 1999 and 2021 were retrospectively evaluated. Data regarding demographics, comorbidities, malignancies, and mortality were collected. Data were retrieved using the MdClone platform from a large Health Maintenance Organization. The cohort was subdivided into EO-CRC (age ≤50 years) and LO-CRC (age ≥51 years) groups. 61,679 patients diagnosed with CRC were included in our analysis, 30,456 (49.4%) males, and 4,891 (7.9%) Arabs, with an average age at diagnosis of 70.1±13.1 years. 5561 (9%) patients were included in the EO-CRC group. Over the last decades, higher rates of EO-CRC were diagnosed compared to the previous decade, 9.8% vs 8.3%, p<0.001. A higher percentage of EO-CRC patients were females (52.8% vs 50.4%), had a family history of CRC (9.9% vs 5.5%), were Arabs (18.7% vs 6.9%), and were smokers (32.7% vs 30.2%) compared to LO-CRC patients. Significantly lower rates of comorbidities such as ischemic heart disease, diabetes mellitus, hypertension, obesity, and iron deficiency anemia were found among EO-CRC patients, with a lower all-cause mortality (27.7% vs 63.1%, p<0.001). 348 (6.3%) of the EO-CRC patients had another Lynch-related cancer until age 50 years compared to 45 (0.1%) at the LO-CRC. Young individuals with increased risk for CRC need special consideration and should be referred early for screening and endoscopic investigation, particularly those with a family history of CRC, smokers, and those of Arab ethnicity.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) affect gastrointestinal motility, slowing gastric emptying and colonic transit. GLP-1RAs have an impact on gastric residue before endoscopy, but only limited data are available regarding its effect on the adequacy of colonic preparation. We investigated the association between GLP-1RA use and inadequate bowel preparation (IBP) for colonoscopy., Methods: We performed a multicenter retrospective study with GLP-1RA cases matched with controls (using propensity scores for age, sex, diabetes mellitus [DM], obesity, and co-morbidities). Data on demographics, medication use, procedural indications, and colonoscopy findings were collected. IBP ("poor preparation" on Aronchik scale or Boston Bowel preparation scale <5) was the primary outcome., Results: 4876 patients treated with GLP-1RAs were included in the analysis and compared with 4876 controls selected from 333 648 patients without GLP-1RA use. Among the GLP-1RA patients, 10% (n = 487) had IBP compared with 197 (4%) of the control group ( P <0.001). Subgroup analysis showed a higher rate of IBP among diabetic patients treated with GLP-1RA (284/2364 [12%]) than among diabetic patients without GLP-1RA treatment (118/2364 [5%]; P <0.001). Additionally, 203/2512 nondiabetic patients treated with GLP-1RAs had IBP (8%) compared with 79 of the nondiabetic non-GLP-1RA group (3%; P <0.001). On multivariate analysis, diabetes and GLP-1RA use were both found to be independent risk factors for IBP (odds ratio [OR] 1.4 and OR 2.7, respectively; both P <0.001)., Conclusion: Our findings highlight the necessity for special attention and tailored recommendations for both diabetic and nondiabetic patients treated with GLP-1RAs in terms of colonic preparation prior to colonoscopy., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. We aimed to investigate the potential similarities and differences regarding the disease among Arabs and Jews. Retrospective study included all patients older than 18 years with NAFLD diagnosis according to ICD-10 codes. Data regarding demographics, comorbidities, and outcomes were retrieved using the MdClone platform from "Clalit" in Israel. Data concerning 34,090 Arab patients and 173,500 Jewish patients with NAFLD were included. Arab patients were significantly younger at diagnosis (35.0 ± 13 years vs. 43.6 ± 15 years, p < 0.001) and had higher rates of obesity and diabetes mellitus (69.5% vs. 56.5% and 27.0% vs. 22.7%, p < 0.001, respectively). Arab patients had higher rates of cirrhosis and portal hypertension-related complications (2.5% vs. 2.0%, p < 0.001), esophageal varices (0.9% vs. 0.5%, p < 0.001), spontaneous bacterial peritonitis (0.3% vs. 0.1%, p < 0.001), and hepatorenal syndrome (0.3% vs. 0.1%, p < 0.001). There was no significant difference in the prevalence of hepatocellular carcinoma between study groups (0.4% vs. 0.5%, p = 0.156). Liver transplantation was performed in 0.2% of Arab NAFLD patients compared to 0.07% of Jewish NAFLD patients (p < 0.001). Lower rates of all-cause mortality were found among the Arab NAFLD patients versus Jewish NAFLD patients (7.7% versus 11.5%, p < 0.001). According to the Cox regression model, Arab ethnicity is a risk factor for death with OR of 1.36. Significant differences regarding comorbidities, complications, liver transplantations rates, and all-cause mortality were found among NAFLD patients of different ethnicities, hence specific population need specific consideration in prevention, early diagnosis and follow up., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Hiatal hernia (HH) is a common finding in gastroscopy. The aim of the present study was to investigate the frequency rate of HH among patients who underwent esophagogastroduodenoscopy (EGD) according to their age, gender, and procedural indication., Methods: A multicenter, retrospective study including all EGDs was conducted across seven endoscopy departments between 2016 and 2021. Demographic information, procedural indications, and findings from the initial EGD were collected., Results: Of the 162,608 EGDs examined, 96,369 (59.3%) involved female patients. HH was identified in 39,619 (24.4%) of all EGDs performed, comprising small HH in 31,562 (79.6%) and large HH in 3,547 (9.0%). The frequency of HH was 16.5% in the age group of ≤50 years and 37.3% in those aged ≥81 years. HH was diagnosed in 38.7% (11,370) of patients with heartburn/reflux symptoms, 31.5% of those with dysphagia, 28.5% of those with positive fecal occult blood tests, and 24.3% of those who would undergo bariatric surgery. Age (odds ratio 1.030), female gender (odds ratio 1.309), reflux symptoms (odds ratio 2.314), and dysphagia (odds ratio 1.470) were identified as predictors for HH., Conclusions: Risk factors for HH diagnosed by EGD in symptomatic patients were shown to be advanced age, female gender, and the presence of heartburn or dysphagia., Competing Interests: The authors declare that there are no conflicts of interest in this study., (© The Author(s) 2024. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

Background/Objectives : Terminal ileitis (TI) is often identified on CT scans in emergency settings. Diagnosing Crohn's disease (CD) as a cause of TI is crucial due to its significant long-term implications. This study aimed to differentiate CD from other causes of acute TI and develop a predictive model for CD diagnosis. Methods : A retrospective case-control study was conducted at Shamir Medical Center including adults diagnosed with acute TI from January 2012 to December 2020. Patients with a history of inflammatory bowel disease or prior intestinal surgery were excluded. Patients were categorized into CD and non-CD groups based on their subsequent clinical course. A logistic regression model was developed and subsequently validated with additional patients hospitalized between 2021 and 2023. Results : Among 135 patients, 37 (27.4%) were diagnosed with CD. CD patients were younger (median age 27 vs. 39 years, p = 0.003), predominantly male (83.8% vs. 51%, p = 0.001), and had higher rates of chronic abdominal pain, diarrhea, anemia, and weight loss prior to hospitalization. Significant laboratory differences included higher platelet counts ( p = 0.006) and lower mean corpuscular volume (MCV) ( p = 0.001) in CD patients. Radiologic signs of complicated disease were more common in CD (35.1% vs. 4.1%, p < 0.001). The predictive model incorporating gender, abdominal pain history, and MCV showed an area under the curve (AUC) of 0.87, with a sensitivity of 100% and specificity of 63.6% in the validation group of 18 patients. Conclusions : This study identified key predictors of CD in patients presenting with acute TI and developed a predictive model with a substantial diagnostic capability. Use of this model for early identification and treatment of CD may potentially improve patient outcomes. Further prospective validation of this model is warranted.

Background: Gastrointestinal angiodysplasia (GIAD) is a rare diagnosis among the general population. We aimed to identify risk factors for GIADs and to determine the frequency rate in the general population., Methods: A population-based retrospective study was performed including patients diagnosed with upper (stomach/duodenum) or lower (small bowel/colon) GIADs based on diagnostic codes from a large health maintenance organization. Control groups were matched for age and gender. Additional data including demographics, comorbidities, malignancies, and medications were collected., Results: 991 upper GIADs and 3336 lower GIADs were included, compared to 7217 and 32,802 controls. The overall prevalence of GIAD was 0.092 %. 88 % of the upper and 85 % of the lower GIADs were diagnosed at ages ≥60, peaking at a prevalence of 0.37 % for ages 71-80. The most significant risk factors for GIADs included liver cirrhosis (OR 4.0 for lower GIAD and OR 7.0 for upper GIAD, p < 0.001), hypertension (OR 2.3 for lower GIAD and OR 2.8 for upper GIAD, p < 0.001) and aortic stenosis (OR 2.8 for lower GIAD and OR 2.0 for upper GIAD, p < 0.001). Other significant risk factors included ischemic heart disease, chronic renal failure, female gender, and chronic obstructive pulmonary disease. Interestingly, both upper and lower GIADs were found to be significantly less frequent in patients with malignancy., Conclusion: Identification of the clinical conditions and demographic factors associated with GIAD may improve our understanding of the etiology and the optimal treatment modalities for this rare condition., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The study aimed to explore patients' experiences and perceptions throughout the various stages of endoscopic procedures and examine the association between patient-centered communication and the patient's experience. A total of 191 patients responded to pre- and post-procedure surveys that inquired about fear and pain, patients' satisfaction regarding the information provided to them, perceptions and experience. Pain was associated with post-procedure fear (r = 0.63, p < 0.01) and negatively associated with reported patient experience at the end of the visit (r = -0.17, p < 0.01). Significant positive associations were found between patient experience and satisfaction from the information provided before (r = 0.47, p < 0.01) and the information provided after the procedure (r = 0.51, p < 0.001). A predictive model found that perceptions toward the physicians, satisfaction from information provided before discharge, and feelings of trust are predictors of the patient experience (F = 44.9, R 2 = 0.61, p < 0.001). Patients' satisfaction with information provided before and after the procedure can positively affect the patients' experience, leading to a decrease in fear and anxiety and increasing compliance with medical recommendations. Strategies for PCC with endoscopic patients should be developed and designed in a participatory manner, taking into account the various aspects associated with the patient experience.

Background: Colorectal cancer (CRC) incidence at ages <50 years is increasing worldwide. Screening initiation was lowered to 45 years in the United States. The cost-effectiveness of initiating CRC screening at 45 years in Israel was assessed with the aim of informing national policy and addressing internationally relevant questions., Methods: A validated CRC screening model was calibrated to Israeli data and examined annual fecal immunochemical testing (FIT) or colonoscopy every 10 years from 45 to 74 years (FIT45-74 or Colo45-74) versus from 50 to 74 years (FIT50-74 or Colo50-74). The addition of a fourth colonoscopy at 75 years was explored, subanalyses were performed by sex/ethnicity, and resource demands were estimated., Results: FIT50-74 and Colo50-74 reduced CRC incidence by 57% and 70% and mortality by 70% and 77%, respectively, versus no screening, with greater absolute impact in Jews/Other versus Arabs but comparable relative impact. FIT45-74 further reduced CRC incidence and mortality by an absolute 3% and 2%, respectively. With Colo45-74 versus Colo50-74, CRC cases and deaths increased slightly as three colonoscopies per lifetime shifted to 5 years earlier but mean quality-adjusted life-years gained (QALYGs) per person increased. FIT45-74 and Colo45-74 cost 23,800-53,900 new Israeli shekels (NIS)/QALYG and 110,600-162,700 NIS/QALYG, with the lowest and highest values among Jewish/Other men and Arab women, respectively. A fourth lifetime colonoscopy cost 48,700 NIS/QALYG. Lowering FIT initiation to 45 years with modest participation required 19,300 additional colonoscopies in the first 3 years., Conclusions: Beginning CRC screening at 45 years in Israel is projected to yield modest clinical benefits at acceptable costs per QALYG. Despite different estimates by sex/ethnicity, a uniform national policy is favored. These findings can inform Israeli guidelines and serve as a case study internationally., (© 2024 American Cancer Society.)

Background: Surveillance of high-risk individuals for pancreatic ductal adenocarcinoma (PDAC) is recommended. This study aimed to determine the prevalence and outcomes of PDAC and its precursor lesions in BRCA1/2 pathogenic variants (PVs) carriers undergoing pancreatic surveillance., Methods: A retrospective multicenter cohort study of pancreatic surveillance outcomes in Israeli BRCA1/2 carriers preferably with a family history of PDAC., Results: A total of 180 asymptomatic carriers participated in the screening programs, including 57 (31.7%) with BRCA1 PVs, 121 (67.2%) with BRCA2 PVs, and 12 (6.6%) with PVs in BRCA1/2 and other genes, for a median follow-up period of 4 years. Ninety-one individuals (50.5%) fulfilled the International Cancer of the Pancreas Screening (CAPS) criteria for surveillance whereas 116 (64.4%) fulfilled the American College of Gastroenterology (ACG) criteria. There were four cases of adenocarcinoma and four cases of grade 1-neuroendocrine tumor (G1-NET). All were BRCA2 carriers, and two had no family history of PDAC. Three cancer patients were at resectable stages (IA, IIA, IIB) whereas one had a stage IIIB tumor. Of the G1-NET cases, one had surgery and the others were only followed. Success rate for detection of confined pancreatic carcinoma was thus 1.6% (three of 180) in the whole cohort, 1.6% (two of 116) among individuals who fulfilled ACG criteria and 2.2% (two of 91) in those fulfilling CAPS criteria for surveillance., Conclusions: Despite the low detection rate of PDAC and its' high-risk neoplastic precursor lesions among BRCA1/2 carriers undergoing pancreatic surveillance, 75% of cancer cases were detected at a resectable stage., (© 2023 American Cancer Society.)

The recognition of dominantly inherited micro-satellite instable (MSI) cancers caused by pathogenic variants in one of the four mismatch repair (MMR) genes MSH2, MLH1, MSH6 and PMS2 has modified our understanding of carcinogenesis. Inherited loss of function variants in each of these MMR genes cause four dominantly inherited cancer syndromes with different penetrance and expressivities: the four Lynch syndromes. No person has an "average sex "or a pathogenic variant in an "average Lynch syndrome gene" and results that are not stratified by gene and sex will be valid for no one. Carcinogenesis may be a linear process from increased cellular division to localized cancer to metastasis. In addition, in the Lynch syndromes (LS) we now recognize a dynamic balance between two stochastic processes: MSI producing abnormal cells, and the host's adaptive immune system's ability to remove them. The latter may explain why colonoscopy surveillance does not reduce the incidence of colorectal cancer in LS, while it may improve the prognosis. Most early onset colon, endometrial and ovarian cancers in LS are now cured and most cancer related deaths are after subsequent cancers in other organs. Aspirin reduces the incidence of colorectal and other cancers in LS. Immunotherapy increases the host immune system's capability to destroy MSI cancers. Colonoscopy surveillance, aspirin prevention and immunotherapy represent major steps forward in personalized precision medicine to prevent and cure inherited MSI cancer., (© 2023. BioMed Central.)

There is accumulating evidence that treatment of chronic hepatitis C (HCV) leads to improvements in liver fibrosis. We aimed to investigate the improvement in fibrosis stage following treatment with direct-acting antivirals (DAAs) and factors associated with fibrosis regression. Fibroscan ® was performed for patients treated with DAAs, at least 3 years post-HCV eradication. The fibrosis stage at the onset of treatment was compared with the current fibrosis stage. A total of 209 patients were enrolled in this study (56% males; age 58.8 ± 13.3 years; age at treatment 54 ± 10.9 years). Genotype subgrouping was as follows: 1a (16%), 1b (58%), 2a (4%), 3 (18%), and 4a (2%). Overall, 71% of patients were considered treatment-naïve, with a mean follow-up time of 4.5 ± 1.3 years. Fibrosis improvement was observed among 57% of patients; fibrosis progression was seen among 7% of patients and no change was seen in 36% of patients. Moreover, 28% of these patients regressed from F3/F4 to F2 or less. In our multivariable analysis, the age at treatment and advanced fibrosis stage were found to be factors significantly associated with fibrosis regression. In conclusion, fibrosis improvement was observed among 57% of HCV patients after treatment with DAAs. Age and advanced fibrosis at baseline were found to be factors associated with fibrosis regression.

Background: Colorectal cancer (CRC) is a feared complication of inflammatory bowel disease (IBD). We aimed to investigate the prevalence and risk factors of CRC among a large cohort of IBD patients., Methods: Data on IBD patients free of CRC at baseline was extracted using the MDClone platform of the Clalit health maintenance organization in Israel. We investigated the frequency rate of CRC among IBD patients compared to a control group without IBD. Possible risk factors, including comorbidities and IBD-related medications, were investigated in a multivariate analysis., Results: During a follow-up of 139,448 years among Crohn's disease (CD) patients and 139,533 years among ulcerative colitis (UC) patients, a frequency rate of CRC was 1.5% (191) among 12,888 CD patients and 2.1% (261) among 12,381 UC patients compared to 1.2% among 57,334 controls. In a multivariate analysis of UC patients, age at diagnosis (OR 1.030, p  < 0.001), primary sclerosing cholangitis (OR 2.487, p  = 0.005), diabetes mellitus (OR 2.01, p  < 0.001), and glucocorticoids treatment (OR 1.465, p  = 0.008) were found to be predictors of CRC. For CD patients, age at diagnosis (OR 1.035, p  < 0.001), primary sclerosing cholangitis (OR 2.25, p  = 0.029), and glucocorticoids treatment (OR 2.07, p  < 0.001) were found to be predictors for CRC, but not diabetes mellitus., Conclusion: Despite the continuously decreasing rates of CRC among IBD patients, these are still higher in IBD patients compared to the general population. IBD patients, particularly those with risk factors, require special consideration in follow-up for CRC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Abu-Freha, Cohen, Gordon, Weissmann, Kestenbaum, Vosko, Abu-Tailakh, Ben-Shoshan, Cohen and Shirin.)

Background: Autosomal recessive conditions are common in consanguineous populations. Since consanguinity is common in the Israeli Arab population, we evaluated the rate of MUTYH polyposis (MAP) among polyposis patients in this population and studied Pathogenic Variants (PVs) spectrum., Methods: We reviewed health records of all Arab and Druze polyposis patients referred for counseling during 2013-2020 who fulfilled the Israeli Genetic Society criteria for MUTYH/APC testing, in a tertiary center in Northern Israel and four additional gastro-genetic clinics in Israel., Results: The Northern cohort included 37 patients from 30 unrelated families; 8(26.6%) carried bi-allelic MUTYH PVs. The major variant p.Glu452del was detected in 6/8 Druze and Muslim families who shared the same haplotype. Other PVs detected in both cohorts included p.Tyr56Ter, p.His57Arg, c.849+3A>C, p.Ala357fs, and p.Tyr151Cys. Among bi-allelic carriers, 88% reported consanguinity, and 100% had positive family history for polyposis or colorectal cancer (CRC). Generally, the age of CRC was 10 years younger than reported in the general MAP population., Conclusions: MAP accounted for 27% of polyposis cases in the Arab population of Northern Israel. PVs spectrum is unique, with high frequency of the founder variant p.Glu452del. Our results may inform the genetic testing strategy in the Israeli Arab population., Competing Interests: Conflict of interest No conflict of interest declared by the authors., (Copyright © 2023. Published by Elsevier Ltd.)

Hepatitis C Virus (HCV) infection is a leading etiology of liver cirrhosis and its associated complications, namely, decompensated cirrhosis. As such, hepatitis C potentially necessitates liver transplantation and may result in death. Recently, HCV treatment has evolved. Current HCV treatment is effective in curing HCV; some of the agents are pan-genotypic. Numerous countries have adopted an initiative to eliminate HCV. Achieving elimination poses many challenges; it requires improved availability and accessibility of pan-genotypic therapy. Barriers exist at the level of the collective healthcare system and at the level of the individual healthcare providers and patients. Therefore, organized national and local efforts are needed. Surmounting these barriers calls for interventions concerning screening, linkage to care, and treatment delivery. Pertinent barriers include inadequate availability of screening, ill-equipped laboratory testing before treatment, and insufficient access to treatment. Interventions should seek to decentralize laboratory testing and treatment provision, increase funding for resources and personnel, and spread awareness. Special consideration should be allocated to at-risk populations, such as intravenous drug users, refugees, and prisoners. Computerized medical filing and telemedicine have the potential to refine HCV management by enhancing detection, availability, accessibility, and cost-effectiveness.

Inflammatory bowel diseases are increasing among different ethnic groups. We aimed to compare the clinical characteristics, complications, and outcomes among Arab and Jewish people sharing the same healthcare system. All patients older than 18 years with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) between the years 2000 and 2021 were included. Data regarding demographics, disease characteristics, extraintestinal manifestation, treatment, comorbidities, and mortality were retrieved. A total of 1263 (9.8%) Arab CD patients were compared with 11,625 Jewish CD patients, and 1461 (11.8%) Arab UC patients were compared to 10,920 Jewish patients. Arab CD patients were younger at diagnosis, 36.11 ± 16.7 compared to 39.98 ± 19.4 years, p < 0.001, 59.5% males compared to 48.7%, p < 0.001; in addition, Arab CD patients had a higher rate of anal fissure, perianal abscess, erythema nodosum, diabetes mellitus, obesity, liver cirrhosis, and male infertility. Arab CD patients were less frequently treated with azathioprine or mercaptopurine compared with Jewish patients. No significant difference was found in the rate of anti-TNF treatment, but a higher rate of steroids treatment was found. The all-cause mortality of CD patients was lower among Arab patients (8.4% vs. 10.2%, p = 0.039). Significant differences were found regarding disease characteristics, course, comorbidities, and treatment among Arab and Jewish patients with IBD.

(1) Background: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease. Aims: We aimed to investigate the frequency of comorbidities and malignancies among NAFLD patients compared to the general population. (2) Methods: A retrospective study included adult patients with a NAFLD diagnosis. A control group was matched for age and gender. Demographics, comorbidities, malignancies, and mortality were collected and compared. (3) Results: 211,955 NAFLD patients were analyzed in comparison to 452,012 matched general population controls. Significantly higher rates of diabetes mellitus (23.2% vs. 13.3%), obesity (58.8% vs. 27.8%), hypertension (57.2% vs. 39.9%), chronic ischemic heart disease (24.7% vs. 17.3%), and CVA (3.2% vs. 2.8%) were found among NAFLD patients. Patients with NAFLD had significantly higher rates of the following malignancies: prostate cancer (1.6% vs. 1.2%), breast cancer (2.6% vs. 1.9%), colorectal cancer (1.8% vs. 1.4%), uterine cancer (0.4 vs. 0.2%), kidney cancer (0.8% vs. 0.5%), but a lower rate of lung cancer (0.9% vs. 1.2%) and stomach cancer (0.3% vs. 0.4%). The all-cause mortality rate among NAFLD patients was significantly lower in comparison to the general population (10.8% vs. 14.7%, p < 0.001). (4) Conclusions: Higher rates of comorbidities and malignancies among NAFLD patients were observed, but a lower rate of all-cause mortality was found.

Background: The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants ( path&#95;MMR ) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time., Methods: The PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path&#95;MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender., Findings: Gynaecological cancers were more frequent than colorectal cancers in path&#95;MSH2, path&#95;MSH6 and path&#95;PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path&#95;MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path&#95;MMR carriers undergoing colonoscopy surveillance, particularly path&#95;MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers., Interpretation: In path&#95;MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome., Funding: We acknowledge funding from the Norwegian Cancer Society, contract 194751-2017., Competing Interests: R.B. has received honoraria for lectures and advisory boards from AbbVie, Amgen, AstraZeneca, Bayer, BMS, Boehringer-Ingelheim, Illumina, Lilly, Merck-Serono, MSD, Novartis, Qiagen, Pfizer, Roche, and Targos MP Inc. R.B. is a Co-Founder and Scientific Advisor for Targos Mol. Pathology Inc. Kassel/Germany. T.T.S. is the CEO and co-owner of Healthfund Finland Oy and reports consultation fees from Boehringer Ingelheim Finland and Amgen. FB is supported by JANSSEN PHARMACEUTICALS (clinical trial for Familial Adenomatous polyposis). RH is supported by the 10.13039/501100002424Fujifilm Germany and Janssen-Pharmaceuticals. LK is consultant of Sandoz, Novartis and Abbott. GM reports consultancy fees from Johnson & Johnson., (© 2023 The Author(s).)

Background: Hepatitis C Virus (HCV) is a common cause of chronic liver disease and its ensuing complications. In the last years, there has been a revolution of the treatment for patients with HCV regarding efficacy, simplicity, safety and duration of treatment. The role of the family physician is vital in all steps of care: screening, diagnosis, linkage to treatment, treatment and follow-up., Objectives: This review aims to summarise the family physician and the important updated recommendations for diagnosis and treatment of patients with chronic HCV., Methods: The updated recommendations were reviewed and summarised in a short and simple review., Results: Patients with any risk factor for HCV should first be screened for HCV antibodies. In the case of positive antibodies, reflex testing for RNA polymerase chain reaction (PCR) should be done without waiting for genotype. For patients with positive PCR, fibrosis assessment should be conducted using laboratory panels (Fibrosis-4 index (FIB-4) or aspartate aminotransferase to platelet ratio index (APRI)); if advanced fibrosis is suspected, additional non-invasive fibrosis assessment is needed, such as fibrotest or liver elastography. Naïve non-cirrhotic or compensated cirrhosis (Child-Pugh-Score A) could be treated with pangenotypic drugs, Glecaprevir/pibrentasvir (Maviret) for eight weeks, or Sofosbuvir/velpatasvir (Epclusa) for 12 weeks., Conclusion: Patients without advanced fibrosis and comorbidities can be treated by the educated family physician. However, patients with comorbidities, cirrhosis or coinfection (HIV, Hepatitis B Virus (HBV)) should be referred to the liver clinic. In case of screening patients with risk factors or likelihood of dormant HCV, health organisations should provide the appropriate resources, logistics, finances and workforce.

(1) Background: Fecal occult blood test (FOBT) is the modality of choice in most countries for colorectal cancer (CRC) screening. We aimed to investigate the risk factors for CRC among patients with a positive FOBT in real life. (2) Methods: This was a retrospective study that included patients who tested positive for FOBT. Data regarding the comorbidities and laboratories were collected and compared between CRC and non-CRC groups. (3) Results: Positive FOBT was found among 45,500 (5.36%) subjects and CRC was found in 1502 (3.3%). CRC patients were older, age 62.7 ± 7.15 years compared with 59.33 ± 7.3 years (p < 0.001), and had significantly higher rates of hypertension (48.4% vs. 44.7%, p = 0.002), iron-deficiency anemia (20.6% vs. 16.4, p < 0.001), family history of CRC (7.3% vs. 5.1%, p < 0.001), and previous CRC (6.5% vs. 0.3%, p < 0.001). Lower levels of hemoglobin, iron, and ferritin were found in the CRC group. Age, family history of CRC, and previous CRC were found to be significant risk factors for diagnosis of CRC after positive FOBT with OR of 1.057, 1.4, and 15.9, respectively. (4) Conclusions: Iron-deficiency anemia, family history of CRC, previous colorectal cancer, and low hemoglobin, iron, and ferritin levels should direct physicians to give high priority to colonoscopy scheduling.

Sex-based medicine is an important emerging discipline within medicine. We investigated the clinical characteristics, complications, and outcomes of Nonalcoholic Fatty Liver Disease (NAFLD) in females compared to males. Demographics, comorbidities, malignancy, complications, outcomes, and all-cause mortality of NAFLD patients older than 18 years were analyzed. The data were extracted using the MDClone platform from “Clalit” in Israel. A total of 111,993 (52.8%) of the study subjects were females with an average age of 44.4 ± 14.7 years compared to 39.62 ± 14.9 years in males, p < 0.001. Significantly higher rates of hypertension, diabetes mellitus, obesity, dementia, and thyroid cancer and lower rates of ischemic heart disease (22.3% vs. 27.3%, p < 0.001) were found among females. Females had a higher rate of cirrhosis, 2.3% vs. 1.9%, p < 0.001, and a lower rate of hepatocellular carcinoma, 0.4% vs. 0.5%, p < 0.001. In the multivariate analysis, a relationship between age, diabetes mellitus, and cirrhosis development were found among males and females. A lower age-adjusted mortality rate was found among females, 94.5/1000 vs. 116/1000 among males. In conclusion, older age at diagnosis, higher rates of hypertension, diabetes mellitus, obesity, cirrhosis, and a lower age-adjusted all-cause mortality rate were found among females with NAFLD.

Liver cirrhosis (LC) is a common disease with varied primary causes and ethnic disparities. Clinical characteristics and outcomes of Arab Bedouin (AB) and Jewish patients with LC were retrospective collected and compared. We included 1048 patients, 95 (9%) Arab Bedouin and 953 (91%) Jewish patients. The incidence of cirrhosis was much lower among AB. Age at diagnosis was 47 ± 18 years among Bedouins compared to 61 ± 13 years (p < 0.001) among Jews. The most frequent causes of cirrhosis among Bedouin patients were fatty liver 21.1%, cryptogenic 20%, hepatitis B 17.9% and autoimmune hepatitis 15.8%, while hepatitis C (39.2%), fatty liver (17.2%) and alcoholic liver disease (14.4%) were most common among Jewish patients. An all-cause mortality of 48.4% was observed in AB patients compared to 66.4% in Jewish patients (p < 0.001). Significant disparities regarding incidence, clinical characteristics and outcomes of cirrhosis among Arab Bedouin compared with Jewish population were found., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants., Methods: CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path&#95;MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path&#95;MMR carriers who were first- or second-degree relatives of Lynch syndrome probands., Results: In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path&#95;MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path&#95;MSH2 50% and 39%; for path&#95;MSH6 13% and 17% and for path&#95;PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups., Conclusions: Prospectively observed CRC incidences (PLSD) in path&#95;MLH1 and path&#95;MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path&#95;MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path&#95;PMS2 carriers subjected to colonoscopy, but not significantly so., (© 2022. The Author(s).)

Background: Since the outbreak of COVID-19, a significant decline in endoscopic procedures has been observed., Aims: We investigated the change of incidence, clinical characteristics, disease stage and mortality of patients with gastric cancer (GC) or colorectal cancer (CRC) diagnosed in 2020 compared to the pre-pandemic year 2019., Methods: Demographic, clinical and laboratory data on all patients diagnosed with GC or CRC at the Soroka University Medical Center were retrospectively collected and compared. Number of cases, time of diagnosis, clinical presentation, staging at diagnosis and mortality rates were compared., Results: Two hundred sixteen patients were diagnosed with CRC in 2019, whereas only 162 were diagnosed in 2020 (25% reduction), while 36 GC diagnoses were made in 2019 compared to 24 in 2020 (33% reduction). The age-adjusted incidence was calculated to be 24.28 for CRC and 5.0 for GC in 2020 compared to 29.93 and 5.32 in 2019, respectively. CRC patients had a significantly lower rate of rectal bleeding as their presenting symptom in 2020 compared with 2019, 8.1 vs. 19% ( p = 0.003), but higher rate of diarrhea as their presenting symptom, 4.3 vs. 1% ( p = 0.044). No significant differences regarding other presenting symptoms, comorbidities, surgery or mortality rates were found between the groups diagnosed in 2019 or 2020., Conclusion: A decrease in GC and CRC incidence was observed during the year 2020; lower rate of rectal bleeding and higher rate of diarrhea as presenting symptoms were noted in 2020, but no significant difference was found regarding other presenting symptoms, disease stage, surgery or mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abu-Freha, Hizkiya, Abu-Abed, Michael, Jacob, Rouvinov, Schwartz, Reshef, Netz, Pinsk and Etzion.)

Background: Liver cirrhosis (LC) is a common disease diagnosed in all ages. With the increasing population age, LC is noticeable more in the clinics., Aim: To distinguish the clinical characteristics, complications, and survival of patients with liver cirrhosis., Methods: A retrospective study enrolled patients diagnosed with liver cirrhosis at Soroka University Medical Center. Patients with cirrhosis diagnosed at an age older than 65 years (group 1) were compared with patients diagnosed at an age younger than 65 years (group 2)., Results: We included 1046 patients; 411 (39.3%) in group 1 and 635 (60.7%) in group 2. Fatty liver and cryptogenic liver disease were found to cause cirrhosis at a significantly higher rate in the elderly (23.4% vs. 13.9%, p < 0.001, 15.3% vs. 6.3%, p < 0.001, respectively). A higher rate of non-hepatocellular carcinoma cancers and mortality (17.5% vs. 9.1%, p < 0.001, 76.6% vs. 57%, respectively) was found among cirrhotic elderly patients, but a lower rate of oesophageal varices (47.7% vs. 60.1%, p = 0.002). Twenty-year follow-up Kaplan-Meier survival analysis for mortality estimated poor survival in the elderly (log-rank p < 0.001). The adjusted Cox proportional hazards regression model showed an association of age > 65 with an all-cause mortality hazard ratio of 2.26 (95% CI 1.89-2.69)., Conclusion: Higher rates of fatty liver, cryptogenic cirrhosis, non-HCC cancers, and mortality were found among patients diagnosed with cirrhosis in the elderly., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Data for Israel from the Rome Foundation Global Epidemiology Study on the disorders of gut-brain interaction (DGBI) were used to assess the national prevalence of all 22 DGBI, the percentage of respondents meeting diagnostic criteria for at least one DGBI, and the impact on burden of disease in Israel., Methods: The survey was conducted through the Internet with multiple built-in quality-assurance techniques and included the Rome IV diagnostic questionnaire and an in-depth supplemental questionnaire., Key Results: 2012 Israeli participants completed the survey nationwide: mean age 44.6 ± 16.4 years, 50% females. The national distribution was very close to the latest Israeli census. 36.4% (95% CI 34.3, 38.4) met diagnostic criteria for at least one DGBI, with 4.4% for any esophageal disorder, 6.5% for any gastroduodenal disorder, 30.8% for any bowel disorder, and 5.3% for any anorectal disorder. The rates were higher for women. Having any DGBI was associated negatively with psychosocial variables (including quality of life, somatization, and concern about digestive problems), and healthcare utilization (including doctor visits, use of medications, and abdominal surgeries)., Conclusions & Inferences: The results of this study provide the first in-depth assessment of the prevalence and burden of Rome IV DGBI in Israel and facilitate comparisons with other countries. As 36.4% of the 2,012 participants met diagnostic criteria for at least one DGBI, and 23.5% of those met criteria for more than one DGBI, the burden of DGBI in Israel is high, indicating a need to focus on research and training for patient care., (© 2022 John Wiley & Sons Ltd.)

Objectives: We investigated the causes of low COVID-19 vaccination rates among a minority population and highlighted interventions for increasing the vaccination rate. Methods: We reviewed the experience during the mass vaccination campaign period among the Arab Bedouin (AB) in Israel, attempting to determine important causes of low vaccination rates and gathered information from real-life experience and through direct contact with the population during the campaign. Results: Causes for low vaccination rates in the AB are related to the health system infrastructure, crisis management strategies, and population characteristics. Long-standing socioeconomic inequalities, limited resources, and language and culture barriers present special challenges to the task of COVID-19 vaccination campaigns. Key interventions for increasing vaccination rates among minority populations include raising awareness, improving vaccination access, and directly targeting risk-groups. To maximize the effectiveness of these interventions they should be culturally adapted and executed according to the needs of each individual target community. Conclusion: Culturally adapted awareness campaigns, interventions, and improved access to vaccines can be accomplished by cooperation between relevant governing and community bodies to increase COVID-19 vaccination rates among minorities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abu-Freha, Alsana, El-Saied, Azbarga, Aloka, Goda and Abu Tailakh.)

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.

Hepatitis B and hepatitis C (HBV/HCV) are important global public health concerns. We aimed to evaluate the association between maternal HBV/HCV carrier status and long-term offspring neurological hospitalisations. A population-based cohort analysis compared the risk for long-term childhood neurological hospitalisations in offspring born to HBV/HCV carrier vs. non-carrier mothers in a large tertiary medical centre between 1991 and 2014. Childhood neurological diseases, such as cerebral palsy, movement disorders or developmental disorders, were pre-defined based on ICD-9 codes as recorded in hospital medical files. Offspring with congenital malformations and multiple gestations were excluded from the study. A Kaplan-Meier survival curve was constructed to compare cumulative neurological hospitalisations over time, and a Cox proportional hazards model was used to control for confounders. During the study period (1991-2014), 243,682 newborns met the inclusion criteria, and 777 (0.3%) newborns were born to HBV/HCV mothers. The median follow-up was 10.51 years (0-18 years). The offspring from HBV/HCV mothers had higher incidence of neurological hospitalisations (4.5 vs. 3.1%, hazard ratio (HR) = 1.91, 95% CI 1.37-2.67). Similarly, the cumulative incidence of neurological hospitalisations was higher in children born to HBV/HCV carrier mothers (Kaplan-Meier survival curve log-rank test p < 0.001). The increased risk remained significant in a Cox proportional hazards model, which adjusted for gestational age, mode of delivery and pregnancy complications (adjusted HR = 1.40, 1.01-1.95, p = 0.049). We conclude that maternal HBV or HCV carrier status is an independent risk factor for the long-term neurological hospitalisation of offspring regardless of gestational age and other adverse perinatal outcomes.

(1) Background: Spontaneous bacterial peritonitis (SBP) is a feared complication of liver cirrhosis. We investigated the prevalence of SBP, positive ascitic fluid cultures, and risk factors for mortality. (2) Methods: A retrospective analysis of all patients with cirrhosis hospitalized or in follow-up in a single center between 1996 and 2020. The clinical data, long-term complications, and mortality of SBP patients were compared with those of non-SBP patients. Ascitic fluid positive culture was compared with those without growth. (3) Results: We included 1035 cirrhotic patients, of which 173 (16.7%) developed SBP. Ascitic fluid culture growth was found in 47.4% of the SBP cases, with Escherichia coli bacteria detected in 38%, 24.4% grew ESBL-producing bacteria, and 14.5% displayed multidrug resistance. In a Cox regression model, SBP, male sex, prolonged INR at diagnosis, and hepatocellular carcinoma were found to be risk factors for mortality in cirrhotic patients. The long-term all-cause mortality was 60% in non-SBP and 90% in SBP patients. (4) Conclusions: Only a minority of cirrhotic patients developed SBP, 47.4% of which had positive ascitic fluid cultures with high antibiotic resistance. Growth of ESBL and multidrug resistant organisms is becoming more frequent in the clinical setting, reaching SBP mortality of 90%.

Aim: Nuclear factor kappa B (NF-κB) is known to play an important role in the inflammatory process which takes place after ischemic stroke. The major objective of the present study was to examine the effects of MEDS-23, a potent inhibitor of NF-κB, on clinical outcomes and brain inflammatory markers in post-ischemic stroke rats., Main Methods: Initially, a Toxicity Experiment was performed to determine the appropriate dose of MEDS-23 for use in animals, as MEDS-23 was analyzed in vivo for the first time. We used the middle cerebral artery occlusion (MCAO) model for inducing ischemic stroke in rats. The effects of MEDS-23 (at 10 mg/kg, ip) on post-stroke outcomes (brain inflammation, fever, neurological deficits, mortality, and depression- and anxiety-like behaviours) was tested in several efficacy experiments., Key Findings: MEDS-23 was found to be safe and significantly reduced the severity of some adverse post-stroke outcomes such as fever and neurological deficits. Moreover, MEDS-23 significantly decreased prostaglandin E2 levels in the hypothalamus and hippocampus of post-stroke rats, but did not prominently alter the levels of interleukin-6 and tumor necrosis factor-α., Significance: These results suggest that NF-κB inhibition is a potential therapeutic strategy for the treatment of ischemic stroke.

Despite established efficacy in bipolar disorder patients, lithium (Li) therapy has serious side effects, particularly chronic kidney disease. We examined the safety and behavioral effects of combined chronic low-dose aspirin plus low-dose Li in rats to explore the toxicity and therapeutic potential of this treatment. Rats were fed regular or Li-containing food (0.1% [low-dose, LLD-Li] or 0.2% [standard-dose, STD-Li]) for six weeks. Low-dose aspirin (1 mg/kg) was administered alone or together with Li. Renal function and gastric mucosal integrity were assessed. The effects of the combination treatment were evaluated in depression-like and anxiety-like behavioral models. Co-treatment with aspirin did not alter plasma Li levels. Chronic STD-Li treatment resulted in significant polyuria and polydipsia, elevated blood levels of creatinine and cystatin C, and increased levels of kidney nephrin and podocin-all suggestive of impaired renal function. Aspirin co-treatment significantly damped STD-Li-induced impairments in kidney parameters. There were no gastric ulcers or blood loss in any treatment group. Combined aspirin and LLD-Li resulted in a significant increase in sucrose consumption, and in the time spent in the open arms of an elevated plus-maze compared with the LLD-Li only group, suggestive of antidepressant-like and anxiolytic-like effects, respectively. Thus, we demonstrate that low-dose aspirin mitigated the typical renal side effects of STD-Li dose and enhanced the beneficial behavioral effects of LLD-Li therapy without aggravating its toxicity.

We investigated whether maternal hepatitis B virus (HBV) or hepatitis C virus (HCV) carrier status increases the risk for long-term oncologic morbidity of their offspring up to the age of 18 years. A population-based cohort study was conducted, including all singleton deliveries between the years 1991 and 2014 at a tertiary medical center. Our study included: HBV carriers ( n  = 588), HCV carriers ( n  = 183) and non-carriers ( n  = 241,570. No significant differences regarding oncologic morbidity were found between offspring of HBV carriers (0.2%), HCV carriers (0%) and non-carriers (0.6%; p  = 0.216, respectively). To conclude: maternal HBV or HCV carrier status is not a risk factor for long-term oncologic morbidity of the offspring.

Background: Recently, three updated guidelines for post-polypectomy colonoscopy surveillance (PPCS) have been published. These guidelines are based on a comprehensive summary of the literature, while some recommendations are similar, different surveillance intervals are recommended after detection of specific types of polyps., Aim: In this review, we aimed to compare and contrast these recommendations., Methods: The updated guidelines for PPCS were reviewed and the recommendations were compared., Results: For patients with 1-4 adenomas <10 mm with low-grade dysplasia, irrespective of villous components, or 1-4 serrated polyps <10 mm without dysplasia, the European Society of Gastrointestinal Endoscopy (ESGE) and British Society of Gastroenterology (BSG), the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and Public Health England (PHE) (BSG/ACPGBI/PHE) guidelines do not recommend colonoscopic surveillance and instead recommend that the participate in routine CRC screening program (typically based on the fecal immunochemical test), while the USMSTF recommends surveillance colonoscopies 7-10 years after diagnosis of 1-2 tubular adenomas <10 mm and 3-5 years for 3-4 tubular adenomas of the same size. The USMSTF define adenomas with tubulovillous or villous histology as high-risk adenomas; thus, surveillance colonoscopy is recommended after 3 years. However, the ESGE and BSG do not consider such histology as a criterion for repeating colonoscopy at this short interval. For patients with 1-2 sessile serrated polyps (SSPs) <10 mm and those with 3-4 SSPs <10 mm, the USMSTF recommends surveillance colonosocopy after 5-10 and 3-5 years, respectively., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Problem: Celiac disease is an autoimmune disease, patients with celiac have increased risk for infections, and offspring of celiac mothers have increased morbidity. The aim of the study was to assess long-term infectious morbidity among offspring of pregnant women with celiac disease., Method of Study: A population-based cohort study was conducted, including all singleton deliveries between the years 1991-2014 at a tertiary medical center. The offsprings were subdivided into two groups: offsprings of mothers with and without celiac disease. Data on demographics, maternal, perinatal, and long-term hospitalizations for infectious morbidity were compared between the two groups., Results: During the study period there were 210 (0.09%) deliveries of mothers with celiac, and they were compared to 242170 (99.91%) deliveries of non-celiac mothers. Cumulative infectious morbidity was significantly higher in offspring of mothers with celiac compared to offspring of mothers without celiac (Kaplan-Meier, log-rank p = .004). Specifically, among the offspring of mothers with celiac significantly higher rates of bacteremia was noted (1.0% vs. 0.1%; p = .001), and infections of the central nervous system (1% vs. 0.2%; p = .028). In the Cox multivariable model which accounted for confounding variables, being born to mothers with celiac disease was associated with significantly increased risk for long-term infectious morbidity of the offspring (adjusted HR = 1.6, 95% CI 1.165-2.357, p = .005)., Conclusions: Maternal celiac disease is an independent risk factor for long-term infectious morbidity for the offspring., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Sex and gender can affect the prevalence and prognosis of diseases. Our aim was to assess similarities and differences for males and females who underwent an upper endoscopy, with regards to indications and results. We reviewed all upper endoscopy reports from 2012 to 2016. Data regarding demographics, indications, and procedure findings were collected. The upper endoscopy findings were compared regarding the most common indications: gastroesophageal reflux, abdominal pain, gastrointestinal bleeding, and anemia. We investigated 12,213 gastroscopies among males (age, 56.7 ± 17.4) and 15,817 among females (age, 56.0 ± 17.3, p = 0.002). Males who underwent an upper endoscopy for gastroesophageal reflux had higher rates of esophagitis (7.7% vs. 3.4%, p < 0.001) and Barret's esophagus (4.4% vs. 1.5%, p < 0.001). Females who underwent an upper endoscopy for abdominal pain had a higher rate of hiatal hernia, whereas males had higher rates of esophagitis, helicobacter pylori infection, gastritis, gastric ulcer, duodenitis, and duodenal ulcer ( p < 0.001). Gastrointestinal bleeding as an indication for upper endoscopy showed that helicobacter, duodenitis, and duodenal ulcers are more common among males compared to females ( p < 0.001). Males with anemia who underwent an upper endoscopy had higher rates of esophagitis ( p = 0.021) gastritis ( p = 0.002), duodenitis ( p < 0.001), and duodenal ulcer ( p < 0.001). We found significant differences regarding the pathological gastroscopy findings between males and females in relation to the different indications.

The objective of the study was to investigate the long-term effects of maternal hepatitis B virus (HBV) or hepatitis C virus (HCV) carrier status on the long-term infectious morbidity of their offspring. A population-based cohort study was conducted, including all singleton deliveries between the years 1991 and 2014 at a tertiary medical centre. The mothers were subdivided into three groups: HBV carriers, HCV carriers and non-carriers. Data on demographics, maternal, perinatal and long-term hospitalization for infectious morbidity were compared between the groups. During the study period, 242 905 (99.7%) non-carrier mothers, 591 (0.2%) HBV carriers and 186 (0.1%) HCV carriers were observed. Hospitalizations related to infectious morbidity was significantly higher in the offspring of HBV carriers compared with HCV and non-carriers (15.6% vs 11.3% vs 11.0%; P = .002, respectively; Kaplan-Meier, log-rank P < .001). Specifically, a significantly higher rate of hospitalizations gastrointestinal infectious morbidity was noted among the offspring of HBV carrier mothers (3.6% in the HBV carrier group, 1.6% in the HCV carrier group and 1.6% in the non-carrier group [P = .001]). There was a respiratory infectious morbidity of 8.1% among the offspring of HBV carriers, 8.6% among HCV carriers and 5.5% in non-carriers (P = .005). Using a Cox multivariable model, controlling for confounding variables, maternal HBV carrier status was associated with a significantly increased long-term infectious morbidity of the offspring, with an adjusted HR of 1.7 (95% CI, 1.388-2.077, P < .001). Maternal HBV carrier status is an independent risk factor for long-term infectious morbidity of the offspring, particularly for gastrointestinal and respiratory infections., (© 2020 John Wiley & Sons Ltd.)

Adherence to treatment of chronic Hepatitis B Virus (HBV) is an important issue and can affect the complication rate. Nucleos(t)ide analogue as oral treatments are used for patients with necro-inflammatory activity and high viral load, with the goal of decline the complication rate such cirrhosis and hepatic cancer. We aimed to investigate the adherence to chronic HBV treatment. Chronic HBV patients with dispensing medication rates (DMR) of at least 80% were defined as high adherence group (HAG) and those who dispensed less than 80% as low adherence group (LAG). The study included 273 patients. 90 patients (33%) were in the LAG and 183 (67%) in the HAG. The All-cause mortality in the LAG was 15.6%, and 8.7% among the HAG ( p -value = 0.09). 185 patients were of Jewish origin (mean age of 52.96 ±14.6 years, 30% women) and 88 patients of Arab Bedouin (AB) origin (mean age of 40.86 ± 13.96 years ( p -value < 0.001), 42% women). The proportion of Jewish patients with high adherence was 71% (131 patients) versus 59% (52 patients) in AB patients ( p -value = 0.054). The all-causes mortality was 14.6% among Jewish origin and 3.4% of AB ( p -value = 0.01). We conclude that, two third of HBV carriers are with high level adherence to treatment in southern Israel, with lower but marginally significant all-cause mortality. No-significant differences in adherence patterns were noted between Arab Bedouin and Jews.

This study aimed to investigate the long-term effect of maternal hepatitis B virus (HBV) or hepatitis C virus (HCV) carrier status on offspring endocrine morbidity. A population-based cohort study included all singleton deliveries between the years 1991-2014 at the Soroka University Medical Center, Beer-Sheva, Southern Israel. The mothers were subdivided into three groups, HBV carriers, HCV carriers and non-carriers. Data regarding the long-term endocrine morbidity of their offspring were compared between the groups. The study included 242,905 (99.7%) non-carrying mothers, 591 (0.2%) mothers who were carriers for HBV and 186 (0.1%) mothers who were carriers for HCV. The Kaplan-Meier's survival curve demonstrated a significantly higher cumulative endocrine morbidity in children born to mothers with HCV (log-rank test, p  = 0.002). Specifically, higher rates of hypoglycemia were noted among the offspring born to mothers who were carriers of HCV (1.1%; p = 0.001) compared with the offspring of mothers who were either carriers of HBV (0.2%) or non-carriers (0.1%). A Cox regression model controlled for maternal age, gestational age, maternal diabetes, hypertensive disorders of pregnancy, found maternal HCV carrier status to be independently associated with pediatric endocrine morbidity in the offspring (adjusted hazard ratio = 5.05, 95% CI: 1.625-15.695, p = 0.005). Maternal HCV carrier status is an independent risk factor for long-term endocrine morbidity.

Objective: Maternal HBV or HCV carrier status is a cause for concern regarding both the course of pregnancy and the short-term perinatal outcomes. Our main aim was to evaluate whether offspring born to carrier mothers during pregnancy, also suffer from long-term pediatric respiratory morbidity (until 18 years of age)., Method of Study: A population-based cohort analysis was conducted at a single tertiary medical center. The study included all singleton deliveries between the years 1991-2014, comparing incidence of respiratory-related hospitalization of offspring born to mothers who were carrier of HBV or HCV during their pregnancy to those born to nonexposed mothers. Respiratory morbidities were based on a predefined set of ICD-9 codes. A Kaplan-Meier survival curve was used to compare cumulative hospitalization incidence between the groups and a Cox regression model was used to adjust for confounding variables., Results: During the study period, 242,342 deliveries met the inclusion criteria. Of them, 771 (0.31%) were to HBV or HCV mother carriers during pregnancy. A Kaplan-Meier curve demonstrated that children born to HBV or HCV carriers had higher cumulative incidence of respiratory morbidity (Log rank test p = 0.007). In the Cox regression model, while controlling for maternal age, diabetes mellitus, hypertensive disorders, caesarian section and gestational age at birth, maternal HBV or HCV carrier status was noted as an independent risk factor for long-term respiratory morbidity in the offspring (adjusted HR = 1.43, 95% CI 1.07-1.90, p = 0.015)., Conclusions: Maternal HBV or HCV carrier status in pregnancy may increase offspring susceptibility to long-term respiratory morbidity., Competing Interests: Declaration of competing interest All authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Arab Bedouins (AB) in Israel are traditionally a semi-nomadic population. Their average birth rate is extremely high (birth rate of 5.43, as well is their high consanguinity rate (44%), despite having decreased from 60% in 1992. Additionally, their mean inbreeding coefficient is 0.0238.The high rate of consanguinity results in a high prevalence of recessive genetic and multifactorial disorders as well as high infant mortality rate (11 per 1000 live births). Various genetic diseases are prevalent in AB, exemplifying how extensive the impact of consanguinity is on the community. Targeted screening programs are provided for prevalent severe genetic diseases. However, despite initial success, genetic screening is still underutilized in AB. AB, the Ministry of Health, the Ministry of Education, and different social associations should plan and manage programmed interventions. These programs should work intensively to further educate and raise awareness regarding consanguinity and its potential harms, to increase trust and collaboration between the community and the public health system, to expand screening and premarital consultations, and to create a genetic bank (specific mutations/whole genome) for the AB community.

Background: More than 360 million people have chronic hepatitis B or C (HBV/HCV) infection worldwide, many of which are women at childbearing age. While the risk of perinatal HBV/HCV has been well established, the long-term implications on offspring health, have been less studied. We aimed to evaluate the association between maternal HBV/HCV carrier status and long-term gastrointestinal (GI) morbidities in offspring., Aims & Methods: A population-based cohort analysis compared the risk for long-term childhood GI morbidities in children born to HBV/HCV carrier mothers vs the risk in those who were born to noncarriers. Childhood GI morbidities were predefined based on ICD-9 codes, as recorded in hospital medical files. Children with congenital malformations and multiple gestations were excluded from the analysis. A Kaplan-Meier survival curve was constructed to compare the cumulative GI morbidities over time, and a Cox proportional hazards model was used to control for confounders., Results: During the study period (1991-2014), 242 342 newborns met the inclusion criteria: 771 (0.3%) were born to HBV/HCV mothers and 241 571 (99.7%) were not. The median follow-up was 10.51 years (0-18 years). Offspring to HBV/HCV mothers had a higher incidence of GI diseases (9.3% vs 5.4%, OR = 1.82; 95% CI 1.43-2.32; Kaplan-Meier log-rank = 0.001). The increased risk remained significant in the Cox proportional hazards models, which adjusted for gestational age, mode of delivery and pregnancy complications (adjusted HR = 2.26, 95% CI: 1.79-2.85; P < .001)., Conclusion: Maternal HBV or HCV carrier status is an independent risk factor for long-term the GI morbidity of offspring., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Colorectal cancer (CRC) is the second most common cancer in Israel, with about 3,100 new cases annually. The available screening methods are occult fecal blood testing, stool DNA, sigmoidoscopy, colonoscopy and virtual colonoscopy. Each modality has different sensitivity, specificity, participation rates, complications, availability and mortality reduction rate. In Israel, the fecal immunochemical testing (FIT) is available for populations aged 50-74 years. However, many of the patients are still diagnosed with CRC at stages 2-4. A new standard of care modality should be established with the objective of reducing CRC incidence and mortality. Colonoscopy is currently the most successful modality that reduces CRC incidence. Cost, limited availability and participation rates should be considered as challenging factors in establishing colonoscopy for primary screening. However, a plan to gradually implement a national colonoscopy screening program in parallel to FIT testing before phasing out of the current dominating modalities will be successful and cost effective in the long term. Such a program will be cost effective because early detection and thus lowering its incidence prevents the need for highly expensive therapies associated with more progressive disease. Although colonoscopy is very effective, a new technology of capsule endoscopy may be a more favorable screening option in case it does not require bowel preparation. When such capsule endoscopy becomes available, the medical community will likely change its approach and use colonoscopy for therapeutic purposes. Conclusion: A national program using colonoscopy as the main component of CRC screening should be implemented gradually to increase early detection and lower incidence rate.

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.

Background: Serological markers used for diagnostic purposes and disease stratification in inflammatory bowel disease. We aimed to investigate the frequency of ASCA and ANCA among Arab Bedouin IBD patients and its relationship to disease phenotype and course., Methods: From cohort of 68, 25 Crohn's disease (CD) and 25 Ulcerative colitis (UC) patients were recruited (72%). ASCA IgG was determined by ELISA assay. Immunofluorescence analysis of ANCA was performed., Results: The IgG ASCA was detected in 13 (52%) of the CD patients and in three (12%) UC patients. The prevalence of ANCA among UC patients was positive with 76%, sub-grouped, atypical ANCA in 9 patients (36%), pANCA in six patients (24%) and cANCA in 4 patients (16%). The detection of ASCA among CD patients was found not to be a reliable predictor of young age at diagnosis, gender, ileal involvement, anti-TNF treatment or surgery. UC patients with positive ANCA were younger, mean age 40.2 ± 11.9 compared with 57.3 ± 21.2 (p = 0.03), and diagnosed at a younger age, 29.2 ± 11.8 compared with 43.5 ± 15.3 (p = 0.05)., Conclusion: The frequency of ASCA among Bedouin CD patients and ANCA among UC patients was high, however ASCA was not found to have a predictive value for disease phenotype or course. Positive ANCA in UC patients was predictive for younger age and age at diagnosis.

It is well recognized that cancer cells subvert the phenotype of stromal naïve fibroblasts and instruct the neighboring cells to sustain their growth agenda. The mechanisms underpinning the switch of fibroblasts to cancer-associated fibroblasts (CAFs) are the focus of intense investigation. One of the most significant hallmarks of the biological identity of CAFs is that their tumor-promoting phenotype is stably maintained during in vitro and ex vivo propagation without the continual interaction with the adjacent cancer cells. In this review, we discuss robust evidence showing that the master cytokine Transforming Growth Factor-β1 (TGFβ-1) is a prime mover in reshaping, via epigenetic switches, the phenotype of stromal fibroblasts to a durable state. We also examine, in detail, the pervasive involvement of TGFβ-1 signaling from both cancer cells and CAFs in fostering cancer development, taking colorectal cancer (CRC) as a paradigm of human neoplasia. Finally, we review the stroma-centric anticancer therapeutic approach focused on CAFs-the most abundant cell population of the tumor microenvironment (TME)-as target cells., Competing Interests: The authors declare no conflict of interest.

We assessed the molecular characteristics and the frequency of mutations in mismatch-repair genes among Bedouin patients with colorectal cancer (CRC) in Israel. Bedouin patients with a diagnosis of CRC at a major hospital in the southern part of Israel were deemed eligible for this study. The primary screening method was immunohistochemical staining for mismatch-repair proteins (MLH1, MSH2, MSH6, and PMS2). For subjects with abnormal immunohistochemical staining, we performed microsatellite instability (MSI) analyses, and for tumors with a loss of MLH1 expression we also performed BRAF testing. In MSI high cases we searched further for germline mutations. Of the 24 patients enrolled, four subjects (16.7%) had MSI high tumors: one subject was found to harbor a biallelic PMS2 mutation, one subject had Lynch syndrome (LS) with MSH6 mutation and two subjects had a loss of MLH1/PMS2 proteins/BRAF wild type /normal MLH1 sequence. Ten patients (41.7%) were younger than 50 at the time of diagnosis and none had first degree relatives with CRC. In conclusion, in this cohort of 24 consecutive Arab Bedouins with CRC, one patient was found to harbor a constitutional mismatch repair deficiency, one patient had LS with MSH6 mutation, and two patients had unresolved loss of MLH1/PMS2 proteins/BRAF wild type phenotype.

Aim: The aim of this study was to assess the yield of endoscopic evaluation in isolated unintentional weight loss (UWL) patients compared with patients with weight loss and additional symptoms or signs., Patients and Methods: A retrospective review of all patients who underwent an endoscopic evaluation for the investigation of UWL at Soroka University Medical Center between 2006 and 2012. Data on clinical indication, endoscopic, and laboratory finding were retrieved. Severe inflammation, ulcers, achalasia, and neoplasias were considered clinically significant endoscopic findings (CSEF) that could explain weight loss. Detection rates of CSEF were compared between endoscopic studies for which UWL was the sole indication (group 1) and those performed for UWL and at least one other indication (group 2)., Results: During the study period, 1843 patients with UWL were evaluated with 2098 endoscopic procedures. Of these, 1540 underwent esophagogastroduodenoscopy (EGD) and 558 underwent colonoscopy. EGD was performed in 229 (14.8%) patients in group 1 (mean age: 60.9±16.4, 43.3% men), and in 1311 (85.2%) patients in group 2 (mean age: 60.5±18.5, 45% men). Pathological endoscopic findings were identified in 712 (46%) EGDs. Of these, 155 (10%) studies detected significant outcomes: six (3.9%) in group 1 and 149 (96.1%) in group 2. Of the 558 colonoscopies performed, 105 (18.8%) were performed in group 1 (mean age: 61.7±17.5, 43% men) and 453 (82.2%) in group 2 patients (mean age: 62.9±14.6, 49% men). Abnormal findings were found in 190 (33.8%) of the procedures. CSEF were found in 34 (6%) patients: two in group 1 and 32 in group 2., Conclusion: The diagnostic yield of endoscopy for investigation of patients with UWL is non-negligible, and should be considered as part of its baseline evaluation, especially in older individuals and those who present with other gastrointestinal manifestations.

Background/aim: Cancer-associated fibroblasts (CAFs) play an important role in tumor development and progression. The prevailing consensus favors the view that a specific epigenetic signature underpins the stable CAF phenotype. The aim of the present study was to assess global DNA methylation in CAFs during the adenoma-carcinoma sequence in non-familial sporadic human colorectal cancer (CRC)., Patients and Methods: Immunohistochemical staining of nuclear 5-methylcytosine (5'-meCyt) was performed in matched samples of colonic tumor tissue and normal colonic mucosa excised from six patients with adenomas and four with adenocarcinomas. The staining intensity was expressed semi-quantitatively as the immunohistochemical staining score (ISS)., Results: ISS values of human colonic CAFs and adenomatous samples were 14.00±2.2 and 14.08±1.8, respectively, showing no statistically significant difference. In contrast, a marked trend was found towards global DNA hypomethylation in CAFs from adenocarcinomatous specimens compared to matched normal mucosa: ISS: 9.25±2.44 (range=6-11) vs. 16.17±0.75, respectively, p<0.03., Conclusion: Final stages of cancer development in CRC are associated with global DNA hypomethylation in stromal CAFs., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)