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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.

Liver cirrhosis (LC) is a common disease diagnosed in all ages. With the increasing population age, LC is noticeable more in the clinics.To distinguish the clinical characteristics, complications, and survival of patients with liver cirrhosis.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).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).Higher rates of fatty liver, cryptogenic cirrhosis, non-HCC cancers, and mortality were found among patients diagnosed with cirrhosis in the elderly.

Background: The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_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_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_MSH2, path_MSH6 and path_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_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_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers.Interpretation: In path_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. Background: The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_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_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_MSH2, path_MSH6 and path_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_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_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers. Interpretation: In path_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.

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

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.

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.

(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%.

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.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.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).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.

(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.

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

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 &lt, 0.001) and Barret’s esophagus (4.4% vs. 1.5%, p &lt, 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 &lt, 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 &lt, 0.001). Males with anemia who underwent an upper endoscopy had higher rates of esophagitis (p = 0.021) gastritis (p = 0.002), duodenitis (p &lt, 0.001), and duodenal ulcer (p &lt, 0.001). We found significant differences regarding the pathological gastroscopy findings between males and females in relation to the different indications.

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.

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.

The advent of direct-acting antivirals (DAAs) has transformed the landscape of hepatitis C virus (HCV) management. We aimed to prospectively (real-time) evaluate the feasibility of using a response-guided therapy approach, based on mathematical modeling of early viral kinetics, to reduce the duration of DAAs therapy. Patients were treated with DAAs according to the physicians’ preference. HCV was measured at baseline and at day 2 and weeks 1, 2 and 4 after treatment initiation. The primary endpoint was the proportion of patients with sustained-virological response (SVR) at 12 and/or 24 weeks post-treatment. Twenty-nine patients (mean age 54 ± 16, 44% females, 73% with HCV genotype 1), were enrolled and all completed therapy. Treatment duration was shortened in 11 of the 29 patients (38%). SVR was achieved in 28 of the 29 patients (97%). Relapse occurred post treatment in a single case of a non-cirrhotic male with genotype 3, who was treated with sofosbuvir/velpatasvir for 6 weeks. Virus sequencing did not identify baseline or treatment emergent resistance associated substitutions. Real-time mathematical modeling of early HCV kinetics can be utilized for shortening DAAs duration in approximately 40% of patients without compromising treatment efficacy.Clinical trial registration: ClinicalTrials.gov Identifier: NCT03603327.

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 &plusmn, 14.6 years, 30% women) and 88 patients of Arab Bedouin (AB) origin (mean age of 40.86 &plusmn, 13.96 years (p-value &lt, 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.

Purpose Polyps are a common finding on colonoscopy procedures. After completing polypectomy, patients are to be followed up with endoscopy. The purpose of the study was to assess the adherence of gastroenterologists to international post-polypectomy guidelines. Methods Israeli gastroenterologists answered a questionnaire, consisting of 30 items, regarding the recommendation for post-polypectomy surveillance following colonoscopy. Results One hundred and twelve gastroenterologists, representing 23% of the total number of Israeli gastroenterologists, participated in this study, by responding to the web-based questionnaire (mean age is 47 ± 10 years, males, 74 (66%)). From the total responses, 57.4% were compatible with the updated European post-polypectomy guidelines. The recommendations appeared remarkably inappropriate when applied to polyps that were identified as having low-risk tubular adenoma, tubular adenoma with high-grade dysplasia, and small serrated adenoma. In 37.2% of questionnaires, the recommended time to follow-up colonoscopy was shorter than currently stated in the guidelines. The appropriate polypectomy technique was chosen by 62% of the responses. Gastroenterologists younger than 45 years of age adhered more strongly to the international guidelines, particularly in cases of piecemeal polypectomy or high-risk adenoma polypectomy. Conclusions Gastroenterologists follow the clinical guidelines for post-polypectomy surveillance intervals partially. 57.4% of the recommendations were compatible with the guidelines, whereas 37% of the recommendations were for shorter interval.

Background and Aim: Hijab pins ingestion is increasing. Some women hold the pin between their teeth while arranging the Hijab and the inadvertent ingestion of the pin can be the result of any careless movements. The aims of our study were to investigate the clinical outcomes of patients who underwent endoscopic pin removal via gastroscopy as opposed to patients who were treated conservatively with clinical observation, and to compare clinical and endoscopic data pertaining to patients who underwent early versus late gastroscopy.Methods: Muslim women hospitalized in a tertiary hospital from 2005-2015 due to ingestion of Hijab pin ingestion were included. Patients who underwent gastroscopy during 12 hours from the time of admission to Emergency Room (ER) were included in the “early” gastroscopy group, while endoscopy performed at a later time defined the “late” gastroscopy group.Results: During the study period 37 women were included. Twenty four patients (65%, mean age 20 ± 8.9) underwent gastroscopy; and thirteen (35%, mean age 19.9 ± 1.6) were hospitalized for observation. Six patients (25%) had normal gastroscopy; by 8 patients (33%) the pin was located in the antrum, 6 (25%) body, 2 (8.3%) and 1 (4.1%) in the duodenum. Fifteen patients underwent early gastroscopy and nine underwent late gastroscopy. The Duration of hospitalization was significantly shorter among patients who underwent early gastroscopy 1-day (1, 1) median, (IQR) compared with 2 days (1, 3) p < 0.02. Severe complications were found in one patient (2.7%) with stomach perforation which required surgery.Conclusion: Most pins will pass spontaneously, however severe complication may arise inadvertent Hijab pin ingestion. Early gastroscopy shortens the hospital stay.

Background: The advent of direct-acting antivirals (DAAs) has transformed the landscape of hepatitis C virus (HCV) management. However, the high cost of DAAs therapy has become a major barrier to HCV elimination. We aimed to prospectively evaluate the efficacy and safety of reducing the duration of DAAs therapy using response-guided therapy approach based on mathematical modeling of viral kinetics. Methods: Patients were treated with DAAs according to the physicians’ preference. HCV was measured at baseline and at day 2 and weeks 1, 2 and 4 after treatment initiation. The primary endpoint was the proportion of patients with sustained-virological response (SVR) at 12 and/or 24 weeks post-treatment. Findings: Twenty-nine patients (mean age 54±16, 44% females, 73% with HCV genotype 1), were enrolled and all completed therapy. Sofosbuvir/velpatasvir, elbasvir/grazoprevir, sofosbuvir/ledipasvir and glecaprevir/pibrentasvir, were administered in 38%, 27%, 21% and 14% of patients, respectively. Treatment duration was shortened in 11 of the 29 patients (38%). SVR was achieved in 28 of the 29 patients (97%). Relapse occurred post treatment in a single case of a non-cirrhotic male with genotype 3, who was treated with sofosbuvir/velpatasvir for 6 weeks. Virus sequencing did not identify baseline or treatment emergent resistance associated substitutions. Interpretation: Real-time modeling can be utilized for shortening DAAs duration in approximately 40% of patients without compromising treatment efficacy. Implementation of this model on a wider scale may lead to significant cost-saving and to improved access to anti-HCV care. Trial Registration: ClinicalTrials.gov Identifier: NCT03603327. Funding Statement: This research was supported in part by Clalit Health Services and the National Institutes of Health (NIH) and extramural NIH grants R01-AI078881 and R01GM121600. Declaration of Interests: OE has consulted for Gilead and Abbvie and received lecture fees from Gilead, Abbvie and MSD. HD has consulted for CoCrystal Inc. None of the other authors has any financial interest or conflict of interest related to this research. Ethics Approval Statement: The study was approved by the institutional review boards of Soroka and Rabin Medical Centers and was conducted in compliance with the Declaration of Helsinki, Good Clinical Practice guidelines, and local regulatory requirements. All patients provided written informed consent.

Background Liver cirrhosis (LC) is a common disease with varied primary causes and ethnic disparities. We aimed to determine the frequency, clinical characteristics, and outcomes of liver cirrhosis among the Arabs population in southern Israel.Methods This retrospective and follow-up study enrolled all patients diagnosed with liver cirrhosis at the gastroenterology and hepatology department or the internal medicine ward. Patient records were reviewed for demographic, clinical data, and mortality. Clinical primary outcomes were defined as death, hepatocellular carcinoma or liver transplantation.Results We included 820 patients 69 (8.4%) Arabs and 752 (91.6%) Jewish patients. Incidence of cirrhosis was much lower among Arabs patients, 5-10/100,000/year, compared with 20-40/100,000 per year in Jewish patients. Age at diagnosis was 42.6±16.9 years among Bedouins compared to 61±13 years (p

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.

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.

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.

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

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&ndash, 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&ndash, Meier&rsquo, s survival curve demonstrated a significantly higher cumulative endocrine morbidity in children born to mothers with HCV (log-rank test, p&thinsp, =&thinsp, 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&thinsp, 5.05, 95% CI: 1.625&ndash, 15.695, p = 0.005). Maternal HCV carrier status is an independent risk factor for long-term endocrine morbidity.

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

Unintentional weight loss (UWL) is a common symptom, particularly among older patients. In one site, patients with UWL have increased morbidity and mortality; in the other site, the prognosis of the patients is related to primary cause of the UWL. The differential diagnosis of the underlying diseases leading to UWL is broad and includes both malignant and nonmalignant gastrointestinal (GI) diseases, as well as endocrine, infectious, cardiopulmonary, and psychiatric disorders and side effects of medications. Patients with UWL should be investigated. The diagnostic approach to patients with UWL includes comprehensive medical history, physical examination, laboratory testing, imaging, and endoscopy. The imaging and endoscopy should be targeted according to the symptom, physical examination findings, and laboratory results. The treatment of UWL should be targeted to the primary disease causing weight loss. Non-pharmacologic nutrition intervention is the important treatment, and some pharmacologic treatment could be helpful in part of the patients.

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.