EXPRESS: Early Onset Colorectal Cancer, not just the Age: data from a large health organization.

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.

Glucagon-like peptide-1 receptor agonists significantly affect the quality of bowel preparation for colonoscopy.

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.

Sex Differences in Colonoscopy Indications and Findings: Results from a Large Multicenter Database.

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.

The impact of glucagon-like peptide-1 receptor agonist on the gastric residue in upper endoscopy.

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.

Hiatal hernia: risk factors, and clinical and endoscopic aspects in gastroscopy.

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.

Evaluation of Acute Terminal Ileitis in Hospitalized Patients: Development of a Predictive Model to Distinguish Crohn's Disease from Other Etiologies.

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.

Epidemiology and risk factors for angiodysplasias of the upper and lower gastrointestinal tract: A large population-based study.

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.

A Patient-Centered Approach to Communication during Endoscopic Procedures: The Importance of Providing Information to Patients.

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, R2 = 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.

Nonalcoholic Fatty Liver Disease and Ethnicity: Lessons Learned from the Arab Population in Israel.

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.

Colorectal cancer screening at age 45 years in Israel: Cost-effectiveness and global implications.

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.

The benefit of pancreatic cancer surveillance in carriers of germline BRCA1/2 pathogenic variants.

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.

Dominantly inherited micro-satellite instable cancer - the four Lynch syndromes - an EHTG, PLSD position statement.

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.

Liver Fibrosis Regression and Associated Factors in HCV Patients Treated with Direct-Acting Antiviral Agents.

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.

Colorectal cancer among inflammatory bowel disease patients: risk factors and prevalence compared to the general population.

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.

Hepatitis C Elimination: Opportunities and Challenges in 2023.

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.

Ethnic Issues and Disparities in Inflammatory Bowel Diseases: What Can We Learn from the Arab Population in Israel?

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.

Comorbidities and Malignancy among NAFLD Patients Compared to the General Population, A Nation-Based Study.

(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.

Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database.

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.

High prevalence of MUTYH associated polyposis among minority populations in Israel, due to rare founder pathogenic variants.

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.

Comorbidities and Outcomes among Females with Non-Alcoholic Fatty Liver Disease Compared to Males.

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.