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There is an increasing interest in inappropriate proton pump inhibitors prescription (InPPIp), as defined by the National Institute for Clinical Excellence (NICE) guidelines.To evaluate the rate, trend over time and factors associated with InPPIp upon discharge from internal medicine departments.We evaluated patients discharged from internal medicine departments with a PPI prescription in 2014 and 2017 at an academic referral center according to a developed algorithm.A total of 3,982 patients were included (50.8% women, 74% ≥ 65 years). The rate of InPPIp was 44.3% (95% CI 42.8-45.9) for the entire cohort; 68.1% for subjects aged65 years and 36.0% for those aged ≥ 65 years (p0.001); 43.2% in 2014 and 45.6% in 2017 (p = 0.130). In a decision-tree analysis, after the exclusion of 448 patients with gastrointestinal indications, 89.4% (1,580/1,766) of all InPPIp cases were of patients without dual antiplatelet treatment (DAPT) and 8.6% (151/1,766) were of patients younger than 65 years, who were taking aspirin.The rate of InPPIp is high, especially among patients not receiving DAPT and young patients taking aspirin. Time trend analysis showed no improvement over time. Our algorithm may serve as an automated quality measuring tool to reduce InPPIp.

Current guidelines are inconsistent regarding the follow-up of patients with 1-2 diminutive (1-5 mm) non-advanced adenomas (DNAAs).To evaluate the risk of metachronous advanced neoplasia (AN), defined as cancer or advanced adenoma (AA), among patients with either normal colonoscopy or 1-2 DNAAs.A retrospective cohort study. Cohort I included 2,347 subjects with normal colonoscopy and 483 subjects with polypectomy of 1-2 DNAAs followed by colonoscopy. Cohort II included 11,881 subjects with normal colonoscopy and 1,342 subjects with 1-2 DNAAs followed through the cancer registry.In cohort I, the rate of AN, cancer and AA among the polypectomy group vs. normal colonoscopy was 5.0% vs. 2.5%, Hazard Ratio (HR) 2.96 (95%CI [Confidence Interval]1.86-4.78) for AN; 0.6% vs. 0.3%, HR 3.32 (95%CI 0.85-13) for cancer; 4.3% vs. 2.2% HR 2.91 (95%CI 1.75-4.86) for AA. In cohort II, cancer occurred in 0.4% of the polypectomy group and 0.2% of the normal colonoscopy group, HR 2.27 (95% CI 0.56-9.19).Compared to subjects with normal colonoscopy, subjects with polypectomy of 1-2 DNAAs, are at increased risk for AA when followed by colonoscopy, while the risk for cancer is non-significantly increased. Our findings suggest that patients with 1-2 DNNAs should be followed more tightly than patients with normal colonoscopy.

Intrahepatic cholestasis of pregnancy and preeclampsia are two major pregnancy complications. We aimed to investigate the association between intrahepatic cholestasis of pregnancy (ICP) and preeclampsia. Single-center retrospective study. Study group included 180 women (162 singletons and 18 twin gestations) who were diagnosed with ICP based on clinical presentation, elevated liver enzymes and bile acids. The reference group included 1618 women (1507 singletons and 111 twin gestations) who delivered during the study period, and were matched according to age, gravidity, parity and singleton or twin gestation. The incidence of ICP was 0.36%. The incidence of preeclampsia was higher in women with ICP compared to reference group (7.78% vs 2.41%, aOR, 3.74 95% CI 12.0–7.02, p

Postcolonoscopy colorectal cancer (PCCRC) can arise from missed cancers, missed premalignant lesions, incomplete resection, and new cancers with an accelerated route to cancer.1.

Sustained virological response (SVR) results in reduced incidence of hepatocellular carcinoma (HCC) and mortality among chronic hepatitis C (CHC) patients with advanced fibrosis. Since both advanced fibrosis and liver steatosis (LS) may coexist in CHC patients, we evaluated their individual effects on a composite outcome of all-cause mortality and HCC in CHC patients with SVR following direct-acting antivirals (DAA) treatment. We retrospectively evaluated inception cohort of 515 CHC patients who achieved SVR following treatment with DAA, with a mean follow-up of 24 months. Baseline liver fibrosis was assessed by transient elastography, and LS was validated by at least three independent ultrasonographic examinations. 211 of 515 patients (41%) had baseline LS. Patients with LS had a higher cumulative rate of all-cause mortality and HCC at 2 years of follow-up compared to patients without LS (15.75% and 2.79%, respectively, P < 0.001), although they did not have increased incidence of advanced fibrosis or cirrhosis. Consistently, multivariate analysis showed that LS was associated with a significant 7.5-fold increased risk of all-cause mortality and HCC (HR 7.51, 95% C.I 3.61-13.36, P < 0.001) even upon adjustment to components of the metabolic syndrome, whereas advanced fibrosis showed only a trend towards statistical significance (HR 2.32, 95% C.I 0.97-6.59, P = 0.06). In conclusion, LS is a major predictor of all-cause mortality and HCC in patients who achieved SVR following DAA treatment regardless of fibrosis stage. These patients should be rigorously screened for HCC.

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.

Background: Patients with nonalcoholic fatty liver disease (NAFLD) and with abnormal liver function tests (LFTs) most commonly present with elevated hepatocellular enzymes (H pattern), but a subset of patients is found to have elevated cholestatic enzymes (C pattern) or a mixed (M) pattern. Aims and Methods: To determine whether the epidemiologic background and comorbidities, as well as the degree of liver fibrosis, differ between NAFLD patients with different patterns of elevated LFTs by retrospectively analyzing data of 106 patients with a biopsy-proven diagnosis of NAFLD. The pattern of elevated LFTs was determined by adopting the “R-Ratio” formula commonly used for drug-induced liver injury. Results: Advanced fibrosis (F > 2) was found in 15 out of 48 (31.3%) patients with a C pattern of elevated LFTs as compared to 2 out of 44 (4.5%) in M patients and 2 out of 11 (18.2%) in H patients (p = 0.004). Group C patients are older and also had a higher prevalence of diabetes, a higher mean hemoglobin A1c, and a higher prevalence of hypertension, as well as a trend for a higher prevalence of hypertriglyceridemia. Conclusions: Using a simple formula incorporating routine LFTs can help to categorize NAFLD patients as low or high risk for advanced fibrosis stage and metabolic-associated comorbidities.

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.

OBJECTIVE To investigate associations between pre-gestational dyslipidemia, expressed as the ratio between triglycerides (TG) and high-density lipoprotein cholesterol (HDL), and adverse maternal and neonatal outcomes. METHODS A retrospective cohort analysis included women with TG and HDL measurements available up to 52 weeks before conception who delivered a singleton, non-anomalous infant. The study population was stratified according to a TG/HDL ratio cutoff of 3. Primary maternal outcomes included gestational diabetes or hypertensive disorders of pregnancy and neonatal outcomes after delivery before 37 weeks. RESULTS Among 5226 women included, 4446 (85.1%) had TG/HDL

Background Liver fibrosis predicts liver-related morbidity and mortality in patients with non-alcoholic fatty liver disease (NAFLD). Non-invasive scores correlate with the degree of liver fibrosis in these patients. Aims and methods To investigate the accuracy of noninvasive scoring systems in predicting long-term outcomes and cancer incidence of patients with NAFLD, we performed a single-center retrospective study of patients with biopsy proven NAFLD. Mean follow up period was 100 months. Outcomes included liver-related complications, hospitalizations, overall mortality and the development of any malignancies. Results 32 patients had advanced fibrosis (F3-F4) per biopsy at baseline and 121 patients had mild to moderate fibrosis (F0-F2). Both advanced histologic fibrosis stage as well as higher non-invasive scores predicted repeated hospitalizations and longer hospitalization stays. In a multivariate analysis, liver fibrosis (p = 0.002), FIB-4 score (p

Immunohistochemistry (IHC) testing for mismatch repair proteins (MMRP) in patients with colorectal cancer can be performed on endoscopic biopsy material or the surgical resection material. Data are continuing to accumulate regarding the deleterious effect of neoadjuvant chemoradiation on MMRP expression. However, despite continuing rise in the use of endoscopic biopsies for IHC, most pathology departments still use mainly the surgical materials for IHC testing. In this study we compared the quality of stains among 96 colon cancer subjects with paired endoscopic and surgical material available for MLH1, MSH2, MSH6, and PMS2 stains (96 × 4, yielding 384 paired stains). Each slide received both a quantitative score (immunoreactivity [0-3] × percent positivity [0-4]) and a qualitative score (absent; weak and focal; strong). The quantitative scores of all MMRP were significantly higher among the endoscopic material (P

Antithrombotic and antiplatelet therapy is widely used for primary and secondary prevention of venous and arterial diseases. Hemorrhage is a frequent complication in patients taking these drugs, especially during and post invasive procedures. There are several oral anticoagulants and antiplatelet drugs that differ from each other in the mechanism of action and metabolism, the need for drug monitoring, antidote, and the peri-procedural management of the drug. The risk of bleeding in gastrointestinal endoscopic procedures can be high (≥ 1.5%), depending on the procedure. Patients taking antithrombotic and antiplatelet therapy should undergo evaluation before endoscopic procedure in order to stratify their risk for bleeding during the procedure on the one hand, and the risk of thromboembolism- if the drug is interrupted, on the other hand. This review provides general recommendations and approaches for patients undergoing elective gastrointestinal endoscopic procedures while receiving antithrombotic or antiplatelet drugs.

Background & aims Liver fibrosis is the single most important prognostic factor in patients with non-alcoholic fatty liver disease (NAFLD). The predictive value of the AST to Platelet Ratio Index (APRI) score, originally developed for fibrosis assessment in hepatitis C virus (HCV) patients, is much less known in the context of NAFLD patients. Methods We retrospectively compared the performance of APRI and fibrosis 4 calculator (FIB-4) scores in NAFLD patients with documented liver biopsies, to their performance in chronic HCV patients. Results 153 patients with biopsy-proven NAFLD and 297 patients with biopsy-proven chronic HCV infection were included. The APRI score was a good predictor for advanced fibrosis in NAFLD patients (area under the ROC curve 0.8307) although it was modestly inferior as compared to the well-validated FIB-4 score (area under the ROC curve 0.8959). The predictive value of APRI score in NALFD patients was inferior as compared to its predictive value in HCV patients (area under the ROC curve of 0.8307 versus 0.9965). In contrast to FIB-4, APRI score was not a good discriminator between intermediate stages of fibrosis in NAFLD patients. Conclusions APRI and Fib-4 scores are reasonable tools to allocate NAFLD patients with advanced fibrosis. FIB-4 may better discriminate between intermediate fibrosis stages.

Maternal thyroid gland dysfunction may adversely affect pregnancy outcome. We aimed to examine the association between subclinical thyroid dysfunction, both hypothyroidism and hyperthyroidism, to adverse pregnancy outcome.Retrospective cohort study of all women with an available first trimester thyroid function testing and known pregnancy outcome, categorized to subclinical hypothyroidism, or hyperthyroidism and evaluated for complication during gestation and delivery.Four thousand five hundred and four women were included in the final analysis - 3231 were euthyroid, 73 (1.6%) were categorized as subclinical hyperthyroidism and 1200 (26.6%) had subclinical hypothyroidism. Low thyroid-stimulating hormone (TSH) levels, i.e. subclinical hyperthyroidism, correlates with higher rates of placental abruption and extremely low birth weight, below 1500 g. Also, the risk for preterm delivery prior to 34 gestational weeks is higher among women with subclinical hypothyroidism, with greater risk among those with a higher TSH level. (OR 1.81, 95% CI 1.0-3.28 for TSH 2.5-4.0 mIU/L and OR 2.33, 95% CI 1.11-4.42 for those with TSH 4 4.0 mIU/L).Subclinical hypothyroidism is associated with an increased risk for preterm delivery prior to 34 gestational weeks. Additionally, subclinical hyperthyroidism may also have a role in adverse pregnancy outcome - low birth weight and placental abruption - although this needs to be further explored.

To compare perinatal outcome of women after third trimester oral glucose tolerance test (GTT) following normal glucose challenge test (GCT) stratified by test results.Retrospective cohort study of women delivered in a tertiary, university affiliated medical center (2007-2012). Inclusion criteria were women with a normal 50 g GCT (140 mg/dl) followed by GTT, who delivered a live-born fetus28 gestational weeks. Gestational diabetes mellitus (GDM) was defined as ≥2 pathological values on GTT (Carpenter and Coustan's criteria). Perinatal outcome was stratified by GTT results: normal (if all 4 values were normal), single pathological value or GDM. Logistic regression analysis was utilized to adjust outcomes to potential confounders.Overall, 323 women met inclusion criteria. Of them, 277 (85.8%) had 4 normal values, 32 (9.9%) had a single pathological value and 14 (4.3%) had late-onset GDM. Infants of mothers diagnosed and treated as GDM had lower birth weights, compared to non-diabetics and those with a single pathological value GTT. Mothers with GTT ≥1 pathological values had statistically insignificant higher rates of cesarean delivery. However, this difference was not significant after adjustment to potential confounders.Treatment of late-onset GDM may lead to lower birthweights, presumably due to glucose control. No association was found with cesarean delivery or neonatal outcome.

Background and Aims The current guidelines for surveillance after polypectomy do not distinguish between diminutive (1-5 mm) and small (6-9 mm) polyps with low-grade dysplasia (LGD). We aimed to evaluate the risk for advanced neoplasia on follow-up colonoscopy. Methods We retrospectively analyzed 443 patients whose worst finding at index colonoscopy was polypectomy of 1 to 5 or 6 to 9 mm polyps with LGD and those who underwent a follow-up colonoscopy. Results During a mean follow-up of 32.0 months (interquartile range 13-48 months), advanced neoplasia was found in 26 patients (5.9%). Among all included patients (n = 443), advanced neoplasia was found in 13 of 310 patients (4.2%) of the 1- to 5–mm group versus 13 of 133 patients (9.8%) of the 6- to 9-mm group (hazard ratio [HR], 3.49; 95% confidence interval [CI], 1.6-7.6). Among the patients with 1 to 2 polyps resected (n = 313), advanced neoplasia was found in 8 of 231 patients (3.5%) of the 1- to 5-mm group versus 8 of 82 patients (9.8%) of the 6- to 9-mm group (HR 3.97; 95% CI, 1.47-10.7). Among the patients with ≥3 polyps resected (n = 130), advanced neoplasia was found in 5 of 79 patients (6.3%) of the 1- to 5-mm group versus 5 of 51 patients (9.8%) of the 6- to 9-mm group (HR 2.4; 95% CI, 0.7-8.36). Fair bowel preparation also was associated with the risk for advanced neoplasia at follow-up (HR 3.87, 95% CI, 1.70-8.82). Conclusions Our findings suggest that among patients with up to 9-mm adenomatous polyps, a polyp size of 6 to 9 mm, >2 polyps, and fair bowel preparation are associated with advanced neoplasia.

A 50-year-old man was investigated for painless jaundice. The histologic pattern on the liver biopsy study met the criteria of autoimmune hepatitis. Further clinical and laboratory investigation revealed multi-organ involvement, including Mikulicz's disease of the salivary glands and pancreatic insufficiency. The diagnosis of IgG4-related disease was suggested by a finding of elevated blood levels of IgG4. IgG4-related disease is an inflammatory fibrosing condition characterized by T-cell infiltration of affected organs, presence of IgG4-positive plasma cells, and elevated levels of IgG4 in serum. In the present case, the liver histopathology was compatible with one of several well-defined types of liver involvement in IgG4-related disease. IgG4-related disease may mimic malignant tumors of the biliary tract, pancreas, or liver. Undiagnosed patients may progress to end-stage fibrosis or undergo unnecessary surgery. It is highly important that IgG4-related disease be recognized because it is a treatable condition that responds well to steroids.