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Background and aim: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Given the anti-fibrotic and antioxidant properties of coffee, this systematic review and meta-analysis aims to provide updated results on the impact of coffee consumption on NAFLD incidence, prevalence, and risk of significant liver fibrosis. Methods: We conducted a comprehensive search in MEDLINE (OvidSP) and Scopus from January 2010 through January 2021. Relative risks for the highest versus the lowest level of coffee consumption were pooled using random-effects models. Heterogeneity and publication bias were evaluated using the Higgins’ I2 statistic and Egger’s regression test, respectively. Results: Eleven articles consisting of two case-control studies, eight cross-sectional studies, and one prospective cohort study were included in the meta-analysis. Of those, three studies with 92,075 subjects were included in the analysis for NAFLD incidence, eight studies with 9558 subjects for NAFLD prevalence, and five with 4303 subjects were used for the analysis of liver fibrosis. There was no association between coffee consumption and NAFLD incidence (RR 0.88, 95% CI 0.63–1.25, p = 0.48) or NAFLD prevalence (RR 0.88, 95% CI 0.76–1.02, p = 0.09). The meta-analysis showed coffee consumption to be significantly associated with a 35% decreased odds of significant liver fibrosis (RR 0.65, 95% CI 0.54–0.78, p < 0.00001). There was no heterogeneity (I2 = 11%, p = 0.34) and no evidence of publication bias (p = 0.134). Conclusion: This meta-analysis supports the protective role of coffee consumption on significant liver fibrosis in patients with NAFLD. However, the threshold of coffee consumption to achieve hepatoprotective effects needs to be established in prospective trials.

Background This study aimed to compare fecal calprotectin (FC) levels with other commonly used parameters as part of patient care during evaluation for inflammatory bowel disease (IBD). Methods We recruited adult IBD patients with ulcerative colitis (UC) and Crohn’s disease (CD) and compared the results of the patient’s biopsy results (i.e., inflamed versus noninflamed) for six sites (i.e., ileum, ascending colon, transverse colon, descending colon, sigmoid colon, rectum) with concentrations of C-reactive protein (CRP), total leucocytes and fecal calprotectin (FC). Results We found that FC was significantly elevated in a concentration-dependent manner that correlated with the number of active inflammation sites reported in biopsy. Although CRP and leucocyte measurements trended upwards in line with inflammation reported from biopsy, the results were highly variable and highlighted poor reliability of these biomarkers for indicating IBD inflammation. Conclusions These results strongly suggest that FC correlates best with biopsy reports and is a superior marker than CRP and leucocytes.

Decompensated cirrhosis due to nonalcoholic steatohepatitis (NASH), and autoimmune liver diseases (AILD) are the most common indications for liver transplantation (LT). AILD include autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). NASH and AILD share some peculiarities as they can recur in the new graft, compromising the quality of life, and graft and patient survival. De novo NASH or AIH connotes the development of these liver diseases in patients transplanted for other indications. The diagnosis of recurrent or de novo liver disease usually requires a liver biopsy aside from recurrent PSC, which can be diagnosed with compatible imaging studies and exclusion of other causes of biliary strictures. The treatment of recurrent NASH is lifestyle modifications aiming for weight loss. Recurrent and de novo AIH is usually treated with corticosteroids with or without azathioprine. Recurrent PBC should be treated with ursodeoxycholic acid. There are no proven treatment options for recurrent PSC. Patients with graft failure should be considered for repeat LT. Future investigations should use standardized diagnostic criteria for each disease, seek diagnostic biomarkers, and evaluate treatments that improve outcomes.

Graft-versus-host disease (GVHD) is a complication of hematopoietic stem cell transplantation that frequently affects the gastrointestinal (GI) tract. The best biopsy sites to establish the diagnosis have not been clearly established. To determine the best sites for obtaining biopsies in evaluating GI GVHD. All cases of biopsy-proven GI GVHD (GVHD+) were isolated from a pathology database over a 2-year period at a single tertiary center (n = 46). Demographic, clinical, and endoscopic data were extracted. For comparison, 46 consecutive GVHD-negative cases (GVHD−) were obtained. Sensitivities in diagnosing GVHD in the upper and lower GI tract were calculated. In the GVHD− group, they were commonly investigated with an esophagogastroduodenoscopy (EGD) (60 vs. 22 % in the GVHD+ group, p

Alpha-fetoprotein (AFP) is a common tumor marker for hepatocellular carcinoma (HCC). We report a unique case of an AFP-producing gastric cancer in an elderly man with known chronic hepatitis B (HBV) and a markedly elevated AFP. Thorough diagnostic imaging failed to reveal a HCC, but a gastric adenocarcinoma was found on endoscopy. After successful resection, the serum AFP normalized. On histopathologic examination, the cancer demonstrated focal positive staining for AFP, in keeping with a hepatoid gastric adenocarcinoma. Endoscopy should be considered in clinical situations where increased serum AFP is detected but no HCC is found.

BACKGROUND: Although the fecal occult blood test (FOBT) was developed for colorectal cancer screening in the outpatient setting, it continues to be used among hospitalized patients. No previous study has evaluated the knowledge, beliefs and attitudes of practicing physicians on the use of FOBT among hospitalized patients and compared practices among physicians with different medical specialty training.OBJECTIVE: To survey physicians in the Winnipeg Regional Health Authority (WRHA) and Canadian gastroenterologists (GIs) on the use of FOBT in hospitals.METHODS: A survey was distributed by e-mail to internists (n=198), emergency medicine (EM) physicians (n=118), general surgeons (n=47) and family medicine (FM) physicians with admitting privileges (n=29) in the WRHA. Canadian GIs were surveyed through the membership database of the Canadian Association of Gastroenterology (CAG) (n=449). The survey included items regarding demographics of the respondents and their current use of FOBT in hospitals.RESULTS: Response rates ranged from 18% among CAG members to 69% among FM physicians in the WRHA. General internal medicine, general surgeon and GI respondents were less likely to order a FOBT and less likely to believe that an FOBT was useful in assessing emergency room or hospitalized patients when compared with FM and EM respondents (PCONCLUSIONS: The present survey suggests that FOBTs are commonly used in hospitals by EM and FM physicians for indications such as anemia and black stools.

INTRODUCTION AND AIM. The effect of the new direct acting antiviral drugs (DAAs) for chronic hepatitis C (HCV) on glycemic control is unknown. MATERIALS AND METHODS. We conducted a retrospective cohort study of patients who were treated for chronic HCV with direct-acting antiviral medications at a single academic institution between May 2013 and April 2016. Univariate analysis was performed comparing subjects pre- and post-treatment. RESULTS. One hundred seventy-five consecutive adult patients were treated for chronic HCV and met enrollment criteria. The majority (80.8%) were genotype 1 and overall cohort sustained virologic response at week 12 (SVR12) was 97.8%. Thirty-one (18.5%) had diabetes mellitus (DM); twenty-six had pre- and post-treatment HbA1c values. Of these, 76.9% were male and 61.5% had cirrhosis. Ninety-six percent were prescribed sofosbuvir-based therapy and all but one (96.8%) achieved SVR12. Three patients were started on treatment despite meeting the definition for poorly controlled DM (HbA1c > 9 mg/dL). There was no significant difference when comparing pre-treatment (7.36 mg/dL, 95% CI 6.55-8.16) to post-treatment HbA1c (7.11 mg/dL, 95% CI 6-34-7.88, p = 0.268). Thirty-one percent of subjects required dose escalation or the initiation of insulin based therapy during treatment. DISCUSSION. Although chronic HCV is as associated with exacerbation of insulin resistance. our results showed HbA1c to be unaffected by eradication chronic HCV with DAA in diabetic patients with and without cirrhosis. Paradoxically, almost 1/3 of patients required escalation of anti-diabetic therapy during treatment. Long-term studies are warranted to understand the relationship between HCV viral eradication and insulin metabolism.

Background Sessile serrated adenomas (SSAs) and hyperplastic polyps (HP) are the two most common types of serrated colon polyps (SCPs). SSAs are suspected to be the precursor lesions for many colorectal cancers, and hence there is an emphasis on their detection and removal. On the other hand, recent guidelines such as those from the European Union consider HPs of limited clinical significance. Objective Evaluate the reclassification rate of recently diagnosed HPs to SSAs and the predictors of such reclassification. Design, Setting, Intervention, Main Outcome Measurements The provincial pathology database was searched for all colon polyps reported in the 6 pathology laboratories in the city of Winnipeg in 2009. All retrieved pathology slides for previously reported right-sided HPs and a 20% random sample of left-sided HPs were reassessed by two pathologists with a special interest in GI pathology. Polyp size, colon location, and age and sex of the study participants were evaluated as potential predictors of reclassification. Results A total of 4096 pathology reports by 25 different pathologists were reviewed. Twenty percent of the polyps were reported as SCPs. Seventeen percent of right-sided previously reported HPs and 20% of those >5 mm were reclassified as SSAs. Size >5 mm (odds ratio [OR] 4.2; 95% confidence interval [CI], 1.5-11.4) and location in the right side of the colon (OR 4.7; 95% CI, 1.4-15.4) were independent predictors of reclassification. Limitations Retrospective review. Conclusion A significant proportion of recently reported right-sided HPs may be SSAs. Surveillance recommendations for SCPs should consider the size and location of SCPs and not just the reported type.

Objective.To evaluate the prevalence of bone marrow lesions (BML) and their association with pain severity in a population-based cohort of symptomatic early knee osteoarthritis (OA).Methods.Subjects with knee pain (n = 255), age 40–79 years, were evaluated by radiograph and magnetic resonance imaging (MRI) and classified into OA stages: no OA (NOA), preradiographic OA (PROA), and radiographic OA (ROA). BML were graded 0–3 (none, mild, moderate, severe) in 6 regions and defined as (1) BMLsum = the sum of 6 scores; and (2) BMLmax = the worst score at any region. Pain was assessed by the Western Ontario and McMaster Universities OA Index (WOMAC). Linear regression analysis was completed to assess the association of Total WOMAC Pain (primary outcome) versus BMLsum or BMLmax. Secondary outcomes were WOMAC Pain on Walking and WOMAC Pain on Climbing Stairs. All analyses were adjusted for age, sex, body mass index, OA stage, joint effusion, and meniscal damage.Results.BML were present in 11% of NOA, 38% of PROA, and 71% of ROA subjects (p < 0.001). No association was seen for BMLsum or BMLmax versus Total WOMAC Pain or Pain on Walking. However, BMLsum was associated with Pain on Climbing Stairs [regression coefficients (RC) = 0.09, 95% CI 0.00–0.18]. BMLmax was associated with Pain on Climbing Stairs, with the strongest association for severe BML (RC 0.60, 95% CI 0.04–1.17).Conclusion.BML were present in 38% of PROA and 71% of ROA subjects in this symptomatic knee cohort. BML were significantly associated with Pain on Climbing Stairs but not Total WOMAC or Pain on Walking.

In Canada, the seroprevalences of the hepatitis B virus (HBV) and the hepatitis C virus (HCV) are believed to vary significantly among different ethnic groups and at-risk populations. Data regarding the prevalence of HBV and HCV in Southeast Asian Canadians may vary significantly from the general population. Because this population may be less likely to participate in epidemiological studies, it is possible that HBV and HCV seroprevalences are under-reported. The authors of this study correlated questionnaire answers regarding vaccination status to serological profiles collected from an Asian health fair in British Columbia to assess the seroprevalences of HBV and HBC in this population., BACKGROUND: The seroprevalences of hepatitis B virus (HBV) and hepatitis C virus (HCV) are 0.4% and 0.8%, respectively, in Canada, but varying rates have been reported in different populations. OBJECTIVES: To determine the seroprevalences of HBV and HCV among attendees of an Asian health fair in the Lower Mainland, British Columbia, as well as to correlate questionnaire answers regarding vaccination status to serological profiles. METHODS: Attendees at an Asian health fair were invited to participate in the present study on a voluntary basis. They provided answers to a questionnaire including ethnicity and vaccination status. Blood was then drawn for HBV and HCV serology. Active HBV was defined as HBV surface antigen (HBsAg) positive while HCV seroprevalence was defined as HCV antibody reactive. Previous exposure to HBV was defined as HBV core antibody (anti-HBc) positive and HBsAg negative. Nonimmunity was defined as anti-HBc negative and HBV surface antibody negative. Only those with correct demographic information matched to serological results were included in the study. RESULTS: There were 192 consenting attendees of the fair, of whom 112 were included in the study. Of the participants, 91% were Chinese. Active HBV infection was found in three participants (2.7% [95% CI 0.6% to 7.6%]) and HCV infection was found in two participants (1.8% [95% CI 0.2% to 6.3%]). More than 40% of participants had been previously exposed to HBV (42% [95% CI 33% to 51%]). Almost 20% demonstrated nonimmunity to HBV (19% [95% CI 12% to 27%]). There was significant discordance when questionnaire answers regarding vaccination status were compared with serological profiles. CONCLUSION: The seroprevalences of HBV and HCV in this cohort were 2.7% and 1.8%, respectively – higher than nationally reported rates. Our results highlight that the lack of knowledge of HBV infection and vaccination status remains a significant clinical issue in the Asian community of British Columbia.

BACKGROUND: The fecal occult blood test (FOBT), widely used as a colorectal cancer screening tool, continues to be used in hospitalized patients. However, the utility of this test for hospitalized patients is unclear.OBJECTIVE: To assess FOBT use in a large urban regional health authority.METHODS: Reports of all FOBTs performed between April 1, 2011 and March 30, 2012 from two academic and four community hospitals in Winnipeg (Manitoba) were extracted. Of 650 hospitalizations with a positive FOBT result and 1254 with a negative FOBT result, random samples of 230 and 97 charts, respectively, were reviewed. Information including demographics, admission diagnos(es), indication(s) for ordering the FOBT and clinical management was extracted.RESULTS: Thirty-four percent (650 of 1904) of hospitalizations with an FOBT had a positive FOBT result. Family medicine physicians ordered approximately one-half of the reviewed FOBTs. The most common indication for ordering an FOBT was anemia. Of those with a positive FOBT, 66% did not undergo further gastrointestinal investigations. Of those with a positive FOBT and overt gastrointestinal bleeding and/or melena who underwent endoscopy, 60% had their endoscopy performed before the FOBT result being reported while 38% underwent their endoscopy ≥3 days after the stool sample was collected. There were minimal differences in clinical practices between academic and community hospitals.CONCLUSIONS: The present study suggests that FOBT results in hospitalized patients may have little beneficial impact on clinical management. Hospital laboratories may be better served in directing resources to other tests.

CMI-206, trans -2[3-methoxy-4-propoxy-5(N′-butyl-N′-hydroxyureidyl)phenyl]-5-(3,4,5-trimethoxyphenyl) tetrahydrofuran, was synthesized and was found to antagonize PAF receptor binding and inhibit 5-lipoxygenase activity both in vitro and in vivo .

Objective : The primary aim of DNA quantification in forensic DNA analysis is to determine and optimize the amount of DNA for the downstream profiling analysis. Additionally, it may be used as a parameter for the cut-off of the subsequent profiling, especially for touch DNA samples collected from property crime scenes which often contain low amount of DNA and yield no profiles. The choice of quantification kit should have both high accuracy and precision. This work aims to examine the latter of five selected commonly used real-time quantitative PCR (qPCR) kits, namely, Applied Biosystems Quantifiler® kit, Quantifiler® Y kit, Quantifiler® Duo kit, Promega Plexor® HY system and QIAGEN Quantiplex HYres kit, and to seek for a qPCR system fitted for the purpose of initial screening of touched DNA evidence for profiling. Material and Methods : In this work, we first tested the precision of the five selected qPCR kits using their respective DNA standard and human blood samples as substrates. Subsequently, we compared the capability of Quantiplex in predicting the presence of DNA with that of Quantifiler when applying a cut-off threshold of 0.0049 ng/µL and 0.023 ng/µL, i.e. their respective lowest detection limit, with reference to DNA typing analysis. Results : Our results demonstrated that Quantiplex exhibits a higher precision and consistency than the others, especially at low DNA concentration i.e. 0.016 to 0.023 ng/µL. We also showed that, by using a total of 332 simulated touch DNA samples, Quantiplex is a fairly reliable predictor of the AmpFlSTR® Identifiler® profiling results. Conclusion : Quantiplex can be employed as a cost-effective screening of samples of volume crime cases. [ 268 words ]

Two distinct biochemical signals are delivered by the CD95/Fas death receptor. The molecular basis for the differential mitochondrially independent (type I) and mitochondrially dependent (type II) Fas apoptosis pathways is unknown. By analyzing 24 Fas-sensitive tumor lines, we now demonstrate that expression/activity of the PTEN tumor suppressor strongly correlates with the distinct Fas signals. PTEN loss-of-function and gain-of-function studies demonstrate the ability to interconvert between type I and type II Fas pathways. Importantly, from analyses of Bcl-2 transgenic Pten(+/-) mice, Pten haploinsufficiency converts Fas-induced apoptosis from a Bcl-2-independent to a Bcl-2-sensitive response in primary thymocytes and activated T lymphocytes. We further show that PTEN influences Fas signaling, at least in part, by regulating PEA-15 phosphorylation and activity that, in turn, regulate the ability of Bcl-2 to suppress Fas-induced apoptosis. Thus, PTEN is a key molecular rheostat that determines whether a cell dies by a mitochondrially independent type I versus a mitochondrially dependent type II apoptotic pathway upon Fas stimulation.

Glucosamine (GS) and chondroitin sulfate (CS) are common over-the-counter (OTC) supplements used in the treatment of osteoarthritis. These medications are seemingly safe, but there are increasing reports of hepatotoxicity with these supplements. We reported a unique case of drug-induced cholestasis caused by GS and CS in a combination tablet. The etiology of the jaundice was overlooked despite extensive investigations over a three-month period. Unlike drug-induced hepatocellular injury, drug-induced cholestatic jaundice with GS and CS has only been reported twice before. This case emphasizes the importance of a complete medication history, especially OTC supplements, in the assessment of cholestasis.

Epibatidine, an alkaloid isolated from skin of the poison frog, Epipedobates tricolor, has been shown to be a very potent analgesic with a non-opioid mechanism of action. We found that epibatidine was about 120 times more potent and has longer duration than nicotine in analgesia, which could be antagonized by pretreatment with mecamylamine. Furthermore, epibatidine competed with high affinity (IC50 = 70 pM, Ki = 43 pM) for [3H]cytisine binding in rat brain preparations. These results indicated that the analgesic activity of epibatidine is attributed to its unique property as the most potent nicotinic acetylcholine receptor agonist.