European Journal of Gastroenterology & Hepatology

Thromboelastography versus standard coagulation testing in the assessment and reversal of coagulopathy among cirrhotics: a systematic review and meta-analysis The utility of thromboelastography/thromboelastometry currently has unvalidated clinical benefit in the assessment and reversal of coagulopathy among cirrhotic patients as compared to standard coagulation testing. A novel systematic review and meta-analysis was conducted in order to assess pooled outcome data among patients receiving thromboelastography/thromboelastometry as compared to standard coagulation testing. As compared to standard coagulation testing, there was a significant reduction in the number of patients requiring pRBC, platelet, and fresh frozen plasma transfusions among thromboelastography/thromboelastometry group with pooled OR 0.53 (95% CI 0.32–0.85; P = 0.009), 0.29 (95% CI 0.12–0.74; P = 0.009), and 0.19 (95% CI 0.12–0.31; P < 0.00001), respectively. Similarly, there was a significant reduction in number of pRBC, platelet, and fresh frozen plasma units transfused in the thromboelastography/thromboelastometry group with pooled MD −1.53 (95% CI −2.86 to −0.21; P = 0.02), −0.57 (95% CI −1.06 to −0.09; P = 0.02), and −2.71 (95% CI −4.34 to −1.07; P = 0.001), respectively. There were significantly decreased total bleeding events with pooled OR 0.54 (95% CI 0.31–0.94; P = 0.03) and amount of intraoperative bleeding during liver transplantation with pooled MD −1.46 (95% CI −2.49 to −0.44; P = 0.005) in the thromboelastography/thromboelastometry group. Overall, there was no significant difference in mortality between groups with pooled OR 0.91 (95% CI 0.63–1.30; P = 0.60). As compared to standard coagulation testing, a thromboelastography/thromboelastometry-guided approach to the assessment and reversal of cirrhotic coagulopathy improves overall number of patients exposed to blood product transfusions, quantity of transfusions, and bleeding events.

Effect of alpha agonists on the prevention of postparacentesis circulatory dysfunction in patients with refractory or recurrent ascites: a meta-analysis Postparacentesis circulatory dysfunction (PCD) is one of the commonest complications encountered in patients with refractory or recurrent ascites. Alpha agonists like clonidine and midodrine have been studied in various clinical trials for the prevention of PCD with varied results. This meta-analysis was done to evaluate the effect of alpha agonists on prevention of PCD in patients of refractory or recurrent ascites. A standard meta-analysis protocol was developed and registered in the International Prospective register of Ongoing Systematic Reviews. After performing a comprehensive literature search in MEDLINE, Cochrane, and International Clinical Trial Registry Platform, reviewers assessed eligibility and extracted data from five relevant articles. Preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines were followed in selection, analysis, and reporting of findings. Random effects model was used to estimate effect size. Quality assessment was done using the risk of bias assessment tool and meta-regression for probable variables affecting effect size. The random effect model analysis revealed a mean reduction of 2.63 ng/ml/h (95% CI: −4.46 to −0.8; P = 0.005) in plasma renin activity (PRA), mean reduction of 255.37 pg/ml (95% CI: −441.23 to −69.5; P = 0.007) in plasma aldosterone levels, and a mean increase of 0.14 mg/dl (95% CI: −0.13 to 0.41; P = 0.32) in serum creatinine levels favouring add-on alpha agonist group. In meta-regression, change in PRA (P = 0.79) and plasma aldosterone (P = 0.93) did not show a significant difference due to variation in follow-up duration across various studies. Add-on alpha agonists bring about a significant reduction in PRA and plasma aldosterone compared to standard medical treatment and thus prevents the occurrence of PCD in patients with refractory or recurrent ascites.

Validation of the English version of the difficulty of life scale for patients with ulcerative colitis Objective Patients with ulcerative colitis have abdominal symptoms that affect their quality of life in multiple ways. The difficulty of life scale was developed in Japan to measure these patients’ degree of daily difficulties. We aimed to assess this scale for English-speaking patients and to evaluate its validity and reliability. Methods The original Japanese version of the difficulty of life scale was translated into English and administered to 100 consecutive outpatients with ulcerative colitis at a university hospital in London. Medical information was obtained from participants’ medical records. Factor validity, construct validity using the Short Inflammatory Bowel Disease Questionnaire, known group validity with clinically different groups, internal consistency and test-retest reliability were analyzed statistically. Results Three factors were extracted by exploratory factor analysis, as in the original scale. The construct validity was supported by the association between the Difficulty of Life Scale and Short Inflammatory Bowel Disease Questionnaire scores (Pearson’s correlation coefficient: 0.73–0.83). Patients with visible bleeding or who were prescribed corticosteroids reported significantly greater difficulty than did those without them, demonstrating a significant effect size. The scaling success rate was acceptable. Internal consistency was confirmed (Cronbach’s alpha: 0.68–0.89). The intraclass correlation coefficients were >0.75, thus confirming the test–retest reliability. Conclusion The English version of the difficulty of life scale is a reliable and valid disease-specific scale for ulcerative colitis. It can be used to communicate the challenge of daily living between patients with this long-term condition and health care providers.

Clostridium difficile caused changes in fatty acids profile and resolvin D1 content in plasma of infected patients Objectives Clostridium difficile infection (CDI) is an acute gastrointestinal infection caused by anaerobic, toxin-producing bacteria. During the course of CDI, there is a general inflammatory state. In order to gain a deeper understanding of the role of fatty acids (FAs) in the pathogenesis of acute infection we analyzed their plasma content in both patients with CDI and controls. Methods The study groups included 40 patients with CDI and 40 healthy volunteers. Plasma FA content was analyzed by gas chromatography, resolvin D1 (RvD1) level using ELISA assay, and we assessed the white blood cell (WBC) count, neutrophil count and C-reactive protein (CRP) level. Results Patients with CDI were characterized by significantly higher values of WBC, neutrophils, platelets and CRP compared with the control group. The saturated FA index was statistically higher and total n-3 FA was significantly decreased in the plasma of CDI patients as compared with the control group. RvD1 content was significantly higher in the control group as compared with patients with CDI. Conclusion In patients with good outcomes, we probably observed the effective resolution of inflammation, as reflected in n-3 FA metabolism and their significant decrease in plasma. This may indicate the therapeutic role of n-3 FA in CDI infection.

Whipple’s disease: diagnosis and predictive factors of relapse Background Whipple’s disease is a very rare disease needing a long-term treatment. The most frequent symptoms are recurrent arthralgia or arthritis, chronic diarrhea, abdominal pain, and weight loss. Objectives In this article, we have highlighted the main clinical features and diagnostic procedures that lead to the diagnosis and comment on the clinical response, treatment, and the factors of relapse. Methods Subjects were recruited from the Internal Medicine and Rheumatologic Departments of an University Hospital from November 1997 to January 2016. Overall, 12 subjects were finally diagnosed. Results Mean age was 54.3 years (age range: 30–81), with more male patients (58.3%). Almost all patients had articular symptoms and impaired general condition (91.7%); and a majority had digestive symptoms (75%). Regardless of the symptoms, the most efficient diagnostic tools were the PCR screening on the gastrointestinal biopsies and saliva (83.3 and 72.7% positive results, respectively). More than half of the patients relapsed (55.6%). The relapsing patients were older [63.2 (44–81)] and mostly male with a majority (60%) of digestive symptoms and a delayed diagnosis. Conclusions In current practice, it is highly difficult to diagnose Whipple’s disease. In order to decrease the delay between the first symptoms and the diagnosis, effective tools such as saliva and stools PCR should be used because higher delays of diagnosis lead to a higher number of relapses.

High rates of serology testing for coeliac disease, and low rates of endoscopy in serologically positive children and adults in Israel: lessons from a large real-world database Background: Although coeliac disease is common worldwide, little is known regarding screening patterns in unselected populations, and on real-life adherence to professional guidelines for coeliac disease diagnosis and management. Objective: To explore current practices in the diagnosis and management of coeliac disease, using data from a large Health Maintenance Organization in Israel that covers 54% of the population. Methods: A population-based electronic database of about 4.5 million individuals was reviewed during the period of 1 January 2008 to 31 December 2015. Rates and results of coeliac disease serology testing and endoscopy procedures were examined. Subgroup analysis was performed by age, sex, ethnicity and socioeconomic status. Results: Coeliac disease serology cumulative testing rate was 17.1% and 8.9% in the paediatric and adult population, respectively. The cumulative incidence of positive coeliac disease serology was 0.45% in children and 0.17% in adults, and was associated with age, sex, ethnicity and socioeconomic status sub-groups (P-value < 0.01). Gastrointestinal endoscopies were not subsequently performed in 44.1% of children and 47.1% of adults with positive coeliac disease serology. Within the study period, 36% of children and 56% of adults never achieved coeliac disease serology normalization. Conclusion: In a large real-life database, screening for coeliac disease was common. However, confirmatory intestinal biopsies were under-utilized, and coeliac disease serology often remained positive over a long period time in both children and adults.

Developing a better biopsychosocial understanding of pain in inflammatory bowel disease: a cross-sectional study Objective Pain is frequently reported by patients with inflammatory bowel disease (IBD). Pain in IBD is not fully explained by disease activity or other clinical findings, and a recent systematic review suggested that psychosocial factors have an important role in IBD-pain. The aim of this study was to investigate psychosocial factors associated with pain in IBD. Methods 297 adults (>16 years) with IBD were recruited from outpatient clinics (n = 114) and online (n = 183). Participants completed validated questionnaires assessing pain and potential emotional, cognitive and behavioural correlates. Socio-demographic and clinical factors including disease activity were also recorded. Results 243 (81.8%) of participants reported pain. Of these 243, mean age was 36 years; 153 (63%) had Crohn’s disease, 90 (37%) had ulcerative colitis, and 165 (67.9%) were female. 62.6% reported mild, 31.6% moderate and 5.8% severe pain. 40.3% of participants with pain met established criteria for chronic pain and 18.5% reported opioid use. Female gender, smoking, surgery and steroid use were associated with greater pain severity. Psychosocial factors associated with pain-related interference included depression, catastrophising, fear avoidance, lower self-efficacy and worse mental well-being. Regression models explained 45.6% of the variance in pain severity and 49.7% of pain interference. Psychosocial factors explained 9.5% and 24% of this variance respectively when controlling for demographic and clinical variables. Conclusions Pain in IBD is significantly associated with cognitive and behavioural factors as well as low mood. This study contributes to a biopsychosocial understanding of pain in IBD and identifies important targets for future interventions.

MSH6 gene pathogenic variant identified in familial pancreatic cancer in the absence of colon cancer Objectives Lynch syndrome is characterized by pathogenetic variants in the mismatch repair genes and autosomal dominant inheritance with incomplete penetrance. Lynch syndrome is characterized by colorectal and, with lesser and variable extent, extracolonic cancers. We describe a family with MSH6-dependent Lynch syndrome and familial pancreatic cancer and other tumours (gastric and endometrial), in the absence of colorectal neoplasia. Methods Patients were analysed by sequencing, Next Generation or Sanger, to identify germinal pathogenic variants in hereditary cancer genes. Results We identified the MSH6 gene pathogenic variant c.2194C>T, p.(Arg732Ter) in a family with hereditary pancreatic cancer without diagnosed cases of colorectal adenocarcinoma. Seven family members were affected by the MSH6 pathogenic variant. Three had pancreatic adenocarcinoma at 65, 57 and 44 years; one had endometrial cancer at 36 years. None of the remaining three subjects (75, 45 and 17 years old) had developed any cancer yet. Conclusions Lynch syndrome should be suspected in families with familial pancreatic cancer, even in the absence of colon cancers. Specifically, our observation supports the association between the MSH6 c.2194C>T pathogenic variant and extracolonic tumours and it suggests that MSH6 pathogenic variants are associated with familial pancreatic cancer more frequently than assumed.

Systematic analysis of therapeutic patterns and healthcare use during 12 months before inflammatory bowel disease-related hospitalization in Switzerland Background and aims Given the lack of data, we aimed to systematically analyze therapeutic patterns and health resource utilization in the year before inflammatory bowel disease (IBD)-related hospitalization. Methods Based on claims data of the Helsana health insurance group, therapy patterns and health resource utilization were assessed, and costs reimbursed by mandatory basic health insurance were calculated during a one-year period before an index hospitalization between 1 January 2013 to 31 December 2015. Results We analyzed 344 IBD patients (140 ulcerative colitis [40.7%], 204 Crohn’s disease [59.3%]). Drug regimens applied in the year before index hospitalization were as follows: no IBD drugs (43.6% ulcerative colitis, 43.1% Crohn’s disease); 5-ASA (45.7% ulcerative colitis, 19.1% Crohn’s disease); local steroids (17.9% ulcerative colitis, 17.6% Crohn’s disease); systemic steroids (38.6% ulcerative colitis, 29.4% Crohn’s disease); immunomodulators (10.7% ulcerative colitis, 18.1% Crohn’s disease); biologics (10% ulcerative colitis, 24% Crohn’s disease); and calcineurin inhibitors (2.1% ulcerative colitis, 1.5% Crohn’s disease). Forty-five percent of ulcerative colitis patients and 31.4% of Crohn’s disease patients had no diagnostic procedures [computed tomography (CT), MRI, radiograph, sonography, colonoscopy, and calprotectin] in the year before hospitalization. Total annual health care costs before index hospitalization was EUR 4060 (interquartile range (IQR) 2360–7390) for ulcerative colitis and EUR 4900 (IQR 1520–14 880) for Crohn’s disease patients, respectively. Conclusions Over 40% of ulcerative colitis and Crohn’s disease patients did not receive any treatment in the year before index hospitalization. Efforts should be launched to timely diagnose and adequately treat IBD outpatients.

Environmental exposures and the risk of inflammatory bowel disease: a case-control study from Saudi Arabia Background and aims: Environmental exposures play a key role in inflammatory bowel disease pathogenesis. The incidence of IBD has increased in the Arabic Peninsula with a disease phenotype that seems to differ from that of Western countries. We aimed to examine the association between environmental exposures and the risk of IBD in Saudi Arabia. Patients and methods: We performed a case-control study comparing Saudi individuals with confirmed IBD and healthy controls. All subjects completed a detailed questionnaire that included data on demographics, clinical characteristics, childhood exposures, socioeconomic exposures, and parent factors. Associations between risk factors and inflammatory bowel disease were investigated through univariate and multivariate regression analysis. Results: The analysis included 82 patients and 160 controls. According to multiple logistic regression analysis, holding a University/Master degree education level or a PhD degree reduced the risk of inflammatory bowel disease by 10-fold (odds ratio = 0.1, confidence interval = 0.1–0.3), receiving seven vaccines or more during childhood increased the risk of developing inflammatory bowel disease by nine-fold (odds ratio = 9.2, confidence interval = 2.9–29.4) and maternal use of oral contraceptives pills increased the risk by 11-fold (odds ratio = 11.4, confidence interval = 3.3–39.3). Conclusion: Inflammatory bowel disease occurrence was independently associated with education level, number of childhood vaccination, and maternal use of oral contraceptives pills in this population of inflammatory bowel disease patients. This is the first study examining environmental exposures as risk factors for inflammatory bowel disease in Saudi Arabia.