Important relation between self-efficacy, sense of coherence, illness perceptions, depression and anxiety in patients with inflammatory bowel disease.

INTRODUCTION: Anxiety and depression are common disturbances in patients with inflammatory bowel diseases (IBD), and were found to impact the disease course. Illness perceptions (IPs), self-efficacy (SE) and sense of coherence (SOC) are important psychological functions, used by the individual to cope with his chronic disease. AIMS: to investigate the association of IP, SE and SOC on anxiety and depression among patients with IBD. PATIENTS AND METHODS: Patients filled questionnaires including: demographic, socioeconomic and clinical features. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale. IP, SE and SOC were assessed using the Brief Illness perception Questionnaire, IBD-SE and SOC scales. RESULTS: The study sample consisted of 299 patients with IBD, median age 34.15, 63% females, 70.9% had Crohn's disease, filled the questionnaires. In the multivariate analysis, lower results in IP, SE and SOC were found to be associated with significantly increase anxiety (OR 8.35, p<0.001; OR 4.18, p=0.001; OR 4.67, p<0.001, respectively) and depression (OR 15.8, p=0.001; OR 10.99, p=0.029; OR 6.12, p=0.014. CONCLUSIONS: Anxiety and depression are associated with IP, SE and SOC in patients with IBD. Clinicians should be aware of this impact, recognise their patients' psychological abilities to cope with the disease and improve those abilities, when needed, in order to achieve a better coping with the disease and to prevent the development of anxiety and depression.

Older age, longer procedures and tandem endoscopic-ultrasound as risk factors for post-endoscopic retrograde cholangiopancreatography bacteremia.

BACKGROUND: Clinically significant post-endoscopic retrograde cholangiopancreatography (ERCP) bacteremia (PEB) occurs in up to 5% of cases, while antibiotic prophylaxis is recommended only when an ERCP is unlikely to achieve complete biliary drainage. However, the current recommendations may not cover all potential risk factors for PEB. AIM: To identify novel risk factors for PEB and evaluate appropriateness of antibiotic prophylaxis. METHODS: A retrospective study of 1082 ERCP procedures performed between January 2012 - December 2013 in a single tertiary medical center. Data collection included: Demographic and clinical characteristics such as pre and post procedure antibiotic treatment and bacterial blood cultures. Exclusion criteria were: (1) Age < 18 years; (2) Positive bacterial blood culture before ERCP; (3) Scheduled antibiotic treatment prior to ERCP; (4) Hospitalization longer than 14 d before ERCP; and (5) missing critical data. Stepwise Logistic Regression analysis and Decision Tree algorithms were used for prediction modeling of PEB. RESULTS: A total of 626 ERCPs performed in 434 patients were included. Mean age 66.49 ± 15.4 years and 46.5% were males. PEB prevalence was 3.7%. Antibiotic prophylaxis was administrated in 139/626 (22.2%) cases but was indicated according to the guidelines only in 44/626 (7%) cases. In all the PEB cases, prophylaxis was deemed not indicated. A stepwise logistic regression [receiver operating characteristic (ROC), 0.766], identified 3 variables as independent risk factors for PEB: Age at ERCP ≥ 75 years (OR, 3.780, 95%CI: 1.519-9.408, P = 0.004); Tandem EUS/ERCP with fine needle aspiration (FNA) (OR, 14.528, 95%CI: 3.571-59.095, P < 0.001); ERCP duration longer than 60 min (OR, 5.396, 95%CI: 1.86-15.656, P = 0.002). In a decision tree model (ROC, 0.778) the probability for PEB without any risk factors was 1% regardless of prophylaxis administration. CONCLUSION: The prevalence of PEB in our study is similar to previous reports, despite the fact that antibiotic prophylaxis was administrated more readily than recommended. ERCP duration longer than 60 min, tandem EUS-ERCP with FNA and age above 75 years are significant risk factors for PEB. These factors should be further evaluated as indications for prophylactic antibiotic treatment before ERCP.

Bedouin Children With Celiac Disease: Less Symptoms but More Severe Histological Features at Presentation.

Background: The prevalence of celiac disease (CD) has dramatically increased with wide variability in clinical presentations between different geographical areas. However, the contribution of ethnic disparities in pediatric celiac disease is still unclear, especially in patients of Bedouin origin. Objective: We aimed to compare the clinical presentation and histological severity of celiac disease between Bedouin and Jewish children in southern Israel. Methods: This is a retrospective study in which we collected the demographic and clinical data, laboratory results, and histological severity of CD in two ethnic groups: Bedouins and Jews. The study included patients who were diagnosed between 1997 and 2015 in a tertiary hospital in southern Israel. Results: Data from 844 children with CD (271 Jewish and 573 Bedouins), 505 females (59.8%), were analyzed. Gastrointestinal symptoms and diabetes were more prevalent among the Jewish population (p < 0.001 and p = 0.008, respectively), while family history, failure to thrive, iron deficiency anemia, and histological severity were significantly more prevalent among the Bedouin group. Upon multivariate logistic regression analysis, only the presence of iron deficiency anemia and Bedouin origin were associated with more advanced histological disease (OR of 2.03 (95% C.I 1.31; 4.308) (P < 0.009) and OR 1.78 (95% C.I 1.31; 4.308) (P < 0.003) respectively). Conclusion: The clinical presentation of celiac disease in Bedouin children is characterized by anemia with less gastrointestinal symptoms, but more severe histological damage. These differences might be explained either by a delay in the diagnosis of the disease in this population or by variable environmental, cultural, and nutritional factors unique to this ethnic group.

New-Onset of Crohn's Disease Is Associated with Antistreptolysin O Positive Titers.

OBJECTIVE: Different infectious agents have been presumed to be candidates acting as an etiologic factor or trigger of Crohn's disease (CD). Group A Streptococcus (GAS) is a common human infection agent that can also trigger post-infectious immune-mediated conditions. The current study aimed to examine whether the immunogenic activity induced by GAS may trigger new-onset of CD. METHODS: Data for antistreptolysin O (ASO) level, throat culture for GAS, and history of streptococcal infection were collected from 91 patients with CD that were divided into three groups including; new-onset CD, CD in remission and active CD. The data were compared with the control group. RESULTS: All participants had negative results of throat culture for GAS and had no history of documented streptococcal infection in the past year. Our results indicate that new-onset CD, but not CD in remission or active CD, is associated with significantly increased positive ASO compared to controls. Half of the patients in the new-onset CD group were ASO positive, which was significantly higher compared to the control group in a univariant (OR: 4.00; 95% CI 1.27-12.58; P=0.02) and multivariant analysis (OR: 4.41; 95% CI 1.35-14.37; P=0.014). CONCLUSION: Our study is the first to focus on ASO levels in patients with CD and to demonstrate a significant association between ASO and new-onset of CD. Large prospective randomized controlled studies are needed to confirm the validity of this data and to further clarify the clinical significance of our findings.

The Safety and Feasibility of a New Through-the-scope Balloon-assisted Enteroscopy in Children.

OBJECTIVES: Small bowel involvement in Crohn disease (CD) is clinically important for diagnosis and treatment. Single and double-balloon enteroscopy have already become important diagnostic tools in such cases. The on-demand NaviAid AB device enables deep advancement into the small bowel, using an anterograde or retrograde approach. In adults, this procedure is feasible, safe, and rapid. This work aimed to assess the safety and feasibility of NaviAid AB enteroscopy in pediatric patients. METHODS: Single-center, prospective study using the through-the-scope balloon-assisted-enteroscopy (TTS-BAE) NaviAid AB device for the evaluation of the small bowel in children with suspected or known inflammatory bowel disease (IBD). The system consists of a single-use balloon catheter inserted through the instrument channel of a standard colonoscope. It consists of an inflation/deflation system (NaviAid SPARK), which is inflated to anchoring pressure. The repetitive push-pull technique enables the advancement of the colonoscope along the small intestine. RESULTS: Fifty analyzed endoscopic procedures (30 retrograde, 20 anterograde) were performed in 34 children (52.9% boys, mean age 13.7 years). Average maximal depth of insertion (MDI), advancement depth using the NaviAid AB and average total procedure time were 138 cm (range 100-190 cm), 81 cm (range 40-120 cm), and 12.8 minutes (range 7.3-19.0 minutes), respectively, for the anterograde approach and 143 cm (range 100-170 cm), 64 cm (range 20-95 cm), and 21.9 minutes (range 13.9-32.0 minutes), respectively, for the retrograde approach. No serious or device-related adverse events were reported. CONCLUSIONS: NaviAid AB enteroscopy in children is safe, feasible, and enables assessment of the small intestine in a short period of time.

Is administration of proton pump inhibitors in functional dyspepsia worth the risk of developing gastric cancer: a Markov model to bridge the gap between scientific evidence and clinical practice.

OBJECTIVE: To formulate a decision analysis model based on recently published data that addresses the dilemma, whether improvement in quality of life rationalises continued proton pump inhibitors (PPI) use despite the risk of gastric cancer (GC) in patients with functional dyspepsia (FD). DESIGN: A Markov model consisting of an initial decision regarding treatment with PPI (denoting it by PPI strategy) or any other treatment without PPI (denoting it by placebo strategy) was designed. DATA SOURCES: Data from prospective cross-sectional studies indicating risk stratification for GC after the use of PPI, combined with a Markov model that comprised the following states: Live, GC stages 1-4, Death. OUTCOME MEASURES: The primary outputs included quality-adjusted life years (QALYs) and life expectancy (LE). The improvement in utility in FD without PPI as compared with PPI use was tested (PPI vs placebo strategies). Sensitivity analyses were performed to evaluate the robustness of the model and address uncertainty in the estimation of model parameters. SETTING: We considered only patients whose symptoms were relieved with PPIs and thus, had a better quality of life compared with patients who did not receive PPIs. RESULTS: The base case model showed that PPIs compared with placebo decreased LE by 58.4 days with a gain of 2.1 QALY. If utility (quality of life of patients with FD using PPI compared with patients with FD without PPI) improved by more than 0.8%, PPI use is considered better than placebo. Older patients benefited less from PPI treatment than did younger patients. CONCLUSION: To bridge the gap between evidence and decision making, we found that even a small improvement in the QALY justified continuing PPI treatment.

Early Surgery Versus Biologic Therapy in Limited Nonstricturing Ileocecal Crohn's Disease-A Decision-making Analysis.

BACKGROUND: Surgery is the preferred option for patients with symptomatic localized fibrostenotic ileocecal Crohn's disease (CD) but not for those with predominantly active inflammation without obstruction. The benefit of early surgery in patients with a limited nonstricturing ileocecal CD over biologic treatment is still a debate. OBJECTIVE: Our objective is to formulate a decision analysis model based on recently published data to explore whether early surgery in patients with limited nonstricturing CD is preferred over biologic treatment. METHODS: We constructed a Markov model comparing 2 strategies of treatment: (1) early surgery vs (2) biologic treatment. To estimate the quality-adjusted life years (QALYs) and the costs in each strategy, we simulated 10,000 virtual patients with the Markov model using a Monte Carlo simulation 100 times. Sensitivity analyses were performed to evaluate the robustness of the model and address uncertainties in the estimation of model parameters. RESULTS: The costs were $29,457 ± $407 and $50,382 ± $525 (mean ± SD) for early surgery strategy and biologic treatment strategy, respectively. The QALY was 6.24 ± 0.01 and 5.81 ± 0.01 for early surgery strategy and biologic treatment strategy, respectively. CONCLUSION: The strategy of early surgery dominates (higher QALY value [efficacy] and less cost) compared with the strategy of biologic treatment in patients with limited ileocecal CD.

Endoscopic Ultrasound-Guided Radiofrequency Ablation: A New Therapeutic Approach for Pancreatic Neuroendocrine Tumors.

CONTEXT: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is rapidly emerging as feasible therapy for patients with pancreatic neuroendocrine tumors (pNETs) in selected cases, as a result of its favorable safety profile. OBJECTIVE: To assess the feasibility, safety, and efficacy of EUS-RFA in a cohort of patients with functional and nonfunctional pNETs (NF-pNETs). DESIGN: Data on pNET patients treated with EUS-RFA between March 2017 and October 2018 at two tertiary centers was retrospectively analyzed. RESULTS: The cohort included 18 adults (eight women, 10 men), aged 60.4 ± 14.4 years (mean ± SD), seven insulinoma patients, and 11 patients with NF-pNETs. Twenty-seven lesions with a mean diameter of 14.3 ± 7.3 mm (range 4.5 to 30) were treated. Technical success defined as typical postablative changes on a surveillance imaging was achieved in 26 out of 27 lesions. Clinical response with normalization of glucose levels was observed in all (seven of seven) insulinoma cases within 24 hours of treatment. Overall, there were no major complications 48 hours postprocedure. No clinically significant recurrences were observed during mean follow-up of 8.7 ± 4.6 months (range 2 to 21 months). CONCLUSIONS: EUS-guided RFA of pNETs is a minimally invasive, safe, and technically feasible procedure for selected patients.

Sense of coherence in people with and without inflammatory bowel diseases - is there a difference?

BACKGROUND AND AIMS: Sense of coherence (SOC) is a theoretical concept reflecting a person's resources and orientation, which enable individuals to cope with stressors in a health-promoting manner. In several multifactorial chronic diseases, such as diabetes mellitus and systemic lupus erythematosus, SOC was correlated with disease development. It was also related with the emotional distress in patients with inflammatory bowel disease (IBD).The aim of this study was to investigate the possible correlation between low SOC scores and the presence of IBD. METHODS: A total of 183 Crohn's disease (CD) and 71 ulcerative colitis (UC) patients completed questionnaires including demographic data and the 13 items for the SOC questionnaire. The IBD patients were matched to 124 healthy people according to age, gender, education, employment status and marital status. RESULTS: In the CD cohort, 96 patients were matched to the healthy cohort according to the propensity score value, and in the UC cohort 57 were matched. Patients with Crohns' disease had a median SOC score of 63 (IQR 56-71), and healthy matching controls of 62.5 (IQR 55.25- 68.75) p=0.369. Patients with ulcerative patients had a median SOC score of 66 (IQR 56-73) and healthy controls 62 (IQR 55-69) p=0.354. CONCLUSIONS: In our study SOC was not related to the development of IBD. The question of whether SOC is associated with the development of chronic disease and particularly with IBD remains open.

G-EYE colonoscopy is superior to standard colonoscopy for increasing adenoma detection rate: an international randomized controlled trial (with videos).

BACKGROUND AND AIMS: Colorectal cancer (CRC) is largely preventable with routine screening and surveillance colonoscopy; however, interval cancers arising from precancerous lesions missed by standard colonoscopy still occur. An increased adenoma detection rate (ADR) has been found to be inversely associated with interval cancers. The G-EYE device includes a reusable balloon integrated at the distal tip of a standard colonoscope, which flattens haustral folds, centralizes the colonoscope's optics, and reduces bowel slippage. The insufflated balloon also aims to enhance visualization of the colon during withdrawal, thereby increasing the ADR. METHODS: In this randomized, controlled, international, multicenter study (11 centers), patients (aged ≥50 years) referred to colonoscopy for screening, surveillance, or changes in bowel habits were randomized to undergo either balloon-assisted colonoscopy by using an insufflated balloon during withdrawal or standard high-definition colonoscopy. The primary endpoint was the ADR. RESULTS: One thousand patients were enrolled between May 2014 and September 2016 to undergo colonoscopy by experienced endoscopists; 803 were finally analyzed (standard colonoscopy n = 396; balloon-assisted colonoscopy n = 407). Baseline parameters were similar in both groups. Balloon-assisted colonoscopy provided a 48.0% ADR compared with 37.5% in the standard colonoscopy group (28% increase; P = .0027). Additionally, balloon-assisted colonoscopy provided for a significant increase in detection of advanced (P = .0033) flat adenomas (P < .0001) and sessile serrated adenomas/polyps (P = .0026). CONCLUSION: Balloon-assisted colonoscopy yielded a higher ADR and increased the detection of advanced, flat, and sessile serrated adenomas/polyps when compared with standard colonoscopy. Improved detection by the G-EYE device could impact the quality of CRC screening by reducing miss rates and consequently reducing interval cancer incidence. (Clinical trial registration number: NCT01917513.).

The Relationship between Gender, Severity of Disease, Treatment Type, and Employment Outcome in Patients with Inflammatory Bowel Disease in Israel.

Introduction: Since individuals with IBD typically experience symptoms during their prime years of employment, it raises the question about IBD impact on employment status. Most studies concentrated on absenteeism from work with varying results in different populations. However, absenteeism reflects only one dimension of the ability to work and does not expose the problem of inability to hold a full-time job. Aims: To evaluate the influence of IBD on unemployment and working hours in Israel. Secondary aims were to investigate the correlation between working hours and the type of medical treatment and the impact of severity of disease. Patients and Methods: Demographic data, employment status, number of weekly working hours, and disease parameters. The data was compared to that of the general Israeli population extracted from the website of the Central Bureau of Statistics. Results: 242 IBD patients were interviewed. Patients median age was 37.04(IQR 30.23-44.68) years and 88 (36.4%) were men and 154 (63.6%) women. Diagnosis of CD was established in 167 (69%) patients and UC in 65 (26.9%). There was no significant reduction in employment rates or working hours among the IBD patients comparing to the general population. Immunosuppressive or biologic treatment did not influence employment status. The unemployed patients had higher disease severity (median 7.33, IQR 5-10.66) compared to employed patients (median 6, IQR 3.66-7.66; p=0.003). Conclusions: Although IBD patients in Israel do not have higher unemployment, those with severe disease have lower proportion of employment.

Expression of Duodenal Iron Transporter Proteins in Diabetic Patients with and without Iron Deficiency Anemia.

The role of iron transport proteins in the pathogenesis of anemia in patients with diabetes mellitus (T2DM) is still unclear. We investigated the expression of duodenal transporter proteins in diabetic patients with and without iron deficiency anemia (IDA). Methods. Overall, 39 patients were included: 16 with T2DM and IDA (group A), 11 with T2DM without IDA (group B), and 12 controls (group C). Duodenal mucosal expression of divalent metal transporter 1 (DMT1), ferroportin 1 (FPN), hephaestin (HEPH), and transferrin receptor 1 (TfR) was evaluated by Western blotting. Chronic disease activity markers were measured as well. Results. FPN expression was increased in group A compared to group B and controls: 1.17 (0.72-1.46), 0.76 (0.53-1.04), and 0.71 (0.64-0.86), respectively (p = 0.011). TfR levels were over expressed in groups A and B compared to controls: 0.39 (0.26-0.61), 0.36 (0.24-0.43), and 0.18 (0.16-0.24), respectively, (p = 0.004). The three groups did not differ significantly with regard to cellular HEPH and DMT1 expression. The normal CRP and serum ferritin levels, accompanied with normal FPN among diabetic patients without IDA, do not support the association of IDA with chronic inflammatory state. Conclusion. In patients with T2DM and IDA, duodenal iron transport protein expression might be dependent on body iron stores rather than by chronic inflammation or diabetes per se.

Crohn's Disease Behavior and Location is Altered when Associated with Primary Sclerosing Cholangitis.

BACKGROUND: Up to 3.4% of Crohn's disease (CD) patients will be diagnosed with concomitant primary sclerosing cholangitis (PSC). Despite the worldwide increase incidence of CD, data on the clinical characteristics of PSC-CD patients are scarce. OBJECTIVES: To clinically characterize CD in patients who have concomitant PSC. METHODS: A retrospective case-control analysis was conducted with 18 CD patients with concomitant PSC who attended the Inflammatory Bowel Disease Center at the Tel Aviv Sourasky Medical Center between 2011-2014 (PSC-CD patients). They were matched by age, gender, and disease duration to 90 control patients (those with CD who did not have concomitant PSC). Disease phenotype (according to the Montreal classification), demographics, and clinical data were compared in the two groups. RESULTS: PSC-CD patients were characterized by a disease that was more frequently limited to the colon (L2) (50% vs. 16%, P = 0.004) and by a non-stricturing and non-penetrating inflammatory phenotype (83% vs. 33%, P = 0.0001) compared to controls who had an increased prevalence of the penetrating phenotype (B3) (6% vs. 33% P < 0.05). Use of 5-aminosalicylic acid agents as a single therapy was significantly more prevalent among PSC-CD patients than in controls (39% vs. 7%, P < 0.005). In contrast, biologic therapy was significantly less common among PSC-CD patients compared to controls (17% vs. 52%, P = 0.0086). CONCLUSIONS: Patients with PSC-CD are clinically distinct from patients with isolated CD, and are characterized by predominant colonic involvement and an inflammatory, non-stricturing and non-penetrating phenotype.

Corrigendum to "Expression of Duodenal Iron Transporter Proteins in Diabetic Patients with and without Iron Deficiency Anemia".

[This corrects the article DOI: 10.1155/2018/7494821.].

Adolescent transition clinic in inflammatory bowel disease: quantitative assessment of self-efficacy skills.

OBJECTIVES: There is no model for the process of transition of adolescents with inflammatory bowel diseases (IBD) to the adult care protocol. We recently established a transition clinic where 17-year-old to 18-year-old IBD patients are seen by a multidisciplinary team including pediatric and adult gastroenterologists with expertise in IBD treatments, an IBD nurse, and a psychologist. We quantitatively describe this model and its benefits, and correlate demographic and transition parameters to self-efficacy in IBD adolescent patients before and after transition. PATIENTS AND METHODS: All adolescent IBD patients enrolled in our transition clinic between January 2013 and December 2015 were included. They completed a self-efficacy questionnaire ('IBD-yourself') before and after the transition. The scores were correlated to demographic, disease, and transition parameters. RESULTS: Thirty of the 36 enrolled patients (mean age: 19±1.8 years, range: 17-27) had Crohn's disease. Twenty-seven patients completed the transition protocol, which included an average of 3-4 meetings (range: 2-8) over 6.9±3.5 months. Self-efficacy scores in all domains of the questionnaire were significantly higher after completion of the transition. The weighted average score of the questionnaire's domains was 1.85±0.3 before and 1.41±0.21 after transition (P<0.0001). Age, sex, disease duration, duration of transition, and the number of meetings in the clinic correlated with the questionnaire's scores in the domains of coping with IBD, knowledge of the transition process, and medication use. CONCLUSION: A well-planned adolescent IBD transition clinic contributes significantly toward improved self-efficacy in IBD. We recommend its implementation in IBD centers to enable a personalized transition program tailored to the needs of adolescents with IBD in specific domains.

Cost effectiveness of routine duodenal biopsies in iron deficiency anemia.

AIM: To investigate the cost effectiveness of routine small bowel biopsies (SBBs) in patients with iron deficiency anemia (IDA) independent of their celiac disease (CD) serology test results. METHODS: We used a state transition Markov model. Two strategies were compared: routine SBBs during esophagogastroduodenoscopy (EGD) in all patients with IDA regardless their celiac serology status (strategy A) vs SBBs only in IDA patients with positive serology (strategy B). The main outcomes were quality adjusted life years (QALY), average cost and the incremental cost effectiveness ratio (ICER). One way sensitivity analysis was performed on all variables and two way sensitivity analysis on selected variables were done. In order to validate the results, a Monte Carlo simulation of 100 sample trials with 10, and an acceptability curve were performed. RESULTS: Strategy A of routine SBBs yielded 19.888 QALYs with a cost of $218.10 compared to 19.887 QALYs and $234.17 in strategy B. In terms of cost-effectiveness, strategy A was the dominant strategy, as long as the cost of SBBs stayed less than $67. In addition, the ICER of strategy A was preferable, providing the cost of biopsy stays under $77. Monte Carlo simulation demonstrated that strategy A yielded the same QALY but with lower costs than strategy B. CONCLUSION: Our model suggests that EGD with routine SBBs is a cost-effective approach with improved QALYs in patients with IDA when the prevalence of CD is 5% or greater. SBBs should be a routine screening tool for CD among patients with IDA, regardless of their celiac antibody status.

Real-world Helicobacter pylori diagnosis in patients referred for esophagoduodenoscopy: The gap between guidelines and clinical practice.

BACKGROUND AND AIMS: Histopathology is the most accurate test to detect H. pylori when performed correctly with unknown validity in daily practice clinic settings. We aimed to determine the rate of potentially false-negative H. pylori results that might be due to continued use of proton pump inhibitors (PPIs) in routine endoscopy practice. We also aimed to establish whether gastroenterologists recommend routine cessation of PPIs before esophagogastroduodenoscopy (EGD) and whether they regularly document that biopsies for H. pylori testing have been taken while the patients are on PPI treatment. METHODS: Detailed information about three known factors (PPIs, antibiotics and prior H. pylori eradication treatment), which may cause histology or rapid urease test (RUT) to be unreliable, had been prospectively collected through interviews using a questionnaire before each test. Gastric biopsies were stained with H&E for histological analysis. RESULTS: A total of 409 individuals at three academic gastroenterology institutions were tested 200 times with histology. Fifty-six per cent (68 of 122) of all negative tests fell in the category of continuing PPI use, which had the potential to make the histology and RUT results unreliable. CONCLUSIONS: These data demonstrate a clear and important gap between current guidelines and real-world practice with regards to the diagnosis of H. pylori during EGD. A negative histology or RUT should be considered false negative until potential protocol violations are excluded. Documentation of PPI use during the EGD should be an integral part of the EGD report. The current practice of taking biopsies for H. pylori testing in patients under PPIs should be reevaluated.

Serum alpha-1 antitrypsin: a noninvasive marker of pouchitis.

BACKGROUND: Patients with ulcerative colitis undergoing total proctocolectomy with ileal pouch-anal anastomosis may develop pouchitis. Alpha-1-antitrypsin (AAT) is an acute phase reactant produced mainly by hepatocytes, but also locally in the gut. Data on noninvasive biomarkers of pouchitis are scarce. METHODS: To identify biomarkers that correlate with pouch inflammation, ulcerative colitis pouch patients were prospectively recruited and underwent clinical, endoscopic, and histologic evaluations. The Pouchitis Disease Activity Index (PDAI) was calculated, and pouchitis was defined by a score ≥7. Serum and fecal AAT, C-reactive protein (CRP), fecal calprotectin, ferritin and albumin levels were measured. RESULTS: Seventy-one ulcerative colitis pouch patients (mean age 43.8 ± 8.3 yr, 50.7% males) were included. The main indication for ileal pouch-anal anastomosis was intractable colitis (83.1%). Median serum AAT level (183.0 mg/dL, 155.1-232.0) was significantly higher in patients with a PDAI ≥7 compared with those with a PDAI <7 (167.6 mg/dL, 151.0-181.0) (P = 0.03). Serum AAT, CRP, and fecal calprotectin levels significantly correlated with PDAI scores: r = 0.583, P < 0.001; r = 0.584, P < 0.001; and r = 0.606, P = 0.001, respectively. Serum AAT and CRP levels correlated significantly (r = 0.650, P < 0.001), as did serum AAT and fecal calprotectin levels (r = 0.663, P < 0.001). Fecal AAT levels did not correlate with any tested biomarker. Receiver operating characteristic analysis demonstrated sensitivity, specificity, and positive predictive value of 55.6%, 100%, and 100%, respectively, for diagnosing pouchitis at a serum AAT cutoff level of 189 mg/dL. CONCLUSIONS: Serum AAT is a specific noninvasive biomarker of pouchitis. AAT levels correlate with disease activity and CRP and calprotectin levels.

Prognosis of primary sclerosing cholangitis in israel is independent of coexisting inflammatory bowel Disease.

BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is a rare chronic progressive cholestatic disorder. We assessed its characteristics and natural history in Israel and compared its outcome with respect to coexisting inflammatory bowel disease (IBD). METHODS: Data on characteristics, course and outcome were retrospectively retrieved on patients diagnosed with PSC from five large Israeli medical centers between 1988 and 2012. Patients with isolated PSC were compared with those with coexisting IBD to identify predictors of outcome. RESULTS: Of 141 patients (56% males) with confirmed PSC, 98 (69.5%) had coexisting IBD. The average age at presentation was 38.8 ± 15.4 years and duration of follow-up was 7.93 ± 6.26 years. The crude estimated point prevalence was 4 cases per 105 persons. Demographics and clinical characteristics were similar among all patients except for symptoms at diagnosis (which were more prevalent among PSC­IBD patients) and utilization of multiple diagnostic modalities (which was more prevalent among isolated-PSC patients). More than one-third of the entire cohort had cirrhosis. A total of 15 patients (10.6%) died and 19 patients (13.5%) developed malignancy during follow-up. Nine patients (6.3%) underwent liver transplantation. Mean survival for the entire cohort was 26.3 ± 1.4 years and mean transplant-free survival was 23.5 ± 1.6 years. Cox proportional hazard regression for transplantation or death revealed two independent risk factors: cirrhosis and malignancy [hazard ratio 4.25 (p = 0.004) and 2.58 (p = 0.046), respectively]. CONCLUSIONS: Survival rate of PSC patients in Israel is longer than reported rates worldwide and is independent of coexisting IBD.

Histone deacetylase inhibitors for purging HIV-1 from the latent reservoir.

A reservoir of latently infected memory CD4(+) T cells is believed to be the source of HIV-1 reemergence after discontinuation of antiretroviral therapy. HIV-1 eradication may depend on depletion of this reservoir. Integrated HIV-1 is inaccessible for expression, in part because of histone deacetylases (HDACs). One approach is to exploit the ability of HDAC inhibitors to induce HIV-1 expression from an integrated virus. With effective antiretroviral therapy, newly expressed HIV-1 is incapable of reinfecting naive cells. With HIV-1 expression, one assumes the infected cell dies and there is a progressive reduction in the size of the reservoir. The concept was tested using the HDAC inhibitor valproic acid. However, valproic acid is weak in inducing HIV-1 from latency in vitro. As such, clinical trials revealed a small or no effect on reducing the number of latently infected T cells in the peripheral blood. However, the new HDAC inhibitors vorinostat, belinostat and givinostat are more effective at targeting specific HDACs for HIV-1 expression than valproic acid. Here, we review studies on HDAC inhibitor-induced expression of latent HIV-1, with an emphasis on new and specific HDAC inhibitors. With increased potency for HIV-1 expression as well as safety and ease of oral administration, new HDAC inhibitors offer a unique opportunity to deplete the latent reservoir. An additional benefit is the antiinflammatory properties of HDAC inhibitors, including downregulation of HIV-1 coreceptor expression.