Ihab I. El-Hajj

A Randomized Double-Blind Placebo-Controlled Trial of Rifaximin in Patients with Abdominal Bloating and Flatulence

AIMS:To study the efficacy of rifaximin, a nonabsorbable antibiotic, in relieving chronic functional symptoms of bloating and flatulence.METHODS:Randomized double-blind placebo-controlled trial consisting of three 10-day phases: baseline (phase 1), treatment with rifaximin 400 mg b.i.d. or placebo (phase 2), and post-treatment period (phase 3). Primary efficacy variable was subjective global symptom relief at the end of each phase. A symptom score was calculated from a symptom diary. Lactulose H2-breath test (LHBT) was performed at baseline and end of study.RESULTS:One hundred and twenty-four patients were enrolled (63 rifaximin and 61 placebo). Baseline characteristics were comparable and none had an abnormal baseline LHBT. Rome II criteria were met in 58.7% and 54.1%, respectively. At the end of phase 2, there was a significant difference in global symptom relief with rifaximin versus placebo (41.3%vs 22.9%, p= 0.03). This improvement was maintained at the end of phase 3 (28.6%vs 11.5%, p= 0.02). Mean cumulative and bloating-specific scores dropped significantly in the rifaximin group (p <0.05). Among patients with IBS, a favorable response to rifaximin was noted (40.5%vs 18.2%; p= 0.04) persisting by the end of phase 3 (27%vs 9.1%; p= 0.05). H2-breath excretion dropped significantly among rifaximin responders and correlated with improvement in bloating and overall symptom scores (p= 0.01). No adverse events were reported.CONCLUSIONS:Rifaximin is a safe and effective treatment for abdominal bloating and flatulence, including in IBS patients. Symptom improvement correlates with reduction in H2-breath excretion. Future trials are needed to examine the efficacy of long-term or cyclic rifaximin in functional colonic disorders.

Clinical epidemiology of inflammatory bowel disease in Lebanon

Background: The objectives of this study were to determine the prevalence and incidence of inflammatory bowel disease (IBD) in a representative Lebanese cohort and to describe practice prevalence trends, disease characteristics, and impact on quality of life (QoL) of IBD patients in Lebanon. Methods: All of a university‐based health programs 2000–2004 computerized records that listed a diagnosis of Crohns disease (CD) or ulcerative colitis (UC) were reviewed. In addition, data on patients seen in the gastroenterology clinics and data from the IBD registry at the American University of Beirut Medical Center (AUBMC) from the same period were analyzed. Results: Of 15,073 insured individuals, 8 had a diagnosis of CD and 16 of UC, giving an age‐adjusted prevalence of 53.1 per 100,000 people for CD and 106.2 per 100,000 people for UC. The mean age at diagnosis for patients with CD and UC was 28.8 ± 11.1 and 32.0 ± 13.4 years, respectively, and there was a slight female predominance. The mean annual incidence was 4.1 per 100,000 people for UC and 1.4 per 100,000 people for CD (range, 0–6.9/100,000 for both). Of the 10,383 patients seen in the gastroenterology clinic from 2000 to 2004, 251 (2.4%) had IBD (142 UC, 100 CD, and 9 indeterminate), a ratio that trended upward over time (range, 1.8%–2.7%). The median IBD Quality‐of‐Life (IBDQ) questionnaire score was 124.9 ± 30.5, indicating that the disease had a moderately severe impact on QoL. Conclusions: The prevalence of IBD in this representative Lebanese cohort falls in the intermediate range of that reported for white populations in Europe and North America. Future studies are needed to examine local risk factors, disease genotypes and phenotypes, and epidemiologic time trends. The psychosocial burden of IBD in Lebanon appears significant.

A randomized, controlled, double-blind trial of the adjunct use of tegaserod in whole-dose or split-dose polyethylene glycol electrolyte solution for colonoscopy preparation

BACKGROUND Problems of compliance, quality, and safety of colon preparation regimens have prompted continued investigation with alternative forms of cleansing. OBJECTIVE To evaluate the efficacy of tegaserod as an adjunct to a polyethylene glycol electrolyte solution (PEG-E), given as a whole dose or split dose, in colonoscopy preparation. DESIGN Randomized, placebo-controlled, double-blind trial. SETTING A single university-based hospital. PATIENTS Patients who were undergoing elective colonoscopy. INTERVENTIONS A 4-arm randomization scheme that compared tegaserod with a placebo, each with whole-dose or split-dose PEG-E preparation. MAIN OUTCOME MEASUREMENTS Efficacy of colon cleansing was the primary outcome. Secondary outcomes included adherence, tolerability, adverse effects, and patient perceptions of their preparation quality. RESULTS A total of 382 patients completed the trial. Patients who received the split-dose preparation had significantly better colon cleansing than those who received the whole-dose preparation (88.9% vs 42.6%, P < .001). The addition of tegaserod did not significantly improve the overall colonoscopy preparation quality compared with a placebo. However, there were fewer poor preparations in the whole-dose PEG-E group (12.4% vs 1.1%, P = .002, Bonferroni correction removes significance) and more excellent preparations in the split-dose group (53.3% vs 38.3%, P = .035, Bonferroni correction removes significance) in favor of tegaserod. Interobserver and intraobserver variability analysis showed substantial agreement among endoscopists. Adherence was significantly lower in the whole-dose group versus the split-dose PEG-E group (68.8% vs 91%, P < .001), independent of the use of tegaserod. Adverse effects were not different between study groups. LIMITATIONS A 4-arm randomization and the single-center nature of the study. CONCLUSIONS Tegaserod has a marginal effect on the quality of colonoscopy preparation when used as an adjuvant to PEG-E. The split-dose PEG-E was superior to the whole-dose PEG-E and resulted in better colon cleansing, adherence, and tolerance.

Clinical trial: a randomized controlled cross‐over study of flupenthixol + melitracen in functional dyspepsia

Background  Functional dyspepsia is a prevalent condition associated with diminished quality of life (QoL) and high economic burden.

Trauma-associated growth of suspected dormant micrometastasis

BackgroundCancer patients may harbor micrometastases that remain dormant, clinically undetectable during a variable period of time. A traumatic event or surgery may trigger the balance towards tumor growth as a result of associated angiogenesis, cytokine and growth factors release.Case presentationWe describe a patient with non-small lung cancer who had a rapid tumor growth and recurrence at a minor trauma site of his skull bone.ConclusionThis case is an illustration of the phenomenon of tumor growth after trauma or surgery and its associated cellular mechanisms. This phenomenon deserves further investigation and study.

Homozygous Mutations in the Conserved ATP Hinge Region of the Wilson Disease Gene: Association With Liver Disease

Objective To determine whether any correlation exists between the phenotype and genotype of 2 Lebanese families with members affected with Wilson disease (WD). Background WD is an autosomal-recessive disorder of copper transport with significant phenotypic diversity. Most patients are compound heterozygous making it difficult to establish a clear link between phenotype and genotype. Study We investigated 14 members from 2 Lebanese families (H and Z) with 5 members affected with WD. Mutation analysis of the ATP7B gene, and clinical assessments were carried out for both families. We also performed a literature search retrieving reported phenotypes of all patients homozygous to mutations in any of the 21 exons of the ATP7B. Results Patients of the H and Z-families were found homozygous for the respective Asn1270Ser and Pro1273Leu mutations in the adenosine triphosphate (ATP) hinge region of exon 18. Of the healthy members, 6 were heterozygous and 3 had normal sequences. Clinically, 4 patients had liver cirrhosis and 1 had asymptomatic transaminitis. One of the patients also had neurologic symptoms. Screening the literature for patients homozygous for mutations in the ATP hinge region identified 25 patients including ours. The overall prevalence of the hepatic phenotype among patients homozygous for mutation in exon 18 was 80% and was significantly higher than those in exons 7, 14, and 21. Conclusions We hereby report the association of liver disease with homozygous mutations in the conserved ATP hinge region of exon 18 of the ATP7B gene.

A Prospective Multicenter Study Evaluating Learning Curves and Competence in Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography Among Advanced Endoscopy Trainees: The Rapid Assessment of Trainee Endoscopy Skills Study

BACKGROUND & AIMS: On the basis of the Next Accreditation System, trainee assessment should occur on a continuous basis with individualized feedback. We aimed to validate endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) learning curves among advanced endoscopy trainees (AETs) by using a large national sample of training programs and to develop a centralized database that allows assessment of performance in relation to peers. METHODS: ASGE recognized training programs were invited to participate, and AETs were graded on ERCP and EUS exams by using a validated competency assessment tool that assesses technical and cognitive competence in a continuous fashion. Grading for each skill was done by using a 4‐point scoring system, and a comprehensive data collection and reporting system was built to create learning curves by using cumulative sum analysis. Individual results and benchmarking to peers were shared with AETs and trainers quarterly. RESULTS: Of the 62 programs invited, 20 programs and 22 AETs participated in this study. At the end of training, median number of EUS and ERCP performed/AET was 300 (range, 155–650) and 350 (125–500), respectively. Overall, 3786 exams were graded (EUS, 1137; ERCP‐biliary, 2280; ERCP‐pancreatic, 369). Learning curves for individual end points and overall technical/cognitive aspects in EUS and ERCP demonstrated substantial variability and were successfully shared with all programs. The majority of trainees achieved overall technical (EUS, 82%; ERCP, 60%) and cognitive (EUS, 76%; ERCP, 100%) competence at conclusion of training. CONCLUSIONS: These results demonstrate the feasibility of establishing a centralized database to report individualized learning curves and confirm the substantial variability in time to achieve competence among AETs in EUS and ERCP. ClinicalTrials.gov: NCT02509416.

Primary Coloduodenal Fistula in a Patient with Crohn's Disease

The posterior surface of the proximal transverse colon and the anterior surface of the descending duodenum are intimately related, predisposing to fistulization in this area. We herein describe a rare case of benign duodenocolic fistula secondary to Crohns disease. We emphasize the clinical presentation with fecaloid vomiting, as well as the establishment of the diagnosis by endoscopy, which are both extremely rare. The presence of a colonic stricture supports the hypothesis that the disease started in the colon rather than in the duodenum, and mandates surgical rather than medical therapy. Our case illustrates the possibility of coloduodenal fistula in patients with long-standing Crohns disease, which should be considered in patients presenting with fecaloid vomiting, abdominal pain, and weight loss.

Familial Mediterranean fever mimicking septic arthritis.

We report the case of a young Lebanese female who presented with recurrent episodes of left knee and calf swelling and a synovial fluid leucocyte count suggestive of septic arthritis, however bacteriologic cultures were negative. Familial Mediterranean fever (FMF) was suspected in view of a positive family history and genetic analysis for the mutations in the pyrin/marenostrin (MEFV) gene revealing a homozygote mutation at methionine-694-valine. The arthritis was controlled with prophylactic colchicine therapy. FMF should be considered in the differential diagnosis of acute monoarticular arthritis with elevated synovial fluid white blood cells counts in regions with high incidence of FMF.

Familial antiphospholipid antibodies and acquired circulating anticoagulants

Familial clustering of elevated antiphospholipid antibody levels has been described, but the reports are heterogeneous with regard to the characterization of the antiphospholipid syndrome (APS), coexisting autoimmune diseases and clinical implications. We report a familial occurrence of APS in two patients, in the presence of SLE in the mother and absence of autoimmune diseases in the daughter along with acquired circulating inhibitors in both cases: platelet inhibitor and factor IX inhibitor, respectively.