Citations

AbstractBackground and AimHamartomatous polyposis syndromes (HPS) are a group of rare inherited autosomal dominant disorders. Small bowel polyposis is one of the manifestations of HPS. Double‐balloon enteroscopy (DBE) with polypectomy may obviate repeated small bowel surgeries for polyp intussusception, obstruction, or bleeding. The efficacy and safety of DBE‐assisted polypectomy in HPS patients with clinically significant small bowel polyposis were evaluated.MethodsAll HPS patients who underwent DBE from January 2007 to April 2011 were identified using a prospectively maintained database. Data on patient demographics, pre‐DBE radiological studies, polyp characteristics, procedural outcomes, and complications were abstracted.ResultsTwenty‐two patients underwent a total of 34 DBE procedures. Pre‐DBE imaging included computed tomography enterography (n = 15), computed tomography enteroclysis (n = 5), small bowel follow‐through (n = 1), and magnetic resonance enterography (n = 1). Any small bowel polyp ≥ 1 cm in size on radiological imaging was referred for DBE‐assisted polypectomy. Antegrade and retrograde DBE were successful in reaching and resecting targeted polyps in 90% (18/20) and 71.4% (10/14) of procedures, respectively. The overall success rate for DBE‐assisted polypectomy was 82.3% (95% confidence interval: 66.5–91.6%). The median size of resected polyps was 2 cm (range 1–5 cm) and all were hamartomas. Minor adverse events occurred in four (11.8%) procedures, including abdominal pain (n = 2), immediate post‐polypectomy bleeding (n = 1), and self‐limited hematochezia (n = 1).ConclusionsDBE‐assisted polypectomy was successful in over 80% of HPS patients with an acceptable margin of safety. To the knowledge of the authors, this is one of the largest single‐center studies to report on the performance and safety of DBE‐assisted polypectomy in HPS patients.

Summary Background Coeliac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten‐free diet ( GFD ), which is difficult for many patients. Larazotide acetate is a first‐in‐class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae. Aim To evaluate the efficacy and tolerability of larazotide acetate during gluten challenge. Methods This exploratory, double‐blind, randomised, placebo‐controlled study included 184 patients maintaining a GFD before and during the study. After a GFD run‐in, patients were randomised to larazotide acetate (1, 4, or 8 mg three times daily) or placebo and received 2.7 grams of gluten daily for 6 weeks. Outcomes included an experimental biomarker of intestinal permeability, the lactulose‐to‐mannitol ( LAMA ) ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale ( GSRS ) and anti‐transglutaminase antibody levels. Results No significant differences in LAMA ratios were observed between larazotide acetate and placebo groups. Larazotide acetate 1‐mg limited gluten‐induced symptoms measured by GSRS ( P = 0.002 vs. placebo). Mean ratio of anti‐tissue transglutaminase IgA levels over baseline was 19.0 in the placebo group compared with 5.78 ( P = 0.010), 3.88 ( P = 0.005) and 7.72 ( P = 0.025) in the larazotide acetate 1‐, 4‐, and 8‐mg groups, respectively. Adverse event rates were similar between larazotide acetate and placebo groups. Conclusions Larazotide acetate reduced gluten‐induced immune reactivity and symptoms in patients with coeliac disease undergoing gluten challenge and was generally well tolerated; however, no significant difference in LAMA ratios between larazotide acetate and placebo was observed. Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with coeliac disease.

SummaryBackgroundPatients with eosinophilic oesophagitis (EoE) commonly have asthma and atopy.AimsTo determine the predictive factors of EoE in patients with asthma.MethodsA retrospective analysis of a large database identified 156 asthma patients with EoE and 276 patients without EoE between 2000 and 2010. Clinical and laboratory characteristics were first analyzed in half of each group. Significant differences and modelling were then applied to the other half of each group in a split half analysis.ResultsOdds ratios and P‐values found to predict the presence of EoE in asthma patients were: allergic vs. non‐allergic asthma (4.07, <0.01), food allergies (45, <0.01), allergic rhinitis (2.13, =0.01) and peripheral eosinophilia (4.51, <0.01). The use of inhaled corticosteroids was negatively associated with EoE (0.41, <0.01) for asthma patients and (0.37, P < 0.01) for allergic type asthma patients. EoE patients were also younger (27.4 vs. 41.6 years old, P < 0.01). By logistic regression analysis, allergic asthma, presence of peripheral eosinophilia and use of inhaled steroids remained significant. From these parameters, a 3.5‐point scoring system model for EoE in asthma was formed with an ROC = 0.787 on split analysis.ConclusionsIn descending order, peripheral eosinophilia, allergic asthma and allergic rhinitis are associated with EoE in patients with asthma. Steroid inhalers appear to have a protective effect against EoE. An accurate and simple scoring system can be used as a screening tool to predict the presence of EoE in patients with asthma and dysphagia. EoE should be viewed as part of a generalised allergic phenotype rather than isolated oesophageal disease.

Background Two recent studies identified a mutation (p.Asp620Asn) in the vacuolar protein sorting 35 gene as a cause for an autosomal dominant form of Parkinson disease . Although additional missense variants were described, their pathogenic role yet remains inconclusive. Methods and results We performed the largest multi-center study to ascertain the frequency and pathogenicity of the reported vacuolar protein sorting 35 gene variants in more than 15,000 individuals worldwide. p.Asp620Asn was detected in 5 familial and 2 sporadic PD cases and not in healthy controls, p.Leu774Met in 6 cases and 1 control, p.Gly51Ser in 3 cases and 2 controls. Overall analyses did not reveal any significant increased risk for p.Leu774Met and p.Gly51Ser in our cohort. Conclusions Our study apart from identifying the p.Asp620Asn variant in familial cases also identified it in idiopathic Parkinson disease cases, and thus provides genetic evidence for a role of p.Asp620Asn in Parkinson disease in different populations worldwide.

Object Patients with brachial plexus injury (BPI) present with a combination of motor weakness/paralysis, sensory deficits, and pain. Brachial plexus injury is generally not believed to be associated with headaches. However, CSF leaks may be associated with CSF volume–depletion (low-pressure) headaches and can occur in BPI secondary to nerve root avulsion. Only a few cases of headaches associated with BPI have been reported. It is unknown if headaches in patients with BPI occur so rarely, or if they are just unrecognized by physicians and/or patients in which the focus of attention is the affected limb. The aim of this study was to determine the prevalence of CSF volume–depletion headaches in patients with BPI. Methods All adult patients presenting at the Mayo brachial plexus clinic with traumatic BPI were asked to complete a questionnaire addressing the presence and quality of headaches following their injury. The patients' clinical, injury, and imaging characteristics were subsequently reviewed. Results Between December 2008 and July 2010, 145 patients completed the questionnaire. Twenty-two patients reported new onset headaches occurring after their BPI. Eight of these patients experienced positional headaches, suggestive of CSF volume depletion. One of the patients with orthostatic headaches was excluded because the headaches immediately followed a lumbar puncture for a myelogram. Six of the other 7 patients with positional headaches had a clear preganglionic BPI. The available imaging studies in these 6 patients revealed evidence of CSF leaks: pseudomeningoceles (n = 5), CSF tracking into soft tissues (n = 3), CSF tracking into the intraspinal compartment (n = 3), CSF tracking into the pleural space (n = 2), and low-positioned cerebellar tonsils (n = 2). Conclusions In this retrospective study, 15.2% of patients (22 of 145 patients) with traumatic BPI suffered from a new-onset headache. Seven of these patients (4.8%) experienced postural headaches clearly suggestive of CSF volume depletion likely secondary to a CSF leak associated with the BPI, whereas the other 15 patients (10.3%) suffered headaches that may have represented a variant of CSF depletion headaches without a postural characteristic or a headache from another cause. These data suggest that CSF volume–depletion headaches occur in a significant proportion of patients with BPI and have been underrecognized and underreported.

Abstract High-resolution peripheral quantitative computed tomography (HR-pQCT) has recently been introduced as a clinical research tool for in vivo assessment of bone quality. The utility of this technology to address important skeletal health questions requires translation to standardized multicenter data pools. Our goal was to evaluate the feasibility of pooling data in multicenter HR-pQCT imaging trials. Reproducibility imaging experiments were performed using structure and composition-realistic phantoms constructed from cadaveric radii. Single-center precision was determined by repeat scanning over short-term (&lt;72 hours), intermediate-term (3–5 months), and long-term intervals (28 months). Multicenter precision was determined by imaging the phantoms at nine different HR-pQCT centers. Least significant change (LSC) and root mean squared coefficient of variation (RMSCV) for each interval and across centers was calculated for bone density, geometry, microstructure, and biomechanical parameters. Single-center short-term RMSCVs were &lt;1% for all parameters except cortical thickness (Ct.Th) (1.1%), spatial variability in cortical thickness (Ct.Th.SD) (2.6%), standard deviation of trabecular separation (Tb.Sp.SD) (1.8%), and porosity measures (6% to 8%). Intermediate-term RMSCVs were generally not statistically different from short-term values. Long-term variability was significantly greater for all density measures (0.7% to 2.0%; p &lt; 0.05 versus short-term) and several structure measures: cortical thickness (Ct.Th) (3.4%; p &lt; 0.01 versus short-term), cortical porosity (Ct.Po) (15.4%; p &lt; 0.01 versus short-term), and trabecular thickness (Tb.Th) (2.2%; p &lt; 0.01 versus short-term). Multicenter RMSCVs were also significantly higher than short-term values: 2% to 4% for density and micro–finite element analysis (µFE) measures (p &lt; 0.0001), 2.6% to 5.3% for morphometric measures (p &lt; 0.001), whereas Ct.Po was 16.2% (p &lt; 0.001). In the absence of subject motion, multicenter precision errors for HR-pQCT parameters were generally less than 5%. Phantom-based multicenter precision was comparable to previously reported in in vivo single-center precision errors, although this was approximately two to five times worse than ex vivo short-term precision. The data generated from this study will contribute to the future design and validation of standardized procedures that are broadly translatable to multicenter study designs. © 2013 American Society for Bone and Mineral Research.