Time filter

Source Type

Mudde A.C.A.,Harvard University | Lexmond W.S.,Harvard University | Blumberg R.S.,Harvard University | Nurko S.,Harvard University | And 3 more authors.
World Allergy Organization Journal | Year: 2016

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus and commonly classified as a Th2-type allergy. Major advances in our understanding of the EoE pathophysiology have recently been made, but clinicians struggle with highly unpredictable therapy responses indicative of phenotypic diversity within the patient population. Here, we summarize evidences for the existence of EoE subpopulations based on diverse inflammatory characteristics of the esophageal tissue in EoE. Additionally, clinical characteristics of EoE patients support the concept of disease subtypes. We conclude that clinical and experimental evidences indicate that EoE is an umbrella term for conditions that are unified by esophageal eosinophilia but that several disease subgroups with various inflammatory esophageal patterns and/or different clinical features exist. We further discuss strategies to study the pathophysiologic differences as observed in EoE patients in murine experimental EoE. Going forward, models of EoE that faithfully mimic EoE subentities as defined in humans will be essential because mechanistic studies on triggers which regulate the onset of diverse EoE subpopulations are not feasible in patients. Understanding how and why different EoE phenotypes develop will be a first and fundamental step to establish strategies that integrate individual variations of the EoE pathology into personalized therapy. © 2016 Mudde et al.

Raphael B.P.,Center for Advanced Intestinal Rehabilitation | Nurko S.,Center for Motility and Functional Gastrointestinal Disorders | Jiang H.,Harvard University | Hart K.,Center for Motility and Functional Gastrointestinal Disorders | And 4 more authors.
Journal of Pediatric Gastroenterology and Nutrition | Year: 2011

Background and Objectives: Gastrointestinal dysmotility is common in pediatric short-bowel syndrome, leading to prolonged parenteral nutrition dependence. There is limited literature regarding the safety and efficacy of cisapride for this indication. The aim of the study was to describe the safety and efficacy of cisapride for enteral intolerance in pediatric short-bowel syndrome. Methods: Open-labeled pilot study in a limited access program for cisapride. Indications were short-bowel syndrome with underlying dysmotility and difficulty advancing enteral feeds despite standard therapies and without evidence of anatomic obstruction. Patients received cisapride 0.1 to 0.2 mg/kg per dose for 3 to 4 doses per day. We collected electrocardiogram, nutrition, and anthropometric data prospectively at study visits. Results: Ten patients with mean (SD) age of 30.3 (30.5) months were enrolled in our multidisciplinary pediatric intestinal rehabilitation program. Median (interquartile range [IQR]) duration of follow-up was 8.7 (3.1-14.3) months. Median (IQR) residual bowel length was 102 (85-130) cm. Median (IQR) citrulline level was 14.5 (10.5-31.3) μmol/L. Diagnoses included isolated gastroschisis (n = 3), gastroschisis with intestinal atresia (n = 4), necrotizing enterocolitis (n = 2), and long-segment Hirschsprung disease (n = 1). Six subjects had at least 1 prior bowel-lengthening procedure. Median (IQR) change in percentage enteral energy intake was 19.9% (15.4%-29.8%) during follow-up (P = 0.01). Seven patients improved in enteral tolerance during treatment and 2 were weaned completely from parenteral nutrition. Complications during therapy were prolonged corrected QT interval (n = 2), gastrointestinal bleeding (n = 2), D-lactic acidosis (n = 1), and death due to presumed sepsis (n = 1). Longitudinal analysis (general estimating equation model) showed a strong positive association between cisapride duration and improved enteral tolerance. Mean percentage of enteral intake increased by 2.9% for every month of cisapride treatment (P < 0.0001). Conclusions: Cisapride is a potentially useful therapy in patients with pediatric short-bowel syndrome with gastrointestinal dysmotility. We observed modest improvement in feeding tolerance where prior treatments failed; however, patients treated with cisapride require careful cardiac monitoring because corrected QT prolongation occurred in 20% of our cohort. Copyright © 2011 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Rosen R.,Center for Motility and Functional Gastrointestinal Disorders | Levine P.,Center for Motility and Functional Gastrointestinal Disorders | Lewis J.,Center for Motility and Functional Gastrointestinal Disorders | Mitchell P.,Childrens Hospital Boston | Nurko S.,Center for Motility and Functional Gastrointestinal Disorders
Journal of Pediatric Gastroenterology and Nutrition | Year: 2010

Background: Because of complications and its invasive nature, fundoplication is often a treatment of last resort for children with gastroesophageal reflux. Gastroesophageal reflux testing does not always predict who will benefit from antireflux surgery. Furthermore, there are no studies to determine whether a higher preoperative reflux burden, including acid and nonacid reflux, is associated with an improved postfundoplication outcome. The aim of the study was to determine predictors of fundoplication outcome including acid and nonacid reflux burden. Patients and Methods: We retrospectively reviewed preoperative pH-multichannel intraluminal impedance tracings and medical records of 34 patients who underwent fundoplication. Patients were categorized as improved or not improved, and the demographic and reflux characteristics were compared between groups. Multivariate analysis was performed to determine predictors of outcome. Results: No single reflux marker, including the number of acid, nonacid, total events, or the percentage of time that reflux was in the esophagus, predicted fundoplication outcome (P > 0.1). Neither a positive symptom index nor a positive symptom sensitivity index predicted postoperative improvement (P > 0.4). Receiver operating characteristic curve analysis failed to reveal an ideal value to maximize sensitivity for either the symptom index or the symptom sensitivity index. Conclusions: pH- multichannel intraluminal impedance testing may not be a useful tool in predicting fundoplication outcome. Copyright © 2010 by Lippincott Williams & Wilkins.

Loading Center for Motility and Functional Gastrointestinal Disorders collaborators
Loading Center for Motility and Functional Gastrointestinal Disorders collaborators