Immunopathogenesis of eosinophilic esophagitis

Background: Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus associated with dysphagia in adults and refractory reflux syndromes in children. Methods: Immunological and genetic approaches have been used to better understand the pathophysiology of the underlying inflammation. Results and Conclusions: Evidence has accumulated that EoE represents a T-helper (Th) 2-type inflammatory disease, in which allergens play a role in triggering the disease. The majority of the patients suffer from concurrent allergic rhinitis, asthma, and eczema, and have a history of atopy. The chronic inflammatory response in EoE is associated with tissue damage and remodeling, both of which lead to esophageal dysfunction and bolus impaction. The new insights into the pathophysiology have resulted in the development of the first pharmacological therapies of EoE.

Case-control analysis on metformin and cancer of the esophagus

PURPOSE Metformin use has been associated with decreased cancer risks, though data on esophageal cancer are scarce. We explored the relation between use of metformin or other anti-diabetic drugs and the risk of esophageal cancer. METHODS We conducted a case-control analysis in the UK-based general practice research database (GPRD, now clinical practice research datalink, CPRD). Cases were individuals with an incident diagnosis of esophageal cancer between 1994 and 2010 at age 40-89 years. Ten controls per case were matched on age, sex, calendar time, general practice, and number of years of active history in the GPRD prior to the index date. Various potential confounders including diabetes mellitus, gastro-esophageal reflux, and use of proton-pump inhibitors were evaluated in univariate models, and the final results were adjusted for BMI and smoking. Results are presented as odds ratios (ORs) with 95 % confidence intervals (CI). RESULTS Long-term use (≥30 prescriptions) of metformin was not associated with a materially altered risk of esophageal cancer (adj. OR 1.23, 95 % CI 0.92-1.65), nor was long-term use of sulfonylureas (adj. OR 0.93, 95 % CI 0.70-1.23), insulin (adj. OR 0.87, 95 % CI 0.60-1.25), or of thiazolidinediones (adj. OR 0.71, 95 % CI 0.37-1.36). CONCLUSION In our population-based study, use of metformin was not associated with an altered risk of esophageal cancer.

Erosive tooth wear in children.

Erosive tooth wear in children is a common condition. Besides the anatomical differences between deciduous and permanent teeth, additional histological differences may influence their susceptibility to dissolution. Considering laboratory studies alone, it is not clear whether deciduous teeth are more liable to erosive wear than permanent teeth. However, results from epidemiological studies imply that the primary dentition is less wear resistant than permanent teeth, possibly due to the overlapping of erosion with mechanical forces (like attrition or abrasion). Although low severity of tooth wear in children does not cause a significant impact on their quality of life, early erosive damage to their permanent teeth may compromise their dentition for their entire lifetime and require extensive restorative procedures. Therefore, early diagnosis of erosive wear and adequate preventive measures are important. Knowledge on the aetiological factors of erosive wear is a prerequisite for preventive strategies. Like in adults, extrinsic and intrinsic factors, or a combination of them, are possible reasons for erosive tooth wear in children and adolescents. Several factors directly related to erosive tooth wear in children are presently discussed, such as socio-economic aspects, gastroesophageal reflux or vomiting, and intake of some medicaments, as well as behavioural factors such as unusual eating and drinking habits. Additionally, frequent and excessive consumption of erosive foodstuffs and drinks are of importance.

Natural course of pontocerebellar hypoplasia type 2A

INTRODUCTION Pontocerebellar hypoplasia Type 2 (PCH2) is a rare autosomal recessive condition, defined on MRI by a small cerebellum and ventral pons. Clinical features are severe developmental delay, microcephaly and dyskinesia.Ninety percent carry a p.A307S mutation in the TSEN54-gene. Our aim was to describe the natural course including neurological and developmental features and other aspects of care in a homogeneous group of PCH2 patients all carrying the p.A307S mutation. PATIENTS AND METHODS Patients were recruited via the German patients' organizations. Inclusion criteria were imaging findings of PCH2 and a p.A307S mutation. Data were collected using medical reports and patient questionnaires discussed in a standardized telephone interview. RESULTS Thirty-three patients were included. When considering survival until age 11 years, 53% of children had died Weight, length and head circumference, mostly in the normal range at birth, became abnormal, especially head circumference (-5.58 SD at age 5 yrs). Neurologic symptoms: Choreathetosis was present in 88% (62% with pyramidal signs), 12% had pure spasticity. Epileptic seizures were manifest in 82%, status epilepticus in 39%. Non-epileptic dystonic attacks occurred in 33%. General symptoms: feeding difficulties were recorded in 100%, sleep disorder in 96%, apneas in 67% and recurrent infections in 52%; gastroesophageal reflux disease was diagnosed in 73%, 67% got percutaneous endoscopic gastrostomy and 36% a Nissen-fundoplication. Neurodevelopmental data: All children made progress, but on a low level: such as fixing and following with the eyes was seen in 76%, attempting to grasp objects (76%), moderate head control (73%), social smile (70%), rolling from prone to supine (58%), and sitting without support (9%). Ten percent lost achieved abilities on follow-up. The presence of prenatal symptoms did not correlate with outcome. CONCLUSION Phenotype of this genetically homogeneous group of PCH2 children was severe with reduced survival, but compatible with some developmental progress. Our data support the hypothesis of an early onset degeneration which thereafter stabilizes.

Association Between Baseline Impedance Values and Response Proton Pump Inhibitorsin Patients With Heartburn

BACKGROUND & AIMS: Esophageal impedance measurements have been proposed to indicate the status of the esophageal mucosa, and might be used to study the roles of the impaired mucosal integrity and increased acid sensitivity in patients with heartburn. We compared baseline impedance levels among patients with heartburn who did and did not respond to proton pump inhibitor (PPI) therapy, along with the pathophysiological characteristics of functional heartburn (FH). METHODS: In a case-control study, we collected data from January to December 203 on patients with heartburn and normal findings from endoscopy who were not receiving PPI therapy and underwent impedance pH testing at hospitals in Italy. Patients with negative test results were placed on an 8-week course of PPI therapy (84 patients received esomeprazole and 36 patients received pantoprazole). Patients with more than 50% symptom improvement were classified as FH/PPI responders and patients with less than 50% symptom improvement were classified as FH/PPI nonresponders. Patients with hypersensitive esophagus and healthy volunteers served as controls. In all patients and controls, we measured acid exposure time, number of refluxes, baseline impedance, and swallow-induced peristaltic wave indices. RESULTS: FH/PPI responders had higher acid exposure times, numbers of reflux events, and acid refluxes compared with FH/PPI nonresponders (P < .05). Patients with hypersensitive esophagus had mean acid exposure times and numbers of reflux events similar to those of FH/PPI responders. Baseline impedance levels were lower in FH/PPI responders and patients with hypersensitive esophagus, compared with FH/PPI nonresponders and healthy volunteers (P < .001). Swallow-induced peristaltic wave indices were similar between FH/PPI responders and patients with hypersensitive esophagus. CONCLUSIONS: Patients with FH who respond to PPI therapy have impedance pH features similar to those of patients with hypersensitive esophagus. Baseline impedance measurements might allow for identification of patients who respond to PPIs but would be classified as having FH based on conventional impedance-pH measurements.

Consensus report of the European Federation of Conservative Dentistry: erosive tooth wear-diagnosis and management

OBJECTIVE Due to an increased focus on erosive tooth wear (ETW), the European Federation of Conservative Dentistry (EFCD) considered ETW as a relevant topic for generating this consensus report. MATERIALS AND METHODS This report is based on a compilation of the scientific literature, an expert conference, and the approval by the General Assembly of EFCD. RESULTS ETW is a chemical-mechanical process resulting in a cumulative loss of hard dental tissue not caused by bacteria, and it is characterized by loss of the natural surface morphology and contour of the teeth. A suitable index for classification of ETW is the basic erosive wear examination (BEWE). Regarding the etiology, patient-related factors include the pre-disposition to erosion, reflux, vomiting, drinking and eating habits, as well as medications and dietary supplements. Nutritional factors relate to the composition of foods and beverages, e.g., with low pH and high buffer capacity (major risk factors), and calcium concentration (major protective factor). Occupational factors are exposition of workers to acidic liquids or vapors. Preventive management of ETW aims at reducing or stopping the progression of the lesions. Restorative management aims at reducing symptoms of pain and dentine hypersensitivity, or to restore esthetic and function, but it should only be used in conjunction with preventive strategies. CONCLUSIONS Effective management of ETW includes screening for early signs of ETW and evaluating all etiological factors. CLINICAL RELEVANCE ETW is a clinical condition, which calls for the increased attention of the dental community and is a challenge for the cooperation with other medical specialities.

Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort

U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12 months; p<0.001), with worse quality of life, and higher levels of anxiety and depression. They also had a higher incidence of nasal polyps and gastro-oesophageal reflux with lower lung function. Sputum eosinophil count was higher in severe asthma compared to mild/moderate asthma (median count 2.99% versus 1.05%; p=0.004) despite treatment with higher doses of inhaled and/or oral corticosteroids.Consistent with other severe asthma cohorts, U-BIOPRED is characterised by poor symptom control, increased comorbidity and airway inflammation, despite high levels of treatment. It is well suited to identify asthma phenotypes using the array of "omic" datasets that are at the core of this systems medicine approach.