Etiology and Pathogenesis of Idiopathic Achalasia.

This review examines the etiology and pathogenesis of idiopathic achalasia. This disease is clinically characterized by dysphagia of solids and liquids due to the presence of simultaneous or absent esophageal contractions and impaired or absent relaxation of the lower esophageal sphincter. It includes a review of (a) etiology and pathogenesis of this inflammatory process that damage the ganglion cells of the Auerbach plexus that is limited to the esophagus; (b) genetic abnormalities and polymorphisms associated with this disease that may help explain its heterogeneity expressed by the different motility abnormalities of its phenotypes as well as differences in its clinical progression. These different genetic abnormalities may be responsible for the slow progression of types I or II phenotypes; (c) indirect evidence of viruses present in these patients that may initiate its development; (d) the abnormalities of the muscle layer that may be responsible for the dilation of the body of the esophagus that ultimately causes the sigmoid-like esophagus in the very last phase of this disease. This progression to the end-stage phase tends to occur in about 5% of patients. And, (e) the chronic inflammatory abnormalities in the squamous mucosa that may be the cause of the dysplastic and neoplastic changes that may lead to squamous cell carcinoma whose incidence in this disease is increased. These mucosal abnormalities are usually present in patients with markedly dilated body of the esophagus and severe food stasis.

Clostridium difficile strain NAP-1 is not associated with severe disease in a nonepidemic setting.

BACKGROUND & AIMS: Recent outbreaks of Clostridium difficile infection (CDI) in North America and in Europe with very high case-fatality rates have been associated with infection by North American Pulsed Field Type I (NAP-1) isolates. This study examined whether NAP-1 strains are associated with worse outcomes of CDI in a nonepidemic, nosocomial setting. METHODS: All cases of CDI that occurred over a 13-month period at a tertiary medical center were examined for risk factors associated with increased severity of CDI and other outcomes. Stool samples from each patient were cultured for C difficile and the resulting isolates were strain-typed by pulsed-field gel electrophoresis. RESULTS: Strain types were obtained from 236 of 272 CDI samples; the NAP-1 strain was identified in 59 (25%). In this inpatient cohort of patients with CDI, the incidence of in hospital death was 12.1% and of death caused by CDI was 4.0%. Of the patients with CDI, 22.1% met the combined outcome end point of severe CDI. In both univariate and multivariate analyses, patients infected with the NAP-1 strain did not have worse outcomes compared with those infected with non-NAP-1 strains. Infection with the NAP-1 strain was correlated with admission from outside health care facilities regardless of whether symptoms of CDI began before or after admission to the study hospital. CONCLUSIONS: The NAP-1 strain of C difficile was found to cause 25% of cases of CDI in the hospital where the study was performed. However, compared with non-NAP-1 strains, CDI was not associated with increased severity of disease in this nonepidemic setting.