P62-positive aggregates are homogenously distributed in the myocardium and associated with the type of mutation in genetic cardiomyopathy.

Genetic cardiomyopathy is caused by mutations in various genes. The accumulation of potentially proteotoxic mutant protein aggregates due to insufficient autophagy is a possible mechanism of disease development. The objective of this study was to investigate the distribution in the myocardium of such aggregates in relation to specific pathogenic genetic mutations in cardiomyopathy hearts. Hearts from 32 genetic cardiomyopathy patients, 4 non-genetic cardiomyopathy patients and 5 controls were studied. Microscopic slices from an entire midventricular heart slice were stained for p62 (sequestosome-1, marker for aggregated proteins destined for autophagy). The percentage of cardiomyocytes with p62 accumulation was higher in cardiomyopathy hearts (median 3.3%) than in healthy controls (0.3%; P < .0001). p62 accumulation was highest in the desmin (15.6%) and phospholamban (7.2%) groups. P62 accumulation was homogeneously distributed in the myocardium. Fibrosis was not associated with p62 accumulation in subgroup analysis of phospholamban hearts. In conclusion, accumulation of p62-positive protein aggregates is homogeneously distributed in the myocardium independently of fibrosis distribution and associated with desmin and phospholamban cardiomyopathy. Proteotoxic protein accumulation is a diffuse process in the myocardium while a more localized second hit, such as local strain during exercise, might determine whether this leads to regional myocyte decay.

Finding balance between minimally invasive surgery and laryngotracheal resection in the management of adult laryngotracheal stenosis.

Management of adult laryngotracheal stenosis is complex and several treatment options are known. The present study focuses on finding the right balance between minimally invasive surgery and laryngotracheal resection by reviewing a single institution's experiences. Retrospective analysis was performed of all adult and adolescent patients with laryngotracheal stenosis who underwent treatment in a tertiary referral center, between 1990 and 2012. Age, gender, etiology, treatment, recurrence, pre- and post-operative peak flow (PF), and pre- and post-treatment subjective complain scores (SCS) were registered. 87 patients with 267 interventions were analyzed. There were 238 dilatation tracheoscopies, 22 open surgeries and various other endoscopic procedures registered. Idiopathic stenoses required the most dilatation tracheoscopies, while post-tracheotomy stenoses required the least. Patients in the post-intubation and post-tracheotomy groups were significantly more often treated with open surgery compared to those in the granulomatosis with polyangiitis (GPA) and idiopathic groups. The gain in PF flow after dilatation tracheoscopy was significantly higher in the idiopathic group compared to the other groups. The median SCS of dyspnoea decreased in the whole population, while other SCS did not change remarkably. Repeated endoscopic procedures are recommended in patients with severe systemic disease which do not allow open surgery or when other comorbidities contraindicate open surgery. Open surgery very often offers the definitive solution in the treatment of laryngotracheal stenosis and cannot be avoided when the laryngeal or the tracheal framework is damaged. Patients' personal preferences have to be considered in the pre-operative assessment process.