Pediatric tracheostomies in patients less than 2 years of age: Analysis of complications and long-term follow-up.

PURPOSE: Identify variables that are predictive of morbidity and mortality in children under the age of two undergoing tracheostomy and to provide longitudinal data on this patient population. METHODS: Patients were retrospectively identified using Current Procedural Terminology codes 31600, 31601, 31610 from 2009 to 2016. RESULTS: Median age at time of tracheostomy was 0.43 years (interquartile range, 0.27-0.61). Patients were followed for a median of 1.39 years (range 0.03-4.25). Overall mortality rate in this cohort was 23.5% with the majority (81.3%) of deaths occurring >30 days following tracheostomy. The most frequently encountered major complication was cardiopulmonary arrest (10.29%) in the short-term follow up period (<30 days) and accidental decannulation (32.81%) during long-term follow up (>30 days). Peristomal skin breakdown was less likely to develop in patients who did not receive paralytics following tracheostomy. Most patients (54.4%) were discharged to home following initial admission and experienced a mean of 2.10 readmissions for any reason during the follow-up period. 64.4% of patients underwent surveillance direct laryngoscopy and bronchoscopy during the follow-up period and suprastomal granuloma formation was detected in 31.2% of these patients. 9 patients underwent decannulation at a median of 2 years from original tracheostomy placement. CONCLUSION: Pediatric patients under the age of 2 undergoing tracheostomy exhibit high morbidity during both the initial hospital admission and the subsequent months following discharge. However, major complications were low and mortality was not directly related to tracheostomy status in any case.

Dural Marginal Zone Lymphoma in a Patient With a Hepatitis C Virus Infection.

Primary dural marginal zone lymphomas (MZLs) are exceptionally rare, with fewer than 100 cases reported to date. While the association between hepatitis C virus (HCV) infection and lymphoma is well established, it is unclear if this association extends to all anatomic sites. Here we report a case of dural MZL in a 61-year-old woman with an HCV infection. To our knowledge, this is the first report of a dural MZL associated with an HCV infection in an immunocompetent patient and was successfully treated with radiotherapy and rituximab. As such, future cases of primary MZL found in the dura should prompt consideration of co-infection with microbials such as HCV and upfront treatment with anti-virals should be considered.

AlphaScreen HTS and live-cell bioluminescence resonance energy transfer (BRET) assays for identification of Tau-Fyn SH3 interaction inhibitors for Alzheimer disease.

Alzheimer disease (AD) is the most common neurodegenerative disease, and with Americans' increasing longevity, it is becoming an epidemic. There are currently no effective treatments for this disorder. Abnormalities of Tau track more closely with cognitive decline than the most studied therapeutic target in AD, amyloid-ß, but the optimal strategy for targeting Tau has not yet been identified. On the basis of considerable preclinical data from AD models, we hypothesize that interactions between Tau and the Src-family tyrosine kinase, Fyn, are pathogenic in AD. Genetically reducing either Tau or Fyn is protective in AD mouse models, and a dominant negative fragment of Tau that alters Fyn localization is also protective. Here, we describe a new AlphaScreen assay and a live-cell bioluminescence resonance energy transfer (BRET) assay using a novel BRET pair for quantifying the Tau-Fyn interaction. We used these assays to map the binding site on Tau for Fyn to the fifth and sixth PXXP motifs to show that AD-associated phosphorylation at microtubule affinity regulating kinase sites increases the affinity of the Tau-Fyn interaction and to identify Tau-Fyn interaction inhibitors by high-throughput screening. This screen has identified a variety of chemically tractable hits, suggesting that the Tau-Fyn interaction may represent a good drug target for AD.