Utilization of a Risk Stratification Tool and Volume-Based Cuff Leak Test to Assess Postextubation Stridor.

BACKGROUND: Postextubation stridor (PES) is an imminently life-threatening event. Maximizing patient safety requires a systematic approach to screen patients for PES risk factors and a standardized test to evaluate that risk. This retrospective study of adult subjects was based on quality assurance data including standardized surveillance screening criteria and a volume-based cuff leak test (CLT) to evaluate PES risk among predominantly surgical-trauma and neurotrauma subjects. Data characterizing PES subjects also were collected. METHODS: Data were collected between May 2010-December 2017 for all intubated subjects in our surgical-trauma, neurotrauma, and medical ICUs. Respiratory therapists were trained in performing both PES risk assessment surveillance and a volume-based CLT. A pre hoc cutoff leak volume of < 110 mL defined a true positive test result when associated with PES, and a leak ≥ 110 mL defined a true negative test if PES was absent. Multiple comparisons were analyzed by Kruskal-Wallis tests and dichotomous variables assessed by Fisher exact tests. Alpha was set at 0.05. RESULTS: In 681 pre-extubation CLTs ∼85% produced true-negative results and 15% consisted of true-positive (∼4%), false-negative (∼5%), and false-positive (∼6%) results. Positive and negative predictive values were 0.42 (0.32-0.54) and 0.94 (0.92-0.96), respectively. The PES likelihood ratio was 7.0, and correct classification was 89%. Of the 115 PES incidences occurring in 112 PES cases, 67% were female and 48% had suffered acute brain injury. CONCLUSIONS: Among predominantly surgical-trauma and neurotrauma subjects with a CLT, leak volume of ≥ 110 mL was associated with a PES risk of ∼6%, whereas the risk of PES was 7 times greater when the leak volume was < 110 mL

Mobility gene expression differences among wild-type, Mmp20 null and Mmp20 over-expresser mice plus visualization of 3D mouse ameloblast directional movement

Abstract Enamel forming ameloblasts move away from the dentino-enamel junction and also move relative to each other to establish enamel shape during the secretory stage of enamel development. Matrix metalloproteinase-20 (MMP20) is a tooth specific proteinase essential for proper enamel formation. We previously reported that MMP20 cleaves cadherins and may regulate ameloblast movement. Here, we used an Amelx promoter driven tdTomato reporter to label mouse ameloblasts. With these transgenic mice, we assessed ameloblast mobility group dynamics and gene expression. Three-dimensional imaging of mouse ameloblasts were observed in hemi-mandibles by using a tissue clearing technique. The three-dimensional ameloblast layer in Tg(Amelx-Mmp20) mice that overexpress MMP20 was uneven and the ameloblasts migrated away from this layer. Mouse ameloblast movement toward incisal tips was monitored by ex vivo time-lapse imaging. Gene expression related to cell migration and adhesion was analyzed in ameloblasts from wild-type mice, Mmp20 −/− mice with no functional MMP20 and from Tg(Amelx-Mmp20) overexpressing mice. Gene expression was altered in Mmp20 −/− and Tg(Amelx-Mmp20) mice compared to wild type. Among the genes assessed, those encoding laminins and a gap junction protein were upregulated in Mmp20 −/− mice. New techniques and findings described in this study may lead to an improved understanding of ameloblast movement during enamel formation

FBXO7 mutations in Parkinson's disease and multiple system atrophy

Mutations in the F-box only protein 7 (FBXO7) gene, located on chromosome 22q12-q13, have recently been identified as having distinct clinical features in patients with hereditary Parkinson's disease (PD). Pathologically, a-synucleinepositive inclusions have been identified using anti-FBXO7 antibody staining techniques. In the present study, we screened entire exons of FBXO7 from 271 patients (231 PD and 40 multiple system atrophy [MSA]), of which 221 samples were of Japanese origin. The PD patients (n = 231) comprised 31 autosomal dominant, 82 autosomal recessive, and 118 sporadic forms. The 40 cases of MSA consisted of 8 autosomal dominant, 2 autosomal recessive, and 30 sporadic forms. We detected a Turkish patient with autosomal recessive inheritance, harboring a homozygous truncating mutation, Arg498Stop (p.R498X), in the FBXO7 gene. Consequently, we evaluated her and assessed the correlation between her clinical manifestations and genotypic analysis, although the FBXO7 p.R498X gene has lower frequency than others. Her age at onset was 17 years, and she clinically manifested with progressive parkinsonism and cognitive decline. In contrast, no pathogenic mutations in FBXO7 among PD and MSA patients of Japanese or other ethnicities were observed. Based on recent literature, we reviewed and compared the clinical findings and population differences between documented FBXO7 cases. (C) 2016 Elsevier Inc. All rights reserved

High efficacy of brigatinib for brain metastases in ALK fusion gene‐positive non‐small cell lung cancer: A case series

Abstract Anaplastic lymphoma kinase (ALK) fusion gene‐positive lung cancer often shows brain metastasis at initial diagnosis or during the course of treatment. However, molecular‐targeted drugs are known to pass through the blood–brain barrier and present positive effects for central nervous system lesions. There are few reports suggesting how effective molecular‐targeted drug therapy alone is for brain metastasis lesions of ALK fusion‐positive lung cancer, especially after the first use of ALK‐tyrosine kinase inhibitor (TKI) or for bulky brain metastases. A patient in his mid‐fifties with stage IV pleural dissemination developed brain metastases after 10 years of crizotinib use, but showed a complete response after switching to brigatinib. Moreover, a patient in her early sixties with stage III recurrent large brain metastases 5 years after chemoradiation therapy experienced dramatic tumor shrinkage with brigatinib. In each case of ALK fusion gene‐positive lung cancer with brain metastases, brigatinib showed a high efficacy and was well‐tolerated after previous ALK‐TKI and for bulky lesions