In acute and chronic lung disease, widespread disruption of tissue architecture underlies compromised pulmonary function. Pulmonary fibroblasts have been implicated as critical effectors of tissue-destructive extracellular matrix (ECM) remodeling by mobilizing a spectrum of proteolytic enzymes. Although efforts to date have focused on the catabolism of type I collagen, the predominant component of the lung interstitial matrix, the key collagenolytic enzymes employed by pulmonary fibroblasts remain unidentified. Herein, membrane type-1 matrix metalloprotease (MT1-MMP) is identified as the dominant and direct-acting protease responsible for the type I collagenolytic activity mediated by both mouse and human pulmonary fibroblasts. Furthermore, MT1-MMP is shown to be essential for pulmonary fibroblast migration within three-dimensional (3-D) hydrogels of cross-linked type I collagen that recapitulate ECM barriers encountered in the in vivo environment. Together, these findings demonstrate that MT1-MMP serves as a key effector of type I collagenolytic activity in pulmonary fibroblasts and earmark this pericellular collagenase as a potential target for therapeutic intervention.
The establishment of a low-dose CT lung cancer screening program improved the ability to screen patients as demonstrated by the number of patients screened and those diagnosed with a malignancy. These findings were also consistent with the findings from the National Lung Screening Trial study.
We examined national outcomes and patterns of care for pediatric patients with medulloblastoma (MB) in a large observational cohort. Materials/Methods: Using the National Cancer Database (NCDB), we evaluated clinical features, factors affecting receipt of proton beam therapy (PBT), and survival outcomes among patients diagnosed with MB. The association between intervention, co-variables, and outcome was assessed in a multivariable Cox analysis and through logistic regression analysis. Survival was estimated using the Kaplan-Meier method. Results: Among the 4,032 patients in the NCDB with pediatric brain tumors, 1,300 patients met the inclusion criteria of histologic diagnosis and location, receipt of chemotherapy and radiation, and age 18 years. The median age and follow-up were 8.4 and 4.5 years respectively. Five-year survival was 79.0%. In univariate analysis, inferior outcome (overall survival) was associated with rural residence (HR Z 2.78; 95% CI: 1.47-5.29; p < 0.01) and histology (large cell; HR Z 1.78; 95% CI: 1.08-2.94; p < 0.05). In multivariable analysis, both remained significant predictors of survival (large cell: HR Z 1.68; p < 0.05; rural residence: HR Z 2.74; p < 0.01). In 2013, the utilization rate of PBT (23% of patients) in the U.S. surpassed IMRT (16%), more frequently for patients with better socioeconomic status (i.e., higher income, p < 0.05; or more favorable insurance status, p < 0.05). Conclusion: As one of the largest datasets reported of pediatric MB, the observed variations in treatment intervention and survival outcomes may represent a target for further research.
Adult intensivists have increasing exposure to individuals with congenital diseases surviving into adulthood. Solid knowledge bases and early recognition of the possible sequelae of congenital disorders are crucial in caring for these patients. We present a challenging case of shock and relapse of Diamond-Blackfan anemia in a 42-year-old man lost to follow-up for 18 years and highlighted the importance of healthcare transitions into adulthood and the challenges faced by health care systems to develop new strategies successfully transitioning complex pediatric patients to adult care.
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