American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Mar 2020
Genomic Underpinnings of Tumor Behavior in in situ and Early Lung Adenocarcinoma.
Rationale: We have a limited understanding of the molecular underpinnings of early adenocarcinoma (ADC) progression. We hypothesized that the behavior of early ADC can be predicted based on genomic determinants. Objectives: To identify genomic alterations associated with resected indolent and aggressive early lung ADCs. ⋯ Mutations of KRAS, TP53, and NF1 were found to increase in frequency from AIS and MIA to ADC. A cancer progression model revealed selective early and late drivers. Conclusions: Our results reveal several genetic driver events, clonality, and mutational signatures associated with poor outcome in early lung ADC, with potential future implications for the detection and management of ADC.
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Am. J. Respir. Crit. Care Med. · Mar 2020
Comparative StudyPrevalence, Characteristics, and Prognosis of Early COPD: The Copenhagen General Population Study.
Rationale: Identification of younger adults at high risk of developing chronic obstructive pulmonary disease (COPD) could lead to implementation of preventive measures before disease onset and halt progression. Objectives: To investigate the prevalence, characteristics, and prognosis of individuals with early COPD in the general population. Methods: We investigated 105,630 randomly chosen adults from a Danish contemporary population-based cohort. ⋯ Compared with individuals without COPD, those with early COPD had multivariable adjusted hazard ratios of 6.42 (95% confidence interval, 3.39-12.2) for acute obstructive lung disease hospitalizations, 2.03 (1.43-2.88) for acute pneumonia hospitalizations, and 1.79 (1.28-2.52) for all-cause mortality. Conclusions: Among individuals under 50 years of age and 10 pack-years or greater of tobacco consumption from the general population, 15% fulfill criteria of early COPD. Individuals with early COPD more often have chronic respiratory symptoms and severe lung function impairment, and an increased risk of acute respiratory hospitalizations and early death.
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Am. J. Respir. Crit. Care Med. · Mar 2020
Comparative StudyTemporal Trends in Critical Care Outcomes in United States Minority Serving Hospitals.
Rationale: Whether critical care improvements over the last 10 years extend to all hospitals has not been described. Objectives: To examine the temporal trends of critical care outcomes in minority and non-minority-serving hospitals using an inception cohort of critically ill patients. Measurements and Main Results: Using the Philips Health Care electronic ICU Research Institute Database, we identified minority-serving hospitals as those with an African American or Hispanic ICU census more than twice its regional mean. ⋯ This disparity in temporal trends was particularly noticeable among African American individuals, where each additional calendar year was associated with a 3% (95% CI, 0.96-0.97) lower adjusted critical illness mortality within a non-minority-serving hospital, but no change within minority-serving hospitals (hazard ratio, 0.99; 95% CI, 0.97-1.01). Similarly, although ICU and hospital lengths of stay decreased by 0.08 (95% CI, -0.08 to -0.07) and 0.16 (95% CI, -0.16 to -0.15) days per additional calendar year, respectively, in non-minority-serving hospitals, there was little temporal change for African American individuals in minority-serving hospitals. Conclusions: Critically ill African American individuals are disproportionately cared for in minority-serving hospitals, which have shown significantly less improvement than non-minority-serving hospitals over the last 10 years.
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Am. J. Respir. Crit. Care Med. · Mar 2020
Aetiology, Risk Factors, and Biomarkers in Systemic Sclerosis with Interstitial Lung Disease.
Systemic sclerosis (SSc) is a complex, multiorgan, autoimmune disease. Lung fibrosis occurs in ∼80% of patients with SSc; 25% to 30% develop progressive interstitial lung disease (ILD). The pathogenesis of fibrosis in SSc-associated ILD (SSc-ILD) involves cellular injury, activation/differentiation of mesenchymal cells, and morphological/biological changes in epithelial/endothelial cells. ⋯ The course of SSc-ILD is variable, ranging from minor, stable disease to a progressive course, whereas all patients with IPF experience progression of disease. Although appropriately treated patients with SSc-ILD have better chances of stabilization and survival, a relentlessly progressive course, akin to IPF, is seen in a minority. Better understanding of cellular and molecular pathogenesis, genetic risk, and distinctive features of SSc-ILD and identification of robust prognostic biomarkers are needed for optimal disease management.