ABSTRACT
Rationale: We showed that levels of a murine mitochondrial noncoding RNA, mito-ncR-LDL805 , increase in alveolar epithelial type 2 cells exposed to extracts from cigarette smoke. The transcripts translocate to the nucleus, upregulating nucleus-encoded mitochondrial genes and mitochondrial bioenergetics. This response is lost after chronic exposure to smoke in a mouse model of chronic obstructive pulmonary disease. Objectives: To determine if mito-ncR-LDL805 plays a role in human disease, this study aimed to (i) identify the human homologue, (ii) test if the smoke-induced response occurs in human cells, (ii) determine causality between the subcellular localization of the transcript and increased mitochondrial bioenergetics, and (iii) analyze mito-ncR-LDL805 transcript levels in samples from patients with chronic obstructive pulmonary disease. Methods: Levels and subcellular localization of the human homologue identified from an RNA transcript library were assessed in human alveolar epithelial type 2 cells exposed to smoke extract. Lipid nanoparticles were used for nucleus-targeted delivery of mito-ncR-LDL805 transcripts. Analyses included in situ hybridization, quantitative PCR, cell growth, and Seahorse mitochondrial bioenergetics assays. Measurements and Main Results: The levels of human homologue transiently increased and the transcripts translocated to the nuclei in human cells exposed to smoke extract. Targeted nuclear delivery of transcripts increased mitochondrial bioenergetics. Alveolar cells from humans with chronic obstructive pulmonary disease had reduced levels of the mito-ncR-LDL805 . Conclusions: mito-ncR-LDL805 mediates mitochondrial bioenergetics in murine and human alveolar epithelial type 2 cells in response to cigarette smoke exposure, but this response is likely lost in diseases associated with chronic smoking, such as chronic obstructive pulmonary disease, due to its diminished levels. Impact: This study describes a novel mechanism by which epithelial cells in the lungs adapt to the mitochondrial stress triggered by exposure to cigarette smoke. We show that a noncoding RNA in mitochondria is upregulated and translocated to the nuclei of alveolar epithelial type 2 cells to trigger expression of genes that restore mitochondrial bioenergetics. Mitochondria function and levels of the noncoding RNA decrease under conditions that lead to chronic obstructive pulmonary disease, suggesting that the mitochondrial noncoding RNA can serve as potential therapeutic target to restore function to halt disease progression.
ABSTRACT
BACKGROUND: Endoscopic esophageal stenting is used as an alternative to surgical repair for esophageal perforation. Multi-institutional studies supporting stenting are lacking. The purpose of this study was to compare the outcomes of surgical repair and esophageal stenting in patients with esophageal perforation using a nationally representative database. We hypothesized that mortality between these approaches would not be different. METHODS: The Premier Healthcare Database was used to compare adult inpatients with esophageal perforation receiving either surgical repair or esophageal stenting from 2009 to 2019. Patients receiving intervention ≤7 days of admission were included in the analysis. Patients receiving both stent and repair on the same day were excluded. The composite outcome of interest was death or discharge to hospice. Logistic regression was used to evaluate independent predictors of death or hospice, adjusting for comorbidities. RESULTS: There were 2543 patients with esophageal perforation identified who received repair (1314 [51.7%]) or stenting (1229 [48.3%]). Stenting increased from 7.0% in 2009 to 78.1% in 2019. Patients receiving repair were more likely to be female and White and had fewer Elixhauser comorbidities. Death or discharge to hospice was more common after stent (134/1314 [10.2%] repair vs 199/1229 [16.2%] stent; P < .001); however, after adjustment for comorbidities, logistic regression suggested that death or hospice discharge was similar between approaches (stent vs repair: odds ratio, 1.074; 95% CI, 0.81-1.42; P = .622). Hospital length of stay was shorter after stenting (stent vs repair coefficient, -4.09; P < .001). CONCLUSIONS: In patients with esophageal perforation, the odds for death or discharge to hospice were similar for esophageal stenting compared with surgical repair.
Subject(s)
Esophageal Perforation , Adult , Humans , Female , Male , Esophageal Perforation/etiology , Esophageal Perforation/surgery , Treatment Outcome , Retrospective Studies , Stents/adverse effectsABSTRACT
PURPOSE/OBJECTIVES: Outcomes of T2N0 lung cancer patients treated with stereotactic radiotherapy are not well known. METHODS AND MATERIALS: We conducted a single institution retrospective review of patients with T2N0 NSCLC who were treated with SBRT. The local, regional, distant control rates were calculated from available clinical data. Survival outcomes were determined using the Kaplan Meier method. RESULTS: Fifty-six patients met our selection criteria. The two-year local control rate was 84.2%. The two and 5-year disease-free survival (DFS) and OS were 31.9% and 15.3% and 39.9% and 12.1%, respectively. Centroid BED10 > 150Gy was associated with improved DFS, (p = 0.014), and OS on univariable analysis (p=0.0132). CONCLUSIONS: SBRT provides good local control for T2N0 NSCLC, but systemic failure remains problematic.
ABSTRACT
OBJECTIVE: Extrapleural pneumonectomy for therapy of mesothelioma has been associated with significant perioperative mortality and morbidity. Postoperative complications of this procedure require a unique management approach. We developed treatment algorithms for most of the common complications of extrapleural pneumonectomy resulting in reduced mortality and hospital stay. Complications after extrapleural pneumonectomy were further analyzed to elucidate means of prevention, early detection, and treatment. METHODS: A total of 496 patients undergoing extrapleural pneumonectomy were reviewed for mortality rates, with a subset of 328 consecutive patients between 1980 and 2000 who were examined for detailed morbidity data by using a prospective clinical database. RESULTS: Median age was 58 years (range, 28-77 years), with a 10-day (range, 4-101 days) median length of stay. One hundred ninety-eight (60.4%) of 328 patients experienced minor and major complications, and 11 of 328 patients died, for an overall mortality rate of 3.4%. Complications included the following: atrial fibrillation (145 [44.2%]), prolonged intubation (26 [7.9%]), vocal cord paralysis (22 [6.7%]), deep vein thrombosis (21 [6.4%]), technical complications (patch dehiscence, hemorrhage, or both; 20 [6.1%]), tamponade (12 [3.6%]), acute respiratory distress syndrome (12 [3.6%]), cardiac arrest (10 [3%]), constrictive physiology (9 [2.7%]), aspiration (9 [2.7%]), renal failure (9 [2.7%]), empyema (8 [2.4%]), tracheostomy (6 [1.8%]), myocardial infarction (5 [1.5%]), pulmonary embolus (5 [1.5%]), and bronchopleural fistula (2 [0.6%]). Clinical data demonstrated the following: (1) prophylaxis for atrial fibrillation is recommended; (2) early ambulation, aspiration precautions, endoscopic assessment of the vocal cords, and avoidance of fluid overload are crucial; (3) perioperative diagnosis and aggressive management of deep vein thrombosis are important; (4) immediate reoperation and open cardiac massage are essential for relief of cardiac herniation and tamponade from cardiac patch dysfunction; (5) diaphragmatic patch dehiscence, hemorrhage, or both require immediate reoperation; (6) early signs of infection might indicate bronchopleural fistula or empyema and should be treated with thoracoscopic or open drainage and staged removal of patch material; and (7) excessive perioperative mediastinal shift is treated with a catheter placed intraoperatively. CONCLUSION: Complications after extrapleural pneumonectomy require a unique approach to management, and mortality can be minimized by early detection and aggressive treatment.
