Thoracoscopic lobectomy is associated with a lower incidence of major complications, including atrial fibrillation, compared with lobectomy by means of thoracotomy. The underlying factors responsible for this advantage should be analyzed to improve the safety and outcomes of other thoracic procedures.
Despite substantial evidence that nitric oxide (NO) and/or endogenous S-nitrosothiols (SNOs) exert protective effects in a variety of cardiovascular diseases, the molecular details are largely unknown. Here we show that following left coronary artery ligation, mice with a targeted deletion of the S-nitrosoglutathione reductase gene (GSNOR ؊/؊ ) have reduced myocardial infarct size, preserved ventricular systolic and diastolic function, and maintained tissue oxygenation. These profound physiological effects are associated with increases in myocardial capillary density and S-nitrosylation of the transcription factor hypoxia inducible factor-1␣ (HIF-1␣) under normoxic conditions. We further show that S-nitrosylated HIF-1␣ binds to the vascular endothelial growth factor (VEGF) gene, thus identifying a role for GSNO in angiogenesis and myocardial protection. These results suggest innovative approaches to modulate angiogenesis and preserve cardiac function.angiogenesis ͉ HIF-1␣ ͉ myocardial infarction ͉ nitric oxide ͉ S-nitrosylation
Background-Downregulation of -adrenergic receptors (ARs) under conditions of heart failure requires receptor targeting of phosphoinositide 3-kinase (PI3K)-␥ and redistribution of ARs into endosomal compartments. Because support with a left ventricular assist device (LVAD) results in significant improvement of cardiac function in humans, we investigated the effects of mechanical unloading on regulation of PI3K␥ activity and intracellular distribution of ARs. Additionally, we tested whether displacement of PI3K␥ from activated ARs would restore agonist responsiveness in failing human cardiomyocytes. Methods and Results-To test the role of PI3K on AR endocytosis in failing human hearts, we assayed for PI3K activity in human left ventricular samples before and after mechanical unloading (LVAD). Before LVAD, failing human hearts displayed a marked increase in AR kinase 1 (ARK1)-associated PI3K activity that was attributed exclusively to enhanced activity of the PI3K␥ isoform. Increased ARK1-coupled PI3K activity in the failing hearts was associated with downregulation of ARs from the plasma membrane and enhanced sequestration into early and late endosomes compared with unmatched nonfailing controls. Importantly, LVAD support reversed PI3K␥ activation, normalized the levels of agonist-responsive ARs at the plasma membrane, and depleted the ARs from the endosomal compartments without changing the total number of receptors (sum of plasma membrane and early and late endosome receptors). To test whether the competitive displacement of PI3K from the AR complex restored receptor responsiveness, we overexpressed the phosphoinositide kinase domain of PI3K (which disrupts ARK1/PI3K interaction) in primary cultures of failing human cardiomyocytes. Adenoviral-mediated phosphoinositide kinase overexpression significantly increased basal contractility and rapidly reconstituted responsiveness to -agonist. Conclusions-These results suggest a novel paradigm in which human ARs undergo a process of intracellular sequestration that is dynamically reversed after LVAD support. Importantly, mechanical unloading leads to complete reversal in PI3K␥ and ARK1-associated PI3K activation. Furthermore, displacement of active PI3K from ARK1 restores AR responsiveness in failing myocytes.
In this retrospective analysis, TL was significantly less expensive than PLT from the preoperative evaluation through 30 days postoperatively, with overall savings of approximately USD 2000 per patient. In light of equivalent QALY outcomes, this cost-utility analysis supports increased adoption of TL as a cost-minimisation strategy. The use of TL for the 50,000 lobectomies performed in the United States each year would represent a savings of approximately USD 100 million.
OBJECTIVE We sought to evaluate the effect of tumor size, location, and clinical nodal status on outcomes after thoracoscopic lobectomy for lung cancer. METHODS All patients who underwent attempted thoracoscopic lobectomy for lung cancer between June 1999 and October 2010 at a single institution were reviewed. A model for morbidity including published risk factors as well as tumor size, location, and clinical N status was developed by multivariable logistic regression. RESULTS During the study period, 916 thoracoscopic lobectomies met study criteria: 329 for peripheral, clinical N0 tumors ≤3cm and 504 for tumors that were central, clinical node positive, or >3cm; tumor location could not be documented for 83 patients. Conversions to thoracotomy occurred in 36 patients (4%); patients with clinically node positive disease had higher conversion rates [11 conversions in 153 clinical N1-N3 patients (7.2%) vs 25 in 763 clinical N0 patients (3.3%), p=0.03]. Overall operative mortality was 1.6% (14 patients) and morbidity was 32% (296 patients). Although patients with larger tumors (p=0.006) and central tumors (p=0.01) had increased complications by univariate analysis, tumor size >3cm (p=0.17) and central location (p=0.5) did not significantly predict overall morbidity in multivariate analysis. Clinical node status did not predict increased complications by univariate or multivariate analysis. Significant predictors of morbidity in multivariable analysis were increasing age, decreasing FEV1, prior chemotherapy, and congestive heart failure. CONCLUSIONS Thoracoscopic lobectomy for lung cancers that are central, clinically node positive, or larger than 3 cm does not confer increased morbidity compared to peripheral, clinical N0 cancers that are smaller than 3 cm.
Background: We sought to evaluate trends and clinical and economic outcomes between robotic-assisted lobectomy (RL), video-assisted thoracoscopic lobectomy (VL), and open pulmonary lobectomy (OL). Methods: Patients who underwent a lobectomy for malignancy from January 1, 2008, to September 30, 2015, were identified in the Premier Healthcare Database. Propensity score matched (PSM) comparisons were performed between RL versus VL and RL versus OL. Patient characteristics were applied to generate propensity scores. In-hospital and perioperative 30-day outcomes and costs were compared within matched cohorts.Results: From 2008 to 2015, there was a marked decline for OL (71% to 43%, P<0.0001) with a significant increase in RL (1% to 17%, P<0.0001) and VL (28% to 41%, P<0.0001). In the early period (January 2008 to December 2012), total operating room time was longer (P<0.0001) and admission to ICU was more common for RL compared to VL or OL (P<0.0001) although the total length of ICU stay was shorter for RL compared to VL or OL (P<0.0001). In the late period (January 2013 to September 2015), RL was associated with significantly lower rates of complications (P<0.05), conversions, and shorter length of stay than VL and OL. When hospital volume was not considered, costs were higher for RL than VL and OL. In hospitals where >25 lobectomies were performed annually, the total cost of RL was comparable to VL (P=0.09) and OL (P=0.11). Conclusions: During the study period, the utilization of RL increased substantially and was associated with improved perioperative outcomes compared with VL and OL. When annual hospital volume was >25 cases, these clinical advantages persisted and there was no significant cost difference between RL, VL, or OL. RL is an effective and cost-comparable approach for lobectomy in patients with lung malignancy.
The Society for Translational Medicine and The Chinese Society for Thoracic and Cardiovascular Surgery conducted a systematic review of the literature in an attempt to improve our understanding in the postoperative management of chest tubes of patients undergoing pulmonary lobectomy. Recommendations were produced and classified based on an internationally accepted GRADE system. The following recommendations were extracted in the present review: (I) chest tubes can be removed safely with daily pleural fluid of up to 450 mL (non-chylous and non-sanguinous), which may reduce chest tube duration and hospital length of stay (2B); (II) in rare instances, e.g., persistent abundant fluid production, the use of PrR <0.5 when evaluating fluid output to determine chest tube removal might be beneficial (2B); (III) it is recommended that one chest tube is adequate following pulmonary lobectomy, except for hemorrhage and space problems (2A); (IV) chest tube clearance by milking and stripping is not recommended after lung resection (2B); (V) chest tube suction is not necessary for patients undergoing lobectomy after first postoperative day (2A); (VI) regulated chest tube suction [-11 (-1.08 kPa) to -20 (1.96 kPa) cmHO depending upon the type of lobectomy] is not superior to regulated seal [-2 (0.196 kPa) cmHO] when electronic drainage systems are used after lobectomy by thoracotomy (2B); (VII) chest tube removal recommended at the end of expiration and may be slightly superior to removal at the end of inspiration (2A); (VIII) electronic drainage systems are recommended in the management of chest tube in patients undergoing lobectomy (2B).
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