Clinical impact of type 2 diabetes mellitus on outcomes after one-lung ventilation during thoracic surgery: a retrospective cohort study.

BACKGROUND: The preoperative presence of diabetes mellitus (DM) has been recently demonstrated to be a risk factor for adverse events after thoracic surgery. However, the specific effects of presence of DM preoperatively on thoracic surgery is not known. This study aimed to investigate the association between preoperative DM and clinical outcomes and the short-term survival rates after thoracic surgery. METHODS: In this retrospective, observational, and matched-pair analysis study, patients receiving thoracic surgery from a tertiary university hospital in 2 consecutive years were grouped as either type 2 DM (T2DM) or controlled within the first 24 hours after surgery. Multivariate Cox regression was conducted to investigate the impact of T2DM within the first 24 hours of admission on in-intensive care unit (ICU) and hospital survival. RESULTS: Among the included thoracic patients, 41 (8.4%) had T2DM and 450 (91.6%) did not have T2DM. In the single-factor analyses, T2DM patients were shown to have a higher preoperative white blood cells (WBCs) count, increased release of immunoglobulin A, complement C3 and C4, impaired kidney function with high level of urea, and low expression of alanine aminotransferase (ALT) and monoamine oxidase (MAO). In multivariate analyses, the preoperative urea level was associated with a low-grade risk of dying for the ICU survival time. In contrast, preoperative complement C3 level favored a positive contribution in-ICU survival. Besides the complement C3 level, immunoglobulin A level remained a positive contribution in regression models of hospital survival. CONCLUSIONS: Pre-admission T2DM was not associated with an increased in-ICU and hospital mortality among patients with thoracic surgery. Furthermore, they were accompanied by impaired kidney function, activated inflammation and liver function.

Mitophagy-Mediated mtDNA Release Aggravates Stretching-Induced Inflammation and Lung Epithelial Cell Injury via the TLR9/MyD88/NF-κB Pathway.

BACKGROUND: In animal models of ventilation-induced lung injury, mitophagy triggers mitochondria damage and the release of mitochondrial (mt) DNA, which activates inflammation. However, the mechanism of this process is unclear. METHODS: A model of cyclic stretching (CS)-induced lung epithelial cell injury was established. The genetic intervention of phosphatase and tensin homolog-induced kinase 1 (PINK1) expression via lentivirus transfection was used to identify the relationship between PINK1-mediated mitophagy and mtDNA release in stretching-induced inflammatory response and injury. Pharmacological inhabitation of Toll-like receptor 9 (TLR9) and myeloid differentiation factor 88 (MyD88) expression was performed via their related inhibitors, while pre-treatment of exogenous mtDNA was used to verify the role of mtDNA in stretching-induced inflammatory response and injury. RESULTS: Using a cell culture model of CS, we found that knocking down PINK1 in lung epithelial cells reduced mitophagy activation and mtDNA release, leading to milder inflammatory response and injury; conversely, up-regulating PINK1 exacerbated stretching-induced inflammation and injury, and similar effects were observed by upregulating TLR9 to induce expression of MyD88 and nuclear factor-κB (NF-κB)/p65. Down-regulating MyD88 protected lung epithelial cells from stretching injury and decreased NF-κB/p65 expression. CONCLUSION: These findings suggest that PINK1-dependent mitophagy and associated TLR9 activation is indeed a major factor in stretch-induced cell injury via a mechanism in which released mtDNA activates TLR9 and thereby the MyD88/NF-κB pathway. Inhibiting this process may be a therapeutic approach to prevent inflammation and cell injury in patients on mechanical ventilation.

Non-intubated anesthesia in patients undergoing video-assisted thoracoscopic surgery: A systematic review and meta-analysis.

INTRODUCTION: Non-intubated anesthesia (NIA) has been proposed for video-assisted thoracoscopic surgery (VATS), although how the benefit-to-risk of NIA compares to that of intubated general anesthesia (IGA) for certain types of patients remains unclear. Therefore, the aim of the present meta-analysis was to understand whether NIA or IGA may be more beneficial for patients undergoing VATS. METHODS: A systematic search of Cochrane Library, Pubmed and Embase databases from 1968 to April 2019 was performed using predefined criteria. Studies comparing the effects of NIA or IGA for adult VATS patients were considered. The primary outcome measure was hospital stay. Pooled data were meta-analyzed using a random-effects model to determine the standard mean difference (SMD) with 95% confidence intervals (CI). RESULTS AND DISCUSSION: Twenty-eight studies with 2929 patients were included. The median age of participants was 56.8 years (range 21.9-76.4) and 1802 (61.5%) were male. Compared to IGA, NIA was associated with shorter hospital stay (SMD -0.57 days, 95%CI -0.78 to -0.36), lower estimated cost for hospitalization (SMD -2.83 US, 95% CI -4.33 to -1.34), shorter chest tube duration (SMD -0.32 days, 95% CI -0.47 to -0.17), and shorter postoperative fasting time (SMD, -2.76 days; 95% CI -2.98 to -2.54). NIA patients showed higher levels of total lymphocytes and natural killer cells and higher T helper/T suppressor cell ratio, but lower levels of interleukin (IL)-6, IL-8 and C-reactive protein (CRP). Moreover, NIA patients showed lower levels of fibrinogen, cortisol, procalcitonin and epinephrine. CONCLUSIONS: NIA enhances the recovery from VATS through attenuation of stress and inflammatory responses and stimulation of cellular immune function.

Conscious Sedation versus General Anesthesia for Patients with Acute Ischemic Stroke Undergoing Endovascular Therapy: A Systematic Review and Meta-Analysis.

The aim of this study is to compare the effect of conscious sedation (CS) with general anesthesia (GA) on clinical outcomes in patients with acute ischemic stroke (AIS) undergoing endovascular therapy (EVT). MEDLINE, EMBASE, and Cochrane Central Registers of Controlled Trials (from inception to July 2017) were searched for reports on CS and GA of AIS undergoing EVT. Two reviewers assessed the eligibility of the identified studies and extracted data. Data were analyzed using the fixed-effects model, and the sources of heterogeneity were explored by sensitive analysis. Trial sequential analysis was conducted to monitor boundaries for the limitation of global type I error, and GRADE system was demonstrated to evaluate the quality of evidence. A total of thirteen studies were finally identified. Pooled analysis of the incidence of mRS score ≦ 2 after hospital discharge and one or three months in the CS group was higher than that in the GA group. The all-causing mortality of AIS patients in the CS group was lower than that in the GA group. There were no differences in the proportion of IA rtPA and thrombolysis between the two groups. Compared with AIS patients receiving GA, the all-causing mortality in the AIS patients receiving CS was decreased, while incidence of mRS score ≦ 2 at hospital discharge and one or three months was increased.

High Tidal Volume Induces Mitochondria Damage and Releases Mitochondrial DNA to Aggravate the Ventilator-Induced Lung Injury.

OBJECTIVE: This study aimed to determine whether high tidal volume (HTV) induce mitochondria damage and mitophagy, contributing to the release of mitochondrial DNA (mtDNA). Another aim of the present study was to investigate the role and mechanism of mtDNA in ventilator-induced lung injury (VILI) in rats. METHODS: Rats were tracheotomized and allowed to breathe spontaneously or mechanically ventilated for 4 h. After that, lung injury was assessed. Inhibition of toll-like receptor 9 (TLR9), named ODN2088, was used to determine the involvement of TLR9/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway in VILI. The mitochondrial damage and release of mtDNA were assessed. Pharmacological inhibition of mtDNA (chloroquine) was used to determine whether mtDNA trigger inflammation via TLR9 in VILI. EDU-labeled mtDNA deriving from mitophagy was assessed by immunofluorescence. The role of mitophagy in VILI was shown by administration of antimycin A and cyclosporine A. MAIN RESULTS: Rats subjected to HTV showed more severe pulmonary edema and inflammation than the other rats. The decreased expression of TLR9, MyD88, and NF-κB were observed following the use of ODN2088. Mechanical ventilation (MV) with HTV damaged mitochondria which resulted in dysfunctional ATP synthesis, accumulation of reactive oxygen species, and loss of mitochondrial membrane potential. Moreover, the results of distribution of fluorescence in rats upon HTV stimulation indicated that mtDNA cleavage was associated with mitophagy. The expression levels of mitophagy related genes (LC3B-II/LC3B-I, PINK1, Parkin, and mitofusin 1) in animals ventilated with HTV were significantly upregulated. Administration of antimycin A aggregated the histological changes and inflammation after MV, but these effects were attenuated when administered in the presence of cyclosporine A. CONCLUSION: MV with HTV induces mitochondrial damage and mitophagy, contributing to the release of mtDNA, which may be induced VILI in rat via TLR9/MyD88/NF-κB signaling pathway.

Differential expression of HIF-1α, AQP-1, and VEGF under acute hypoxic conditions in the non-ventilated lung of a one-lung ventilation rat model.

AIMS: One-lung ventilation (OLV) is a standard practice in thoracic surgery. However, OLV can give rise to arterial hypoxemia. Hypoxia-inducible transcription factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF) and aquaporin-1 (AQP-1) may be involved in arterial hypoxemia and contribute to cellular injury. Therefore, in the present study, these moieties were investigated in an OLV rat model. MAIN METHODS: Forty Sprague-Dawley (S-D) rats were randomly divided into four groups: right lung mechanical ventilation for 0.5 h (Group A); 1 h (Group B); 2 h (Group C) and mechanical ventilation of both lungs (control group). Rat lung tissue was examined using electron microscopy. Serum and lung tissue levels of VEGF were measured by ELISA, Western blot analyses were used to detect the protein expression of HIF-1α and immunohistochemical staining and real-time polymerase chain reaction (PCR) were performed to examine protein expression and gene levels, respectively, of VEGF and AQP-1 after hypoxia. KEY FINDINGS: Electron microscopy revealed that increased duration of OLV was correlated with greater destruction of the non-ventilated lung. The protein expression of HIF-1α was significantly increased in the non-ventilated lungs of the experimental hypoxia groups (A-C) compared to the control group, whereas VEGF and AQP-1 protein expression and gene levels were decreased in the non-ventilated lungs of the hypoxia groups (A-C) compared to the control group. SIGNIFICANCE: The OLV caused hypoxia in the non-ventilated lung and subsequent injury. The altered expression of HIF-1α, VEGF, and AQP-1 may be involved in the pathological process of lung injury caused by hypoxia.