Efficacy of Intraoperative Recurrent Laryngeal Nerve Monitoring During Thoracoscopic Esophagectomy for Esophageal Cancer: A Systematic Review and Meta-Analysis.

Background: Recurrent laryngeal nerve paralysis (RLNP), a severe complication of mini-invasive esophagectomy, usually occurs during lymphadenectomy adjacent to recurrent laryngeal nerve. This systematic review and meta-analysis aimed to evaluate the efficacy of intraoperative nerve monitoring (IONM) in reducing RLNP incidence during mini-invasive esophagectomy. Methods: Systematic literature search of PubMed, EMBASE, EBSCO, Web of Knowledge, and Cochrane Library until June 4, 2021 was performed using the terms "(nerve monitoring) OR neuromonitoring OR neural monitoring OR recurrent laryngeal nerve AND (esophagectomy OR esophageal)." Primary outcome was postoperative RLNP incidence. Secondary outcomes were sensitivity, specificity, and positive and negative predictive values for IONM; complications after esophagectomy; number of dissected lymph nodes; operation time; and length of hospital stay. Results: Among 2,330 studies, five studies comprising 509 patients were eligible for final analysis. The RLNP incidence was significantly lower (odds ratio [OR] 0.33, 95% confidence interval [CI] 0.12-0.88, p < 0.05), the number of dissected mediastinal lymph nodes was significantly higher (mean difference 4.30, 95%CI 2.75-5.85, p < 0.001), and the rate of hoarseness was significantly lower (OR 0.14, 95%CI 0.03-0.63, p = 0.01) in the IONM group than in the non-IONM group. The rates of aspiration (OR 0.31, 95%CI 0.06-1.64, p = 0.17), pneumonia (OR 1.08, 95%CI 0.70-1.67, p = 0.71), and operation time (mean difference 7.68, 95%CI -23.60-38.95, p = 0.63) were not significantly different between the two groups. The mean sensitivity, specificity, and positive and negative predictive values for IONM were 53.2% (0-66.7%), 93.7% (54.8-100%), 71.4% (0-100%), and 87.1% (68.0-96.6%), respectively. Conclusion: IONM was a feasible and effective approach to minimize RLNP, improve lymphadenectomy, and reduce hoarseness after thoracoscopic esophagectomy for esophageal cancer, although IONM did not provide significant benefit in reducing aspiration, pneumonia, operation time, and length of hospital stay.

The Impact of Skip vs. Non-Skip N2 Lymph Node Metastasis on the Prognosis of Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Objective: The skip N2 metastases were frequent in non-small-cell lung cancer (NSCLC) and the better prognosis of NSCLC with a skip over non-skip N2 lymph node metastases is controversial. The primary aim of this study is to investigate the prognosis effect of skip N2 lymph node metastases on the survival of NSCLC. Setting: A literature search was conducted in PubMed, EMBASE, and Cochrane Library with the term of "N2" or "mediastinal lymph node" or "mediastinal nodal metastases", and "lung cancer" and "skip" or "skipping" in the title/abstract field. The primary outcomes of interests are 3- and 5-year survival in NSCLC. Participants: Patients who underwent complete resection by lobectomy, bilobectomy, or pneumonectomy with systemic ipsilateral lymphadenectomy and were staged as pathologically N2 were included. Primary and Secondary Outcome Measures: The 3- and 5-year survival of NSCLC was analyzed. The impact of publication year, number of patients, baseline mean age, gender, histology, adjuvant therapy, number of skip N2 stations, and survival analysis methods on the primary outcome were also analyzed. Results: A total of 21 of 409 studies with 6,806 patients met the inclusion criteria and were finally included for the analysis. The skip N2 lymph node metastases NSCLC had a significantly better overall survival (OS) than the non-skip N2 NSCLC [hazard ratio (HR), 0.71; 95% CI, 0.62-0.82; P < 0.001; I 2 = 40.4%]. The skip N2 lymph node metastases NSCLC had significantly higher 3- and 5-year survival rates than the non-skip N2 lymph node metastases NSCLC (OR, 0.75; 95% CI, 0.66-0.84; P < 0.001; I 2 = 60%; and OR, 0.78; 95% CI, 0.71-0.86; P < 0.001; I 2 = 67.1%, respectively). Conclusion: This meta-analysis suggests that the prognosis of skip N2 lymph node metastases NSCLC is better than that of a non-skip N2 lymph node.

Pulmonary function after segmentectomy versus lobectomy in patients with early-stage non-small-cell lung cancer: a meta-analysis.

OBJECTIVE: Segmentectomy is widely performed for early-stage lung cancer. However, the effects of segmentectomy versus lobectomy on pulmonary function remain unclear. We performed a meta-analysis with the aim of comparing segmentectomy and lobectomy in terms of preservation of pulmonary function in patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: We conducted a literature search of PubMed using the terms 'pulmonary function' AND 'segmentectomy' AND 'lobectomy'. The primary outcomes of interest were the forced expiratory volume in 1 second (FEV1), FEV1 as percent of predicted (%FEV1), change in FEV1 (Δ%FEV1), and the ratio of postoperative to preoperative FEV1. RESULTS: Thirteen studies comprising 2027 patients met the inclusion and exclusion criteria and were included for analysis, including 787 patients in the segmentectomy group and 1240 patients in the lobectomy group. Patients in the segmentectomy group showed significantly better preservation of FEV1 and %FEV1 compared with the lobectomy group. The reduction in FEV1 after surgery was significantly less in the segmentectomy group compared with the lobectomy group, and Δ%FEV1 was significantly higher in the segmentectomy group than in the lobectomy group. CONCLUSION: Segmentectomy results in better preservation of pulmonary function compared with lobectomy in patients with early-stage NSCLC.

Notch1 signaling mediated dysfunction of bone marrow mesenchymal stem cells derived from cyanotic congenital heart disease.

Bone marrow mesenchymal stem cells (BMSCs) derived from cyanotic congenital heart disease (CCHD) exhibit deficient multi-lineage differentiation potential due to the abnormal accumulation of D-galactose. However, the underlying mechanisms have not yet been explored. Here, the multi-lineage differentiation potential of the BMSCs from CCHD and non-CCHD (NCHD) patients were assessed. BMSCs from CCHD patients exhibited inferior multi-lineage differentiation potential with reduced Notch1 protein and mRNA level. Bisulfite sequencing PCR results showed the methylation level of Notch1 promoter was raised, which inhibited the binding of NF-Ya. Exposure BMSCs from NCHD patients with D-galactose under hypoxia (4% O2) decreased the expression of Notch1. And activating Notch1 partially restored the deficient BMSCs of CCHD patients. In conclusion, the impaired multi-lineage differentiation potential of BMSCs from CCHD patients is owing to the decreased Notch1 level with a remarkable hypermethylation in its promoter region. Activated Notch1 signaling pathway could partially restore the deficient BMSCs in the CCHD patients, which may provide a new method on cell therapy in patients with CCHD.

Repair or replacement for severe ischemic mitral regurgitation: A meta-analysis.

BACKGROUND: The best surgical option for severe ischemic mitral regurgitation (IMR) is still controversial. The aim of this study was to perform a meta-analysis to compare the clinical outcomes of mitral valve repair (MVP) with replacement (MVR). METHODS: A literature search was conducted in PubMed, Embase, and Medline using the terms "ischemic mitral regurgitation" and "repair or annuloplasty or reconstruction" and "replacement" in the title/abstract field. The primary outcomes of interest were perioperative mortality and long-term survival. Secondary outcomes were mitral regurgitation (MR) recurrence and reoperation. RESULTS: Of 276 studies, 13 studies met the inclusion and exclusion criteria. A total of 1993 patients were included in these studies, consisting of 1259 (63%) repair cases, and 734 (37%) replacement cases. Perioperative mortality was lower with MVP compared with MVR [OR 0.61; (95% CI, 0.43-0.87; P < .05)]. There was no difference with respect to long-term survival [HR 0.75; (95% CI, 0.52-1.09; P = .14)] and reoperation [OR 0.77; (95% CI, 0.38-1.57; P = .47)]. MVP is associated with a higher recurrence of MR [OR = 4.09; (95% CI, 1.82-9.19; P < .001)]. CONCLUSION: MVP is associated with a lower perioperative mortality but a higher recurrence of MR compared with MVR for severe IMR. No differences were found with respect to long-term survival and reoperation.

Hypoxia induces senescence of bone marrow mesenchymal stem cells via altered gut microbiota.

Systemic chronic hypoxia is a feature of many diseases and may influence the communication between bone marrow (BM) and gut microbiota. Here we analyse patients with cyanotic congenital heart disease (CCHD) who are experiencing chronic hypoxia and characterize the association between bone marrow mesenchymal stem cells (BMSCs) and gut microbiome under systemic hypoxia. We observe premature senescence of BMSCs and abnormal D-galactose accumulation in patients with CCHD. The hypoxia that these patients experience results in an altered diversity of gut microbial communities, with a remarkable decrease in the number of Lactobacilli and a noticeable reduction in the amount of enzyme-degraded D-galactose. Replenishing chronic hypoxic rats with Lactobacillus reduced the accumulation of D-galactose and restored the deficient BMSCs. Together, our findings show that chronic hypoxia predisposes BMSCs to premature senescence, which may be due to gut dysbiosis and thus induced D-galactose accumulation.

Alda-1 Attenuates Lung Ischemia-Reperfusion Injury by Reducing 4-Hydroxy-2-Nonenal in Alveolar Epithelial Cells.

OBJECTIVES: Excessive oxidative stress is a main cause of lung ischemia-reperfusion injury, which often results in respiratory insufficiency after open-heart surgery for a cardiopulmonary bypass. Previous studies demonstrate that the activation of aldehyde dehydrogenase-2 could significantly reduce the oxidative stress mediated by toxic aldehydes and attenuate cardiac and cerebral ischemia-reperfusion injury. However, both the involvement of aldehydes and the protective effect of the aldehyde dehydrogenase-2 agonist, Alda-1, in lung ischemia-reperfusion injury remain unknown. DESIGN: Prospective laboratory and animal investigation were conducted. SETTING: State Key Laboratory of Cardiovascular Disease. SUBJECTS: Primary human pulmonary alveolar epithelial cells, human pulmonary microvascular endothelial cells, and Sprague-Dawley rats. INTERVENTIONS: A hypoxia/reoxygenation cell-culture model of human pulmonary alveolar epithelial cell, human pulmonary microvascular endothelial cell, and an isolated-perfused lung model were applied to mimic lung ischemia-reperfusion injury. We evaluated the effects of Alda-1 on aldehyde dehydrogenase-2 quantity and activity, on aldehyde levels and pulmonary protection. MEASUREMENTS AND MAIN RESULTS: We have demonstrated that ischemia-reperfusion-induced pulmonary injury concomitantly induced aldehydes accumulation in human pulmonary alveolar epithelial cells and lung tissues, but not in human pulmonary microvascular endothelial cells. Moreover, Alda-1 pretreatment significantly elevated aldehyde dehydrogenase-2 activity, increased surfactant-associated protein C, and attenuated elevation of 4-hydroxy-2-nonenal, apoptosis, intercellular adhesion molecule-1, inflammatory response, and the permeability of pulmonary alveolar capillary barrier, thus alleviated injury. CONCLUSIONS: Our study indicates that the accumulation of 4-hydroxy-2-nonenal plays an important role in lung ischemia-reperfusion injury. Alda-1 pretreatment can attenuate lung ischemia-reperfusion injury, possibly through the activation of aldehyde dehydrogenase-2, which in turn removes 4-hydroxy-2-nonenal in human pulmonary alveolar epithelial cells. Alda-1 pretreatment has clinical implications to protect lungs during cardiopulmonary bypass.

Role of augmented transferrin during the retraining for undeveloped left ventricle.

Transposition of great arteries (TGA) is a common congenital heart disease. Left ventricle (LV) is rapidly regressing and pulmonary artery banding (PAB) is utilized to retrain the undeveloped LV. Hence, it offered a unique human disease model to investigate the process of LV hypertrophy under pressure overload. Eight late referred children with TGA were enrolled. The plasma was collected at the 30 min. before and 48 hrs after PAB, and 25 proteins were identified as having significant change in proteomic analysis. Transferrin (TF) and ceruloplasmin were then confirmed. After 48 hrs incubation with TF, the size of human induced pluripotent stem cell-derived cardiomyocytes increased by two times as large as control. Meanwhile, protein synthesis and the expression of natriuretic peptide precursor A and B were significantly enhanced. TF treatment also activated both extracellular signal-regulated kinase 1/2 and activated protein kinase singling pathways. Our data provided a link to molecular components and pathways that might be involved in LV retraining. TF severed as the carrier to delivery irons, and could directly stimulate cardiomyocytes hypertrophy. TF administration may hold therapeutic potential for the biological LV retraining.