The efficacy and safety of immune-checkpoint inhibitors plus chemotherapy versus chemotherapy for non-small cell lung cancer: An updated systematic review and meta-analysis.

BACKGROUND: Immune-checkpoint inhibitors(ICIs) combined with chemotherapy are emerging as an effective first-line treatment in advanced non-small cell lung cancer (NSCLC); however, reports on the magnitude of effectiveness and safety are conflicting. METHODS: Relevant articles published before February 2022 were searched in PubMed, Embase, and the Cochrane Library. The study included all randomized controlled trials that evaluated ICIs with chemotherapy versus chemotherapy for the treatment of NSCLC. Among the outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAEs). RESULTS: Our meta-analysis included a total of 12 studies. Overall analysis indicated that ICIs plus chemotherapy could significantly improve OS (HR = 0.79; 95% CI: 0.74-0.84; I2 = 44.4%, P = 0.055), PFS (HR = 0.62; 95% CI: 0.59-0.67; I2 = 75.3%, P = 0.000), and ORR (RR = 1.48; 95% CI: 1.27-1.73; I2 = 79.0%, P = 0.000) when compared to chemotherapy treatments. Subgroup analysis showed that PD-1/PD-L1 inhibitors combined with chemotherapy significantly improved OS, PFS, and ORR when compared with chemotherapy with decreased grade 1-2 TRAEs. In addition, female patients with nonsquamous histology might receive more OS benefit from ICIs plus chemotherapy when compared to chemotherapy alone. Despite the fact that CTLA-4 inhibitors combined with chemotherapy increased PFS, there were no benefits gained in OS nor ORR. When PD-L1/CTLA-4 inhibitors were added to chemotherapy, the risk of grade 3-5 adverse events increased whereas PD-1 inhibitors did not. CONCLUSIONS: ICIs plus chemotherapy, compared with chemotherapy, were associated with significantly improved PFS, ORR, and OS in NSCLC therapy. However, PD-L1/CTLA-4 inhibitors plus chemotherapy could increase the risk of grade 3-5 adverse events, but not PD-1 inhibitors plus chemotherapy.

Association between obstructive sleep apnea and Alzheimer's disease-related blood and cerebrospinal fluid biomarkers: A meta-analysis.

INTRODUCTION: Recent studies indicate that Alzheimer's disease- (AD) related biomarkers, including amyloid ß (Aß40 and Aß42) and tau proteins (P-tau and T-tau), in blood and cerebrospinal fluid (CSF) are associated with obstructive sleep apnea (OSA). However, the results have been inconsistent. Therefore, the primary purpose of this meta-analysis was to determine the relationship between blood and CSF AD-related biomarkers and OSA. METHODS: We searched the Embase, PubMed, Scopus, and Cochrane Library databases for relevant articles till February 2022. RESULTS: Eight articles were finally included after the literature screening, including 446 patients with OSA and 286 controls. Pooled analysis showed that CSF Aß42 (SMD = -0.220, P = 0.136), T-tau (SMD = 0.012, P = 0.89), and P-tau (SMD = 0.099, P = 0.274) levels were not different between patients with OSA and controls. In patients with moderate to severe OSA, CSF Aß42 (SMD = -0.482, P = 0.031) were significantly lower than in controls. Blood T-tau (SMD = 0.560, P = 0.026), P-tau (SMD = 0.621, P < 0.001), and Aß40 (SMD = 0.656, P < 0.001) levels were significantly higher in patients with OSA than in controls. Blood Aß42 (SMD = 0.241, P = 0.232) were not different between patients with OSA and controls. CONCLUSION: OSA is associated with changes in AD-related markers. Higher OSA severity may be associated with the development of AD. AD-related biomarkers, especially in the blood, are clinically efficient, less invasively assessed and monitored, and may be useful for detecting OSA and related cognitive impairments. Further studies are needed to confirm these results.

Association between the circulating superoxide dismutase and obstructive sleep apnea: a meta-analysis.

PURPOSE: Although it has been reported that superoxide dismutase (SOD) is related to obstructive sleep apnea (OSA), the results are controversial. In addition, the effects of the continuous positive airway pressure (CPAP) treatment on SOD levels are also inconsistent. The primary purpose of the present meta-analysis is to determine the relationship between the circulating SOD levels and OSA. METHODS: The studies included in this meta-analysis were selected from the PubMed, Embase, Cochrane Library, and Scopus databases. Two researchers independently reviewed the studies. Data analysis was performed using Stata 15.1. The overall effects were measured using the standardized mean difference (SMD) with a 95% confidence interval (CI). A random-effects model or a fixed-effects model was used, depending on the heterogeneity of the studies. RESULTS: A total of 14 studies were included, comprising 1240 patients and 457 controls. The results showed that the circulating SOD levels of the patients with OSA were significantly lower than that of the control group (SMD = - 1.645, 95% CI = - 2.279 to - 1.011, P < 0.001). We also studied changes in the circulating SOD levels in patients with OSA after the CPAP treatment. No significant difference was observed in the circulating SOD levels after the CPAP treatment (SMD = - 0.028, 95% CI = - 0.218 to 0.162, P = 0.772). CONCLUSION: The results suggested that patients with OSA have reduced levels of SOD and were related to disease severity. The results also indicated that circulating SOD levels may be a reliable marker for detecting systemic oxidative stress in patients with OSA. However, the circulating SOD levels were not affected by the short-term (4-12 weeks) CPAP treatment. Therefore, further large-scale, well-designed randomized controlled trials with a longer CPAP therapy (more than 6 months preferably) and good adherence to the treatment are needed to investigate this issue.

Effects of Continuous Positive Airway Pressure on Cell Adhesion Molecules in Patients with Obstructive Sleep Apnea: A Meta-Analysis.

PURPOSE: Previous studies have confirmed that patients with obstructive sleep apnea (OSA) have higher systemic inflammatory markers, including intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), and E-selectin compared to control subjects. However, the effects of continuous positive airway pressure (CPAP) therapy on circulating levels of ICAM-1, VCAM-1, and E-selectin in OSA patients remain inconsistent. Therefore, the primary purpose of the present meta-analysis is to estimate the effect of CPAP therapy on these cell adhesion molecules (CAMs) in patients with OSA. METHODS: The PubMed, Scopus, Embase, and Cochrane Library databases were searched. The overall effects were measured by the standardized mean difference (SMD) with a 95% confidence interval (CI). A random effects model or a fixed-effects model was used, depending on the heterogeneity of the studies. RESULTS: A total of 11 studies were included, comprising 650 OSA patients. The pooled results showed that CPAP therapy significantly decreased ICAM-1 (SMD = - 0.283, 95% CI - 0.464 to - 0.101, p = 0.002) and E-selectin levels (SMD = - 0.349, 95% CI - 0.566 to - 0.133, p = 0.002). In contrast, there was no significant improvement of VCAM-1 levels after CPAP treatment (SMD = - 0.160, 95% CI - 0.641 to 0.320, p = 0.513). CONCLUSIONS: Our meta-analysis demonstrated that CPAP treatment significantly decreased the circulating levels of ICAM-1 and E-selectin in OSA patients. Thus, ICAM-1 and E-selectin may be effective markers to evaluate CPAP therapy for reducing OSA cardiovascular risk in clinical practice.

Changes in insular cortex metabolites in patients with obstructive sleep apnea syndrome.

The aim of this study was to investigate the changes in insular cortex metabolites and the correlation with clinical manifestations in patients with obstructive sleep apnea syndrome (OSA). Lateral insular metabolite levels were measured and relevant ratios were calculated in OSA patients and healthy individuals, including N-acetyl aspartate/creatine (NAA/Cr), choline/creatine (Cho/Cr), inositol/creatine (Ins/Cr), glutamate compound/creatine (Glx/Cr), N-acetyl aspartate/choline (NAA/Cho), and lactic acid (Lac). Participants' scores on the Hamilton Anxiety Scale (HAMA), the Hamilton Depression Scale (HAMD), the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale (ESS) were also evaluated. Apnea-Hypopnea Index, the lowest arterial oxygen saturation, and the mean arterial oxygen saturation (MSaO2) values were monitored by polysomnography. NAA/Cr, Glx/Cr, and NAA/Cho values in the insular cortex were significantly decreased, whereas HAMA, HAMD, PSQI, and ESS scores were significantly higher in OSA patients compared with the control participants. HAMA and HAMD scores showed a significant negative correlation with the NAA/Cho value in the insular cortex and a positive correlation with PSQI and ESS scores. PSQI scores were correlated positively with the Cho/Cr and Ins/Cr ratios in the left insular cortex, but correlated negatively with the NAA/Cho ratio. The symptoms of anxiety and depression in OSA patients may be associated with insular neuron damage or dysfunction; proton magnetic resonance spectroscopy can provide an objective imaging basis for the early diagnosis and treatment of OSA in clinical practice.