High pretreatment D-dimer level is an independent unfavorable prognostic factor of small cell lung cancer: A systematic review and meta-analysis

Background:High pretreatment level of D-dimer in small cell lung cancer (SCLC) is commonly encountered, but the impact of high pretreatment D-dimer level on the prognosis of SCLC patients remains undetermined. Therefore, we conducted this meta-analysis focusing specifically on the prognostic value of high pretreatment D-dimer level in SCLC patients comprehensively.Methods:We searched systematically in PubMed, Embase, and Web of Science for relevant studies published before January 28, 2019. Outcomes including 1-year overall survival (OS), progression-free survival (PFS) rates, and hazard ratios (HRs) of OS and PFS from multivariate analysis were extracted and analyzed.Results:A total of 5 cohort studies consisting of 813 SCLC patients (473 patients with high pretreatment level of D-dimer and 340 with normal level of D-dimer) were finally included for meta-analysis. We found that patients with high pretreatment level of D-dimer had significantly shorter 1-year OS (47.6% vs 79.9%; fixed effects: risk ratio [RR] = 2.506; 95% confidence interval [CI] = [1.948, 3.224]; P < .001) and PFS (15.8% vs 34.0%; random effects: RR = 1.294; 95% CI = [1.060, 1.579]; P = .011) rates than those with normal level of D-dimer. Moreover, high pretreatment D-dimer level was further proved to remain as an unfavorable predictor of OS (fixed effects: HR = 1.865; 95% CI = [1.469, 2.367]; P < .001; I² = 7.6%) and PFS (fixed effects: HR = 1.513; 95% CI = [1.183, 1.936]; P = .001; I² = 0.0%) in patients with SCLC.Conclusion:High pretreatment level of D-dimer was found to be an independent unfavorable prognostic factor in SCLC patients. However, more studies with sufficient adjustment for confounding factors are encouraged to confirm our conclusions.     

The relationship between NLR/PLR/LMR levels and survival prognosis in patients with non-small cell lung carcinoma treated with immune checkpoint inhibitors

Background:The relationship between neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) and the dire prognosis of non-small cell lung carcinoma patients who received immune checkpoint inhibitors (ICIs) are not known yet.Methods:We screened the articles that meet the criteria from the database. The relationship between NLR/PLR/LMR levels and the survival and prognosis of non-small cell lung cancer patients treated with ICIs was analyzed. Summarize hazard ratio (HR) with 95% confidence interval (CI) to study progression-free survival (PFS) and overall survival (OS).Results:Thirty-four studies involving 3124 patients were enrolled in the final analysis. In short, high pre-treatment NLR was related to poor OS (HR = 2.13, 95% CI:1.74–2.61, P < .001, I² = 83.3%, P < .001) and PFS (HR = 1.77, 95% CI:1.44–2.17, P < .001, I² = 79.5%, P < .001). Simultaneously, high pre-treatment PLR was related to poor OS (HR = 1.49, 95% CI:1.17–1.91, P < .001, I² = 57.6%, P = .003) and PFS (HR = 1.62, 95% CI:1.38–1.89, P < .001, I² = 47.1%, P = .036). In all subgroup analysis, most subgroups showed that low LMR was related to poor OS (HR = 0.45, 95% CI: 0.34–0.59, P < .001) and PFS (HR = 0.60, 95% CI: 0.47–0.77, P < 0.001, I² = 0.0%, P < .001).Conclusion:High pre-treatment NLR and pre-treatment PLR in non-small cell lung carcinoma patients treated with ICIs are associated with low survival rates. Low pre-treatment and post-treatment LMR are also related to unsatisfactory survival outcomes. However, the significance of post-treatment NLR and post-treatment PLR deserve further prospective research to prove.     

Laparo-endoscopic single-site surgery vs conventional laparoscopic surgery for endometrial cancer: A systematic review and meta-analysis

Objective:To systematically review and evaluate the safety, advantages and clinical application value of laparo-endoscopic single-site surgery (LESS) for endometrial cancer by comparing it with conventional laparoscopic surgery (CLS).Methods:We conducted a systematic review of the published literature comparing LESS with CLS in the treatment of endometrial cancer. English databases including PubMed, Embase, Ovid, and the Cochrane Library and Chinese databases including Chinese National Knowledge Infrastructure, Wanfang and China Biology Medicine were searched for eligible observational studies up to July 10, 2019. We then evaluated the quality of the selected comparative studies before performing a meta-analysis using the RevMan 5.3 software. The complications, surgical time, blood loss during surgery, postoperative length of hospital stay and number of lymph nodes removed during surgery were compared between the 2 surgical approaches.Results:Four studies with 234 patients were finally included in this meta-analysis. We found that there was no statistically significant difference in complications between the 2 surgical approaches [odds ratio (OR): 0.63, 95% confidence interval (CI): 0.18–2.21, P = .47, I² = 0%]. There was no statistically significant difference in blood loss between the 2 surgical approaches [mean difference (MD): –61.81, 95% CI: –130.87 to –7.25, P = .08, I² = 74%]. There was no statistically significant difference in surgical time between the 2 surgical approaches (MD: –11.51, 95% CI: –40.19 to 17.16, P = .43, I² = 81%). There was also no statistically significant difference in postoperative length of hospital stay between the 2 surgical approaches (MD: –0.56, 95% CI: –1.25 to –0.13, P = .11, I² = 72%). Both pelvic and paraaortic lymph nodes can be removed with either of the 2 procedures. There were no statistically significant differences in the number of paraaortic lymph nodes and total lymph nodes removed during surgery between the 2 surgical approaches [(MD: –0.11, 95% CI: –3.12 to 2.91, P = .29, I² = 11%) and (MD: –0.53, 95% CI (–3.22 to 2.16), P = .70, I² = 83%)]. However, patients treated with LESS had more pelvic lymph nodes removed during surgery than those treated with CLS (MD: 3.33, 95% CI: 1.05–5.62, P = .004, I² = 32%).Conclusion:Compared with CLS, LESS did not reduce the incidence of complications or shorten postoperative hospital stay. Nor did it increase surgical time or the amount of bleeding during surgery. LESS can remove lymph nodes and ease postoperative pain in the same way as CLS. However, LESS improves cosmesis by leaving a single small scar.     

Treatments of unruptured brain arteriovenous malformations: A systematic review and meta-analysis

Background:The best therapeutic option for unruptured brain arteriovenous malformations (bAVMs) patients is disputed.Objective:To assess the occurrence of obliteration and complications of patients with unruptured bAVMs after various treatments.Methods:A systematic literature search was performed in PubMed, EMBASE, Web of Science, and so on to identify studies fulfilling predefined inclusion criteria. Baseline, treatment, and outcomes data were extracted for statistical analysis.Results:We identified 28 eligible studies totaling 5852 patients. The obliteration rates were 98% in microsurgery group (95% confidence interval (CI): 96%–99%, I² = 74.5%), 97% in surgery group (95%CI: 95%–99%, I² = 18.3%), 87% in endovascular treatment group (95%CI: 80%–93%, I² = 0.0%), and 68% in radiosurgery group (95%CI: 66%–69%, I² = 92.0%). The stroke or death rates were 1% in microsurgery group (95%CI: 0%–2%, I² = 0.0%), 0% in surgery group (95%CI: 0%–1%, I² = 0.0%), 4% in endovascular treatment group (95%CI: 0%–8%, I² = 85.8%), and 3% in radiosurgery group (95%CI: 3%–4%, I² = 82.9%). In addition, the proportions of hemorrhage were 2% in microsurgery group (95%CI: 1%–4%, I² = 0.0%), 23% in endovascular treatment group (95%CI: 7%–39%), and 12% in radiosurgery group (95%CI: 12%–13%, I² = 99.2%). As to neurological deficit, the occurrence was 9% in microsurgery group (95%CI: 6%–11%, I² = 94.1%), 20% in surgery group (95%CI: 13%–27%, I² = 0.0%), 14% in endovascular treatment group (95%CI: 10%–18%, I² = 64.0%), and 8% in radiosurgery group (95%CI: 7%–9%, I² = 66.6%).Conclusions:We found that microsurgery might provide lasting clinical benefits in some unruptured bAVMs patients for its high obliteration rates and low hemorrhage. These findings are helpful to provide a reference basis for neurosurgeons to choose the treatment of patients with unruptured bAVMs.     

When to Perform Surgical Resection or Radiofrequency Ablation for Early Hepatocellular Carcinoma?: A Nomogram-guided Treatment Strategy

Radiofrequency ablation (RFA) is indicated for early-stage hepatocellular carcinoma (HCC), but the comparative efficacy between RFA and surgical resection (SR) is inconclusive. We aim to develop a prognostic nomogram for predicting recurrence-free survival (RFS) after RFA. We also evaluate the possibility of using nomogram in improving treatment algorithm.We retrospectively enrolled 836 patients with Barcelona Clínic Liver Cancer very-early/early-stage HCC receiving SR or RFA. A visually-orientated nomogram was constructed with Cox proportional hazards model, and number and size of tumor, platelet count, albumin level, and model for end-stage liver disease score were included. The concordance index of the nomogram was 0.69.Radiofrequency ablation patients were stratified into low and high-risk groups by the median of nomogram scores. The RFS and overall survival (OS) of 2 risk groups were compared with SR patients with propensity score matching analysis. SR provided better RFS and OS compared with high-risk (nomogram score ≥9.8) RFA patients in the propensity model. The 5-year RFS rates were 36% versus 11%, whereas the 5-year OS rates were 74% versus 60% for SR and high-risk RFA groups, respectively (both P < 0.05). However, SR was associated with better RFS (5-year RFS rates 41% vs 29%), but similar OS (5-year OS rates 80% vs 81%), compared with low-risk (nomogram score <9.8) RFA patients in the propensity model (P < 0.05 and P > 0.05, respectively).In conclusion, this user-friendly nomogram offers individualized recurrence risk estimation and stratification for early HCC patients receiving curative RFA. The nomogram can be integrated into current treatment algorithm. SR should be considered the first-line treatment for high-risk patients to achieve better long-term survival.     

Prevalence and risk factors of hypertension among Hui population in China: A systematic review and meta-analysis based on 30,565 study participants

Background:Hypertension (HTN) has been considered as a health concern in developing countries. And Hui is a minority group with a large population in China. Its genetic background, inadequate access to health services, eating habits, religious belief, ethnic customs, and other factors differ from that of other ethnic groups, which may influence the prevalence of HTN. However, there is no current meta-analysis on the prevalence and risk factors of HTN among Hui population. Thus we conducted a systematic review aiming to estimate the pooled prevalence and risk factors of HTN among Hui population.Methods:PubMed, The Cochrane library, Web of science, CINAHL Complete, Weipu Database (VIP), China Knowledge Resource Integrated Database (CNKI), Wanfang Database, and SinoMed were systematically searched from inception to February 28, 2020 with publication language restricted to English and Chinese. We included cross-sectional, case–control, or cohort studies that focused on prevalence and risk factors of HTN among Hui population. Two investigators independently assessed the risk of bias of the studies included in the review using tools developed by JBI. Meta-analysis was conducted using Stata 12.0 software package.Results:Twenty-three studies were identified with a total of 30,565 study participants. The overall pooled prevalence of HTN was 28% (95% confidence interval [CI]: 24%–32%, I² = 98.8%, P < .001). Stratified by gender, the pooled prevalence of HTN in Hui was 26% (95%CI: 20%–33%, I² = 97.6%, P < .001) for males and 30% (95%CI: 23%–37%, I² = 98.3%, P < .001) for females. Pooled prevalence of HTN in Hui was 2% (95%CI: 2%–6%, I² = 70.6%, P = .065), 10% (95%CI: 3%–17%, I² = 83.7%, P < .001), 22% (95%CI: 12%–32%, I² = 87.9%, P < .001), 37% (95%CI: 20%–53%, I² = 94.0%, P < .001), 39% (95%CI: 24%–54%, I² = 97.7%, P < .001) and 42% (95%CI: 29%–56%, I² = 95.6%, P < .001) for those aged 18 to 29, 30 to 39, 40 to 49, 50 to 59, 60 to 69, and ≥70 years, respectively. Pooled prevalence of HTN in Hui was 22% (95%CI: 14%–29%, I² = 97.9%, P < .001) in urban areas and 23% (95%CI: 16%–30%, I² = 95.8%, P < .001) in rural areas. Daily salt intake (odd ratio [OR] = 3.94, 95%CI: 3.03–5.13, I² = 90.2%, P < 001), family history (OR = 3.50, 95%CI: 2.60–4.71, I² = 95.3%, P < .001), smoking (OR = 1.84, 95%CI: 1.61–2.09, I² = 59.6%, P < .001), drinking (OR = 1.74, 95%CI: 1.26–2.39, I² = 95.3%, P = .001), weekly meat intake (OR = 1.92, 95%CI: 1.04–3.54, I² = 96.5%, P = .036), body mass index (OR = 2.20, 95%CI: 1.81–2.66, I² = 91.3%, P < .001), and areas (OR = 1.29, 95%CI: 1.10–1.51, I² = 81.5%, P = .001) were risk factors of HTN in Hui, while physical exercise (OR = 0.76, 95%CI: 0.66–0.88, I² = 62.7%, P < .001) was protective factor.Conclusions:The pooled prevalence of HTN among Hui people was 28%, daily salt intake, family history, drinking, smoking, weekly meat intake, body mass index, areas, and physical exercise were all risk factors for HTN among Hui population. Early screening and treatment of HTN among Hui population should be given due attention.     

LKB1 expression and the prognosis of lung cancer: A meta-analysis

Background:In the past few decades, many lines of evidence implicate the importance of liver kinase B1 (LKB1) as a tumor suppressor gene in the development and progression of solid tumours. However, the prognostic and clinicopathological value of LKB1 in patients with lung cancer are controversial. This article aimed to investigate the latest evidence on this question.Methods:A systematic literature searched in the PubMed, Web of Science, Embase, Cochrane library, Scopus until September 20, 2020. The association between overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), clinicopathological features and LKB1 were analysed by meta-analysis.Results:Eleven studies including 1507 patients were included in this meta-analysis. The pooled results revealed that low LKB1 expression was significantly associated with poor overall survival (OS) (HR = 1.67, 95% CI: 1.07–2.60, P = .024) in lung cancer. However, no association was found between LKB1 expression and DFS/PFS (HR = 1.29, 95% CI: 0.70–2.39, P = .410). Pooled results showed that low LKB1 expression was associated with histological differentiation (poor vs moderate or well, OR = 4.135, 95% CI:2.524–6.774, P < .001), nodal metastasis (absent vs present, OR = 0.503, 95% CI: 0.303–0.835, P = .008) and smoking (yes vs no, OR = 1.765, 95% CI: 1.120–2.782, P = .014).Conclusion:These results suggest that low expression of LKB1 can be considered as a unfavorable prognostic biomarker for human lung cancer, which should be further researched.     

The Prognostic Value of Platelet Count in Patients With Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Thrombocytopenia has been acknowledged to be a crucial risk factor for cirrhosis formation and hepatocarcinogenesis in chronic liver diseases. However, to date, the association between platelet count (PLT) and the prognosis of hepatocellular carcinoma (HCC) remains inconsistent and controversial.The aim of the present study was to determine whether PLT could be used as a useful predictor of survival in patients with HCC.We performed systematic review in online databases, including PubMed, EmBase, and Web of Science, from inception until 2014. Studies were included if a statistical relationship was investigated between PLT and survival for HCC, and hazard ratio (HR) and 95% confidence intervals (CIs) for overall survival (OS) or recurrence-free survival (RFS) were provided. The quality of each included study was assessed by Newcastle–Ottawa scale score. To synthesize these studies, a random-effects model or a fixed-effects model was applied as appropriate. Then, we calculated heterogeneity, performed sensitivity analysis, tested publication bias, and did subgrouped and meta-regression analysis.Finally, we identified 33 eligible articles (published from 1998 to 2014) involved 5545 patients by retrieval. A low level of preoperative PLT was found to be significantly associated with a poor survival of HCC. Irrespective of the therapy used, the pooled HRs for OS and RFS were 1.41 (95% CI, 1.14–1.75) and 1.44 (95% CI, 1.13–1.83), respectively. Specifically, in patients who underwent liver resection, the pooled HRs for OS and RFS were 1.67 (95% CI, 1.22–2.27) and 1.44 (95% CI, 1.04–1.99), respectively. Furthermore, patients with preoperative thrombocytopenia (PLT < 100 × 10⁹/L) had a worse OS (HR: 1.73, 95% CI, 1.29–2.32) and RFS (HR: 1.57, 95% CI, 1.31–1.87) in comparison with patients without thrombocytopenia. All our findings showed no significant changes due to the removal of any study or the use of an opposite-effects model, and there was no significant publication bias. The limitations of this meat-analysis were nonuniform cut-off values of PLT, high between-study heterogeneities, potential confounders, and a bias of publication year.A low preoperative PLT level results in an unfavorable outcome in HCC. PLT is a simple, inexpensive, and useful predictor of survival in patients with HCC.     

Clinicopathological and prognostic value of preoperative lymphocyte to monocyte ratio for hepatocellular carcinoma following curative resection: A meta-analysis including 4,092 patients

Background:Previous studies have reported that lymphocyte-to-monocyte ratio (LMR) had novel prognostic value in hepatocellular carcinoma (HCC). The purpose of this meta-analysis was to synthetically evaluate the prognostic role of preoperative LMR in HCC patients following curative resection.Methods:Eligible studies were acquired through searching Pubmed, Web of Science, Cochrane Library and EMbase update to September 2019. Merged hazard ratios (HRs) and 95% confidence intervals (CIs) were applied as effect sizes.Results:A total of ten studies containing 4,092 patients following liver resection were enrolled in this meta-analysis. The pooled results demonstrated that preoperative elevated LMR indicated superior survival outcome (HR: 0.58, 95% CI: 0.34–0.96, P = .035) and recurrence-free survival (RFS)/disease-free survival/time to recurrence (HR = 0.76, 95% CI: 0.58–0.98, P = .034). The significant prognostic role of preoperative LMR was detected in the subgroup of all publication year, country of origin, sample sizes <300, TNM stage of I–IV and LMR cut-off value ≤4. Furthermore, high LMR was significantly associated with male, high AFP, large tumor size, incomplete tumor capsule, advanced TNM stage and BCLC stage, and presence of PVTT.Conclusion:Elevated preoperative LMR indicated superior survival outcome in HCC patients following curative resection, and might serve as a novel prognostic biomarker.     

Preoperative Standardized Uptake Value of Metastatic Lymph Nodes Measured by 18F-FDG PET/CT Improves the Prediction of Prognosis in Gastric Cancer

This study assessed whether preoperative maximum standardized uptake value (SUVmax) of metastatic lymph nodes (LNs) measured by ¹⁸F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) could improve the prediction of prognosis in gastric cancer.One hundred fifty-one patients with gastric cancer and pathologically confirmed LN involvement who had undergone preoperative ¹⁸F-FDG PET/CT prior to curative surgical resection were retrospectively enrolled. To obtain nodal SUVmax, a transaxial image representing the highest ¹⁸F-FDG uptake was carefully selected, and a region of interest was manually drawn on the highest ¹⁸F-FDG accumulating LN. Conventional prognostic parameters and PET findings (primary tumor and nodal SUVmax) were analyzed for prediction of recurrence-free survival (RFS) and overall survival (OS). Furthermore, prognostic accuracy of survival models was assessed using c-statistics.Of the 151 patients, 38 (25%) experienced recurrence and 34 (23%) died during follow-up (median follow-up, 48 months; range, 5–74 months). Twenty-seven patients (18%) showed positive ¹⁸F-FDG nodal uptake (range, 2.0–22.6). In these 27 patients, a receiver-operating characteristic curve demonstrated a nodal SUVmax of 2.8 to be the optimal cutoff for predicting RFS and OS. The univariate and multivariate analyses showed that nodal SUVmax (hazard ratio [HR] = 2.71, P < 0.0001), pathologic N (pN) stage (HR = 2.58, P = 0.0058), and pathologic T (pT) stage (HR = 1.77, P = 0.0191) were independent prognostic factors for RFS. Also, nodal SUVmax (HR = 2.80, P < 0.0001) and pN stage (HR = 2.28, P = 0.0222) were independent prognostic factors for OS. A predictive survival model incorporating conventional risk factors (pT/pN stage) gave a c-statistic of 0.833 for RFS and 0.827 for OS, whereas a model combination of nodal SUVmax with pT/pN stage gave a c-statistic of 0.871 for RFS (P = 0.0355) and 0.877 for OS (P = 0.0313).Nodal SUVmax measured by preoperative ¹⁸F-FDG PET/CT is an independent prognostic factor for RFS and OS. Combining nodal SUVmax with pT/pN staging can improve survival prediction precision in patients with gastric cancer.     

Efficiency and safety of ablation procedure for the treatment of atrial fibrillation in valve surgery: A PRISMA-compliant cumulative systematic review and meta-analysis

Background:Atrial fibrillation is the main complication of patients who suffer from valvular heart disease (VHD), which may lead to an increased susceptibility to ventricular tachycardia, atrial dysfunction, heart failure, and stroke. Therefore, seeking a safe and effective therapy is crucial in prolonging the lives of patients with VHD and improving their quality of life.Methods:Our target database included PubMed, Web of Science, Embase, and Cochrane Library, from which published articles were retrieved from inception to June 2020. We retrieved all randomized controlled trials (RCTs) that compared patients undergoing valve surgery with (VSA) or without ablation (VS) procedure. Studies to be included were screened and data extraction was performed independently by 2 investigators. The Cochrane risk-of-bias table was used to evaluate the methodological quality of the included RCTs. The mean difference (MD) with 95% confidence interval (CI) and relative risk (RR) ratio was calculated to analyze the data. Heterogeneity was evaluated using I² and chi-square tests. Egger test and the trim and fill analysis were used to further determine publication bias.Results:Fourteen RCTs that included 1376 patients were eventually selected for this meta-analysis. Surgical ablation was found to be effective in restoring sinus rhythm in valvular surgery patients at discharge (RR 2.91, 95% CI [1.17, 7.20], I² 97%, P = .02), 3 to 6 months (RR 2.85, 95% CI [2.27, 3.58], I² 49%, P < .00001), 12 months, and more than 1 year after surgery (RR 3.54, 95% CI [2.78, 4.51], I² 27%, P < .00001). All-cause mortality (RR 0.98, 95% CI [0.64, 1.51], I² 0%, P = .94) and stroke (RR 1.29, 95% CI [0.70, 2.39], I² 0%, P = .57) were similar in the VSA and VS groups. Compared with VS, VSA prolonged cardiopulmonary bypass time (MD 30.44, 95% CI [17.55, 43.33], I² 88%, P < .00001) and aortic cross-clamping time (MD 19.57, 95% CI [11.10, 28.03], I² 89%, P < .00001). No significant differences were found between groups with respect to the risk of bleeding (RR 0.64, 95% CI [0.37, 1.12], I² 0%, P = .12), heart failure (RR 1.11, 95% CI [0.63, 1.93], I² 0%, P = .72), and low cardiac output syndrome (RR 1.41, 95% CI [0.57, 3.46], I² 18%, P = .46). However, the demand for implantation of a permanent pacemaker was significantly higher in the VSA group (RR 1.84, 95% CI [1.15, 2.95], I² 0%, P = .01).Conclusion:Although we found high heterogeneity in the restoration of sinus rhythm at discharge, we assume that the comparison is valid at this time, given the current state in the operating room. This study provides evidence of the efficacy and security of concomitant ablation intervention for patients with VHD and atrial fibrillation. Surgical ablation would increase the safety of implantation of a permanent pacemaker in the population that underwent valve surgery.     

Association between SOCS3 hypermethylation and HBV-related hepatocellular carcinoma and effect of sex and age: A meta-analysis

Background:Suppressor 3 of cytokine signaling (SOCS3) hypermethylation has been reported to participate in hepatocellular carcinoma (HCC) development and progression, but conflicting results were published. This study aimed to analyze the clinical effects of SOCS3 hypermethylation in HCC and the effects of sex and age on SOCS3 hypermethylation in HCC.Methods:Databases were searched for relevant case-control and cohort studies on SOCS3 hypermethylation in HBV-related HCC. In vitro and in vivo studies and studies of patients with serious comorbidities were excluded. Review Manager 5.2 was used to estimate the effects of the results among the selected studies. Forest plots, sensitivity analysis, and bias analysis for the included studies were also conducted.Results:Finally, 8 relevant studies met the inclusion criteria. A significant difference in SOCS3 hypermethylation in HCC was found between tumor and nontumor groups (the odds ratio [OR] = 2.01, 95% confidence interval [CI]: 1.48–2.73, P < .00001; P for heterogeneity = .39, I² = 5%). The meta-analysis suggested no significant difference in the effect of sex (OR = 1.00, 95% CI: 0.76–1.31, P = .76; P for heterogeneity = .44, I² = 0%) and age on SOCS3 hypermethylation in HCC (OR = 1.11, 100% CI: 0.78–1.29, P = .03; P for heterogeneity = .14, I² = 36%). Limited publication bias was observed in this study.Conclusion:SOCS3 hypermethylation is associated with HBV-related HCC. Sex and age do not affect the association between SOCS3 hypermethylation and HCC. SOCS3 might be a treatment target for HCC.     

Diagnostic utility of CT for abdominal injury in the military setting: A systematic review and meta-analysis

Background:It is critical to accurately identify patients with abdominal injury who truly need to undergo laparotomy during the war in timely fashion. The diagnostic utility of computed tomography (CT) for evaluating abdominal injury in the military setting remains uncertain.Methods:PubMed, EMBASE, and Cochrane Library databases were searched. Meta-analyses were performed by using a random-effect model. We pooled the area under the summary receiver operating characteristic curves with standard errors, the Q indexes with standard errors, the sensitivities with 95% confidence intervals (CIs), the specificities with 95% CIs, the positive likelihood ratios with 95% CIs, the negative likelihood ratios with 95% CIs, and the diagnostic odds ratios with 95% CIs. The heterogeneity among studies were evaluated by the I² and P value.Results:Overall, 5 retrospective studies were included. The area under the summary receiver operating characteristic curve was 0.9761 ± 0.0215 and the Q index was 0.9302 ± 0.0378. The pooled sensitivity was 0.97 (95% CI = 0.92–0.99) without a significant heterogeneity among studies (I² = 0%, P = .4538). The pooled specificity was 0.95 (95% CI = 0.93–0.97) with a significant heterogeneity among studies (I² = 90.6%, P < .0001). The pooled positive likelihood ratio was 10.71 (95% CI: 2.91–39.43) with a significant heterogeneity among studies (I² = 89.2%, P < .0001). The pooled negative likelihood ratio was 0.07 (95% CI = 0.02–0.27) with a significant heterogeneity among studies (I² = 57.5%, P = .0516). The pooled diagnostic odds ratio was 177.48 (95% CI = 18.09–1741.31) with a significant heterogeneity among studies (I² = 75.9%, P = .0023).Conclusion:Diagnostic accuracy of CT for abdominal injury is excellent in the military setting. Further work should explore how to shrink CT equipment for a wider use in wartime.     

Overexpression of macrophage-colony stimulating factor-1 receptor as a prognostic factor for survival in cancer: A systematic review and meta-analysis

Background:The relation between the expression of macrophage-colony stimulating factor-1 receptor (CSF-1R) and prognosis of cancer patients has been evaluated in multiple studies, but the results remain controversial. We, therefore, performed a meta-analysis and systematic review to figure out the role of CSF-1R in the prognosis of patients with cancer.Methods:Several databases were searched, including Web of Science, PubMed, and EMBASE. All human studies were published as full text. The Newcastle–Ottawa risk of bias scale was applied to evaluate the research. We extracted hazard ratios (HRs) with 95% confidence interval (95% CI) which assessed progression-free survival (PFS) and overall survival (OS) in order to assess the impacts of CSF-1R on the prognosis of cancer patients.Results:A total of 12 citations were identified, with studies including 2260 patients in different cancer types that met the eligibility criteria. It was suggested in a pooled analysis that the over-expression of CSF-1R was significantly related to worse PFS (HR: 1.68; P < .001, 1.25–2.10, 95% CI) and also poorer OS (HR=1.28; P < .001, 1.03–1.54, 95% CI). Analysis in subgroups indicated over-expressed CSF-1R was significantly associated with worse OS in hematological malignancy (HR = 2.29; P < .001, 1.49–3.09, 95% CI; model of fixed-effects; I² = 0.0%, P < .001). Sensitivity analysis suggested that there was no study influencing the stability of the results.Conclusions:The overexpression of CSF-1R was significantly predictive of worse prognosis in those who suffer from different kinds of malignancies, particularly in hematological malignancy, which indicates that it might be a potential biomarker of prognosis in cancer survival and a potential molecular target in the treatment of malignant tumors.     

Risk of herpes zoster associated with biological therapies for psoriasis and psoriatic arthritis: A systematic review and meta-analysis

Background:Biological therapy is effective for the treatment of psoriasis and psoriatic arthritis; however, adverse effects related to immunosuppression, such as viral infections, have been reported. Amongst these infections, herpes zoster (HZ) is common.Objective:To evaluate the risk of HZ in psoriasis and psoriatic arthritis patients treated with biological therapy.Data sources:A comprehensive literature search of PubMed, Embase, and Web of Science was performed using certain keywords until October 9, 2020. Nine studies were included after a detailed assessment.Study eligibility criteria:The eligibility criteria included randomized controlled trials (RCTs) and observational studies of patients with psoriasis or psoriatic arthritis treated with biological therapies; compared with non-biological therapies, non-biological systemic therapies, or controls; with the incidence of HZ reported in case and control groups. The Cochrane risk of bias tool and Newcastle-Ottawa scale were used to assess the quality of the RCTs and observational studies, respectively. Data were extracted from 9 eligible studies and then analyzed using Stata software (Version 12.0).Results:The risk of HZ in biological therapies was higher than that in non-biological (odds ratios [OR]: 1.48; 95% confidence interval [CI]: 1.18–1.86; I² = 0%) and non-biological systemic (OR: 1.32; 95% CI: 1.02–1.71; I² = 0%) therapies. Furthermore, the risk of HZ associated with tumor necrosis factor-α inhibitors increased significantly (OR: 1.50; 95% CI: 1.11–2.02; I² = 0%). Notably, infliximab (OR: 2.43; 95% CI: 1.31–4.50; I² = 0%) and etanercept (OR: 1.65; 95% CI: 1.07–2.56; I² = 0%) increased the risk of HZ, while adalimumab (OR: 1.21; 95% CI: 0.64–2.30; I² = 0%), ustekinumab (OR: 2.20; 95% CI: 0.89–5.44; I² = 0%), alefacept (OR: 1.46; 95% CI: 0.20–10.47; I² = 0%), and efalizumab (OR: 1.58; 95% CI: 0.22–11.34; I² = 0%) did not.Limitations:Few RCTs have reported HZ incidents; thus, our results require confirmation via large-scale RCTs.Conclusions and implications of key findings:Biological therapies, especially tumor necrosis factor-α inhibitors, may lead to the risk of HZ in psoriasis and psoriatic arthritis patients. Amongst these agents, infliximab and etanercept have been shown to significantly increase the risk of HZ. Additionally, younger age and female sex may be risk factors.Systematic review registration number:INPLASY202110027.     

Effects of regular breakfast habits on metabolic and cardiovascular diseases: A protocol for systematic review and meta-analysis

Background:Breakfast, which is considered as an important meal of the day, is being ignored by an increasing number of people as the pace of modern life accelerates. Although a large number of previous studies have reported the relationship between skipping breakfast and type 2 diabetes mellitus, most of them were cross-sectional studies. It remains unclear how skipping breakfast affects such specific cardio-metabolic diseases as hypertension, strokes and hypercholesterolemia.Methods:The protocols and reports of this meta-analysis are based on a meta-analysis of observational studies in epidemiological guidelines (MOOSE). Relevant studies were systematically retrieved from PubMed, Embase, Web of Science and the Cochrane Library, and were restricted to English from the inception to May 10, 2019. All the results were obtained by RRs, and outcomes of interests should include the occurrence of cardiovascular and metabolic diseases.Results:Fourteen cohort studies in total were eventually included. Compared with people having breakfast frequency_{≦3times/week}, those with a frequency_{>3 times/week} have reduced the risk of type 2 diabetes mellitus, obesity, Metabolic Syndrome, Low high-density lipoprotein cholesterolemia, Cardiovascular Diseases, cardiovascular Mortality, hypertension and strokes, with (RR = 0.8 [95% CI: 0.7–0.91], P = .142, I² = 37.6%), (RR = 0.74 [95% CI: 0.59–0.94], P < .001, I² = 89%), (RR = 0.86 [95% CI:0.75–0.99], P = .512, I² = 0%), (RR = 0.75 [95% CI:0.61–0.93], P = .643, I² = 0%), (RR = 0.87 [95% CI:0.81–0.93], P = .479, I² = 0%), (RR = 0.63 [95% CI:0.51–0.78], P = .396, I² = 0%), (RR = 0.92 [95% CI:0.86–0.98], P = .419, I² = 0.7%), and (RR = 0.89 [95% CI:0.79–0.99], P = .238, I² = 29%), respectively.Conclusions:A regular daily breakfast habit benefits the cardio-metabolism to a great extent, reducing the risk of Cardiovascular Diseases, type 2 diabetes mellitus, obesity, hypertension, strokes, Metabolic Syndrome, cardiovascular Mortality, Low high-density lipoprotein cholesterolemia, and Abdominal obesity, while it is not significantly related to hypercholesterolemia and coronary heart disease regardless of gender. Nevertheless, skipping breakfast once a week may greatly reduce the benefits of cardio-metabolism. Therefore, public institutions should promote and encourage citizens to cultivate regular daily breakfast habits.     

Overexpression of MMP14 predicts the poor prognosis in gastric cancer: Meta-analysis and database validation

Background:Plenty of studies have showed matrix metalloproteinase 14 (MMP14) expression might be associated with the prognosis of gastric cancer (GC). However, no definite conclusion has been obtained for the contradictory results.Methods:We searched PubMed, Web of science, Embase, and Cochrane library for eligible studies. The association between MMP14 expression and prognostic outcomes of GC was evaluated. Hazard ratio (HR) and 95% confidence interval (CI) were integrated to show the effect of MMP14 expression on the overall survival (OS) or recurrence-free survival (RFS). Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was used to validate the association of MMP14 expression with OS or RFS in GC. A brief bioinformatics analysis was also performed to determine the prognostic role of MMP14 expression in GC.Results:High MMP14 expression was associated with shorter OS compared to low MMP14 expression in GC (HR = 1.95, P < .01). Patients with high MMP14 expression tended to have worse differentiation (P = .03), deeper tumor invasion (P < .01), earlier lymph node metastasis (P < .01), earlier distant metastasis (P < .01) and more advanced clinical stage (P < .01) compared to those with low MMP14 expression. The data from TCGA and GEO showed MMP14 was overexpressed in tumor tissues compared to normal tissues (P < .05), and high MMP14 expression was significantly related to shorter OS (HR = 1.70, 95% CI = 1.32–2.20, P < .01) and RFS (HR = 1.45, 95% CI = 1.15–1.83, P < .01) compared to low MMP14 expression in GC. Expression of MMP14 was linked to functional networks involving the biological process, metabolic process, response to stimulus, cell communication and so on. Functional network analysis suggested that MMP14 regulated the protein digestion and absorption, extracellular matrix receptor interaction, focal adhesion, ribosome, spliceosome, and so on.Conclusion:High MMP14 expression was associated with worse prognosis of GC compared to low MMP14 expression. MMP14 expression could serve as a prognostic factor and potential therapeutic target of GC.     

Thymosin alpha-1 therapy improves postoperative survival after curative resection for solitary hepatitis B virus-related hepatocellular carcinoma: A propensity score matching analysis

Thymosin alpha-1 (Tα1) is an immunomodulatory and antiviral agent with potential effects on chronic hepatitis B and liver cancer. Its impact on solitary hepatocellular carcinoma (HCC) remains controversial, so we aimed to investigate the efficacy of Tα1 in solitary HBV-related HCC patients after curative resection.Between May 2010 and April 2016, 468 patients with solitary HBV-related HCC after curative resection were analyzed. Propensity score matching (PSM) was used to minimize confounding variables. Risk factors were identified by the Cox proportional hazards model. Recurrence-free survival (RFS) rates, overall survival (OS) rates, immunological, and virologic response were compared.The median follow up was 60.0 months. Immunological response improved in the Tα1 group compared with the control group (P < .001) but the virologic response was similar between 2 groups after 24 months. Patients with Tα1 therapy had better RFS and OS before (P = .018 and P < .001) and after (P = .006 and P < .001) propensity matching. Multivariate analysis revealed that Tα1 therapy was an independent prognostic factor for both OS (P < .001, HR = 0.308, 95% CI: 0.175–0.541) and RFS (P < .001, HR = 0.381, 95% CI: 0.229–0.633).Tα1 as an adjuvant therapy improves the prognosis of solitary HBV-related HCC patients after curative liver resection.     

Prognostic value of EGFR and p-EGFR in nasopharyngeal carcinoma: A systematic review and meta-analysis

Purpose:To evaluate the prognostic effect and clinical significance of epidermal growth factor receptor and its phosphorlated form (EGFR/p-EGFR) in nasopharyngeal carcinoma.Methods:A systematic review and meta-analysis was designed. We visited PubMed, Embase, China National Knowledge Infrastructure Database, Database of Chinese sci-tech periodicals, WanFang Database, and China Biology Medicine disc to search for Chinese and English publications of prospective studies and retrospective studies investigating the association of EGFR/p-EGFR and nasopharyngeal carcinoma prognosis from inception to April 2021. The inclusion criteria were that the samples should be pathologically confirmed as nasopharyngeal carcinoma and the expression of EGFR/p-EGFR should be detected via immunohistochemistry; the study should analyze the prognostic significance of EGFR/p-EGFR in nasopharyngeal carcinoma; hazard ratio (HR) and 95% confidence interval (CI) should be reported in the study or could be derived from survival curves; and the outcomes of the study should include overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS).Results:A total of 18 studies evaluating 1451 samples were included. For studies that reported OS as an outcome, EGFR overexpression indicated worse OS of nasopharyngeal carcinoma patients. The heterogeneity between studies was high (I² = 91%, P < .01), and a random-effect model was used to combine the effect size (HR = 1.71, 95% CI [1.21, 2.41], P < .01). Further sensitivity analysis and prespecified subgroup analysis were performed to detect the source of heterogeneity, and the results showed that the heterogeneity could not be eliminated. Publication bias assessed by funnel plots and Begg test and Egger test was low (Begg test: P = .846 and Egger test: P = .074). p-EGFR was not correlated with the OS of nasopharyngeal carcinoma patients (HR = 1.01, 95% CI [0.88, 1.15], P = .92). For studies that reported DFS, EGFR overexpression was associated with worse DFS in patients with nasopharyngeal carcinoma (HR = 2.53, 95% CI [1.84, 3.47], P < .01). For studies that reported PFS, EGFR overexpression was not correlated with the PFS of nasopharyngeal carcinoma patients (HR = 1.86, 95% CI [0.90, 3.82], P = .09). For studies that reported DMFS, EGFR overexpression was not correlated with the DMFS of nasopharyngeal carcinoma patients, and high heterogeneity between studies was detected (I² = 97%, P < .01). A random-effect model was used to combine the effect size (HR = 1.80, 95% CI [0.56, 5.76], P = .32). A sensitivity analysis was conducted. Publication bias was detected to be low (Begg test: P = .817 and Egger test: P = .954). There was no correlation between p-EGFR overexpression and DMFS in patients with nasopharyngeal carcinoma (HR = 1.20, 95% CI [0.95, 1.52], P = .12).Conclusion:In nasopharyngeal carcinoma patients, EGFR overexpression could be used as a biomarker that predicts poor OS and DFS, but not a prognostic biomarker for PFS and DMFS. The overexpression of p-EGFR was not shown to be associated with the prognosis of nasopharyngeal carcinoma patients and could not be used as a prognostic biomarker.Ethics and dissemination:This study was registered on the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), and reported as stated by the Preferred Reporting Items for Systematic reviews and Meta-Analyses. Neither ethical approval nor informed consent was required since this study was conducted based on previous publications.INPLASY registration number:INPLASY 202150010     

The efficacy and safety of gemcitabine-based induction chemotherapy for locally advanced nasopharyngeal carcinoma treated with concurrent chemoradiation: A meta-analysis

Objectives:To assess the efficacy and toxicity of gemcitabine-based induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal carcinoma (LA-NPC).Methods:Both observational studies (OBS) and randomized controlled trials (RCT) were included in the meta-analysis. Systematic online searches were conducted in Web of Sciences, PubMed, Embase, meeting proceedings and ClinicalTrials.gov from the inception to May 25, 2020. The primary endpoint of interest was overall survival.Results:five OBSs and 2 RCTs including 1680 patients were incorporated in the analysis. The evidence from the RCTs showed that adding gemcitabine-based induction chemotherapy to CCRT significantly improved progression free survival (hazard ratio (HR): 0.60, 95% confidence interval (CI): 0.40–0.88; P = .010; chi square P = .25; I² = 24%) and overall survival (HR: 0.47; 95% CI: 0.28–0.80; P = 0.005; chi square P = .49, I² = 0%) and was related to a higher risk of hematological toxicities. Furthermore, based on the data of OBSs, overall survival (HR: 0.52; 95% CI: 0.31–0.88; P = .02; chi square P = .37, I² = 6%) was significantly improved in patients treated with gemcitabine-based induction chemotherapy compared to those treated with taxane-based induction chemotherapy. However, the progression free survival (HR: 0.67; 95% CI: 0.45–1.01; P = .06; chi square P = .74; I² = 0%) showed no significant difference.Conclusions:For LA-NPC patients, adding gemcitabine-based induction chemotherapy to CCRT significantly improved overall survival and progression free survival with a higher risk of hematological toxicities when compared to CCRT alone. Also, gemcitabine-based regimen could be used as an alternative induction chemotherapy regimen to taxane-based regimen in the treatment of LA-NPC.