Search

BackgroundThe number of people with dementia is soaring. Cognitive reserve has been thought to be associated with dementia risk. It is not clear at which period in the life course and which cognitive reserve proxies contribute to the reduced risk of dementia.MethodsBy scanning four databases (PubMed, Embase, Web of Science, and MEDLINE) up to Jun 3, 2023, longitudinal studies of life-course cognitive reserve and risk of dementia were found. The HRs and 95% CIs for each study were summarized using random effects models. Subgroup analyses and sensitivity analyses were conducted. Utilizing funnel plots, Begg and Egger tests, publication bias was investigated.ResultsA total of 27 studies were included, containing 10 in early-life, 10 in middle-life, and 13 in late-life. All studies used validated questionnaires to measure cognitive reserve, and dementia diagnosis followed recognized worldwide guidelines. All included studies were of medium or low risk. Cognitive reserve in early-life (Hazard ratio (HR): 0.82; 95% confidence interval (CI): 0.79–0.86), middle-life (HR: 0.91; 95% CI: 0.84–0.98) and late-life (HR: 0.81; 95% CI: 0.75–0.88) all have protective effects on dementia risk. Multiple sensitivity analyses showed consistent results.ConclusionDementia risk is reduced by the buildup of cognitive reserves during life-course. Accumulation of proxies for cognitive reserve in early and late life had the greatest effect on dementia risk reduction. Social connection may be an effective approach to lower dementia risk.

Purpose: To compare the effects of whole-body vibration training (WBVT) with different frequencies on the balance ability of older adults.Methods: Randomized controlled trials (RCTs) on the WBVT interventions on balance ability in older adults were searched through PubMed, Web of Science, The Cochrane Library, ProQuest, Embase, Opengrey, China National Knowledge Infrastructure (CNKI), Wanfang, and China Science and Technology Journal Database (CSTJ) databases from the establishment of the database to August 2022, and all literature that met the PICOS (Participants, Intervention, Comparison, Outcomes, Study design) criteria were enrolled. Two reviewers screened and assessed the methodological quality of the included literature according to the physiotherapy evidence database (PEDro) scale criteria. Statistical analysis was performed using Stata 14.0 software after data extraction.Results: Twenty-five RCTs with a total of 1267 subjects were finally included. The results of the pairwise comparison of the Network Meta-analysis showed that the Timed Up and Go Test (TUGT) values of Low-frequency whole-body vibration training (LF-WBVT) was lower than the placebo and traditional rehabilitation groups, and the difference was statistically significant [WMD = −1.37, 95% CI (−2.53, −0.20)] [WMD = −1.84, 95% CI(-3.17,-0.51)]. The Five-repetition Sit-to-Stand Test (5STS) values of LF-WBVT, Medium-frequency whole-body vibration training (MF-WBVT), and High-frequency whole-body vibration training (HF-WBVT) were lower than the placebo and traditional rehabilitation groups, but none of them were statistically significant. In addition, the TUGT and 5STS values of HF-WBVT had a tendency to be lower than those of LF-WBVT and MF-WBVT, but neither of them was statistically different. The cumulative probability ranking results of both TUGT and 5STS showed that HF-WBVT was the best protocol.Conclusion: Current evidence shows that HF-WBVT may be the best protocol for improving balance in older adults. Due to the study’s limitations, the conclusion obtained in this study still needs to be further confirmed by more high-quality studies.Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021250405].

Abstract Background Cardiovascular events (CVEs) was considered as one of the primary cause to reduce the quality of life in breast cancer patients with aromatase inhibitors (AIs) treatment, which has not been sufficiently addressed. The aim of this study was to assess the correlation between risk of CVEs and AIs in patients with breast cancer. Methods Included studies were obtained from the databases of Embase, Pubmed, Cochrane Library, Clinical Trials.gov, and reference lists. The main outcome measures were overall incidence, odds ratios (ORs), and 95% confidence intervals (CIs). Furthermore, the association and the risk differences among different tumor types, AIs,ages,or treatment regimens were conducted. Fixed-effect or random-effect models were applied in the statistical analyses according to the heterogeneity. Our analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results Seventeen studies, which included 44,411 subjects, were included in our analyses. The overall incidence of CVEs in AIs group was 13.02% (95% CI: 8.15–20.17%) and almost all of the high-grade CVEs occurred in patients treated with AIs. The pooled ORs of CVEs was 0.9940 (95% CI: 0.8545–1.1562). Under sub-group analysis, the incidence of CVEs related to exemestane was higher than that of controls (OR = 1.1564, 95% CI: 1.0656–1.2549), but no statistical differences in risk of CVEs were found in other sub-group analysis. No evidence of publication bias was found for incidence of CVEs in our meta-analysis by a funnel plot. Conclusions These results suggest that patients with breast cancer treated with AIs do not have a significant risk of developing CVEs in comparison with the controls, and exemestane might not be considered as the alternative AI to the breast cancer patients from the perspective of CVEs. Further studies are recommended to investigate this association and the risk differences among different tumor types, AIs or treatment regimens.

The aim of this work was to evaluate the efficacy and safety of botulinum toxin A (BTX-A) treatment in patients with neurogenic detrusor overactivity. PUBMED, EMBASE, and Cochrane Library were identified on 13 May 2017 to identify relevant randomized controlled trials. All data obtained were analyzed using Stata 12.0. Five randomized controlled trials were included in this study. Compared to placebo, the BTX-A groups had significantly fewer urinary incontinence (UI) episodes per day and per week (BTX-A with 300 U for frequency of UI per day at week 2, mean difference (MD): −1.13, 95% confidence interval (CI): −1.89 to −0.37; 200 U; BTX-A with 300 U for frequency of UI per week at week 6, MD: −11.42, 95% CI: −13.91 to −8.93; BTX-A with 200 U for frequency of UI per week at week 6, MD: −10.72, 95% CI: −13.40 to −8.04), increased in maximum cystometric capacity at week 6 (BTX-A with 300 U, MD: 154.88, 95% CI: 133.92–175.84; BTX-A with 200 U, MD: 141.30, 95% CI: 121.28–161.33), decreased maximum detrusor pressure at week 6 (BTX-A with 300 U, MD: −31.72, 95% CI: −37.69 to −25.75; BTX-A with 200 U, MD: −33.47, 95% CI: −39.20 to −27.73). For adverse effects, BTX-A was often associated with more complications and urinary tract infections (BTX-A with 300 U: relative risk (RR):1.42, 95% CI: 1.15–1.76; BTX-A with 200 U: RR: 1.42, 95% CI: 1.11–1.82). This meta-analysis suggests that treatment with BTX-A is effective and safe for neurogenic detrusor overactivity, and recommends using BTX-A with 300 U or with 200 U, as suitable dosage.

Background and Objectives: To systematically investigate the association between the dietary inflammatory index (DII) and gestational diabetes mellitus (GDM), with a focus on the role of BMI in this relationship. Methods and Study Design: A comprehensive search was conducted in PubMed, Embase, Web of Science, The Cochrane Library, Medline, CINAHL Complete, Chinese Periodical Full-text Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and China Wanfang Database for relevant observational studies published up to August 2023. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. The pooled effect size was calculated using a random-effects model. Subgroup and meta-regression analyses were performed to explore potential sources of heterogeneity. Results: The study included 54,058 participants from 10 studies. Pregnant women with a higher DII, indicating a pro-inflammatory diet, had a significantly increased risk of GDM compared to those with a lower DII, indicating an anti-inflammatory diet (pooled OR: 1.17, 95% CI: 1.01-1.36; I²=70%, p <0.001). Subgroup analyses revealed a stronger association in normal weight stratification (OR: 1.25, 95%CI: 1.04-1.51), case-control studies (OR: 1.45, 95%CI: 1.03-2.05), Asia (OR: 1.26, 95%CI: 1.10-1.43), Europe (OR: 1.27, 95%CI: 1.09-1.48), 3-day dietary record as a dietary assessment tool (OR: 1.30, 95%CI: 1.16-1.46), physical activity adjustment (OR: 1.28, 95%CI: 1.13-1.46), and energy intake adjustment (OR: 1.33, 95%CI: 1.19-1.48). Meta-regression analysis confirmed that geographical region significantly influenced heterogeneity between studies (p <0.05). Conclusions: An elevated DII is independently linked to a higher risk of GDM, especially in women of normal weight. [ABSTRACT FROM AUTHOR]

Background and objective: Lateral pelvic lymph node (LPLN) metastasis is one of the prominent reasons for local recurrence (LR) in patients with rectal cancer (RC). The evaluation criteria of lateral lymph node dissection (LLND) for patients in eastern (mainly in Japan) and western countries have been controversial. The aim of this study was to analyse the risk factors for LPLN metastasis in order to guide surgical methods. Methods: We searched relevant databases (Embase (Ovid), Medline (Ovid), PubMed, Cochrane Library, and Web of Science) for articles published between 1 January 2000 and 05 October 2022 to evaluate the risk factors for LPLN metastasis in patients with RC in this meta-analysis. Results: A total of 24 articles with 5843 patients were included in this study. The overall results showed that female sex, age <60 years, pretherapeutic CEA level >5 ng/ml, clinical T4 stage (cT4), clinical M1 stage (cM1), distance of the tumour from the anal verge (AV) <50 mm, tumour centre located below the peritoneal reflection (Rb), short axis (SA) of LPLN ≥8mmbefore nCRT, short axis (SA) of LPLN ≥5mmafter nCRT, border irregularity of LPLN, tumour size ≥50 mm, pathological T3-4 stage (pT3-4), pathological N2 stage (pN2), mesorectal lymph node metastasis (MLNM), lymphatic invasion (LI), venous invasion (VI), CRM (+) and poor differentiation were significant risk factors for LPLN metastasis (P <0.05). Conclusion: This study summarized almost all potential risk factors of LPLN metastasis and expected to provide effective treatment strategies for patients with LRC. According to the risk factors of lateral lymph node metastasis, we can adopt different comprehensive treatment strategies. High-risk patients can perform lateral lymph node dissection to effectively reduce local recurrence; In low-risk patients, we can avoid overtreatment, reduce complications and trauma caused by lateral lymph node dissection, and maximize patient survival and quality of life. [ABSTRACT FROM AUTHOR]

Background: Controversy has persisted over the clinical benefits of low-dose sacubitril/valsartan in patients with heart failure (HF). Hypothesis: Low-dose sacubitril/valsartan might also be effective and safe in HF patients. Methods: Electronic databases including PubMed, Ovid, and Cochrane Library were systematically retrieved from inception to August 5, 2021. Review manager 5.4 and Stata 15.1 were employed in this systematic review and meta-analysis. Key efficacy outcomes of interest included HF hospitalization, all-cause mortality, left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), together with New York Heart Association (NYHA) functional class. The safety outcome was systolic blood pressure (SBP). The grading of recommendations assessment, development, and evaluation approach was conducted to evaluate the quality of evidence for each outcome. Results: A total of 1269 studies were screened and 9 real-world studies met the inclusion criteria were included in the meta-analysis, with 1697 participants. Compared with low-dose sacubitril/valsartan, high-dose sacubitril/valsartan significantly reduced the risk of HF hospitalization (odds ratio [OR]: 0.4, 95% confidence interval [CI]: 0.27-0.61, p < .0001) and the risk of all-cause mortality (OR: 0.23, 95% CI: 0.11-0.47, p < .0001). However, there were no appreciable differences in improvements of NYHA (OR: 0.59, 95% CI: 0.15-2.35, p = .45), changes of LVEF (mean difference [MD]: 2.73%, 95% CI: -2.24% to 7.7%, p = .28), changes of NT-proBNP (MD: 43.09, 95% CI: -28.41 to 114.59, p = .24) and changes of SBP (MD: 3.01, 95% CI: -4.62 to 10.64, p = .44) between groups with low-dose and high-dose sacubitril/valsartan. Conclusions: Compared with high-dose sacubitril/valsartan, low-dose sacubitril/valsartan was associated with increased risks of HF hospitalization and all-cause mortality. However, no distinct between-group differences in improvements of NYHA, changes of LVEF, changes of NT-proBNP and changes of SBP were observed. [ABSTRACT FROM AUTHOR]

Introduction ‒ The association between interleukin-6 (IL-6) gene −572 G^C polymorphism and myocardial infarction (MI) risk has not been established. We adopted this meta-analysis for further insight into the case–control studies. Materials and methods ‒ To investigate the genetic association, we searched multiple databases, including Web of Science, EMbase, CBM disc, PubMed and CNKI. Also, we manually identified the searched references. All the statistical analyses were conducted using Stata 11.0. Results ‒ A total of five studies were identified, involving 2,526 MI cases and 3,027 controls. The results revealed a significant association between IL-6 gene −572 G^C polymorphism and MI, implying that the IL-6 gene −572 C allele may be a protective factor for MI (for C allele vs K allele: OR = 0.85, 95% CI = 0.73–0.99, p = 0.041; for C/C vs G/G: OR = 0.55, 95% CI = 0.31–0.98, p = 0.044; for C/C vs G/C + G/G: OR = 0.60, 95% CI = 0.41–0.89, p = 0.011). However, in the subgroup analysis with regard to ethnicity, no significant correlation was identified between IL-6 gene −572 G^C polymorphism and MI among Europeans. Conclusion ‒ The IL-6 gene −572 C allele may be a protective factor for MI. Future studies involving larger sample bases are still recommended. [ABSTRACT FROM AUTHOR]

Background/Aims: Patients with myocardial infarction and hypoxemia require supplemental oxygen. However, the current therapeutic paradigm is contradicted by several recent studies in which the post-infarcted heart appears to benefit from systemic hypoxia. With this systematic review and meta-analysis, we aimed to discover whether systemic hypoxia is beneficial or detrimental to the infarcted myocardium. Methods: We conducted an electronic search of the PubMed, EMBASE, and Web of Science databases and extracted the outcomes of cardiac function, geometry, and hemodynamics. A random-effect model was applied when the I² value of greater than 50%. The sensitivity analysis was performed by omitting one study at a time, and publication bias was assessed using Egger's test. In addition, the quality of studies was evaluated using the risk of bias tool devised by the Systematic Review Centre for Laboratory Animal Experimentation. Results: Six reports comprising 14 experiments were ultimately screened from among 10,323 initially identified preclinical studies. Few studies reported the method of randomization and none described allocation concealment, random outcome assessment or blinding. Overall, chronic hypoxia was found to have a beneficial effect on the ejection fraction (standard mean difference [SMD] = 5.39; 95% confidence interval [CI], 3.83 to 6.95; P < 0.001) of the infarcted heart, whereas acute hypoxia significantly improved hemodynamics, as indicated by an increase in the maximal rate of rise of left ventricular pressure (SMD = 1.27; 95% CI, 0.27 to 2.28; P = 0.013) and cardiac output (SMD = 1.26; 95% CI, 0.34 to 2.18; P = 0.007) and a decrease in total systematic vascular resistance (SMD = -0.89; 95% CI, -1.24 to -0.53; P < 0.001). Furthermore, a reduced oxygen content increased the stroke volume (P = 0.010). However, hypoxia reduced the end-systolic (SMD = -2.67; 95% CI, -4.09 to -1.26; P < 0.001) and end-diastolic (SMD = -3.61; 95% CI, -4.65 to -2.57; P < 0.001) left ventricular diameters and increased the total pulmonary resistance (SMD = 0.76; 95% CI, 0.20 to 1.33; P = 0.008), pulmonary arterial mean pressure (SMD = 2.02; 95% CI, 0.23 to 3.81; P = 0.027), and left atrial pressure (SMD = 1.20; 95% CI, 0.57 to 1.82; P < 0.001). Conclusion: Hypoxia significantly improved heart function after infarction, with particular beneficial effects on systolic function and hemodynamics. However, it had slightly adverse effects on pulmonary circulation and left ventricular geometry. A lower inspired oxygen concentration may improve cardiac function, although further research is needed to determine the optimum level of hypoxia. Finally, more studies of hypoxia and myocardial infarction in larger species are required before these findings can be incorporated into therapeutic guidelines. [ABSTRACT FROM AUTHOR]

Objectives: To assess the analgesic efficacy of transversus abdominis plane (TAP) block in patients undergoing colorectal surgery (CRS).Materials and Methods: The databases of PubMed, ISI Web of Science, and Embase were searched, and randomized controlled studies (RCTs) that compared TAP block to control for relief of postoperative pain in patients who underwent CRS were included. Outcomes, including postoperative pain at rest and with movement, morphine use, postoperative nausea and vomiting, and the length of hospital stay, were analyzed using STATA software. The weighted mean differences (WMDs) with 95% confidence intervals (95% CIs) or relative risk with 95% CI were used to present the strength of associations.Results: A total of 7 RCTs with 511 patients were included. The results of this study suggested that TAP block significantly relieved postoperative pain during postanesthetic recovery after CRS at rest and during movement (WMDs were -0.98 [95% CI -1.57 to -0.38] and -0.68 [-1.07 to -0.30], respectively), and also decreased pain intensity during movement 24 h after CRS (WMD: -0.57 [95% CI -1.06 to -0.08]). TAP block significantly reduced opioid consumption within 24 h when compared to controls, with a WMD of 15.66 (95% CI -23.93 to -7.39). However, TAP block did not shorten the length of hospital stay.Conclusions: TAP block was an effective approach for relief of postoperative pain and reduced postoperative consumption of morphine. More RCTs with large sample sizes are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Importance: The increased social and economic burdens for osteoporosis-related fractures worldwide make the prevention of such injuries a major public health goal. Previous studies have reached mixed conclusions regarding the association between calcium, vitamin D, or combined calcium and vitamin D supplements and fracture incidence in older adults.Objective: To investigate whether calcium, vitamin D, or combined calcium and vitamin D supplements are associated with a lower fracture incidence in community-dwelling older adults.Data Sources: The PubMed, Cochrane library, and EMBASE databases were systematically searched from the inception dates to December 24, 2016, using the keywords calcium, vitamin D, and fracture to identify systematic reviews or meta-analyses. The primary randomized clinical trials included in systematic reviews or meta-analyses were identified, and an additional search for recently published randomized trials was performed from July 16, 2012, to July 16, 2017.Study Selection: Randomized clinical trials comparing calcium, vitamin D, or combined calcium and vitamin D supplements with a placebo or no treatment for fracture incidence in community-dwelling adults older than 50 years.Data Extraction and Synthesis: Two independent reviewers performed the data extraction and assessed study quality. A meta-analysis was performed to calculate risk ratios (RRs), absolute risk differences (ARDs), and 95% CIs using random-effects models.Main Outcomes and Measures: Hip fracture was defined as the primary outcome. Secondary outcomes were nonvertebral fracture, vertebral fracture, and total fracture.Results: A total of 33 randomized trials involving 51 145 participants fulfilled the inclusion criteria. There was no significant association of calcium or vitamin D with risk of hip fracture compared with placebo or no treatment (calcium: RR, 1.53 [95% CI, 0.97 to 2.42]; ARD, 0.01 [95% CI, 0.00 to 0.01]; vitamin D: RR, 1.21 [95% CI, 0.99 to 1.47]; ARD, 0.00 [95% CI, -0.00 to 0.01]. There was no significant association of combined calcium and vitamin D with hip fracture compared with placebo or no treatment (RR, 1.09 [95% CI, 0.85 to 1.39]; ARD, 0.00 [95% CI, -0.00 to 0.00]). No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of nonvertebral, vertebral, or total fractures. Subgroup analyses showed that these results were generally consistent regardless of the calcium or vitamin D dose, sex, fracture history, dietary calcium intake, and baseline serum 25-hydroxyvitamin D concentration.Conclusions and Relevance: In this meta-analysis of randomized clinical trials, the use of supplements that included calcium, vitamin D, or both compared with placebo or no treatment was not associated with a lower risk of fractures among community-dwelling older adults. These findings do not support the routine use of these supplements in community-dwelling older people. [ABSTRACT FROM AUTHOR]

Purpose: This meta-analysis aimed to compare the efficacy and safety of teriparatide vs. bisphosphonates in the management of osteoporosis.Methods: A total of 1,967 patients from eight randomized controlled trials were analyzed; outcomes included bone mineral density (BMD) of the femoral neck, total hip and lumbar spine, vertebral and nonvertebral fractures and any adverse event. A subgroup analysis of treatment effectiveness was performed according to the etiology of osteoporosis; i.e., glucocorticoid-induced osteoporosis (GIO) vs. post-menopausal osteoporosis (PO).Results: Teriparatide increased the BMD of the lumbar spine, femoral neck and total hip to a greater extent than bisphosphonates. Patients treated with teriparatide also had a lower risk of vertebral fractures compared with bisphosphonates; however, no difference in risk of nonvertebral fractures (or adverse events) was found. GIO subgroups showed larger increases in BMD of the lumbar spine, total hip and femoral neck in patients treated with teriparatide compared with bisphosphonates. The PO subgroup showed larger increases in BMD of the lumbar spine in patients treated with teriparatide compared with bisphosphonates. Patients in the GIO subgroup (but not the PO subgroup) were less likely to suffer a vertebral fracture on teriparatide as compared with bisphosphonates. In contrast, no significant difference in the percentage of nonvertebral fractures was noted between the two types of treatment for either subgroup.Conclusion: Teriparatide significantly increased the BMD of lumbar spine, total hip and femoral neck, particularly in GIO-induced osteoporosis. Teriparatide did not lower the risk of nonvertebral fractures when compared with bisphosphonates. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the effectiveness of erythropoietin (EPO) for improving cancer-associated malignant anemia. A search was performed for randomized clinical trials, conducted according to the Cochrane manual, using electronic databases including PubMed, EMBASE, the Cochrane Library and ClinicalTrails.gov up to 15 August 2015. A total of 6 eligible studies from 5 articles enrolling a total of 453 patients were entered into the current meta-analysis. Upon EPO treatment, there were significant differences in the change in hemoglobin (HB) levels compared with the placebo at short-term follow-up [mean difference (MD)=0.66; 95% confidence interval (CI), 0.14-1.18; I2=Not applicable; P=0.01) and long-term follow-up (MD=0.10; 95% CI, 0.02-0.18; I2=Not applicable; P=0.01) under the random effects model. For changes in hematocrit (HCT) compared with the placebo, the results revealed there were significant differences at short-term follow-up (MD=2.47; 95% CI, 0.75-4.19; I2=Not applicable; P=0.005) and long-term follow-up (MD=7.60; 95% CI, 6.15-9.05; I2=Not applicable; P<0.00001) under the random effects model. Compared with the placebo in short-term follow-up under the fixed effects model with homogeneity, the result was a significant difference for the transfusion ratio [relative risk (RR)=0.81; 95% CI, 0.67- 0.97; I2=34%; P=0.02) and the transfusion requirements (MD=-0.45; 95% CI, -0.92, 0.03; I2=6%; P=0.07). Funnel plots did not detect any publication bias. These results suggest that EPO was beneficial to alleviate cancer-associated anemia and improve survival outcomes for patients with cancer. [ABSTRACT FROM AUTHOR]

Background: Nivolumab (BMS-936558/ONO-4538) was the first monoclonal antibody targeting programmed death (PD)-1. So far, a number of clinical trials on nivolumab have showed satisfactory efficacy in treating non-small-cell lung cancer (NSCLC). Herein, we present a meta-analysis evaluating the efficacy and safety of nivolumab for previously treated advanced NSCLC patients. Methods: Electronic databases were searched for eligible literature. Data of objective response rate (ORR), disease control rate, overall survival, progression-free survival, and adverse effects (AEs) were extracted and pooled. Outcomes analyzed and presented in this study were according to the original data from nivolumab 3 mg/kg. Results: In general, nine trials with 817 patients were included in this meta-analysis. The pooled ORR, disease control rate, 1-year overall survival rate, and 1-year progression-free survival rate were 20% (95% confidence interval [CI]: 17%-23%), 36% (95% CI: 22%-51%), 47% (95% CI: 40%-53%), 21% (95% CI: 18%-24%), respectively. In addition, the rate of grade 3-4 AEs was only 8% (95% CI: 6%-12%). Subgroup analysis showed no significant difference in terms of ORR between squamous and non-squamous NSCLC (odds ratio 1.23, 95% CI: 0.63-2.39, P=0.51). However, significantly greater ORR was presented in programmed cell death ligand 1 (PD-L1) positive cohort (ORR 31%, 95% CI: 24%-38%), compared to PD-L1 negative cohort (ORR 12%, 95% CI: 9%-17%). The odds ratio for objective response to nivolumab in PD-L1 positive cases relative to negative cases was 3.08 (95% CI: 1.87-5.08, P,0.0001). Conclusion: In conclusion, nivolumab is a promising second-line agent for previously treated advanced NSCLC with manageable AEs. Both squamous and non-squamous NSCLC patients showed similar efficacy. In addition, patients with positive PD-L1 expression had better response from nivolumab. Microabstract: We present a meta-analysis evaluating the efficacy and safety of nivolumab for previously treated advanced NSCLC patients. In our study, nivolumab is a promising secondline agent for previously treated advanced NSCLC with manageable AEs. Both squamous and non-squamous NSCLC patients showed similar efficacy. In addition, patients with positive PD-L1 expression had better response from nivolumab. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy and safety of Ahmed glaucoma valve implantation (AGV) with trabeculectomy in the management of glaucoma patients. Methods: A comprehensive literature search (PubMed, Embase, Google, and the Cochrane library) was performed, including a systematic review with meta-analysis of controlled clinical trials comparing AGV versus trabeculectomy. Efficacy estimates were the weighted mean differences (WMDs) for the percentage intraocular pressure reduction (IOPR %) from baseline to end-point, the reduction in glaucoma medications, and the odds ratios (ORs) for complete and qualified success rates. Safety estimates were the relative risks (RRs) for adverse events. All outcomes were reported with a 95% confidence interval (CI). Statistical analysis was performed using the RevMan 5.0 software. Results: Six controlled clinical trials were included in this meta-analysis. There was no significant difference between the AGV and trabeculectomy in the IOPR% (WMD = -3.04, 95% CI: -8.36- 2.26; P = 0.26). The pooled ORs comparing AGV with trabeculectomy were 0.46 (0.22, 0.99) for the complete success rate (P = 0.05) and 0.97 (0.78–1.20) for the quantified success rate (P = 0.76). No significant difference in the reduction in glaucoma medicines was observed (WMD = 0.24; 95% CI: -0.27–0.76; P = 0.35). AGV was found to be associated with a significantly lower frequency of all adverse events (RR = 0.71; 95%CI: 1.14–0.97; p = 0.001) than trabeculectomy, while the most common complications did not differ significantly (all p> 0.05). Conclusion: AGV was equivalent to trabeculectomy in reducing the IOP, the number of glaucoma medications, success rates, and rates of the most common complications. However, AGV was associated with a significantly lower frequency of overall adverse events. [ABSTRACT FROM AUTHOR]

Background The increase in childhood obesity is a serious public health concern. Several studies have indicated that breastfed children have a lower risk of childhood obesity than those who were not breastfed, while other studies have provided conflicting evidence. The objective of this meta-analysis was to investigate the association between breastfeeding and the risk of childhood obesity. Methods The PubMed, EMBASE and CINAHL Plus with Full Text databases were systematically searched from start date to 1st August 2014. Based on the meta-analysis, pooled adjusted odds ratio (AOR) and 95% confidence interval (CI) were calculated. I2 statistic was used to evaluate the between-study heterogeneity. Funnel plots and Fail-safe N were used to assess publication bias and reliability of results, and results from both Egger test and Begg test were reported. Results Twenty-five studies with a total of 226,508 participants were included in this meta-analysis. The studies' publication dates ranged from 1997 to 2014, and they examined the population of 12 countries. Results showed that breastfeeding was associated with a significantly reduced risk of obesity in children (AOR = 0.78; 95% CI: 0.74, 0.81). Categorical analysis of 17 studies revealed a dose-response effect between breastfeeding duration and reduced risk of childhood obesity. Conclusion Results of our meta-analysis suggest that breastfeeding is a significant protective factor against obesity in children. [ABSTRACT FROM AUTHOR]

Etanercept (ETN) has been widely applied in the treatment of ankylosing spondylitis (AS). As the use of ETN has increased, associated adverse effects have been reported frequently. Previous meta-analyses have focused on comparing the differences in clinical outcomes between ETN and placebo (PBO). The present meta-analysis evaluated randomised controlled trials (RCTs) to compare the effects of ETN and a PBO or sulfasalazine (SSZ) in patients with AS. The study population characteristics and the main results, including the Assessment in AS 20% response (ASAS 20), the Bath AS Disease Activity Index (BASDAI) and the Bath AS Functional Index (BASFI), were extracted. The pooled odds ratios (ORs) or weighted mean differences (MDs) were calculated using a fixed or random effects model. Fifteen randomised controlled trials (RCTs) involving 2,194 subjects were included. Compared with a PBO, ETN significantly improved the ASAS 20 [P<0.00001; OR, 8.25; 95% confidence interval (CI), 5.92-11.50], BASDAI (P<0.00001; MD, -18.81; 95% CI, -24.47 to -13.15) and BASFI (P<0.00001; standard MD, -0.68; 95% CI, -0.85 to -0.50). In comparison with SSZ, ETN significantly decreased the BASDAI (P<0.00001; MD, -2.40; 95% CI, -2.89 to -1.90) and C-reactive protein (CRP) levels (P<0.0001; MD, -8.01; 95% CI, -11.73 to -4.29). The most common adverse effect of ETN was an injection site reaction. This meta-analysis shows that ETN monotherapy is effective in improving physical function and reducing disease activity in patients with AS. Compared with SSZ, ETN markedly decreased the BASDAI and CRP levels. However, the efficacy of ETN in treating AS requires further evaluation by more RCTs in a larger population of patients prior to recommending ETN as a substitute for synthetic disease-modifying antirheumatic drug (DMARD) monotherapy, or combinations of synthetic DMARDs. [ABSTRACT FROM AUTHOR]

Background To compare the clinical outcomes of external fixator (EF) and intramedullary nails (IN) in the treatment of open tibial fractures. Methods We searched seven electronic databases (PubMed, MEDLINE, EMBASE, OVID, Cochrane library, CNKI, and CBM) for trials of tibial fracture fixation published from 1980 to 2013. The indicators including postoperative infection, malunion, nonunion, soft tissue injury, delayed healing, and healing time were used for quantitative outcome assessments. Results A total of nine trials involving 532 patients (EF, n = 253; IN, n = 279) with open tibia fractures were included in this meta-analysis. The results indicated that the patients undergoing IN had lower incidence of postoperative infection (risk radio [RR] = 3.85; 95% confidence intervals [CI], 2.67-5.54; P < 0.0001), malunion (RR = 2.31; 95% CI, 1.40-3.81; P = 0.001), nonunion (RR = 1.41; 95% CI, 1.06-1.88; P = 0.02) and less healing time (weighted mean difference [WMD] = 6.19; 95% CI, 1.42-10.96; P = 0.01) compared with EF. However, regarding to the soft tissue injury (RR = 0.74; 95% CI, 0.34-1.62; P = 0.45) and delayed healing (RR = 1.38; 95% CI, 0.79-2.43; P = 0.26), there is no significantly difference between EF and IN approach. Conclusion In conclusion, the use of IN is more effective than EF and may be considered as first-line approach in fixation of open tibial fractures. [ABSTRACT FROM AUTHOR]

Blood exosomes, which are extracellular vesicles secreted by living cells into the circulating blood, are regarded as a relatively noninvasive novel tool for monitoring brain physiology and disease states. An increasing number of blood cargo-loaded exosomes are emerging as potential biomarkers for preclinical and clinical Alzheimer’s disease. Therefore, we conducted a meta-analysis and systematic review of molecular biomarkers derived from blood exosomes to comprehensively analyze their diagnostic performance in preclinical Alzheimer’s disease, mild cognitive impairment, and Alzheimer’s disease. We performed a literature search in PubMed, Web of Science, Embase, and Cochrane Library from their inception to August 15, 2020. The research subjects mainly included Alzheimer’s disease, mild cognitive impairment, and preclinical Alzheimer’s disease. We identified 34 observational studies, of which 15 were included in the quantitative analysis (Newcastle-Ottawa Scale score 5.87 points) and 19 were used in the qualitative analysis. The meta-analysis results showed that core biomarkers including Aβ1–42, P-T181-tau, P-S396-tau, and T-tau were increased in blood neuron-derived exosomes of preclinical Alzheimer’s disease, mild cognitive impairment, and Alzheimer’s disease patients. Molecules related to additional risk factors that are involved in neuroinflammation (C1q), metabolism disorder (P-S312-IRS-1), neurotrophic deficiency (HGF), vascular injury (VEGF-D), and autophagy-lysosomal system dysfunction (cathepsin D) were also increased. At the gene level, the differential expression of transcription-related factors (REST) and microRNAs (miR-132) also affects RNA splicing, transport, and translation. These pathological changes contribute to neural loss and synaptic dysfunction. The data confirm that the above-mentioned core molecules and additional risk-related factors in blood exosomes can serve as candidate biomarkers for preclinical and clinical Alzheimer’s disease. These findings support further development of exosome biomarkers for a clinical blood test for Alzheimer’s disease. This meta-analysis was registered at the International Prospective Register of Systematic Reviews (Registration No. CRD4200173498, 28/04/2020).

Background and AimThe effectiveness of total neoadjuvant therapy (TNT) on patients with locally advanced rectal cancer (LARC) is controversy. This study aims to compare the prognostic value of TNT with standard neoadjuvant chemoradiotherapy (CRT) for LARC.MethodsWe searched databases (Embase [Ovid], Medline [Ovid], PubMed, Cochrane Library, and Web of Science) for articles published between January 1, 2000, and March 10, 2022. Studies on evaluating the effects of TNT and standard CRT on the prognosis of LARC were included. The primary outcomes were overall survival (OS) and disease-free survival (DFS).Results19 primary studies, involving 10 randomized controlled trials, 3 prospective studies and 6 retrospective studies, with data on 5,074 patients treated for LARC were included in the meta-analysis. Statistical analyses revealed that, compared with standard CRT, TNT significantly improved OS (hazard ratio [HR]=0.77, 95% confidence interval [CI]=0.65–0.90, I2 = 30%, P = 0.17), DFS (HR = 0.85, 95% CI = 0.74–0.97, I² = 11%, P = 0.35), distant metastases-free survival (DMFS, HR = 0.76, 95% CI = 0.65–0.90, I² = 0%, P = 0.50), pathological complete response rate (pCR, OR = 1.89, 95% CI = 1.61–2.22, I² = 0%, P = 0.47), and R0 resection rate (OR = 1.33, 95% CI = 1.07–1.67, I² = 16%, P = 0.28), but local recurrence-free survival (LRFS, HR = 1.12, 95% CI = 0.90–1.39, I² = 4%, P = 0.37).ConclusionsComprehensive literature research shows that TNT showed excellent short-term efficacy in terms of pCR and R0 resection rate while also improved the long-term outcomes of OS, DFS and DMFS, might become a new standard of treatment in patients with LARC. Even so, more studies and longer follow-up were still warranted.

Abstract Background Mounting evidence shows that microRNA-34a (miR-34a) is involved in cancer prognosis. Therefore, we summarize the predictive role of miR-34a for survival in patients with gastrointestinal cancers (GICs). Methods All eligible studies were found by searching PubMed, Web of Science and EMBASE, and survival results were extracted. Then, the hazard ratio (HR) with the corresponding 95% confidence interval (CI) was calculated to evaluate the prognostic role of miR-34a in GICs. The association between miR-34a expression and clinicopathological characteristics was estimated by odds ratios (ORs) and 95% CIs. Results A total of 20 studies were included in this meta-analysis. For overall survival (OS), lower miR-34a expression could probably predict poorer outcome in GICs, with a pooled HR of 1.86 (95% CI: 1.52–2.28, P

Background and Aim: The risk factors for bile leakage after hepatectomy without biliary reconstruction are controversial. This study investigated the risk factors for bile leakage after hepatectomy without biliary reconstruction.Methods: We searched databases (Embase (Ovid), Medline (Ovid), PubMed, Cochrane Library, and Web of Science) for articles published between January 1, 2000, and May 1, 2021, to evaluate the risk factors for bile leakage after hepatectomy without biliary reconstruction.Results: A total of 16 articles were included in this study, and the overall results showed that sex (OR: 1.21, 95% CI: 1.04–1.42), diabetes (OR: 1.21, 95% CI: 1.05–1.38), left trisectionectomy (OR: 3.53, 95% CI: 2.32–5.36), central hepatectomy (OR: 3.28, 95% CI: 2.63–4.08), extended hemihepatectomy (OR: 2.56, 95% CI: 1.55–4.22), segment I hepatectomy (OR: 2.56, 95% CI: 1.50–4.40), intraoperative blood transfusion (OR:2.40 95%CI:1.79–3.22), anatomical hepatectomy (OR: 1.70, 95% CI: 1.19–2.44) and intraoperative bleeding ≥1,000 ml (OR: 2.46, 95% CI: 2.12–2.85) were risk factors for biliary leakage. Age >75 years, cirrhosis, underlying liver disease, left hepatectomy, right hepatectomy, benign disease, Child–Pugh class A/B, and pre-operative albumin