First-line treatment with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in type 2 diabetic population at low risk of cardiovascular disease: a meta-analysis.

Background: The benefit of first-line use of sodium-dependent glucose transport 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) with low risk of cardiovascular diseases are not clear. Methods: PubMed, EMBASE and Cochrane Library databases were searched to identify eligible randomized controlled trials. We used the odds ratio (OR) and mean difference (MD) and the corresponding 95% confidence interval (CI) to assess the dichotomous and continuous variable, respectively. Results: Thirteen studies involving 2,885 T2DM at low risk of cardiovascular diseases were included. Compared to placebo, first line use of SGLT2i significantly reduced glycosylated hemoglobin type A1C (HbA1c) (MD: -0.72), weight (MD: -1.32) and fasting plasma glucose (FPG) (MD: -27.05) levels. Compared with metformin, SGLT2i reduced body weight (MD: -1.50) and FPG (MD: -10.13) more effectively, with similar reduction for HbA1c (MD: -0.05). No significant increased safety adverse was found for SGLT2i, including nasopharyngitis (OR: 1.07), urinary tract infection (OR: 2.31), diarrhea (OR: 1.18) and hypoglycemia (OR: 1.06). GLP-1RAs significantly reduced HbA1c (MD: -1.13), weight (MD: -2.12) and FPG (MD: -31.44) levels as first-line therapy compared to placebo. GLP-1RAs significantly increased occurrence of diarrhea (OR: 2.18), hypoglycemia (OR: 3.10), vomiting (OR: 8.22), and nausea (OR: 4.41). Conclusion: First line use of SGLT2i and GLP-1RAs is effective in reducing HbA1c, weight, and FPG levels in T2DM patients at low risk for cardiovascular disease. SGLT2i may be superior to metformin in controlling body weight and FPG. GLP-1RAs may increase the occurrence of diarrhea, hypoglycemia, vomiting, and nausea. Systematic review registration: PROSPERO (International Prospective Register of Systematic Reviews. https://www.york.ac.uk/inst/crd, CRD42022347233).

Effects of aerobic and combined aerobic-resistance exercise on motor function in sedentary older adults: A randomized clinical trial.

BACKGROUND: Sedentary behavior is widespread among older adults and accelerates the decline of motor function. Nevertheless, there is insufficient evidence concerning the effectiveness of regular exercise in enhancing the same in sedentary older adults. OBJECTIVE: To compare the effects of 24 weeks of aerobic and combined aerobic-resistance exercise on the motor function of sedentary older adults. METHODS: Sixty healthy sedentary older (65-80 years) were randomly enrolled. Participants were randomly divided into 3 groups (1:1:1): aerobic exercise group (AEG), combined aerobic-resistance exercise group (CEG), and health education group (HEG). The training group underwent a five-day-a-week regimen, with each session lasting for 40 minutes (including 10 min warm-up and cool-down). HEG received only monthly health lectures. We assessed lower limb muscle strength (30-second sit-to-stand ability), single-dual task gait, static and dynamic balance functions at baseline and after 24 weeks of intervention using per-protocol analysis. RESULTS: Among 60 elderly healthy who were randomized (mean age 70.59 ± 3.31 years; 28 women (46%)), 42 (70%) completed the evaluation after 24 weeks. Both the aerobic exercise and combined aerobic-resistance exercise groups exhibited improved 30-second sit-to-stand ability, static balance in closed-eye standing mode, and dynamic balance (P< 0.05). However, there were no statistically significant changes in the single-task gait parameters of stride length, stride width, and stride speed (P> 0.05). Additionally, compared to the aerobic exercise group, the combined exercise group showed an increase in dual-task gait speed and medial and lateral dynamic stability indices (P< 0.05). CONCLUSION: Both the aerobic exercise and combined aerobic-resistance exercise programs are effective in enhancing lower limb muscle strength, dynamic balance, and static balance while standing with eyes closed in sedentary older adults. Furthermore, the combined aerobic-resistance exercise program is more effective in improving dual-task gait speed as well as medial and lateral dynamic balance.

Reduced radiation dose and volume of contrast medium in heart rate-based, one-stop computed tomography angiography of coronary, carotid and cerebrovascular arteries.

BACKGROUND: Computed tomography angiography (CTA) is a reliable, non-invasive screening method for diagnosing panvascular disease. By using low contrast agent volume, CTA imaging enables one-stop multi-organ scanning, thereby minimizing the potential risk of contrast-induced nephropathy in patients with impaired renal function. PURPOSE: To evaluate the feasibility of one-stop CTA following a heart rate (HR)-based protocol using a low volume of contrast medium (CM) for examination of the coronary, carotid and cerebrovascular arteries. MATERIAL AND METHODS: Sixty patients undergoing coronary carotid, and cerebrovascular CTA after a single injection of CM were recruited and randomly divided into two groups. Group A (n = 30) underwent CTA following a traditional protocol. The timing of the scans in Group B (n = 30) was determined according to the patient's HR. RESULTS: The CT values for the thoracic aorta (432.2 ± 104.28 HU), anterior cerebral artery (303.96 ± 99.29 HU), and right coronary artery (366.70 ± 85.10 HU) in Group A did not differ significantly from those in Group B (445.80 ± 106.13, 293.73 ± 75.25 and 344.13 ± 111.04 HU, respectively). The qualities of most of the scanned images for both groups were scored as 3 or 4 (on a five-point scale). The radiation dose and the volume of CM were significantly higher in Group A (303.05 ± 110.95 mGy) (100 mL) than in Group B (239.46 ± 101.12 mGy) (50 mL). CONCLUSION: The radiation dose and volume of CM were significantly reduced in CTA following the HR-based protocol. The personalized administration of CM also simplified the scanning process.

Association of CCL4 rs10491121 and rs1634507 gene polymorphisms with cancer susceptibility: trial sequential analysis and meta-analysis.

Background: Although numerous case-control studies have explored the association between CC cytokine ligand-4 (CCL4) expression and cancer susceptibility, their results have been conflicting. This study aimed to determine the still-unknown connection of CCL4 rs10491121 and rs163450 polymorphisms with cancer susceptibility. Methods: Several databases, such as Web of Science, PubMed, and EMBASE, were searched for papers published since the creation of the database until November 2, 2022. Using RevMan 5.4 and StataMP 17 softwares, meta-analysis and subgroup analysis were performed after article screening and data extraction. For sensitivity analyses, one-by-one exclusion method was used, and then, the comprehensive effect was estimated and compared with that before exclusion. Trial sequential analysis (TSA)was performed using TSA 0.9.5.10 beta software. Results: Seven case-control studies encompassing 3559 cases and 4231 controls were included. The P value was greater than 0.05 for all models, indicating the absence of an evident relationship of CCL4 gene rs10491121 and rs1634507 polymorphisms with cancer susceptibility. However, in the subgroup analysis of rs10491121, the P values in all models studied by us except GA vs. AA were <0.05 considering the Chinese subgroup, suggesting that the G allele is a risk factor for cancer in the Chinese population. Besides, in the subgroup analysis of rs1634507 considering oral cancer, the co-dominant model GG vs. TT, dominant model GG + GT vs. TT, and allele model G vs. T groups showed OR < 1 and P < 0.05, indicating that the G allele was a protective factor of oral cancer. However, for other cancer types, all the models studied by us except GG vs. GT showed OR > 1 and P < 0.05, indicating that the G allele was a risk factor for these other cancers. Despite the statistically significant results, sensitivity analysis had some stability limitations, and TSA results suggested the possibility of false positives. Conclusion: For rs10491121, we identified an association between the G allele and increased cancer risk in the Chinese population. For rs1634507, the G allele was not found to be associated with reduced risk of oral cancer and increased risk of other cancers studied by us.

Efficacy and safety of paxlovid (nirmatrelvir/ritonavir) in the treatment of COVID-19: An updated meta-analysis and trial sequential analysis.

Our study is aimed to access the efficacy and safety outcomes for coronavirus disease 2019 (COVID-19) patients treated with Paxlovid. According to inclusion and exclusion criteria, databases were used to retrieve articles from 1 January 2020 to 1 January 2023. Article screening, quality evaluation and data extraction were completed and cross-checked. The meta-analysis and trial sequential analysis (TSA) were conducted using RevMan, StataMP, and TSA software. A total of 42 original articles were included. Overall meta-analysis results showed that for death, hospitalisation, death or hospitalisation, emergency department (ED) visit, intensive care unit (ICU) admission, and extra oxygen requirement outcomes, every odds ratio (OR) was <1 and p < 0.05. For rebound outcome, the OR was >1 and p > 0.05. For adverse events (AEs) outcome, the OR was >1 and p < 0.05. In conclusion, Paxlovid effectively reduced the risks of death, hospitalisation, death or hospitalisation, ED visit, ICU admission, and extra oxygen requirement. There was no significant statistical difference considering rebound, but people should pay attention to possible AEs. However, for rebound and AEs outcomes, observations in certain subgroups suggested conclusions contrary to the overall meta-analysis. Trial sequential analysis indicated these two outcomes have a risk of false negative or false positive conclusions, so additional original studies are needed for further validation.

Influenza vaccination is associated with a decreased risk of atrial fibrillation: A systematic review and meta-analysis.

Background: Evidence from longitudinal studies has shown that influenza infection is linked to an increased risk of arrhythmia. Therefore, we aimed to assess the role of influenza vaccination in arrhythmia prevention. Materials and methods: The PubMed, Embase, and Cochrane Library databases were searched to identify studies that investigated the potential effects of the influenza vaccine on arrhythmia risk published until October 25th, 2021. The study was registered with PROSPERO (CRD42022300815). Results: One RCT with 2,532 patients and six observational studies with 3,167,445 patients were included. One RCT demonstrated a non-significant benefit of the influenza vaccine against arrhythmias [odds ratio (OR) = 0.43, 95% confidence interval (CI): 0.11-1.64; P = 0.20] in patients after myocardial infarction or those with high-risk stable coronary heart disease. A meta-analysis based on observational studies showed that vaccination was associated with a significantly lower risk of arrhythmia (OR: 0.82, 95% CI: 0.70-0.97; P = 0.02; I 2 = 76%). Additionally, subgroup analysis showed a decreased risk of atrial fibrillation (AF) (OR: 0.94, 95% CI: 0.90-0.98; P = 0.006; I 2 = 0%) and a non-significant but positive trend concerning ventricular arrhythmias (VAs) (OR: 0.68, 95% CI: 0.42-1.11; P = 0.12; I 2 = 85%) after influenza vaccination. Conclusion: Based on the current evidence, influenza vaccination may be associated with a reduced risk of arrhythmia, especially AF. Influenza vaccination may be an effective tool for the prevention of arrhythmias. The effect of influenza vaccination on the risk of VAs and arrhythmias in patients at low risk for cardiovascular diseases should be further studied. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42022300815].

Fibroblast growth factor-23 and the risk of cardiovascular diseases and mortality in the general population: A systematic review and dose-response meta-analysis.

Background: In the past decade, fibroblast growth factor 23 (FGF23) has been recognized as an important biomarker of cardiovascular diseases. This study aimed to assess the relationship between FGF23 and the risk of cardiovascular diseases (CVDs) in general populations. Methods: The protocol was registered prospectively in PROSPERO (CRD42021281837) and two authors independently searched for relevant studies in the PubMed, EMBASE, and Cochrane Library databases. The random effects model was applied. Results: In total, 29 prospective studies involving 135,576 participants were included. In the general population, the category analysis revealed that elevated FGF23 levels were related to increased risks of myocardial infarction (MI) (RR: 1.40, 95%CI: 1.03-1.89), stroke (RR: 1.20, 95%CI: 1.02-1.43), heart failure (HF) (RR: 1.37, 95%CI: 1.23-1.52), CVD events (RR: 1.22, 95%CI: 0.99-1.51), cardiovascular mortality (RR: 1.46, 95%CI: 1.29-1.65), and all-cause mortality (RR: 1.50, 95%CI: 1.29-1.74). In the continuous analysis, per doubling of FGF23 was associated with increased risks of MI (RR: 1.08, 95%CI: 0.94-1.25), stroke (RR: 1.21, 95%CI: 0.99-1.48), HF (RR: 1.24, 95%CI: 1.14-1.35), CVD events (RR: 1.12, 95%CI: 0.99-1.27), cardiovascular mortality (RR: 1.43, 95%CI: 1.09-1.88), all-cause mortality (RR: 1.37, 95%CI: 1.15-1.62). Furthermore, the dose-response analysis demonstrated a potentially non-linear relationship between FGF23 and stroke, HF, and all-cause mortality. In contrast, a potentially linear relationship between FGF23 and cardiovascular mortality was observed (p for non-linearity = 0.73). Conclusion: The present study suggests that increased serum FGF23 levels are positively related to CVD events and mortality in the general population. The clinical application of FGF23 levels to predict CVD risk requires further research.

Relationship between serum growth differentiation factor 15, fibroblast growth factor-23 and risk of atrial fibrillation: A systematic review and meta-analysis.

Background and objective: Growth differentiation factor-15 (GDF-15) and fibroblast growth factor-23 (FGF-23) are considered predictors of the incidence of cardiovascular diseases. The present meta-analysis aimed to elucidate the associations between GDF-15 and FGF-23 in the risk of atrial fibrillation (AF). Methods: An electronic search was conducted in the Cochrane Library, PubMed, and Embase databases from inception until February 27, 2021. The study protocol was registered in the PROSPERO database (CRD42020182226). Results: In total, 15 studies that enrolled 36,017 participants were included. Both serum FGF-23 and GDF-15 were elevated in patients with AF. Analysis of categorical variables showed higher serum FGF-23 levels were associated with an increased risk of AF [relative risk (RR) = 1.28, 95% confidence interval (CI): 1.05-1.56]. In contrast, this association was not found with GDF-15 (RR = 0.91, 95% CI: 0.20-4.04). In dose-response analysis, a linear positive association was noted between serum FGF-23 levels and the risk of AF (P nonlinear = 0.9507), with a RR elevation of 7% for every 20 pg/ml increase in the serum FGF-23 levels (95% CI: 1.02-1.13). No remarkable relationship was found between serum GDF-15 levels and the risk of AF, and the overall RR for the association between a 100 ng/L increment in GDF-15 levels and AF was 1.01 (95% CI: 0.998-1.02). Conclusion: Our study showed a positive linear correlation between serum FGF-23 levels and the risk of AF. However, no significant association was found between GDF-15 and the risk of AF. Further studies are warranted to clarify whether serum FGF-23 levels may be considered in predicting the risk of AF.Systematic Review Registration: http:www.york.ac.uk/inst/crd, identifier CRD42020182226.

Association of TLR3 gene 1377C/T (rs3775290) and TLR7 gene C/G (rs3853839) polymorphism with hand, foot, and mouth disease caused by human enterovirus 71 infection susceptibility and severity in the Chinese Han population: A meta-analysis of case-control studies.

BACKGROUND: Several case-control studies have been conducted on the relationship between rs3775290 C/T and rs3853839 C/G single nucleotide polymorphisms of the Toll-like receptor (TLR) gene and hand, foot, and mouth disease (HFMD) susceptibility and severity. This meta-analysis aimed to offer a systemic review of HFMD susceptibility and severity among the Chinese Han population associated with the C/T (rs3775290) polymorphism of the TLR3 gene or C/G (rs3853839) polymorphism of the TLR7 gene. METHODS: A computer search was conducted using PubMed, Web of Science, Embase, CNKI, CBM, VIP, and WanFang databases. The time ranges were from database establishment to 30/7/2021. Articles selected according to the inclusion and exclusion criteria underwent data extraction and methodological quality evaluation. RevMan 5.4 and Stata 16.0 were adopted for meta-analysis, and the incorporated odds ratio (OR) values and 95% confidence intervals (CIs) were calculated. Sensitivity and publication bias assessments were performed. RESULTS: 8 articles with 9 studies were selected. Among them, there were 858 cases and 577 controls in TLR3 rs3775290 studies as well as 2151 cases and 1554 controls in TLR7 rs3853839 studies. Regarding rs3775290 of TLR3, susceptibilities of the severe type of T-possessing individuals were larger than those of C-possessing individuals [OR = 1.34, 95%CI (1.10, 1.64), P = .004]. The susceptibility of individuals with the severe TT genotype was 1.61 times that of individuals with the CC genotype [95%CI (1.07, 2.43), P=0.02], while susceptibility to HFMD was not influenced by the genotype. In terms of the rs3853839 of the TLR7 gene, C allele carriers have a higher risk of developing HFMD than G allele carriers. The susceptibility to HFMD in CC+CG individuals was 1.24 times than that in GG individuals [95%CI (1.07, 1.43), P = .004]. However, no relationship was found between this polymorphism and severity of the severe type. No significant publication bias was observed in this study. CONCLUSIONS: rs3775290 (C/T) of TLR3 is associated with susceptibility to the severe type, whereas rs3853839 (C/G) of TLR7 is associated with susceptibility to HFMD. However, owing to the limited quantity and quality of the research, the aforementioned conclusions are yet to be justified by more high-quality research.

Association of PTPN22 SNP1858 (rs2476601) and Gene SNP1123 (rs2488457) Polymorphism With Primary Immune Thrombocytopenia Susceptibility: A Meta-Analysis of Case-Control Studies and Trial Sequential Analysis.

Objective: Systematic review of the association of protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene 1858 and 1123 sites single nucleotide polymorphism (SNP) with the susceptibility of primary immune thrombocytopenia (ITP). Method: Database searched includes PubMed, Embase, Web of Science, CNKI, CBM, VIP and WanFang Data. The retrieval period is from the establishment of the database to 30 June 2021. After screening articles according to inclusion and exclusion criteria, the data were extracted and methodological quality of the included studies was evaluated. Meta-analysis was performed using RevMan 5.4 and Stata 16.0 software. The combined OR value and its 95%CI were calculated. Sensitivity analysis and publication bias assessment were performed. Trial sequential analysis (TSA) was performed using TSA 0.9.5.10 Beta software. Results: A total of 10 studies with 10 articles were included, with a total of 932 cases and 2,112 controls. The results of meta-analysis showed that for SNP1858, the susceptibility of TT genotype to ITP was 5.01 times higher than CC genotype [95%CI (1.81, 13.86), p = 0.002]. For SNP1123, G allele carriers were more susceptible to ITP than C allele carriers [OR = 1.23, 95%CI (1.05, 1.45), p = 0.01], and GG genotype carriers were 1.51 times more susceptible to ITP than CC genotype carriers [95%CI (1.11, 2.06), p = 0.009]. Although the results are statistically significant, the results of sensitivity analysis showed certain limitations of stability, and the TSA analysis still indicated the possibility of false positive. No significant publication bias was observed. Conclusion: PTPN22 gene SNP1858 (rs2476601) and SNP1123 (rs2488457) polymorphisms are associated with susceptibility to primary immune thrombocytopenia. Due to the limitation of the number and quality of the included studies, the above conclusions need to be verified by more high-quality studies.

Liver Fibrosis Scores and Clinical Outcomes in Patients With COVID-19.

Background and Aims: We investigated the association between liver fibrosis scores and clinical outcomes in patients with COVID-19. Methods: We performed a post-hoc analysis among patients with COVID-19 from the trial study Outcomes Related to COVID-19 treated with Hydroxychloroquine among Inpatients with symptomatic Disease (ORCHID) trial. The relationship between aspartate aminotransferase (AST) to platelet ratio index (APRI), non-alcoholic fatty liver disease fibrosis score (NFS), Fibrosis-4 index (FIB-4), and discharge and death during the 28-days of hospitalization was investigated. Results: During the 28 days after randomization, 237 (80.6%) patients were discharged while 31 (10.5%) died among the 294 patients with COVID-19. The prevalence for advanced fibrosis was estimated to be 34, 21.8, and 37.8% for FIB-4 (>2.67), APRI (>1), and NFS (>0.676), respectively. In multivariate analysis, FIB-4 >2.67 [28-days discharge: hazard ratio (HR): 0.62; 95% CI: 0.46-0.84; 28-days mortality: HR: 5.13; 95% CI: 2.18-12.07], APRI >1 (28-days discharge: HR: 0.62; 95% CI: 0.44-0.87; 28-days mortality: HR: 2.85, 95% CI: 1.35-6.03), and NFS >0.676 (28-days discharge: HR: 0.5; 95% CI: 0.35-0.69; 28-days mortality: HR: 4.17; 95% CI: 1.62-10.72) was found to significantly reduce the discharge rate and increase the risk of death. Additionally, FIB-4, APRI, and NFS were found to have good predictive ability and calibration performance for 28-day death (C-index: 0.74 for FIB-4, 0.657 for APRI, and 0.745 for NFS) and discharge (C-index: 0.649 for FIB-4, 0.605 for APRI, and 0.685 for NFS). Conclusion: In hospitalized patients with COVID-19, FIB-4, APRI, and NFS may be good predictors for death and discharge within 28 days. The link between liver fibrosis and the natural history of COVID-19 should be further investigated.

Body mass index and atrial fibrillation recurrence post ablation: A systematic review and dose-response meta-analysis.

Objectives: The aim of this study was to evaluate the shape of the dose-response relationship between body mass index (BMI) and atrial fibrillation (AF) recurrence in patients who have undergone radiofrequency ablation. Methods: Studies investigating BMI and AF recurrence in patients with AF after ablation were identified through electronic searches in the PubMed, EMBASE, and Cochrane Library databases. The potential non-linear relationship was fitted using robust error meta-regression. Our study was registered with PROSPERO (CRD42019121373). Results: Twenty-six cohort studies with 7,878 cases/26,450 individuals were included, and a linear dose-response relationship between BMI and AF recurrence (P non-linearity = 0.12) was found. The risk of AF recurrence in patients with a BMI over 28 was significantly increased. Specifically, for each 5 kg/m2 increase in BMI, the risk of AF recurrence increased by 15% (95% CI: 1.08-1.22) with moderate heterogeneity (I 2 = 53%). Subgroup analyses showed that the pooled risk ratio was not significantly changed in subgroup analysis adjustment for the following important potential intermediate factors: left atrial diameter and obstructive sleep apnea. Conclusion: This study showed that there is a borderline positive linear association between BMI and AF recurrence post ablation. Overweight and obesity are significantly associated with AF recurrence. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42019128770.