Effect of Statins on Serum Levels of TNF-alpha and Interleukin-6 in Patients with Kidney Disease: A Meta-analysis of Randomized Clinical Trials.

BACKGROUND AND OBJECTIVES: Some clinical trials have indicated the beneficial effects of statins in patients with kidney disease, while others have reported no positive effect of statins in these patients. We conducted this meta-analysis to identify the effects of statins on serum levels of interleukin-6 (IL-6) and Tumor Necrosis Factor Alpha (TNF-α) in patients with kidney disease. DESIGNS AND METHODS: A systematic literature search was performed using PubMed, Scopus, and Web of Science databases to identify all studies published from inception to August, 2022. The major outcome variable was the Weighted Mean Difference (WMD). Eligible studies were stratified based on target population, intervention duration, dosage and type of statins, and solubility of statins. RESULTS: Meta-analysis performed on seven publications (8 studies), including 213 patients with kidney disease and 188 control individuals, indicated that the concentration of IL-6 was marginally decreased in patients with kidney disease following statin therapy disease (WMD = -1.15 pg/mL; 95% CI = -2.33 to 0.04, P = 0.05, 2 =68.5%)). The findings of subgroup analysis based on the dosage of statins showed that neither highintensity nor moderate/low-intensity statin treatment could significantly influence the serum level of IL-6. Lipophilic statins were more effective than hydrophilic statins, and they marginally decreased the levels of IL6 (WMD = -1.21 pg/mL; 95% CI = -2.43 to 0, P = 0.05, I2 = 55.7%)). Meta-analysis of four publications (five studies) with 157 patients with kidney disease and 132 control subjects showed that statins reduced the serum levels of TNF-α in patients with kidney disease when compared with control individuals (WMD= -2.66 pg/mL; 95% CI = -4.26 to -1.06, P < 0.001, I2 = 63%). CONCLUSION: Statins only marginally decreased the concentration of IL-6 in patients with kidney disease, but neither high-intensity nor moderate/low-intensity statin treatment could significantly influence the level of IL6. However, statins reduced serum levels of TNF-α in patients with kidney disease.

Statin Therapy and Lipid Indices in Chronic Kidney Disease: A Systematic Review and Meta-analysis of Randomized Control Trials.

BACKGROUND: Several studies have demonstrated the improvement in serum lipoproteins by statins in patients with Chronic Kidney Diseases (CKDs), including End-Stage Renal Disease (ESRD). However, the results of these studies are inconclusive. AIM: We aimed to systematically investigate the effect of statins on lipid profiles of patients with CKD by performing a meta-analysis of Randomized Controlled Trials (RCTs). METHODS: Major electronic databases (Scopus, MEDLINE/PubMed, and ISI Web of Science) were searched from inception to August, 2023, to find randomized controlled trials (RCTs) evaluating the effect of different statins on serum lipoproteins in CKD patients. Weighted Mean Difference (WMD) with 95% Confidence Intervals (CI) was used to estimate the effect size. Trial Sequential Analysis (TSA) was performed to confirm the robustness of the evidence. RESULTS: A total of 18 publications were identified. It was found that statins reduced serum levels of Low-Density Lipoprotein (LDL)-C (WMD = -27.81 mg/dl, 95% CI = -34.47 to -21.15, P < 0.001) and total cholesterol (WMD = -25.44 mg/dl, 95% CI = -34.71 to -16.18, P < 0.001) in patients with CKD compared to the control group. Nonetheless, the effect of statins on High-Density Lipoprotein (HDL)-C (WMD = 0.57 mg/dl, 95% CI = -0.71 to 1.85, P = 0.38) and Triglyceride (TG) (WMD = -9.08 mg/dl, 95% CI = -22.22 to 2.06, P = 0.11) was not statistically significant. The results of TSA confirmed the robustness of the evidence and were consistent with the pooled effect size. The findings of subgroup analysis and time response analysis were also significant. CONCLUSION: It was found that statin therapy reduced the levels of LDL-C and total cholesterol in patients with CKD.

MTHFR gene polymorphisms and susceptibility to myocardial infarction: Evidence from meta-analysis and trial sequential analysis.

Background: This meta-analysis aimed to provide a comprehensive assessment of the association between Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, specifically C677T and A1298C, and the susceptibility to myocardial infarction (MI). Methods: A systematic literature search was conducted in MEDLINE, Web of Science, and Scopus until April 2023 to identify studies investigating the relationship between MTHFR gene polymorphisms (C677T and A1298C) and the risk of MI. Results: The analysis included 66 studies involving 16,860 cases and 20,403 controls for the C677T polymorphism and 18 studies comprising 3162 cases and 3632 controls for the A1298C polymorphism. Significant associations were observed between the C677T polymorphism and MI risk in various genetic models: dominant (OR = 1.16, 95 % CI = 1.06-1.28, P = 0.008), recessive (OR = 1.20, 95 % CI = 1.12-1.28, P < 0.001), allelic (OR = 1.13, 95 % CI = 1.06-1.21, P < 0.001), TT vs. CC (OR = 1.19, 95 % CI = 1.05-1.36, P < 0.001), and CT vs. CC (OR = 1.11, 95 % CI = 1.02-1.21, P = 0.01). Furthermore, an overall analysis indicated a marginally significant association between the A1298C polymorphism and MI risk in the recessive model (OR = 1.27, 95 % CI = 1.06-1.51, P = 0.008), allelic model (OR = 1.18, 95 % CI = 1.01-1.39, P = 0.03), and CC vs. AA model (OR = 1.22, 95 % CI = 1.01-1.47, P = 0.04). Meta-regression analysis revealed that none of the potential factors contributed to the observed heterogeneity. Conclusions: This meta-analysis revealed an association between MTHFR gene C677T and A1298C polymorphisms and the risk of MI.

Multiple myeloma cell-derived exosomes promote favorable tumor functional performance by polarizing macrophages toward M2-like cells.

It has long been hypothesized that leukemic cells are able to modulate the fate of resident cells in the tumor microenvironment (TME) toward either supporting or immunosuppressive cells for the development of tumors. Exosomes can be a potential culprit in imposing tumor desire. There is evidence about the impact of tumor-derived exosomes on different immune cells in different malignancies. However, findings about macrophages are contradictory. Here, we evaluated the potential influence of multiple myeloma (MM)-cell-derived exosomes on the polarization of macrophages by examining hallmarks of M1 and M2 macrophages. After treatment of M0 macrophages with isolated exosomes (from U266B1), gene expression (Arg-1, IL-10, TNF-α and IL-6), immunophenotyping markers (CD206), cytokine secretion (IL-10 and IL-6), nitric oxide (NO) production, and redox potentiality of target cells were assessed. Our results revealed significantly increased expression of the genes involved in the development of M2-like cells but not M1 cells. The CD 206 marker and IL-10 protein levels were significantly increased at different time points. The expression of IL-6 mRNA and IL-6 protein secretion did not change significantly. MM-cell-derived exosomes induced significant changes in NO production and intracellular ROS levels in M0 cells.

Effect of Statins on the Blood Lipid Profile in Patients with Different Cardiovascular Diseases: A Systematic Review with Meta-analysis of Randomized Clinical Trials.

BACKGROUND: Statins are the main lipid-lowering drugs and are used in the prevention of cardiovascular diseases (CVDs). Since the results have been, to some extent, inconsistent in the clinical trials concerning different types of CVDs, a systematic review and meta-analysis was performed to prove the effect of statins on decreasing elevated levels of total cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in patients with CVDs. METHODS: Literature search was performed on major electronic databases (MEDLINE/ PubMed, Scopus, and ISI Web of Science) from inception up to July 2021 to find randomized controlled trials (RCTs) evaluating the effect of different statins on different types of CVDs. The effect size was determined using weighted mean difference (WMD) and corresponding 95% confidence interval (CI). RESULTS: Statin therapy significantly decreased levels of total cholesterol (WMD = -33.37 mg/dl, 95% CI: -45.98 to -20.76, P<0.001), LDL-C (WMD = -29.42 mg/dl, 95% CI: -36.81 to -22.03, P<0.001), and TG (WMD = -15.19 mg/dl, 95% CI = -26.41 to -3.97, P<0.001), and increased levels of HDL-C (WMD = 1.55 mg/dl, 95% CI: 0.20, to 2.90, P=0.02) in patients with different CVDs. CONCLUSION: Statin therapy was found effective in lowering levels of total cholesterol, LDL-C, and TG, and increasing levels of HDL-C in patients with different CVDs.

Effect of Statins on Serum level of hs-CRP and CRP in Patients with Cardiovascular Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Several studies have reported that statins have anti-inflammatory effects. Nevertheless, results of clinical trials concerning the effect of statins on the levels of C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) have been inconsistent. Therefore, we performed a systematic review and meta-analysis of randomized clinical trials (RCTs) evaluating the effect of statins on CRP and hs-CRP levels in patients with cardiovascular diseases (CVDs). METHODS: Literature search of the major databases was performed to find eligible RCTs assessing the effect of statins on serum levels of CRP and hs-CRP from the inception until the last week of April 2021. The effect sizes were determined for weighted mean difference (WMD) and 95% confidence intervals (CI). RESULTS: 26 studies were identified (3010 patients and 2968 controls) for hs-CRP and 20 studies (3026 patients and 2968 controls) for CRP. Statins reduced the serum levels of hs-CRP (WMD = -0.97 mg/L; 95% CI: -1.26 to -0.68 mg/L; P < 0.001) and CRP (WMD = -3.05 mg/L; 95% CI: -4.86 to -1.25 mg/L; P < 0.001) in patients with CVDs. Statins decreased the serum levels of hs-CRP in patients receiving both high-intensity and moderate/low-intensity treatments with these drugs. In addition, the duration of treatment longer than 10 weeks decreased hs-CRP levels. Only high-intensity statin treatment could marginally decrease serum levels of CRP in CVDs patients. CONCLUSIONS: This meta-analysis showed the efficacy of statins to reduce the concentrations of CRP and hs-CRP in patients with different types of CVDs.

Effect of statins on the plasma/serum levels of inflammatory markers in patients with cardiovascular disease; a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: The anti-inflammatory properties of statins have been suggested by several researches. However, clinical trials have reported incongruous findings regarding the effect of statins on the levels of inflammatory markers other than high-sensitive C-reactive protein. Therefore, a systematic review and meta-analysis of randomized clinical trials were conducted to illuminate the effect of statins on serum levels of TNF-α, MCP-1, VCAM1, and IL-6 in patients with cardiovascular diseases (CVDs). METHODS: To find eligible studies, a systematic literature search of the main databases were conducted up to July 2021. The calculation of the effect sizes was conducted by standardized mean difference (SMD) and 95% confidence intervals (CI). RESULTS: The pooled analyses revealed that statins significantly reduced the TNF-α concentration (SMD = - 0.99 pg/mL; 95% CI - 1.43 to - 0.55 pg/mL; P < 0.001). Regarding dosage, high intensity (SMD = - 0.65 pg/mL; 95% CI - 1.19 to - 0.10, P = 0.02) and moderate/low (SMD = - 1.16 pg/mL; 95% CI - 1.84 to - 0.47, P = 0.001) intensity statins significantly decreased TNF-α levels. Moderate/low intensity statins administration in < 10 weeks treatment duration decreased serum level of TNF-α (SMD = - 0.91 pg/mL; 95% CI - 1.38 to - 0.44, P < 0.001). Lipophilic statins with high intensity dosage significantly decreased level of TNF-α (SMD = - 0.73 pg/mL; 95% CI - 1.43 to - 0.03, P = 0.04). Statins did not change serum levels of MCP-1, VCAM1, and IL-6 in CVD patients. CONCLUSIONS: The analyses indicated that statins have beneficial effects in decreasing serum levels of TNF-α in patients with CVDs.

Cognitive Orientation to Daily Occupational Performance (CO-OP) in Children with Cerebral Palsy: A Systematic Review with Meta-analysis.

Background: Cognitive orientation to daily occupational performance (CO-OP) is a client-centered treatment approach that was developed in the 1990s by occupational therapists. Purpose: Exploring current evidence about the effectiveness of CO-OP on children with cerebral palsy (CP). Method: Major electronic databases were searched. A narrative synthesis of current literature and meta-analyses on randomized control trials (RCTs) were conducted on changes in occupational performance. Findings: Seven studies with 103 participants were included. Four studies were RCTs with moderate levels of evidence, and three studies had single-subject designs. Although beneficial effects of CO-OP on goal achievement and transferring learned skills were reported, meta-analyses showed that CO-OP had no significant effect on the performance (WMD = 1.52, 95% CI = -1.58 to 4.63, P = .33) and satisfaction domains (WMD = 1.71, 95% CI = -1.14 to 4.57, P = .24) of Canadian Occupational Performance Measure scores compared to alternative interventions. Implications: CO-OP improves occupational performance but not more than alternative interventions. Results are inconclusive due to small sample sizes and heterogeneity of alternative interventions and participants. Therefore, research with a larger number of participants with sound RCT methods is needed.

Metabolic phenotypes and risk of colorectal cancer: a systematic review and meta-analysis of cohort studies.

BACKGROUND: The association of obesity with colorectal cancer (CRC) may vary depending on metabolic status. OBJECTIVE: This meta-analysis aimed to investigate the combined impacts of obesity and metabolic status on CRC risk. METHODS: The Scopus, PubMed, and web of sciences databases were systematically searched up to Jun 2021 to find all eligible publications examining CRC risk in individuals with metabolically unhealthy normal-weight (MUHNW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUHO) phenotypes. RESULTS: A total of 7 cohort studies with a total of 759,066 participants were included in this meta-analysis. Compared with healthy normal-weight people, MUHNW, MHO, and MUHO individuals indicated an increased risk for CRC with a pooled odds ratio of 1.19 (95% CI = 1.09-1.31) in MUHNW, 1.14 (95% CI = 1.06-1.22) in MHO, and 1.24 (95% CI = 1.19-1.29) in MUHO subjects. When analyses were stratified based on gender, associations remained significant for males. However, the elevated risk of CRC associated with MHO and MUHO was not significant in female participants. CONCLUSIONS: The individuals with metabolic abnormality, although at a normal weight, have an increased risk for CRC. Moreover, obesity is associated with CRC irrespective of metabolic status.

Effect of curcumin on C-reactive protein as a biomarker of systemic inflammation: An updated meta-analysis of randomized controlled trials.

It has been suggested that curcumin is a potential agent for lowering the levels of C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP), as markers of inflammation. In the current meta-analysis, we attempted to clarify the efficacy of curcumin supplementation in lowering the concentrations of CRP and hs-CRP in patients with autoinflammatory conditions. Nine studies were found evaluating the effect of curcumin on CRP levels, while 23 studies were identified for hs-CRP. CRP concentration was decreased significantly compared to the placebo (WMD = -3.67 mg/L, 95% CI = -6.96 to -0.38, p = 0.02). There was a significant effect of curcumin at dose ≤1,000 mg/day on the CRP concentration. CRP concentration significantly decreased after >10-week intervention compared with placebo.hs-CRP concentration in the intervention group was significantly lower than that of placebo group. A significant effect of curcumin consumption was detected on the serum level of hs-CRP in studies with prescribing ≤1,000 mg/day, and those with ≤10-week duration of intervention. Curcumin consumption resulted in a reduction of hs-CRP in a non-linear fashion with stronger effects with less than 2000 mg curcumin per day. Curcumin seems to be beneficial in decreasing the hs-CRP and CRP levels in proinflammatory settings.

Effects of Pre/Probiotic Supplementation on Breast Milk Levels of TGF-b1, TGF-b2, and IgA: A Systematic Review and Meta-Analysis of Randomized-Controlled Trial.

Background: Previous studies have proposed that the maternal intake of pre/probiotics may affect the immune composition of breast milk. Nevertheless, the available findings are contradictory. This meta-analysis aimed to examine the impact of maternal supplementation with pre/probiotics on the levels of total immunoglobulin A (IgA), secretory IgA (SIgA), transforming growth factor beta 1 (TGF-ß1), and TGF-2 in breast milk. Methods: PubMed and Scopus were systematically searched using a comprehensive search strategy for eligible randomized-controlled trials published up to February 2021. A random-effects model was applied to pool weighted mean difference and 95% confidence interval (CI) as effect size. Cochran's Q statistic and the I2 statistic were used to measure the between-study variance. Egger's regression test was used to assess publication bias. Results: A total of 12 different studies, with a total sample size of 1722 individuals (probiotic group: 858, placebo group: 864), were included in this meta-analysis. In the overall analysis, compared with placebo, maternal supplementation with pre/probiotics had no significant effect on concentrations of total IgA, SIgA, TGF-ß1, and TGF-ß2 in the breast milk. In the subgroup analysis, pre/probiotics did not affect total IgA, TGF-ß1, and TGF-ß2 in both colostrum/transitional and mature milk. However, a significant increase in SIgA was found in colostrum/transitional milk following pre/probiotic administration (WMD = 19.33, 95% CI: 0.83-37.83; p = 0.04), without evidence for remarkable heterogeneity (I2 = 0.0, p = 0.57). Conclusions: Maternal supplementation with pre/probiotics may increase SIgA in colostrum/transitional milk, without any effect on total IgA, TGF-ß1, and TGF-ß2.

The negative impact of obesity on the occurrence and prognosis of the 2019 novel coronavirus (COVID-19) disease: a systematic review and meta-analysis.

PURPOSE: The 2019 novel coronavirus (COVID-19) is an emerging pandemic, with a disease course varying from asymptomatic infection to critical disease resulting to death. Recognition of prognostic factors is essential because of its growing prevalence and high clinical costs. This meta-analysis aimed to evaluate the global prevalence of obesity in COVID-19 patients and to investigate whether obesity is a risk factor for the COVID-19, COVID-19 severity, and its poor clinical outcomes including hospitalization, intensive care unit (ICU) admission, need for mechanical ventilation, and mortality. METHODS: The study protocol was registered in PROSPERO (CRD42020203386). A systematic search of Scopus, Medline, and Web of Sciences was conducted from 31 December 2019 to 1 June 2020 to find pertinent studies. After selection, 54 studies from 10 different countries were included in the quantitative analyses. Pooled odds ratios (OR) with 95% confidence intervals (CIs) were calculated to assess the associations. RESULTS: The prevalence of obesity was 33% (95% CI 30.0%-35.0%) among patients with COVID-19. Obesity was significantly associated with susceptibility to COVID-19 (OR = 2.42, 95% CI 1.58-3.70; moderate certainty) and COVID-19 severity (OR = 1.62, 95% CI 1.48-1.76; low certainty). Furthermore, obesity was a significant risk factor for hospitalization (OR = 1.75, 95% CI 1.47-2.09; very low certainty), mechanical ventilation (OR = 2.24, 95% CI 1.70-2.94; low certainty), intensive care unit (ICU) admission (OR = 1.75, 95% CI 1.38-2.22; low certainty), and death (OR = 1.23, 95% CI 1.06-1.41; low certainty) in COVID-19 patients. In the subgroup analyses, these associations were supported by the majority of subgroups. CONCLUSION: Obesity is associated with COVID-19, need for hospitalization, mechanical ventilation, ICU admission, and death due to COVID-19. LEVEL OF EVIDENCE: Level I, systematic reviews and meta-analyses.

Comparing safety of proton-pump inhibitors versus H2-receptor antagonists in kidney transplant recipients: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Multiple studies have been conducted to compare the safety of proton-pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) as acid-suppressive treatment in kidney transplant recipients with conflicting results. This systematic review and meta-analysis aimed to evaluate the risk of adverse effects in kidney transplant patients receiving PPIs compared to those treated with H2RAs. METHODS: A systematic search was performed on the databases from inception to June 2021. The treatment effects were expressed as odds ratio (OR), weighted mean differences (WMD) and their 95% confidence intervals (CI) and pooled by a random-effects model. RESULTS AND DISCUSSIONS: Eight studies, consisting 4,844 patients, were included. Patients were followed for a mean duration of 23.57 months after transplantation. Compared with H2RAs, PPIs exposure was associated with similar rate of biopsy-proven acute rejection (BPAR) (OR = 1.05, 95% CI 0.83-1.34, p = 0.67), mortality (OR = 1.31, 95% CI 0.56-3.07, p = 0.533), graft loss (OR = 1.06, 95% CI 0.59-1.93, p = 0.842), Clostridioides difficile infection (OR = 1.37, 95% CI 0.49-3.85, p = 0.545) and pneumonia (OR = 1.83, 95% CI 0.95-3.52, p = 0.072). The estimated glomerular filtration rate (eGFR) at 12 months was lower in patients who received PPIs than those treated with H2RAs (WMD = -1.01, 95% CI -1.89 to -0.12 ml/min/1.73m2 , p = 0.02). The PPI-treated kidney transplant patients experienced higher rate of antibody-mediated rejection (AMR) (OR = 1.87, 95% CI 1.03-3.04, p = 0.039) and hypomagnesemia (OR = 2.16, 95% CI 1.46-3.20, p Ë‚ 0.001). WHAT IS NEW AND CONCLUSIONS: Compared with H2RAs, PPIs were not associated with higher risks of BPAR, mortality, graft loss or infection-related outcomes. However, taking PPIs was associated with higher rates of AMR and hypomagnesemia, and lower eGFR at one year after transplantation. Further well-controlled studies are needed to assess the impact of acid-suppressive strategy on long-term outcomes in KTRs.

Effect of resveratrol on C-reactive protein: An updated meta-analysis of randomized controlled trials.

We conducted a meta-analysis on the available randomized clinical trials (RCTs) to assess the role of resveratrol in lowering C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) levels, as markers of inflammation, in various inflammatory disorders. Literature search through Medline/PubMed, Scopus, ISI Web of Science, and Cochrane Library yielded 35 RCTs (24 studies for hs-CRP and 11 studies for CRP). Pooled results revealed that resveratrol supplementation significantly reduced the hs-CRP (MWD = -0.40 mg/L; 95% CI: -0.70 to -0.09 mg/L; p = .01) and CRP (MWD = -0.31 mg/L; 95% CI: -0.47 to -0.15 mg/L; p < .001) levels in serum. Subgroup analysis revealed that resveratrol in group with ≥10 weeks significantly reduces hs-CRP levels (MWD = -0.48 mg/L; 95% CI: -0.92 to -0.04 mg/L; p = .03) and CRP (WMD = -0.47 mg/L, 95% CI = -0.69 to -0.25, p < .001). A dose of ≥500 mg/day supplementation improves the levels of CRP, but not hs-CRP. This meta-analysis demonstrates that resveratrol consumption is effective in lowering the levels of CRP and hs-CRP in inflammatory conditions, especially if supplementation takes place for ≥10 weeks with ≥500 mg/day.

Vitamin D Receptor gene polymorphisms and susceptibility to type 2 diabetes: evidence from a meta-regression and meta-analysis based on 47 studies.

BACKGROUND: Evidence from various studies suggest that vitamin D receptor (VDR) gene polymorphisms are associated with type 2 diabetes (T2D); However, these results have been disputable. Here we conducted a meta-analysis to comprehensively evaluate the effect of VDR gene polymorphisms and susceptibility to T2D. METHODS: All relevant studies reporting the association between VDR gene polymorphisms and susceptibility to T2D published up to August 2020 were identified by comprehensive systematic database search in web of science, Scopus, and Medline. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure strength of association. The methodological quality of each study was assessed according to the Newcastle-Ottawa Scale. Subgroup and meta-regression analysis were also performed. RESULTS: A total of 47 case-control studies were included in this meta-analysis. The overall population results revealed a significant association between FokI, and BsmI (heterozygote model) polymorphisms and T2D in the overall analysis. However, no association was found with the TaqI and ApaI polymorphisms. Moreover, the pooled results of subgroup analysis by ethnicity suggested significant association between FokI, TaqI, and BsmI polymorphisms and T2D in some subgroups. Meta-regression analyses indicated that none of the publication year, ethnicity, and genotyping method were the source of heterogenicity in all four polymorphisms. CONCLUSIONS: This meta-analysis suggested a significant association between VDR gene FokI, and BsmI (heterozygote model) polymorphisms and T2D susceptibility in overall population and ethnic-specific analysis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-020-00704-z.

The association between psoriasis and psoriatic arthritis with the risk of osteoporosis, osteopenia and bone fractures: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The possible association between psoriatic/psoriatic arthritis (PsA) and bone loss has been observed; however, studies have yielded inconclusive results. This meta-analysis aimed to assess whether there is an increase in the risk of osteoporosis, osteopenia and fractures in patients with psoriasis/PsA, compared with healthy individuals. METHODS: PubMed and Scopus were systematically searched from their inception to September 2020 to identify relevant studies. Relative risk, hazard ratio or odds ratio (OR), with their corresponding 95% confidence intervals (95% CI) were calculated and pooled using a random-effects model. RESULTS: A total of 12 different studies, with a total of 199 389 296 participants, were included. Overall, no significant relationship was observed between psoriasis/PsA and the risk of osteoporosis (psoriasis: OR = 1.28, 95%CI = 0.86-1.90; PsA: OR = 1.32, 95%CI = 0.79-2.19) and osteopenia (psoriasis: OR = 1.50, 95%CI = 0.75-3.02; PsA: OR = 1.61, 95%CI = 0.67-3.85). However, in the subgroup analysis, psoriasis was significantly associated with an increased risk of osteoporosis in men (OR = 1.27, 95%CI = 1.02-1.59) and studies with cohort design (OR = 1.04, 95%CI = 1.003-1.09). Psoriasis was also related to the risk of osteopenia in studies on a combination of both genders (OR = 2.86, 95%CI = 2.70-3.02). The pooled analysis demonstrated a significantly higher risk of fractures among patients with psoriasis (OR = 1.29, 95%CI = 1.02-1.63) and PsA (OR = 2.88, 95%CI = 1.51-5.48), compared with participants without psoriasis/PsA. CONCLUSIONS: Patients with psoriasis/PsA have an increased risk of fractures. There is little evidence supporting the relation of psoriasis to osteoporosis/osteopenia.

Effect of resveratrol on inflammatory cytokines: A meta-analysis of randomized controlled trials.

The aim of the current study was to perform a meta-analysis of randomized clinical trials regarding the effect of resveratrol in decreasing the levels of inflammatory cytokines, including interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-α in a combination of inflammatory diseases. Literature search was carried out in Scopus, ISI web of science, Medline, and Cochrane Library databases by up to September 2020. The pooled effect size was determined through measuring the weighted mean differences (WMD) and their corresponding 95% confidence intervals (CI) for the difference between the resveratrol-receiving and control groups. Finally, 33 publications, including 3 studies on IL-1, 26 studies on IL-6, 4 studies on IL-8, and 21 studies on TNF-α met our final inclusion criteria and included in the quantitative analysis. Analysis in the overall population showed a significant effect of resveratrol consumption in reducing serum TNF-α levels (WMD = -0.66 pg/ml, 95% CI = -1.05 to -0.27, P = 0.001). A significant reduction of IL-6 concentration was observed only in the patients receiving ≥500 mg/day dose of resveratrol (WMD = -1.89 pg/ml, 95% CI = -3.73 to -0.05, P = 0.04) with inter-study heterogeneity (I2 = 94.4%, P < 0.001). Nonetheless, no significant alteration was observed in IL-1 (WMD = -0.14 pg/ml, 95% CI = -0.31 to 0.03, P = 0.10) and IL-8 (WMD = 0.18 pg/ml, 95% CI = -1.04 to 1.40, P = 0.73) levels following resveratrol consumption. Based on the present findings, resveratrol is able to decrease TNF-α and IL-6 (in ≥500 mg/day dose) levels but not IL-1 and IL-8 levels.

Effect of probiotic fermented dairy products on incidence of respiratory tract infections: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Previous studies have suggested that the consumption of probiotic fermented dairy products (PFDP) may have a protective effect on respiratory tract infections (RTIs). However, the results of studies are inconclusive. We aimed to systematically investigate the effect of PFDP on RTIs by performing a meta-analysis of randomized controlled trials (RCTs). METHODS: PubMed and Scopus databases were systematically searched up to October 2020 to identify eligible RCTs. Meta-analysis outcomes were risk of incidence of upper (URTIs ) and lower (LRTIs ) respiratory tract infections. A random-effects model was used to pool the relative risks (RR) and corresponding 95 % confidence intervals (CI) for outcomes following conception of PFDP. RESULTS: A total of 22 RCTs, with a total sample size of 10,190 participants, were included in this meta-analysis. Compared with placebo, consumption of PFDP had a significant protective effect against RTIs in the overall analysis (RR = 0.81, 95 %CI: 0.74 to 0.89) and in children (RR = 0.82, 95 %CI: 0.73 to 0.93), adults (RR = 0.81, 95 %CI: 0.66 to 1.00), and elderly population (RR = 0.78, 95 %CI: 0.61 to 0.98). The significant decreased risk of RTIs was also observed for URTIs (RR = 0.83, 95 %CI: 0.73 to 0.93), while, this effect was marginal for LRTIs (RR = 0.78, 95 %CI: 0.60 to 1.01, P = 0.06). The disease-specific analysis showed that PFDP have a protective effect on pneumonia (RR = 0.76, 95 %CI: 0.61 to 0.95) and common cold (RR = 0.68, 95 %CI: 0.49 to 0.96). CONCLUSIONS: Consumption of PFDP is a potential dietary approach for the prevention of RTIs.

Effect of curcumin on proinflammatory cytokines: A meta-analysis of randomized controlled trials.

It has been suggested that curcumin has the potential for lowering inflammation. In the current meta-analysis, we attempted to clarify the efficacy of curcumin/turmeric supplementation in reducing concentrations of interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-α in patients with an inflammatory background. The main databases were searched to identify eligible trials evaluating the effect of curcumin in reducing IL-1, IL-6, IL-8, and TNF-α in serum up to March 2021. The effect sizes for weighted mean difference (WMD) and 95% confidence intervals (CI) were calculated. Overall, 32 randomized controlled trials (RCTs) were included. There was a significant decrease in the serum levels of IL-1 (WMD = -2.33 pg/ml, 95% CI = -3.33 to -1.34, P < 0.001) and TNF-α (WMD = -1.61 pg/ml, 95% CI = -2.72, -0.51, P < 0.001) compared to the placebo group following treatment. Nonetheless, curcumin/turmeric supplementation was non-significantly associated with reduced levels of IL-6 (WMD = -0.33 pg/ml, 95% CI = -0.99-0.34, P = 0.33) and increased levels of IL-8 (WMD = 0.52 pg/ml, 95% CI = -1.13-2.17, P = 0.53). The dose-responses analysis indicated that curcumin/turmeric supplementation resulted in IL-1 and IL-8 alteration in a non-linear model. Subgroup analysis according to duration and dose of treatment and target population revealed diverse outcomes. Curcumin could have a beneficial effect in reducing the proinflammatory cytokines IL-1 and TNF-α, but not IL-6 and IL-8 levels.

The effect of dual-task conditions on gait and balance performance in children with cerebral palsy: A systematic review and meta-analysis of observational studies.

Dual-task conditions are commonly experienced in daily routines. The aim of the present systematic review is to investigate the effect of dual-task conditions on gait and balance performance in children with cerebral palsy (CP) and to perform meta-analyses where applicable. Five databases, "ProQuest", "PubMed", "OTSeeker", "Scopus", and "PEDro" from the incipient date of databases up to Aug 24, 2020 were searched for studies focusing on the effects of dual-task conditions on gait and balance performance in children with CP. After removing irrelevant articles and applying inclusion and exclusion criteria, nine articles were included in the present systematic review and meta-analysis. The results of the meta-analysis showed that walking speed was slower during dual-task conditions compared to single-task conditions in children with CP (WMD = -0.29 m/s, 95% CI = -0.34, -0.24, P ≤ 0.001) and walking speed decreased in children with CP during dual-task conditions in comparison with the typical development (TD) control group (WMD = -0.19 m/s, 95% CI = -0.23 to -0.15, P ≤ 0.001). The results of subgroup analysis based on the type of task indicated that adding concurrent tasks to walking degrades walking speed under varied dual-task conditions. Additionally, theoretical synthesis of the literature demonstrated that other gait and balance variables are changed by performing cognitive and motor secondary tasks differently. Although these changes may be compensatory strategies to retain their stability, there was not sufficient evidence to reach a firm conclusion. Research gaps and recommendations for future studies are discussed.