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Effects of coenzyme Q10 supplementation on inflammation, angiogenesis, and oxidative stress in breast cancer patients: a systematic review and meta-analysis of randomized controlled- trials.
Alimohammadi, M, Rahimi, A, Faramarzi, F, Golpour, M, Jafari-Shakib, R, Alizadeh-Navaei, R, Rafiei, A
Inflammopharmacology. 2021;(3):579-593
Abstract
BACKGROUND/OBJECTIVE Systemic inflammation and oxidative stress (OS) are associated with breast cancer. CoQ10 as an adjuvant treatment with conventional anti-cancer chemotherapy has been demonstrated to help in the inflammatory process and OS. This systematic review and meta-analysis of randomized clinical trials (RCTs) aimed to evaluate the efficacy of CoQ10 supplementation on levels of inflammatory markers, OS parameters, and matrix metalloproteinases/tissue inhibitor of metalloproteinases (MMPs/TIMPs) in patients with breast cancer. METHODS A systematic literature search was carried out using electronic databases, including PubMed, Web of Science, Scopus, Google Scholar, and Embase, up to December 2020 to identify eligible RCTs evaluating the effect of CoQ10 supplementation on OS biomarkers, inflammatory cytokines, and MMPs/TIMPs. From 827 potential reports, 5 eligible studies consisting of 9 trials were finally included in the current meta-analysis. Quality assessment and heterogeneity tests of the selected trials were performed using the PRISMA checklist protocol and the I2 statistic, respectively. Fixed and random-effects models were assessed based on the heterogeneity tests, and pooled data were determined as the standardized mean difference (SMD) with a 95% confidence interval (CI). RESULTS Our meta-analysis of the pooled findings for inflammatory biomarkers of OS and MMPs showed that CoQ10 supplementation (100 mg/day for 45-90 days) significantly decreased the levels of VEGF [SMD: - 1.88, 95% CI: (- 2. 62 to - 1.13); I2 = 93.1%, p < 0.001], IL-8 [SMD: - 2.24, 95% CI: (- 2.68 to - 1.8); I2 = 79.6%, p = 0.001], MMP-2 [SMD: - 1.49, 95% CI: (- 1.85 to - 1.14); I2 = 76.3%, p = 0.005] and MMP-9 [SMD: - 1.58, 95% CI: (- 1.97 to - 1.19); I2 = 79.6%, p = 0.002], but no significant difference was observed between CoQ10 supplementation and control group on TNF-α [SMD: - 2.30, 95% CI: (- 2.50 to - 2.11); I2 = 21.8%, p = 0.280], IL-6 [SMD: - 1.56, 95% CI: (- 1.73 to - 1.39); I2 = 0.0%, p = 0.683], IL-1β [SMD: - 3.34, 95% CI: (- 3.58 to - 3.11); I2 = 0.0%, p = 0.561], catalase (CAT) [SMD: 1.40, 95% CI: (1.15 to 1.65); I2 = 0.0%, p = 0.598], superoxide dismutase (SOD) [SMD: 2.42, 95% CI: (2.12 to 2.71); I2 = 0.0%, p = 0.986], glutathione peroxidase (GPx) [SMD: 2.80, 95% CI: (2.49 to 3.11); I2 = 0.0%, p = 0.543]], glutathione (GSH) [SMD: 4.71, 95% CI: (4.26 to 5.16); I2 = 6.1%, p = 0.302] and thiobarbituric acid reactive substances (TBARS) [SMD: - 3.20, 95% CI: (- 3.53 to - 2.86); I2 = 29.7%, p = 0.233]. CONCLUSION Overall, the findings showed that CoQ10 supplementation reduced some of the important markers of inflammation and MMPs in patients with breast cancer. However, further studies with controlled trials for other types of cancer are needed to better understand and confirm the effect of CoQ10 on tumor therapy.
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Efficacy and Treatment Burden of Intravitreal Aflibercept Versus Intravitreal Ranibizumab Treat-and-Extend Regimens at 2 Years: Network Meta-Analysis Incorporating Individual Patient Data Meta-Regression and Matching-Adjusted Indirect Comparison.
Ohji, M, Lanzetta, P, Korobelnik, JF, Wojciechowski, P, Taieb, V, Deschaseaux, C, Janer, D, Tuckmantel, C
Advances in therapy. 2020;(5):2184-2198
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Abstract
PURPOSE To compare visual outcomes and treatment burden between intravitreally administered aflibercept (IVT-AFL) and ranibizumab (RBZ) treat-and-extend (T&E) regimens in patients with wet age-related macular degeneration (wAMD) at 2 years. METHODS A systematic literature review was carried out in Medline, EMBASE, and CENTRAL in October 2018. Matching-adjusted indirect comparison (MAIC) and/or individual patient data meta-regression was used to connect ALTAIR (assessing IVT-AFL T&E) with other studies, adjusting for between-trial differences in baseline visual acuity and age or baseline visual acuity, age, and polypoidal choroidal vasculopathy (PCV) status. Sensitivity analyses were conducted to test the robustness of the results, including direct MAIC between IVT-AFL T&E (ALTAIR) and RBZ T&E (CANTREAT and TREX-AMD trials). RESULTS Six randomized controlled trials (RCTs) (ALTAIR, VIEW 1 and 2, CATT, CANTREAT, and TREX) were included in the analysis. IVT-AFL T&E was assessed in one study, ALTAIR (n = 255), while RBZ T&E was assessed in two trials (n = 327). At 2 years, the median difference (95% credibility interval) between IVT-AFL T&E and RBZ T&E regarding the numbers of Early Treatment Diabetic Retinopathy Study (ETDRS) letters gained was not significant (M1: - 2.29 [- 8.10, 3.58]; M2: - 0.55 [- 6.34, 5.29]). IVT-AFL T&E was associated with significantly fewer injections than RBZ-T&E (M1: - 6.12 [- 7.60, - 4.65]; M2: - 5.93 [- 7.42, - 4.45]). Results of the sensitivity analyses were consistent with the main scenarios. CONCLUSION Patients with wAMD receiving an IVT-AFL T&E regimen achieved and maintained improvement in visual acuity with fewer injections over 2 years compared with RBZ T&E. IVT-AFL T&E may therefore serve as the optimal therapy for wAMD, as it was associated with clinical efficacy and minimized treatment burden.
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PHACOEMULSIFICATION CATARACT SURGERY WITH PROPHYLACTIC INTRAVITREAL BEVACIZUMAB FOR PATIENTS WITH COEXISTING DIABETIC RETINOPATHY: A Meta-Analysis.
Feng, Y, Zhu, S, Skiadaresi, E, McAlinden, C, Tu, R, Gao, R, Stephens, JW, Wang, Q, Huang, J
Retina (Philadelphia, Pa.). 2019;(9):1720-1731
Abstract
PURPOSE To evaluate the clinical effectiveness of intravitreal bevacizumab (IVB) injection combined with cataract surgery in the treatment of patients with cataract and coexisting diabetic retinopathy (DR). METHODS Pertinent comparative studies were identified through systemic searches of PubMed, EMBASE, and the Cochrane Controlled Trials Register up to March 1, 2016. Outcome measures included corrected distance vision acuity, central macular thickness, and progression of DR and maculopathy. A meta-analysis was performed using RevMan (Cochrane Collaboration, Oxford, United Kingdom). RESULTS Six studies describing a total of 283 eyes were identified. The meta-analysis results showed that corrected distance vision acuity measured at 1 month and 3 months after cataract surgery was significantly better in the IVB groups than in the control groups (P < 0.00001 and P = 0.01), whereas the corrected distance vision acuity at 6 months did not vary significantly between the 2 groups (P = 0.24). Similarly, the central macular thickness at 1, 3, and 6 months after surgery was significantly thinner in the IVB groups than in the control groups (P = 0.01, P = 0.0004, and P = 0.01, respectively). At 6 months, the progression of postoperative DR and maculopathy occurred more frequently in the control group than in the IVB group (P = 0.0001 and P < 0.0001, respectively). CONCLUSION Our meta-analysis indicates that cataract surgery combined with IVB seems to be an effective treatment in patients with coexisting DR in the short term (up to 6 months). More randomized, prospective, and large-sample-sized trials are needed to evaluate the long-term effects of IVB at the time of cataract surgery in patients with DR.
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Efficacy of ranibizumab for the treatment of diabetic retinopathy: A protocol for systematic review of randomized controlled trial.
Ren, YB, Su, XJ, Qi, YX, Luan, HQ, Sun, Q
Medicine. 2019;(17):e15409
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Abstract
BACKGROUND Previous clinical trials have reported that ranibizumab can be used to treat diabetic retinopathy (DR) effectively. However, no study has been conducted to evaluate its efficacy for patients with DR systematically. Thus, this study will specifically and systematically assess the efficacy and safety of ranibizumab for DR. METHODS Cochrane Library, EMBASE, PUBMED, Web of Science, Google Scholar, Cumulative Index to Nursing and Allied Health Literature, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database will be searched from inceptions to the March 20, 2019 for studies related to the topic. This study will only consider publicly released randomized controlled trials for evaluating the effect and safety of ranibizumab for DR. No language restrictions will be imposed for all databases search. Methodological quality of each included trial will be assessed by Cochrane risk of bias tool. Statistical analysis will be performed by Stata 12.0 software. RESULTS This study will provide recent summary evidence of ranibizumab for DR. Primary outcomes include percentages with retinopathy improvement, and cumulative probabilities for retinopathy worsening. Secondary outcome consist of visual function, best-corrected visual acuities, central subfield thickness, total macular volume, peripheral visual field loss, retinal neovascularization, and adverse events. CONCLUSION The findings of this study may provide theoretical basis for clinical practice refer and may benefit more patients with DR.
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Sorafenib as first-line therapy in patients with advanced Child-Pugh B hepatocellular carcinoma-a meta-analysis.
McNamara, MG, Slagter, AE, Nuttall, C, Frizziero, M, Pihlak, R, Lamarca, A, Tariq, N, Valle, JW, Hubner, RA, Knox, JJ, et al
European journal of cancer (Oxford, England : 1990). 2018;:1-9
Abstract
BACKGROUND Sorafenib has demonstrated survival benefit in first-line treatment of advanced hepatocellular carcinoma (HCC); utility of sorafenib in patients with advanced HCC and Child-Pugh B (CP-B) liver function remains a subject of debate. METHODS A systematic review identified studies using first-line sorafenib in patients with advanced HCC and CP-A/B liver function. Meta-regression analysis comprising linear regression was conducted to explore the association between the baseline factors and overall survival (OS). Differences between efficacy/safety and tolerability parameters were explored using meta-analysis. RESULTS Thirty studies (12 Asian) comprising 8678 patients (August 2002 - September 2012) were included (four randomised controlled trials, 26 cohort studies). Median age was 61 years and 83% were men. Hepatitis B/C status was positive in 35%/22%, respectively. The CP status was available for 8577 patients (99%); CP-A, 79% and CP-B, 19%. Median OS on sorafenib for entire cohort was 7.2 months; 8.8 months in CP-A and 4.6 months in CP-B. Multivariable meta-regression analysis showed significant negative association between OS and proportion of patients with the Eastern Cooperative Oncology Group performance status 2 (P = 0.04) and CP-B liver function (P = 0.001). Among four studies reporting multivariable comparison of the CP status, CP-B was associated with significantly worse OS (P < 0.001). There were no differences in the response rate to sorafenib between patients with CP-A (4.6%) and CP-B (4.2%) liver function. Safety and tolerability were similar; 35% of patients with CP-A/B liver function developed grade III/IV adverse events (P = 0.7). Meta-regression analysis showed similar rates of treatment discontinuation without progression (P = 0.31) and treatment-related death (P = 0.94) in patients with CP-B liver function. CONCLUSION CP-B liver function (versus CP-A) is associated with worse OS (but the similar response rate, safety and tolerability of first-line sorafenib, is unlikely to be clinically meaningful).
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Overview of Systematic Reviews and Meta-analyses on Systemic Adverse Events Associated With Intravitreal Anti-Vascular Endothelial Growth Factor Medication Use.
Thulliez, M, Angoulvant, D, Pisella, PJ, Bejan-Angoulvant, T
JAMA ophthalmology. 2018;(5):557-566
Abstract
IMPORTANCE The systemic safety of intravitreal anti-vascular endothelial growth factor (anti-VEGF) medications is still a matter of debate. OBJECTIVE This overview of systematic reviews evaluates systemic adverse events associated with intravitreal anti-VEGF treatments in patients with neovascular age-related macular degeneration, diabetic macular edema, or retinal vein occlusion. DESIGN, EVIDENCE, AND REPORTING This systematic search of PubMed and the Cochrane Central Register of Controlled Trials database includes meta-analyses and systematic reviews. We describe the summary measures of association between anti-VEGF treatments and outcomes reported in each systematic review. MAIN OUTCOMES AND MEASURES The quality of the systematic reviews was assessed with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and A Measurement Tool to Assess Systematic Reviews (AMSTAR) checklist, version 1. FINDINGS We retrieved 21 systematic reviews published between January 1, 2011, and June 30, 2016. Of these, 11 analyzed systemic adverse events as the primary outcome. The median (interquartile range) PRISMA and AMSTAR scores were 23 of 27 (15-27) and 8 of 11 (5-11), respectively, but 5 reviews (25%) scored below 20 and 7, respectively. All reviews used an objective scale to assess methodological risk of bias in their included studies, the Cochrane Risk of Bias Tool being the most commonly used (16 reviews [76%]). Anti-VEGF treatments did not increase the risk of systemic adverse events when compared with control regimens; similarly, there was no increase in systematic adverse events when treatment was given on a monthly schedule vs an as-needed regimen. Compared with ranibizumab, bevacizumab did not appear to be associated with an increase in the risk of systemic adverse events in the most recent and exhaustive reviews. Compared with control treatments, ranibizumab may be associated with an increase in the risk of nonocular hemorrhage in patients with age-related macular degeneration. CONCLUSIONS AND RELEVANCE This overview of reviews and meta-analyses suggest that anti-VEGF treatments do not increase the risk of systemic adverse events, but that caution might be advisable in older patients with age-related macular degeneration who may be at higher risk of hemorrhagic events when receiving ranibizumab.
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Antivascular endothelial growth factor agents pretreatment before vitrectomy for complicated proliferative diabetic retinopathy: a meta-analysis of randomised controlled trials.
Zhao, XY, Xia, S, Chen, YX
The British journal of ophthalmology. 2018;(8):1077-1085
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BACKGROUND/AIMS: To evaluate the efficacy of antivascular endothelial growth factor (anti-VEGF) agents pretreatment before vitrectomy for patients with complicated proliferative diabetic retinopathy (PDR). METHODS The PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched up to June 2017 to identify related studies. The Peferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed. The StataSE V.12.0 software was used to analyse the relevant data. The weighted mean difference, relative risk and their 95% CIs were used to assess the strength of the association. RESULTS 14 randomised controlled trials involving 613 patients were assessed, the anti-VEGF pretreatment group included 289 patients and the control group included 324 patients. Our analysis indicated that anti-VEGF pretreatment before vitrectomy for complicated PDR could facilitate much easier surgery regarding less intraoperative bleeding, less endodiathermy, shorter duration of surgery, less iatrogenic retinal breaks, less frequency of using silicone oil and relaxing retinotomy (P<0.05). Additionally, anti-VEGF pretreatment could also achieve better postoperative best-corrected visual acuity, less early recurrent vitreous haemorrhage (VH) and quicker absorption of recurrent VH (P<0.05). However, the incidence of late recurrent VH, recurrent retinal detachment or related secondary surgery could not be reduced (P>0.05). CONCLUSION The pretreatment of anti-VEGF agents before vitrectomy for patients with complicated PDR might facilitate much easier surgery and better visual rehabilitation, reduce the rate of early recurrent VH and accelerate its absorption. Moreover, future better-designed studies with larger sample sizes are required to further evaluate the efficacy of different anti-VEGF agents and reach a firmer conclusion.