Ammar Ismail

Cardioprotective mechanisms of phytochemicals against doxorubicin-induced cardiotoxicity

Doxorubicin (DOX) is an anthracycline antibiotic, which is effectively used in the treatment of different malignancies, such as leukemias and lymphomas. Its most serious side effect is dose-dependent cardiotoxicity, which occurs through inducing oxidative stress apoptosis. Due to the myelosuppressive effect of dexrazoxane, a commonly-used drug to alleviate DOX-induced cardiotoxicity, researchers investigated the potential of phytochemicals for prophylaxis and treatment of this condition. Phytochemicals are plant chemicals that have protective or disease preventive properties. Preclinical trials have shown antioxidant properties for several plant extracts, such as those of Aerva lanata, Aronia melanocarpa, Astragalus polysaccharide, and Bombyx mori plants. Other plant extracts showed an ability to inhibit apoptosis, such as those of Astragalus polysaccharide, Azadirachta indica, Bombyx mori, and Allium stavium plants. Unlike synthetic agents, phytochemicals do not impair the clinical activity of DOX and they are particularly safe for long-term use. In this review, we summarized the results of preclinical trials that investigated the cardioprotective effects of phytochemicals against DOX-induced cardiotoxicity. Future human trials are required to translate these cardioprotective mechanisms into practical clinical implications.

Regional versus local anesthesia for arteriovenous fistula creation in end-stage renal disease: a systematic review and meta-analysis:

There is a consensus in the literature that regional anesthesia (RA) improves local hemodynamic parameters in comparison to local anesthesia (LA) during arteriovenous fistula (AVF) surgical construction. However, the effects of both techniques on fistula patency and failure rates are still controversial. The aim of this meta-analysis is to synthesize evidence from published randomized trials and observational studies regarding the safety and efficacy of RA versus LA in AVF surgical construction. A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central retrieved six randomized trials (462 patients) and one retrospective study (408 patients). Pooling data using RevMan software (version 5.3) showed that RA was superior to LA in terms of primary fistula patency rate (RR = 1.22, 95% CI [1.08, 1.37], p = 0.0010); however, both types were comparable in terms of primary fistula failure rate (RR = 0.81, 95% CI [0.47, 1.40], p = 0.46). In comparison to LA, RA was associated with improved hemodynamic parameters including fistula blood flow (MD = 25.08, 95% CI [19.40, 30.76], p<0.00001), brachial artery diameter (SMD = 2.63, 95% CI [2.17, 3.08], p<0.00001), and outflow venous diameter (SMD = 0.93, 95% CI [0.30, 1.75], p = 0.004). Postoperative complications were comparable between both groups (OR = 0.23, 95% CI [0.05, 0.97], p = 0.05). In conclusion, RA was associated with higher primary patency rates of AVF and improved local blood flow in comparison to LA; however, both procedures were comparable in terms of primary failure rates and postoperative complications. Larger well-designed trials with longer follow-up periods should compare both techniques in terms of long-term patency rates and safety outcomes.

Self-gripping versus sutured mesh fixation methods for open inguinal hernia repair: A systematic review of clinical trials and observational studies.

Background. We performed this systematic review and meta‐analysis to compare the outcomes of Lichenstein hernia repair using either self‐gripping mesh or techniques of sutured mesh fixation. Methods. We searched PubMed, Cochrane CENTRAL, Scopus, Embase, and Web of Science for all clinical trials and observational studies that compared self‐gripping mesh versus sutured mesh fixation in Lichtenstein hernia repair. Combined outcomes were pooled as odds ratios or mean differences in a fixed‐effect model, using Comprehensive Meta‐Analysis software for Windows. Results. Twelve randomized, controlled trials and 5 cohort studies (n = 3,722 patients) were included in the final analysis. The two groups, using self‐gripping mesh or sutured mesh fixation, did not differ significantly in terms of recurrence rate (odds ratio = 0.66, 95% confidence interval 0.18–2.44; P = .54) or postoperative chronic groin pain (odds ratio = 0.75, 95% confidence interval 0.54–1.05; P = .09). The operative time was less in the self‐gripping mesh group (mean difference = −7.85, 95% confidence interval −9.94 to −5.76; P < .0001). For safety analysis, there were comparable risks between self‐gripping mesh and sutured mesh fixation groups in terms of postoperative infection (odds ratio = 0.81, 95% confidence interval 0.53–1.23; P = .32), postoperative hematoma (odds ratio = 0.97, 95% confidence interval 0.7–1.36; P = .9), and urinary retention (odds ratio = 0.66, 95% confidence interval 0.18–2.44; P = .54). Conclusion. Data from our analysis did not favor either of the two fixation techniques over the other in terms of recurrence or postoperative chronic groin pain. Decreased operative time in the self‐gripping mesh group cannot justify a recommendation for its routine use. Longer follow‐up studies are needed to compare the risk of long‐term recurrence for both meshes.

Evidence for association between hepatitis C virus and Parkinson’s disease

Parkinson’s disease (PD) is a globally prevalent neurodegenerative disorder, characterized by progressive neuronal loss in the substantia nigra and formation of Lewy bodies. These pathological characteristics are clinically translated into motor symptoms, such as bradykinesia, rigidity, resting tremors, and postural instability. Emerging data from epidemiological studies suggest a possible association between PD and hepatitis C virus (HCV) infection, which affects up to 71 million individuals worldwide. Preclinical studies have shown that HCV can penetrate and replicate within the brain macrophages and microglial cells, increasing their production of pro-inflammatory cytokines that can directly cause neuronal toxicity. Other studies reported that interferon, previously used to treat HCV infection, can increase the risk of PD through inhibition of the nigrostriatal dopaminergic transmission or induction of neuroinflammation. In this article, we provide a comprehensive review on the possible association between HCV infection and PD and highlight recommendations for further research and practice in this regard.

Safety and efficacy of ocrelizumab in rheumatoid arthritis patients with an inadequate response to methotrexate or tumor necrosis factor inhibitors: a systematic review and meta-analysis

We conducted this systematic reviews and meta-analysis to investigate the safety and efficacy of ocrelizumab in patients with active rheumatoid arthritis (RA) who exhibited resistance or intolerance to methotrexate or biological therapy. We performed a web-based literature search of PubMed, Google Scholar, EBSCO, Scopus, Embase, and Web of science for studies that compared ocrelizumab plus methotrexate versus methotrexate plus placebo in RA patients. Data were extracted from eligible studies and pooled as risk ratios (RR), using RevMan software. Pooling data from four RCTs (2230 patients) showed that ocrelizumab plus methotrexate were superior to methotrexate plus placebo at 24 weeks in terms of improvement on the American college of rheumatology (ACR20, ACR50, and ACR70) criteria (p < 0.00001), disease activity score 28-ESR (RR = 3.77, 95% CI [2.47, 5.74], p < 0.00001), and Sharp/van der Heijde radiological score (RR = 1.63, 95% CI [1.43, 1.85], p < 0.00001). These effects were consistent among all ocrelizumab doses. The rates of serious adverse events were comparable between the ocrelizumab and placebo containing groups (RR = 1, 95% CI [0.78, 1.28], p = 0.98). However, infusion related reactions were significantly higher in ocrelizumab group (RR = 2.13, 95% CI [1.69, 2.68], p < 0.00001), compared to placebo group. The combination of ocrelizumab plus methotrexate was superior to methotrexate plus placebo on all clinical and radiographic improvement scales. The incidence of adverse events, including serious adverse events, was comparable between both groups. Future trials should investigate the efficacy of ocrelizumab alone and develop strategies to alleviate its related infusion reactions.

Efficacy and safety of atazanavir/ritonavir-based antiretroviral therapy for HIV-1 infected subjects: a systematic review and meta-analysis

Atazanavir (ATZ) is a well-tolerated protease inhibitor that can be boosted with ritonavir (r) to treat infection with resistant strains of human immunodeficiency virus 1 (HIV-1). The aim of this meta-analysis was to compare the efficacy, safety, and metabolic effects of ATZ/r regimen versus commonly used antiretroviral drugs such as lopinavir (LPV) and darunavir (DRV) in HIV-1-infected patients. We searched PubMed, Scopus, Embase and Cochrane CENTRAL, using relevant keywords. Data were extracted from eligible randomized trials and pooled as risk ratios (RR) or standardized mean differences (SMD) in a meta-analysis model using RevMan software. Nine randomized controlled trials (RCTs) (3292 patients) were eligible for the final analysis. After 96 weeks of treatment, the pooled effect estimate did not favor either ATZ/r or LPV/r in terms of virological failure rate (RR 1.11, 95% CI [0.74, 1.66]). However, ATZ/r was marginally superior to LPV/r in terms of increasing the proportion of patients with HIV RNA <50 copies/ml (RR 1.09, 95% CI [1.01, 1.17]). The pooled effect estimate did not favor ATZ/r over DRV/r regarding the change in plasma levels of total cholesterol, triglycerides, or high-density lipoprotein at 24, 48, and 96 weeks. Moreover, no significant difference was found between the two regimens (ATZ/r and DRV/r) in terms of change in visceral (SMD -0.06, 95%CI [-0.33, 0.21]) or subcutaneous adipose tissue (SMD 0.12, 95% CI [-0.15, 0.39]). The ATZ/r regimen was generally as effective and well-tolerated as the LPV/r regimen for the treatment of HIV-1 patients. Compared to the DRV/r regimen, ATZ/r has no favorable effect on the plasma lipid profile or adipose tissue distribution.

Autologous blood for conjunctival autograft fixation in primary pterygium surgery: A systematic review and meta-analysis.

OBJECTIVE The study aimed to perform a systematic review and meta-analysis of randomized controlled trials comparing the efficacy and complications of autologous blood versus using fibrin glue and surgical sutures for conjunctival autograft fixation in primary pterygium surgery. DESIGN Systematic review with quantitative meta-analysis. METHODS Four authentic databases have been searched using relevant keywords. Eligible studies were obtained, and their data were extracted into an online form. Analysis was done using Review Manager for windows. Dichotomous outcomes were reported as risk ratio, while continuous data were reported as mean difference. RESULTS Seven studies were included in the analysis. Most of the included studies were of moderate quality according to Cochrane Risk of Bias assessment tool. There was no difference between the three techniques in recurrence rates (Risk Ratio (RR) 0.80, 95% CI [0.45 to 1.44], p= 0.46). Graft retraction and displacement were more profound in the autologous blood group vs fibrin glue and suture groups (RR 3.22, 95% CI [1.48 to7.02], p= 0.003) and (RR 5.27, 95% CI [2.24 to 12.38], p> 0.001) respectively. In terms of operative time, fibrin glue took shorter while suturing took longer time compared to blood coagulum (Mean Difference (MD) =1.57, 95% CI [0.90, 2.25], p> 0.00001) and (MD -20.47, 95% CI [-38.05 to -2.88], p =0.02). CONCLUSION Autologous blood for conjunctival autograft fixation in primary pterygium surgery was associated with lower graft stability than fibrin glue or sutures. However, it did not account for higher recurrence rates than the fibrin glue or sutures. Patient satisfaction and postoperative symptoms are relatively better in the blood coagulum group than the other techniques. The overall quality of evidence is low. Further well designed randomized controlled trials are still needed.

02.01 Safety and efficacy of ocrelizumab in rheumatoid arthritis patients with an inadequate response to methotrexate or tumour necrosis factor inhibitors: A systematic review and meta-analysis

Background We conducted this systematic reviews and meta-analysis to investigate the safety and efficacy of ocrelizumab in patients with active rheumatoid arthritis (RA) who exhibited resistance or intolerance to methotrexate or TNF inhibitors. Materials and methods We performed a web-based literature search of PubMed, Google Scholar, EBSCO, Scopus, Embase, and Web of science for studies that compared ocrelizumab plus methotrexate versus methotrexate plus placebo in RA patients. Data were extracted from eligible studies and pooled as risk ratios (RR), using RevMan software. Results Pooling data from four RCTs (2230 patients) showed that ocrelizumab plus methotrexate were superior to methotrexate plus placebo at 24 weeks in terms of the American college of rheumatology (ACR20, ACR50, and ACR70) improvement criteria (p<0.00001), disease activity score 28-ESR (RR=3.77, 95% CI [2.47, 5.74], p<0.00001), and Sharp/van der Heijde radiological improvement score (RR=1.63, 95% CI [1.43, 1.85], p<0.00001). These effects were consistent among all ocrelizumab doses. The rates of serious adverse events were comparable between the ocrelizumab and placebo containing groups (RR=1, 95% CI [0.78, 1.28], p=0.98). However, infusion related reactions were significantly higher in ocrelizumab group (RR=2.13, 95% CI [1.69, 2.68], p<0.00001), compared to placebo group. Conclusion The combination of ocrelizumab plus methotrexate was superior to methotrexate plus placebo on all clinical and radiographic improvement scales. The incidence of adverse events, including serious adverse events, was comparable between both groups. Future trials should investigate the efficacy of ocrelizumab alone and develop strategies to alleviate its related infusion reactions.