Kacimi, Salah Eddine Oussama

Abstract Funding Acknowledgements Type of funding sources: None. Immunomodulatory effect of different statin regimens on regulatory T-cells among patients with acute coronary syndrome: a systematic review and network meta-analysis of randomized clinical trials Introduction In patients with acute coronary syndrome (ACS), studies suggest that statin therapy, besides its role in reducing the progression of atherosclerosis through its pharmacological effect, plays a pivotal role in controlling the pathogenesis of ACS through the anti-inflammatory effects of suppressor regulatory T cells (Tregs). Purpose We conducted a network meta-analysis (NMA) to determine the effects of low-dose conventional statin therapy (CST) (20 mg/day or less) and high-dose intensive statin therapy (IST) (40 mg/day or more) on the frequency of Tregs and their associated cytokines (IFN-γ, IL-10, TGF-β), compared to placebo. Methods The PubMed, Cochrane Library, and EMBASE databases were searched for randomized clinical trials (RCTs) to identify relevant articles published until June 2021. We pooled data extracted from the included studies using the standardized mean difference (SMD). A random-effects model was used to conduct this NMA. Heterogeneity was evaluated using Cochran's Q- and the I2-test. GRADE(Grading of Recommendations, Assessment, Development and Evaluations) was used to assess the study's quality. Data analysis was conducted using R software. Results A total of 505 patients were enrolled in the 5 RCTs. The NMA indicated a significant increase in Treg frequency in the CST group compared with the control group (SMD 1.77; 95% CI: 0.77 – 2.76; P-value = 0.0005) and a larger increase in the Treg frequency associated with the IST group compared with the control group (SMD 2.12; 95% CI: 1.15 – 3.10; P-value < 0.0001). However, there was significant heterogeneity and inconsistency among the included studies (τ2 = 0.6096; τ = 0.7808; I2 = 91.2% [80.5%; 96.0%]). When compared to the placebo, both CST and IST increased levels of secreted IL-10 (SMD 2.69; 95% CI: 2.07 – 3.31; P-value < 0.0001 and (SMD 2.14; 95% CI: 1.76 – 2.52; P-value < 0.0001), respectively. In comparison to the control group, CST was associated with increased levels of TGF-β (SMD 3.83; 95% CI: 0.63 – 7.0; P-value = 0.0189). This association was not seen in the IST group. IFN-γ levels decreased significantly in both the IST and CST groups (SMD -1.52; 95% CI: -1.94 – -1.10; P-value < 0.0001) and (SMD -2.34; 95% CI: -2.73 – -1.95; P-value < 0.0001) respectively. Conclusions Our study suggests that both high and low dose statin groups showed increased Treg frequency compared to the placebo group. IST showed larger benefits. Statin therapy also increased IL-10 and TGF-β cytokine levels and decreased IFN-γ levels. Therefore, statins have the potential to be the main treatment to reduce the incidence of cardiovascular events and improve cardiac function in patients with ACS through immunomodulatory effect on Treg.

e22509 Background: Chronic inflammatory states are linked with increased cancer risk. However, it is unclear if chronic sinusitis (CS) is involved in the development of certain malignancies. Several observational studies reported conflicting results regarding its association with cancer risk. Methods: We searched MEDLINE, EMBASE, Scopus, and Web of Science from their inception till October 2020. The fully adjusted risk estimates were abstracted independently and pooled using the generic inverse variant random-effects model. The Newcastle Ottawa Scale (NOS) was used to assess the quality of included studies. Results: Of 184 articles meeting our eligibilty criteria, 6 cohort and 6 case-control studies reporting data from USA (n = 2), Japan (n = 3), Singapore (n = 1), Taiwan (n = 5), and France (n = 1) were included in the final analysis. Compared to patients without CS (n = 562818), the RR of overall cancer risk in patients with CS (n = 51436) pooled from two studies was = 1.06 (95% CI: 1.00 - 1.13, P = 0.037). CS was associated with an increased cancer risk of head and neck (RR = 1.42, 95%CI: 1.28 - 1.58, P < 0.001), nasopharyngeal (NP) (RR = 1.62, 95%CI: 1.40 - 1.88, P < 0.001), sinonasal (RR = 1.75, 95% CI: 1.34 - 2.29, P < 0.001), and lung cancers (RR = 1.19, 95% CI: 1.14 - 1.23, P < 0.001). No significant assocation was identified with colorectal (RR = 1.02, 95% CI: 0.72 – 1.45, P = 0.89), liver (RR = 1.06, 95% CI: 0.77 - 1.45, P = 0.73), prostate (RR = 1.43, 95% CI: 0.87 – 2.33, P = 0.16), bladder (RR = 1.20, 95% CI: 0.82 - 1.75, P = 0.36), and stomach cancer (RR = 0.97, 95% CI: 0.88 - 1.06, P = 0.47). On the subgroup analysis, CS was associated with an increased risk of lung cancer in females (HR = 2.32, 95% CI: 1.23–4.39) but not in males (HR = 1.32, 95% CI: 0.79 – 2.21). In addition, the association between CS and NP cancer disappeared 1 year or more after diagnosis with RR = 1.82, 95% CI: 0.98 – 3.39) when pooling results from the three studies reporting the interval between CS diagnosis and cancer occurence. According to the NOS, 8 of the included studies were with low risk of bias, 2 with moderate risk, and 2 with high risk of bias. Conclusions: Our analysis found a significant association between CS and risk of overall, head and neck, nasopharyngeal, sinonasal, and lung cancers. Paradoxically, The risk of CS and NP cancer was significant only in subjects with a shorter duration of CS diagnosis, suggesting that CS is a coexistent complication of yet undiagnosed NP cancer. The results of this meta-analysis should be interpreted carefully due to the high heterogeneity and the small number of included studies in the site-specific cancer analyses. This association warrants further investigation using proper study design taking into consideration the years of follow-up, the interval between CS diagnosis and cancer occurrence, as well as gender disparities.