Ticagrelor versus clopidogrel in dual antiplatelet therapy after minor stroke or transient ischemic attack: an updated network meta-analysis.

BACKGROUND: Dual antiplatelet therapy (DAPT) with clopidogrel plus aspirin is a well-established practice after a minor stroke or transient ischemic attack (TIA). However, ticagrelor plus aspirin may be an alternative. AIMS: We systematically searched PubMed, Embase, and Cochrane Central from inception to January 2024. We included randomized controlled trials (RCTs) enrolling adults with acute minor stroke or TIA within 72 hours of the onset of the symptoms. RESULTS: A total of 8 RCTs were included in our meta-analysis. Ticagrelor plus aspirin (RR, 0.70; 95% CrI 0.52, 0.91) and clopidogrel plus aspirin (RR, 0.79; 95% CrI 0.64, 0.98) were superior to aspirin in preventing stroke recurrence in overall analysis. Excluding studies with dual antiplatelet up to 90 days, ticagrelor plus aspirin was the only strategy that maintained superiority compared with aspirin regarding stroke recurrence (RR, 0.70; 95% CrI 0.51, 0.95) and ischemic stroke (RR, 0.68; 95% CrI 0.47, 0.94). There was no significant difference between treatment groups regarding hemorrhagic stroke, functional disability, and mortality. CONCLUSIONS: DAPTs were superior to aspirin in preventing recurrence or ischemic stroke. Although no significant difference was observed between DAPTs, ticagrelor plus aspirin may be related to worse major bleeding results, including intracranial bleeding. Ticagrelor plus aspirin is a considerable option for patients after a minor stroke or TIA.

Efficacy of anti-amyloid-ß monoclonal antibody therapy in early Alzheimer's disease: a systematic review and meta-analysis.

BACKGROUND: Studies targeting amyloid-ß in patients with Alzheimer's disease (AD) have conflicting results and early initiation of therapy may yield better outcomes. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Clinicaltrials.gov for randomized trials comparing monoclonal antibodies (mAbs) with placebo in MCI or mild dementia due to AD. RESULTS: Nineteen studies comprising 15,275 patients were included. In patients with early AD, mAbs reduced the rate of decline, in both the Clinical Dementia Rating Scale, the sum of boxes (CDR-SB; MD -0.30; 95% CI -0.42,-0.19; p < 0.01), and the Alzheimer's Disease Assessment Scale, cognitive subscore (ADAS-cog; SMD -0.80; 95% CI -10.25,-0.35; p < 0.01). The results were similar between clinical stages for CDR-SB (MCI, MD -0.19; 95% CI -0.35,-0.03; p = 0.02; mild dementia, MD -0.45; 95% CI -0.65,-0.25; p < 0.01; subgroup differences, p = 0.13), as well as for ADAS-Cog (MCI, SMD -0.83; 95% CI -1.49,-0.17; p = 0.01; mild dementia, SMD -0.69; 95% CI -1.32 to -0.05; p = 0.03; subgroup differences, p = 0.47). The risk of amyloid-related imaging abnormalities (ARIA) was significantly higher in patients taking mAbs, including ARIA-edema (RR 7.7; 95% CI 4.60 to 13.00; p < 0.01), ARIA-hemorrhage (RR 1.8; 95% CI 1.22 to 2.59; p < 0.01), and symptomatic or serious ARIA (RR 14.1; 95% CI 7.30 to 27.14; p < 0.01). CONCLUSION: Anti-amyloid-ß mAbs attenuate cognitive and functional decline compared with placebo in early AD; whether the magnitude of this effect is clinically important remains uncertain, especially relative to the safety profile of these medications. Starting immunotherapy in patients with MCI was not significantly different than starting in the mild dementia stage. PROSPERO REGISTRY: CRD42023430698.

Modified Atkins diet for drug-resistant epilepsy: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness and side-effect profile of the modified Atkins diet (MAD) compared to the usual diet (UD) in reducing seizure frequency among patients with drug-resistant epilepsy (DRE). METHODS: In February 2023, we conducted an extensive search in PubMed, EMBASE, and Cochrane databases to find randomized controlled trials (RCTs) comparing MAD to UD in patients with drug-resistant epilepsy (DRE) on standard anti-seizure medication (ASM). We used random-effects meta-analyses and the Risk of Bias 2 tool to evaluate treatment effects and assess the quality of the included RCTs, respectively. RESULTS: Six studies were evaluated in the meta-analysis, including 575 patients, of whom 288 (50.1 %) were randomized to the MAD. Average follow-up period was 12 weeks. MAD plus standard drug therapy was associated with a higher rate of 50 % or greater reduction in seizure frequency compared to UD plus drug therapy (RR 6.28; 95 % CI 3.52-10.50; p<0.001), both in children (RR 6.28; 95 % CI 3.43-11.49; p<0.001) and adults with DRE (RR 6.14; 95 % CI 1.15-32.66; p = 0.033). MAD was also associated with a higher seizure freedom rate compared to UD (RR 5.94; 95 % CI 1.93-18.31; p = 0.002). Five studies reported adverse events with MAD; constipation was reported in 17 % of patients (95 % CI 5-44 %), lethargy in 11 % (95 % CI 4-25 %), and anorexia in 12 % (95 % CI 8-19 %). Due to limited information about the ASM regimens, we were unable to further analyze the interaction between MAD and ASM. SIGNIFICANCE: This meta-analysis, comprising 575 patients from 6 RCTs, revealed that MAD led to higher rates of seizure freedom and underscored its role in seizure frequency reduction by 50 % or more in both adults and children, with no significant adverse events concerns.

Biologicals in IgE-mediated food allergy.

PURPOSE OF REVIEW: A better understanding of the most recent scientific literature in the use of biological therapy in the treatment of patients with IgE-mediated food allergy. RECENT FINDINGS: A systematic review and meta-analysis demonstrated safety and effectiveness of omalizumab in the treatment of food allergy. The findings support the potential use of omalizumab as a monotherapy or as an adjunct to oral immunotherapy in IgE-mediated cow's milk allergy. The potential use of other biologics in the management of food allergy is subject of speculation. SUMMARY: Different biological therapies are under evaluation for food allergic patients. The advance in literature will guide for a personalized treatment in the near future. However, additional research is needed to better understand the best candidate for each treatment, the optimal dose and timing.

Blocking activation of CD4-CD8- T cells modulates their cytotoxic potential and decreases the expression of inflammatory and chemotactic receptors.

CD4-CD8- (double negative - DN) T cells represent a small fraction of circulating T lymphocytes but are a major source of pro-inflammatory cytokines in patients with infectious diseases, including chronic Chagas cardiomyopathy (CCC), one of the deadliest cardiopathies known. Chagas disease is caused by an infection with the protozoan parasite Trypanosoma cruzi and can lead to either an asymptomatic form or a high-mortality cardiac disease. While circulating DN T cells represent a major inflammatory cytokine-expressing cell population in Chagas disease, their potential to be recruited to the heart and to perform cytotoxicity has not been determined. Our previous studies showed that blocking DN T cell activation decreases the expression of IFN-gamma, a cytokine involved in the severity of CCC. Here, studying a well-characterized cohort of Chagas patients with CCC or the asymptomatic form of Chagas disease (indeterminate form, IND), we evaluated the expression of cytotoxic molecules, cytokine and chemokine receptors in γδ+ and αß+ DN T cells by multiparameter flow cytometry, and investigated whether blocking the activation of DN T cells influences the expression of these molecules. We observed that DN T cells from CCC display a higher expression of granzyme A, perforin, inflammatory molecules, and inflammatory chemokine receptors than cells from IND. Messenger RNA coding for these molecules is also upregulated in the heart of CCC patients. Importantly, blocking the activation of DN T cells from CCC modulates their cytotoxic potential and the expression of inflammatory and of chemokine receptors, suggesting that targeting DN T cell activation may be a valid strategy to reduce recruitment to the heart, inflammation, cytotoxicity and, thereby diminish CCC progression and severity.