Risultati per: Nota 84

Circulation, Volume 150, Issue Suppl_1, Page A4146493-A4146493, November 12, 2024. Immune checkpoints are a group of immune regulatory plasma membrane proteins expressed on antigen-presenting cells and T cells, which are crucial for maintaining self-immune tolerance and modulating the effectiveness of T cell immune responses. The importance of selected immune checkpoints in cardiovascular diseases have been widely recognized. However, we identified a significant knowledge gap in the comprehensive understanding of immune checkpoint signaling across multiple levels in cardiovascular diseases. To bridge this gap, we developed a framework that encompasses disease stages and cell types regulated by immune checkpoint axes within the contexts of three major aortic diseases such as abdominal aortic aneurysm, atherosclerosis, and diabetic aortic pathology. Initially, at the transcriptional level, we analyzed the expressions of 58 pairs of immune checkpoint genes in mouse aorta across three models of abdominal aortic aneurysm, four models of hyperlipidemia and atherosclerosis, and three models of diabetes, each representing various stages of the respective diseases. At the single-cell level, we investigated the gene enrichment within separate clusters of aortic cells under diseased conditions. From the results, we found that among the immunosuppressive or double functional immune checkpoints, CD155 expression patterns were different from that of CD274 in more than 50% samples, suggesting that CD155 may play immunosuppressive/anti-inflammatory roles in aortic diseases that are different from CD274. Therefore, we performed flow cytometry to investigate potential regulation of the TIGIT/CD155 axis at the cellular levels in four organs of ApoE-/- mice compared to wild type. The results identified that TIGIT/CD155 axis is upregulated in aortic CD45+ leukocytes but not in CD45- non-leukocyte cellular compartments. CD155 enrichments were identified in CD45+CD11b+CD11c+ cells in blood and kidney, as well as in CD45+CD11b-CD11c+ cells in the lung. Furthermore, among the three functional markers used to identify the subclusters of heterogeneous aortic antigen-presenting cells—CD206, CX3CR1, and CD103—positive correlations were observed between CD155 expressions and the anti-inflammatory marker CD206, while correlations with CX3CR1 and CD103 were absent. These results have demonstrated that CD155-CD206 pathway may play surrogative roles to CD274 in suppressing inflammation and immune responses in atherosclerosis and aortic diseases.

New England Journal of Medicine, Volume 390, Issue 12, Page 1129-1139, March 2024.

Stroke, Volume 55, Issue Suppl_1, Page A84-A84, February 1, 2024. Introduction and Aims:The ANGEL-ASPECT trial demonstrated the effectiveness of endovascular therapy (EVT) in acute ischemic stroke (AIS) patients with large infarct. We did a secondary analysis to explore the efficacy of EVT according to Alberta Stroke Program Early Computed Tomography Score (ASPECT) and National Institutes of Health Stroke Scale (NIHSS).Methods:ANGEL-ASPECT trial was a randomized clinical trial involving patients with acute anterior-circulation large-vessel occlusion and an ASPECT score of 3-5 or an infarct-core volume of 70-100ml. Patients were randomly assigned to EVT or standard medical treatment (SMT) alone. We categorized patients based on the combination of ASPECT (≤3 or 4-5) and NIHSS (0.05).Conclusions:EVT was associated with better outcomes in AIS patients with large infarct and mild-to-moderate stroke severity (NIHSS

A partire dal 27 giugno 2023 è disponibile un aggiornamento dei documenti allegati alla Nota 100 (schede di prescrizione ed elenco dei farmaci)

L’Agenzia Italiana del Farmaco ha aggiornato la Nota 96 (determina AIFA n. 48/2023 pubblicata nella Gazzetta Ufficiale n. 43 del 20 febbraio 2023) sui criteri di appropriatezza prescrittiva della supplementazione con vitamina D e suoi analoghi (colecalciferolo, calcifediolo) per la prevenzione e il trattamento degli stati di carenza nell’adulto

Stroke, Volume 54, Issue Suppl_1, Page A84-A84, February 1, 2023. Introduction:Alteration of the gastrointestinal (GI) tract by resection or bypass surgery might affect the absorption of both warfarin and direct oral anticoagulants (DOACs). The clinical trials of DOACs excluded individuals with altered GI tract, hence there are limited pharmacokinetic data for them. Only several cases have been reported suggesting atrial fibrillation-related stroke due to reduced absorption of DOACs after GI surgery. We aimed to investigate the efficacy of warfarin and DOACs who underwent GI surgery using nationwide population-based data.Methods:This was a retrospective cohort study using claim-based national data from 2013 to 2020 from Korean Health Insurance Review and Assessment Service (HIRA). Patients with nonvalvular AF (NVAF) taking oral anticoagulants (OACs) were included. The patients taking OACs due to other indications than NVAF were excluded. Cox proportional hazard models with time-varying covariates were used to investigate the impact of GI surgery in patients taking warfarin and DOACs.Results:Of the 311,782 patients (mean age 72, male 56.7%) with NVAF, 3,807 underwent GI surgery. Warfarin and DOACs were prescribed in 14.3% and 85.7% of the patients, respectively. Overall, warfarin was associated with a higher risk of ischemic stroke compared with DOACs (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.44-1.59). In the GI surgery group, the hazard ratio for ischemic stroke for warfarin compared with DOACs was 2.70 (95% CI, 1.63-4.45, Figure). In the no GI surgery group, warfarin also had a higher risk of ischemic stroke compared with DOACs (HR 1.51, 95% CI 1.44-1.59). Among DOAC-treated patients, GI surgery was not associated with a risk of ischemic stroke (HR 0.87, 95% CI 0.67-1.12).Conclusions:DOACs were more effective for stroke prevention than warfarin in patients with NVAF whose GI tracts were altered due to previous surgery. GI surgery did not affect the risk of stroke in patients with NVAF taking DOAC.

L’introduzione della Nota 100 da parte dell’Agenzia italiana del farmaco ha riconfigurato le modalità di prescrizione di alcune classi di farmaci per il trattamento del diabete mellito di tipo 2, che possono essere prescritti anche dal medico di famiglia

Stroke, Volume 53, Issue Suppl_1, Page A84-A84, February 1, 2022. Introduction:Inflammatory responses are a fundamental pathological consequence of stroke, in which microglial activation plays a central role. Our previous study has found interferon regulatory factor 5 (IRF5) and 4 (IRF4) regulate microglial activation in young stroke mice. However, whether the IRF5-IRF4 regulatory axis has the same effect in aged brains is not known. Numerous neurochemical changes occur with aging, and stroke mainly affects the elderly. Therefore, to study the IRF5-IRF4 axis with aged animals is clinically more relevant and translational. In this study, we exclusively used aged mice (18-20 months) to examine the role of IRF5-IRF4 axis in stroke.Methods:Aged, microglial IRF5 or IRF4 conditional knockout (CKO) male mice (with LysMCre) were subjected to a 60-min middle cerebral artery occlusion (MCAO) (n=6/gp for stroke and =4/gp for sham). Infarct volumes and neurological deficits were quantified at 3d after MCAO. Flow cytometry was performed to evaluate microglial activation and peripheral leukocyte infiltration in the ischemic brain. ELISA was conducted to determine the plasma cytokine levels.Results:IRF5 CKO mice had significantly smaller cortical infarct size than the flox controls (48.07±5.51% vs. 66.9±5.51%, p=0.0206); larger infarct volumes were seen in IRF4 CKO vs. flox controls in the cortex and hemisphere (Cortex: 58.93±5.16% vs. 38.38±5.16%, p= 0.0049; Hemisphere: 68.73±5.16% vs. 44.63±5.16%, p=0.0008). Significantly improvement on the corner test and neurological deficit score was seen in IRF5 CKO vs. flox mice, and an opposite pattern showed in IRF4 CKO vs. flox controls. Flow cytometry showed IRF5 CKO microglia had significantly lower levels of IL-1β and CD68 than controls; whereas significantly higher levels of IL-1β and TNF-α were seen in IRF4 CKO vs. control microglia. Plasma levels of IL-6 and IL-12 p40were decreased in IRF5 CKO vs. flox mice, and the anti-inflammatory cytokines (IL-4/IL-10) levels were higher in IRF5 CKO, and lower in IRF4 CKO mice vs. their flox controls respectively.Conclusion:IRF5 signaling drives microglial pro-inflammatory responses and is detrimental to stroke; whereas IRF4 signaling leads to a microglial anti-inflammatory response and protects against ischemia in aged mice.

Risultati positivi dalla Nota che amplia agli mmg la prescrizione di anticoagulanti orali diretti per i soli pazienti con fibrillazione atriale non valvolare. Un percorso che coinvolge sempre di più il territorio e la medicina generale nella presa in carico di pazienti cronici.