Risultati per: Nota 98

Stroke, Volume 55, Issue Suppl_1, Page A98-A98, February 1, 2024. Rationale:Direct-acting oral anticoagulants (DOACs) are commonly prescribed with antiseizure medications (ASMs) due to concurrency and causal links between atrial fibrillation (AF) and epilepsy. However, enzyme-inducing-ASMs (EI-ASMs) may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk.Methods:We leveraged large-scale healthcare data to conduct an emulated target trial among a nationally representative cohort with AF and epilepsy. Thromboembolic and bleeding event rates were contrasted between adults on DOACs + EI-ASMs versus active comparators on DOACs + non-enzyme inducing ASMs. Data-adaptive high-dimensional propensity score matching was employed to control for observed confounders and proxies for unobserved confounders. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazard models with robust variance estimators to account for clustering within matched pairs.Results:Among incident ASM + DOAC users, we identified 14,078 and 14,158 episodes that met eligibility criteria for assessment of thromboembolic and bleeding outcomes, respectively. Incidence per 1,000 person-years was 88.5 for thromboembolic events and 68.3 for major bleeding events. Compared with use of non-enzyme inducing ASMs, use of EI-ASMs with DOACs was not associated with a difference in thromboembolic events (aHR=1.10, 95% CI: 0.82-1.46), but was associated with a reduction in major bleeding events (aHR=0.63, 95% CI: 0.44-0.89).Conclusions:EI-ASMs were not associated with alteration in DOAC efficacy. These real-world data are reassuring for the care of adults with epilepsy who require anticoagulation, particularly across a larger global community where EI-ASMs remain mainstays. Further research is needed on the reduction in bleeding risk with EI-ASMs, as this may be suggestive of pharmacokinetic interactions lowering DOAC levels without negating therapeutic effects.

Circulation, Volume 148, Issue Suppl_1, Page A18622-A18622, November 6, 2023. BACKGROUND:We have shown that the late-pregnant (LP) rodent exhibits a higher susceptibility to myocardial ischemia-reperfusion injury (IRI) compared to non-pregnant (NP). The molecular mechanisms remain unclear. The dysregulation of multiple microRNAs (miRs) in IRI suggests their potential as promising targets for therapeutic interventions.Methods:Female Sprague-Dawley rats in both NP and LP states underwent occlusion of the left anterior descending coronary artery (LAD) for a duration of 45 minutes, followed by reperfusion for 3 hours or 24 hours. Expression of miR was assessed via fluorescentin situhybridization. MicroRNA-microarray profiling was conducted on hearts of NP and LP rats subjected to IRI. Female H9c2 rat cardiomyoblast cells were transfected with miR mimics and inhibitors, and subjected to hypoxia/reoxygenation. Blood samples were obtained from NP, LP, and ischemic heart disease (IHD) patients. MiR98 inhibitor was administered at the initiation of reperfusion.Results:MicroRNA-microarray analysis revealed upregulation of microRNA-98-5p (miR-98) in LV of LP at baseline, and a further upregulation after IRI. The expression of Stat3 and Pgc-1α were decreased in LV of LP rats compared to NP rats upon IRI. Fluorescentin situhybridization revealed expression of miR-98 in cardiomyocytes in NP rats, which was increased in LP rats. Overexpression of miR-98in vitroin female H9c2 cells decreased Stat3 and Pgc-1α levels, and promoted apoptosis, oxidative stress, and inflammatory markers. MiR-98 inhibitor in LP rats at the onset of reperfusion reduced infarct size, apoptosis, oxidative stress, and inflammatory markers and was associated with upregulation of Stat3 and Pgc-1α. In humans, plasma miR-98 levels were significantly higher in healthy LP compared to healthy NP individuals and even higher in LP patients with IHD patients.CONCLUSIONS:We show the detrimental effects of miR-98 by promoting cardiomyocyte oxidative stress, inflammation, and apoptosis via its targets Stat3 and Pgc-1α in the context of late pregnancy. MiR-98 could be a novel cardio-protective strategy or biomarker in late pregnancy.

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 A98-A98, February 1, 2023. Introductions:Clinical trials have shown that aspiration thrombectomy is as safe and effective as stent-retriever thrombectomy. Multiple improvements have been made to the aspiration technique over the last few years. In this study, we aim to assess the effect of aspiration catheter bore size on the outcomes of A direct aspiration first pass technique (ADAPT) thrombectomy.Methods:We included patients who underwent ADAPT thrombectomy for M1 or internal carotid artery terminus (ICA-T) occlusions in the Stroke Thrombectomy and Aneurysm (STAR) database. Patients included between July 2016 and July 2022. We compared baseline characteristics, procedural metrics and outcomes between patients who underwent thrombectomy using small bore (0.035”-0.060”), medium bore (0.062”-0.068”) and large bore (0.070”-0.074”) catheters.Results:A total of 1158 patients were included; 576 (49.7%) females, 645 (70%) White, and 464 (40.6%) received IV-tPA. No difference was noticed in age, sex, and vascular risk factors between the 3 different groups. There was higher rate of IV-tPA in the small-bore catheter group (48.8%) compared to the medium and large bore catheter groups (38.4% and 36.7%, respectively) (P=0.03). Procedure duration was shorter when using medium (20 min) and large (18 min) compared to small bore catheters (30 min) (P=0.01). Both medium and large bore catheters were associated with higher rate of successful recanalization (88.9% and 87.9%, respectively) compared to small bore catheters (81.6%) (P=0.010). However, the difference in successful recanalization or procedure duration between medium and large bore catheters was not significant. No difference was noted in the rate of symptomatic hemorrhagic transformation (sICH) (4.7%, 5.3%, and 7.1%; P=0.345), 90-day favorable outcome (modified Rankin Scale 0-2) (41.8%, 39.3%, 40.8%; P=0.766) or 90-day mortality (18.1%, 23.5%, 24.4%; P=0.111) between the groups.Conclusions:Higher rate of successful recanalization and shorter procedure duration were observed when using medium and large bore aspiration catheters compared with small bore catheters in ADAPT technique. However, these procedural benefits were not observed when comparing large bore to medium bore catheters.

Monitoraggio Iss, 233 casi per 100mila abitanti contro 296

Record negativo vaccini da inizio campagna, -22,3%

Circulation, Volume 146, Issue Suppl_1, Page A12697-A12697, November 8, 2022. Introduction:The co-chaperone Bcl2-associated athanogene-3 (BAG3), along with its cofactor heat shock protein 70 (HSP70), is fundamental for protein quality control and cell survival in a healthy heart. However, elevated expression of BAG3 is also associated with metastasis in breast and other cancers, and small molecules such as JG-98 that disrupt BAG3-HSP70 binding have been shown to reduce cancer cell proliferation. We previously showed JG-98 is cardiotoxic in neonatal rat ventricular myocytes.Hypothesis:As BAG3-HSP70 is fundamental for autophagic protein turnover, JG-98 will reduce tumor size but have cardiotoxic effects.Methods:BT474 Resistant breast cancer cells were injected bilaterally into mammary fat pads of female athymic nude mice. When tumors reached 25 mm2, mice received a baseline echocardiography and were randomized to intraperitoneal injections of either PBS/DMSO vehicle or 3 mg/kg JG-98 twice weekly for 3 weeks (n = 4/group) or 6 weeks (n=10/group). Tumor growth was monitored using calipers and echocardiography was performed prior to sacrifice.Results:After 3 weeks, tumor volume increased by ~44% in Vehicle treated mice but decreased by 17% in JG-98 treated mice, effectively halting tumor growth. However, cardiac echocardiography did not reveal any functional or structural differences between the vehicle and JG-98 treated mice after either 3 or 6 weeks. JG-98 did result in dysregulation of BAG3 and its interactome in the LV. JG-98 slightly increased BAG3 levels in the LV at 3 weeks, but slightly decreased levels at 6 weeks. This agrees with data showing acute stress upregulates BAG3, but chronic stress downregulates it. Similarly, we found altered protein expression of the BAG3 binding partners HSBP8, HSPB5, and HSP70.Conclusions:JG-98 had no overt cardiotoxic effects, suggesting the adult heart may be resistant to disrupted BAG3-HSP70. However, we also observed dysregulated protein levels in the BAG3-mediated autophagy pathways that could precede dysfunction with more chronic treatment. Furthermore, mutations in BAG3 or altered expression levels could sensitize individuals to JG-98 treatment. Further work is necessary to understand the cardiac impact of cancer therapeutics that target BAG3.

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 A98-A98, February 1, 2022. Background and purpose:Post-stroke immunosuppression is associated with increased infection risk and mortality of stroke patients. However, the mechanisms driving post-stroke immunosuppression are not fully elucidated and strategies to prevent this fatal complication are lacking. We investigated the role of programmed death-ligand 1 (PD-L1) on post-stroke lymphocyte deficiency in a murine model of intracerebral hemorrhage (ICH).Methods:ICH was induced by intracerebral injection of autologous blood or collagenase IV to male C57BL/6 (B6) mice. Mice were randomly assigned into two groups to received anti-PD-1 antibody and vehicle respectively via intraperitoneal injection operating at 1 hour after ICH. Neurological function assessment, immunofluorescence, Elisa, flow cytometry, lung colony calculated were analyzed.Results:In a mice model of ICH, we identified that neuron-derived programmed death ligand 1 (PD-L1) are downregulated and released to the blood post ICH. Increased PD-L1 induced T cell and NK cell deficiency via their expressed PD-1, which are associated with increased lung infection post-ICH. Blocking PD-L1 pathway via an anti-PD-1 monoclonal antibody prevented the spleen atrophy of ICH mice, and improved peripheral T and NK cell numbers and function. Anti PD-1 antibody treated mice showed improved clinical outcome and reduced pulmonary bacterial burden.Conclusions:This study identified brain-derived PD-L1 to the periphery as a new pathway that lead to post-stroke immunosuppression, targeting PD-L1 could be a potential treatment strategy to reduce post-stroke infection risk.Key words:Programmed death ligand 1,intracerebral hemorrhage, neuron,immunosuppression, inflammationShort title:PD-L1 and post-stroke immunosuppression