Risultati per: Guida pratica all’uso farmaci ipoglicemizzanti inclusi nella Nota 100 AIFA

Schillaci: La resistenza è un’emergenza globale. No al fai da te’

UniCamillus, oggi 99,6% dei piccoli trattato nel modo sbagliato

Sitd, crescita fenomeni preoccupa soprattutto tra i giovani

‘Necessaria la sorveglianza delle infezioni nelle strutture sanitarie’

Medicinali più consumati sono per cuore, intestino e sangue

Al via al Tavolo tecnico; IA e farmacogenetica per ottimizzare

Circulation, Volume 150, Issue Suppl_1, Page A4144107-A4144107, November 12, 2024. Background:Sex, cholesterol and immune responses play significant roles in atherosclerosis development. Cholesterol lowering and global anti-inflammatory therapy have therapeutic limitations. Immune modulation with ApoB-100 peptide-based nanoparticles, named P210-PAM, reduced atherosclerosis in ApoE–/–mice carrying humanHLA-A*0201allele (A2Kb-Tg)when administered before significant atherosclerosis formed. In this study, we investigated the potential interaction among sex, cholesterol and immune responses in modulating atherosclerosis with P210-PAM therapy.Methods:A2Kb-Tgmice of both sexes fed high fat diet for 8 weeks were injected s.q. 3x with P210-PAM at 2–3-week intervals with or without change to normal chow at the second injection time point. PBS injections served as controls. Aortic atherosclerosis, splenic monocyte/macrophage and T cells were evaluated.Results:P210-PAM therapy without diet change had no effect on established atherosclerosis in both sexes (Table). P210-PAM therapy in female mice with diet change significantly inhibited growth of established atherosclerosis (Table) and reduced IL1R1 expression on splenic monocyte/macrophages (106.1±16.9, N=12,vs137.5±23.6, N=13; P

Circulation, Volume 150, Issue Suppl_1, Page A4144115-A4144115, November 12, 2024. Background:The apoB-100 peptide P210 is an atherosclerosis-related antigen. P210 conjugated-nanoparticles (P210-PAM) are internalized by antigen-presenting cells to elicit T cell responses and reduce atherosclerosis in mice. However, if and how P210 modulates human T cell responses is not known. We investigated the intrinsic T cell response to P210 in both healthy and atherosclerotic cardiovascular disease (ASCVD) subjects.Methods:We evaluated the T cell response to unconjugated P210 or P210-PAM in PBMCs of healthy subjects (N=15) and stable ASCVD patients (N=27) using the Activation Induced Marker (AIM) assay, where a change of 1.5-fold relative to unstimulated cells is considered the activation threshold and a value of 1 considered no response. Under IRB approval, PBMCs from stable ASCVD patients were collected within 1 year of acute MI or stroke, or a diagnosis of peripheral artery disease (PAD). To investigate effects on innate cells, monocytes from healthy subjects were phenotyped by flow cytometry staining after stimulation with P210-PAM.Results:P210 significantly increased CD4+CD69+CD154+ T cells in healthy subjects compared to ASCVD patients (2.2±1.9 vs 0.8±0.6 fold-change; P=0.01) without affecting other T cell activation markers. In healthy subjects, CD4+CD69+CD154+ T cell response to P210-PAM stimulation was similar compared to P210 stimulation (1.5±0.7 vs 2.2±1.9 fold-change) but was significantly increased in ASCVD patients (1.8±1.8 vs 0.8±0.7 fold-change, respectively; P=0.02). CD4+CD134+CD137+ T cells were also significantly increased by P210-PAM compared to P210 in ASCVD patients (2.8±2.0 vs 1.9±1.8 fold-change; P

Circulation, Volume 150, Issue Suppl_1, Page A4140896-A4140896, November 12, 2024. Background:Recent revisions in the guidelines for pre-clinical heart failure (HF), particularly concerning B-type natriuretic peptide (BNP) levels between 35-100 pg/mL, indicate a more detailed approach.Research question:1) BNP is influenced by several factors, including age, leading to potential variation in BNP’s predictive value for future HF events. 2) Risk stratification for HF in the pre-HF state (BNP levels: 35-100 pg/mL) has not been established.Hypothesis:We hypothesized that variations in BNP values predicting HF events exist in association with specific clinical variables.Methods:We prospectively evaluated consecutive HF patients in Stage A/B (stage A/B: 731/4,537) from the multicenter observational CHART-2 (Chronic Heart Failure Registry and Analysis in the Tohoku District-2) Study. Previous studies identified the following parameters for BNP levels: age, body mass index (BMI), and estimated glomerular filtration rate (eGFR). We assessed their 10-year HF-related events.Results:The enrolled patients had the following characteristics: mean age 67.6±12.0 years, 71.1% male, BMI 24.2±12.0 kg/m2, and eGFR 67.4±19.2 ml/min/1.73m2. As shown inFigures 1A-C, variations in AUC and cut-off values exist in each category (A: age quartiles, B: BMI per WHO criteria, and C: eGFR). The minimum cut-off value was 38.25 pg/mL in the youngest quartile. We performed risk stratification for those with BNP values of 35-100 pg/mL (n=1412) using classification and regression tree (CART) methods, identifying these cut-off values as shown inFigure 2. The hazard ratios (HR) for HF events were significantly higher in type 2 (age 50.9 pg/mL) (HR: 3.94, 95% CI: 2.88-5.38) compared to type 1 (both, P35 pg/mL) encompasses all at-risk patients in Stage A/B.