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Circulation, Volume 150, Issue Suppl_1, Page A4144620-A4144620, November 12, 2024. Background:Drug-eluting balloons (DEB) are promising alternatives to drug-eluting stents (DES) for managing de novo coronary artery disease (CAD). Given the scarcity of available data, our objective was to evaluate the outcomes of DES versus DEB in CAD patients.Methods:Databases such as PubMed, Embase, Cochrane Library, and Google Scholar were searched to identify studies comparing clinical outcomes between DCB and DES in de novo CAD patients. Using a random-effects model, pooled estimates of the mean difference (MD) and odds ratio (OR) were calculated along the 95% confidence intervals (CI), with statistical significance set at p

Circulation, Volume 150, Issue Suppl_1, Page A4141371-A4141371, November 12, 2024. Background:Approximately 1 of 5 catheter ablations for atrial fibrillation (AF) are repeat procedures. Despite this, little is known about risk factors for recurrence in patients undergoingrepeatablation compared with those undergoingde novoablation.Objective:To compare predictors of AF recurrence followingde novoandrepeatcatheter ablation.Methods:To compare AF recurrence between those with and without prior ablation, we conducted a retrospective cohort study of patients undergoing catheter ablation for treatment of symptomatic and drug-refractory AF. In this analysis, early recurrence was defined as 30 seconds of AF, atrial flutter, or atrial tachycardia within a 3-month blanking period, while late recurrence was defined as recurrent arrhythmia at >3 months. Multivariable Cox proportional hazard regression analysis was used to identify independent factors associated with recurrence.Results:Among 659 patients, 487 (mean age 63.3 +/- 10.1 years, 33% female, CHA2DS2-VASc 2.8 +/- 1.8, 62% paroxysmal) underwentde novoablation and 172 (mean age 65.1 +/- 10.0 years, 34% female, CHA2DS2-VASc 3.1 +/- 1.9, 60% paroxysmal) underwentrepeatablation with average follow up of 24.4+/-18.4 months. Multivariable modeling revealed that left atrial volume index (LAVi) [HR 1.015, p2 years follow-up. The left atrial volume index and early recurrence are the strongest predictors of late recurrence.

Circulation, Volume 150, Issue Suppl_1, Page A4136210-A4136210, November 12, 2024. Background:In the management of acute myocardial infarction (AMI) following percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) plays a crucial role in preventing recurrent ischemic events. Recent studies have explored the feasibility and safety of de-escalating DAPT from ticagrelor to clopidogrel.Methods:We conducted a systematic review and meta-analysis by searching several databases, including Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, MEDLINE (including MEDLINE InProcess) (OvidSP), Web of Science, Embase (OvidSP), and Scopus. We assessed the risk of bias using the ROB2 Cochrane tools for randomized controlled trials (RCTs). The analysis was performed using RevMan Cochrane software.Results:A total of ten studies including observational and clinical studies involving N=18,001patients (11,458 de-escalated from ticagrelor to clopidogrel after 12 months and 6,543 remained on ticagrelor after 12 months post-PCI) were included. There was no difference in the risk of all-cause death (RR 0.98; 95% CI 0.69 to 1.38; p=0.90), cardiovascular death (RR 1.09; 95% CI 0.68 to 1.74; p=0.73), myocardial infarction (RR 0.90; 95% CI 0.71 to 1.14; p=0.37) and stroke (RR 0.81; 95% CI 0.50 to 1.32; p=0.41) between the two groups.Conclusion:In conclusion, transitioning from ticagrelor to clopidogrel in acute myocardial infarction following percutaneous coronary intervention appears to be a feasible strategy for de-escalating dual antiplatelet therapy (DAPT). While maintaining efficacy in preventing adverse cardiovascular events, such as stent thrombosis, this approach may mitigate bleeding risks associated with prolonged ticagrelor use.

Circulation, Volume 150, Issue Suppl_1, Page A4140540-A4140540, November 12, 2024. Background:Timely initiation of temporary mechanical circulatory support (tMCS), escalation and de-escalation strategies are key components for treatment of cardiogenic shock (CS). However, little is known about tMCS strategies and outcomes based on etiology of CS and chronicity of heart failure. We evaluated differences of tMCS strategies and outcome in patients supported with Impella in acute myocardial infarction related CS (AMI-CS), de novo heart failure related CS (de novo HF-CS), and acute on chronic heart failure related CS (acute on chronic HF-CS).Methods and Results:The Japan Registry for Percutaneous Ventricular Assist Device (J-PVAD) is multicenter, observational registry enrolling all consecutive patients treated with Impella in Japan. We conducted a retrospective analysis of patients with Impella in J-PVAD between February 2020 and December 2022. Among 3678 CS patients supported with Impella. 2418 (65.7%) patients were presented with AMI-CS, 758 (20.6%) patients with de novo HF-CS, and 502 (13.7%) patients with acute on chronic HF-CS. The median time from hospital entry to initiation of Impella were 127 min, 339 min, and 1117 min in AMI-CS, de novo HF-CS, and acute on chronic HF-CS, respectively (P < 0.001 for each). 2233 (92.4%) patients with AMI-CS underwent percutaneous coronary intervention during index hospitalization with median door-balloon-time of 108 min. Patients treated with multiple mechanical circulatory supports were 51.4%, 64.2%, and 55.2% in AMI-CS, de novo HF-CS, and acute on chronic HF-CS, respectively. Using de novo CS-HF as a reference, the risk for in-hospital mortality for AMI-CS and acute on chronic HF-CS were: odds ratio (OR) 1.24 [95% confidence interval (CI) 1.04–1.50], P = 0.02 and OR 1.43 (95% CI 1.12–1.81), P = 0.004, respectively.Conclusions:In CS patients supported with Impella, time course and utilization of tMCS varied in AMI-CS, de novo HF-CS, and acute on chronic HF-CS. De novo HF-CS had significantly better mortality relative to AMI-CS and acute-on-chronic CS. Further research is required for tMCS strategies based on etiology of CS and chronicity of heart failure.

Circulation, Volume 150, Issue Suppl_1, Page A4134148-A4134148, November 12, 2024. Background&Rationale:Human endogenous retroviral (HERV) elements are embedded in 8% of our genome. They remain quiescent but can be transiently activated by viral infection to induce an interferon (IFN) response. In pulmonary arterial hypertension (PAH), HERV-K expression is elevated in myeloid cells, and thus can promote inflammation observed in pulmonary arteries (PAs) with progressive obstructive remodeling. PAH is linked to a mutation or a decrease in BMPR2 expression which our laboratory has recently shown in monocytes (MONO). HERVs are silenced by SUMOylated (S) TRIM28 (KAP1, a methylase) and SPEN (a histone deacetylase) factors that are also sequestered by the lnc RNAXISTwhich is increased in females to inactivate the extra X-chromosome. When TRIM28 is phosphorylated (P) by DNA-PK, it loses methylase activity and can act as a transcription factor.Hypothesis:ReducedBMPR2in MONO results in DNA-PK mediated P-TRIM28 causing demethylation ofXISTtargets (X-related genes) andHERV-Kthus increasing their expression. Competitive SPEN binding to the increasedXISTalso de-repressesHERV-K.Approach:We used THP-1 MONOs withBMPR2shRNA and induced pluripotent stem cell (i) MONOs derived fromBMPR2mutant PAH patients and assessedHERV-K,XIST, IFNs and related our findings to DNA-PK–P-TRIM28 and sequestration of SPEN.Results:XISTandHERV-KmRNA were significantly elevated in THP-1 MONOs with shBMPR2 vs. shControl and in PAH-iMONO vs. control iMONO based on gender. ReducedBMPR2also increased IFN genes. These findings were consistent with nuclear DNA-PK and P-TRIM28 shown to bind in affinity purification mass spectrometry analysis. Bisulfite conversion assay demonstrated decreased methylation of HERV-K inBMPR2-deficient MONOs attributed to a reduction in the methylase S-TRIM28. RNA-IP in THP-1 MONOs with shBMPR2 vs. shControl indicated increased binding ofXISTwith TRIM28 and SPEN, suggesting a competitive reduction in binding to HERV-K.Conclusions:Loss of BMPR2 increasesXISTandHERV-Kin MONO related to DNA-PK induced P-TRIM28 and reduced methylase S-TRIM28. IncreasedHERV-Kmay also be a function of the increase inXISTsequestering its deacetylase SPEN. These molecular features underlie a chronicHERV-K-IFN inflammatory response in PAH. They may explain the female predisposition to PAH, because the increase inXISTin females heightens the propensity to activateHERV-K-IFN signaling and chronic inflammation in PAs infiltrated by MONO.

Circulation, Volume 150, Issue Suppl_1, Page A4144239-A4144239, November 12, 2024. Background:The previous our study showed that vasomotion may be better preserved after drug-coated balloon (DCB) treatment than after stenting. However, there is no information available on the relationship between endothelial function and tissue characterization after DCB treatment.Aims:The purpose of this study was to investigate the relationship between endothelial function and tissue characterization after DCB for de-novo coronary lesion.Methods:We prospectively studied 19 patients who underwent acetylcholine provocation test and intravascular imaging at 8-month after DCB treatment. To evaluate endothelial-dependent vasomotion, the mean lumen diameter of the distal segment, beginning 5 mm and ending 15 mm distal to the edge of the treated segment, was quantitatively measured by angiography during the acetylcholine provocation test. Tissue characterization was assessed with integrated backscatter intravascular ultrasound (IB-IVUS).Results:There was a positive correlation between endothelial-dependent vasomotion and the proportion of lipid plaque in treated segments (r2=0.610, p=0.009). On the other hand, there were negative correlations between endothelial-dependent vasomotion and the proportion of dense fibrous or calcified plaque in treated segments (r2=-0.709, p=0.001, r2=-0.773, p

Circulation, Volume 150, Issue Suppl_1, Page A4136584-A4136584, November 12, 2024. Introduction:Niacin is a non-statin lipid-lowering therapy that has been shown to lower triglycerides and improve other risk factors for cardiovascular diseases. However, previous studies have reported inconsistent effects of niacin on mortality, and its effect on long-term prognosis has not been well studied.Goals:The aim of this study is to examine the association of niacin therapy with long-term all-cause mortality.Methods:In a nationwide historical cohort of 1,139,630 US Veterans with normal baseline kidney function, we examined the association of de novo niacin prescription from 2004 to 2006 with all-cause mortality during a 14-year follow-up. Associations were examined in Cox proportional hazard models adjusted for demographics, major comorbidities, and laboratory measurements. Prescription time-distribution matching was used to control for survival bias.Results:We identified 133,450 new users of niacin. Overall, patients had a mean (standard deviation) age of 60 (13) years, with 6% female, 78% White, 16% Black, and 6% Hispanic. Niacin users were more likely to be male, White, current, or former smokers and had higher frequencies of comorbidities. Niacin use (vs. non-use) was associated with a lower risk of death (Hazard ratio: 0.89, 95% confidential interval: 0.88-0.90) in the fully adjusted model (Model 4, Figure).Conclusion:In a large national cohort of US Veterans, niacin use was associated with a lower risk of death. Further studies are needed to corroborate the potential benefits of niacin on survival.

Circulation, Volume 150, Issue Suppl_1, Page A4140472-A4140472, November 12, 2024. Introduction:Hypertension (HTN) is a major risk factor for cardiovascular disease, and its prevention and management are influenced by health knowledge. This paper reviews the findings of a community-based HTN health knowledge program in Puerto Rico, facilitated by Community Health Workers (CHWs), also known as Promotores de Salud, who maintain a close relationship with their communities.Hypothesis:CHWs will positively impact a community’s HTN health knowledge and self-reported confidence in making lifestyle/behavior modifications with the use of Empowered to Serve (ETS) Health modules.Methods:American Heart Association (AHA) partnered with One Stop Career Center, a community-based organization in Puerto Rico. The program utilized AHA ETS modules focused on HTN prevention and management. CHWs instructed and implemented these modules across 10 community-based settings from 09/20/23 to 12/26/23. Participants were given a multiple-choice survey before and after each module. Descriptive Analysis and Two Proportion Z Test was performed on the surveys.CHWs also conducted a community discussion, distributed blood pressure devices, and referred participants to a self-measured blood pressure program.Results:The total count for pre-surveys was 214 and post-surveys was 224. Majority of participants identified as female (67.9% female) and Hispanic (95.2%), with 46.4% completed high school or less.Comparing pre- and post-surveys, confidence scores improved in monitoring blood pressure at home (41.0%, n/N=34/83 to 68.5%, n/N=61/89; p value=

Circulation, Volume 150, Issue Suppl_1, Page A4146046-A4146046, November 12, 2024. Background:Toll-like receptor 3 plays a role in the development of calcific aortic valve disease (CAVD). However, there are currently no pharmacological treatments for CAVD, and the discovery of de novo molecules targeting a specific protein is a time-intensive and financially demanding process. It is hypothesized that language models, trained on encodings of molecular graphs, can tailor the design of novel molecules with specific molecular and pharmacological properties.Objective:This study aims to develop a chemical language model tailored for designing novel molecules that target the inhibition of TLR3.Methods:A language model was pre-trained on 25,000 chemical structures sourced from the ChEMBL database. Each chemical structure was represented through Simplified Molecular Input Line Entry System (SMILES) strings, which were subsequently tokenized into discrete atomic and functional group tokens. The model leverages an Average-Stochastic Gradient Descent Weight-Dropped Long Short-Term Memory (AWD-LSTM) architecture. Transfer learning was employed for domain-specific fine-tuning of the pre-trained language model on the target chemical structures.Results:The model achieved strong performance by unfreezing the pre-trained language model’s parameters for fine-tuning in all layers. Specifically, it achieved an accuracy of 85.49%, a weighted F1-score of 83.28%, and a perplexity of 1.44. This approach yielded better results compared to partially freezing the model’s parameters, where only the latter layers were fine-tuned. The partial freezing approach resulted in an accuracy of 85.06%, a weighted F1-score of 82.44%, and a perplexity of 1.44.Conclusion:A chemical language model was developed for designing novel molecules that target the inhibition of TLR3. This provides an efficient and automated method for developing novel molecules with specific molecular and pharmacological properties.