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A metanalysis of available randomized controlled trials and observational studies comparing self-expanding and balloon-expandable bioprostheses in patients with small aortic annulus and aortic stenosis for short and midterm hemodynamic and clinical outcomes was performed. 21 studies with a total 8647 patients (self-expanding, n=4,336 patients vs balloon-expandable, n= 4,311 patients) were included. Self-expanding bioprostheses had a lower post-operative mean gradient at 30 days (MD -5.16, 95%CI 4.7-5.5, p value <0.001) and at one year (MD -6.6, 95%CI 6.1-7.03, p value <0.001), with a larger indexed Effective Orifice Area (0.17, 95%CI 0.13-0.22, p value <0.001and 0.17, 95%CI 0.08-0.27, p value < 0.001) at both time intervals. Balloon-expandable bioprostheses had a higher risk of 30-day and 1-year severe prosthesis-patient mismatch (RR 1.07, 95%CI 1.04-1.09, p value < 0.001; RR 1.07, 95%CI 1.04-1.11, p value <0.001). 30-day and 1 year paravalvular leaks (RR 0.99, 95%CI 0.98-0.99, p value < 0.001; RR 0.89, 95%CI 0.82-0.95, p value <0.001) and permanent pacemaker implantation (RR 0.97, 95%CI .94-0.99, p value 0.01, I2= 40%,) were lower in balloon-expandable group. Balloon-expandable bioprostheses were associated with lower risk of in-hospital stroke (RR 0.99, 95%CI 0.98-1,p value= 0.01). In conclusion, in patients with small aortic annulus and aortic stenosis, SE bioprostheses have superior haemodynamic performance but higher rates of PVL, PPI and in-hospital stroke. BE bioprostheses were associated with a higher risk of severe PPM.
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INTRODUCTION: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute myocardial infarction (AMI), which primarily affects young women without traditional cardiovascular risk factors, often presenting as sudden cardiac death. This study aims to investigate the prevalence, characteristics, predictors, and outcomes of cardiac arrest in SCAD patients. METHODS: The DISCO IT/SPA registry, an international retrospective multicenter study, enrolled 375 SCAD patients from 26 centers in Italy and Spain. Patients were categorized based on the presence or absence of cardiac arrest at admission. Data on demographics, clinical presentation, treatment, angiographic findings, and outcomes were collected. Angiograms were independently reviewed, and outcomes included major adverse cardiovascular events (MACE) and in-hospital bleeding. RESULTS: Among 375 SCAD patients, 20 (5.3%) presented with cardiac arrest. Both groups were similar in age, gender distribution, and conventional risk factors, except for a lower prevalence of dyslipidemia in the cardiac arrest group. ST-segment elevation myocardial infarction (STEMI) presentation and angiographic type 2b were independent predictors of cardiac arrest. Revascularization was more frequent in the cardiac arrest group. In-hospital outcomes, except for longer hospitalization, did not differ. On follow-up (average 21 months), MACE rates were similar between groups. CONCLUSIONS: Cardiac arrest is a notable complication in SCAD, mostly presenting with ventricular fibrillation. The prognosis of SCAD patients presenting with cardiac arrest did not differ from those without, reporting a similar rate of events both in-hospital and during long-term follow-up. STEMI presentation and angiographic type 2b were identified as independent predictors of cardiac arrest in SCAD.
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Anomalias dos Vasos Coronários , Parada Cardíaca , Sistema de Registros , Doenças Vasculares , Humanos , Feminino , Masculino , Parada Cardíaca/epidemiologia , Parada Cardíaca/etiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Anomalias dos Vasos Coronários/epidemiologia , Anomalias dos Vasos Coronários/diagnóstico por imagem , Anomalias dos Vasos Coronários/complicações , Anomalias dos Vasos Coronários/diagnóstico , Doenças Vasculares/congênito , Doenças Vasculares/epidemiologia , Doenças Vasculares/diagnóstico , Doenças Vasculares/complicações , Adulto , Espanha/epidemiologia , Idoso , Itália/epidemiologia , Angiografia Coronária/métodos , Seguimentos , Fatores de RiscoRESUMO
BACKGROUND: The impact of prosthesis-patient mismatch (PPM) on major endpoints after transcatheter aortic valve replacement (TAVR) is controversial and the effects on progression of heart damage are poorly investigated. Therefore, our study aims to evaluate the prevalence and predictors of PPM in a "real world" cohort of patients at intermediate and low surgical risk, its impact on mortality and the clinical-echocardiographic progression of heart damage. METHODS: 963 patients who underwent TAVR procedure between 2017 and 2021, from the RECOVERY-TAVR international multicenter observational registry, were included in this analysis. Multiparametric echocardiographic data of these patients were analyzed at 1-year follow-up (FU). Clinical and echocardiographic features were stratified by presence of PPM and PPM severity, as per the most current international recommendations, using VARC-3 criteria. RESULTS: 18% of patients developed post-TAVR. PPM, and 7.7% of the whole cohort had severe PPM. At baseline, 50.3% of patients with PPM were male (vs 46.2% in the cohort without PPM, P = .33), aged 82 (IQR 79-85y) years vs 82 (IQR 78-86 P = .46), and 55.6% had Balloon-Expandable valves implanted (vs 46.8% of patients without PPM, P = .04); they had smaller left ventricular outflow tract (LVOT) diameter (20 mm, IQR 19-21 vs 20 mm, IQR 20-22, P = .02), reduced SVi (34.2 vs 38 mL/m2, P < .01) and transaortic flow rate (190.6 vs 211 mL/s, P < .01). At predischarge FU patients with PPM had more paravalvular aortic regurgitation (moderate-severe AR 15.8% vs 9.2%, P < .01). At 1-year FU, maladaptive alterations of left ventricular parameters were found in patients with PPM, with a significant increase in end-systolic diameter (33 mm vs 28 mm, P = .03) and a significant increase in left ventricle end systolic indexed volume in those with moderate and severe PPM (52 IQR 42-64 and 52, IQR 41-64 vs 44 IQR 35-59 in those without, P = .02)). No evidence of a significant impact of PPM on overall (P = .71) and CV (P = .70) mortality was observed. Patients with moderate/severe PPM had worse NYHA functional class at 1 year (NYHA III-IV 13% vs 7.8%, P = .03). Prosthesis size≤23 mm (OR 11.6, 1.68-80.1) was an independent predictor of PPM, while SVi (OR 0.87, 0.83-0.91, P < .001) and LVOT diameter (OR 0.79, 0.65-0.95, P = .01) had protective effect. CONCLUSIONS: PPM was observed in 18% of patients undergoing TAVR. Echocardiographic evaluations demonstrated a PPM-related pattern of early ventricular maladaptive alterations, possibly precursor to a reduction in cardiac function, associated with a significant deterioration in NYHA class at 1 year. These findings emphasize the importance of prevention of PPM of any grade in patients undergoing TAVR procedure, especially in populations at risk.
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The past decade has seen growing awareness of the challenges faced by LGBTQIA+ scientists, including discrimination in the workplace and the lack of representation. Initiatives such as 500 Queer Scientists, Pride in STEM and the Microbiology Society's LGBTQIA+ events have been instrumental in promoting inclusivity in science, technology, engineering, mathematics and medicine (STEMM). The Microbiology Society and its members have played a pivotal role in these efforts and summarized here are their initiatives towards safer and more inclusive scientific and research environments. Starting with a series of interviews and blog posts about the experiences of LGBTQIA+ microbiologists in research, the Society has promoted the organization of networking and social events and developed guidelines for creating more inclusive scientific conferences. These initiatives have not only improved the representation and visibility of LGBTQIA+ individuals in microbiology, but have also served as a blueprint for similar efforts in other scientific areas. Nevertheless, despite improvements in some areas, full inclusion of LGBTQIA+ scientists is still hindered by societal and institutional policies around the world. Here, we propose novel measures to support and empower LGBTQIA+ microbiological communities within learned societies.
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Microbiologia , Minorias Sexuais e de Gênero , Humanos , Feminino , Masculino , Sociedades CientíficasRESUMO
The Forkhead box P2 (FOXP2) is an evolutionary conserved transcription factor involved in the maintenance of neuronal networks, implicated in language disorders. Some evidence suggests a possible link between FOXP2 genetic variability and frontotemporal dementia (FTD) pathology and related endophenotypes. To shed light on this issue, we analysed the association between single-nucleotide polymorphisms (SNPs) in FOXP2 and FTD in 113 patients and 223 healthy controls. In addition, we investigated SNPs in two putative targets of FOXP2, CNTNAP2, Contactin-associated protein-like 2 and PRNP, prion protein genes. Overall, 27 SNPs were selected by a tagging approach. FOXP2-rs17213159-C/T resulted associated with disease risk (OR = 2.16, P = 0.0004), as well as with age at onset and severity of dementia. Other FOXP2 markers were associated with semantic and phonological fluency scores, cognitive levels (MMSE) and neuropsychological tests. Associations with language, cognitive and brain atrophy measures were found with CNTNAP2 and PRNP genetic variability. Overall, although preliminary, results here presented suggest an influence of regulatory pathways centred on FOXP2 as a molecular background of FTD affecting neurological function of multiple brain areas.
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Carboxylic ester hydrolases with the capacity to degrade polyesters are currently highly sought after for their potential use in the biological degradation of PET and other chemically synthesized polymers. Here, we describe MarCE, a carboxylesterase family protein identified via genome mining of a Maribacter sp. isolate from the marine sponge Stelligera stuposa. Based on phylogenetic analysis, MarCE and its closest relatives belong to marine-associated genera from the Cytophaga-Flavobacterium-Bacteroides taxonomic group and appear evolutionarily distinct to any homologous carboxylesterases that have been studied to date in terms of structure or function. Molecular docking revealed putative binding of BHET, a short-chain PET derivative, onto the predicted MarCE three-dimensional structure. The synthetic ester-degrading activity of MarCE was subsequently confirmed by MarCE-mediated hydrolysis of 2 mM BHET substrate, indicated by the release of its breakdown products MHET and TPA, which were measured, respectively, as 1.28 and 0.12 mM following 2-h incubation at 30°C. The findings of this study provide further insight into marine carboxylic ester hydrolases, which have the potential to display unique functional plasticity resulting from their adaptation to complex and fluctuating marine environmentsw.
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Carboxilesterase , Filogenia , Carboxilesterase/genética , Carboxilesterase/metabolismo , Carboxilesterase/química , Animais , Poríferos/microbiologia , Ésteres/metabolismo , Expressão Gênica , Simulação de Acoplamento Molecular , Organismos Aquáticos/genética , Organismos Aquáticos/enzimologiaRESUMO
The long-term safety and effectiveness of transcatheter aortic valve replacement (TAVR) compared with surgical aortic valve replacement (SAVR) in low surgical risk has not been evaluated in a pooled analysis. An electronic database search was conducted for randomized controlled trials with a maximal 5 years clinical and echocardiographic follow-up including low surgical risk patients who underwent TAVR or SAVR. We calculated odds ratio (OR) and 95% confidence intervals (CIs) using a random-effects model. Subgroups analysis was performed for permanent pacemaker implantation and paravalvular leaks. Three randomized controlled trials were included with a total of 2,611 low surgical risk patients (Society of Thoracic Surgeons score <4%). Compared with SAVR, the TAVR group had similar rates of all-cause mortality (OR 0.94,95% CI 0.65 to 1.37, p = 0.75) and disabling stroke (OR 0.84, 95% CI 0.52 to 1.36, p = 0.48). No significant differences were registered in the TAVR group in terms of major cardiovascular events (OR 0.96, 95% CI 0.67 to 1.38, p = 0.83), myocardial infarction (OR 0.69, 95% CI 0.34 to 1.40, p = 0.31), valve thrombosis (OR 3.11, 95% CI 0.29 to 33.47, p = 0.35), endocarditis (OR 0.71,95% CI 0.35 to 1.48, p = 0.36), aortic valve reintervention (OR 0.93, 95% CI 0.52 to 1.66, p = 0.80), and rehospitalization (OR 0.80, 95% CI 0.52 to 1.02, p = 0.07) compared with SAVR. However, TAVR patients had a higher risk of paravalvular leaks (OR 8.21, 95% CI 4.18 to 16.14, p <0.00001), but lower rates of new-onset atrial fibrillation (OR 0.27,95% CI 0.17 to 0.30, p <0.0001). The rates of permanent pacemaker implantation were comparable from 1 year up to a maximum of 5 years (OR 1.32, 95% CI 0.88 to 1.97, p = 0.18). Lastly, TAVR had a greater effective orifice area (0.10 cm2/m2, 95% CI 0.05 to 0.15, p = 0.0001), but similar transvalvular mean gradients (0.60, 95% CI 3.94 to 2.73, p = 0.72). In conclusion, TAVR patients had similar long-term outcomes compared with SAVR, except for an elevated risk of paravalvular leaks in the TAVR group and increased rates of atrial fibrillation in the SAVR cohort.
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Estenose da Valva Aórtica , Ensaios Clínicos Controlados Aleatórios como Assunto , Substituição da Valva Aórtica Transcateter , Humanos , Estenose da Valva Aórtica/cirurgia , Seguimentos , Complicações Pós-Operatórias/epidemiologia , Medição de Risco/métodos , Fatores de Risco , Substituição da Valva Aórtica Transcateter/métodosRESUMO
Background: Percutaneous coronary intervention (PCI) is a widely used revascularization strategy for coronary artery disease. The choice between imaging-guided and physiology-guided PCI has been a subject of debate. This meta-analysis aims to systematically compare outcomes between imaging and physiology-guided PCI and management of intermediate coronary lesions (ICLs). Methods: A comprehensive literature search was conducted across major databases for studies published up to December 2023 following PRISMA guidelines. Seven eligible studies comparing imaging-guided and physiology-guided PCI were selected for the final analysis. Relevant outcome measures included major adverse cardiovascular events (MACE), target vessel revascularization (TVR), target vessel failure (TVF), and target lesion revascularization (TLR). Subgroup analysis was performed for ICLs. Results: A total of 5701 patients were included in the meta-analysis. After a mean follow-up of 2.1 years, imaging-guided PCI was associated with lower rates of TVR compared to physiology-guided PCI (OR 0.70, 95% CI 0.52-0.95, p = 0.02); concerning MACE, TVF, and TLR, no differences were found. When the analysis was restricted to studies considering ICLs management, there were no differences between the two techniques. Meta regression analysis did not show any impact of acute coronary syndromes (ACS) presentation on MACE and TVR. Conclusions: The findings suggest that imaging-guided PCI may reduce the need for future revascularization of the target vessel compared to the functional-guided approach, and this result was not influenced by ACS presentation. These results may have important implications for clinical practice, guiding interventional cardiologists in selecting the most appropriate guidance strategy.
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Microplastic (MP) contamination represents an issue of global concern for both aquatic and terrestrial ecosystems, but only in recent years, the study of MPs has been focused on freshwaters. Several monitoring surveys have detected the presence of a wide array of MPs differing in size, shape, and polymer composition in rivers and lakes worldwide. Because of their role of sink for plastic particles, the abundance of MPs was investigated in waters, and deep and shoreline sediments from diverse lakes, confirming the ubiquity of this contamination. Although diverse factors, including those concerning anthropogenic activities and physical characteristics of lakes, have been supposed to affect MP abundances, very few studies have directly addressed these links. Thus, the aim of the present study was to explore the levels of MP contamination in mountain and subalpine lakes from Northern Italy. Fourteen lakes dislocated at different altitudes and characterized by dissimilar anthropic pressures were visited. Lakeshore sediments were collected close to the drift line to assess MPs contamination. Our results showed the presence of MPs in lakeshore sediments from all the lakes, with a mean (± standard deviation) expressed as MPs/Kg dry sediment accounting to 14.42 ± 13.31 (range 1.57-61.53), while expressed as MPs/m2, it was 176.07 ± 172.83 (range 25.00-666.67). The MP abundance measured for Garda Lake was significantly higher compared to all the other ones (F1,13 = 7.344; P < 0.001). The pattern of contamination was dominated by fibers in all the lakes, but they were the main contributors in mountain lakes. These findings showed that the MP abundance varied according to the altitude of the lakes, with higher levels measured in subalpine lakes located at low altitudes and surrounded by populated areas.
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Monitoramento Ambiental , Sedimentos Geológicos , Lagos , Microplásticos , Poluentes Químicos da Água , Lagos/química , Itália , Sedimentos Geológicos/química , Microplásticos/análise , Poluentes Químicos da Água/análise , AltitudeRESUMO
AIMS: Data on glycoprotein IIb/IIIa inhibitor (GPI) use in real-world acute coronary syndrome (ACS) patients following the introduction of potent P2Y12 inhibitors and newer-generation stents are scant. Here, we aimed to assess the utilization, effectiveness, and safety of GPI in a large prospective multicentre cohort of contemporary ACS patients. METHODS AND RESULTS: SPUM-ACS prospectively recruited patients presenting with ACS between 2009 and 2017. The primary endpoint of the present study was major adverse cardiovascular events (MACE), a composite of all-cause death, non-fatal myocardial infarction, and non-fatal stroke at 1 year. Secondary endpoints were defined as any bleeding events, Bleeding Academic Research Consortium (BARC) 3-5 bleeding, and net adverse cardiovascular events (NACE). A total of 4395 ACS patients were included in the analysis. GPI-treated patients had more total coronary artery occlusion (56% vs. 35%, P < 0.001) and thrombus (60% vs. 35%, P < 0.001) at angiography. Among the propensity score-matched (PSM) population (1992 patients equally split into two groups), GPI-treated patients showed lower risk of MACE [PSM adjusted hazard ratio (HR) 0.70, 95% CI 0.49-0.99], but a higher risk of any (PSM adjusted HR 1.46, 95% CI 1.06-1.99) and major bleedings (PSM adjusted HR 1.73, 95% CI 1.09-2.76), resulting in a neutral effect on NACE (PSM adjusted HR 0.87, 95% CI 0.65-1.17). These results remained consistent across all subgroups. CONCLUSIONS: In patients with ACS undergoing percutaneous coronary intervention and receiving potent P2Y12 inhibitors, we observed a reduced risk of MACE and an increased risk of major bleedings at 1 year in patients treated with GPI. Although the routine use of GPI is currently not recommended, they might be considered in selected patients following a personalized balancing between ischaemic and bleeding risks.
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Síndrome Coronariana Aguda , Hemorragia , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Complexo Glicoproteico GPIIb-IIIa de Plaquetas , Humanos , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/diagnóstico , Masculino , Feminino , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Idoso , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Prospectivos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Pessoa de Meia-Idade , Resultado do Tratamento , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Fatores de Risco , Fatores de Tempo , Medição de Risco , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/administração & dosagemRESUMO
INTRODUCTION: Among different coronary stents implanted in High Bleeding Risk (HBR) patients with an indication for short antiplatelet therapy, no comparisons in terms of efficacy have been provided. METHODS: A Network Meta Analysis was performed including all randomized controlled trials comparing different coronary stents evaluated in HBR patients. Major Adverse Cardiovascular Events (MACEs) as defined by each included trial were the primary end point, whereas TLR (target lesion revascularization), TVR (target vessel revascularization), stent thrombosis and total and major (BARC3-5) bleedings were the secondary ones. RESULTS: A total of four studies (ONYX ONE, LEADERS FREE, SENIOR and HBR in BIO-RESORT) including 6637 patients were analyzed with different kind of stents and dual antiplatelet therapy (DAPT) length (1 or 6 months) on 12 months follow-up. About one-third of these patients were defined HBR due to indication for oral anticoagulation. All drug eluting stents (DESs) reduced risk of MACE compared to Bare Metal Stents (BMSs) when followed by a 1-month DAPT. At SUCRA analysis, Orsiro was the device with the highest probability of performing best. Rates of TLR and TVR were significantly lower when using Resolute Onyx, Synergy and BioFreedom stents in comparison to BMS when followed by 1-month DAPT, with Synergy ranking best. Synergy also showed a significantly lower number of stent thrombosis compared to BMS (RR 0.28, 95% CI 0.06-0.93), while Orsiro and Resolute Integrity showed the highest probability of performing best. CONCLUSION: In HBRs patients, all DESs were superior to BMSs in terms of efficacy and safety. Among DESs, Orsiro was the one with the highest ranking in terms of MACE, mainly driven by a reduced incidence of repeated revascularization and stent thrombosis.
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Doença da Artéria Coronariana , Stents Farmacológicos , Hemorragia , Metanálise em Rede , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Humanos , Doença da Artéria Coronariana/terapia , Trombose Coronária/etiologia , Trombose Coronária/prevenção & controle , Terapia Antiplaquetária Dupla , Hemorragia/prevenção & controle , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/administração & dosagem , Desenho de Prótese , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: Patients with IDH1/2-mutant lower-grade glioma have a high frequency of seizures. We aimed to investigate the correlations between seizures and tumor/patient characteristics and the impact of surgery and adjuvant treatments (AT) on seizure control along the disease trajectory. METHODS: We retrospectively included patients with IDH1/2-mutant lower-grade glioma who underwent surgery at the neurosurgery divisions of the University of Turin and Milan and were treated at the Division of Neuro-Oncology of Turin. Inclusion criteria were a diagnosis according to the 2021 WHO Classification and presentation with seizures; exclusion criteria were presence of CDKN2A/B homozygous deletion, intense/ring contrast enhancement on MRI at presentation, and small tissue biopsy. We evaluated seizure freedom for 2 months after surgery, 6 months from starting observation or AT, at recurrence, and for 6 months after treatments of recurrence. RESULTS: We included 150 patients. There were 77 (51%) and 31 (21%) patients with IDH-mutant/1p19q-codeleted grade 2 and 3 oligodendroglioma and 30 (20%) and 12 (8%) with IDH-mutant grade 2 and 3 astrocytoma, respectively. Total resection was accomplished in 68 (45%). Seventy-five patients (50%) received AT while the remaining 75 were observed with MRI. After 6 months after AT, 28 of 29 patients (96.5%) displayed seizure reduction, 5 of 28 (18%) being seizure-free. 66 of 124 patients (53%) had seizures at recurrence. After 6 months after second-line treatments, 60 of 66 patients (91%) had seizure reduction, 11 (17%) being seizure-free. In multivariable analyses, grade 3 histology positively correlated with seizure freedom at 2 months after surgery (OR 3.5, 1.4-8.9, p = 0.008), 6 months after AT (OR 9.0, 1.5-54.9, p = 0.017), and 6 months after treatment of recurrence (OR 4.9, 1.5-16.5, p = 0.009). Adjuvant radiotherapy reduced seizures at recurrence in a univariate analysis (OR 0.14, 0.03-0.7, p = 0.020). Patients with seizure freedom after surgery and AT displayed longer progression-free survival (PFS) (65, 24.5-105, vs 48 months, 32-63.5, p = 0.037). DISCUSSION: This study analyzed seizure control in patients with IDH1/2-mutant lower-grade glioma across multiple time points. Grade 3 correlated with better seizure control throughout the entire disease trajectory, and seizure freedom after surgery and AT correlated with a longer PFS regardless of tumor grade. These results could serve as an external control arm in clinical trials evaluating the efficacy on seizures of antitumor agents in patients with IDH-mutant lower-grade glioma.
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Neoplasias Encefálicas , Glioma , Isocitrato Desidrogenase , Mutação , Convulsões , Humanos , Isocitrato Desidrogenase/genética , Masculino , Feminino , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Pessoa de Meia-Idade , Convulsões/genética , Convulsões/etiologia , Convulsões/terapia , Glioma/genética , Glioma/terapia , Glioma/complicações , Glioma/diagnóstico por imagem , Estudos Retrospectivos , Adulto , Idoso , Oligodendroglioma/genética , Oligodendroglioma/terapia , Oligodendroglioma/complicações , Oligodendroglioma/cirurgia , Oligodendroglioma/patologia , Gradação de Tumores , Astrocitoma/genética , Astrocitoma/terapia , Astrocitoma/complicações , Astrocitoma/cirurgia , Astrocitoma/diagnóstico por imagemRESUMO
Given the importance of maximizing resection for prognosis in patients with HGG and the potential risks associated with ventricle opening, this study aimed to assess the actual increase in post-surgical complications related to lateral ventricle opening and its influence on OS and PFS. A retrospective study was conducted on newly diagnosed HGG, dividing the patients into two groups according to whether the lateral ventricle was opened (69 patients) or not opened (311 patients). PFS, OS, subependymal dissemination, distant parenchymal recurrences, the development of hydrocephalus and CSF leak were considered outcome measures. A cohort of 380 patients (154 females (40.5%) and 226 males (59.5%)) was involved in the study (median age 61 years). The PFS averaged 10.9 months (±13.3 SD), and OS averaged 16.6 months (± 16.3 SD). Among complications, subependymal dissemination was registered in 15 cases (3.9%), multifocal and multicentric progression in 56 cases (14.7%), leptomeningeal dissemination in 12 (3.2%) and hydrocephalus in 8 (2.1%). These occurrences could not be clearly justified by ventricular opening. The act of opening the lateral ventricles itself does not carry an elevated risk of dissemination, hydrocephalus or cerebrospinal fluid (CSF) leak. Therefore, if necessary, it should be pursued to achieve radical removal of the disease.
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BACKGROUND AND OBJECTIVE: In everyday clinical practice, medical decision is currently based on clinical guidelines which are often static and rigid, and do not account for population variability, while individualized, patient-oriented decision and/or treatment are the paradigm change necessary to enter into the era of precision medicine. Most of the limitations of a guideline-based system could be overcome through the adoption of Clinical Decision Support Systems (CDSSs) based on Artificial Intelligence (AI) algorithms. However, the black-box nature of AI algorithms has hampered a large adoption of AI-based CDSSs in clinical practice. In this study, an innovative AI-based method to compress AI-based prediction models into explainable, model-agnostic, and reduced decision support systems (NEAR) with application to healthcare is presented and validated. METHODS: NEAR is based on the Shapley Additive Explanations framework and can be applied to complex input models to obtain the contributions of each input feature to the output. Technically, the simplified NEAR models approximate contributions from input features using a custom library and merge them to determine the final output. Finally, NEAR estimates the confidence error associated with the single input feature contributing to the final score, making the result more interpretable. Here, NEAR is evaluated on a clinical real-world use case, the mortality prediction in patients who experienced Acute Coronary Syndrome (ACS), applying three different Machine Learning/Deep Learning models as implementation examples. RESULTS: NEAR, when applied to the ACS use case, exhibits performances like the ones of the AI-based model from which it is derived, as in the case of the Adaptive Boosting classifier, whose Area Under the Curve is not statistically different from the NEAR one, even the model's simplification. Moreover, NEAR comes with intrinsic explainability and modularity, as it can be tested on the developed web application platform (https://neardashboard.pythonanywhere.com/). CONCLUSIONS: An explainable and reliable CDSS tailored to single-patient analysis has been developed. The proposed AI-based system has the potential to be used alongside the clinical guidelines currently employed in the medical setting making them more personalized and dynamic and assisting doctors in taking their everyday clinical decisions.
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Algoritmos , Inteligência Artificial , Sistemas de Apoio a Decisões Clínicas , Sistemas de Apoio a Decisões Clínicas/organização & administração , HumanosRESUMO
BACKGROUND: The impact of statin therapy on cardiovascular outcomes after ST-elevation acute myocardial infarction (STEMI) in real- world patients is understudied. AIMS: To identify predictors of low adherence and discontinuation to statin therapy within 6 months after STEMI and to estimate their impact on cardiovascular outcomes at one year follow-up. METHODS: We evaluated real-world adherence to statin therapy by comparing the number of bought tablets to the expected ones at 1 year follow-up through pharmacy registries. A total of 6043 STEMI patients admitted from 2012 to 2017 were enrolled in the FAST STEMI registry and followed up for 4,7 ± 1,6 years; 304 patients with intraprocedural and intrahospital deaths were excluded. The main outcomes evaluated were all-cause death, cardiovascular death, myocardial infarction, major and minor bleeding events, and ischemic stroke. The compliance cut-off chosen was 80% as mainly reported in literature. RESULTS: From a total of 5744 patients, 418 (7,2%) patients interrupted statin therapy within 6 months after STEMI, whereas 3337 (58,1%) presented >80% adherence to statin therapy. Statin optimal adherence (>80%) resulted as protective factor towards both cardiovascular (0.1% vs 4.6%; AdjHR 0.025, 95%CI 0.008-0.079, p < 0.001) and all-cause mortality (0.3% vs 13.4%; Adj HR 0.032, 95%CI 0.018-0.059, p < 0.001) at 1 year follow-up. Further, a significant reduction of ischemic stroke incidence (1% vs 2.5%, p = 0.001) was seen in the optimal adherent group. Statin discontinuation within 6 months after STEMI showed an increase of both cardiovascular (5% vs 1.7%; AdjHR 2.23; 95%CI 1.37-3.65; p = 0,001) and all-cause mortality (14.8% vs 5.1%, AdjHR 2.32; 95%CI 1.73-3.11; p ã0,001) at 1 year follow-up. After multivariate analysis age over 75 years old, known ischemic cardiopathy and female gender resulted as predictors of therapy discontinuation. Age over 75 years old, chronic kidney disease, previous atrial fibrillation, vasculopathy, known ischemic cardiopathy were found to be predictors of low statin adherence. CONCLUSIONS: n our real-world registry low statin adherence and discontinuation therapy within 6 months after STEMI were independently associated to an increase of cardiovascular and all-cause mortality at 1 year follow-up. Low statin adherence led to higher rates of ischemic stroke.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Adesão à Medicação , Sistema de Registros , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Masculino , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Feminino , Adesão à Medicação/estatística & dados numéricos , Idoso , Pessoa de Meia-Idade , Seguimentos , Fatores de Tempo , Resultado do TratamentoRESUMO
Introduction: There are no clear indications for the best choice of anti-seizure medications to control brain tumor related epilepsy. In vitro studies have shown an antitumoral effect of Levetiracetam and Lacosamide on glioblastoma IDH-wild type. Research question: This study investigates whether the use of levetiracetam and/or lacosamide impacts survival rates. The secondary aim was to evaluate the efficacy of both ASMs in controlling seizures. Materials and methods: In this observational retrospective single-cohort study, patients underwent chemoradiation protocol after GBM surgery. They were grouped as follows: (1) use of levetiracetam, (2) use of lacosamide, (3) simultaneous use of levetiracetam and lacosamide, (4) no ASM usage. Survival curves were plotted using the Kaplan-Meier method coupled with a log-rank test for difference assesments. To evaluate the pharmacological efficacy of post-operative seizure control, a negative binomial regression was conducted. Results: The study included 272 patients, 174 of which underwent adjuvant chemoradiation treatment. Patients without ASM therapy had a non-significant longer median OS (compared to the other groups (log-rank = 0.37). The IRR of seizure relapse was 2.57 (p = 0.007) times higher in lacosamide users, and MGMT promoter methylation demonstrated a protective effect against postoperative seizure onset (p = 0.05), regardless of the aforementioned confounding factors. Discussion and conclusions: In patients diagnosed with GBM IDH-WT undergoing chemoradiation therapy, the use of levetiracetam or lacosamide for controlling BTRE does not seem to modify survival. Lacosamide users exhibited a higher IRR of postoperative seizures compared to levetiracetam users, and MGMT promoter methylation appears to be a protective factor.