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PURPOSE: Directly imaging the function of cerebral perforating arteries could provide valuable insight into the pathology of cerebral small vessel diseases (cSVD). Arterial pulsatility has been identified as a useful biomarker for assessing vascular dysfunction. In this study, we investigate the feasibility and reliability of using dual velocity encoding (VENC) phase-contrast MRI (PC-MRI) to measure the pulsatility of cerebral perforating arteries at 7 T. METHODS: Twenty participants, including 12 young volunteers and 8 elder adults, underwent high-resolution 2D PC-MRI scans with VENCs of 20 cm/s and 40 cm/s at 7T. The sensitivity of perforator detection and the reliability of pulsatility measurement of cerebral perforating arteries using dual-VENC PC-MRI were evaluated by comparison with the single-VENC data. The effects of temporal resolution in the PC-MRI acquisition and aging on the pulsatility measurements were investigated. RESULTS: Compared to the single VENCs, dual-VENC PC-MRI provided improved sensitivity of perforator detection and more reliable pulsatility measurements. Temporal resolution impacted the pulsatility measurements, as decreasing temporal resolution led to an underestimation of pulsatility. Elderly adults had elevated pulsatility in cerebral perforating arteries compared to young adults, but there was no difference in the number of detected perforators between the two age groups. CONCLUSION: Dual-VENC PC-MRI is a reliable imaging method for the assessment of pulsatility of cerebral perforating arteries, which could be useful as a potential imaging biomarker of aging and cSVD.
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Arterias Cerebrales , Imagen por Resonancia Magnética , Flujo Pulsátil , Humanos , Femenino , Masculino , Adulto , Anciano , Reproducibilidad de los Resultados , Arterias Cerebrales/diagnóstico por imagen , Arterias Cerebrales/fisiología , Flujo Pulsátil/fisiología , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Adulto Joven , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Circulación Cerebrovascular/fisiología , Velocidad del Flujo Sanguíneo/fisiología , Angiografía por Resonancia Magnética/métodos , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
BACKGROUND: Type 2 diabetes (T2D) patients have an increased risk of heart failure (HF). There are limited data on the association between HF and T2D in specific healthcare settings. This study sought to analyse the prevalence and incidence of HF in a contemporary cohort of T2D patients attending cardiology and endocrinology outpatient clinics. METHODS: We conducted an observational multicentre prospective study (DIABET-IC) that enrolled patients with a T2D diagnosis attending cardiology and endocrinology outpatient clinics in 30 centres in Spain between 2018 and 2019. The prevalence at the start of the study and the incidence of HF after a 3 year follow-up were calculated. HF was defined as the presence of typical symptoms and either: a) LVEF < 40%; or b) LVEF ≥ 40% with elevated natriuretic peptides and echocardiographic abnormalities. RESULTS: A total of 1249 T2D patients were included in the present analysis (67.6 ± 10.1 years, 31.7% female). HF was present in 490 participants at baseline (prevalence 39.2%), 150 (30.6%) of whom had a preserved ejection fraction. The presence of adverse social determinants and chronic conditions such as chronic kidney disease and atherosclerotic cardiovascular disease were more frequent in HF patients. During the study period, there were 58 new diagnoses of HF (incidence 7.6%) among those without baseline HF. The incidence rate was 3.0 per 100 person-years. Independent predictors of incident HF were smoking, left ventricular ejection fraction, NT-ProBNP, history of tachyarrhythmia and treatment with pioglitazone, oral anticoagulants, or diuretics. Despite an average suboptimal glycaemic control, the use of antidiabetic drugs with cardiovascular benefits was low (30.4% for sodium-glucose cotransporter-2 inhibitors and 12.5% for glucagon-like peptide-1 receptor agonists). CONCLUSIONS: In this contemporary cohort of T2D patients attending cardiology and endocrinology outpatient clinics, the prevalence and incidence of HF were high, comorbidities were frequent, and the use of antidiabetic agents with cardiovascular benefit was low. Outpatient care seems to be a unique opportunity for a comprehensive T2D approach that encompasses HF prevention, diagnosis, and treatment.
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Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Femenino , Masculino , Estudios Prospectivos , Incidencia , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Prevalencia , Persona de Mediana Edad , España/epidemiología , Anciano , Factores de Tiempo , Medición de Riesgo , Factores de Riesgo , Pronóstico , Función Ventricular Izquierda , Hipoglucemiantes/uso terapéuticoRESUMEN
OBJECTIVE: Catecholaminergic signaling has been a target for therapy in different type of cancers. In this work, we characterized the ADRß2, DRD1 and DRD2 expression in healthy tissue and endometrial tumors to evaluate their prognostic significance in endometrial cancer (EC), unraveling their possible application as an antitumor therapy. METHODS: 109 EC patients were included. The expression of the ADRß2, DRD1 and DRD2 proteins was evaluated by immunohistochemistry and univariate and multivariate analysis to assess their association with clinic-pathological and outcome variables. Finally, HEC1A and AN3CA EC cell lines were exposed to different concentrations of selective dopaminergic agents alone or in combination to study their effects on cellular viability. RESULTS: ADRß2 protein expression was not associated with clinico-pathological parameters or prognosis. DRD1 protein expression was reduced in tumors samples but showed a significant inverse association with tumor size and stage. DRD2 protein expression was significantly associated with non-endometrioid EC, high grade tumors, tumor size, worse disease-free survival (HR = 3.47 (95%CI:1.35-8.88)) and overall survival (HR = 2.98 (95%CI:1.40-6.34)). The DRD1 agonist fenoldopam showed a reduction of cellular viability in HEC1A and AN3CA cells. The exposure to domperidone, a DRD2 antagonist, significantly reduced cell viability compared to the control. Finally, DRD1 agonism and DRD2 antagonism combination induced a significant reduction in cell viability of the AN3CA cells compared to monotherapy, close to being an additive response than a synergistic effect (CI of 1.1 at 0.5% Fa). CONCLUSION: DRD1 and DRD2 expression levels showed a significant association with clinico-pathological parameters. Both the combined activation of DRD1 and blockage of DRD2 may form an innovative strategy to inhibit tumor growth in EC.
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Neoplasias Endometriales , Receptores de Dopamina D2 , Femenino , Humanos , Pronóstico , Receptores de Dopamina D2/metabolismo , Neoplasias Endometriales/tratamiento farmacológicoRESUMEN
Intracellular transport of cargoes in the cell is essential for the organization and functioning cells, especially those that are large and elongated. The cytoskeletal networks inside large cells can be highly complex, and this cytoskeletal organization can have impacts on the distance and trajectories of travel. Here, we experimentally created microtubule networks with varying mesh sizes and examined the ability of kinesin-driven quantum dot cargoes to traverse the network. Using the experimental data, we deduced parameters for cargo detachment at intersections and away from intersections, allowing us to create an analytical theory for the run length as a function of mesh size. We also used these parameters to perform simulations of cargoes along paths extracted from the experimental networks. We find excellent agreement between the trends in run length, displacement, and trajectory persistence length comparing the experimental and simulated trajectories.
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INTRODUCTION: While brains of patients with Alzheimer's disease and related tauopathies have evidence of altered RNA processing, we lack a mechanistic understanding of how altered RNA processing arises in these disorders and if such changes are causally linked to neurodegeneration. METHODS: Using Drosophila melanogaster models of tauopathy, we find that overall activity of nonsense-mediated mRNA decay (NMD), a key RNA quality-control mechanism, is reduced. Genetic manipulation of NMD machinery significantly modifies tau-induced neurotoxicity, suggesting that deficits in NMD are causally linked to neurodegeneration. Mechanistically, we find that deficits in NMD are a consequence of aberrant RNA export and RNA accumulation within nuclear envelope invaginations in tauopathy. We identify a pharmacological activator of NMD that suppresses neurodegeneration in tau transgenic Drosophila, indicating that tau-induced deficits in RNA quality control are druggable. DISCUSSION: Our studies suggest that NMD activators should be explored for their potential therapeutic value to patients with tauopathies.
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Degradación de ARNm Mediada por Codón sin Sentido , Tauopatías , Animales , Drosophila melanogaster/genética , Drosophila/genética , Tauopatías/genética , ARNRESUMEN
BACKGROUND: Intravitreal injections are a common ophthalmologic procedure. While infections following these injections are rare, they can lead to endophthalmitis, with potentially serious consequences. Various methods have been proposed to prevent endophthalmitis, including the use of antisepsis and antibiotics in patient preparation. PURPOSE: To evaluate the antiseptic efficacy of aqueous chlorhexidine (CHX) and povidone-iodine (PI) when used alone and in combination with lidocaine gel (LG) in vitro. METHODS: Two independent experimental trials were conducted. The first trial determined the minimum inhibitory concentrations (MICs) and the minimum bactericidal concentrations (MBCs) of CHX and PI against six bacterial strains. The second trial evaluated the bactericidal efficacy of the antiseptic agents (CHX 0.1% and PI 5%) and their combination with LG against the same bacterial strains. RESULTS: CHX was more effective than PI in reducing the number of colonies forming units (cfus) of the tested bacteria. The order in which the antiseptic and LG were administered affected their effectiveness, with CHX administered before LG resulting in greater reduction of bacterial growth. CONCLUSIONS: CHX 0.1% is more effective than PI 5% as an antiseptic agent. Application of CHX and PI prior to the use of lidocaine gel results in a more effective reduction of microorganisms.
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INTRODUCTION AND OBJECTIVES: The development of specific heart failure (HF) units has improved the management of patients with this disease due to improved organization and resource management. The Spanish Society of Cardiology (SEC) has defined 3 types of HF units (community, specialized, and advanced) based on their complexity and service portfolio. Our aim was to compare the characteristics, treatment, and outcomes of patients with HF according to the type of unit. METHODS: We analyzed data from the SEC-Excelente-IC quality accreditation program registry, with 1716 patients consecutively included in two 1-month cutoffs (March and October) from 2019 to 2021 by 45 SEC-accredited HF units. We compared the characteristics, treatment and 1-year outcomes between the 3 types of units. RESULTS: Of the 1716 patients, 13.2% were treated in community units, 65.9% in specialized units, and 20.9% in advanced units. The rates of mortality (27.5 vs 15.5/100 patients-year; P<.001), admissions for HF (39.7 vs 29.2/100 patients-year; P=.019), total decompensations (56.1 vs 40.5/100 patients-year; P=.003), and combined death/admission for HF (45.2 vs 31.4/100 patients-year; P=.005) were higher in community units than in specialized/advanced units. Follow-up in a community unit was an independent predictor of higher mortality and admissions at 1 year. CONCLUSIONS: Compared with follow-up by more specialized units, follow-up in a community unit was associated with a higher decompensation rate and increased 1-year mortality.
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BACKGROUND: Heart failure (HF) is a major health problem in Western countries, and a leading cause of hospitalizations and death. There is a scarcity of data on the influence of sex on HF outcomes in elderly patients. The aim of the present study was to analyze differences between men and women in clinical characteristics, in-hospital mortality, 30-day HF readmission rates, cardiovascular mortality and HF readmission rates at 1 year after discharge in patients older than 75 years hospitalized for HF in Spain. METHODS: Retrospective analysis of patients discharged with a main diagnosis of HF from all Spanish public hospitals between 2016 and 2019. Patients aged 75 years or older were selected, and a comparison was made between male and female patients. RESULTS: From 2016 to 2019, a total of 354,786 episodes of HF in this age subgroup were identified, 59.2% being women. The overall mean age was 85.2 ± 5.4 years, being higher in women (85.9 ± 5.5 vs. 84.2 ± 5.3 years, p < 0.001). Risk-adjusted in-hospital mortality was lower in women (odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.92-0.97; p < 0.001). Female sex also showed a protective effect for 30-day readmissions, with an OR of 1.06 (95% CI: 1.04-1.09; p < 0.001). One-year cardiovascular mortality (24.1% vs. 25.0%; p < 0.001) and one-year HF readmission rates (30.8% vs. 31.6%; p = 0.001) were lower in women. CONCLUSIONS: Almost 60% of hospital admissions for HF in people aged 75 years or older between 2016 and 2019 in Spain were female patients. Female sex seems to play a protective role on in-hospital mortality and the rate of admissions and mortality at 1 year after discharge.
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Insuficiencia Cardíaca , Mortalidad Hospitalaria , Readmisión del Paciente , Humanos , Femenino , Masculino , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Anciano de 80 o más Años , Mortalidad Hospitalaria/tendencias , Estudios Retrospectivos , Anciano , España/epidemiología , Factores Sexuales , Readmisión del Paciente/estadística & datos numéricos , Factores de Riesgo , Enfermedad Aguda , Factores de Tiempo , Factores de Edad , Medición de Riesgo , Pronóstico , Tasa de Supervivencia/tendenciasRESUMEN
Gastrointestinal Stromal Tumors (GIST) are the most frequent mesenchymal neoplasia of the digestive tract. Genomic alterations in KIT, PDFGRA, SDH, and BRAF genes are essential in GIST oncogenesis. Therefore, the mutations in these genes have demonstrated clinical implications. Tumors with deletions in KIT-exon 11 or duplications in exon 9 are associated with a worse prognosis. In contrast, KIT-exon 11 substitutions and duplications are associated with a better clinical outcome. Moreover, mutations in Kit exon 9 and 11 are actionable, due to their response to imatinib, while mutations in PDGFRA respond to sunitinib and/or avapritinib. Although, molecular testing on tissue samples is effective; it is invasive, requires adequate amounts of tissue, and a long experimental process is needed for results. In contrast, liquid biopsy has been proposed as a simple and non-invasive method to test biomarkers in cancer. The most common molecule analyzed by liquid biopsy is circulating tumor DNA (ctDNA). GISTs ctDNA testing has been demonstrated to be effective in identifying known and novel KIT mutations that were not detected using traditional tissue DNA testing and have been useful in determining progression risk and response to TKI therapy. This allows the clinician to have an accurate picture of the genetic changes of the tumor over time. In this work, we aimed to discuss the implications of mutational testing in clinical outcomes, the methods to test ctDNA and the future challenges in the establishment of alternatives of personalized medicine.
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Tumores del Estroma Gastrointestinal , Humanos , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/genética , Mesilato de Imatinib/farmacología , Mesilato de Imatinib/uso terapéutico , Sunitinib/uso terapéutico , Pronóstico , Mutación , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/uso terapéutico , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genéticaRESUMEN
BACKGROUND AND AIMS: There is little evidence on the impact of current recommendations on the use of antiplatelet therapy during the perioperative and periprocedural period in our setting. The aim of this study was to analyze the incidence and clinical impact of inappropriate use of antiplatelet therapy in a population of patients undergoing surgery or a diagnostic or therapeutic procedure in "real life" in Spain. METHODS: A prospective multicenter observational study of patients treated with antiplatelet agents requiring intervention was conducted. The incidence of thrombotic and hemorrhagic events at 30 days was analyzed according to peri-intervention management of antiplatelet therapy. RESULTS: We included 643 patients (31.9% women, 39.0% over 75 years of age), most of them (87.7%) receiving aspirin as antiplatelet therapy at a dose of 100mg/day. Indications for antiplatelet therapy were ischemic heart disease (44.9%), cerebrovascular disease (21.7%), and peripheral vascular disease (23.0%). Ischemic risk was low in 74.3%, while 51.6% had a low bleeding risk of the intervention. Periprocedural management was considered appropriate in 61.7% of cases. 30-day incidence of the combined primary endpoint of thrombotic events and major bleeding (12.1% versus 5.0%; p=0.002) and 30-day mortality (5.2% versus 1.5%; p=0.008) were significantly higher in patients with inappropriate periprocedural management of antiplatelet agents. CONCLUSIONS: Despite current recommendations for the use of antiplatelet drugs in the perioperative/periprocedural period, their implementation in the "real world" remains low. Inappropriate use is associated with an increased incidence of adverse events, both thrombotic and hemorrhagic.
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In the context of the COVID-19 pandemic, social media platforms such as Twitter have been of great importance for users to exchange news, ideas, and perceptions. Researchers from fields such as discourse analysis and the social sciences have resorted to this content to explore public opinion and stance on this topic, and they have tried to gather information through the compilation of large-scale corpora. However, the size of such corpora is both an advantage and a drawback, as simple text retrieval techniques and tools may prove to be impractical or altogether incapable of handling such masses of data. This study provides methodological and practical cues on how to manage the contents of a large-scale social media corpus such as Chen et al. (JMIR Public Health Surveill 6(2):e19273, 2020) COVID-19 corpus. We compare and evaluate, in terms of efficiency and efficacy, available methods to handle such a large corpus. First, we compare different sample sizes to assess whether it is possible to achieve similar results despite the size difference and evaluate sampling methods following a specific data management approach to storing the original corpus. Second, we examine two keyword extraction methodologies commonly used to obtain a compact representation of the main subject and topics of a text: the traditional method used in corpus linguistics, which compares word frequencies using a reference corpus, and graph-based techniques as developed in Natural Language Processing tasks. The methods and strategies discussed in this study enable valuable quantitative and qualitative analyses of an otherwise intractable mass of social media data.
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In Alzheimer's disease, neurons acquire phenotypes that are also present in various cancers, including aberrant activation of the cell cycle. Unlike cancer, cell cycle activation in post-mitotic neurons is sufficient to induce cell death. Multiple lines of evidence suggest that abortive cell cycle activation is a consequence of pathogenic forms of tau, a protein that drives neurodegeneration in Alzheimer's disease and related "tauopathies." Here we combine network analyses of human Alzheimer's disease and mouse models of Alzheimer's disease and primary tauopathy with studies in Drosophila to discover that pathogenic forms of tau drive cell cycle activation by disrupting a cellular program involved in cancer and the epithelial-mesenchymal transition (EMT). Moesin, an EMT driver, is elevated in cells harboring disease-associated phosphotau, over-stabilized actin, and ectopic cell cycle activation. We further find that genetic manipulation of Moesin mediates tau-induced neurodegeneration. Taken together, our study identifies novel parallels between tauopathy and cancer.
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Pretreatment processes - recognized as critical steps for efficient biomass refining - have received much attention over the last two decades. In this context, deep eutectic solvents (DES) have emerged as a novel alternative to conventional solvents representing a step forward in achieving more sustainable processes with both environmental and economic benefits. This paper presents an updated review of the state-of-the-art of DES-based applications in biorefinery schemes. Besides describing the fundamentals of DES composition, synthesis, and recycling, this study presents a comprehensive review of existing techno-economic and life cycle assessment studies. Challenges, barriers, and perspectives for the scale-up of DES-based processes are also discussed.
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Disolventes Eutécticos Profundos , Lignina , Biomasa , Solventes , ReciclajeRESUMEN
BACKGROUND: The prevalence of heart failure (HF) increases with age, and it is one of the leading causes of hospitalization and death in older patients. However, there are little data on in-hospital mortality in patients with HF ≥ 75 years in Spain. METHODS: A retrospective analysis of the Spanish Minimum Basic Data Set was performed, including all HF episodes discharged from public hospitals in Spain between 2016 and 2019. Coding was performed using the International Classification of Diseases, 10th Revision. Patients ≥ 75 years with HF as the principal diagnosis were selected. We calculated: (1) the crude in-hospital mortality rate and its distribution according to age and sex; (2) the risk-standardized in-hospital mortality ratio; and (3) the association between in-hospital mortality and the availability of an intensive cardiac care unit (ICCU) in the hospital. RESULTS: We included 354,792 HF episodes of patients over 75 years. The mean age was 85.2 ± 5.5 years, and 59.2% of patients were women. The most frequent comorbidities were renal failure (46.1%), diabetes mellitus (35.5%), valvular disease (33.9%), cardiorespiratory failure (29.8%), and hypertension (26.9%). In-hospital mortality was 12.7%, and increased with age [odds ratio (OR) = 1.07, 95% CI: 1.07-1.07, P < 0.001] and was lower in women (OR = 0.96, 95% CI: 0.92-0.97, P < 0.001). The main predictors of mortality were the presence of cardiogenic shock (OR = 19.5, 95% CI: 16.8-22.7, P < 0.001), stroke (OR = 3.5, 95% CI: 3.0-4.0, P < 0.001) and advanced cancer (OR = 2.6, 95% CI: 2.5-2.8, P < 0.001). In hospitals with ICCU, the in-hospital risk-adjusted mortality tended to be lower (OR = 0.85, 95% CI: 0.72-1.00, P = 0.053). CONCLUSIONS: In-hospital mortality in patients with HF ≥ 75 years between 2016 and 2019 was 12.7%, higher in males and elderly patients. The main predictors of mortality were cardiogenic shock, stroke, and advanced cancer. There was a trend toward lower mortality in centers with an ICCU.
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INTRODUCTION: Heart failure (HF) is one of the leading causes of hospitalization and death in elderly patients. However, there is limited evidence on readmission and mortality 1-year after discharge for HF. METHODS: Retrospective analysis of the Minimum Basic Data Set, including HF episodes, discharged from Spanish hospitals between 2016 and 2018 in ≥ 75 years. We calculated: (a) the rate of readmissions due to circulatory system diseases (CSD) 365 days after index episode; (b) in-hospital mortality in readmissions; and (c) predictors of mortality and readmission. RESULTS: We included 178,523 patients (59.2% women) aged 85.1 ± 5.5 years. The most frequent comorbidities were arrhythmias (56.0%) and renal failure (39.5%). During the follow-up, 48,932 patients (27.4%) had at least one readmission for CSD and a crude rate of 40.2%, the most frequent one HF (52.8%). The median between the date of readmission and discharge from the last admission was 70 days [IQI 24; 171] for the first readmission. The most relevant predictors of the number of readmissions were valvular heart disease and myocardial ischemia. During the readmissions, 26,757 patients (79.1%) died, representing a cumulative in-hospital mortality of 47,945 (26.9%). The factors in the index episode predictors of mortality during readmissions were cardio-respiratory failure and stroke. The number of readmissions was a risk factor for in-hospital mortality (OR 1.13; 95% CI 1.11-1.14). CONCLUSIONS: The readmission rate for CSD 1-year after the index episode of HF in patients ≥ 75 years was 28.4%. The cumulative in-hospital mortality rate during the readmissions was 26.9%, and the number of rehospitalizations was identified as one of the main predictors of mortality.
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Insuficiencia Cardíaca , Readmisión del Paciente , Anciano , Humanos , Femenino , Masculino , Estudios Retrospectivos , Mortalidad Hospitalaria , España/epidemiología , Insuficiencia Cardíaca/terapia , Factores de Riesgo , Hospitales PúblicosRESUMEN
INTRODUCTION AND OBJECTIVES: There is scarce real-world evidence on the management of perioperative antithrombotic treatment according to current recommendations. The aim of this study was to analyze the management of antithrombotic treatment in patients undergoing surgery or another invasive intervention and to assess the consequences of this management on the occurrence thrombotic or bleeding events. METHODS: This prospective, observational, multicenter and multispecialty study analyzed patients receiving antithrombotic therapy who underwent surgery or another invasive intervention. The primary endpoint was defined as the incidence of adverse (thrombotic and/or hemorrhagic) events after 30 days of follow-up with respect to management of perioperative antithrombotic drugs. RESULTS: We included 1266 patients (male: 63.5%; mean age 72.6 years). Nearly half of the patients (48.6%) were under chronic anticoagulation therapy (mainly for atrial fibrillation; CHA2DS2-VASC: 3.7), while 53.3% of the patients were under chronic antiplatelet therapy (mainly for coronary artery disease). Low ischemic and hemorrhagic risk was found in 66.7% and 51.9%, respectively. Antithrombotic therapy management was in line with current recommendations in only 57.3% of the patients. Inappropriate management of antithrombotic therapy was an independent risk factor for both thrombotic and hemorrhagic events. CONCLUSIONS: The implementation of recommendations on the perioperative/periprocedural management of antithrombotic therapy in real-world patients is poor. Inappropriate management of antithrombotic treatment is associated with an increase in both thrombotic and hemorrhagic events.
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Anticoagulantes , Fibrilación Atrial , Humanos , Masculino , Anciano , Anticoagulantes/uso terapéutico , Fibrinolíticos/uso terapéutico , Fibrinolíticos/efectos adversos , Estudios Prospectivos , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Hemorragia/complicaciones , Factores de Riesgo , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Sistema de Registros , Inhibidores de Agregación Plaquetaria/efectos adversosRESUMEN
INTRODUCTION: Estimation of peri-procedural risk in patients with tricuspid regurgitation (TR) undergoing isolated tricuspid valve surgery (ITVS) is of paramount importance. The TRI-SCORE is a new surgical risk scale specifically developed for this purpose, which ranged from 0 to 12 points and included eight parameters: right-sided heart failure signs, daily dose of furosemide ≥125 mg, glomerular filtration rate <30 mL/min, elevated bilirubin (with a value of 2 points), age ≥70 years, New York Heart Association Class III-IV, left ventricular ejection fraction <60% and moderate/severe right ventricular dysfunction (with a value of 1 point). The objective of the study was to evaluate the performance of the TRI-SCORE in an independent cohort of patients undergoing ITVS. METHODS: A retrospective observational study was performed in four centres, including consecutive adult patients undergoing ITVS for TR between 2005 and 2022. The TRI-SCORE and the traditional risk scores used in cardiac surgery (Logistic EuroScore (Log-ES) and EuroScore-II (ES-II)) were applied for each patient, and discrimination and calibration of the three scores were evaluated in the entire cohort. RESULTS: A total of 252 patients were included. The mean age was 61.5±11.2 years, 164 (65.1%) patients were female, and TR mechanism was functional in 160 (63.5%) patients. The observed in-hospital mortality was 10.3%. The estimated mortality by the Log-ES, ES-II and TRI-SCORE was 8.7±7.3%, 4.7±5.3% and 11.0±16.6%, respectively. Patients with a TRI-SCORE ≤4 and >4 had an in-hospital mortality of 1.3% and 25.0%, p=0.001, respectively. The discriminatory capacity of the TRI-SCORE had a C-statistic of 0.87 (0.81-0.92), which was significantly higher than both the Log-ES (0.65 (0.54-0.75)) and ES-II (0.67 (0.58-0.79)), p=0.001 (for both comparisons). CONCLUSION: This external validation of the TRI-SCORE demonstrated good performance to predict in-hospital mortality in patients undergoing ITVS, which was significantly better than the Log-ES and ES-II, which underestimated the observed mortality. These results support the widespread use of this score as a clinical tool.
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Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Tricúspide , Adulto , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Volumen Sistólico , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Resultado del Tratamiento , Función Ventricular Izquierda , Factores de Riesgo , Estudios RetrospectivosRESUMEN
The main goal of this study is to evaluate the field performance of crumb-rubber-modified asphalt mixtures used as a surface layer on high-volume traffic roads. For this purpose, several road sections were constructed under different climate conditions and using control mixtures (manufactured with traditional SBS polymer-modified binders) and crumb-rubber-modified mixtures. After the construction of the different road sections, cores were taken at different periods of their service life (up to 63 months) and they were tested in the laboratory in order to assess the evolution of the density, stiffness and fatigue resistance of the layers. Based on the results obtained from tests, it can be concluded that under real severe traffic and climate conditions, asphalt mixtures manufactured with crumb-rubber-modified bitumen offer ageing and mechanical performance very similar to that offered by asphalt mixtures manufactured with traditional SBS-modified bitumen. Based on these considerations, this application can be an interesting solution to minimize environmental problems caused by end-of-life tires in landfills.
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Cancer is one of the main causes of death worldwide. To date, and despite the advances in conventional treatment options, therapy in cancer is still far from optimal due to the non-specific systemic biodistribution of antitumor agents. The inadequate drug concentrations at the tumor site led to an increased incidence of multiple drug resistance and the appearance of many severe undesirable side effects. Nanotechnology, through the development of nanoscale-based pharmaceuticals, has emerged to provide new and innovative drugs to overcome these limitations. In this review, we provide an overview of the approved nanomedicine for cancer treatment and the rationale behind their designs and applications. We also highlight the new approaches that are currently under investigation and the perspectives and challenges for nanopharmaceuticals, focusing on the tumor microenvironment and tumor disseminate cells as the most attractive and effective strategies for cancer treatments.
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Antineoplásicos , Neoplasias , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Humanos , Nanomedicina , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Preparaciones Farmacéuticas , Distribución Tisular , Microambiente TumoralRESUMEN
This article presents a new methodology of analysis based on a fast-running experimental procedure to characterise the mechanical response of asphalt mortars in terms of stiffness, ductility, and fatigue resistance. This was achieved using the DMA (Dynamic Mechanical Analyser) three-point bending configuration. The study was carried out by considering the employment of different types of fillers such cement and CaCO3 and different types of binders such as conventional asphalt binder (B35/50) or modifided polymer-modified bitumen (PMB 25/55-65). From the results of this study, the filler was found to have a greater influence on the stiffness and ductility of the asphalt material, while bitumen had a higher effect on the fatigue life of the asphalt mortar. Fatigue life was observed to increase with the use of a polymer-modified binder, while a lower degree of permanent deformation and higher bearing capacity achieved by the use of cement instead of calcium carbonate as active fillers.