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Background: Age-related remodelling has the potential to affect the microvascular response to hyperemic stimuli. However, its precise effects on the vasodilatory response to adenosine and contrast medium, as well as its influence on fractional flow reserve (FFR) and contrast fractional flow reserve (cFFR), have not been previously investigated. We investigate the impact of age on these indices. Methods: We extrapolated data from the post-revascularization optimization and physiological evaluation of intermediate lesions using fractional flow reserve (PROPHET-FFR) and The Multi-center Evaluation of the Accuracy of the Contrast MEdium INduced Pd/Pa RaTiO in Predicting (MEMENTO) studies. Only lesions with a relevant vasodilatory response to adenosine and contrast medium were considered of interest. A total of 2080 patients, accounting for 2294 pressure recordings were available for analysis. The cohort was stratified into three age terciles. Age-dependent correlations with FFR, cFFR, distal pressure/aortic pressure (Pd/Pa) and instantaneous wave-free ratio (iFR) were calculated. The vasodilatory response was calculated in 1619 lesions (with both FFR and cFFR) as the difference between resting and hyperaemic pressure ratios and correlated with aging. The prevalence of FFR-cFFR discordance was assessed. Results: Age correlated positively to FFR (r = 0.062, p = 0.006), but not with cFFR (r = 0.024, p = 0.298), Pd/Pa (r = -0.015, p = 0.481) and iFR (r = -0.026, p = 0.648). The hyperemic response to adenosine (r = -0.102, p ≤ 0.0001) and to contrast medium (r = -0.076, p = 0.0023) showed a negative correlation with age. When adjusted for potential confounders, adenosine induced hyperaemia was negatively associated with age (p = 0.04 vs p = 0.08 for cFFR). Discordance decreased across age terciles (14.64% vs 12.72% vs 10.12%, p = 0.032). Conclusions: As compared to adenosine, contrast induced hyperaemia appeared to be less affected by age. cFFR may be considered a more stable and reproducible tool to assess epicardial stenosis in elderly patients. Clinical Trial Registration: PROPHET-FFR STUDY, Clinicaltrials.gov (NCT05056662).
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BACKGROUND/AIM: The interaction between the ethylene-vinyl acetate (EVA) with distinct materials utilized for obtaining dental models can affect the performance of resulting mouthguards. This study attempted to evaluate the effect of different materials for conventional (dental stone) or 3D-printed (resin) models on EVA's physical and mechanical properties and surface characteristics. MATERIAL AND METHODS: EVA sheets (Bioart) were laminated over four model types: GIV, conventional Type IV dental stone model (Zhermak); ReG, resin-reinforced Type IV dental stone model (Zero Stone); 3DnT, 3D resin printed model (Anycubic) without surface treatment; 3DT, 3D-printed model (Anycubic) with water-soluble gel (KY Jelly Lubricant, Johnson & Johnson) coating during post-curing process. The EVA specimens were cut following the ISO 37-II standard (n = 30). Shore A hardness was measured before and after plasticization on the contact (internal) or opposite (external) surfaces with the model. The breaking force (F, N), elongation (EL, mm), and ultimate tensile strength (UTS, MPa) were measured using a universal testing machine. Macro-photography and scanning electron microscopy were adopted for classifying the EVA surface alteration. Data were analyzed by one-way ANOVA with repeated measures, followed by Tukey's test (α = .05). RESULTS: Plasticization significantly decreased Shore A values for the tested EVA regardless of the model type (p < .001). Higher F, El, and UTS values were verified for the EVA with 3DT and GIV models compared to ReG and 3DnT (p < .001). 3DnT models resulted in severe surface alteration and a greater reduction of the mechanical properties of the EVA. CONCLUSION: The interaction of EVA with 3D resin-printed models without surface treatment or resin-reinforced Type IV dental stone models significantly affected the physical and mechanical properties of this material. The utilization of water-soluble gel coating during the post-curing process of 3D resin printed models improved the mechanical properties of the EVA, similarly when this material was plasticized over conventional Type IV dental stone model.
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Differentiated thyroid cancer is the most common malignancy of the endocrine system. Although most thyroid nodules are benign, given the high incidence of thyroid nodules in the population, it is important to understand the differences between benign and malignant thyroid cancer and the molecular alterations associated with malignancy to improve detection and signal potential diagnostic, prognostic, and therapeutic targets. Proteomics analysis of benign and malignant human thyroid tissue largely revealed changes indicating modifications in RNA regulation, a common cancer characteristic. In addition, changes in the immune system and cell membrane/endocytic processes were also suggested to be involved. Annexin A1 was considered a potential malignancy biomarker and, similarly to other annexins, it was found to increase in the malignant group. Furthermore, a bioinformatics approach points to the transcription factor Sp1 as being potentially involved in most of the alterations seen in the malignant thyroid nodules.
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Neoplasias de la Tiroides , Nódulo Tiroideo , Humanos , Nódulo Tiroideo/diagnóstico , Anexinas/genética , ARN Mensajero/genética , Proteómica , Neoplasias de la Tiroides/patologíaRESUMEN
Background: Human umbilical cord matrix-mesenchymal stromal cells (hUCM-MSC) have demonstrated beneficial effects in experimental acute myocardial infarction (AMI). Reperfusion injury hampers myocardial recovery in a clinical setting and its management is an unmet need. We investigated the efficacy of intracoronary (IC) delivery of xenogeneic hUCM-MSC as reperfusion-adjuvant therapy in a translational model of AMI in swine. Methods: In a placebo-controlled trial, pot-belied pigs were randomly assigned to a sham-control group (vehicle-injection; n = 8), AMI + vehicle (n = 12) or AMI + IC-injection (n = 11) of 5 × 105 hUCM-MSC/Kg, within 30â min of reperfusion. AMI was created percutaneously by balloon occlusion of the mid-LAD. Left-ventricular function was blindly evaluated at 8-weeks by invasive pressure-volume loop analysis (primary endpoint). Mechanistic readouts included histology, strength-length relationship in skinned cardiomyocytes and gene expression analysis by RNA-sequencing. Results: As compared to vehicle, hUCM-MSC enhanced systolic function as shown by higher ejection fraction (65 ± 6% vs. 43 ± 4%; p = 0.0048), cardiac index (4.1 ± 0.4 vs. 3.1 ± 0.2â L/min/m2; p = 0.0378), preload recruitable stroke work (75 ± 13 vs. 36 ± 4â mmHg; p = 0.0256) and end-systolic elastance (2.8 ± 0.7 vs. 2.1 ± 0.4â mmHg*m2/ml; p = 0.0663). Infarct size was non-significantly lower in cell-treated animals (13.7 ± 2.2% vs. 15.9 ± 2.7%; Δ = -2.2%; p = 0.23), as was interstitial fibrosis and cardiomyocyte hypertrophy in the remote myocardium. Sarcomere active tension improved, and genes related to extracellular matrix remodelling (including MMP9, TIMP1 and PAI1), collagen fibril organization and glycosaminoglycan biosynthesis were downregulated in animals treated with hUCM-MSC. Conclusion: Intracoronary transfer of xenogeneic hUCM-MSC shortly after reperfusion improved left-ventricular systolic function, which could not be explained by the observed extent of infarct size reduction alone. Combined contributions of favourable modification of myocardial interstitial fibrosis, matrix remodelling and enhanced cardiomyocyte contractility in the remote myocardium may provide mechanistic insight for the biological effect.
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INTRODUCTION AND OBJECTIVES: Randomized controlled trials comparing stress cardiac magnetic resonance (CMR) and single-photon emission computed tomography (SPECT) suggest similar diagnostic accuracy for detecting obstructive coronary artery disease (CAD). There are few data on whether this remains true in routine clinical practice. The aim of this study was to assess clinical and angiographic characteristics of patients undergoing invasive coronary angiography (ICA) after stress CMR or SPECT, and to compare their positive predictive value with published results from the CE-MARC trial. METHODS: In this retrospective tertiary-center analysis, we included 429 patients undergoing ICA after a positive stress CMR or positive SPECT performed within the previous 12 months. Obstructive CAD was defined as any coronary artery stenosis ≥50% in a vessel compatible with the ischemic territory on stress testing. RESULTS: Of the total 429 patients, 356 (83%) were referred after a positive SPECT, and 73 (17%) after a positive stress CMR. Patients did not differ according to age, cardiovascular risk factors, previous revascularization or left ventricular dysfunction, but patients with SPECT were more frequently male (p=0.046). The prevalence of obstructive CAD was similar in patients with positive SPECT vs. positive stress CMR (76.1% vs. 80.8%, respectively, p=0.385). The positive predictive values of both techniques were similar to those reported in the CE-MARC trial. CONCLUSION: In this tertiary center analysis, stress CMR and SPECT showed similar positive predictive values, comparable to those reported in the CE-MARC trial. This finding supports the emerging adoption of CMR in clinical practice for the diagnosis and management of CAD.
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Enfermedad de la Arteria Coronaria , Imagen de Perfusión Miocárdica , Humanos , Masculino , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Imagen de Perfusión Miocárdica/métodos , Estudios Retrospectivos , Tomografía Computarizada de Emisión de Fotón Único/métodosRESUMEN
The clinical value of fractional flow reserve and non-hyperaemic pressure ratios are well established in determining an indication for percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD). In addition, over the last 5 years we have witnessed a shift towards the use of physiology to enhance procedural planning, assess post-PCI functional results, and guide PCI optimisation. In this regard, clinical studies have reported compelling data supporting the use of longitudinal vessel analysis, obtained with pressure guidewire pullbacks, to better understand how obstructive CAD contributes to myocardial ischaemia, to establish the likelihood of functionally successful PCI, to identify the presence and location of residual flow-limiting stenoses and to predict long-term outcomes. The introduction of new functional coronary angiography tools, which merge angiographic information with fluid dynamic equations to deliver information equivalent to intracoronary pressure measurements, are now available and potentially also applicable to these endeavours. Furthermore, the ability of longitudinal vessel analysis to predict the functional results of stenting has played an integral role in the evolving field of simulated PCI. Nevertheless, it is important to have an awareness of the value and challenges of physiology-guided PCI in specific clinical and anatomical contexts. The main aim of this European Association of Percutaneous Cardiovascular Interventions clinical consensus statement is to offer up-to-date evidence and expert opinion on the use of applied coronary physiology for procedural PCI planning, disease pattern recognition and post-PCI optimisation.
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Cardiología , Enfermedad de la Arteria Coronaria , Reserva del Flujo Fraccional Miocárdico , Intervención Coronaria Percutánea , Humanos , Resultado del Tratamiento , Enfermedad de la Arteria Coronaria/cirugía , Angiografía Coronaria/métodosRESUMEN
OBJECTIVE: This study is to evaluate fracture resistance, failure mode, and gap formation at the restorative interface of unrestored or restored non-carious cervical lesions (NCCLs) submitted to a short-term erosive environment. MATERIALS AND METHODS: Artificial NCCLs were produced in vitro in bovine incisors, and were randomly divided into four restorative resins groups (n = 22): nanohybrid-NR; bulk-fill-BR; flow with a nanohybrid layer-FNR; bulk-fill with a nanohybrid layer-BNR; and a group unrestored-UR (n = 16). Half of the specimens were submitted to an erosive challenge (per 5 min, 3 × a day for 7 days, before and after restoration), and the other half, was immersed in artificial saliva. After, all teeth undergone thermal (5 ºC, 37 ºC, and 55 ºC, 3600 cycles) and mechanical (50 N, 2 Hz, 300,000 cycles) aging. Eighty teeth were subjected to compressive loading, and resistance and failures were analyzed, while 24 teeth were evaluated for gaps by microcomputed tomography. Statistical tests were performed (p < 0.05). RESULTS: The restorative approaches affected fracture resistance (η2p = 0.14, p = 0.023), and gap formation (η2 = 0.18, p = 0.012) and so did the immersion medium (fracture η2p = 0.09, p = 0.008; gap η2 = 0.09, p = 0.017). BNR showed the highest resistance, while UR the lowest. FNR showed the highest gaps in both immersion media. Neither the resin groups nor the immersion media were associated with failure mode. CONCLUSIONS: The erosive immersion medium based in acid beverages has been shown to affect NCCLs with or without restoration, but when Bulk-Fill resin is covered by nanohybrid resin, the performance is good. CLINICAL RELEVANCE: Erosion negatively affects restorations, but unrestored NCCL shows worse biomechanical performance in stress-bearing situations.
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Resinas Compuestas , Materiales Dentales , Animales , Bovinos , Bebidas , Restauración Dental Permanente/métodos , Ensayo de Materiales , Microtomografía por Rayos XRESUMEN
INTRODUCTION AND OBJECTIVES: Obstructive coronary artery disease (CAD) remains the most common etiology of heart failure with reduced ejection fraction (HFrEF). However, there is controversy whether invasive coronary angiography (ICA) should be used initially to exclude CAD in patients presenting with new-onset HFrEF of unknown etiology. Our study aimed to develop a clinical score to quantify the risk of obstructive CAD in these patients. METHODS: We performed a cross-sectional observational study of 452 consecutive patients presenting with new-onset HFrEF of unknown etiology undergoing elective ICA in one academic center, between January 2005 and December 2019. Independent predictors for obstructive CAD were identified. A risk score was developed using multivariate logistic regression of designated variables. The accuracy and discriminative power of the predictive model were assessed. RESULTS: A total of 109 patients (24.1%) presented obstructive CAD. Six independent predictors were identified and included in the score: male gender (2 points), diabetes (1 point), dyslipidemia (1 point), smoking (1 point), peripheral arterial disease (1 point), and regional wall motion abnormalities (3 points). Patients with a score ≤3 had less than 15% predicted probability of obstructive CAD. Our score showed good discriminative power (C-statistic 0.872; 95% CI 0.834-0.909: p<0.001) and calibration (p=0.333 from the goodness-of-fit test). CONCLUSIONS: A simple clinical score showed the ability to predict the risk of obstructive CAD in patients presenting with new-onset HFrEF of unknown etiology and may guide the clinician in selecting the most appropriate diagnostic modality for the assessment of obstructive CAD.
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Enfermedad de la Arteria Coronaria , Insuficiencia Cardíaca , Disfunción Ventricular Izquierda , Humanos , Masculino , Enfermedad de la Arteria Coronaria/complicaciones , Angiografía Coronaria/efectos adversos , Insuficiencia Cardíaca/complicaciones , Estudios Transversales , Volumen Sistólico , Factores de Riesgo , Valor Predictivo de las PruebasRESUMEN
Thyroid cancer is a common malignancy of the endocrine system. Nodules are routinely evaluated for malignancy risk by fine needle aspiration biopsy (FNAB), and in cases such as follicular lesions, differential diagnosis between benign and malignant nodules is highly uncertain. Therefore, the discovery of new biomarkers for this disease could be helpful in improving diagnostic accuracy. Thyroid nodule biopsies were subjected to a precipitation step with both the insoluble and supernatant fractions subjected to proteome and peptidome profiling. Proteomic analysis identified annexin A1 as a potential biomarker of thyroid cancer malignancy, with its levels increased in malignant samples. Also upregulated were the acetylated peptides of annexin A1, revealed by the peptidome analysis of the supernatant fraction. In addition, supernatant peptidomic analysis revealed a number of acetylated histone peptides that were significantly elevated in the malignant group, suggesting higher gene transcription activity in malignant tissue. Two of these peptides were found to be robust malignancy predictors, with an area under the receiver operating a characteristic curve (ROC AUC) above 0.95. Thus, this combination of proteomics and peptidomics analyses improved the detection of malignant lesions and also provided new evidence linking thyroid cancer development to heightened transcription activity. This study demonstrates the importance of peptidomic profiling in complementing traditional proteomics approaches.
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Adenocarcinoma , Anexina A1 , Neoplasias de la Tiroides , Humanos , Histonas , Acetilación , Proteómica , Biopsia con Aguja Fina , Agitación Psicomotora , PéptidosRESUMEN
The authors review the current role of cardiac catheterization in the characterization of aortic stenosis, its main clinical applications, its pitfalls, and its additional value to the information provided by echocardiography. Discrepancies that may arise between these two modalities are discussed and further explained. Hemodynamic variables besides transvalvular pressure drop are described, and emphasis is given to an integrative approach to aortic stenosis assessment, that includes invasive and noninvasive evaluation.
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Chemotherapy-associated cardiotoxicity is a common adverse event. Immune checkpoint inhibitors (ICI) - a new class of monoclonal antibodies - have revolutionized the management of various diseases. Their use is expected to increase in the near future and their cardiac side effects have been increasingly recognized. CLINICAL CASE: We describe a case of a 67-year-old female patient with urothelial carcinoma undergoing treatment with pembrolizumab who presented to the emergency department with progressive fatigue, retrosternal pain and palpitations for three days. On admission she was diagnosed with acute heart failure (HF). The electrocardiogram revealed a right bundle branch block and ventricular bigeminy. Blood tests showed elevated troponin I, while transthoracic echocardiography revealed severe left ventricular dysfunction. Coronary angiography excluded coronary artery disease. Cardiac magnetic resonance revealed moderate left ventricular dysfunction and late gadolinium enhancement typical of myocarditis. Endomyocardial biopsy confirmed the diagnosis of lymphocytic myocarditis. In the first 48h of hospitalization, she developed transient complete AV block. Corticoid and HF therapy were initiated, leading to symptom improvement and disappearance of the rhythm disturbances. She was discharged on the 12th day, maintaining moderate LV dysfunction, which improved only mildly at a subsequent outpatient assessment. She died suddenly 35 days after discharge. CONCLUSION: Lymphocytic myocarditis is a serious cardiac side effect of ICI therapy. Pembrolizumab is increasingly used, so it is important to be aware of its effects, in order to perform an early diagnosis and provide adequate treatment. Corticosteroid therapy seems to be crucial in preventing disease progression and enabling ventricular remodeling.
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Antineoplásicos , Carcinoma de Células Transicionales , Miocarditis , Neoplasias de la Vejiga Urinaria , Disfunción Ventricular Izquierda , Femenino , Humanos , Anciano , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Medios de Contraste , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Gadolinio/uso terapéutico , Miocarditis/diagnósticoRESUMEN
BACKGROUND: Patients undergoing heart valve surgery are routinely evaluated for the presence of coronary artery disease (CAD). Currently, concomitant valve intervention and surgical revascularization is recommended when there is obstructive CAD. The aim of our study was to evaluate the prevalence of CAD, its treatment strategies, and their prognostic implications in a contemporary population of patients with valvular heart disease (VHD) referred for valve surgery (HVS). METHODS: In a multicenter registry, consecutive patients with formal indication for HVS referred for a preoperative routine invasive coronary angiogram (ICA) were analyzed. Baseline characteristics, CAD prevalence and revascularization patterns, as well as their impact on short and mid-term all-cause mortality, were assessed. RESULTS: Overall, 1133 patients were included; most had aortic stenosis (69%) and obstructive CAD was present in 307 (27.1%). HVS was ultimately performed in 82.3%. In patients with CAD, 53.4% were revascularized. After a mean follow-up time of 29.06±18.46 months, all-cause mortality rate was 12.9%. In multivariate analysis, not having HVS (HR 6.845, 95% CI=4.281-10.947, P<0.001), obstructive CAD (HR 2.762, 95% CI=1.764-4.326, P<0.01), COPD (HR 2.043, 95% CI=1.014-4.197, P=0.022), and age (HR 1.030, 95% CI=1.009-1.063, P=0.047), were independent predictors of all-cause mortality. In patients with obstructive CAD who underwent HVS, revascularization was not significantly associated with survival (HR 2.127, 95% CI=0.0-4.494, P=0.048; log rank P=0.042). CONCLUSIONS: In a contemporary cohort of patients with VHD and surgical indication, overall obstructive CAD prevalence was 27%. CAD presence and severity were associated with higher mortality. However, revascularization was not associated with a survival benefit, except in patients with left anterior descending artery disease.
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Estenosis de la Válvula Aórtica , Enfermedad de la Arteria Coronaria , Enfermedades de las Válvulas Cardíacas , Estenosis de la Válvula Aórtica/cirugía , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/cirugía , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/epidemiología , Enfermedades de las Válvulas Cardíacas/cirugía , Válvulas Cardíacas , Humanos , Prevalencia , Medición de Riesgo , Factores de RiesgoRESUMEN
BACKGROUND: Thyroid nodules are a challenge in clinical practice and thyroid ultrasonography is essential for assessing the risk of malignancy. The use of ultrasound-based malignancy risk classification systems has been recommended by several scientific societies but radiologist's adherence to these guidelines may vary. The authors aimed to analyze the quality of the information provided by the thyroid ultrasound report, to assess the malignancy risk of thyroid nodules, in Portugal. METHODS: Multicenter and retrospective study, conducted in three of the five Portuguese NUTS2 corresponding to about 88.3% of the mainland population. We included 344 consecutive unselected participants aged ≥ 18 years who underwent thyroid ultrasonography in 2019. The description of six features of the dominant thyroid nodule was analyzed: maximum size, shape, margins, composition, echogenicity and echogenic foci. A utility score, including these six features, was used as an indicator of the report's quality. A score of 4 was considered as a minimum value. RESULTS: Maximum diameter was reported for all nodules. Shape, margins, composition, echogenicity and echogenic foci were reported in 8.1%, 25.0%, 76.5%, 53.2% and 20.9%, respectively. Only 21.8% of the nodules had a score ≥ 4. At least one of four suspicious features, including marked hypoechogenicity, microcalcifications, irregular margins and non-oval shape, was identified in 8.7% of the nodules. Cervical lymph nodes' status was reported in 93% of the exams. The risk category was only reported in 7.8% of the participants. CONCLUSION: The adherence of Portuguese radiologists to a standardized reporting model and to an ultrasound-based malignancy risk stratification system is still low and has implications for the correct characterization of the malignancy risk of nodules and the decision to perform fine-needle aspiration biopsy.
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Nódulo Tiroideo , Adolescente , Humanos , Estudios Retrospectivos , Medición de Riesgo , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/patología , UltrasonografíaRESUMEN
Introduction: During the Covid-19 pandemic there has been a general belief that hospital admissions for non-infectious causes, especially cardiovascular diseases, have fallen. Objectives: To assess the impact of the pandemic on admissions for ST-elevation myocardial infarction (STEMI) during the first pandemic wave. Methods: We performed a multicenter retrospective analysis of consecutive patients presenting with STEMI in two Portuguese hospital centers in two sequential periods - P1 (March 1 to April 30) and P2 (May 1 to June 30). Patient's clinical data and hospital outcomes were compared between the years 2017 to 2019 and 2020 for both periods. Results: During P1 in 2020, a reduction in the number of STEMI patients was observed in comparison with previous years (26.0±4.2 vs. 16.5±4.9 cases per month; p=0.033), as well as an increase in the number of mechanical complications (0.0% vs. 3.0%; p=0.029). Percutaneous coronary interventions in the setting of failed thrombolysis were more frequent (1.9% vs. 9.1%; p=0.033). An overall trend for longer delays in key timings of STEMI care bundles was noted. Mortality was higher during P1 compared to previous years (1.9% vs. 12.1%; p=0.005). Conclusions: During the first Covid-19 wave fewer patients presented with STEMI at the catheterization laboratory for percutaneous coronary intervention. These patients presented more mechanical complications and higher mortality.
Introdução: Recentemente durante a pandemia por Covid-19 houve uma perceção global de uma diminuição de admissões hospitalares por causas não infeciosas, em particular por doenças cardiovasculares. Objetivos: Avaliar o impacto da pandemia nas admissões por enfarte agudo do miocárdio com supradesnivelamento de ST (STEMI), na primeira onda da pandemia. Métodos: Análise multicêntrica e retrospetiva de doentes consecutivos admitidos em dois hospitais portugueses por STEMI em dois períodos sequenciais - P1 (1 de março a 30 de abril) e P2 (1 de maio a 30 de junho). Foi realizada uma comparação dos dados clínicos e de evolução hospitalar entre 2017 a 2019 e 2020 para os dois períodos. Resultados: No P1 de 2020 observou-se, relativamente a anos prévios, uma redução do número de doentes com STEMI (26,0±4,2 versus 16,5±4,9 casos por mês; p=0,033) e um aumento do número de complicações mecânicas (0,0% versus 3,0%; p=0,029). Os casos de angioplastia após trombólise falhada foram mais frequentes (1,9% versus 9,1%; p=0,033). Observou-se uma tendência global para um maior atraso nos tempos-chave de abordagem de doentes com STEMI. A taxa de mortalidade destes doentes no P1 foi superior comparativamente a anos prévios (1,9% versus 12,1%; p=0,005). Conclusões: Durante a primeira onda da pandemia Covid-19 houve uma redução do número de doentes submetidos a angioplastia coronária por STEMI. Esses apresentaram mais complicações mecânicas e uma maior mortalidade.
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In order to better understand the effect of structure, halogen substitution, metal ions and ligand flexibility on antiproliferative activity, eight Cu(II) complexes and eight Pt(II) complexes were obtained of 2,4-X1,X2-6-((pyridine-2-ylmethylamino)methyl)phenol and 2,4-X1,X2-6-((pyridine-2-ylmethylamino)ethyl)phenol (where X is Cl, Br, or I) ligands. The compounds were characterized with various techniques, such as FT-IR, NMR, elemental analysis and single-crystal X-ray diffraction (SCXRD). The X-ray structures showed that ligand acts as a bidentate and tridentate donor in Cu(II) and Pt(II) complexes, respectively. This difference in structures is due to the use or non-use of base in the preparation of complexes. Also, complexation of Cl2-H2L1 with CuCl2·2H2O gives two different types of structures: polymer (Cl2-H2L1-Cupolymer) and dimer (Cl2-H2L1-Cudimer), according to the crystal color. In addition, 1H NMR spectrum for platinum complexes display two set of signals that can be attributed to the presence of two isomers in solution. All complexes induced moderate to high reduction in A2780 and HCT116 cancer cell viability. However, only complexes bearing iodo- substituted in ligands exhibited significantly low cytotoxicity in normal fibroblasts when compared with cancer cell lines. The antiproliferative effect exhibited by I2-H2L2-Cu complex in A2780 cell line was due to induction of cell death mechanisms, namely by apoptosis and autophagy. I2-H2L2-Cu complex does not cause DNA cleavage but a slight delay in cell cycle was observed for the first 24 h of exposition. High cytotoxicity was related with the induction of intracellular ROS. This increase in intracellular ROS was not accompanied by destabilization of the mitochondrial membrane which is an indication that ROS are being triggered externally by I2-H2L2-Cu complex and in agreement with an extrinsic apoptosis activation. I2-H2L2-Cu complex has a pro-angiogenic effect, increasing the vascularization of the CAM in chicken embryos. This is also a very important characteristic in cancer treatment since the increased vascularization in tumors might facilitate the delivery of therapeutic drugs. Taken together, these results support the potential therapeutic of the I2-H2L2-Cu complex.
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Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , Cobre/farmacología , Halógenos/farmacología , Platino (Metal)/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Cobre/química , División del ADN , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Halógenos/química , Humanos , Ligandos , Estructura Molecular , Platino (Metal)/química , Relación Estructura-ActividadRESUMEN
OBJECTIVE: The aim of this study was to evaluate the influence of different light-curing units (LCUs) with distinct tip diameters and light spectra for activating bulk-fill resins. MATERIALS AND METHODS: The specimens (n = 10) were made from a conventional composite (Amaris, VOCO) and bulk-fill resins (Aura Bulk Fill, SDI; Filtek One, 3M ESPE; Tetric Bulk Fill, Ivoclar Vivadent) with two diameters, 7 or 10 mm, × 2 mm thickness. Following 24 hours of specimen preparation, the degree of conversion (DC) was evaluated using the Fourier-transform infrared unit. Knoop hardness (KHN) readings were performed on the center and periphery of the specimens. Data were assessed for homoscedasticity and submitted to one-way and three-way analysis of variance followed by the Tukey's and Dunnett's tests, depending on the analysis performed (α = 0.05). RESULTS: LCUs and specimen diameter significantly affected the DC. The Tetric Bulk Fill provided increased DC results when light-cured with Valo (54.8 and 53.5%, for 7 and 10 mm, respectively) compared with Radii Xpert (52.1 and 52.9%, for 7 and 10 mm, respectively). No significant differences in KHN results were noted for the conventional resin composite (Amaris) compared with LCUs (p = 0.213) or disc diameters (p = 0.587), but the center of the specimen exhibited superior KHN (p ≤ 0.001) than the periphery. CONCLUSION: The light spectrum of the multipeak LCU (Valo) significantly increased the DC and KHN of the bulk-fill resin composite with additional initiator to camphorquinone (Tetric Bulk Fill) compared with the monowave LCU (Radii Xpert). The tip size of the LCUs influenced the performance of some of the resin composites tested.
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The need for permanent pacemaker implantation (PPMI) is a burdensome complication of transcatheter aortic valve implantation (TAVI). The aim of our study was to evaluate different anatomical, clinical, electrocardiographic, and procedural variables associated with the development of conduction abnormalities after TAVI across the entire device spectrum. Single-center prospective cohort of consecutive patients who underwent TAVI since March 2017. Final cohort was studied to detect areas of calcium within aortic valve characterized by leaflet sector and region. Membranous septum (MS) length was assessed throughout a modified coronal view. Device selection and positioning were performed according to the operator criteria. Device selection and positioning were performed according to the operator criteria. From the 273 patients included, 57 underwent PPMI (20.8%). Univariate analysis determined right bundle branch block (RBBB), QRS duration, MS length and calcium within LVOT of non-coronary cuspid as independent predictors. After multivariable logistic regression, both RBBB (OR 6.138; 95% CI 1.23-30.73, P = 0.027) and MS length (OR 0.259; 95% CI 0.164-0.399, P < 0.005) emerged as statistically significant. As a model, they could predict PPMI in 88.7%, independently of which valve used. Youden index analysis yielded 7.69 mm as the optimal cut-off with a negative and positive predictive value of 94.7 and 71.9%, respectively. In our experience, both RBBB pattern and short membranous septum (< 8 mm) were strongly and independently associated with new permanent pacemaker implantation, regardless of the device type. Our findings suggest that this simple evolved measure of MS length may guide device selection and implantation technique and facilitate early discharge.
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Estenosis de la Válvula Aórtica , Prótesis Valvulares Cardíacas , Marcapaso Artificial , Reemplazo de la Válvula Aórtica Transcatéter , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Humanos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del TratamientoRESUMEN
INTRODUCTION AND OBJECTIVES: Use of invasive physiological assessment in patients with coronary artery disease varies widely and is perceived to be low. We aimed to examine adoption rates as well as patterns and determinants of use in an unselected population undergoing invasive coronary angiography over a long time frame. METHODS: We retrospectively determined the per-procedure prevalence of physiological assessment in 40821 coronary cases performed between 2007 and 2018 in two large-volume centers. Adoption was examined according to procedure type and patient- and operator-related variables. Its association with relevant scientific landmarks, such as the release of clinical trial results and practice guidelines, was also assessed. RESULTS: Overall adoption was low, ranging from 0.6% in patients undergoing invasive coronary angiography due to underlying valve disease, to 6% in the setting of stable coronary artery disease (CAD); it was 3.1% in patients sustaining an acute coronary syndrome. Of scientific landmarks, FAME 1, the long-term results of FAME 2 and the 2014 European myocardial revascularization guidelines were associated with changes in practice. Publication of instantaneous wave-free ratio (iFR) trials had no influence on adoption rates, except for a higher proportion of iFR use. In 42.9% of stable CAD patients undergoing percutaneous coronary intervention there was no objective non-invasive evidence of ischemia, nor was physiological assessment performed. Younger operator age (4.5% vs. 4.0% vs. 0.9% for ages <40, 40-55 and >55 years, respectively; p<0.001) and later time of procedure during the day (2.9% between 6 and 8 p.m. vs. 4.4% at other times) were independent correlates of use of invasive physiology. CONCLUSIONS: Our study confirms the low use of invasive physiology in routine practice. The availability of resting indices did not increase adoption. Strategies are warranted to promote guideline implementation and to improve patient care and clinical outcomes.
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Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Reserva del Flujo Fraccional Miocárdico , Cateterismo Cardíaco , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
Methyl-substituted 8-hydroxyquinolines (Hquin) were successfully used to synthetize five-coordinated oxovanadium(IV) complexes: [VO(2,6-(Me)2-quin)2] (1), [VO(2,5-(Me)2-quin)2] (2) and [VO(2-Me-quin)2] (3). Complexes 1-3 demonstrated high catalytic activity in the oxidation of hydrocarbons with H2O2 in acetonitrile at 50 °C, in the presence of 2-pyrazinecarboxylic acid (PCA) as a cocatalyst. The maximum yield of cyclohexane oxidation products attained was 48%, which is high in the case of the oxidation of saturated hydrocarbons. The reaction leads to the formation of a mixture of cyclohexyl hydroperoxide, cyclohexanol and cyclohexanone. When triphenylphosphine is added, cyclohexyl hydroperoxide is completely converted to cyclohexanol. Consideration of the regio- and bond-selectivity in the oxidation of n-heptane and methylcyclohexane, respectively, indicates that the oxidation proceeds with the participation of free hydroxyl radicals. The complexes show moderate activity in the oxidation of alcohols. Complexes 1 and 2 reduce the viability of colorectal (HCT116) and ovarian (A2780) carcinoma cell lines and of normal dermal fibroblasts without showing a specific selectivity for cancer cell lines. Complex 3 on the other hand, shows a higher cytotoxicity in a colorectal carcinoma cell line (HCT116), a lower cytotoxicity towards normal dermal fibroblasts and no effect in an ovarian carcinoma cell line (order of magnitude HCT116 > fibroblasts > A2780).
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Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Oxiquinolina/química , Vanadio/química , Alcoholes/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Catálisis , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Técnicas de Química Sintética , Complejos de Coordinación/síntesis química , Humanos , Hidrocarburos/química , Concentración 50 Inhibidora , Modelos Moleculares , Estructura Molecular , Oxidación-Reducción , Peróxidos/química , Especies Reactivas de Oxígeno/metabolismo , Análisis EspectralRESUMEN
BACKGROUND: Recent studies suggest the use of transcatheter aortic valve implantation (TAVI) as an alternative to surgical aortic valve replacement (SAVR) in lower risk populations, but real-world data are scarce. METHODS: Single-center retrospective study of patients undergoing SAVR (between June 2009 and July 2016, n = 682 patients) or TAVI (between June 2009 and July 2017, n = 400 patients). Low surgical risk was defined as EuroSCORE II (ES II) < 4% for single noncoronary artery bypass graft procedure. TAVI patients were propensity score-matched in a 1:1 ratio with SAVR patients, paired by age, New York Heart Association class, diabetes mellitus, chronic obstructive pulmonary disease, atrial fibrillation, creatinine clearance, and left ventricular ejection fraction < 50%. RESULTS: A total of 158 patients (79 SAVR and 79 TAVI) were matched (mean age 79 ± 6 years, 79 men). TAVI patients had a higher incidence of permanent pacemaker implantation (0% vs. 19%, p < 0.001) and more than mild paravalvular leak (4% vs. 18%, p = 0.009), but comparable rates of stroke, major or life-threatening bleeding, emergent cardiac surgery, new-onset atrial fibrillation, and need for renal replacement therapy. Hospital length-of-stay and 30-day mortality were similar. At a median follow-up of 4.5 years (IQR 3.0-6.9), treatment strategy did not influence all-cause mortality (HR 1.19, 95% CI 0.77-1.83, log rank p = 0.43) nor rehospitalization (crude subdistribution HR 1.56, 95% CI 0.71-3.41, p = 0.26). ES II remained the only independent predictor of long-term all-cause mortality (adjusted HR 1.40, 95% CI 1.04-1.90, p = 0.029). CONCLUSION: In this low surgical risk severe aortic stenosis population, we observed similar rates of 30-day and long-term all-cause mortality, despite higher rates of permanent pacemaker implantation and more than mild paravalvular leak in TAVI patients. The results of this small study suggest that both procedures are safe and effective in the short-term, while the Heart Team remains essential to assess both options on the long-term.