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1.
J Infect Dis ; 223(1): 62-71, 2021 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-33175145

RESUMEN

BACKGROUND: At the COVID-19 spring 2020 pandemic peak in Spain, prevalence of SARS-CoV-2 infection in a cohort of 578 randomly selected health care workers (HCWs) from Hospital Clínic de Barcelona was 11.2%. METHODS: A follow-up survey 1 month later (April-May 2020) measured infection by rRT-PCR and IgM, IgA, and IgG to the receptor-binding domain of the spike protein by Luminex. Antibody kinetics, including IgG subclasses, was assessed until month 3. RESULTS: At month 1, the prevalence of infection measured by rRT-PCR and serology was 14.9% (84/565) and seroprevalence 14.5% (82/565). We found 25 (5%) new infections in 501 participants without previous evidence of infection. IgM, IgG, and IgA levels declined in 3 months (antibody decay rates 0.15 [95% CI, .11-.19], 0.66 [95% CI, .54-.82], and 0.12 [95% CI, .09-.16], respectively), and 68.33% of HCWs had seroreverted for IgM, 3.08% for IgG, and 24.29% for IgA. The most frequent subclass responses were IgG1 (highest levels) and IgG2, followed by IgG3, and only IgA1 but no IgA2 was detected. CONCLUSIONS: Continuous and improved surveillance of SARS-CoV-2 infections in HCWs remains critical, particularly in high-risk groups. The observed fast decay of IgA and IgM levels has implications for seroprevalence studies using these isotypes.


Asunto(s)
Anticuerpos Antivirales/sangre , COVID-19/inmunología , Personal de Salud , Adulto , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Cinética , Masculino , Persona de Mediana Edad , Seroconversión , Estudios Seroepidemiológicos , España/epidemiología
2.
Stroke ; 52(10): 3121-3131, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34253047

RESUMEN

Background and Purpose: The objective of the study was to assess the effectiveness of individual direct oral anticoagulants versus vitamin K antagonists for primary prevention of stroke (ischemic and hemorrhagic) in routine clinical practice in patients with various clinical risk factors depending on their atrial fibrillation (AF) patterns. Methods: A nested case-referent study was conducted using data from 2 national registries of patients with stroke and AF. Stroke cases with previous history of AF were matched to up to 2 randomly selected referent patients with AF and no stroke. The association of individual anticoagulant use with ischemic or hemorrhagic stroke was studied in patients with or without permanent AF using multivariable conditional logistic models, controlled for clinically significant risk factors and multiple other cardiovascular risk factors. Results: In total, 2586 stroke cases with previous AF and 4810 nonstroke referent patients with AF were retained for the study. Direct oral anticoagulant users had lower odds of stroke of any type than vitamin K antagonist users: the adjusted-matched OR for ischemic stroke were 0.70 (95% CI, 0.50­0.98) for dabigatran, 0.68 (95% CI, 0.53­0.86) for rivaroxaban, and 0.73 (95% CI, 0.52­1.02) for apixaban while for hemorrhagic stroke they were 0.31 (95% CI, 0.14­0.68), 0.64 (95% CI, 0.39­1.06), and 0.70 (95% CI, 0.33­1.49), respectively. The effects of individual direct oral anticoagulants relative to vitamin K antagonists were similar in permanent AF and nonpermanent AF patients. Conclusions: Similar results were observed for each direct oral anticoagulant in real life as those observed in the pivotal clinical trials. The pattern of AF did not affect the outcome.


Asunto(s)
Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Accidente Cerebrovascular/prevención & control , Administración Oral , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/complicaciones , Estudios de Casos y Controles , Dabigatrán/uso terapéutico , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Hemorragias Intracraneales/complicaciones , Hemorragias Intracraneales/prevención & control , Accidente Cerebrovascular Isquémico/prevención & control , Masculino , Persona de Mediana Edad , Factores de Riesgo , Resultado del Tratamiento , Vitamina K/antagonistas & inhibidores
3.
Europace ; 21(1): 147-153, 2019 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-30016418

RESUMEN

AIMS: Left ventricular (LV) outflow tract ventricular arrhythmias (OTVA) are associated with hypertension (HT), older age, and LV dysfunction, suggesting that LV overload plays a role in the aetiopathogenesis. We hypothesized that anatomical modifications of the LV outflow tract (LVOT) could predict left vs. right OTVA site of origin (SOO). METHODS AND RESULTS: Fifty-six (32 men, 53 ± 18 years old) consecutive patients referred for OTVA ablation were included. Cardiac multidetector computed tomography was performed before ablation and then imported to the CARTO system to aid the mapping and ablation procedure. Anatomical characteristics of the aortic root as well as aortopulmonary valvular planar angulation (APVPA) were analysed. The LV was the OTVA SOO (LVOT-VA) in 32 (57%) patients. These patients were more frequently male (78% vs. 22%, P = 0.001), older (57 ± 18 vs. 47 ± 18 years, P = 0.055), and more likely to have HT (59% vs. 21%, P = 0.004), compared to right OTVA patients. Aortopulmonary valvular planar angulation was higher in LVOT-VA patients (68 ± 5° vs. 55 ± 6°, respectively; P < 0.001). Absolute size of all aortic root diameters was associated with LVOT origin. However, after indexing by body surface area, only sinotubular junction diameter maintained a significant association (P = 0.049). Multivariable analysis showed that APVPA was an independent predictor of LVOT origin. Aortopulmonary valvular planar angulation ≥62° reached 94% sensitivity and 83% specificity (area under the curve 0.95) for predicting LVOT origin. CONCLUSIONS: The measurement of APVPA as a marker of chronic LV overload is useful for the prediction of left vs. right ventricular OTVA origin.


Asunto(s)
Ventrículos Cardíacos/diagnóstico por imagen , Tomografía Computarizada Multidetector , Disfunción Ventricular Izquierda/diagnóstico por imagen , Función Ventricular Izquierda , Función Ventricular Derecha , Complejos Prematuros Ventriculares/etiología , Remodelación Ventricular , Potenciales de Acción , Adulto , Anciano , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/fisiopatología , Ablación por Catéter , Técnicas Electrofisiológicas Cardíacas , Femenino , Frecuencia Cardíaca , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Válvula Pulmonar/diagnóstico por imagen , Válvula Pulmonar/fisiopatología , Factores de Riesgo , Disfunción Ventricular Izquierda/complicaciones , Disfunción Ventricular Izquierda/fisiopatología , Complejos Prematuros Ventriculares/diagnóstico , Complejos Prematuros Ventriculares/fisiopatología , Complejos Prematuros Ventriculares/cirugía
4.
Europace ; 21(7): 1079-1087, 2019 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-30904923

RESUMEN

AIMS: Ablation of frequent premature ventricular complexes (PVCs) improves left ventricular ejection fraction in patients with left ventricular (LV) systolic dysfunction. This study aims to evaluate the long-term hard outcomes and potential prognostic variables in this population. METHODS AND RESULTS: Prospective multicentre study including 101 consecutive patients [56 ± 12 years old, 62 (61%) men] with LV systolic dysfunction and frequent PVCs who underwent PVC ablation before November 2015. The last evaluation performed was considered the long-term follow-up (LTFUP) evaluation. Mean follow-up was 34 ± 16 months (range 24-84 months). Ablation was successful in 95 (94%) patients. There was a significant reduction in the PVC burden from 21 ± 12% at baseline to 3.8 ± 6% at LTFUP, P < 0.001. Left ventricular ejection fraction improved from 32 ± 8% at baseline to 39 ± 12% at LTFUP (P < 0.001) and New York Heart Association class from 2.2 ± 0.6% to 1.3 ± 0.6% (P < 0.001). Brain natriuretic peptide levels decreased from 136 (78-321) to 68 (32-144) pg/mL (P = 0.007). Most of this improvement occurs during the first 6 months after ablation. Persistent abolition of at least 18 points of the baseline PVC burden was independently and inversely associated with the composite endpoint of cardiac mortality, cardiac transplantation, or hospitalization for heart failure during follow-up [hazard ratio 0.18 (0.05-0.66), P = 0.01]. CONCLUSION: In patients with LV systolic dysfunction, ablation of frequent PVCs induces a significant improvement in functional, structural, and neurohormonal status, which persists at LTFUP. A sustained reduction in the baseline PVC burden is associated with a lower risk of cardiac mortality, cardiac transplantation, or hospitalization for heart failure during follow-up.


Asunto(s)
Ablación por Catéter/métodos , Disfunción Ventricular Izquierda/cirugía , Complejos Prematuros Ventriculares/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Volumen Sistólico , Sístole , Disfunción Ventricular Izquierda/mortalidad , Disfunción Ventricular Izquierda/fisiopatología , Complejos Prematuros Ventriculares/mortalidad , Complejos Prematuros Ventriculares/fisiopatología
6.
Europace ; 20(2): 337-346, 2018 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-28017938

RESUMEN

Aims: Identification of local abnormal electrograms (EGMs) during ventricular tachycardia substrate ablation (VTSA) is challenging when they are hidden within the far-field signal. This study analyses whether the response to a double ventricular extrastimulus during substrate mapping could identify slow conducting areas that are hidden during sinus rhythm. Methods and results: Consecutive patients (n = 37) undergoing VTSA were prospectively included. Bipolar EGMs with >3 deflections and duration <133 ms were considered as potential hidden slow conduction EGMs (HSC-EGM) if located within/surrounding the scar area. Whenever a potential HSC-EGM was identified, a double ventricular extrastimulus was delivered. If the local potential delayed, it was annotated as HSC-EGM. The incidence of HSC-EGM in core, border-zone, and normal-voltage regions was determined. Ablation was delivered at conducting channel entrances and HSC-EGMs. VT inducibility after VTSA obtained was compared with data from a historic control group. 2417 EGMs were analyzed. 575 (23.7%) qualified as potential HSC-EGM, and 198 of them were tagged as HSC-EGMs. Scars in patients with HSC-EGMs (n = 21, 56.7%) were smaller (35.424.7 vs 67.639.1 cm2; P = 0.006) and more heterogeneous (core/scar area ratio 0.250.2 vs 0.450.19; P = 0.02). 28.8% of HSC-EGMs were located in normal-voltage tissue; 81.3% were targeted for ablation. Patients undergoing VTSA incorporating HSC analysis needed less radiofrequency time (17.411 vs 2310.7 minutes; P = 0.016) and had a lower rate of VT inducibility after VTSA than the historic controls (24.3% vs 50%; P = 0.018). Conclusion: Ventricular tachycardia substrate ablation incorporating HSC analysis allowed further arrhythmic substrate identification (especially in normal-voltage areas) and reduced RF time and VT inducibility after VTSA.


Asunto(s)
Estimulación Cardíaca Artificial , Técnicas Electrofisiológicas Cardíacas , Sistema de Conducción Cardíaco/fisiopatología , Frecuencia Cardíaca , Taquicardia Ventricular/diagnóstico , Potenciales de Acción , Anciano , Ablación por Catéter , Femenino , Sistema de Conducción Cardíaco/cirugía , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Valor Predictivo de las Pruebas , Estudios Prospectivos , Taquicardia Ventricular/fisiopatología , Taquicardia Ventricular/cirugía , Factores de Tiempo , Resultado del Tratamiento
7.
Europace ; 20(3): 512-519, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-28069835

RESUMEN

Aims: Ventricular tachycardia (VT) substrate ablation is based on detailed electroanatomical maps (EAM). This study analyses whether high-density multielectrode mapping (MEM) is superior to conventional point-by-point mapping (PPM) in guiding VT substrate ablation procedures. Methods and results: This was a randomized controlled study (NCT02083016). Twenty consecutive ischemic patients undergoing VT substrate ablation were randomized to either group A [n = 10; substrate mapping performed first by PPM (Navistar) and secondly by MEM (PentaRay) ablation guided by PPM] or group B [n = 10; substrate mapping performed first by MEM and second by PPM ablation guided by MEM]. Ablation was performed according to the scar-dechanneling technique. Late potential (LP) pairs were defined as a Navistar-LP and a PentaRay-LP located within a three-dimensional distance of ≤ 3 mm. Data obtained from EAM, procedure time, radiofrequency time, and post-ablation VT inducibility were compared between groups. Larger bipolar scar areas were obtained with MEM (55.7±31.7 vs. 50.5±26.6 cm2; P = 0.017). Substrate mapping time was similar with MEM (19.7±7.9 minutes) and PPM (25±9.2 minutes); P = 0.222. No differences were observed in the number of LPs identified within the scar by MEM vs. PPM (73±50 vs. 76±52 LPs per patient, respectively; P = 0.965). A total of 1104 LP pairs were analysed. Using PentaRay, far-field/LP ratio was significantly lower (0.58±0.4 vs. 1.64±1.1; P = 0.01) and radiofrequency time was shorter [median (interquartile range) 12 (7-20) vs. 22 (17-33) minutes; P = 0.023]. No differences were observed in VT inducibility after procedure. Conclusion: MEM with PentaRay catheter provided better discrimination of LPs due to a lower sensitivity for far-field signals. Ablation guided by MEM was associated with a shorter radiofrequency time.


Asunto(s)
Cateterismo Cardíaco/métodos , Ablación por Catéter/métodos , Técnicas Electrofisiológicas Cardíacas , Sistema de Conducción Cardíaco/cirugía , Taquicardia Ventricular/cirugía , Potenciales de Acción , Anciano , Anciano de 80 o más Años , Cateterismo Cardíaco/efectos adversos , Cateterismo Cardíaco/instrumentación , Catéteres Cardíacos , Ablación por Catéter/efectos adversos , Ablación por Catéter/instrumentación , Técnicas Electrofisiológicas Cardíacas/instrumentación , Femenino , Sistema de Conducción Cardíaco/fisiopatología , Frecuencia Cardíaca , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tempo Operativo , Proyectos Piloto , Valor Predictivo de las Pruebas , España , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatología , Factores de Tiempo , Resultado del Tratamiento
8.
J Electrocardiol ; 51(2): 239-246, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29242053

RESUMEN

PURPOSE: Activation mapping is used to guide ablation of idiopathic outflow tract ventricular arrhythmias (OTVAs). Isochronal activation maps help to predict the site of origin (SOO): left vs right outflow tract (OT). We evaluate an algorithm for automatic activation mapping based on the onset of the bipolar electrogram (EGM) signal for predicting the SOO and the effective ablation site in OTVAs. METHODS: Eighteen patients undergoing ablation due to idiopathic OTVAs were studied (12 with left ventricle OT origin). Right ventricle activation maps were obtained offline with an automatic algorithm and compared with manual annotation maps obtained during the intervention. Local activation time (LAT) accuracy was assessed, as well as the performance of the 10ms earliest activation site (EAS) isochronal area in predicting the SOO. RESULTS: High correlation was observed between manual and automatic LATs (Spearman's: 0.86 and Lin's: 0.85, both p<0.01). The EAS isochronal area were closely located in both map modalities (5.55 ± 3.56mm) and at a similar distance from the effective ablation site (0.15±2.08mm difference, p=0.859). The 10ms isochronal area longitudinal/perpendicular diameter ratio measured from automatic maps showed slightly superior SOO identification (67% sensitivity, 100% specificity) compared with manual maps (67% sensitivity, 83% specificity). CONCLUSIONS: Automatic activation mapping based on the bipolar EGM onset allows fast, accurate and observer-independent identification of the SOO and characterization of the spreading of the activation wavefront in OTVAs.


Asunto(s)
Mapeo Epicárdico/métodos , Taquicardia Ventricular/fisiopatología , Taquicardia Ventricular/cirugía , Obstrucción del Flujo Ventricular Externo/fisiopatología , Obstrucción del Flujo Ventricular Externo/cirugía , Algoritmos , Ablación por Catéter , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad
9.
Europace ; 19(6): 976-982, 2017 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-27353322

RESUMEN

AIMS: This study assessed the benefit of peri-implantable cardioverter-defibrillator implant ventricular tachycardia (VT)-substrate ablation in patients with structural heart disease (SHD). METHODS AND RESULTS: Patients with SHD and indication for secondary prevention ICD implant were prospectively included. Patients presenting with incessant and/or slow VT or frequent (≥2) VT episodes who underwent peri-ICD VT-substrate ablation (the scar dechannelling technique) were compared with those who received ICD alone and did not meet ablation criteria. The primary endpoint was any sustained VT/ICD therapy during follow-up. Of 206 patients included (43.2% non-ischaemic), 70 were assigned to ablation and 136 received ICD implant alone. During a mean follow-up of 45.6 ± 24.7 months, the primary endpoint was more frequent in the non-ablation group (47.1 vs. 22.9%; P< 0.0001). Higher VT recurrence-free survival rate [log-rank P= 0.001; HR = 0.42 (0.24-0.73), P= 0.002] and ICD shock-free survival rate [log-rank P= 0.007; HR = 0.36 (0.17-0.78); P = 0.01] were observed in the ablation group. Higher relative risk reduction was observed in ischaemic [HR = 0.38 (0.18-0.83); P = 0.015] vs. non-ischaemic patients [HR = 0.49 (0.23-1.01); P = 0.08]. Patients with left ventricular ejection fraction (LVEF) <35% showed no differences in VT recurrence between treatment groups (log-rank P = 0.213) although VT burden during follow-up was lower in the ablation group [median (interquartile range) 1 (1-3) vs. 4 (1-10) VT episodes; P = 0.05]. CONCLUSION: First-line peri-ICD implant VT-substrate ablation was associated with decreased VT recurrence and ICD shocks during long-term follow-up in patients with SHD and indication for secondary prevention ICD implant, especially in ischaemic patients. In patients with LVEF <35%, no benefit was observed in terms of VT recurrence-free survival, although VT burden during follow-up was lower in the ablation group.


Asunto(s)
Ablación por Catéter , Desfibriladores Implantables , Cardioversión Eléctrica/instrumentación , Prevención Secundaria/instrumentación , Taquicardia Ventricular/terapia , Anciano , Ablación por Catéter/efectos adversos , Distribución de Chi-Cuadrado , Terapia Combinada , Supervivencia sin Enfermedad , Cardioversión Eléctrica/efectos adversos , Cardioversión Eléctrica/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Recurrencia , Factores de Riesgo , Volumen Sistólico , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/mortalidad , Taquicardia Ventricular/fisiopatología , Factores de Tiempo , Resultado del Tratamiento , Función Ventricular Izquierda
10.
J Infect Dis ; 212 Suppl 2: S226-33, 2015 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-26138826

RESUMEN

Synthesis of the surface glycoprotein GP of Ebola virus (EBOV) is dependent on transcriptional RNA editing, whereas direct expression of the GP gene results in synthesis of nonstructural secreted glycoprotein sGP. In this study, we investigate the role of RNA editing in the pathogenicity of EBOV using a guinea pig model and recombinant guinea pig-adapted EBOV containing mutations at the editing site, allowing expression of surface GP without the need for RNA editing, and also preventing synthesis of sGP. We demonstrate that the elimination of the editing site leads to EBOV attenuation in vivo, explained by lower virus spread caused by the higher virus cytotoxicity and, most likely, by an increased ability of the host defense systems to recognize and eliminate virus-infected cells. We also demonstrate that expression of sGP does not affect pathogenicity of EBOV in guinea pigs. In conclusion, data obtained indicate that downregulation of the level of surface GP expression through a mechanism of GP gene RNA editing plays an important role in the high pathogenicity of EBOV.


Asunto(s)
Ebolavirus/genética , Genes Virales/genética , Fiebre Hemorrágica Ebola/virología , Edición de ARN/genética , Proteínas del Envoltorio Viral/genética , Proteínas Virales/genética , Factores de Virulencia/genética , Animales , Línea Celular , Regulación hacia Abajo/genética , Ebolavirus/patogenicidad , Regulación Viral de la Expresión Génica/genética , Cobayas , Glicoproteínas de Membrana/genética , Mutación/genética
11.
Front Bioeng Biotechnol ; 11: 1223737, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37560536

RESUMEN

Background: There is a significant need for predictive and stable in vitro human liver representations for disease modeling and drug testing. Hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs) are important non-parenchymal cell components of the liver and are hence of relevance in a variety of disease models, including hepatic fibrosis. Pluripotent stem cell- (PSC-) derived HSCs (scHSCs) and LSECs (scLSECs) offer an attractive alternative to primary human material; yet, the suitability of scHSCs and scLSECs for extended in vitro modeling has not been characterized. Methods: In this study, we describe the phenotypic and functional development of scHSCs and scLSECs during 14 days of 2D in vitro culture. Cell-specific phenotypes were evaluated by cell morphology, immunofluorescence, and gene- and protein expression. Functionality was assessed in scHSCs by their capacity for intracellular storage of vitamin A and response to pro-fibrotic stimuli induced by TGF-ß. scLSECs were evaluated by nitric oxide- and factor VIII secretion as well as endocytic uptake of bioparticles and acetylated low-density lipoprotein. Notch pathway inhibition and co-culturing scHSCs and scLSECs were separately tested as options for enhancing long-term stability and maturation of the cells. Results and Conclusion: Both scHSCs and scLSECs exhibited a post-differentiation cell type-specific phenotype and functionality but deteriorated during extended culture with PSC line-dependent variability. Therefore, the choice of PSC line and experimental timeframe is crucial when designing in vitro platforms involving scHSCs and scLSECs. Notch inhibition modestly improved long-term monoculture in a cell line-dependent manner, while co-culturing scHSCs and scLSECs provides a strategy to enhance phenotypic and functional stability.

12.
Lab Chip ; 23(4): 591-608, 2023 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-36655405

RESUMEN

We developed a novel, pump-less directional flow recirculating organ-on-a-chip (rOoC) platform that creates controlled unidirectional gravity-driven flow by a combination of a 3D-tilting system and an optimized microfluidic layout. The rOoC platform was assembled utilizing a layer-to-layer fabrication technology based on thermoplastic materials. It features two organoid compartments supported by two independent perfusion channels and separated by a hydrogel barrier. We developed a computational model to predict wall shear stress values and then measured the flow rate in the microfluidic channels with micro-Particle-Image-Velocimetry (µPIV). The suitability of the rOoC for functional culture of endothelial cells was tested using HUVECs seeded in the perfusion channels. HUVECs aligned in response to the directional flow, formed a barrier and were able to sprout into the organoid compartments. Next, we demonstrated the viability of human stem-cell derived liver organoids in the organoid compartments. Finally, we show the possibility to circulate immune cells in the microfluidic channels that retain viability without being trapped or activated. The rOoC platform allows growing and connecting of two or more tissue or organ representations on-chip with the possibility of applying gradients, endothelial barriers, microvasculature and circulating cells independent of external tubing and support systems.


Asunto(s)
Células Endoteliales , Sistemas Microfisiológicos , Humanos , Células Cultivadas , Hígado , Microfluídica , Dispositivos Laboratorio en un Chip
13.
Biosensors (Basel) ; 12(2)2022 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-35200386

RESUMEN

Organ-on-a-Chip (OoC) systems bring together cell biology, engineering, and material science for creating systems that recapitulate the in vivo microenvironment of tissues and organs. The versatility of OoC systems enables in vitro models for studying physiological processes, drug development, and testing in both academia and industry. This paper evaluates current platforms from the academic end-user perspective, elaborating on usability, complexity, and robustness. We surveyed 187 peers in 35 countries and grouped the responses according to preliminary knowledge and the source of the OoC systems that are used. The survey clearly shows that current commercial OoC platforms provide a substantial level of robustness and usability-which is also indicated by an increasing adaptation of the pharmaceutical industry-but a lack of complexity can challenge their use as a predictive platform. Self-made systems, on the other hand, are less robust and standardized but provide the opportunity to develop customized and more complex models, which are often needed for human disease modeling. This perspective serves as a guide for researchers in the OoC field and encourages the development of next-generation OoCs.


Asunto(s)
Desarrollo de Medicamentos , Dispositivos Laboratorio en un Chip , Humanos , Tecnología
14.
Biosensors (Basel) ; 11(5)2021 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-34069506

RESUMEN

Polydimethylsiloxane (PDMS) has been used in microfluidic systems for years, as it can be easily structured and its flexibility makes it easy to integrate actuators including pneumatic pumps. In addition, the good optical properties of the material are well suited for analytical systems. In addition to its positive aspects, PDMS is well known to adsorb small molecules, which limits its usability when it comes to drug testing, e.g., in organ-on-a-chip (OoC) systems. Therefore, alternatives to PDMS are in high demand. In this study, we use thermoplastic elastomer (TPE) films thermally bonded to laser-cut poly(methyl methacrylate) (PMMA) sheets to build up multilayered microfluidic devices with integrated pneumatic micro-pumps. We present a low-cost manufacturing technology based on a conventional CO2 laser cutter for structuring, a spin-coating process for TPE film fabrication, and a thermal bonding process using a pneumatic hot-press. UV treatment with an Excimer lamp prior to bonding drastically improves the bonding process. Optimized bonding parameters were characterized by measuring the burst load upon applying pressure and via profilometer-based measurement of channel deformation. Next, flow and long-term stability of the chip layout were measured using microparticle Image Velocimetry (uPIV). Finally, human endothelial cells were seeded in the microchannels to check biocompatibility and flow-directed cell alignment. The presented device is compatible with a real-time live-cell analysis system.


Asunto(s)
Dimetilpolisiloxanos/química , Dispositivos Laboratorio en un Chip , Elastómeros , Células Endoteliales , Humanos
15.
BMJ Glob Health ; 6(6)2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34083241

RESUMEN

BACKGROUND: Global malaria mortality estimates are hindered by the low reliability of the verbal autopsy (VA) and the clinical records, the most common sources of information used to estimate malaria-specific mortality. We aimed to determine the accuracy of these tools, as well as of the minimally invasive autopsy (MIA), a needle-based postmortem sampling method, to identify malaria-specific mortality in a large series of deceased patients from Mozambique, using complete autopsy as the gold standard. METHODS: Observational study that included 264 deaths, occurring at a tertiary level hospital in Mozambique, from 1 November 2013 to 31 March 2015 (17 months-long period). Clinical data were abstracted, a computer coded VA was completed using the clinical data as source of information, and an MIA followed by a complete autopsy were performed. Screening for malaria infection was conducted postmortem to all participants using molecular and histological techniques (PCR and immunohistochemistry). FINDINGS: Malaria infection was considered the cause of death in 6/264 (2.3%) cases: 2/54 children (3.7%, both less than 5 years old) and 4/57 (7.0%) maternal deaths. The sensitivity and specificity of the VA, the clinical data and the MIA to identify malaria-specific deaths were 33.3% and 96.1%, 66.7% and 96.1%, and 100% and 100%, respectively. In addition, malaria was identified as a possible contributor in 14 additional patients who died of other diseases. These cases were also accurately identified by the MIA (sensitivity 82.4%, specificity 100%). INTERPRETATION: The high sensitivity and specificity of the MIA in identifying malaria may help to improve current estimates of malaria-specific mortality in endemic areas.


Asunto(s)
Malaria , Autopsia , Causas de Muerte , Niño , Preescolar , Humanos , Malaria/diagnóstico , Mozambique/epidemiología , Reproducibilidad de los Resultados
17.
Eur J Prev Cardiol ; 27(6): 622-632, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31487998

RESUMEN

BACKGROUND: A recent study showed that the presence and characteristics of myocardial scar could independently predict appropriate implantable cardioverter-defibrillator therapies and the risk of sudden cardiac death in patients receiving a de novo cardiac resynchronisation device. DESIGN: The aim was to evaluate the cost-effectiveness of cardiac magnetic resonance imaging-based algorithms versus clinical practice in the decision-making process for the implantation of a cardiac resynchronisation device pacemaker versus cardiac resynchronisation device implantable cardioverter-defibrillator device in heart failure patients with indication for cardiac resynchronisation therapy. METHODS: An incidental Markov model was developed to simulate the lifetime progression of a heart failure patient cohort. Key health variables included in the model were New York Heart Association functional class, hospitalisations, sudden cardiac death and total mortality. The analysis was done from the healthcare system perspective. Costs (€2017), survival and quality-adjusted life years were assessed. RESULTS: At 5-year follow-up, algorithm I reduced mortality by 39% in patients with a cardiac resynchronisation device pacemaker who were underprotected due to misclassification by clinical protocol. This approach had the highest quality-adjusted life years (algorithm I 3.257 quality-adjusted life years; algorithm II 3.196 quality-adjusted life years; clinical protocol 3.167 quality-adjusted life years) and the lowest lifetime costs per patient (€20,960, €22,319 and €28,447, respectively). Algorithm I would improve results for three subgroups: non-ischaemic, New York Heart Association class III-IV and ≥65 years old. Furthermore, implementing this approach could generate an estimated €702 million in health system savings annually in European Society of Cardiology countries. CONCLUSION: The application of cardiac magnetic resonance imaging-based algorithms could improve survival and quality-adjusted life years at a lower cost than current clinical practice (dominant strategy) used for assigning cardiac resynchronisation device pacemakers and cardiac resynchronisation device implantable cardioverter-defibrillators to heart failure patients.


Asunto(s)
Dispositivos de Terapia de Resincronización Cardíaca/economía , Terapia de Resincronización Cardíaca/economía , Toma de Decisiones Clínicas , Costos de la Atención en Salud , Insuficiencia Cardíaca/economía , Insuficiencia Cardíaca/terapia , Imagen por Resonancia Magnética/economía , Selección de Paciente , Anciano , Algoritmos , Terapia de Resincronización Cardíaca/mortalidad , Análisis Costo-Beneficio , Técnicas de Apoyo para la Decisión , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/mortalidad , Humanos , Esperanza de Vida , Masculino , Cadenas de Markov , Persona de Mediana Edad , Modelos Económicos , Estudios Observacionales como Asunto , Valor Predictivo de las Pruebas , Pronóstico , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Estudios Retrospectivos , Factores de Tiempo
18.
Nat Commun ; 11(1): 3500, 2020 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-32641730

RESUMEN

Health care workers (HCW) are a high-risk population to acquire SARS-CoV-2 infection from patients or other fellow HCW. This study aims at estimating the seroprevalence against SARS-CoV-2 in a random sample of HCW from a large hospital in Spain. Of the 578 participants recruited from 28 March to 9 April 2020, 54 (9.3%, 95% CI: 7.1-12.0) were seropositive for IgM and/or IgG and/or IgA against SARS-CoV-2. The cumulative prevalence of SARS-CoV-2 infection (presence of antibodies or past or current positive rRT-PCR) was 11.2% (65/578, 95% CI: 8.8-14.1). Among those with evidence of past or current infection, 40.0% (26/65) had not been previously diagnosed with COVID-19. Here we report a relatively low seroprevalence of antibodies among HCW at the peak of the COVID-19 epidemic in Spain. A large proportion of HCW with past or present infection had not been previously diagnosed with COVID-19, which calls for active periodic rRT-PCR testing in hospital settings.


Asunto(s)
Anticuerpos Antivirales/sangre , Betacoronavirus/inmunología , Infecciones por Coronavirus/epidemiología , Personal de Salud , Neumonía Viral/epidemiología , Adulto , Infecciones Asintomáticas/epidemiología , Betacoronavirus/genética , Betacoronavirus/aislamiento & purificación , COVID-19 , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Salud Laboral , Pandemias , Neumonía Viral/sangre , Neumonía Viral/diagnóstico , ARN Viral/sangre , Factores de Riesgo , SARS-CoV-2 , Estudios Seroepidemiológicos , España/epidemiología
19.
Heart ; 105(5): 378-383, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30242139

RESUMEN

OBJECTIVE: This study aims to evaluate the influence of myocardial scar after premature ventricular complexes (PVC) ablation in patients with left ventricular (LV) dysfunction. METHODS: 70 consecutive patients (58±11 years, 58 (83%) men, 23% (18-32) mean PVC burden) with LV dysfunction and frequent PVCs submitted for ablation were included. A late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) was performed prior to the ablation and a quantitative and qualitative analysis of the scar was done. RESULTS: Left ventricular ejection fraction progressively improved from 34.3%±9% at baseline to 44.4%±12% at 12 months (p<0.01) and 48 (69%) patients were echocardiographic responders. New York Heart Association class improved from 1.96±0.9 points at baseline to 1.36±0.6 at 12 months (p<0.001). Brain natriuretic peptide decreased from 120 (60-284) to 46 (23-81) pg/mL (p=0.04). Twenty-nine (41%) patients showed scar in the preprocedural LGE-CMR with a mean scar mass of 10.4 (5-20) g. Mean scar mass was significantly smaller in responders than in non-responders (0 (0-4.7) g vs 2 (0-14) g, respectively, p=0.017). PVC burden reduction (OR 1.09 (1.01-1.16), p=0.02) and scar mass (OR 0.9 (0.81-0.99), p=0.04) were independent predictors of response, but the former showed a higher accuracy. CONCLUSIONS: Presence of myocardial scar modulates, but does not preclude, the probability of response to PVC ablation in patients with LV dysfunction.


Asunto(s)
Ablación por Catéter , Cicatriz/patología , Imagen por Resonancia Cinemagnética/métodos , Disfunción Ventricular Izquierda , Complejos Prematuros Ventriculares , Adulto , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Ecocardiografía/métodos , Femenino , Humanos , Aumento de la Imagen , Masculino , Persona de Mediana Edad , Miocardio/patología , Péptido Natriurético Encefálico/sangre , Evaluación de Procesos y Resultados en Atención de Salud , Pronóstico , Reproducibilidad de los Resultados , Volumen Sistólico , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/fisiopatología , Complejos Prematuros Ventriculares/diagnóstico , Complejos Prematuros Ventriculares/patología , Complejos Prematuros Ventriculares/cirugía
20.
Heart Rhythm ; 15(6): 814-821, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29427821

RESUMEN

BACKGROUND: Patients with transmural myocardial infarction (MI) who undergo endocardial-only substrate ablation are at increased risk for ventricular tachycardia recurrence. Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) can be used to assess infarct transmurality (IT). However, the degree of IT associated with an epicardial arrhythmogenic substrate (AS) has not been determined. OBJECTIVE: The purpose of this study was to determine the degree of IT observed by LGE-CMR and multidetector computed tomography (MDCT) that predicts the presence of epicardial AS. METHODS: The study included 38 post-MI patients. Ten patients with a subendocardial infarction underwent endocardial-only mapping, and 28 with a classic transmural MI (C-TMI), defined as hyperenhancement ≥75% of myocardial wall thickness (WT), underwent endo-epicardial mapping. LGE-CMR/MDCT data were registered to high-density endocardial or epicardial maps to be analyzed for the presence of AS. RESULTS: Of the 28 post-MI patients with C-TMI, 18 had epicardial AS (64%) and 10 (36%) did not. An epicardial scar area ≥14 cm2 on LGE-CMR identified patients with epicardial AS (sensitivity 1, specificity 1). Mean WT in the epicardial scar area in these patients was lower than in patients without epicardial AS (3.14 ± 1.16 mm vs 5.54 ± 1.78 mm; P = .008). A mean WT cutoff value ≤3.59 mm identified patients with epicardial AS (sensitivity 0.91, specificity 0.93). CONCLUSION: An epicardial scar area ≥14 cm2 on LGE-CMR and mean CT-WT ≤3.59 mm predict epicardial AS in post-MI patients.


Asunto(s)
Mapeo Epicárdico/métodos , Frecuencia Cardíaca/fisiología , Infarto del Miocardio/complicaciones , Taquicardia Ventricular/diagnóstico , Anciano , Femenino , Estudios de Seguimiento , Humanos , Imagenología Tridimensional , Imagen por Resonancia Cinemagnética , Masculino , Tomografía Computarizada Multidetector , Infarto del Miocardio/diagnóstico , Reproducibilidad de los Resultados , Estudios Retrospectivos , Taquicardia Ventricular/etiología , Taquicardia Ventricular/fisiopatología
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