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1.
J Infect Dis ; 223(1): 62-71, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33175145

RESUMO

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.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/imunologia , Pessoal de Saúde , Adulto , Estudos Transversais , Feminino , Seguimentos , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Cinética , Masculino , Pessoa de Meia-Idade , Soroconversão , Estudos Soroepidemiológicos , Espanha/epidemiologia
2.
Stroke ; 52(10): 3121-3131, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34253047

RESUMO

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.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Estudos de Casos e Controles , Dabigatrana/uso terapêutico , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Hemorragias Intracranianas/complicações , Hemorragias Intracranianas/prevenção & controle , AVC Isquêmico/prevenção & controle , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento , Vitamina K/antagonistas & inibidores
3.
Europace ; 21(1): 147-153, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30016418

RESUMO

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.


Assuntos
Ventrículos do Coração/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Função Ventricular Direita , Complexos Ventriculares Prematuros/etiologia , Remodelação Ventricular , Potenciais de Ação , Adulto , Idoso , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Ablação por Cateter , Técnicas Eletrofisiológicas Cardíacas , Feminino , Frequência Cardíaca , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Valva Pulmonar/diagnóstico por imagem , Valva Pulmonar/fisiopatologia , Fatores de Risco , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/fisiopatologia , Complexos Ventriculares Prematuros/diagnóstico , Complexos Ventriculares Prematuros/fisiopatologia , Complexos Ventriculares Prematuros/cirurgia
4.
Europace ; 21(7): 1079-1087, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30904923

RESUMO

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.


Assuntos
Ablação por Cateter/métodos , Disfunção Ventricular Esquerda/cirurgia , Complexos Ventriculares Prematuros/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Volume Sistólico , Sístole , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/fisiopatologia , Complexos Ventriculares Prematuros/mortalidade , Complexos Ventriculares Prematuros/fisiopatologia
6.
Europace ; 20(2): 337-346, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28017938

RESUMO

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.


Assuntos
Estimulação Cardíaca Artificial , Técnicas Eletrofisiológicas Cardíacas , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Taquicardia Ventricular/diagnóstico , Potenciais de Ação , Idoso , Ablação por Cateter , Feminino , Sistema de Condução Cardíaco/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Valor Preditivo dos Testes , Estudos Prospectivos , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/cirurgia , Fatores de Tempo , Resultado do Tratamento
7.
Europace ; 20(3): 512-519, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28069835

RESUMO

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.


Assuntos
Cateterismo Cardíaco/métodos , Ablação por Cateter/métodos , Técnicas Eletrofisiológicas Cardíacas , Sistema de Condução Cardíaco/cirurgia , Taquicardia Ventricular/cirurgia , Potenciais de Ação , Idoso , Idoso de 80 Anos ou mais , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/instrumentação , Cateteres Cardíacos , Ablação por Cateter/efeitos adversos , Ablação por Cateter/instrumentação , Técnicas Eletrofisiológicas Cardíacas/instrumentação , Feminino , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Projetos Piloto , Valor Preditivo dos Testes , Espanha , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
8.
J Electrocardiol ; 51(2): 239-246, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29242053

RESUMO

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.


Assuntos
Mapeamento Epicárdico/métodos , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/cirurgia , Obstrução do Fluxo Ventricular Externo/fisiopatologia , Obstrução do Fluxo Ventricular Externo/cirurgia , Algoritmos , Ablação por Cateter , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Europace ; 19(6): 976-982, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-27353322

RESUMO

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.


Assuntos
Ablação por Cateter , Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Prevenção Secundária/instrumentação , Taquicardia Ventricular/terapia , Idoso , Ablação por Cateter/efeitos adversos , Distribuição de Qui-Quadrado , Terapia Combinada , Intervalo Livre de Doença , Cardioversão Elétrica/efeitos adversos , Cardioversão Elétrica/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Prospectivos , Recidiva , Fatores de Risco , Volume Sistólico , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/mortalidade , Taquicardia Ventricular/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda
10.
J Infect Dis ; 212 Suppl 2: S226-33, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26138826

RESUMO

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.


Assuntos
Ebolavirus/genética , Genes Virais/genética , Doença pelo Vírus Ebola/virologia , Edição de RNA/genética , Proteínas do Envelope Viral/genética , Proteínas Virais/genética , Fatores de Virulência/genética , Animais , Linhagem Celular , Regulação para Baixo/genética , Ebolavirus/patogenicidade , Regulação Viral da Expressão Gênica/genética , Cobaias , Glicoproteínas de Membrana/genética , Mutação/genética
11.
Syst Biol Reprod Med ; 70(1): 261-271, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39217625

RESUMO

Despite that the SARS-CoV-2 pandemic has been controlled, it has affected a large proportion of the population, raising some concerns about potential sequelae in men at reproductive age. To contribute to the clarification of this issue, we performed a retrospective study comparing semen parameters values before and after confirmed SARS-CoV-2 infection in a large cohort of infertile men, compared to a control group that did not undergo SARS-CoV-2 infection. Wilcoxon test on paired samples and general linear regression model showed that SARS-CoV-2 infection has a detrimental effect on semen volume values (p < 0.005). However, semen volume seems to be significantly lower only during the first spermatogenic cycle after SARS-COV-2 infection (p < 0.005) and mainly in unvaccinated patients (p < 0.05). In addition, we detected alterations in progressive motility in patients infected with the alpha SARS-COV-2 strain (p < 0.05). In conclusion, our results show that although SARS-CoV-2 has a small effect on semen volume and sperm motility in infertile men, depending on the infectious strain or vaccination status, pre-infection values of semen parameters appear to be restored over one spermatogenic cycle after infection.


Assuntos
COVID-19 , Infertilidade Masculina , SARS-CoV-2 , Análise do Sêmen , Sêmen , Humanos , Masculino , COVID-19/complicações , COVID-19/fisiopatologia , Estudos Retrospectivos , Adulto , Infertilidade Masculina/virologia , Infertilidade Masculina/fisiopatologia , Infertilidade Masculina/etiologia , Sêmen/virologia , Motilidade dos Espermatozoides
12.
Front Bioeng Biotechnol ; 11: 1223737, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37560536

RESUMO

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.

13.
Lab Chip ; 23(4): 591-608, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36655405

RESUMO

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.


Assuntos
Células Endoteliais , Sistemas Microfisiológicos , Humanos , Células Cultivadas , Fígado , Microfluídica , Dispositivos Lab-On-A-Chip
14.
Biosensors (Basel) ; 12(2)2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35200386

RESUMO

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.


Assuntos
Desenvolvimento de Medicamentos , Dispositivos Lab-On-A-Chip , Humanos , Tecnologia
15.
Biosensors (Basel) ; 11(5)2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34069506

RESUMO

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.


Assuntos
Dimetilpolisiloxanos/química , Dispositivos Lab-On-A-Chip , Elastômeros , Células Endoteliais , Humanos
16.
BMJ Glob Health ; 6(6)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34083241

RESUMO

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.


Assuntos
Malária , Autopsia , Causas de Morte , Criança , Pré-Escolar , Humanos , Malária/diagnóstico , Moçambique/epidemiologia , Reprodutibilidade dos Testes
18.
Eur J Prev Cardiol ; 27(6): 622-632, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31487998

RESUMO

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.


Assuntos
Dispositivos de Terapia de Ressincronização Cardíaca/economia , Terapia de Ressincronização Cardíaca/economia , Tomada de Decisão Clínica , Custos de Cuidados de Saúde , Insuficiência Cardíaca/economia , Insuficiência Cardíaca/terapia , Imageamento por Ressonância Magnética/economia , Seleção de Pacientes , Idoso , Algoritmos , Terapia de Ressincronização Cardíaca/mortalidade , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/mortalidade , Humanos , Expectativa de Vida , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Modelos Econômicos , Estudos Observacionais como Assunto , Valor Preditivo dos Testes , Prognóstico , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Estudos Retrospectivos , Fatores de Tempo
19.
Nat Commun ; 11(1): 3500, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641730

RESUMO

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.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Pessoal de Saúde , Pneumonia Viral/epidemiologia , Adulto , Infecções Assintomáticas/epidemiologia , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , COVID-19 , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Saúde Ocupacional , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , RNA Viral/sangue , Fatores de Risco , SARS-CoV-2 , Estudos Soroepidemiológicos , Espanha/epidemiologia
20.
Heart ; 105(5): 378-383, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30242139

RESUMO

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.


Assuntos
Ablação por Cateter , Cicatriz/patologia , Imagem Cinética por Ressonância Magnética/métodos , Disfunção Ventricular Esquerda , Complexos Ventriculares Prematuros , Adulto , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Ecocardiografia/métodos , Feminino , Humanos , Aumento da Imagem , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Peptídeo Natriurético Encefálico/sangue , Avaliação de Processos e Resultados em Cuidados de Saúde , Prognóstico , Reprodutibilidade dos Testes , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologia , Complexos Ventriculares Prematuros/diagnóstico , Complexos Ventriculares Prematuros/patologia , Complexos Ventriculares Prematuros/cirurgia
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