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1.
BMC Med ; 19(1): 19, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33430856

RESUMO

BACKGROUND: Cross-reactivity to SARS-CoV-2 from exposure to endemic human coronaviruses (eHCoV) is gaining increasing attention as a possible driver of both protection against infection and COVID-19 severity. Here we explore the potential role of cross-reactivity induced by eHCoVs on age-specific COVID-19 severity in a mathematical model of eHCoV and SARS-CoV-2 transmission. METHODS: We use an individual-based model, calibrated to prior knowledge of eHCoV dynamics, to fully track individual histories of exposure to eHCoVs. We also model the emergent dynamics of SARS-CoV-2 and the risk of hospitalisation upon infection. RESULTS: We hypothesise that primary exposure with any eHCoV confers temporary cross-protection against severe SARS-CoV-2 infection, while life-long re-exposure to the same eHCoV diminishes cross-protection, and increases the potential for disease severity. We show numerically that our proposed mechanism can explain age patterns of COVID-19 hospitalisation in EU/EEA countries and the UK. We further show that some of the observed variation in health care capacity and testing efforts is compatible with country-specific differences in hospitalisation rates under this model. CONCLUSIONS: This study provides a "proof of possibility" for certain biological and epidemiological mechanisms that could potentially drive COVID-19-related variation across age groups. Our findings call for further research on the role of cross-reactivity to eHCoVs and highlight data interpretation challenges arising from health care capacity and SARS-CoV-2 testing.


Assuntos
Infecções por Coronavirus , Proteção Cruzada/imunologia , Reações Cruzadas/imunologia , /imunologia , Fatores Etários , /imunologia , Coronavirus/classificação , Coronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Doenças Endêmicas , Hospitalização/estatística & dados numéricos , Humanos , Imunidade Heteróloga/imunologia , Modelagem Computacional Específica para o Paciente , Índice de Gravidade de Doença
2.
PLoS One ; 15(10): e0226464, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33035223

RESUMO

Metaplastic breast carcinoma (MBC) is a clinically aggressive and rare subtype of breast cancer, with similar features to basal-like breast cancers. Due to rapid growth rates and characteristic heterogeneity, MBC is often unresponsive to standard chemotherapies; and novel targeted therapeutic discovery is urgently needed. Histone deacetylase inhibitors (DACi) suppress tumor growth and metastasis through regulation of the epithelial-to-mesenchymal transition axis in various cancers, including basal-like breast cancers. We utilized a new MBC patient-derived xenograft (PDX) to examine the effect of DACi therapy on MBC. Cell morphology, cell cycle-associated gene expressions, transwell migration, and metastasis were evaluated in patient-derived cells and tumors after treatment with romidepsin and panobinostat. Derivations of our PDX model, including cells, spheres, organoids, explants, and in vivo implanted tumors were treated. Finally, we tested the effects of combining DACi with approved chemotherapeutics on relative cell biomass. DACi significantly suppressed the total number of lung metastasis in vivo using our PDX model, suggesting a role for DACi in preventing circulating tumor cells from seeding distal tissue sites. These data were supported by our findings that DACi reduced cell migration, populations, and expression of mesenchymal-associated genes. While DACi treatment did affect cell cycle-regulating genes in vitro, tumor growth was not affected compared to controls. Importantly, gene expression results varied depending on the cellular or tumor system used, emphasizing the importance of using multiple derivations of cancer models in preclinical therapeutic discovery research. Furthermore, DACi sensitized and produced a synergistic effect with approved oncology therapeutics on inherently resistant MBC. This study introduced a role for DACi in suppressing the migratory and mesenchymal phenotype of MBC cells through regulation of the epithelial-mesenchymal transition axis and suppression of the CTC population. Preliminary evidence that DACi treatment in combination with MEK1/2 inhibitors exerts a synergistic effect on MBC cells was also demonstrated.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Depsipeptídeos/administração & dosagem , Inibidores de Histona Desacetilases/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Panobinostat/administração & dosagem , Animais , Neoplasias da Mama/genética , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Depsipeptídeos/farmacologia , Sinergismo Farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Humanos , Neoplasias Pulmonares/genética , Camundongos , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/efeitos dos fármacos , Panobinostat/farmacologia , Modelagem Computacional Específica para o Paciente , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia
3.
PLoS One ; 15(9): e0239447, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32991605

RESUMO

The paper deals with the impact of chosen geometric and material factors on maximal stresses in carotid atherosclerotic plaque calculated using patient-specific finite element models. These stresses are believed to be decisive for the plaque vulnerability but all applied models suffer from inaccuracy of input data, especially when obtained in vivo only. One hundred computational models based on ex vivo MRI are used to investigate the impact of wall thickness, MRI slice thickness, lipid core and fibrous tissue stiffness, and media anisotropy on the calculated peak plaque and peak cap stresses. The investigated factors are taken as continuous in the range based on published experimental results, only the impact of anisotropy is evaluated by comparison with a corresponding isotropic model. Design of Experiment concept is applied to assess the statistical significance of these investigated factors representing uncertainties in the input data of the model. The results show that consideration of realistic properties of arterial wall in the model is decisive for the stress evaluation; assignment of properties of fibrous tissue even to media and adventitia layers as done in some studies may induce up to eightfold overestimation of peak stress. The impact of MRI slice thickness may play a key role when local thin fibrous cap is present. Anisotropy of media layer is insignificant, and the stiffness of fibrous tissue and lipid core may become significant in some combinations.


Assuntos
Artérias Carótidas/patologia , Fenômenos Mecânicos , Modelagem Computacional Específica para o Paciente , Placa Aterosclerótica/patologia , Fenômenos Biomecânicos , Artérias Carótidas/diagnóstico por imagem , Análise de Elementos Finitos , Humanos , Imagem por Ressonância Magnética , Modelos Cardiovasculares , Placa Aterosclerótica/diagnóstico por imagem
4.
Asian Cardiovasc Thorac Ann ; 28(8): 520-532, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32878458

RESUMO

Computational fluid dynamics has become an important tool for studying blood flow dynamics. As an in-silico collection of methods, computational fluid dynamics is noninvasive and provides numerical values for the most important parameters of blood flow, such as velocity and pressure that are crucial in hemodynamic studies. In this primer, we briefly explain the basic theory and workflow of the two most commonly applied computational fluid dynamics techniques used in the congenital heart disease literature: the finite element method and the finite volume method. We define important terminology and include specific examples of how using these methods can answer important clinical questions in congenital cardiac surgery planning and perioperative patient management.


Assuntos
Cardiopatias Congênitas/diagnóstico por imagem , Hemodinâmica , Modelos Cardiovasculares , Modelagem Computacional Específica para o Paciente , Tomada de Decisão Clínica , Cardiopatias Congênitas/fisiopatologia , Cardiopatias Congênitas/terapia , Humanos , Hidrodinâmica , Valor Preditivo dos Testes
5.
Khirurgiia (Mosk) ; (8): 103-106, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32869622

RESUMO

The authors describe modern 3D technologies in hepatobiliary surgery. These approaches reduce the risk of intra- and postoperative complications. Virtual 3D reconstruction with clear visualization of parasitic cyst, adjacent vessels and bile ducts is valuable to create 3D-model of liver. This model may be applied for personalized laparoscopic approach and precise surgical intervention.


Assuntos
Procedimentos Cirúrgicos do Sistema Biliar/métodos , Hepatectomia/métodos , Imageamento Tridimensional , Fígado/cirurgia , Cirurgia Assistida por Computador , Ductos Biliares/diagnóstico por imagem , Ductos Biliares/cirurgia , Humanos , Laparoscopia , Fígado/diagnóstico por imagem , Modelagem Computacional Específica para o Paciente , Complicações Pós-Operatórias/prevenção & controle
6.
Ann Vasc Surg ; 69: 400-412, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32738387

RESUMO

BACKGROUND: To examine intraheartbeat displacements (IHD) and geometrical changes of endografts for abdominal aortic aneurysm repair over the course of years, defined as follow-up displacements (FUD), and to correlate them with computational fluid dynamics (CFD). Despite the widespread use of endovascular aneurysm repair (EVAR), we still know little about endograft behavior after deployment. METHODS: Two cases, treated with either expanded polytetrafluoroethylene on a nitinol stent frame (PI) or with woven polyester fabric sutured to a stainless-steel Z stent skeleton (PII), were submitted to dynamic computed tomography angiography at 1, 12, and 60 months after implantation. After segmentation, IHD were computed as displacements of the reconstructed surface with respect to the diastolic instant. Similarly, FUD were studied using imaging techniques that align temporal successive segmentations. In addition, numerical simulations for blood dynamics were performed to compute viscous forces, specifically wall shear stress and time-averaged wall shear stress (TAWSS). RESULTS: IHD analysis showed slight translations without deformation for the PI endograft with respect to the stiffer stainless-steel endograft behavior of PII. FUD showed in PI motion of the metallic struts mainly focused on the distal main body of the endograft and in the zone overlapping with iliac branches. In PII, we observed a huge FUD in the middle and inferior-anterior regions of the main body. CFD analysis revealed changes of velocity patterns associated with remodeling of the iliac zone for PI and of the main body region for PII, where flow impinges the lumen wall and progressively induces deformation of the endograft wires. Measurement of TAWSS demonstrated flow disturbances in the enlarged region correlated with displacement analysis. CONCLUSIONS: Image-based displacement analysis associated with CFD enabled very subtle evaluations of endograft behavior on different temporal scales. This kind of study could be helpful both for physicians, forecasting evolution during the life span of the endograft, and manufacturers, giving them useful information about endograft implant performance and design.


Assuntos
Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Técnicas de Imagem de Sincronização Cardíaca , Procedimentos Endovasculares/instrumentação , Modelos Cardiovasculares , Modelagem Computacional Específica para o Paciente , Stents , Idoso , Ligas , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/fisiopatologia , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/fisiopatologia , Aortografia , Angiografia por Tomografia Computadorizada , Eletrocardiografia , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Poliésteres , Politetrafluoretileno , Valor Preditivo dos Testes , Desenho de Prótese , Fluxo Sanguíneo Regional , Aço Inoxidável , Estresse Mecânico , Fatores de Tempo , Resultado do Tratamento
7.
Eur J Vasc Endovasc Surg ; 60(4): 539-547, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32741677

RESUMO

OBJECTIVE: The rupture of abdominal aortic aneurysms (AAAs) is associated with high mortality despite surgical developments. The determination of aneurysm diameter allows for follow up of aneurysm growth but fails in precisely predicting aneurysm rupture. In this study, time resolved three dimensional ultrasound (4D ultrasound) based wall motion indices (WMIs) are investigated to see if they are capable of distinguishing between uneven affected regions of the aneurysm wall. METHODS: In a prospective study, 56 patients with an AAA were examined using 4D ultrasound. Local longitudinal, circumferential, and shear strains were computed using custom methods. The deformation of the neck and sac of each aneurysm was characterised by statistical indices of the obtained distributions of local wall strains (WMIs): mean and peak strain, heterogeneity index, and local strain ratio. The locations of regions with highest local peak strain were determined. RESULTS: Compared with the aneurysm neck, the sac is characterised by low mean strain, but highly heterogeneous deformation, described by high local strain ratio and heterogeneity index. Differences were highly significant (p < .001) for all strain components. The regions with the highest circumferential peak strain were found more often in the posterior part of the aneurysm neck (p < .050) and sac (p < .001) regions, compared with other wall regions. No statistically significant correlation was found between the WMIs and maximum AAA diameter, except for longitudinal mean strain, which decreased with the increasing diameter (rho = -.42, p < .010). CONCLUSION: Characterisation of wall kinematics by 4D ultrasound based WMIs provides a new and independent criterion for the distinction of diseased tissue in the AAA sac and the less affected neck region. This is a promising step towards the establishment of new biomarkers to differentiate between the mechanical instability of the AAA and rupture risk.


Assuntos
Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador , Modelos Cardiovasculares , Modelagem Computacional Específica para o Paciente , Ultrassonografia , Idoso , Idoso de 80 Anos ou mais , Aorta Abdominal/fisiopatologia , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/fisiopatologia , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/etiologia , Ruptura Aórtica/fisiopatologia , Fenômenos Biomecânicos , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores de Risco , Estresse Mecânico
8.
Curr Protoc Stem Cell Biol ; 54(1): e118, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32640120

RESUMO

The normal development of the pulmonary system is critical to transitioning from placental-dependent fetal life to alveolar-dependent newborn life. Human lung development and disease have been difficult to study due to the lack of an in vitro model system containing cells from the large airways and distal alveolus. This article describes a system that allows human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) to differentiate and form three-dimensional (3D) structures that emulate the development, cytoarchitecture, and function of the lung ("organoids"), containing epithelial and mesenchymal cell populations, and including the production of surfactant and presence of ciliated cells. The organoids can also be invested with mesoderm derivatives, differentiated from the same human pluripotent stem cells, such as alveolar macrophages and vasculature. Such lung organoids may be used to study the impact of environmental modifiers and perturbagens (toxins, microbial or viral pathogens, alterations in microbiome) or the efficacy and safety of drugs, biologics, and gene transfer. © 2020 Wiley Periodicals LLC. Basic Protocol: hESC/hiPSC dissection, definitive endoderm formation, and lung progenitor cell induction.


Assuntos
Infecções por Coronavirus/patologia , Pulmão/citologia , Organoides/citologia , Pneumonia Viral/patologia , Infecções Respiratórias/patologia , Betacoronavirus , Técnicas de Cultura de Células , Diferenciação Celular , Infecções por Coronavirus/terapia , Endoderma/citologia , Células-Tronco Embrionárias Humanas/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Pulmão/crescimento & desenvolvimento , Pulmão/fisiologia , Modelos Biológicos , Pandemias , Modelagem Computacional Específica para o Paciente , Pneumonia Viral/terapia , Infecções Respiratórias/terapia , Imagem com Lapso de Tempo
9.
J Am Acad Orthop Surg ; 28(17): e735-e743, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32649439

RESUMO

The emergence of COVID-19 as a viral pandemic in early 2020 resulted in notable changes to the daily practice, workflow, and education of orthopaedic residencies internationally. In particular, social distancing, residency restructuring, and redeployment to other services has increased heterogeneity in schedules and made the in-person gathering of trainees for education increasingly challenging. These changes may last until 2024 based on some mathematical models, resulting in notable disruptions to orthopaedic education, especially for junior residents. Therefore, in this study, we describe how we converted our in-person PGY-1 skills course into a "virtual" boot camp based on validated training modules and existing American Board of Orthopaedic Surgeons guidelines. Lessons learned from the experience and potential areas for improvement in the use of newer technology to teach cognitive knowledge and skills modules are highlighted with the hope that this can be useful to other orthopaedic residency programs, during the pandemic and also beyond.


Assuntos
Competência Clínica , Infecções por Coronavirus/prevenção & controle , Educação de Pós-Graduação em Medicina/organização & administração , Internato e Residência/métodos , Procedimentos Ortopédicos/educação , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Realidade Virtual , Adulto , Controle de Doenças Transmissíveis/métodos , Infecções por Coronavirus/epidemiologia , Currículo , Feminino , Humanos , Internato e Residência/tendências , Masculino , Pandemias/estatística & dados numéricos , Modelagem Computacional Específica para o Paciente , Pneumonia Viral/epidemiologia
10.
Methodist Debakey Cardiovasc J ; 16(2): 130-137, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670473

RESUMO

Structural heart interventions (SHIs) are increasingly applicable in a wide range of heart defects, but the intricate and dynamic nature of cardiac structures can make SHIs challenging to perform. Three-dimensional (3D) printed modeling integrates advanced clinical imaging and 3D printing technology to replicate patient-specific anatomy for comprehensive planning and simulation of SHIs. This review discusses the basic principles of patient-specific 3D print model development, print material selection, and model fabrication and highlights how cardiovascular 3D printing can be used in preprocedural planning, device sizing, enhanced communication, and procedure simulation.


Assuntos
Procedimentos Cirúrgicos Cardíacos/tendências , Cardiopatias/diagnóstico por imagem , Cardiopatias/cirurgia , Modelos Cardiovasculares , Modelagem Computacional Específica para o Paciente/tendências , Impressão Tridimensional/tendências , Difusão de Inovações , Previsões , Cardiopatias/fisiopatologia , Humanos
11.
PLoS One ; 15(7): e0233877, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32645021

RESUMO

BACKGROUND: The impact of nutritional supplements on weight gain in HIV-infected children on antiretroviral treatment (ART) remains uncertain. Starting supplements depends upon current weight-for-age or other acute malnutrition indicators, producing time-dependent confounding. However, weight-for-age at ART initiation may affect subsequent weight gain, independent of supplement use. Implications for marginal structural models (MSMs) with inverse probability of treatment weights (IPTW) are unclear. METHODS: In the ARROW trial, non-randomised supplement use and weight-for-age were recorded monthly from ART initiation. The effect of supplements on weight-for-age over the first year was estimated using generalised estimating equation MSMs with IPTW, both with and without interaction terms between baseline weight-for-age and time. Separately, data were simulated assuming no supplement effect, with use depending on current weight-for-age, and weight-for-age trajectory depending on baseline weight-for-age to investigate potential bias associated with different MSM specifications. RESULTS: In simulations, despite correctly specifying IPTW, omitting an interaction in the MSM between baseline weight-for-age and time produced increasingly biased estimates as associations between baseline weight-for-age and subsequent weight trajectory increased. Estimates were unbiased when the interaction between baseline weight-for-age and time was included, even if the data were simulated with no such interaction. In ARROW, without an interaction the estimated effect was +0.09 (95%CI +0.02,+0.16) greater weight-for-age gain per month's supplement use; this reduced to +0.03 (-0.04,+0.10) including the interaction. DISCUSSION: This study highlights a specific situation in which MSM model misspecification can occur and impact the resulting estimate. Since an interaction in the MSM (outcome) model does not bias the estimate of effect if the interaction does not exist, it may be advisable to include such a term when fitting MSMs for repeated measures.


Assuntos
Infecções por HIV/dietoterapia , Apoio Nutricional/métodos , Ganho de Peso/efeitos dos fármacos , Antirretrovirais/uso terapêutico , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Pré-Escolar , Suplementos Nutricionais/análise , Feminino , HIV/patogenicidade , Infecções por HIV/metabolismo , Humanos , Lactente , Masculino , Modelos Estatísticos , Modelagem Computacional Específica para o Paciente , Projetos de Pesquisa
12.
Am J Physiol Heart Circ Physiol ; 319(2): H432-H442, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32618514

RESUMO

Pulmonary artery (PA) morphometry has been extensively explored in adults, with particular focus on intra-acinar arteries. However, scaling law relationships for length and diameter of extensive preacinar PAs by age have not been previously reported for in vivo human data. To understand preacinar PA growth spanning children to adults, we performed morphometric analyses of all PAs visible in the computed tomography (CT) and magnetic resonance (MR) images from a healthy subject cohort [n = 16; age: 1-51 yr; body surface area (BSA): 0.49-2.01 m2]. Subject-specific anatomic PA models were constructed from CT and MR images, and morphometric information-diameter, length, tortuosity, bifurcation angle, and connectivity-was extracted and sorted into diameter-defined Strahler orders. Validation of Murray's law, describing optimal scaling exponents of radii for branching vessels, was performed to determine how closely PAs conform to this classical relationship. Using regression analyses of vessel diameters and lengths against orders and patient metrics (BSA, age, height), we found that diameters increased exponentially with order and allometrically with patient metrics. Length increased allometrically with patient metrics, albeit weakly. The average tortuosity index of all vessels was 0.026 ± 0.024, average bifurcation angle was 28.2 ± 15.1°, and average Murray's law exponent was 2.92 ± 1.07. We report a set of scaling laws for vessel diameter and length, along with other morphometric information. These provide an initial understanding of healthy structural preacinar PA development with age, which can be used for computational modeling studies and comparison with diseased PA anatomy.NEW & NOTEWORTHY Pulmonary artery (PA) morphometry studies to date have focused primarily on large arteries and intra-acinar arteries in either adults or children, neglecting preacinar arteries in both populations. Our study is the first to quantify in vivo preacinar PA morphometry changes spanning infants to adults. For preacinar arteries > 1 mm in diameter, we identify scaling laws for vessel diameters and lengths with patient metrics of growth and establish a healthy PA morphometry baseline for most preacinar PAs.


Assuntos
Envelhecimento , Angiografia por Tomografia Computadorizada , Angiografia por Ressonância Magnética , Modelos Cardiovasculares , Modelagem Computacional Específica para o Paciente , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/crescimento & desenvolvimento , Adolescente , Adulto , Fatores Etários , Estatura , Superfície Corporal , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Adulto Jovem
13.
Am J Physiol Heart Circ Physiol ; 319(2): H360-H369, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32678708

RESUMO

Proper inlet boundary conditions are essential for accurate computational fluid dynamics (CFD) modeling. We developed methodology to derive noninvasive FFRB using CFD and computed tomography coronary angiography (CTCA) images. This study aims to assess the influence of brachial mean blood pressure (MBP) and total coronary inflow on FFRB computation. Twenty-two patients underwent both CTCA and FFR measurements. Total coronary flow was computed from left ventricular mass (LVM) measured from CTCA. A total of 286 CFD simulations were run by varying MBP and LVM at 70, 80, 90, 100, 110, 120, and 130% of the measured values. FFRB increased with incrementally higher input values of MBP: 0.78 ± 0.12, 0.80 ± 0.11, 0.82 ± 0.10, 0.84 ± 0.09, 0.85 ± 0.08, 0.86 ± 0.08, and 0.87 ± 0.07, respectively. Conversely, FFRB decreased with incrementally higher inputs value of LVM: 0.86 ± 0.08, 0.85 ± 0.08, 0.84 ± 0.09, 0.84 ± 0.09, 0.83 ± 0.10, 0.83 ± 0.10, and 0.82 ± 0.10, respectively. Noninvasive FFRB calculated using measured MBP and LVM on a total of 30 vessels was 0.84 ± 0.09 and correlated well with invasive FFR (0.83 ± 0.09) (r = 0.92, P < 0.001). Positive association was observed between FFRB and MBP input values (mmHg) and negative association between FFRB and LVM values (g). Respective slopes were 0.0016 and -0.005, respectively, suggesting potential application of FFRB in a clinical setting. Inaccurate MBP and LVM inputs differing from patient-specific values could result in misclassification of borderline ischemic lesions.NEW & NOTEWORTHY While brachial mean blood pressure (MBP) and left ventricular mass (LVM) measured from CTCA are the two CFD simulation input parameters, their effects on noninvasive fractional flow reserve (FFRB) have not been systematically investigated. We demonstrate that inaccurate MBP and LVM inputs differing from patient-specific values could result in misclassification of borderline ischemic lesions. This is important in the clinical application of noninvasive FFR in coronary artery disease diagnosis.


Assuntos
Pressão Arterial , Artéria Braquial/fisiopatologia , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Reserva Fracionada de Fluxo Miocárdico , Ventrículos do Coração/diagnóstico por imagem , Modelos Cardiovasculares , Tomografia Computadorizada Multidetectores , Modelagem Computacional Específica para o Paciente , Interpretação de Imagem Radiográfica Assistida por Computador , Idoso , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/fisiopatologia , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Hidrodinâmica , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos
15.
Circ Arrhythm Electrophysiol ; 13(7): e008213, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32536204

RESUMO

BACKGROUND: Pulmonary vein isolation (PVI) is an effective treatment strategy for patients with atrial fibrillation (AF), but many experience AF recurrence and require repeat ablation procedures. The goal of this study was to develop and evaluate a methodology that combines machine learning (ML) and personalized computational modeling to predict, before PVI, which patients are most likely to experience AF recurrence after PVI. METHODS: This single-center retrospective proof-of-concept study included 32 patients with documented paroxysmal AF who underwent PVI and had preprocedural late gadolinium enhanced magnetic resonance imaging. For each patient, a personalized computational model of the left atrium simulated AF induction via rapid pacing. Features were derived from pre-PVI late gadolinium enhanced magnetic resonance images and from results of simulations of AF induction. The most predictive features were used as input to a quadratic discriminant analysis ML classifier, which was trained, optimized, and evaluated with 10-fold nested cross-validation to predict the probability of AF recurrence post-PVI. RESULTS: In our cohort, the ML classifier predicted probability of AF recurrence with an average validation sensitivity and specificity of 82% and 89%, respectively, and a validation area under the curve of 0.82. Dissecting the relative contributions of simulations of AF induction and raw images to the predictive capability of the ML classifier, we found that when only features from simulations of AF induction were used to train the ML classifier, its performance remained similar (validation area under the curve, 0.81). However, when only features extracted from raw images were used for training, the validation area under the curve significantly decreased (0.47). CONCLUSIONS: ML and personalized computational modeling can be used together to accurately predict, using only pre-PVI late gadolinium enhanced magnetic resonance imaging scans as input, whether a patient is likely to experience AF recurrence following PVI, even when the patient cohort is small.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Diagnóstico por Computador , Aprendizado de Máquina , Imagem por Ressonância Magnética , Modelos Cardiovasculares , Modelagem Computacional Específica para o Paciente , Veias Pulmonares/cirurgia , Potenciais de Ação , Idoso , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/fisiopatologia , Meios de Contraste/administração & dosagem , Feminino , Frequência Cardíaca , Humanos , Masculino , Meglumina/administração & dosagem , Meglumina/análogos & derivados , Pessoa de Meia-Idade , Compostos Organometálicos/administração & dosagem , Valor Preditivo dos Testes , Estudo de Prova de Conceito , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/fisiopatologia , Recidiva , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento
16.
Jt Dis Relat Surg ; 31(2): 273-280, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584725

RESUMO

OBJECTIVES: This study aims to determine the role of computed tomography (CT)-derived templates, produced by three- dimensional (3D) modeling, image processing and printing technology, in percutaneous transsacral screw fixation and evaluate the effects of their use on surgical success. MATERIALS AND METHODS: This prospective study conducted between June 2018 and December 2019 utilized 15 composite pelvis models for transsacral-transiliac screw fixation. For the procedure, modeled templates were utilized for wiring on the left side of the pelvis models, while the conventional method was performed on the right side of the pelvis models. In the computed tomography images acquired after wiring, appropriate wire position was evaluated. RESULTS: The placed wires held the S1 body appropriately in all of the procedures with or without template use. With the template use, the wires were placed appropriately in the surgical bone corridor suitable for the transsacral-transiliac screw fixation in all of the models. However, with the conventional methods, the wires were not placed in the safe surgical bone corridor in four models. The wire deviation angle in the axial plane was significantly lower in the template group (p=0.001), whereas it was not different between the template group and the conventional method group in the coronal plane (p=0.054). The amount of deviation from the ideal wire entry site was significantly reduced in the template group compared to the conventional method group (p=0.001). CONCLUSION: With the use of 3D modeling and printing technology, CT-derived templates can be produced and utilized for transsacral screw fixation procedures and their use increases surgical success by reducing the surgical margin of error.


Assuntos
Fixação Interna de Fraturas , Ossos Pélvicos , Impressão Tridimensional , Sacro/cirurgia , Tomografia Computadorizada por Raios X/métodos , Parafusos Ósseos , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Humanos , Processamento de Imagem Assistida por Computador , Modelagem Computacional Específica para o Paciente , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/lesões , Ossos Pélvicos/cirurgia , Estudos Prospectivos
17.
Khirurgiia (Mosk) ; (6): 71-75, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32573535

RESUMO

OBJECTIVE: To develop a technique of computer modeling of hemodynamics before conventional CEE. MATERIAL AND METHODS: Classical CEE is performed according to conventional patch technique. Duplex parameters of stenosis and blood flow velocity in the carotid arteries were analyzed by using of a linear transducer 7-7.5 MG (Acuson 128XP scanner, Acuson, USA). Multispiral computed tomography with angiography and subsequent processing of data using the Clear canvas software were performed to visualize the main geometric characteristics of the carotid arteries and features of atherosclerotic plaque. RESULTS: Blood flow hemodynamics is essential in the occurrence of postoperative restenosis. Therefore, computer simulation of blood flow using CFD (Computational Fluid Dynamics) methods based on particular patient's data makes it possible to assess localization of zones with high risk of restenosis. CFD approach implies construction of blood flow parameters at absolutely every point of the vessel considering geometric shape of the vessel and flow characteristics at the entrance and exit from the vessel. Pressure curves at the inlet and outlet are constructed using blood flow velocity curves. Pressure curves are subsequently used in the CFD model. The result of blood flow CFD modeling is non-stationary three-dimensional fields of pressure and velocity in the investigated area. Visual analysis of blood flow dynamics in these fields makes it possible to judge possible problem areas along the blood flow and on the inner wall of the vessel. DISCUSSION: Patch technique of classical CEE is characterized by great risk of parietal thrombosis and hyperproliferation of neointima that explains more frequent development of restenosis. Computer modeling is valuable to consider some important technical aspects in implementation of various surgical techniques for carotid artery reconstruction. CONCLUSION: This result demonstrates an importance of achieving the optimal ratio of the diameter of common, internal and external carotid arteries. Modification of patch based on computer simulation is required for these purposes.


Assuntos
Artérias Carótidas/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Endarterectomia das Carótidas/efeitos adversos , Modelagem Computacional Específica para o Paciente , Ultrassonografia Doppler Dupla/métodos , Velocidade do Fluxo Sanguíneo , Artérias Carótidas/fisiopatologia , Estenose das Carótidas/fisiopatologia , Estenose das Carótidas/cirurgia , Revascularização Cerebral/efeitos adversos , Revascularização Cerebral/métodos , Circulação Cerebrovascular , Endarterectomia das Carótidas/métodos , Hemodinâmica , Humanos , Hidrodinâmica , Prevenção Secundária
18.
Zhonghua Wai Ke Za Zhi ; 58(6): 457-463, 2020 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-32498486

RESUMO

Objective: To examine the clinical effects of the treatment of knee osteoarthritis patients with kinematic alignment technique of total knee replacement (KA-TKA) assisted by patient-specific instrumentation (PSI). Methods: The clinical data of 14 patients with knee osteoarthritis treated with unilateral KA-TKA assisted by PSI at Department of Orthopaedic Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University from May 2018 to August 2019 were analyzed retrospectively. There were 6 males and 8 females, aged 66.6 years (range: 56 to 79 years), 9 left knees and 5 right knees. The operation time, soft tissue release and extra varus or valgus osteotomy were recorded. The data of osteotomy blocks were measured and compared with the corresponding position of the prostheses. The hip knee ankle angle (HKA), the mechanical distal femoral lateral angle (mLDFA) and the proximal tibial medial angle (MPTA) were measured before and 3 months after the operation. The knee joint functional score (KS-F) , knee joint clinical score (KS-C) and the Western Ontario McMaster (WOMAC) Osteoarthritis Index were recorded and compared by paired t test or Wilcoxon non-parametric test. Results: The operation time was (81.8±16.9) minutes (range: 60 to 115 minutes), 2 cases were manually increased varus osteotomy by 2 mm and 1 patient received lateral retinaculum release. There was no extra medial or lateral soft tissue release. Intraoperative measurement of the resection showed that the femoral side mismatch was within 2 mm. The medial and lateral condyle, the medial and lateral posterior condyles were relatively overcut by 0.50 mm, 0.21 mm, 0.93 mm, and 0.71 mm, respectively. The tibial side mismatch was within 1.5 mm, the medial and lateral plateau were relatively undercut by 0.43 mm and 0.32 mm. HKA was corrected from (8.8±5.6) ° to (1.6±4.3) ° (t=20.723, P=0.000) .KS-C improved from 28.21±13.47 preoperative to 78.07±8.01 postoperative (t=-16.570, P=0.000); KS-F improved from 41.00±15.25 preoperative to 84.93±10.85 postoperative (t=-14.675, P=0.000).WOMAC Osteoarthritis Index decreased from 53.5 (25.75) (M(Q(R))) preoperative to 5.5 (5.25) postoperative (Z=-3.297, P=0.001) .No statistically significant difference was found in mLDFA and MPTA before and after surgery. No significant patellofemoral complication was recorded during follow-up time. Conclusions: PSI assisted TKA resection has high accuracy. KA-TKA aims to restore the native anatomy of the knee joint, only corrects the malalignment of lower extremities caused by articular cartilage wear, with less interference to soft tissues, easy to obtain satisfactory knee joint laxity and has a promising early clinical effect.


Assuntos
Artroplastia do Joelho/instrumentação , Artroplastia do Joelho/métodos , Osteoartrite do Joelho/cirurgia , Idoso , Fenômenos Biomecânicos , Mau Alinhamento Ósseo/etiologia , Mau Alinhamento Ósseo/prevenção & controle , Feminino , Humanos , Articulação do Joelho/fisiopatologia , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/fisiopatologia , Modelagem Computacional Específica para o Paciente , Estudos Retrospectivos , Cirurgia Assistida por Computador
19.
J Endovasc Ther ; 27(3): 385-393, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32517556

RESUMO

Purpose: To summarize the experience and outcomes of total endovascular repair of thoracoabdominal aortic disease using 3-dimensional (3D) printed models to guide on-site creation of fenestrations in aortic stent-grafts. Materials and Methods: From April 2018 to March 2019, 34 patients (mean age 58±14 years; 24 men) with thoracoabdominal aortic disease were treated in our department. Nineteen patients had thoracoabdominal aortic dissection and 15 had thoracoabdominal aortic aneurysm. Preoperatively, a 3D printed model of the aorta was made according to computed tomography images. In the operating room, the main aortic stent-graft was completely released in the 3D printed model, and the position of each fenestration or branch was marked on the stent-graft. The fenestrations were then made using an electric pen. Wires were sewn to the edge of the fenestrations using nonabsorbable sutures. After customization, the aortic stent-graft was reloaded into the delivery sheath and deployed. Results: The printing process took ~5 hours (1 hour for image reconstruction, 3 hours for printing, and 1 hour for postprocessing). The physician-modified stent-grafts had a total of 107 fenestrations secured by 102 bridging stent-grafts, including 73 covered stents and 29 bare stents. The average procedure time was 5.6±1.2 hours, including a mean 1.3 hours for stent-graft customization. No renal insufficiency or paraplegia occurred. Two branch arteries were lost during the operation. One patient (3%) died 1 week after surgery from a retrograde dissection rupture. One patient developed a minor cerebral infarction postoperatively. The mean follow-up time was 8.5 months. There was 1 endoleak from a fenestration (coil embolized) and 4 distal ruptures of the aortic dissection (3 treated and 1 observed). Conclusion: Three-dimensional printing can be used to guide creation of fenestrated stent-grafts for the treatment of thoracoabdominal aortic diseases involving crucial branches. This technique appears to be more accurate than the traditional measurement method, with short-term follow-up demonstrating the safety and reliability of the method. However, further research and development are needed.


Assuntos
Aneurisma Dissecante/cirurgia , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Desenho Assistido por Computador , Procedimentos Endovasculares/instrumentação , Impressão Tridimensional , Desenho de Prótese , Stents , Adulto , Idoso , Aneurisma Dissecante/diagnóstico por imagem , Aneurisma Dissecante/fisiopatologia , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/fisiopatologia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/fisiopatologia , Aortografia , Implante de Prótese Vascular/efeitos adversos , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Anatômicos , Modelos Cardiovasculares , Modelagem Computacional Específica para o Paciente , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Fluxo de Trabalho
20.
Phys Med Biol ; 65(18): 185004, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32460261

RESUMO

Motivation and objective. For each institute, the selection and calibration of the most suitable approach to assign material properties for Monte Carlo (MC) patient simulation in proton therapy is a major challenge. Current conventional approaches based on computed tomography (CT) depend on CT acquisition and reconstruction settings. This study proposes a material assignment approach, referred to as MATA (MATerial Assignment), which is independent of CT scanner properties and, therefore, universally applicable by any institute. MATERIALS AND METHODS: The MATA approach assigns material properties to the physical quantity stopping-power ratio (SPR) using a set of 40 material compositions specified for human tissues and linearly determined mass density. The application of clinically available CT-number-to-SPR conversion avoids the need for any further calibration. The MATA approach was validated with homogeneous and heterogeneous SPR datasets by assessing the SPR accuracy after material assignment obtained either based on dose scoring or determination of water-equivalent thickness. Finally, MATA was applied on patient datasets to evaluate dose differences induced by different approaches for material assignment and SPR prediction. RESULTS: The deviation between the SPR after material assignment and the input SPR was close to zero in homogeneous datasets and below 0.002 (0.2% relative to water) in heterogeneous datasets, which was within the systematic uncertainty in SPR estimation. The comparison of different material assignment approaches revealed relevant differences in dose distribution and SPR. The comparison between two SPR prediction approaches, a standard look-up table and direct SPR determination from dual-energy CT, resulted in patient-specific mean proton range shifts between 1.3 mm and 4.8 mm. CONCLUSION: MATA eliminates the need for institution-specific adaptations of the material assignment. It allows for using any SPR dataset and thus facilitates the implementation of more accurate SPR prediction approaches. Hence, MATA provides a universal solution for patient modeling in MC-based proton treatment planning.


Assuntos
Método de Monte Carlo , Modelagem Computacional Específica para o Paciente , Terapia com Prótons , Planejamento da Radioterapia Assistida por Computador/métodos , Calibragem , Humanos , Modelos Biológicos , Tomografia Computadorizada por Raios X , Incerteza
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