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1.
Neuroradiology ; 65(7): 1155-1163, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37022485

RESUMO

PURPOSE: Abnormal venous drainage may affect the prognosis of patients undergoing endovascular reperfusion therapy (ERT). Herein, time-resolved dynamic computed tomography arteriography (dCTA) was applied to evaluate the relationship between the velocity and extent of cortical venous filling (CVF), collateral status and outcomes. METHODS: Thirty-five consecutive patients with acute anterior circulation occlusion who underwent ERT within 24 h of onset and successfully recanalized were enrolled. All patients underwent dCTA before ERT. Slow first or end of CVF was considered to occur when the time point of CVF appearance or disappearance on the affected side occurred after than that on the healthy side, whereas an equal CVF, a CVF reduced by ≤ 50%, or by > 50% on the affected side, were considered good, intermediate, and poor CVF extent, respectively. RESULTS: Slow first CVF (29 patients, 82.8%), slow end of CVF (29, 85.7%), and intermediate extent of CVF (7, 20.0%) were not associated with collateral status or outcomes. Poor extent of CVF (6, 17.1%) was associated with poor collateral status, higher proportion of midline shift, larger final infarct volume, higher modified Rankin Scale (mRS) score at discharge, and higher proportion of in-hospital mortality. All patients with transtentorial herniation had poor extent of CVF, and those with poor CVF extent had an mRS score ≥ 3 at discharge. CONCLUSION: Poor CVF extent, as assessed by dCTA, is a more accurate and specific marker than slow CVF to identify patients at high risk for poor outcomes after ERT.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Arquivamento , Resultado do Tratamento , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Procedimentos Endovasculares/métodos , Isquemia Encefálica/terapia , Circulação Colateral , Estudos Retrospectivos
2.
BMC Neurol ; 20(1): 413, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33183248

RESUMO

BACKGROUND: Contrast encephalopathy is a rare complication of carotid artery stenting (CAS). Contrast encephalopathy is a diagnosis of exclusion that often needs to be distinguished from high perfusion syndrome, cerebral haemorrhage, subarachnoid haemorrhage (SAH), cerebral infarction and so on. CASE PRESENTATION: In this study, we report on a 70-year-old man who was admitted to the hospital with transient ischaemic attacks presenting paroxysmal weakness of limbs in the previous 2 years. He had severe stenosis of the left internal carotid artery diagnosed by digital subtraction angiography (DSA) and underwent CAS. Two hours after the operation, the patient developed paralysis of the right upper limb, unclear speech, fever and restlessness. Emergency skull computed tomography (CT) showed swelling and a linear high-density area in the left cerebral hemisphere. To clarify the components of this high-density area in the traditional CT, the patient had spectral CT, which made the diagnosis of the leakage of contrast clear. After 1 week of supportive treatment, the patient improved. CONCLUSIONS: Spectral CT can easily distinguish the components of high-density areas on traditional CT, which is haemorrhage, calcification or iodine contrast leakage. Therefore, spectral CT is worth consideration for the differential diagnosis of complications of vascular intervention.


Assuntos
Encefalopatias , Artéria Carótida Interna/cirurgia , Meios de Contraste/efeitos adversos , Tomografia Computadorizada por Raios X , Idoso , Angiografia Digital/efeitos adversos , Encefalopatias/induzido quimicamente , Encefalopatias/diagnóstico por imagem , Artéria Carótida Interna/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Humanos , Masculino
3.
Eur Neurol ; 83(2): 121-130, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32544913

RESUMO

BACKGROUND: Cerebral infarction caused by pituitary apoplexy (PA) is rare. To characterize the clinical features of cerebral infarction caused by PA, we performed a systematic review. SUMMARY: The clinical symptoms are mainly sudden headache, hemiplegia, visual impairment, disturbance of consciousness, and ophthalmalgia in patients with cerebral infarction caused by PA. Treatment for this type of infarction is different from treatment for general acute cerebral infarction. Compared to patients who underwent emergency surgery and conservative treatment, patients treated with delayed surgery showed a better prognosis and a lower mortality rate. Compared to patients who underwent craniotomy or conservative treatment, patients who underwent transsphenoidal surgery (TSS) not only improved well but also showed a lower mortality rate. Key Messages: PA rarely causes cerebral infarction, which is a critical condition with a poor prognosis and is more common in men. Delayed surgery and TSS appear to confer a better prognosis in patients with this condition.


Assuntos
Infarto Cerebral/etiologia , Apoplexia Hipofisária/complicações , Infarto Cerebral/terapia , Humanos , Pessoa de Meia-Idade
4.
Kidney Int ; 95(1): 149-159, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30470436

RESUMO

Fabry disease results from loss of activity of the lysosomal enzyme α-galactosidase A (GLA), leading to the accumulation of globoseries glycosphingolipids in vascular endothelial cells. Thrombosis and stroke are life-threatening complications of Fabry disease; however, the mechanism of the vasculopathy remains unclear. We explored the relationship between GLA deficiency and endothelial cell von Willebrand factor (VWF) secretion in in vivo and in vitro models of Fabry disease. Plasma VWF was significantly higher at two months and increased with age in Gla-null compared to wild-type mice. Disruption of GLA in a human endothelial cell line by siRNA and CRISPR/Cas9 resulted in a 3-fold and 5-fold increase in VWF secretion, respectively. The increase in VWF levels was associated with decreased endothelial nitric oxide synthase (eNOS) activity in both in vitro models. Pharmacological approaches that increase nitric oxide bioavailability or decrease reactive oxygen species completely normalized the elevated VWF secretion in GLA deficient cells. In contrast, the abnormality was not readily reversed by recombinant human GLA or by inhibition of glycosphingolipid synthesis with eliglustat. These results suggest that GLA deficiency promotes VWF secretion through eNOS dysregulation, which may contribute to the vasculopathy of Fabry disease.


Assuntos
Doença de Fabry/patologia , alfa-Galactosidase/metabolismo , Fator de von Willebrand/metabolismo , Animais , Linhagem Celular , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Doença de Fabry/genética , Glucosiltransferases/antagonistas & inibidores , Glucosiltransferases/metabolismo , Glicoesfingolipídeos/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Pirrolidinas/farmacologia , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , alfa-Galactosidase/genética
5.
Med Sci Monit ; 25: 3839-3845, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31120864

RESUMO

BACKGROUND The incidence of ischemic stroke increases in winter. This study aimed to explore the effect of winter temperatures on the risk factors, etiology, coagulation, and degree of neurological impairment in patients with ischemic stroke using temperature and rainfall data from the Guangzhou Meteorological Bureau during the winter months of December, January, and February. MATERIAL AND METHODS We divided 112 patients with ischemic stroke into low-temperature and non-low-temperature groups. The low-temperature group experienced an average daily winter temperature of <13°C for five consecutive days within the 14 days before hospital admission and an average temperature of <13°C on admission. The non-low-temperature group experienced an average daily temperature of >13°C in the 14 days before hospital admission and an average daily temperature of >13°C on admission. Neurological deficits were scored and monitored using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) for disability in stroke. Blood pressure and coagulation indices of prothrombin time (PT) and thromboplastin time (TT) were recorded. RESULTS Compared with the non-low-temperature group, the low-temperature group showed a significantly increased proportion of patients with hypertension and large artery atherosclerotic stroke, more prolonged PT, and higher NIHSS scores. However, TT was reduced in the low-temperature group (P<0.05). CONCLUSIONS When the average winter temperature was <13°C, the risk factors, etiology, coagulation factors, and degree of neurological impairment of patients with ischemic stroke were significantly different from patients with ischemic stroke during warmer temperature.


Assuntos
Temperatura Baixa/efeitos adversos , Acidente Vascular Cerebral/etiologia , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Coagulação Sanguínea , Pressão Sanguínea , Determinação da Pressão Arterial , Isquemia Encefálica/fisiopatologia , China , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Tempo de Protrombina , Fatores de Risco , Estações do Ano , Acidente Vascular Cerebral/metabolismo , Temperatura , Fatores de Tempo
6.
Mol Genet Metab ; 125(4): 338-344, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30413389

RESUMO

Fabry disease, a rare, X-linked lysosomal storage disease, arises from deficiency of the lysosomal hydrolase, α-galactosidase A (GLA) which disrupts the catabolism of globo- series glycosphingolipids (GSLs). One potential link between GLA deficiency and vascular dysfunction may be changes in endothelial nitric oxide synthase (eNOS) function. GLA-deficient EA.hy926 cells were obtained by siRNA knockdown of GLA expression and by mutation of GLA with CRISPR/Cas9 gene editing to investigate the effects of GLA deficiency on eNOS. As previously observed with siRNA knockdown of GLA, globotriaosylceramide (Gb3) accumulated in EA.hy926 cells. In contrast, Gb3 did not accumulate in CRISPR/Cas9 gene edited GLA-deficient cells, but instead, globotetraosylceramide (Gb4). However, in both the siRNA and CRISPR/Cas9 models globotriaosylsphingosine (lyso-Gb3) was elevated. As was previously observed with siRNA knockdown of GLA expression, CRISPR/Cas9 GLA-deficient cells had lower eNOS activity. Restoring GLA activity in GLA-deficient cells with exogenous GLA treatment improved eNOS activity. In contrast, treating cells with the glucosylceramide synthase inhibitor, eliglustat, decreased NOS activity. These results suggest that eNOS uncoupling is due to GLA deficiency, and not necessarily due to elevated Gb3 per se. It was observed that lyso-Gb3 inhibits eNOS activity.


Assuntos
Endotélio Vascular/patologia , Regulação Enzimológica da Expressão Gênica , Inativação Gênica , Óxido Nítrico Sintase Tipo III/metabolismo , Triexosilceramidas/metabolismo , alfa-Galactosidase/antagonistas & inibidores , Células Cultivadas , Endotélio Vascular/enzimologia , Humanos , alfa-Galactosidase/genética , alfa-Galactosidase/metabolismo
7.
Kidney Int ; 86(1): 58-66, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24402087

RESUMO

The endothelial dysfunction of Fabry disease results from α-galactosidase A deficiency leading to the accumulation of globotriaosylceramide. Vasculopathy in the α-galactosidase A null mouse is manifested as oxidant-induced thrombosis, accelerated atherogenesis, and impaired arterial reactivity. To better understand the pathogenesis of Fabry disease in humans, we generated a human cell model by using RNA interference. Hybrid endothelial cells were transiently transfected with small interfering RNA (siRNA) specifically directed against α-galactosidase A. Knockdown of α-galactosidase A was confirmed using immunoblotting and globotriaosylceramide accumulation. Endothelial nitric oxide synthase (eNOS) activity was correspondingly decreased by >60%. Levels of 3-nitrotyrosine (3NT), a specific marker for reactive nitrogen species and quantified using mass spectrometry, increased by 40- to 120-fold without corresponding changes in other oxidized amino acids, consistent with eNOS-derived reactive nitrogen species as the source of the reactive oxygen species. eNOS uncoupling was confirmed by the observed increase in free plasma and protein-bound aortic 3NT levels in the α-galactosidase A knockout mice. Finally, 3NT levels, assayed in biobanked plasma samples from patients with classical Fabry disease, were over sixfold elevated compared with age- and gender-matched controls. Thus, 3NT may serve as a biomarker for the vascular involvement in Fabry disease.


Assuntos
Doença de Fabry/complicações , Doença de Fabry/metabolismo , Tirosina/análogos & derivados , Doenças Vasculares/etiologia , Doenças Vasculares/metabolismo , Adolescente , Adulto , Animais , Biomarcadores/metabolismo , Estudos de Casos e Controles , Linhagem Celular , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Doença de Fabry/genética , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III/metabolismo , RNA Interferente Pequeno/genética , Tirosina/metabolismo , Adulto Jovem , alfa-Galactosidase/antagonistas & inibidores , alfa-Galactosidase/genética
8.
Am J Physiol Gastrointest Liver Physiol ; 306(2): G140-6, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24232002

RESUMO

A defect in the gene for the lysosomal enzyme α-galactosidase A (Gla) results in globotriaosylceramide (Gb3) accumulation in Fabry disease and leads to premature death from cardiac and cerebrovascular events. However, gastrointestinal symptoms are often first observed during childhood in these patients and are not well understood. In this study, we demonstrate an age-dependent microvasculopathy of the mesenteric artery (MA) in a murine model of Fabry disease (Gla-knockout mice) resulting from dysregulation of the vascular homeostatic enzyme endothelial nitric oxide synthase (eNOS). The progressive accumulation of Gb3 in the MA was confirmed by thin-layer chromatographic analysis. A total absence of endothelium-dependent dilation was observed in MAs from mice at 8 mo of age, while suppression of ACh-mediated vasodilation was evident from 2 mo of age. Endothelium-independent dilation with sodium nitroprusside was normal compared with age-matched wild-type mice. The microvascular defect in MAs from Fabry mice was endothelium-dependent and associated with suppression of the active homodimer of eNOS. Phosphorylation of eNOS at the major activation site (Ser(1179)) was significantly downregulated, while phosphorylation at the major inhibitory site (Thr(495)) was remarkably enhanced in MAs from aged Fabry mice. These profound alterations in eNOS bioavailability at 8 mo of age were observed in parallel with high levels of 3-nitrotyrosine, suggesting increased reactive oxygen species along with eNOS uncoupling in this vascular bed. Overall, the mesenteric microvessels in the setting of Fabry disease were observed to have an early and profound endothelial dysfunction associated with elevated reactive nitrogen species and decreased nitric oxide bioavailability.


Assuntos
Óxido Nítrico Sintase Tipo III/metabolismo , Circulação Esplâncnica/fisiologia , alfa-Galactosidase/genética , alfa-Galactosidase/fisiologia , Acetilcolina/fisiologia , Envelhecimento/fisiologia , Animais , Western Blotting , Capilares/fisiologia , Doença de Fabry/enzimologia , Doença de Fabry/genética , Metabolismo dos Lipídeos/fisiologia , Artérias Mesentéricas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/efeitos dos fármacos , Doadores de Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Fenótipo , Fosforilação , Espécies Reativas de Nitrogênio/metabolismo , Triexosilceramidas/metabolismo
9.
Methods Mol Biol ; 2613: 271-288, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36587085

RESUMO

Glucosylceramide synthase can be targeted by high affinity small molecular weight inhibitors for the study of glycosphingolipid metabolism and function or for the treatment of glycosphingolipid storage disorders, including Gaucher and Fabry disease. This work is exemplified by the discovery and development of eliglustat tartrate, the first stand-alone small chemical entity approved for the treatment of Gaucher disease type 1. The development of inhibitors of glucosylceramide synthase that have utility for either research or clinical purposes begins with a testing funnel for screening candidate inhibitors for activity against this enzyme and for activity in lowering the content of glucosylceramide in intact cells. Two common assays for glucosylceramide synthase, one enzyme based and another cell based, are the focus of this chapter.


Assuntos
Doença de Gaucher , Humanos , Doença de Gaucher/tratamento farmacológico , Doença de Gaucher/metabolismo , Glucosiltransferases/metabolismo , Glucosilceramidas , Glicoesfingolipídeos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico
10.
Front Neurol ; 14: 1168836, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37492851

RESUMO

Background and purpose: As one common feature of cerebral small vascular disease (cSVD), white matter lesions (WMLs) could lead to reduction in brain function. Using a convenient, cheap, and non-intrusive method to detect WMLs could substantially benefit to patient management in the community screening, especially in the settings of availability or contraindication of magnetic resonance imaging (MRI). Therefore, this study aimed to develop a useful model to incorporate clinical laboratory data and retinal images using deep learning models to predict the severity of WMLs. Methods: Two hundred fifty-nine patients with any kind of neurological diseases were enrolled in our study. Demographic data, retinal images, MRI, and laboratory data were collected for the patients. The patients were assigned to the absent/mild and moderate-severe WMLs groups according to Fazekas scoring system. Retinal images were acquired by fundus photography. A ResNet deep learning framework was used to analyze the retinal images. A clinical-laboratory signature was generated from laboratory data. Two prediction models, a combined model including demographic data, the clinical-laboratory signature, and the retinal images and a clinical model including only demographic data and the clinical-laboratory signature, were developed to predict the severity of WMLs. Results: Approximately one-quarter of the patients (25.6%) had moderate-severe WMLs. The left and right retinal images predicted moderate-severe WMLs with area under the curves (AUCs) of 0.73 and 0.94. The clinical-laboratory signature predicted moderate-severe WMLs with an AUC of 0.73. The combined model showed good performance in predicting moderate-severe WMLs with an AUC of 0.95, while the clinical model predicted moderate-severe WMLs with an AUC of 0.78. Conclusion: Combined with retinal images from conventional fundus photography and clinical laboratory data are reliable and convenient approach to predict the severity of WMLs and are helpful for the management and follow-up of WMLs patients.

11.
J Lipid Res ; 53(2): 282-91, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22058426

RESUMO

Synthesis inhibition is the basis for the treatment of type 1 Gaucher disease by the glucosylceramide synthase (GCS) inhibitor eliglustat tartrate. However, the extended use of eliglustat and related compounds for the treatment of glycosphingolipid storage diseases with CNS manifestations is limited by the lack of brain penetration of this drug. Property modeling around the D-threo-1-phenyl-2-decanoylamino-3-morpholino-propanol (PDMP) pharmacophore was employed in a search for compounds of comparable activity against the GCS but lacking P-glycoprotein (MDR1) recognition. Modifications of the carboxamide N-acyl group were made to lower total polar surface area and rotatable bond number. Compounds were screened for inhibition of GCS in crude enzyme and whole cell assays and for MDR1 substrate recognition. One analog, 2-(2,3-dihydro-1H-inden-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)acetamide (CCG-203586), was identified that inhibited GCS at low nanomolar concentrations with little to no apparent recognition by MDR1. Intraperitoneal administration of this compound to mice for 3 days resulted in a significant dose dependent decrease in brain glucosylceramide content, an effect not seen in mice dosed in parallel with eliglustat tartrate.


Assuntos
Encéfalo/efeitos dos fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Glucosilceramidas/metabolismo , Glucosiltransferases/antagonistas & inibidores , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Encéfalo/metabolismo , Células Cultivadas , Dioxanos/síntese química , Dioxanos/farmacologia , Relação Dose-Resposta a Droga , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Indanos/síntese química , Indanos/farmacologia , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos C57BL , Morfolinas/química , Vimblastina/farmacocinética
12.
Biomech Model Mechanobiol ; 21(4): 1145-1155, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35482145

RESUMO

A better understanding of the time-dependent biomechanical behaviour of the biphasic hip articular cartilage (AC) under physiological loadings is important to understand the onset of joint pathology and guide the clinical treatment. Current computational studies for the biphasic hip AC were usually limited to short-term duration or using elaborate loading. The present study aimed to develop a multiscale computational modelling to investigate the long-term biphasic behaviour of the hip AC under physiological loadings over multiple gait cycles. Two-scale computational modelling including a musculoskeletal model and a finite element model of the natural hip was created. These two models were then combined and used to investigate the biphasic behaviour of hip AC over 80 gait cycles. The results showed that the interstitial fluid pressure in the AC supported over 89% of the loading during gait. When the contact area was located at the AC centre, the contact pressure and fluid pressure increased over time from the first cycle to the 80th cycle, while when the contact area approached the edge, these pressures decreased first dramatically and then slowly over time. The peak stresses and strains in the solid matrix of the AC remained at a low level and increased over time from the first cycle to the 80th cycle. This study demonstrated that the long-term temporal variations of the biphasic behaviour of hip AC under physiological loadings are significant. The methodology has potentially important implications in the biomechanical studies of human cartilage and supporting the development of cartilage substitution.


Assuntos
Cartilagem Articular/fisiologia , Marcha/fisiologia , Articulação do Quadril/fisiologia , Modelos Biológicos , Fenômenos Biomecânicos , Análise de Elementos Finitos , Humanos
13.
Bone Joint Res ; 11(10): 739-750, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36226477

RESUMO

AIMS: To fully quantify the effect of posterior tibial slope (PTS) angles on joint kinematics and contact mechanics of intact and anterior cruciate ligament-deficient (ACLD) knees during the gait cycle. METHODS: In this controlled laboratory study, we developed an original multiscale subject-specific finite element musculoskeletal framework model and integrated it with the tibiofemoral and patellofemoral joints with high-fidelity joint motion representations, to investigate the effects of 2.5° increases in PTS angles on joint dynamics and contact mechanics during the gait cycle. RESULTS: The ACL tensile force in the intact knee was significantly affected with increasing PTS angle. Considerable differences were observed in kinematics and initial posterior femoral translation between the intact and ACLD joints as the PTS angles increased by more than 2.5° (beyond 11.4°). Additionally, a higher contact stress was detected in the peripheral posterior horn areas of the menisci with increasing PTS angle during the gait cycle. The maximum tensile force on the horn of the medial meniscus increased from 73.9 N to 172.4 N in the ACLD joint with increasing PTS angles. CONCLUSION: Knee joint instability and larger loading on the medial meniscus were found on the ACLD knee even at a 2.5° increase in PTS angle (larger than 11.4°). Our biomechanical findings support recent clinical evidence of a high risk of failure of ACL reconstruction with steeper PTS and the necessity of ACL reconstruction, which would prevent meniscus tear and thus the development or progression of osteoarthritis.Cite this article: Bone Joint Res 2022;11(10):708-719.

14.
Front Med (Lausanne) ; 9: 907066, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911407

RESUMO

There is a growing need for precise diagnosis and personalized treatment of disease in recent years. Providing treatment tailored to each patient and maximizing efficacy and efficiency are broad goals of the healthcare system. As an engineering concept that connects the physical entity and digital space, the digital twin (DT) entered our lives at the beginning of Industry 4.0. It is evaluated as a revolution in many industrial fields and has shown the potential to be widely used in the field of medicine. This technology can offer innovative solutions for precise diagnosis and personalized treatment processes. Although there are difficulties in data collection, data fusion, and accurate simulation at this stage, we speculated that the DT may have an increasing use in the future and will become a new platform for personal health management and healthcare services. We introduced the DT technology and discussed the advantages and limitations of its applications in the medical field. This article aims to provide a perspective that combining Big Data, the Internet of Things (IoT), and artificial intelligence (AI) technology; the DT will help establish high-resolution models of patients to achieve precise diagnosis and personalized treatment.

15.
Brain Sci ; 13(1)2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36672011

RESUMO

Many patients show poor outcomes following endovascular reperfusion therapy (ERT), and poor cortical venous outflow is a risk factor for these poor outcomes. We investigated the association between the outflow of the internal jugular vein (IJV) and baseline cortical venous outflow and the outcomes after ERT. We retrospectively enrolled 78 patients diagnosed with an acute anterior circulation stroke and successful ERT. Poor IJV outflow on the affected side was defined as stenosis ≥50% or occlusion of ipsilateral IJV, and poor outflow of bilateral IJVs was defined as stenosis ≥50% or occlusion of both IJVs. Poor cortical venous outflow was defined as a cortical vein opacification score (COVES) of 0 on admission. Multivariate analysis showed that poor outflow of IJV on the affected side was an independent predictor for hemorrhagic transformation. The poor outflow of bilateral IJVs was an independent risk factor for poor clinical outcomes. These patients also had numerical trends of a higher incidence of symptomatic intracranial hemorrhage, midline shift >10 mm, and in-hospital mortality; however, statistical significance was not observed. Additionally, poor IJV outflow was an independent determinant of poor cortical venous outflow. For acute large vessel occlusion patients, poor IJV outflow is associated with poor baseline cortical venous outflow and outcomes after successful ERT.

16.
J Orthop Translat ; 34: 22-41, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35615638

RESUMO

Background: With increasing requirements for medical effects, and huge differences among individuals, traditional surgical instruments are difficult to meet the patients' growing medical demands. 3D printing is increasingly mature, which connects to medical services critically as well. The patient specific surgical guide plate provides the condition for precision medicine in orthopaedics. Methods: In this paper, a systematic review of the orthopedic guide template is presented, where the history of 3D-printing-guided technology, the process of guides, and basic clinical applications of orthopedic guide templates are described. Finally, the limitations of the template and possible future directions are discussed. Results: The technology of 3D printing surgical templates is increasingly mature, standard, and intelligent. With the help of guide templates, the surgeon can easily determine the direction and depth of the screw path, and choose the angle and range of osteotomy, increasing the precision, safety, and reliability of the procedure in various types of surgeries. It simplifies the difficult surgical steps and accelerates the growth of young and mid-career physicians. But some problems such as cost, materials, and equipment limit its development. Conclusions: In different fields of orthopedics, the use of guide templates can significantly improve surgical accuracy, shorten the surgical time, and reduce intraoperative bleeding and radiation. With the development of 3D printing, the guide template will be standardized and simplified from design to production and use. 3D printing guides will be further sublimated in the application of orthopedics and better serve the patients. The translational potential of this paper: Precision, intelligence, and individuation are the future development direction of orthopedics. It is more and more popular as the price of printers falls and materials are developed. In addition, the technology of meta-universe, digital twin, and artificial intelligence have made revolutionary effects on template guides. We aim to summarize recent developments and applications of 3D printing guide templates for engineers and surgeons to develop more accurate and efficient templates.

17.
Materials (Basel) ; 15(8)2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35454571

RESUMO

The proximal femur's numerical simulation could give an effective method for predicting the risk of femoral fracture. However, the majority of existing numerical simulations is static, which does not correctly capture the dynamic properties of bone fractures. On the basis of femoral fracture analysis, a dynamic simulation using incremental element deletion (IED)-based finite element analysis (FEA) was developed and compared to XFEM in this study. Mechanical tests were also used to assess it. Different impact speeds, fall postures, and cortical thicknesses were also studied for their implications on fracture types and mechanical responses. The time it took for the crack to shatter was shorter when the speed was higher, and the crack line slid down significantly. The fracture load fell by 27.37% when the angle was altered from 15° to 135°, indicating that falling forward was less likely to cause proximal femoral fracture than falling backward. Furthermore, the model with scant cortical bone was susceptible to fracture. This study established a theoretical foundation and mechanism for forecasting the risk of proximal femoral fracture in the elderly.

18.
Comput Biol Med ; 141: 105023, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34772508

RESUMO

BACKGROUND AND OBJECTIVE: The dynamic characteristics of the intact knee joint are valuable for treating knee osteoarthritis and designing knee prostheses. However, it remains a challenge to elucidate the detailed dynamics of the knee due to its complexity of anatomical structure and complex interaction with body dynamics. METHODS: In this study, a unique subject-specific musculoskeletal model with a concurrent high-accuracy intact finite element knee model was created and used to simultaneously evaluate the kinematics and mechanics of an intact knee joint during the gait cycle. RESULTS: A medial pivot motion with external rotation, and a large parallel anterior translation were observed in the stance and swing phases, respectively, which is consistent with the in vivo fluoroscopy measurements. The maximum axial contact force on the knee joint, observed at 45% of the gait cycle, is approximately 2.89 times the body weight. The medial cartilage bears 65.7% of the total axial contact force. The results demonstrate that the cartilage-cartilage contact bears most of the joint load (62.5%) compared to the cartilage-meniscus-cartilage contact (37.5%). Regarding contact mechanics, the maximum contact pressure on both sides of the tibial cartilage (8.2 MPa) is almost similar to the first axial loading peak (14%) of the gait cycle. Additionally, the maximum contact pressure (6.01 MPa) was observed during the stance phase of the gait cycle on the patellofemoral joint. CONCLUSIONS: The predicted results on the tibiofemoral and patellofemoral joints provide a theoretical basis for the treatment of knee joint diseases and knee prosthesis design. Moreover, this approach presents a comprehensive tool to evaluate the mechanics at both the body and tissue levels. Therefore, it has a high potential for application in human biomechanics.


Assuntos
Articulação do Joelho , Joelho , Fenômenos Biomecânicos , Análise de Elementos Finitos , Marcha , Humanos
19.
Ann Biomed Eng ; 49(9): 2491-2502, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34142278

RESUMO

An objective of total knee replacement (TKR) is to restore the mechanical function of a normal knee. Joint kinematics and contact mechanics performance are two of the primary indices that indicate the success of TKR devices. The aim of this study was to compare the kinematics and contact mechanics of TKR and normal knee joints. An experimentally evaluated finite-element (FE) knee model was developed and used to investigate the performance of four TKR designs (fixed cruciate-retaining (CR), mobile CR, posterior-stabilized (PS), medial pivot design (MP)) and the normal knee joint during a gait cycle. The predicted kinematic results showed that the MP design presented similar kinematics to those of the normal knee joint and did not demonstrate paradoxical motion of the femur. A considerably larger contact area and lower contact pressure were found on the normal knee joint (1315 mm2, and 14.8 MPa, respectively) than on the TKRs, which was consistent with the previous in-vivo fluoroscopic investigation. The mobile CR and PS designs exhibited the smallest and greatest contact pressures of the four TKR designs, respectively. The results of the present study help to understand the kinematics and contact mechanics in the TKR during the gait cycle, and provide comprehensive information about the performance of the normal knee joint.


Assuntos
Articulação do Joelho/fisiologia , Prótese do Joelho , Modelos Biológicos , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho , Fenômenos Biomecânicos , Feminino , Análise de Elementos Finitos , Marcha/fisiologia , Humanos , Masculino
20.
Ann Biomed Eng ; 49(1): 322-333, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32607843

RESUMO

A computational wear simulator is an efficient tool for evaluating the wear of artificial knee joints. The classical Archard's wear law-based simulator has questionable accuracy and is focused on walking. In this study, an in silico polyethylene wear simulation of total knee replacements was developed considering the various highly demanding daily activities. A good predicted accuracy (error = 8.1%) was found through comparison of the experimental results. A relatively larger averaged wear loss was found under the loading condition (1.53 mg/mc) of daily activities compared with the walking condition (1.32 mg/mc). The squatting movement (2.57 mg/mc) produces the highest overall wear rate. In addition, a relatively larger amount of wear was found on the medial side knee prosthesis than that on the lateral side. The enhanced in silico polyethylene wear simulator provides an accurate and comprehensive tool for wear prediction in preclinical wear testing.


Assuntos
Prótese do Joelho , Modelos Biológicos , Movimento/fisiologia , Artroplastia do Joelho , Fenômenos Biomecânicos , Simulação por Computador , Análise de Elementos Finitos , Humanos , Articulação do Joelho , Teste de Materiais , Polietileno
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