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1.
Medicine (Baltimore) ; 100(41): e27483, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34731127

RESUMO

BACKGROUND: The benefit of loco-regional treatments such as hepatic arterial infusion (HAI) in terms of survival and response rate is unclear. The aim of this work is to quantitatively summarize the results of both randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) comparing fluoropyrimidine-HAI (F-HAI) to systemic chemotherapy (SCT) for the treatment of colorectal liver metastases (CRLMs). METHODS: We searched the Cochrane Library, PubMed, EMBASE, and Web of Science up to July 1, 2021. The outcome measures were tumor response rate and overall survival (OS). Both RCTs and NRSIs comparing HAI to SCT for patients with unresectable CRLMs were included. The outcome measures were tumor response rate and OS. Two reviewers assessed trial quality and extracted data independently. All statistical analyses were performed using standard statistical procedures provided in Review Manager 5.2. RESULTS: A total of 16 studies including 11 RCTs and 5 NRSIs were identified for the present meta-analysis. Nine RCTs compared F-HAI to SCT for patients with unresectable CRLMs and the pooled result indicated that patients who received F-HAI experienced more than twofold response rate than SCT, with a pooled risk ratio of 2.10 (95%CI 1.59-2.79; P < .00001). In addition, the pooled result based on RCTs showed that F-HAI had a significant benefit regarding OS, with a pooled HR of 0.83 (95% CI 0.70-0.99; P = .04). Similarly, the benefit of F-HAI in terms of OS was also observed in the results of NRSIs. CONCLUSIONS: Our results indicated that the F-HAI regimen had a greater tumor response rate and survival advantage than SCT for patients with unresectable CRLMs. Future propensity score-matched analyses with a large sample size should be conducted to support the evidence of our results based on RCTs and NRSIs.


Assuntos
Antimetabólitos/administração & dosagem , Antineoplásicos/administração & dosagem , Infusões Intra-Arteriais/métodos , Neoplasias Hepáticas/tratamento farmacológico , Fígado/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/patologia , Humanos , Fígado/irrigação sanguínea , Fígado/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Ensaios Clínicos Controlados não Aleatórios como Assunto , Estudos Observacionais como Assunto , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Resultado do Tratamento
2.
Pan Afr Med J ; 39: 273, 2021.
Artigo em Francês | MEDLINE | ID: mdl-34754350

RESUMO

Acute mesenteric ischemia (AMI) is due to a sudden decrease or interruption of mesenteric blood flow resulting in inadequate blood supply to the gastrointestinal tract. This causes ischemic and inflammatory lesions often progressing to necrosis in the absence of appropriate treatment. Vascular insufficiency may arise as a result of embolism or arterial thrombosis or venous thrombosis. We here report a rare case of mesenteric venous ischemia caused by coronavirus disease 2019 (COVID-19) in a 33-year-old man in whom diagnosis was based on ultrasound and, in particular, on computed tomography (CT).


Assuntos
COVID-19/complicações , Intestinos/irrigação sanguínea , Isquemia Mesentérica/etiologia , Tomografia Computadorizada por Raios X/métodos , Trombose Venosa/complicações , Dor Abdominal/etiologia , Adulto , COVID-19/diagnóstico , Humanos , Masculino , Isquemia Mesentérica/diagnóstico por imagem , Mesentério/irrigação sanguínea , Veia Porta/diagnóstico por imagem , SARS-CoV-2 , Trombose Venosa/diagnóstico
4.
Crit Care ; 25(1): 381, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34749792

RESUMO

BACKGROUND: COVID-19 is primarily a respiratory disease; however, there is also evidence that it causes endothelial damage in the microvasculature of several organs. The aim of the present study is to characterize in vivo the microvascular reactivity in peripheral skeletal muscle of severe COVID-19 patients. METHODS: This is a prospective observational study carried out in Spain, Mexico and Brazil. Healthy subjects and severe COVID-19 patients admitted to the intermediate respiratory (IRCU) and intensive care units (ICU) due to hypoxemia were studied. Local tissue/blood oxygen saturation (StO2) and local hemoglobin concentration (THC) were non-invasively measured on the forearm by near-infrared spectroscopy (NIRS). A vascular occlusion test (VOT), a three-minute induced ischemia, was performed in order to obtain dynamic StO2 parameters: deoxygenation rate (DeO2), reoxygenation rate (ReO2), and hyperemic response (HAUC). In COVID-19 patients, the severity of ARDS was evaluated by the ratio between peripheral arterial oxygen saturation (SpO2) and the fraction of inspired oxygen (FiO2) (SF ratio). RESULTS: Healthy controls (32) and COVID-19 patients (73) were studied. Baseline StO2 and THC did not differ between the two groups. Dynamic VOT-derived parameters were significantly impaired in COVID-19 patients showing lower metabolic rate (DeO2) and diminished endothelial reactivity. At enrollment, most COVID-19 patients were receiving invasive mechanical ventilation (MV) (53%) or high-flow nasal cannula support (32%). Patients on MV were also receiving sedative agents (100%) and vasopressors (29%). Baseline StO2 and DeO2 negatively correlated with SF ratio, while ReO2 showed a positive correlation with SF ratio. There were significant differences in baseline StO2 and ReO2 among the different ARDS groups according to SF ratio, but not among different respiratory support therapies. CONCLUSION: Patients with severe COVID-19 show systemic microcirculatory alterations suggestive of endothelial dysfunction, and these alterations are associated with the severity of ARDS. Further evaluation is needed to determine whether these observations have prognostic implications. These results represent interim findings of the ongoing HEMOCOVID-19 trial. Trial registration ClinicalTrials.gov NCT04689477 . Retrospectively registered 30 December 2020.


Assuntos
COVID-19/fisiopatologia , Unidades de Terapia Intensiva/tendências , Microvasos/fisiopatologia , Unidades de Cuidados Respiratórios/tendências , Síndrome do Desconforto Respiratório/fisiopatologia , Índice de Gravidade de Doença , Adulto , Idoso , Brasil/epidemiologia , COVID-19/diagnóstico , COVID-19/epidemiologia , Feminino , Humanos , Masculino , México/epidemiologia , Microcirculação/fisiologia , Pessoa de Meia-Idade , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/fisiopatologia , Estudos Prospectivos , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/epidemiologia , Espanha/epidemiologia
5.
Emerg Med Clin North Am ; 39(4): 769-780, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34600636

RESUMO

Abdominal vascular emergencies are an uncommon entity in emergency medicine, but when they present, they are often catastrophic. These time-sensitive and life-threatening diagnoses are often hidden in nonspecific complaints such as nausea, vomiting, or flank pain, so the emergency physician must remain diligent and consider these in the differential diagnoses. The following is an overview of the more common of these abdominal vascular emergencies, in the hope that they help the Emergency Physician avoid the misdiagnosis and subsequent vascular catastrophe that would follow.


Assuntos
Abdome/irrigação sanguínea , Erros de Diagnóstico/prevenção & controle , Traumatismos Abdominais/diagnóstico , Aneurisma da Aorta Abdominal/diagnóstico , Aneurisma da Aorta Abdominal/cirurgia , Estenose da Valva Aórtica/diagnóstico , Arteriopatias Oclusivas/diagnóstico , Técnicas de Diagnóstico do Sistema Digestório , Medicina de Emergência , Humanos , Intestinos/irrigação sanguínea , Isquemia/diagnóstico , Isquemia/terapia , Isquemia Mesentérica/diagnóstico , Isquemia Mesentérica/terapia , Lesões do Sistema Vascular/diagnóstico
6.
Anticancer Res ; 41(10): 5015-5023, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593450

RESUMO

BACKGROUND/AIM: Limb-sparing procedures are frequently applied to improve patient outcomes. The use of vascularized bone grafts is associated with significant improvements in oncologic safety and functional satisfaction. This study highlights the clinical outcomes following tumor resection combined with vascularized bone graft reconstructions. PATIENTS AND METHODS: Twenty-five free vascularized bone grafts (17 fibulas, 5 iliac crests, 3 medial femoral condyles) were assessed with respect to consolidation and hypertrophy, functional and oncologic outcomes, and local complications. RESULTS: The rate of healing of fibular grafts after a median of 5 months was 86%. The rate of achieved unions of iliac crest grafts after a median of 5 months was 80%. In medial femoral condyle bone grafts, union occurred after a median of 4 months. Significant hypertrophy was observed in 13 patients. We identified six complications with highest rates in the fibula-group. Despite the high complications, functional results were highly satisfactory. CONCLUSION: Vascularized bone grafts represent a reconstructive approach, maintaining long-term functionality and cosmetic satisfaction without compromising tumor recurrence outcomes.


Assuntos
Neoplasias Ósseas/cirurgia , Transplante Ósseo/métodos , Procedimentos Cirúrgicos Reconstrutivos/métodos , Sarcoma/cirurgia , Cirurgia Assistida por Computador/métodos , Adolescente , Adulto , Neoplasias Ósseas/irrigação sanguínea , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Sarcoma/irrigação sanguínea , Sarcoma/patologia , Adulto Jovem
7.
Urol Clin North Am ; 48(4): 543-555, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34602174

RESUMO

Erectile dysfunction management is intended to restore capacity for penile erection. Although effective, none of the currently available treatments approved by the US Food and Drug Administration reverse erectile dysfunction pathophysiology. Penile arterial bypass surgery is intended to restore erectile function without the need for the chronic use of vasoactive medications or penile prosthesis placement. In select cases, venous ligation surgery may be beneficial, but this approach is not supported by the most recent guidelines on erectile dysfunction management. The lack of high-quality research surrounding penile vascular surgery has limited its use.


Assuntos
Disfunção Erétil/cirurgia , Impotência Vasculogênica/cirurgia , Humanos , Masculino , Pênis/irrigação sanguínea , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Procedimentos Cirúrgicos Vasculares/métodos
8.
Proc Natl Acad Sci U S A ; 118(41)2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34607955

RESUMO

The COVID-19 pandemic led to widespread mandates requiring the wearing of face masks, which led to debates on their benefits and possible adverse effects. To that end, the physiological effects at the systemic and at the brain level are of interest. We have investigated the effect of commonly available face masks (FFP2 and surgical) on cerebral hemodynamics and oxygenation, particularly microvascular cerebral blood flow (CBF) and blood/tissue oxygen saturation (StO2), measured by transcranial hybrid near-infrared spectroscopies and on systemic physiology in 13 healthy adults (ages: 23 to 33 y). The results indicate small but significant changes in cerebral hemodynamics while wearing a mask. However, these changes are comparable to those of daily life activities. This platform and the protocol provides the basis for large or targeted studies of the effects of mask wearing in different populations and while performing critical tasks.


Assuntos
Encéfalo/fisiologia , Máscaras , Atividades Cotidianas , Adulto , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , COVID-19/prevenção & controle , Feminino , Voluntários Saudáveis , Hemodinâmica , Humanos , Masculino , Microcirculação , Monitorização Fisiológica , Oxigênio/metabolismo , SARS-CoV-2 , Espectroscopia de Luz Próxima ao Infravermelho , Adulto Jovem
9.
BMC Cancer ; 21(1): 1093, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34629067

RESUMO

BACKGROUND: An underlying cause of solid tumor resistance to chemotherapy treatment is diminished tumor blood supply, which leads to a hypoxic microenvironment, dependence on anaerobic energy metabolism, and impaired delivery of intravenous treatments. Preclinical data suggest that dietary strategies of caloric restriction and low-carbohydrate intake can inhibit glycolysis, while acute exercise can transiently enhance blood flow to the tumor and reduce hypoxia. The Diet Restriction and Exercise-induced Adaptations in Metastatic Breast Cancer (DREAM) study will compare the effects of a short-term, 50% calorie-restricted and ketogenic diet combined with aerobic exercise performed during intravenous chemotherapy treatment to usual care on changes in tumor burden, treatment side effects, and quality of life. METHODS: Fifty patients with measurable metastases and primary breast cancer starting a new line of intravenous chemotherapy will be randomly assigned to usual care or the combined diet and exercise intervention. Participants assigned to the intervention group will be provided with food consisting of 50% of measured calorie needs with 80% of calories from fat and ≤ 10% from carbohydrates for 48-72 h prior to each chemotherapy treatment and will perform 30-60 min of moderate-intensity cycle ergometer exercise during each chemotherapy infusion, for up to six treatment cycles. The diet and exercise durations will be adapted for each chemotherapy protocol. Tumor burden will be assessed by change in target lesion size using axial computed tomography (primary outcome) and magnetic resonance imaging (MRI)-derived apparent diffusion coefficient (secondary outcome) after up to six treatments. Tertiary outcomes will include quantitative MRI markers of treatment toxicity to the heart, thigh skeletal muscle, and liver, and patient-reported symptoms and quality of life. Exploratory outcome measures include progression-free and overall survival. DISCUSSION: The DREAM study will test a novel, short-term diet and exercise intervention that is targeted to mechanisms of tumor resistance to chemotherapy. A reduction in lesion size is likely to translate to improved cancer outcomes including disease progression and overall survival. Furthermore, a lifestyle intervention may empower patients with metastatic breast cancer by actively engaging them to play a key role in their treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03795493 , registered 7 January, 2019.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/terapia , Restrição Calórica , Dieta Cetogênica , Exercício Físico , Adaptação Fisiológica , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Terapia Combinada/métodos , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Imageamento por Ressonância Magnética , Refeições , Avaliação de Resultados em Cuidados de Saúde , Qualidade de Vida , Carga Tumoral , Hipóxia Tumoral
10.
Int J Mol Sci ; 22(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34638872

RESUMO

BACKGROUND: Vasculogenic mimicry (VM) is a functional microcirculation pattern formed by aggressive tumor cells. Thus far, no effective drugs have been developed to target VM. Glioblastoma (GBM) is the most malignant form of brain cancer and is a highly vascularized tumor. Vasculogenic mimicry represents a means whereby GBM can escape anti-angiogenic therapies. METHODS: Here, using an in vitro tube formation assay on Matrigel, we evaluated the ability of N6-isopentenyladenosine (iPA) to interfere with vasculogenic mimicry (VM). RhoA activity was assessed using a pull-down assay, while the modulation of the adherens junctions proteins was analyzed by Western blot analysis. RESULTS: We found that iPA at sublethal doses inhibited the formation of capillary-like structures suppressing cell migration and invasion of U87MG, U343MG, and U251MG cells, of patient-derived human GBM cells and GBM stem cells. iPA reduces the vascular endothelial cadherin (VE-cadherin) expression levels in a dose-dependent manner, impairs the vasculogenic mimicry network by modulation of the Src/p120-catenin pathway and inhibition of RhoA-GTPase activity. CONCLUSIONS: Taken together, our results revealed iPA as a promising novel anti-VM drug in GBM clinical therapeutics.


Assuntos
Cateninas/metabolismo , Glioblastoma/tratamento farmacológico , Isopenteniladenosina/farmacologia , Neovascularização Patológica/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Proteína rhoA de Ligação ao GTP/metabolismo , Quinases da Família src/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Caderinas/genética , Caderinas/metabolismo , Cateninas/genética , Linhagem Celular Tumoral , Glioblastoma/irrigação sanguínea , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Proteína rhoA de Ligação ao GTP/genética , Quinases da Família src/genética
11.
Int J Mol Sci ; 22(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34638621

RESUMO

Previously, we showed that mice treated with cyclophosphamide (CTX) 4 days before intravenous injection of breast cancer cells had more cancer cells in the lung at 3 h after cancer injection than control counterparts without CTX. At 4 days after its injection, CTX is already excreted from the mice, allowing this pre-treatment design to reveal how CTX may modify the lung environment to indirectly affect cancer cells. In this study, we tested the hypothesis that the increase in cancer cell abundance at 3 h by CTX is due to an increase in the adhesiveness of vascular wall for cancer cells. Our data from protein array analysis and inhibition approach combined with in vitro and in vivo assays support the following two-prong mechanism. (1) CTX increases vascular permeability, resulting in the exposure of the basement membrane (BM). (2) CTX increases the level of matrix metalloproteinase-2 (MMP-2) in mouse serum, which remodels the BM and is functionally important for CTX to increase cancer abundance at this early stage. The combined effect of these two processes is the increased accessibility of critical protein domains in the BM, resulting in higher vascular adhesiveness for cancer cells to adhere. The critical protein domains in the vascular microenvironment are RGD and YISGR domains, whose known binding partners on cancer cells are integrin dimers and laminin receptor, respectively.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/farmacologia , Metaloproteinase 2 da Matriz/sangue , Microambiente Tumoral/efeitos dos fármacos , Animais , Membrana Basal/efeitos dos fármacos , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Permeabilidade Capilar/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Humanos , Integrina beta1/metabolismo , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Camundongos Knockout , Domínios Proteicos , Microambiente Tumoral/fisiologia
12.
Int J Mol Sci ; 22(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34638895

RESUMO

Beta-Caryophyllene (BCP), a naturally occurring sesquiterpene abundantly found in cloves, hops, and cannabis, is the active candidate of a relatively new group of vascular-inhibiting compounds that aim to block existing tumor blood vessels. Previously, we have reported the anti-cancer properties of BCP by utilizing a series of in-vitro anti-tumor-related assays using human colorectal carcinoma cells. The present study aimed to investigate the effects of BCP on in-vitro, ex-vivo, and in-vivo models of anti-angiogenic assays and evaluate its anti-cancer activity in xenograft tumor (both ectopic and orthotopic) mice models of human colorectal cancer. Computational structural analysis and an apoptosis antibody array were also performed to understand the molecular players underlying this effect. BCP exhibited strong anti-angiogenic activity by blocking the migration of endothelial cells, tube-like network formation, suppression of vascular endothelial growth factor (VEGF) secretion from human umbilical vein endothelial cells and sprouting of rat aorta microvessels. BCP has a probable binding at Site#0 on the surface of VEGFR2. Moreover, BCP significantly deformed the vascularization architecture compared to the negative control in a chick embryo chorioallantoic membrane assay. BCP showed a remarkable reduction in tumor size and fluorescence molecular tomography signal intensity in all the mice treated with BCP, in a dose-dependent relationship, in ectopic and orthotopic tumor xenograft models, respectively. The histological analysis of the tumor from BCP-treated mice revealed a clear reduction of the density of vascularization. In addition, BCP induced apoptosis through downregulation of HSP60, HTRA, survivin, and XIAP, along with the upregulation of p21 expressions. These results suggest that BCP acts at multiple stages of angiogenesis and could be used as a promising therapeutic candidate to halt the growth of colorectal tumor cells.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias Colorretais/prevenção & controle , Neovascularização Patológica/prevenção & controle , Sesquiterpenos Policíclicos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Embrião de Galinha , Membrana Corioalantoide/irrigação sanguínea , Membrana Corioalantoide/efeitos dos fármacos , Neoplasias Colorretais/irrigação sanguínea , Células HCT116 , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Camundongos Nus , Microvasos/efeitos dos fármacos , Ratos Sprague-Dawley
13.
Int J Mol Sci ; 22(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34639215

RESUMO

Hypoxia has an important role in tumor progression via the up-regulation of growth factors and cellular adaptation genes. These changes promote cell survival, proliferation, invasion, metastasis, angiogenesis, and energy metabolism in favor of cancer development. Hypoxia also plays a central role in determining the resistance of tumors to chemotherapy. Hypoxia of the tumor microenvironment provides an opportunity to develop new therapeutic strategies that may selectively induce apoptosis of the hypoxic cancer cells. Melatonin is well known for its role in the regulation of circadian rhythms and seasonal reproduction. Numerous studies have also documented the anti-cancer properties of melatonin, including anti-proliferation, anti-angiogenesis, and apoptosis promotion. In this paper, we hypothesized that melatonin exerts anti-cancer effects by inhibiting hypoxia-induced pathways. Considering this action, co-administration of melatonin in combination with other therapeutic medications might increase the effectiveness of anti-cancer drugs. In this review, we discussed the possible signaling pathways by which melatonin inhibits hypoxia-induced cancer cell survival, invasion, migration, and metabolism, as well as tumor angiogenesis.


Assuntos
Hipóxia/fisiopatologia , Melatonina/uso terapêutico , Neoplasias/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Animais , Apoptose , Movimento Celular , Proliferação de Células , Humanos , Neoplasias/irrigação sanguínea , Neoplasias/metabolismo , Neoplasias/patologia , Transdução de Sinais
14.
J Gen Virol ; 102(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34704923

RESUMO

The highly pathogenic Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a severe respiratory virus. Recent reports indicate additional central nervous system (CNS) involvement. In this study, human DPP4 transgenic mice were infected with MERS-CoV, and viral antigens were first detected in the midbrain-hindbrain 4 days post-infection, suggesting the virus may enter the brainstem via peripheral nerves. Neurons and astrocytes throughout the brain were infected, followed by damage of the blood brain barrier (BBB), as well as microglial activation and inflammatory cell infiltration, which may be caused by complement activation based on the observation of deposition of complement activation product C3 and high expression of C3a receptor (C3aR) and C5a receptor (C5aR1) in neurons and glial cells. It may be concluded that these effects were mediated by complement activation in the brain, because of their reduction resulted from the treatment with mouse C5aR1-specific mAb. Such mAb significantly reduced nucleoprotein expression, suppressed microglial activation and decreased activation of caspase-3 in neurons and p38 phosphorylation in the brain. Collectively, these results suggest that MERS-CoV infection of CNS triggers complement activation, leading to inflammation-mediated damage of brain tissue, and regulating of complement activation could be a promising intervention and adjunctive treatment for CNS injury by MERS-CoV and other coronaviruses.


Assuntos
Encéfalo/patologia , Proteínas do Sistema Complemento/imunologia , Infecções por Coronavirus/patologia , Dipeptidil Peptidase 4/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Animais , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/patologia , Encéfalo/irrigação sanguínea , Encéfalo/imunologia , Encéfalo/virologia , Ativação do Complemento/efeitos dos fármacos , Inativadores do Complemento/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Humanos , Inflamação , Camundongos , Camundongos Transgênicos , Microglia/imunologia , Microglia/patologia
15.
PLoS One ; 16(10): e0257859, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34679094

RESUMO

PURPOSE: To assess the repeatability of multiple automatic vessel density (VD) measurements and the effect of image averaging on vessel detection by optical coherence tomography angiography (OCTA). METHODS: An observational study was conducted in a series of healthy volunteers and patients with macular oedema. Five sequential OCTA images were acquired for each eye using the OptoVue HD device. The effect of the averaging of the 5 acquisitions on vessel detection was analysed quantitatively using a pixel-by-pixel automated analysis. In addition, two independent retina experts qualitatively assessed the change in vessel detection in averaged images segmented in 9 boxes and compared to the first non-averaged image. RESULTS: The automatic VD measurement in OCTA images showed a good repeatability with an overall mean intra-class correlation coefficient (ICC) of 0.924. The mean ICC was higher in healthy eyes compared to eyes with macular oedema (0.877 versus 0.960; p < 0.001) and in the superficial vascular plexus versus the deep vascular complex (0.967 versus 0.888; p = 0.001). The quantitative analysis of the effect of the averaging showed that averaged images had a mean gain of 790.4 pixels/box, located around or completing interruptions in the vessel walls, and a mean loss of 727.2 pixels/box. The qualitative analysis of the averaged images showed that 99.6% of boxes in the averaged images had a gain in vessel detection (i.e., vessels detected in the averaged image but not in the non-averaged image). The loss of pixels was due to a reduction in background noise and motion artifacts in all cases and no case of loss of vessel detection was observed. CONCLUSION: The automatic VD measurement using the OptoVue HD device showed a good repeatability in 5 acquisitions in a row setting. Averaging images increased vessel detection, and in about a third of boxes, decreased the background noise, both in healthy eyes and, in a greater proportion, in eyes with macular oedema.


Assuntos
Vasos Sanguíneos/diagnóstico por imagem , Olho/diagnóstico por imagem , Edema Macular/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagem , Adulto , Idoso , Olho/irrigação sanguínea , Feminino , Angiofluoresceinografia , Voluntários Saudáveis , Humanos , Macula Lutea/diagnóstico por imagem , Macula Lutea/patologia , Edema Macular/patologia , Masculino , Retina/diagnóstico por imagem , Retina/patologia , Vasos Retinianos/patologia , Tomografia de Coerência Óptica , Adulto Jovem
16.
PLoS One ; 16(10): e0257457, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34679077

RESUMO

OBJECTIVE: An evidence regarding which bony flap for reconstruction of mandibular defects following tumour resection is associated with the highest survival rate is still lacking. This network meta-analysis (NMA) aimed to guide surgeons selecting which vascularized osseous flap is associated with the highest survival rate for mandibular reconstruction. METHODS: From inception to March 2021, PubMed, Embase, Scopus, and Cochrane library were searched to identify the eligible studies. The outcome variable was the flap survival rate. The Bayesian NMA accompanied by a random effect model and 95% credible intervals (CrI) was calculated. RESULTS: Twenty-two studies with a total of 1513 patients, comparing four osseous flaps namely fibula free flap (FFF), deep circumferential iliac artery flap (DCIA), scapula flap, and osteocutaneous radial forearm flap (ORFF) were included. The respective survival rates of FFF, DCIA, Scapula, and ORFF were 94.50%, 93.12%, 97%, and 95.95%. The NMA failed to show a statistically significant difference between all comparators (FFF versus DCIA (Odd ratio, 1.8; CrI, 0.58,5.0); FFF versus ORFF (Odd ratio, 0.57; CrI, 0.077; 2.9); FFF versus scapula flap (Odd ratio, 0.25; CrI, 0.026; 1.5); DCIA versus ORFF (Odd ratio, 0.32; CrI, 0.037; 2.1); DCIA versus scapula flap (Odd ratio, 0.14; CrI, 0.015; 1.1) and ORFF versus scapula flap (Odd ratio, 2.3; CrI, 0.16; 34)). CONCLUSION: Within the limitations of the current NMA, FFF, DCIA, Scapula, and ORFF showed a comparable survival rate for mandibular reconstruction. Although the scapula flap reported the highest survival rate compared to other osseous flaps for mandibular reconstruction; however, the decision making when choosing an osseous flap should be based on many factors rather than simply flap survival rate.


Assuntos
Retalhos de Tecido Biológico , Reconstrução Mandibular/métodos , Neoplasias Ósseas/cirurgia , Retalhos de Tecido Biológico/irrigação sanguínea , Retalhos de Tecido Biológico/transplante , Humanos , Mandíbula/cirurgia , Metanálise em Rede , Escápula/irrigação sanguínea , Escápula/transplante
17.
Nat Commun ; 12(1): 5922, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635666

RESUMO

Death from acute hemorrhage is a major problem in military conflicts, traffic accidents, and surgical procedures, et al. Achieving rapid effective hemostasis for pre-hospital care is essential to save lives in massive bleeding. An ideal hemostasis material should have those features such as safe, efficient, convenient, economical, which remains challenging and most of them cannot be achieved at the same time. In this work, we report a rapid effective nanoclay-based hemostatic membranes with nanoclay particles incorporate into polyvinylpyrrolidone (PVP) electrospun fibers. The nanoclay electrospun membrane (NEM) with 60 wt% kaolinite (KEM1.5) shows better and faster hemostatic performance in vitro and in vivo with good biocompatibility compared with most other NEMs and clay-based hemostats, benefiting from its enriched hemostatic functional sites, robust fluffy framework, and hydrophilic surface. The robust hemostatic bandages based on nanoclay electrospun membrane is an effective candidate hemostat in practical application.


Assuntos
Bandagens , Hemorragia/tratamento farmacológico , Hemostáticos/farmacologia , Caulim/farmacologia , Nanoestruturas/química , Ferida Cirúrgica/tratamento farmacológico , Animais , Argila/química , Modelos Animais de Doenças , Hemorragia/sangue , Hemorragia/patologia , Hemostasia/efeitos dos fármacos , Hemostáticos/química , Humanos , Caulim/química , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Fígado/lesões , Masculino , Nanoestruturas/administração & dosagem , Nanoestruturas/ultraestrutura , Povidona/química , Povidona/farmacologia , Ratos , Ratos Sprague-Dawley , Baço/irrigação sanguínea , Baço/efeitos dos fármacos , Baço/lesões , Ferida Cirúrgica/sangue , Ferida Cirúrgica/patologia
18.
Cancer Imaging ; 21(1): 56, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627393

RESUMO

BACKGROUND: The accuracy of estimating microvascular invasion (MVI) preoperatively in hepatocellular carcinoma (HCC) by clinical observers is low. Most recent studies constructed MVI predictive models utilizing radiological and/or radiomics features extracted from computed tomography (CT) images. These methods, however, rely heavily on human experiences and require manual tumor contouring. We developed a deep learning-based framework for preoperative MVI prediction by using CT images of arterial phase (AP) with simple tumor labeling and without the need of manual feature extraction. The model was further validated on CT images that were originally scanned at multiple different hospitals. METHODS: CT images of AP were acquired for 309 patients from China Medical University Hospital (CMUH). Images of 164 patients, who took their CT scanning at 54 different hospitals but were referred to CMUH, were also collected. Deep learning (ResNet-18) and machine learning (support vector machine) models were constructed with AP images and/or patients' clinical factors (CFs), and their performance was compared systematically. All models were independently evaluated on two patient cohorts: validation set (within CMUH) and external set (other hospitals). Subsequently, explainability of the best model was visualized using gradient-weighted class activation map (Grad-CAM). RESULTS: The ResNet-18 model built with AP images and patients' clinical factors was superior than other models achieving a highest AUC of 0.845. When evaluating on the external set, the model produced an AUC of 0.777, approaching its performance on the validation set. Model interpretation with Grad-CAM revealed that MVI relevant imaging features on CT images were captured and learned by the ResNet-18 model. CONCLUSIONS: This framework provide evidence showing the generalizability and robustness of ResNet-18 in predicting MVI using CT images of AP scanned at multiple different hospitals. Attention heatmaps obtained from model explainability further confirmed that ResNet-18 focused on imaging features on CT overlapping with the conditions used by radiologists to estimate MVI clinically.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Aprendizado Profundo , Neoplasias Hepáticas/diagnóstico por imagem , Invasividade Neoplásica , Idoso , Carcinoma Hepatocelular/irrigação sanguínea , Feminino , Hospitais , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Estudos Retrospectivos
20.
Nat Commun ; 12(1): 6072, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663817

RESUMO

Primary congenital glaucoma (PCG) is a severe disease characterized by developmental defects in the trabecular meshwork (TM) and Schlemm's canal (SC), comprising the conventional aqueous humor outflow pathway of the eye. Recently, heterozygous loss of function variants in TEK and ANGPT1 or compound variants in TEK/SVEP1 were identified in children with PCG. Moreover, common variants in ANGPT1and SVEP1 have been identified as risk alleles for primary open angle glaucoma (POAG) in GWAS studies. Here, we show tissue-specific deletion of Angpt1 or Svep1 from the TM causes PCG in mice with severe defects in the adjacent SC. Single-cell transcriptomic analysis of normal and glaucomatous Angpt1 deficient eyes allowed us to identify distinct TM and SC cell populations and discover additional TM-SC signaling pathways. Furthermore, confirming the importance of angiopoietin signaling in SC, delivery of a recombinant ANGPT1-mimetic promotes developmental SC expansion in healthy and Angpt1 deficient eyes, blunts intraocular pressure (IOP) elevation and RGC loss in a mouse model of PCG and lowers IOP in healthy adult mice. Our data highlight the central role of ANGPT1-TEK signaling and TM-SC crosstalk in IOP homeostasis and provide new candidates for SC-targeted glaucoma therapy.


Assuntos
Humor Aquoso/metabolismo , Comunicação Celular/fisiologia , Glaucoma de Ângulo Aberto/patologia , Glaucoma de Ângulo Aberto/terapia , Angiopoietina-1/administração & dosagem , Angiopoietina-1/genética , Angiopoietina-1/metabolismo , Animais , Câmara Anterior/irrigação sanguínea , Câmara Anterior/citologia , Câmara Anterior/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Comunicação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Perfilação da Expressão Gênica , Glaucoma de Ângulo Aberto/genética , Glaucoma de Ângulo Aberto/metabolismo , Pressão Intraocular/efeitos dos fármacos , Pressão Intraocular/genética , Camundongos , Camundongos Knockout , Crista Neural/citologia , Crista Neural/metabolismo , Proteínas/genética , Proteínas/metabolismo , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transdução de Sinais/efeitos dos fármacos , Análise de Célula Única , Malha Trabecular/citologia , Malha Trabecular/metabolismo
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