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1.
Nat Commun ; 11(1): 3812, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32732889

RESUMO

Vascular endothelial cell (EC) dysfunction plays a key role in diabetic complications. This study discovers significant upregulation of Quaking-7 (QKI-7) in iPS cell-derived ECs when exposed to hyperglycemia, and in human iPS-ECs from diabetic patients. QKI-7 is also highly expressed in human coronary arterial ECs from diabetic donors, and on blood vessels from diabetic critical limb ischemia patients undergoing a lower-limb amputation. QKI-7 expression is tightly controlled by RNA splicing factors CUG-BP and hnRNPM through direct binding. QKI-7 upregulation is correlated with disrupted cell barrier, compromised angiogenesis and enhanced monocyte adhesion. RNA immunoprecipitation (RIP) and mRNA-decay assays reveal that QKI-7 binds and promotes mRNA degradation of downstream targets CD144, Neuroligin 1 (NLGN1), and TNF-α-stimulated gene/protein 6 (TSG-6). When hindlimb ischemia is induced in diabetic mice and QKI-7 is knocked-down in vivo in ECs, reperfusion and blood flow recovery are markedly promoted. Manipulation of QKI-7 represents a promising strategy for the treatment of diabetic vascular complications.


Assuntos
Diabetes Mellitus Experimental/patologia , Células Endoteliais/metabolismo , Proteínas de Ligação a RNA/antagonistas & inibidores , Proteínas de Ligação a RNA/metabolismo , Doenças Vasculares/patologia , Animais , Antígenos CD/genética , Aterosclerose/patologia , Caderinas/genética , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular Neuronais/genética , Células Cultivadas , Regulação da Expressão Gênica/genética , Humanos , Hiperglicemia/patologia , Isquemia/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Interferência de RNA , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Proteínas de Ligação a RNA/genética
2.
Plast Reconstr Surg ; 146(2): 227-237, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32740566

RESUMO

BACKGROUND: Preoperative planning of microsurgical perforator free flaps continues to be a discussion topic among microsurgeons. The purpose of this study was to compare the ability of three methods of preoperative vascular mapping-hand-held Doppler imaging, color Doppler ultrasonography, and computed tomographic angiography-to detect perforators and their concordance with surgical findings. METHODS: A prospective study was performed to evaluate the sensitivity, specificity, and accuracy of hand-held Doppler imaging, color Doppler ultrasonography, and computed tomographic angiography to detect free flap perforators. Each patient undergoing a free flap reconstruction was studied preoperatively with the three methods, and the results were compared to the intraoperative findings. RESULTS: Fifty-three patients undergoing autologous tissue reconstruction were included. Most reconstructions (71.7 percent) were performed with anterolateral thigh flaps. The positive predictive value (color Doppler ultrasonography, 100 percent; computed tomographic angiography, 100 percent; hand-held Doppler imaging, 88.6 percent) and negative predictive value (color Doppler ultrasonography, 100 percent; computed tomographic angiography, 94.3 percent; hand-held Doppler imaging, 90.5 percent) rates were significantly different between methods. The high resolution of the color Doppler ultrasonography probe provided a direct vision of the vasculature arborization and efficiently detected vessels with diameters of less than 0.5 mm. The sensitivity, specificity, and accuracy of color Doppler ultrasonography were greater than those of both computed tomographic angiography and hand-held Doppler imaging. There was 100 percent concordance between color Doppler ultrasonography perforators and the surgical findings. CONCLUSIONS: Color Doppler ultrasonography provides a reproducible, harmless, and accurate way to visualize vascular anatomy. It has a high correlation with the surgical findings, signifying advantages over hand-held Doppler and computed tomographic angiography in sensitivity, specificity, and accuracy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Computadores de Mão , Retalho Perfurante/irrigação sanguínea , Procedimentos Cirúrgicos Reconstrutivos/métodos , Ultrassonografia Doppler em Cores/métodos , Doenças Vasculares/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Microcirurgia/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Reprodutibilidade dos Testes , Resultado do Tratamento , Doenças Vasculares/diagnóstico
4.
Wiad Lek ; 73(4): 743-745, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32731708

RESUMO

OBJECTIVE: The aim is to analyze the value of endothelial dysfunction markers during pregnancy. PATIENTS AND METHODS: Materials and methods: We have examined 153 pregnant women to identify endothelial dysfunction markers of endothelin-1, nitrogen oxide (NO) that have been studiedusing immunoenzymometric sets for an uncomplicated and complicated pregnancy. RESULTS: Results: We found that the concentration of endothelin-1 repeatedly exceeded the rates in pregnant women with miscarriages than during physiological pregnancy. The diametrically opposite pattern concerns the level of nitrogen oxide. These changes in the markers of the functional state of the endothelin indicate the development of the dysfunction of this system in women with the pathology of pregnancy. CONCLUSION: Conclusions: Consequently, endothelial dysfunction can be considered to be one of the reasons for miscarriage in the examined women. Therefore, the definition of markersof endothelial dysfunction has prognostic value.


Assuntos
Doenças Vasculares , Aborto Espontâneo , Biomarcadores , Endotelina-1 , Feminino , Humanos , Pré-Eclâmpsia , Gravidez
6.
Phlebology ; 35(8): 550-555, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32639862

RESUMO

The coronavirus disease 2019 (COVID-19) global pandemic has resulted in diversion of healthcare resources to the management of patients infected with SARS-CoV-2 virus. Elective interventions and surgical procedures in most countries have been postponed and operating room resources have been diverted to manage the pandemic. The Venous and Lymphatic Triage and Acuity Scale was developed to provide an international standard to rationalise and harmonise the management of patients with venous and lymphatic disorders or vascular anomalies. Triage urgency was determined based on clinical assessment of urgency with which a patient would require medical treatment or surgical intervention. Clinical conditions were classified into six categories of: (1) venous thromboembolism (VTE), (2) chronic venous disease, (3) vascular anomalies, (4) venous trauma, (5) venous compression and (6) lymphatic disease. Triage urgency was categorised into four groups and individual conditions were allocated to each class of triage. These included (1) medical emergencies (requiring immediate attendance), example massive pulmonary embolism; (2) urgent (to be seen as soon as possible), example deep vein thrombosis; (3) semi-urgent (to be attended to within 30-90 days), example highly symptomatic chronic venous disease, and (4) discretionary/non-urgent- (to be seen within 6-12 months), example chronic lymphoedema. Venous and Lymphatic Triage and Acuity Scale aims to standardise the triage of patients with venous and lymphatic disease or vascular anomalies by providing an international consensus-based classification of clinical categories and triage urgency. The scale may be used during pandemics such as the current COVID-19 crisis but may also be used as a general framework to classify urgency of the listed conditions.


Assuntos
Infecções por Coronavirus/terapia , Sistemas de Apoio a Decisões Clínicas/normas , Técnicas de Apoio para a Decisão , Serviço Hospitalar de Emergência/normas , Doenças Linfáticas/terapia , Pneumonia Viral/terapia , Triagem/normas , Doenças Vasculares/terapia , Tomada de Decisão Clínica , Consenso , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Necessidades e Demandas de Serviços de Saúde/normas , Humanos , Doenças Linfáticas/diagnóstico , Doenças Linfáticas/epidemiologia , Pandemias , Seleção de Pacientes , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Doenças Vasculares/diagnóstico , Doenças Vasculares/epidemiologia
13.
Lancet Haematol ; 7(8): e575-e582, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32619411

RESUMO

BACKGROUND: An important feature of severe acute respiratory syndrome coronavirus 2 pathogenesis is COVID-19-associated coagulopathy, characterised by increased thrombotic and microvascular complications. Previous studies have suggested a role for endothelial cell injury in COVID-19-associated coagulopathy. To determine whether endotheliopathy is involved in COVID-19-associated coagulopathy pathogenesis, we assessed markers of endothelial cell and platelet activation in critically and non-critically ill patients admitted to the hospital with COVID-19. METHODS: In this single-centre cross-sectional study, hospitalised adult (≥18 years) patients with laboratory-confirmed COVID-19 were identified in the medical intensive care unit (ICU) or a specialised non-ICU COVID-19 floor in our hospital. Asymptomatic, non-hospitalised controls were recruited as a comparator group for biomarkers that did not have a reference range. We assessed markers of endothelial cell and platelet activation, including von Willebrand Factor (VWF) antigen, soluble thrombomodulin, soluble P-selectin, and soluble CD40 ligand, as well as coagulation factors, endogenous anticoagulants, and fibrinolytic enzymes. We compared the level of each marker in ICU patients, non-ICU patients, and controls, where applicable. We assessed correlations between these laboratory results with clinical outcomes, including hospital discharge and mortality. Kaplan-Meier analysis was used to further explore the association between biochemical markers and survival. FINDINGS: 68 patients with COVID-19 were included in the study from April 13 to April 24, 2020, including 48 ICU and 20 non-ICU patients, as well as 13 non-hospitalised, asymptomatic controls. Markers of endothelial cell and platelet activation were significantly elevated in ICU patients compared with non-ICU patients, including VWF antigen (mean 565% [SD 199] in ICU patients vs 278% [133] in non-ICU patients; p<0·0001) and soluble P-selectin (15·9 ng/mL [4·8] vs 11·2 ng/mL [3·1]; p=0·0014). VWF antigen concentrations were also elevated above the normal range in 16 (80%) of 20 non-ICU patients. We found mortality to be significantly correlated with VWF antigen (r = 0·38; p=0·0022) and soluble thrombomodulin (r = 0·38; p=0·0078) among all patients. In all patients, soluble thrombomodulin concentrations greater than 3·26 ng/mL were associated with lower rates of hospital discharge (22 [88%] of 25 patients with low concentrations vs 13 [52%] of 25 patients with high concentrations; p=0·0050) and lower likelihood of survival on Kaplan-Meier analysis (hazard ratio 5·9, 95% CI 1·9-18·4; p=0·0087). INTERPRETATION: Our findings show that endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death. Early identification of endotheliopathy and strategies to mitigate its progression might improve outcomes in COVID-19. FUNDING: This work was supported by a gift donation from Jack Levin to the Benign Hematology programme at Yale, and the National Institutes of Health.


Assuntos
Betacoronavirus/patogenicidade , Transtornos da Coagulação Sanguínea/patologia , Infecções por Coronavirus/complicações , Endotélio Vascular/patologia , Pneumonia Viral/complicações , Doenças Vasculares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/metabolismo , Infecções por Coronavirus/virologia , Estado Terminal , Estudos Transversais , Endotélio Vascular/metabolismo , Feminino , Seguimentos , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Prognóstico , Doenças Vasculares/etiologia , Doenças Vasculares/metabolismo , Adulto Jovem
16.
Ann Vasc Surg ; 67: 1-5, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32505678

RESUMO

BACKGROUND: The epidemic potential of coronavirus infection is now a reality. Since the first case detected in late 2019 in China, a fast worldwide expansion confirms it. The vascular patient is at a higher risk of developing a severe form of the disease because of its nature associating several comorbid states, and thus, some vascular surgery communities from many countries have tried to stratify patients into those requiring care during these uncertain times. METHODS: This is an observational study describing the current daily vascular surgery practice at one tertiary academic hospital in Madrid region, Spain-one of the most affected regions worldwide due to the COVID-19 outbreak. We analyzed our surgical practice since March 14th when the lockdown was declared up to date, May 14th (2 months). Procedural surgical practice, organizational issues, early outcomes, and all the troubles encountered during this new situation are described. RESULTS: Our department is composed of 10 vascular surgeons and 4 trainees. Surgical practice has been reduced to only urgent care, totaling 50 repairs on 45 patients during the period. Five surgeries were performed on 3 COVID-19-positive patients. Sixty percent were due to critical limb ischemia, 45% of them performed by complete endovascular approach, whereas less than 10% of repairs were aorta related. We were allocated to use a total of 5 surgical rooms in different locations, none our usual, as it was converted into an ICU room while performing 50% of those repairs with unusual nursery staff. CONCLUSIONS: The COVID-19 outbreak has dramatically changed our organization and practice in favor of urgent or semiurgent surgical care alone. The lack of in-hospital/ICU beds and changing nursery staff changed the whole availability organization at our hospital and was a key factor in surgical decision-making in some cases.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Pandemias , Pneumonia Viral/complicações , Especialidades Cirúrgicas/estatística & dados numéricos , Doenças Vasculares/cirurgia , Procedimentos Cirúrgicos Vasculares/organização & administração , Infecções por Coronavirus/epidemiologia , Humanos , Pneumonia Viral/epidemiologia , Espanha/epidemiologia , Doenças Vasculares/complicações
20.
Eur J Vasc Endovasc Surg ; 60(1): 127-134, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32499169

RESUMO

OBJECTIVE: This study aimed to evaluate the protocol adopted during the emergency phase of the COVID-19 pandemic to maintain elective activity in a vascular surgery unit while minimising the risk of contamination to both patients and physicians, and the impact of this activity on the intensive care (IC) resources. METHODS: The activity of a vascular surgery unit was analysed from 8 March to 8 April 2020. Surgical activity was maintained only for acute or elective procedures obeying priority criteria. The preventive screening protocol consisted of nasopharyngeal swabs (NPS) for all patients and physicians with symptoms and for unprotected contact infected cases, and serological physician evaluations every 15 days. Patients treated in the acute setting were considered theoretically infected and the necessary protective devices were used. The number of patients and the possible infection of physicians were evaluated. The number and type of interventions and the need for post-operative IC during this period were compared with those in the same periods in 2018 and 2019. RESULTS: One hundred and fifty-one interventions were performed, of which 34 (23%) were acute/emergency. The total number of interventions was similar to those performed in the same periods in 2019 and 2018: 150 (33, of which 22% acute/emergency) and 117 (29, 25% acute/emergency), respectively. IC was necessary after 6% (17% in 2019 and 20% in 2018) of elective operations and 33% (11) of acute/emergency interventions. None of the patients treated electively were diagnosed with COVID-19 infection during hospitalisation. Of the 34 patients treated in acute/emergency interventions, five (15%) were diagnosed with COVID-19 infection. It was necessary to screen 14 (47%) vascular surgeons with NPS after contact with infected colleagues, but none for unprotected contact with patients; all were found to be negative on NPS and serological evaluation. CONCLUSION: A dedicated protocol allowed maintenance of regular elective vascular surgery activity during the emergency phase of the COVID-19 pandemic, with no contamination of patients or physicians and minimal need for IC resources.


Assuntos
Infecções por Coronavirus , Procedimentos Cirúrgicos Eletivos , Serviço Hospitalar de Emergência , Controle de Infecções , Pandemias , Pneumonia Viral , Doenças Vasculares , Procedimentos Cirúrgicos Vasculares , Adulto , Betacoronavirus/isolamento & purificação , Protocolos Clínicos , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Procedimentos Clínicos/tendências , Procedimentos Cirúrgicos Eletivos/métodos , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Controle de Infecções/métodos , Controle de Infecções/organização & administração , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Avaliação de Programas e Projetos de Saúde , Doenças Vasculares/epidemiologia , Doenças Vasculares/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Procedimentos Cirúrgicos Vasculares/estatística & dados numéricos
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