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1.
Expert Rev Hematol ; 14(2): 155-173, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33480807

RESUMO

INTRODUCTION: COVID-19 has similarities to the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, as severe patients and non-survivors have frequently shown abnormal coagulation profiles. Immune-mediated pathology is a key player in this disease; hence, the role of the complement system needs assessment. The complement system and the coagulation cascade share an intricate network, where multiple mediators maintain a balance between both pathways. Coagulopathy in COVID-19, showing mixed features of complement-mediated and consumption coagulopathy, creates a dilemma in diagnosis and management. AREAS COVERED: Pathophysiology of coagulopathy in COVID-19 patients, with a particular focus on D-dimer and its role in predicting the severity of COVID-19 has been discussed. A comprehensive search of the medical literature on PubMed was done till May 30th, 2020 with the keywords 'COVID-19', 'SARS-CoV-2', 'Coronavirus', 'Coagulopathy', and 'D-dimer'. Twenty-two studies were taken for weighted pooled analysis of D-dimer. EXPERT OPINION: A tailored anticoagulant regimen, including intensification of standard prophylactic regimens with low-molecular-weight heparin is advisable for COVID-19 patients. Atypical manifestations and varying D-dimer levels seen in different populations bring forth the futility of uniform recommendations for anticoagulant therapy. Further, direct thrombin inhibitors and platelet inhibitors in a patient-specific manner should also be considered.


Assuntos
Transtornos da Coagulação Sanguínea/etiologia , Ativação do Complemento , Animais , Anticoagulantes/uso terapêutico , Biomarcadores , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/imunologia , Transtornos da Coagulação Sanguínea/fisiopatologia , Testes de Coagulação Sanguínea , /imunologia , China/epidemiologia , Comorbidade , Infecções por Coronavirus/sangue , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/epidemiologia , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/fisiopatologia , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Previsões , Humanos , Imunização Passiva , Inflamação/etiologia , Inflamação/fisiopatologia , Quelantes de Ferro/uso terapêutico , Isquemia/sangue , Isquemia/etiologia , Isquemia/fisiopatologia , Camundongos , Prevalência , Síndrome Respiratória Aguda Grave/sangue , Índice de Gravidade de Doença , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Trombofilia/fisiopatologia , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/fisiopatologia
2.
Arterioscler Thromb Vasc Biol ; 40(9): 2322-2331, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32698688

RESUMO

OBJECTIVE: Inflammatory markers, such as hs-CRP (high-sensitivity C-reactive protein), have been reported to be related to peripheral artery disease (PAD). Galectin-3, a biomarker of fibrosis, has been linked to vascular remodeling and atherogenesis. However, its prospective association with incident PAD is unknown; as is the influence of inflammation on the association between galectin-3 and PAD. Approach and Results: In 9851 Atherosclerosis Risk in Communities Study participants free of PAD at baseline (1996-1998), we quantified the association of galactin-3 and hs-CRP with incident PAD (hospitalizations with PAD diagnosis [International Classification of Diseases-Ninth Revision: 440.2-440.4] or leg revascularization [eg, International Classification of Diseases-Ninth Revision: 38.18]) as well as its severe form, critical limb ischemia (PAD cases with resting pain, ulcer, gangrene, or leg amputation) using Cox models. Over a median follow-up of 17.4 years, there were 316 cases of PAD including 119 critical limb ischemia cases. Log-transformed galectin-3 was associated with incident PAD (adjusted hazard ratio, 1.17 [1.05-1.31] per 1 SD increment) and critical limb ischemia (1.25 [1.05-1.49] per 1 SD increment). The association was slightly attenuated after further adjusting for hs-CRP (1.14 [1.02-1.27] and 1.22 [1.02-1.45], respectively). Log-transformed hs-CRP demonstrated robust associations with PAD and critical limb ischemia even after adjusting for galectin-3 (adjusted hazard ratio per 1 SD increment 1.34 [1.18-1.52] and 1.34 [1.09-1.65], respectively). The addition of galectin-3 and hs-CRP to traditional atherosclerotic predictors (C statistic of the base model 0.843 [0.815-0.871]) improved the risk prediction of PAD (ΔC statistics, 0.011 [0.002-0.020]). CONCLUSIONS: Galectin-3 and hs-CRP were independently associated with incident PAD in the general population, supporting the involvement of fibrosis and inflammation in the pathophysiology of PAD.


Assuntos
Proteína C-Reativa/análise , Galectina 3/sangue , Mediadores da Inflamação/sangue , Claudicação Intermitente/sangue , Isquemia/sangue , Doença Arterial Periférica/sangue , Idoso , Biomarcadores/sangue , Estado Terminal , Feminino , Fibrose , Humanos , Incidência , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/epidemiologia , Claudicação Intermitente/terapia , Isquemia/diagnóstico , Isquemia/epidemiologia , Isquemia/terapia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/terapia , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos
4.
Ann Vasc Surg ; 68: 88-92, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32589931

RESUMO

Heparin resistance is an uncommon phenomenon defined as the need for high-dose unfractionated heparin (UFH) of more than 35,000 IU/day to achieve the target activated partial-thromboplastin time ratio or the failure to achieve the desired activated clotting time after a full UFH dose. This rare phenomenon is being more commonly observed in Covid-19 patients in a hypercoagulable state. We describe a Covid-19 patient confirmed by reverse-transcriptase polymerase chain reaction assay, with acute limb ischemia, who developed heparin resistance. The patient was managed by the departments of vascular surgery, anesthesia and intensive care, and the Coagulation Service and Thrombosis Research from San Raffaele Scientific Institute, Milan, Italy.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Resistência a Medicamentos , Heparina/farmacologia , Isquemia/tratamento farmacológico , Extremidade Inferior/irrigação sanguínea , Pneumonia Viral/complicações , Doença Aguda , Idoso , Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Humanos , Isquemia/sangue , Isquemia/etiologia , Masculino , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Tomografia Computadorizada por Raios X
6.
Vascular ; 28(5): 629-642, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32366176

RESUMO

OBJECTIVES: Regulatory T cells (Tregs) mediate immunomodulation and protect against atherosclerosis. It is considered that reducing the amount of pro-inflammatory mediators could be achieved by enhancing the anti-inflammatory response, and this may be considered one of the main targets for therapy development. The inhibitory cytokines secreted by Tregs mainly include interleukin-10 (IL-10) and transforming growth factor-beta (TGF-ß). Based on its known immunosuppressive involvement with other inflammatory disorders, we hypothesized that the newly characterized cytokine interleukin-37 (IL-37) might be associated with the inhibitory functions of Treg in atherosclerosis. Immune regulatory functions of IL-37 have not been completely clarified. Accordingly, we speculated that IL-37 might play a regulatory role in the immunosuppression of Tregs in atherosclerotic disease. METHODS: Real-time polymerase chain reaction and enzyme linked immunosorbent assay were used to test gene expression and protein levels of IL-37 in peripheral blood and localized freshly resected arterial tissues from 84 patients with peripheral arterial occlusive disease and 50 non-atherosclerotic subjects. Results were correlated to disease hallmarks. We also evaluated the ability of recombinant IL-37 to modulate Treg cytokine secretion and T cell inhibition in relation to atherosclerotic disorder in vitro.Results: Our results revealed that IL-37 was increased in patients with chronic lower limb atherosclerotic ischemia, compared to non-atherosclerotic controls. In addition, the expression levels of circulating IL-37 correlated with disease severity of chronic lower limb ischemia. Supplementation with rIL-37 augmented levels of released IL-10 and TGF-ß in supernatants of T cells co-cultured with Tregs in the enrolled patients.Conclusions: Results suggest a role for IL-37 in mediating anti-inflammatory functions in the atherosclerotic process, potentially involving enhancement of Treg inhibitory function and anti-inflammatory cytokine secretion with a particularly marked direct response in severe disease.


Assuntos
Interleucina-1/sangue , Isquemia/sangue , Doença Arterial Periférica/sangue , Linfócitos T Reguladores/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Células Cultivadas , Técnicas de Cocultura , Feminino , Humanos , Interleucina-1/genética , Interleucina-1/farmacologia , Interleucina-10/metabolismo , Isquemia/diagnóstico , Isquemia/imunologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/imunologia , Fenótipo , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Fator de Crescimento Transformador beta/metabolismo
7.
J Med Life ; 13(1): 45-49, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32341700

RESUMO

The problem of lower limb preservation with symptoms of critical ischemia, resulting in necrosis of the distal foot portion, remains open. These cases require solving few tactical questions, such as the primary revascularization method, limb-preserving amputation, stimulation of regeneration, and finally, determining the criteria for auto-dermal transplantation. We analyzed 29 patient cases with critical lower limb ischemia of fourth grade, according to the Fontaine classification (or the sixth category according to Rutherford's classification), who underwent partial foot amputation due to dry gangrene and were threated using PRGF®-ENDORET® platelet-rich plasma and platelet-rich fibrin technology. The control group was comprised of 21 patients who received traditional postoperative wound treatment. All patients went through a combination of transluminal revascularization and platelet-rich plasma to create a "therapeutic" neoangiogenic effect. Indications for these procedures were severe distal arterial occlusion and stenosis. Using transluminal procedures with platelet-rich plasma therapy improves the blood perfusion to the distal portions of the limb in patients with critical ischemia in a short time, which is an informative diagnostic criterion for wound healing after amputation. Plasmatic membranes create an optimal environment for tissue regeneration, thus reducing the wound closure time using an auto-dermal transplant.


Assuntos
Amputação , Pé/cirurgia , Isquemia/terapia , Fibrina Rica em Plaquetas/metabolismo , Plasma Rico em Plaquetas/metabolismo , Citocinas/sangue , Humanos , Isquemia/sangue , Masculino , Pessoa de Meia-Idade , Temperatura Cutânea , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/administração & dosagem , Cicatrização
8.
Medicine (Baltimore) ; 99(16): e19691, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32311945

RESUMO

BACKGROUND: Red cell distribution width level may have relations with the incidence and prognosis of cerebrovascular diseases. Recent researches have reported that red cell distribution width level was linked to the occurrence of stroke. However, the predicted effect of red cell distribution width in stroke is still disputed. We sought to assess the relationship between red cell distribution width and risk of stroke in this meta-analysis. METHODS: Relevant studies were picked out from the databases of Embase, PubMed, and Cochrane Library. Hazard ratio with 95% confidence interval was chosen to analyze each trial, which was extracted from results of the highest and lowest red cell distribution width group. Funnel plots, Begg and Egger test were used to assess publication bias in the meta-analysis. Stata(12.0) was utilized to perform statistic analysis in the process. RESULTS: A total of 6 studies with 5783 patients were included in this meta-analysis. The results showed that red cell distribution width level in patients with stroke was significantly higher than it in those without stroke (HR = 1.34, 95%CI:1.23-1.47, P < .001), in particular ischemic stroke(HR = 1.34,95% confidence interval:1.1-1.54, P < .001). There was no evidence of heterogeneity across the studies (P = .355, I = 5.53%). CONCLUSIONS: The higher red cell distribution width level was associated with an increased risk of stroke, especially ischemic infarction.


Assuntos
Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Índices de Eritrócitos , Humanos , Isquemia/sangue , Isquemia/epidemiologia , Fatores de Risco
9.
Vascular ; 28(4): 368-377, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32252612

RESUMO

OBJECTIVE: Peripheral artery disease patients have been shown to be more susceptible to thrombotic events compared to non-peripheral artery disease patients. Therefore, the aim of this study was to investigate the coagulation profile in peripheral artery disease patients with chronic limb threatening ischemia, moderate peripheral artery disease patients with claudication, and non-peripheral artery disease controls. METHODS: Chronic limb threatening ischemia patients were matched to peripheral artery disease patients with claudication and non-peripheral artery disease controls in a 1:1:1 ratio. Each patient had their cytokines, markers of thrombin generation, coagulation factors, natural anti-coagulants, fibrinolysis, and endothelial injury markers assessed. RESULTS: Markers of thrombin activation, thrombin Fragments F1 + 2 (Frag 1 + 2), and thrombin-anti-thrombin complex were found to be significantly elevated in all peripheral artery disease and chronic limb threatening ischemia patients relative to non-peripheral artery disease controls. Similarly, relative to non-peripheral artery disease controls, inflammatory markers including C-reactive protein, soluble platelet factor 4, and neutrophil gelatinase-associated lipocalin were also found to be significantly upregulated in chronic limb threatening ischemia patients, but not in peripheral artery disease patients with claudication. Furthermore, our data demonstrated significant increases in markers of endothelial injury in chronic limb threatening ischemia patients relative to non-peripheral artery disease controls. Finally, decreases in natural anti-coagulants (protein C and protein S) and coagulation factors FIX, FXI, and FXII were also observed in chronic limb threatening ischemia patients when compared with non-peripheral artery disease controls. CONCLUSIONS: Our data suggest that in relation to non-peripheral artery disease controls, chronic limb threatening ischemia patients are more hypercoagulable. However, peripheral artery disease patients with claudication appear to have similar levels of circulating procoagulant markers as non-peripheral artery disease patients. This may explain the increased risk of thrombotic events observed in chronic limb threatening ischemia patients.


Assuntos
Coagulação Sanguínea , Claudicação Intermitente/sangue , Isquemia/sangue , Doença Arterial Periférica/sangue , Idoso , Antitrombina III , Biomarcadores/sangue , Fatores de Coagulação Sanguínea/análise , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Mediadores da Inflamação/sangue , Claudicação Intermitente/diagnóstico , Isquemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Peptídeo Hidrolases/sangue , Doença Arterial Periférica/diagnóstico , Projetos Piloto , Protrombina
11.
Microvasc Res ; 129: 103967, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31837305

RESUMO

Vascular occlusion test (VOT)-induced reactive hyperemia in brachial artery is crucial to flow-mediated dilation (FMD). Emerging studies have suggested that reactive hyperemia depends on the magnitude of the O2 desaturation (ischemia) in downstream microvessels. Although near-infrared spectroscopy-derived tissue O2 saturation index (TSI) has been used to assess the magnitude of ischemia, the association between FMD and the magnitude of O2 desaturation has not been addressed. Therefore, the aim of the present study was to evaluate whether FMD correlates with the magnitude of muscle O2 desaturation in healthy young individuals and older adults at risk for cardiovascular disease (CVD). Twenty healthy young individuals and 20 others at risk for CVD participated in the study. The magnitude of ischemic stimulus was determined by calculating the area under curve of TSI signal over 5 min of cuff occlusion period. Oxygen resaturation rate was calculated as the upslope of the TSI signal over 10 s following cuff deflation. There was no significant correlation between FMD and the magnitude of ischemic stimulus in both groups assessed (young: R = 0.327; P = 0.159 and older: R = -0.184; P = 0.436). However, a significant correlation between the magnitude of O2 desaturation and O2 resaturation rate in young (R = 0.555; P = 0.011) and older individuals at risk for CVD (R = 0.539; P = 0.014). In conclusion, FMD response did not correlate with the magnitude of muscle O2 desaturation, although it seems to be partially associated with O2 resaturation rate.


Assuntos
Artéria Braquial/fisiologia , Doenças Cardiovasculares/etiologia , Músculo Esquelético/irrigação sanguínea , Consumo de Oxigênio , Oxigênio/sangue , Espectroscopia de Luz Próxima ao Infravermelho , Vasodilatação , Adulto , Fatores Etários , Idoso , Biomarcadores/sangue , Velocidade do Fluxo Sanguíneo , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Feminino , Voluntários Saudáveis , Humanos , Hiperemia/fisiopatologia , Isquemia/sangue , Isquemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fluxo Sanguíneo Regional , Medição de Risco , Fatores de Risco , Adulto Jovem
12.
J Vasc Surg ; 71(6): 2089-2097, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31708302

RESUMO

OBJECTIVE: Plateletcrit (PCT) reflects the total platelet mass in blood and can be calculated from a complete blood count. We examined the effect of PCT on outcomes of endovascular and open interventions for chronic limb ischemia. METHODS: Patients who underwent revascularization for chronic limb ischemia (Rutherford categories 3-6) between June 2001 and December 2014 were retrospectively identified. PCT on admission was recorded. Patients and limbs were divided into tertiles of low (0.046-0.211), medium (0.212-0.271), and high (0.272-0.842) PCT. Patency, limb salvage, major adverse limb events, major adverse cardiac events, and survival rates were calculated using Kaplan-Meier analysis and compared with log-rank test. Cox regression analysis was used for multivariate analysis. RESULTS: A total of 1431 limbs (1210 patients) were identified and divided into low PCT (477 limbs in 407 patients), medium PCT (477 limbs in 407 patients), and high PCT (477 limbs in 396 patients) groups. The patients in the high tertile were 2 years older that the patients in the other two tertiles (P = .009). Five-year primary patency was 65% ± 3% in the low-PCT group compared with 55% ± 3% and 51% ± 3% in the medium and high PCT groups, respectively (P = .004). Five-year secondary patency was 81% ± 2% in the low PCT group compared with 82% ± 2% and 72% ± 3% in the medium and high PCT groups, respectively (P = .02). Five-year limb salvage rate was 86% ± 2% in the low PCT group compared with 79% ± 3% and 74% ± 3% in the medium PCT and high PCT groups, respectively (P = .004). Multivariate regression analysis showed that low PCT was independently associated with primary patency after endovascular interventions (hazard ratio, 0.67 [0.47-0.95]; P = .02) but not after open interventions (hazard ratio, 0.72 [0.43-1.21]; P = .21). CONCLUSIONS: High PCT is associated with poor patency and limb salvage rates after interventions for lower extremity chronic limb ischemia. Multivariate regression analysis confirmed association of low PCT with improved primary patency after endovascular interventions but not after open interventions. High PCT may be a marker of increased platelet reactivity and could be used to identify patients at high risk for early thrombosis and failure after interventions.


Assuntos
Plaquetas , Procedimentos Endovasculares/efeitos adversos , Isquemia/terapia , Doença Arterial Periférica/terapia , Testes de Função Plaquetária , Grau de Desobstrução Vascular , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Idoso , Amputação , Doença Crônica , Bases de Dados Factuais , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Isquemia/sangue , Isquemia/diagnóstico , Isquemia/fisiopatologia , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/mortalidade
13.
J Minim Invasive Gynecol ; 27(2): 548-550, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31574314

RESUMO

Studies have demonstrated that during hysteroscopic myomectomy with bipolar diathermy, carbon monoxide is produced and enters the patient's circulation. However, little is known regarding the immediate or long-term sequelae of transient rises in carboxyhemoglobin levels during hysteroscopic surgery. This paper aims to suggest recommendations for acute evaluation, management, patient counseling, and future research. We present a case of a 36-year-old woman (Gravida 0, Para 0) with abnormal uterine bleeding-leiomyoma and resultant anemia, undergoing hysteroscopic resection of a large submucous myoma. During surgery, the patient was found to have a critically elevated level of carboxyhemoglobin and accompanying electrocardiogram derangements. She was managed with prolonged intubation, 100% O2, and trending of her carboxyhemoglobin levels before extubation. This demonstrates the importance of being cognizant of the potentially toxic gaseous byproducts of bipolar resection and of including intravasation of these byproducts in one's consideration of patient safety during extensive resections. Bipolar hysteroscopic resection of large leiomyomas may result in critically high carboxyhemoglobin levels, which can impair end-organ oxygen delivery with resultant ischemia; the risks of myocardial ischemia should be discussed with the anesthesia team before attempting an extensive resection. Electrocardiogram changes indicative of ischemia should prompt discontinuation of the case. Finally, carboxyhemoglobin poisoning should be included in the differential diagnosis of patients who demonstrate longer-than-expected anesthesia recovery times after bipolar resection of large submucous leiomyomas, and they should be managed with repeat evaluation of carboxyhemoglobin levels, supplemental oxygen, and cardiac monitoring.


Assuntos
Carboxihemoglobina/metabolismo , Isquemia/sangue , Leiomioma/cirurgia , Complicações Pós-Operatórias/sangue , Hemorragia Uterina/cirurgia , Miomectomia Uterina/efeitos adversos , Neoplasias Uterinas/cirurgia , Adulto , Carboxihemoglobina/análise , Estado Terminal/terapia , Eletrocardiografia , Feminino , Humanos , Histeroscopia/efeitos adversos , Histeroscopia/métodos , Isquemia/etiologia , Isquemia/terapia , Leiomioma/sangue , Leiomioma/complicações , Duração da Cirurgia , Complicações Pós-Operatórias/diagnóstico , Hemorragia Uterina/etiologia , Neoplasias Uterinas/sangue , Neoplasias Uterinas/complicações
14.
J Cardiovasc Pharmacol Ther ; 25(2): 158-163, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31550912

RESUMO

BACKGROUND: Critical limb-threatening ischemia (CLTI) is associated with an increased risk of major adverse limb events and mortality. High on-treatment platelet reactivity (HPR) is associated with an increased risk of ischemic events, while low on-treatment platelet reactivity (LPR) is associated with an increased risk of bleeding. This study investigates the frequency with which patients with CLTI on clopidogrel or ticagrelor achieve a "therapeutic window" (TW) of platelet inhibition. METHODS: Data from the "Switch To Ticagrelor in Critical Limb Ischemia Anti-Platelet Study" were assessed retrospectively to determine the incidence of TW of on-treatment platelet reactivity in 50 consecutive patients with CLTI (mean age: 65.2 ± 10.5 years, 54% male). The data included 4 measurements of patients' platelet reactivity using the VerifyNow P2Y12 Assay: baseline and steady state platelet reactivity on clopidogrel 75 mg daily and on ticagrelor 90 mg twice daily. RESULTS: At baseline, 46% of patients on clopidogrel were within TW of on-treatment platelet reactivity compared to 10% of patients on ticagrelor (P < .0001). At steady state, 42% of patients on clopidogrel were within the TW compared to 10% of patients on ticagrelor (P < .0001). Patients on ticagrelor exhibited higher rates of LPR compared to those on clopidogrel at baseline as well as at steady state (baseline 88% vs 18%, steady state 88% vs 28%; P < .0001). CONCLUSION: Although ticagrelor has been proposed as an alternative for patients with HPR on clopidogrel, the current study observes an excess of platelet inhibition with ticagrelor in most patients with CLTI at a dose of 90 mg twice daily.


Assuntos
Clopidogrel/administração & dosagem , Isquemia/tratamento farmacológico , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Agregação Plaquetária/efeitos dos fármacos , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Ticagrelor/administração & dosagem , Idoso , Clopidogrel/efeitos adversos , Estado Terminal , Esquema de Medicação , Monitoramento de Medicamentos , Feminino , Humanos , Isquemia/sangue , Isquemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Inibidores da Agregação de Plaquetas/efeitos adversos , Testes de Função Plaquetária , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
15.
Acta Clin Belg ; 75(1): 1-8, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30591001

RESUMO

Objective: Blood lactate concentration (L) and lactate kinetic (LK) over time might be a helpful marker of the shock severity. The purpose of this study is to analyze whether the L and LK could correlate with the outcome and the therapy of patients with different types of shock.Methods: Design: A 3.5-year retrospective observational study. Patients: Eighteen years of age or older, diagnosed with shock were included. Arterial L measurements were performed upon admission and approximatively 3 and 6 h later. The evolution of lactate over this period of time was correlated with the outcome and therapy. Interventions: Univariate and multivariable statistical tests were performed to examine the relation between the initial L/LK and the in-hospital mortality, total mortality, length of stay (LOS), the LOS at the intensive care unit and the administered therapy. The optimal cut-off point of the LK over time to predict the mortality was calculated.Results: The initial L and the 6 h LK were significantly associated with the outcome. The higher the initial L and lower the LK, the higher the risk of mortality in the hospital or within 6 months. Moreover, the higher the initial L and lower the 6 h LK, the longer was the LOS. A relation between the initial L/LK and the required therapy was found. The optimal cut-off for the 6-h LK is 38.1%. Patients with a 6 h LK >38.1% had a significantly higher chance of survival.Conclusions: A significant relationship between the L/6-h LK and the outcome and treatment was found. The optimal survival cut-off point of 6 h LK in our study was 38.1%.


Assuntos
Isquemia/sangue , Ácido Láctico/sangue , Choque/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores/metabolismo , Feminino , Hidratação/métodos , Humanos , Isquemia/metabolismo , Isquemia/mortalidade , Isquemia/terapia , Ácido Láctico/metabolismo , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Respiração Artificial , Estudos Retrospectivos , Choque/metabolismo , Choque/mortalidade , Choque/terapia , Fatores de Tempo , Vasoconstritores/uso terapêutico , Adulto Jovem
16.
Ann Vasc Surg ; 62: 356-364, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30802587

RESUMO

BACKGROUND: The aim of this study was to evaluate the long-term outcomes of spinal cord stimulation in patients with critical limb ischemia and to test the hypothesis that the dynamics of clinical changes one year after therapy depend both on the clinical determinants associated with the underlying disease and on factors related to systemic atherosclerosis. METHODS: This prospective cohort study included 56 patients with critical limb ischemia. All patients before and after spinal cord stimulation were examined in terms of the dynamics of their clinical changes using the Rutherford scale and transcutaneous oxygen tension (TcPO2, mm Hg) in the affected foot. The active orthostatic test was used to assess the functional state of peripheral perfusion. RESULTS: One year after spinal cord stimulation, 74% of patients showed positive clinical outcomes. No changes were observed in 9.3% of patients, whereas adverse clinical outcomes were revealed in 16.7% of cases. The TcPO2 values were significantly reduced before spinal cord stimulation: 10.5 (6.4-16.0) mm Hg. The functional status of the peripheral microvasculature was also disturbed. One year after therapy, TcPO2 significantly increased and the adaptive mechanisms of the microvasculature were improved in more than 70% of patients. Logistic regression analysis showed that the initially low TcPO2 values (<10 mm Hg) with a lack of gain in TcPO2 during the orthostatic test are associated with the negative clinical outcomes after spinal cord stimulation. The gain in TcPO2 during the orthostatic test to >10 mm Hg is associated with the positive clinical outcomes after spinal cord stimulation. The age-adjusted Charlson Comorbidity Index >5 and duration of critical ischemic symptoms also had a negative effect on the clinical outcomes after spinal cord stimulation. CONCLUSIONS: The positive clinical outcomes were revealed in most patients with critical limb ischemia one year after spinal cord stimulation. The low values of peripheral tissue metabolism with the disturbed functional status of the microvasculature are associated with the negative clinical outcome. The patients with baseline TcPO2 <10 mm Hg can recover if they still have a sufficient microcirculatory reserve capacity. Duration of critical ischemic symptoms and high comorbidity burden with allowance for age are negative factors affecting the clinical outcome.


Assuntos
Isquemia/terapia , Doença Arterial Periférica/terapia , Estimulação da Medula Espinal , Idoso , Biomarcadores/sangue , Monitorização Transcutânea dos Gases Sanguíneos , Estado Terminal , Feminino , Humanos , Isquemia/sangue , Isquemia/diagnóstico , Isquemia/fisiopatologia , Masculino , Microcirculação , Pessoa de Meia-Idade , Oxigênio/sangue , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Estudos Prospectivos , Recuperação de Função Fisiológica , Fluxo Sanguíneo Regional , Fatores de Tempo , Resultado do Tratamento
17.
Eur J Vasc Endovasc Surg ; 59(1): 117-127, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31732468

RESUMO

OBJECTIVE: Diabetes mellitus has reached epidemic proportions. Foot ulceration is a multifactorial complication of diabetes associated with marked morbidity and mortality. Innate immune Toll-like receptor 4 (TLR4) mediated inflammation has been implicated in the systemic pathogenesis of diabetes and may contribute to impairment of wound healing. This study investigates the effect of high glucose and hypoxic conditions on TLR4 activation and signalling in vitro and in vivo. METHODS: Fibroblasts cultured at physiological glucose concentration (5.5 mM) were exposed to glucose concentrations from 0 mM to 25 mM, with duplicates placed in a hypoxic chamber. TLR4 inhibition was assessed in the 25 mM glucose groups. Diabetes was induced in wild type (WT) and TLR4 knockout (KO) C57BL/6 mice by intraperitoneal injection of low dose streptozocin (STZ). Hindlimb ischaemia was induced by femoral artery ligation four weeks post streptozocin, and a full thickness 4 mm skin wound inflicted below the knee. Wound healing was assessed via digital planimetry on days 3, 7, and 14 post surgery. RESULTS: Hypoxic and high glucose (25 mM) conditions led to an increase in TLR4 protein expression, apoptosis, and interleukin (IL)-6 release. Inhibition with a TLR4 neutralising antibody and specific TLR4 antagonist ameliorated the effects of high glucose and ischaemia (p < .05). In vivo, wound healing was significantly impaired in the diabetic ischaemic group at day 14 (p < .05). Diabetic ischaemic wounds in TLR4 KO mice exhibited significantly improved healing rates compared with those in WT mice at all time points. CONCLUSION: Hypoxia stimulates upregulation of TLR4 protein expression and this effect is exaggerated by hyperglycaemia. In TLR4 KO mice, there is a significant improvement in the healing of diabetic ischaemic wounds compared with WT. It is suggested that a synergistic effect between hypoxia and hyperglycaemia impairing wound healing exists, through TLR4 mediated inflammation.


Assuntos
Pé Diabético/patologia , Hiperglicemia/complicações , Isquemia/complicações , Receptor 4 Toll-Like/metabolismo , Cicatrização/fisiologia , Animais , Hipóxia Celular/fisiologia , Células Cultivadas , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Pé Diabético/etiologia , Modelos Animais de Doenças , Fibroblastos , Humanos , Hiperglicemia/sangue , Hiperglicemia/fisiopatologia , Interleucina-6/metabolismo , Isquemia/sangue , Isquemia/fisiopatologia , Masculino , Camundongos , Camundongos Knockout , Cultura Primária de Células , Transdução de Sinais/fisiologia , Pele/citologia , Estreptozocina/toxicidade , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/genética , Regulação para Cima
18.
Acta Clin Belg ; 75(2): 149-154, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30741123

RESUMO

Aim: To evaluate if smoking, quantified by the serum cotinine levels, is related to the evolution of patients with critical limb ischemia (CLI).Method: A pilot study was conducted on CLI patients who addressed at the Second Surgery Clinic of the Emergency County Hospital, Cluj-Napoca, Romania between November 2015 and December 2016. The sample of patients was split into two groups using the threshold of 15 ng/mL for the serum level of cotinine (low cotinine level - LCL vs. high cotinine level - HCL). Furthermore, the ROC analysis was conducted to identify the threshold of cotinine level able to discriminate between CLI patients with and without trophic lesions.Results: The mean age of patients was 60.7 ± 10.5 years with a significantly higher percentage of male patients (84%). A significant association was identified between urban origin and serum cotinine level, which is related to the increased number of cigarettes smoked per day among urban participants. Excepting necrectomy and toe disarticulation, no differences were found between LCL and HCL group regarding symptoms, signs or comorbidities. In smokers with CLI (38/43), a serum cotinine cut-off of 9.765 ng/mL was observed on eight out of 10 CLI patients with necrectomy and five out of 28 patients without necrectomy.Conclusion: Our study showed higher serum cotinine levels associated with a higher number of smoked cigarettes and necrectomy in patients with CLI. The serum cotinine could be a fair screening test for necrectomy in smokers CLI patients.


Assuntos
Arteriopatias Oclusivas , Cotinina/sangue , Isquemia , Doença Arterial Periférica , Adulto , Idoso , Arteriopatias Oclusivas/sangue , Arteriopatias Oclusivas/epidemiologia , Arteriopatias Oclusivas/patologia , Feminino , Humanos , Isquemia/sangue , Isquemia/epidemiologia , Isquemia/patologia , Masculino , Pessoa de Meia-Idade , Necrose , Doença Arterial Periférica/sangue , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/patologia , Projetos Piloto , Fumar/epidemiologia , Úlcera
19.
Bull Exp Biol Med ; 168(1): 150-155, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31773351

RESUMO

We studied the effect of intramuscular administration of a cellular product (mesenchymal stem cells, conditioned media, and erythropoietin) on cytokine levels in blood serum, conditioned media of bone marrow mononuclears, and calf muscles in Wistar rats with hind limb ischemia. It is shown that the cellular product reduces the proinflammatory background at the early stages of the experiment and increases the content proangiogenic factors.


Assuntos
Citocinas/sangue , Membro Posterior/patologia , Isquemia/sangue , Isquemia/patologia , Animais , Eritropoetina/sangue , Masculino , Ratos , Ratos Wistar
20.
Clin Appl Thromb Hemost ; 25: 1076029619877440, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564130

RESUMO

The quotient of concentrations concerning the key proangiogenic factor, that is, the vascular endothelial growth factor (VEGF-A) and the angiogenesis inhibitor, namely, its soluble receptors (sVEGFR-1 or sVEGFR-2), seems to reflect increased hypoxia and intensity of compensation angiogenesis. Therefore, it can be an ischemic and endothelial dysfunction marker reflected in intermittent claudication (IC) or critical limb ischemia (CLI) in patients with symptomatic peripheral arterial disease (PAD). The main objective of this study was to evaluate the levels of VEGF-A/sVEGFR-1 and VEGF-A/sVEGFR-2-presented using a novelty acronym VASCULAR-1 and VASCULAR-2-in patients with IC and CLI, as well as displayed in 4 classes of severity of PAD. VASCULAR-1 and VASCULAR-2 were calculated using the plasma of venous blood sampled from 80 patients with IC (n = 65) and CLI (n = 15) and the control group (n = 30). Patients with CLI were reported to have a slightly higher index of VASCULAR-1 and double VASCULAR-2 levels as compared to patients with IC (P = nonsignificant), and these markers were significantly higher than controls (P < .01 and P < .01, respectively). VASCULAR-2 levels were observed to have an increasing tendency in the subsequent degrees of PAD severity according to the Fontaine classification (P = .02). In view of the need to consider the role of the proangiogenic and antiangiogenic factor in the assessment of the so-called "angiogenic potential," VASCULAR-1 ratio and VASCULAR-2 ratio may be a new useful biomarker of limb ischemia in patients with IC and CLI. However, this requires further studies and evidence on a very large group of patients with PAD.


Assuntos
Moduladores da Angiogênese/sangue , Endotélio/fisiopatologia , Doença Arterial Periférica/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/sangue , Idoso , Biomarcadores/sangue , Extremidades/patologia , Feminino , Humanos , Claudicação Intermitente/sangue , Isquemia/sangue , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/patologia , Fator A de Crescimento do Endotélio Vascular/sangue
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