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1.
Front Cell Dev Biol ; 10: 1026287, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36393850

RESUMO

C3G is a Rap1 guanine nucleotide exchange factor that controls platelet activation, aggregation, and the release of α-granule content. Transgenic expression of C3G in platelets produces a net proangiogenic secretome through the retention of thrombospondin-1. In a physiological context, C3G also promotes megakaryocyte maturation and proplatelet formation, but without affecting mature platelet production. The aim of this work is to investigate whether C3G is involved in pathological megakaryopoiesis, as well as its specific role in platelet mediated angiogenesis and tumor metastasis. Using megakaryocyte-specific C3G knockout and transgenic mouse models, we found that both C3G overexpression and deletion promoted platelet-mediated angiogenesis, induced by tumor cell implantation or hindlimb ischemia, through differential release of proangiogenic and antiangiogenic factors. However, only C3G deletion resulted in a higher recruitment of hemangiocytes from the bone marrow. In addition, C3G null expression enhanced thrombopoietin (TPO)-induced platelet production, associated with reduced TPO plasma levels. Moreover, after 5-fluorouracil-induced platelet depletion and rebound, C3G knockout mice showed a defective return to homeostatic platelet levels, indicating impaired platelet turnover. Mechanistically, C3G promotes c-Mpl ubiquitination by inducing Src-mediated c-Cbl phosphorylation and participates in c-Mpl degradation via the proteasome and lysosome systems, affecting TPO internalization. We also unveiled a positive role of platelet C3G in tumor cell-induced platelet aggregation, which facilitated metastatic cell homing and adhesion. Overall, these findings revealed that C3G plays a crucial role in platelet-mediated angiogenesis and metastasis, as well as in platelet level modulation in response to pathogenic stimuli.

2.
Pain Med ; 23(1): 226, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34689203
3.
Trials ; 22(1): 595, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488845

RESUMO

BACKGROUND: Chronic lower limb ischemia develops earlier and more frequently in patients with type 2 diabetes mellitus. Diabetes remains the main cause of lower-extremity non-traumatic amputations. Current medical treatment, based on antiplatelet therapy and statins, has demonstrated deficient improvement of the disease. In recent years, research has shown that it is possible to improve tissue perfusion through therapeutic angiogenesis. Both in animal models and humans, it has been shown that cell therapy can induce therapeutic angiogenesis, making mesenchymal stromal cell-based therapy one of the most promising therapeutic alternatives. The aim of this study is to evaluate the feasibility, safety, and efficacy of cell therapy based on mesenchymal stromal cells derived from adipose tissue intramuscular administration to patients with type 2 diabetes mellitus with critical limb ischemia and without possibility of revascularization. METHODS: A multicenter, randomized double-blind, placebo-controlled trial has been designed. Ninety eligible patients will be randomly assigned at a ratio 1:1:1 to one of the following: control group (n = 30), low-cell dose treatment group (n = 30), and high-cell dose treatment group (n = 30). Treatment will be administered in a single-dose way and patients will be followed for 12 months. Primary outcome (safety) will be evaluated by measuring the rate of adverse events within the study period. Secondary outcomes (efficacy) will be measured by assessing clinical, analytical, and imaging-test parameters. Tertiary outcome (quality of life) will be evaluated with SF-12 and VascuQol-6 scales. DISCUSSION: Chronic lower limb ischemia has limited therapeutic options and constitutes a public health problem in both developed and underdeveloped countries. Given that the current treatment is not established in daily clinical practice, it is essential to provide evidence-based data that allow taking a step forward in its clinical development. Also, the multidisciplinary coordination exercise needed to develop this clinical trial protocol will undoubtfully be useful to conduct academic clinical trials in the field of cell therapy in the near future. TRIAL REGISTRATION: ClinicalTrials.gov NCT04466007 . Registered on January 07, 2020. All items from the World Health Organization Trial Registration Data Set are included within the body of the protocol.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Noma , Tecido Adiposo , Animais , Ensaios Clínicos Fase II como Assunto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Método Duplo-Cego , Humanos , Isquemia/diagnóstico , Isquemia/terapia , Estudos Multicêntricos como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Resultado do Tratamento
4.
J Med Case Rep ; 15(1): 203, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33863365

RESUMO

BACKGROUND: Abdominal aortic aneurysm and acute appendicitis occur relatively frequently in elderly patients. However, the co-occurrence of the two pathologies is very rare and serious. CASE PRESENTATION: We present the case of an elderly Caucasian patient who was aware of having an abdominal aortic aneurysm but refused treatment and was subsequently admitted to the hospital's emergency department with acute abdominal symptoms. A computed tomography scan raised the possibility of complication due to the characteristics of the aneurysm. The patient then agreed to emergency surgery. Laparotomy revealed the existence of an acute perforated appendicitis with a significant abscess in the right iliac fossa and an uncomplicated aneurysm. Appendectomy was performed and the abscess drained. The postoperative period passed without complications, and the patient again refused surgery for the aneurysm, which due to its anatomical characteristics was not a candidate for standard endovascular treatment. CONCLUSIONS: In light of this experience, we review the literature about the relationship between abdominal aortic aneurysm and acute appendicitis.


Assuntos
Abscesso Abdominal/cirurgia , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Apendicite/complicações , Apendicite/cirurgia , Drenagem/métodos , Abscesso Abdominal/complicações , Doença Aguda , Idoso , Apendicectomia , Apendicite/diagnóstico por imagem , Humanos , Laparotomia
6.
Head Neck ; 42(12): 3538-3550, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32812684

RESUMO

BACKGROUND: Carotid paragangliomas are rare tumors. They are usually unique, non-secreting, resectable, and benign. However, additional rare cases of complex tumors (bilateral, secretory, nonresectable, or malignant) complicate the management and final outcomes. METHODS: Records of paragangliomas from our hospital are reviewed. Criteria defining complex paragangliomas have been previously defined. These are compared with those of the simple group. RESULTS: Fifty patients, two groups: simple (n = 39) and complex (n = 11). The patients in the complex group were significantly younger (47.7 vs 63.8 years). Postoperative nerve complications (45.4% vs 6.3%) and mortality during follow-up (27.3% vs 0%) were significantly more common in the complex group. Vascular complications (0% vs 3.1%) and early mortality (0%) were similarly in both groups. CONCLUSIONS: Patients with complex carotid paragangliomas are heterogeneous. The former are younger, exhibit a high degree of diagnostic and therapeutic complexity, and have poorer morbidity and mortality. Surgical experience and interdisciplinary collaboration are essential.


Assuntos
Tumor do Corpo Carotídeo , Neoplasias de Cabeça e Pescoço , Paraganglioma Extrassuprarrenal , Paraganglioma , Tumor do Corpo Carotídeo/diagnóstico , Tumor do Corpo Carotídeo/cirurgia , Humanos , Paraganglioma/cirurgia , Complicações Pós-Operatórias
7.
Artigo em Inglês | MEDLINE | ID: mdl-32699549

RESUMO

Patients with peripheral artery disease (PAD) are at a high risk not only for the classical cardiovascular (CV) outcomes (major adverse cardiovascular events; MACE) but also for vascular limb events (major adverse limb events; MALE). Therefore, a comprehensive approach for these patients should include both goals. However, the traditional antithrombotic approach with only antiplatelet agents (single or dual antiplatelet therapy) does not sufficiently reduce the risk of recurrent thrombotic events. Importantly, the underlying cause of atherosclerosis in patients with PAD implies both platelet activation and the initiation and promotion of coagulation cascade, in which Factor Xa plays a key role. Therefore, to reduce residual vascular risk, it is necessary to address both targets. In the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial that included patients with stable atherosclerotic vascular disease, the rivaroxaban plus aspirin strategy (versus aspirin) markedly reduced the risk of both CV and limb outcomes, and related complications, with a good safety profile. In fact, the net clinical benefit outcome composed of MACE; MALE, including major amputation, and fatal or critical organ bleeding was significantly reduced by 28% with the COMPASS strategy, (hazard ratio: 0.72; 95% confidence interval: 0.59-0.87). Therefore, the rivaroxaban plus aspirin approach provides comprehensive protection and should be considered for most patients with PAD at high risk of such events.

8.
J. negat. no posit. results ; 5(7): 702-720, jul. 2020. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-194131

RESUMO

OBJETIVO: Reflejar nuestra frustración al perder un paciente, no porque su infrecuente patología sea de por sí muy grave, sino por el acumulo sobreañadido de otros motivos diagnósticos, y terapéuticos en un entorno hospitalario de epidemia Covid-19. MÉTODO: Primero describimos el proceso diagnóstico, terapéutico y evolutivo (27 febrero al 25 marzo 2020) de un varón de 73 años portador de una fístula aorto-entérica secundaria a un bypass aorto-bifemoral, implantado doce años antes en otro hospital. Después presentamos nuestra experiencia (1978-2020) en este tipo de situaciones, y finalmente realizamos una revisión de la literatura (1953-2020) al respecto. RESULTADOS: A) Caso clínico: ausencia de diagnóstico precoz, fracaso de la técnica operatoria elegida, importantes complicaciones postoperatorias (hemorragia, infarto cerebral y neumonía bilateral por coronavirus) que finalizo en exitus. B) Experiencia personal: cuatro casos (incluido el referido). C) Revisión de la literatura: tres revisiones sistemáticas: 564 casos (1953-1993); 386 casos en 58 publicaciones (1991-2006), 823 pacientes en 216 publicaciones (1995-2015) y 20 casos en 14 publicaciones (2016-2020). CONCLUSIÓN: Si en situaciones normales una fístula aorto-entérica es una condición que amenaza seriamente la vida del paciente (hemorragia y/o infección), no debe extrañar que en situaciones excepcionales esa situación de gravedad se incremente. No obstante, de estas malas experiencias estamos obligados a sacar enseñanzas que beneficien a otros en el futuro


OBJECTIVE: To reflect our frustration when losing a patient, not because their infrequent pathology is in itself very serious, but because of the accumulation of other diagnostic and therapeutic reasons in a hospital environment of the Covid-19 epidemic. METHOD: First we describe the diagnostic, therapeutic and evolutionary process (February 27 to March 25, 2020) of a 73-year-old male with an aorto-enteric fistula secondary to an aorto-bifemoral bypass, implanted twelve years earlier in another hospital. Then we present our experience (1978-2020) in this type of situation, and finally we carried out a review of the literature (1953-2020) in this regard. RESULTS: A) Clinical case: absence of early diagnosis, failure of the chosen operative technique, significant postoperative complications (hemorrhage, cerebral infarction and bilateral coronavirus pneumonia) that ended in death. B) Personal experience: four cases (including the referred one). C) Literature review: three systematic reviews: 564 cases (1953-1993); 386 cases in 58 publications (1991-2006), 823 patients in 216 publications (1995-2015) and 20 cases in 14 publications (2016-2020). CONCLUSION: If in normal situations an aorto-enteric fistula is a condition that seriously threatens the patient's life (hemorrhage and / or infection), it should not be surprising that in exceptional situations this serious situation increases. However, from these bad experiences we are obliged to draw lessons that will benefit others in the future


Assuntos
Humanos , Masculino , Idoso , Fístula Intestinal/complicações , Fístula/complicações , Aorta/lesões , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/cirurgia , Insuficiência da Valva Aórtica/cirurgia , Complicações Pós-Operatórias , Hemorragia Gastrointestinal/etiologia , Dispositivos de Oclusão Vascular
9.
Expert Rev Clin Pharmacol ; 13(7): 695-706, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32434452

RESUMO

INTRODUCTION: In this review, the role of the rivaroxaban-plus-aspirin approach (dual pathway inhibition - DPI) in patients with chronic coronary syndrome (CCS) and to perform practical recommendations about its use was updated. AREAS COVERED: The contents of this review were proposed in an expert meeting. To identify relevant articles, a systematic search of Medline/Embase was performed (to July 2019), using the key words 'rivaroxaban', 'vascular dose', 'COMPASS' and 'coronary artery disease' in the search strategy. EXPERT OPINION: Despite current antithrombotic strategies (single/dual antiplatelet therapy) have decreased rates of recurrent cardiovascular events among patients with CCS, residual risk remains unacceptably high. The COMPASS trial showed in CCS patients that compared with aspirin 100 mg rivaroxaban 2.5 mg bid plus aspirin 100 mg reduced the risk of major cardiac events, cardiovascular hospitalization and mortality, without an increase of intracranial or fatal bleedings. Importantly, residual risk with the rivaroxaban plus aspirin approach was lower than with different dual antiplatelet therapy regimens. The rivaroxaban plus aspirin strategy is of particular benefit in patients with CCS and high-risk cardiovascular feature (i.e. ≥2 vascular beds, heart failure, renal insufficiency, peripheral artery disease, previous stroke or diabetes) and should be considered in these populations.


Assuntos
Aspirina/administração & dosagem , Doença da Artéria Coronariana/tratamento farmacológico , Rivaroxabana/administração & dosagem , Aspirina/efeitos adversos , Doença Crônica , Doença da Artéria Coronariana/fisiopatologia , Quimioterapia Combinada , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Hospitalização/estatística & dados numéricos , Humanos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Rivaroxabana/efeitos adversos , Síndrome
10.
J Cardiovasc Surg (Torino) ; 61(2): 256-263, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31985187

RESUMO

We report on the case of spontaneous rupture of an On-X-pure pyrolytic carbon mechanical valve prosthesis implanted seven years earlier, in a mitral position, at our hospital. The patient was admitted with valvular dysfunction and acute pulmonary edema requiring emergency surgery (prosthesis replacement); the absence of a leaflet was confirmed intraoperatively. The patient presented severe respiratory failure, which prolonged the postoperative period. A CT scan showed that the migrated leaflet was located in the aortic bifurcation with no apparent arterial lesion. Four months later, once the patient had recovered, laparotomy and aortotomy were performed in order to retrieve the leaflet, which was found to have become included (neoendothelized) in the aortic wall without compromising the latter's integrity or obstructing the blood flow. A subsequent CT scan confirmed the persistence of the leaflet in its initial position. The literature review highlights two singular facts: 1) this is the second published case of the escape of a leaflet from an On-X prosthesis (the first patient died); 2) this is the first case in which a laparotomy was performed to retrieve the leaflet but finally a decision was made to leave it in situ. Seven months later, the patient remained asymptomatic.


Assuntos
Bioprótese/efeitos adversos , Migração de Corpo Estranho/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Insuficiência da Valva Mitral/cirurgia , Falha de Prótese , Doença Aguda , Procedimentos Cirúrgicos Cardíacos/métodos , Serviço Hospitalar de Emergência , Seguimentos , Migração de Corpo Estranho/diagnóstico por imagem , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/diagnóstico por imagem , Edema Pulmonar/diagnóstico , Edema Pulmonar/etiologia , Reoperação/métodos , Fatores de Tempo , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
12.
Front Immunol ; 10: 1151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31231366

RESUMO

Cell therapy is a progressively growing field that is rapidly moving from preclinical model development to clinical application. Outcomes obtained from clinical trials reveal the therapeutic potential of stem cell-based therapy to deal with unmet medical treatment needs for several disorders with no therapeutic options. Among adult stem cells, mesenchymal stem cells (MSCs) are the leading cell type used in advanced therapies for the treatment of autoimmune, inflammatory and vascular diseases. To date, the safety and feasibility of autologous MSC-based therapy has been established; however, their indiscriminate use has resulted in mixed outcomes in preclinical and clinical studies. While MSCs derived from diverse tissues share common properties depending on the type of clinical application, they markedly differ within clinical trials in terms of efficacy, resulting in many unanswered questions regarding the application of MSCs. Additionally, our experience in clinical trials related to critical limb ischemia pathology (CLI) shows that the therapeutic efficacy of these cells in different animal models has only been partially reproduced in humans through clinical trials. Therefore, it is crucial to develop new research to identify pitfalls, to optimize procedures and to clarify the repair mechanisms used by these cells, as well as to be able to offer a next generation of stem cell that can be routinely used in a cost-effective and safe manner in stem cell-based therapies targeting CLI.

13.
Stem Cell Res Ther ; 9(1): 150, 2018 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-29848379

RESUMO

Thromboangiitis obliterans (TAO), also known as Buerger's Disease, is an occlusive vasculitis linked with high morbidity and amputation risk. To date, TAO is deemed incurable due to the lack of a definitive treatment. The immune system and inflammation are proposed to play a central role in TAO pathogenesis. Due to their immunomodulatory effects, mesenchymal stromal cells (MSCs) are the subject of intense research for the treatment of a wide range of immune-mediated diseases. Thus far, local intramuscular injections of autologous or allogeneic MSCs have shown promising results in TAO. However, sequential intravenous allogeneic MSC administration has not yet been explored, which we hypothesized could exert a systemic anti-inflammatory effect in the vasculature and modulate the immune response. Here, we report the first case of a TAO patient at amputation risk treated with four sequential intravenous infusions of bone marrow-derived allogeneic MSCs from a healthy donor. Following administration, there was significant regression of foot skin ulcers and improvements in rest pain, Walking Impairment Questionnaire scores, and quality of life. Sixteen months after the infusion, the patient had not required any further amputations. This report highlights the potential of sequential allogeneic MSC infusions as an effective treatment for TAO, warranting further studies to compare this approach with the more conventionally used intramuscular MSC administration and other cell-based therapies.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Tromboangiite Obliterante/terapia , Transplante Homólogo/métodos , Administração Intravenosa , Adulto , Humanos , Masculino , Células-Tronco Mesenquimais , Tromboangiite Obliterante/patologia , Resultado do Tratamento
14.
Thromb Res ; 142: 52-6, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26922092

RESUMO

BACKGROUND: Experience is limited with regard to antithrombotic therapy in patients with venous thromboembolism (VTE) following allogeneic hematopoietic stem cell transplantation (HSCT). DESIGN AND METHODS: We described a cohort of patients presenting with symptomatic VTE following allogeneic HSCT, including management patterns and outcomes. RESULTS: Twenty-four patients developed a deep vein thrombosis and/or pulmonary embolism unrelated to a catheter. Median time of VTE diagnosis and duration of antithrombotic therapy were 9.5 and 6months. Eleven patients were treated with full-dose low molecular weight heparin (LMWH). Eleven patients with minor bleeding, thrombocytopenia or renal failure received prophylactic dose LMWH. In two patients an inferior vena cava filter was inserted due to thrombocytopenia and bleeding. There were 2 major and 4 life-threatening bleeding episodes, so LMWH was discontinued permanently. Two deaths were directly attributable to bleeding. Ten patients developed a catheter-associated VTE. Median time to diagnosis and duration of anticoagulation was 2.5 and 3months. Catheter was removed in all patients. LMWH was administered at therapeutic-dose in 4 patients, and was reduced by bleeding in 2 of them. LMWH was administered at prophylactic-dose in 6 patients, and was reduced by renal failure in one patient. There were three episodes of minor bleeding. Rate of clot recurrence was 29.4% (n=10). Patients at recurrence were without antithrombotic treatment (n=4), intermediate-dose LMWH (n=2), low-dose LMWH (n=2) or acenocumarol (n=2). Eight patients with recurrence VTE had extensive chronic graft versus host disease (GVHD). CONCLUSIONS: LMWH was used in most HSCT recipients but half of them may not receive full-dose LMWH. Thrombocytopenia, renal impairment and bleeding were the reasons for reducing LMWH. Also, rates of clinically relevant hemorrhage or recurrent VTE were highly significant. The development of GVHD could mainly explain these findings.


Assuntos
Anticoagulantes/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Adulto , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Gerenciamento Clínico , Feminino , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Trombocitopenia/induzido quimicamente , Resultado do Tratamento , Adulto Jovem
15.
Pain Pract ; 16(7): 842-9, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26407542

RESUMO

BACKGROUND: Pain control in critical limb ischemia (CLI) varies considerably between individuals. OBJECTIVE: To evaluate pharmacogenetically the response to transdermal buprenorphine (BUP-TTS) in patients with CLI who are awaiting revascularization. METHODS: One hundred and seven patients with CLI were treated with BUP-TTS. The following were analyzed: (1) pain perception (visual analog scale (VAS) before and 4 days after treatment) and (2) genetics: glucuronosyltransferase (UGT2B7), cytochrome (CYP3A4), and µ-opioid receptor (OPRM1) gene polymorphisms. RESULTS: Ninety-three patients completed the study. The VAS score by the fourth day of analgesia dropped from 6.82 to 3.38 (P < 0.05). The analgesic response to BUP-TTS was greater in men than in women (P = 0.019). Patients who were AA homozygotes for the CYP3A4 gene showed the best response to analgesic treatment (P = 0.003). The combination of the CYP3A4 gene with UGT2B7 or OPRM1 was favorable to the effect of the CYP3A4 gene (P = 0.045 and P = 0.026, respectively). The combination of UGT2B7 with OPRM1 was ineffective (P = 0.648). The 3 polymorphisms together had no effect on response to treatment (P = 0.461). CONCLUSIONS: BUP-TTS is efficacious in the control of pain in patients with CLI. The homozygous AA carriers of the CYP3A4 gene respond better to treatment with BUP-TTS.


Assuntos
Analgésicos Opioides/administração & dosagem , Buprenorfina/administração & dosagem , Citocromo P-450 CYP3A/genética , Glucuronosiltransferase/genética , Dor/genética , Receptores Opioides mu/genética , Administração Cutânea , Adulto , Feminino , Humanos , Isquemia/complicações , Extremidade Inferior/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Dor/etiologia , Manejo da Dor/métodos , Medição da Dor , Polimorfismo de Nucleotídeo Único
16.
Br J Haematol ; 169(5): 719-25, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25817436

RESUMO

Bleeding is a frequent complication after allogeneic haematopoietic stem cell transplantation (HSCT) and may affect survival. The purpose of this study was to determine the incidence and risk factors for life-threatening bleeding after HSCT by retrospective evaluation of 491 allogeneic HSCT recipients. With a median follow-up of 33 months, 126 out of 491 allogeneic HSCT recipients experienced a haemorrhagic event (25·7%) and 46 patients developed a life-threatening bleeding episode (9·4%). Pulmonary and gastrointestinal bleeding were the most common sites for life-threatening bleeding, followed by central nervous system. In multivariate analyses, the presence of severe thrombocytopenia after day +28 and the development of grade III-IV acute graft-versus-host disease (GVHD) or thrombotic microangiopathy (TMA) retained their association with life-threatening bleeding events. The overall survival at 3 years among patients without bleeding was 67·1% for only 17·1% for patients with life-threatening bleeding (P < 0·001). In conclusion, life-threatening bleeding is a common complication after allogeneic HSCT. Prolonged severe thrombocytopenia, acute grade III-IV GVHD and TMA were associated with its development.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Hemorragia/epidemiologia , Hemorragia/etiologia , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/mortalidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Fatores de Risco , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo
17.
Clin Appl Thromb Hemost ; 21(4): 297-308, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25504999

RESUMO

Anticoagulation therapy is the standard treatment of patients with symptomatic venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism. Until recently, treatment of VTE was based on parenteral or low-molecular-weight heparin for initial therapy (5-10 days) and oral vitamin K antagonists for long-term therapy. Those treatments have some limitations, including parenteral administration (heparins), the need for frequent monitoring and dose adjustments, interactions with several medications, and dietary restrictions (vitamin K antagonists). Rivaroxaban is a new oral direct factor Xa inhibitor with a wide therapeutic window, predictable anticoagulant effect, no food interactions, and few drug interactions. Consequently, no periodic monitoring of anticoagulation is needed, and fixed doses can be prescribed. EINSTEIN program demonstrated that rivaroxaban was as effective as and significantly safer than standard therapy for treatment of VTE. Rivaroxaban was recently authorized so doubts exist about how to use it in daily clinical practice. This document aims to clarify common questions formulated by clinicians regarding the use of this new drug.


Assuntos
Inibidores do Fator Xa/farmacocinética , Inibidores do Fator Xa/uso terapêutico , Rivaroxabana/farmacocinética , Rivaroxabana/uso terapêutico , Tromboembolia Venosa/prevenção & controle , Interações Medicamentosas , Monitoramento de Medicamentos , Humanos , Recidiva , Tromboembolia Venosa/sangue
18.
J Womens Health (Larchmt) ; 23(10): 834-41, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25238019

RESUMO

BACKGROUND: Intermittent claudication (IC) and its consequences have customarily been underestimated in women. Our study aimed to determine the differences on functional and quality-of-life issues between women and men in a large group of claudicants. METHODS: This study was an observational, cross-sectional, nonrandomized, multicenter study of 1,641 claudicants (406 women). Information was collected from patients' medical history, a physical examination, the ankle-brachial index (ABI), the Walking Impairment Questionnaire (WIQ), and the European Quality of Life Questionnaire (EQ-5D). RESULTS: On average, women with IC were older than men with IC (70.0 vs. 67.8 years; p<0.001) and tended to have a different socio-occupational status. Women were more likely to be obese and less likely to smoke or have dyslipidemia (p<0.001). Women were notable for their greater prevalence of cardiac insufficiency (p=0.016) and arrhythmias (p<0.001) and a lower prevalence of ischemic cardiopathy and acute myocardial infarction (p<0.001). At the same time, there was a significantly higher level of osteoarticular diseases in women: arthrosis (p<0.001), arthritis (p<0.001), and lumbar pathology (p=0.006). All the symptoms evaluated that were associated with IC were more frequent in women (p<0.05). The mean ABI was similar in claudicant women and men. Conversely, the parameter estimates of the WIQ were significantly lower in women (by 4.3%, and 6.5%, respectively; p=0.003). Likewise, the EQ-5D score was 7% lower in women than in men (from 0.52 to 0.59; p<0.001). CONCLUSIONS: Women claudicants have higher risk factors and more frequent cardiovascular comorbidity than men do. Women have a lower capacity for exercise and a poorer quality of life than male claudicants, despite having a similar ABI. These poorer outcomes in women can be partially explained by the presence of greater osteoarticular comorbidity.


Assuntos
Atividades Cotidianas/psicologia , Claudicação Intermitente/psicologia , Qualidade de Vida , Caminhada , Distribuição por Idade , Idoso , Índice Tornozelo-Braço , Doenças Cardiovasculares/epidemiologia , Comorbidade , Estudos Transversais , Exercício Físico , Feminino , Humanos , Claudicação Intermitente/epidemiologia , Claudicação Intermitente/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Distribuição por Sexo , Fatores Socioeconômicos , Inquéritos e Questionários
19.
Diabetol Metab Syndr ; 6(1): 21, 2014 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-24533798

RESUMO

INTRODUCTION: Diabetes mellitus (DM) and intermittent claudication (IC) are frequently associated health conditions. Our hypothesis is that the nature, severity and quality of life (QoL) of patients with IC and DM are worse than those of claudicant patients without diabetes. MATERIAL AND METHODS: An observational, cross-sectional and multicentre study of 920 patients with IC, divided into two groups: diabetic (n = 477) and non-diabetic (n = 443). For each group, we examined clinical and biological characteristics (including levels of glucose and lipids), the ankle-brachial index (ABI), responses to the Walking Impairment Questionnaire (WIQ) and the European Quality of Life-5 Dimensions (EQ-5D) questionnaire. RESULTS: Compared with claudicant patients without diabetes, claudicants with diabetes were older (p < 0.001), more likely to be female (p = 0.006), with a higher BMI (p < 0.001), more likely to have a sedentary lifestyle (p < 0.001) and to be a non-smoker (p < 0.001). Claudicant patients with diabetes also had significantly more cardiovascular risk factors (p < 0.001), more frequent ischaemic cardiopathy (p = 0.023) and chronic renal failure (p = 0.002), and fewer prior ictus events (p = 0.003). No significant differences between groups were found with respect to blood pressure, levels of cholesterol or triglycerides. The mean ABI of diabetic-IC patients was slightly lower than IC patients without diabetes (p = 0.016). All WIQ subdomains scores were significantly lower (p < 0.001), indicating poorer walking ability, in claudicant and diabetic patients with compared with those without diabetes. The mean E5-QD global scores and the mean EQ-5D visual analogue scale in the whole series were 0.58 (SD = 0.21) and 55.04 (SD = 21.30), respectively. Both E5-QD scores were significantly lower, indicating poorer QoL, in claudicant patients with diabetes than claudicant patients without diabetes (p < 0.001). CONCLUSION: Patients with IC and DM had more risk cardiovascular factors, cardiovascular conditions, disability and worse haemodynamic status and QoL than claudicant patients without diabetes.

20.
World J Surg ; 38(1): 241-51, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24170151

RESUMO

BACKGROUND: The goal of this article is to present for the first time to the international community the detailed findings and outcomes of the Spanish Vascular Registry (SVR) after 16 years of experience. METHODS: We examined the nationwide registry promoted by the Spanish Society of Angiology and Vascular Surgery (1996-2011). The changes in vascular surgical activity in Spain during the period of study were examined. We evaluated the number of services, medical specialists, consultations, admissions, and operations that occurred in Spain. We also assessed the trends in therapeutic activity and the medical and social impact of vascular pathology. RESULTS: A mean of 60 centers (range = 32-83) participated in the SVR (79.3 % of the total). In the last year of the study period, 94.3 % centers (100 % of teaching centers) participated. The mean number of activities per hospital per year was 5,298 consultations, 2,625 vascular explorations, 630 hospital admissions (61 % elective and 31 % emergency), and 742 surgical procedures. A total of 29,289 carotid stenosis procedures had been registered over 16 years. Both carotid endarterectomy (CEA) and carotid artery stenting (CAS) procedures have increased in frequency over time. In 2011, CAS constituted 19.3 % of all carotid procedures. A total of 31,703 abdominal aortic aneurysm (AAA) operations were registered during the study period. Surgery for ruptured AAA remained stable over time. Since its appearance in the year 2000, endovascular treatment (EVAR) increased steadily over time. Currently, EVAR represents about half of all AAA surgery (50.2 %). The total rate of in-hospital operative deaths was 1.1 %, but in-hospital mortality for open arterial surgery was 4 %. Mortality has decreased of late. CONCLUSIONS: The SVR has enabled us to understand the development and implementation of vascular surgery throughout Spain and to note the increased healthcare activity and the better overall results obtained as a consequence.


Assuntos
Sistema de Registros , Procedimentos Cirúrgicos Vasculares/estatística & dados numéricos , Procedimentos Cirúrgicos Vasculares/tendências , Humanos , Espanha , Fatores de Tempo
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