RESUMO
BACKGROUND: Plaque angiogenesis is associated with atherosclerotic lesion growth, plaque instability and negative clinical outcome. Plaque angiogenesis is a natural occurring process to fulfil the increasing demand of oxygen and nourishment of the vessel wall. However, inadequate formed, immature plaque neovessels are leaky and cause intraplaque haemorrhage. OBJECTIVE: Blockade of VEGFR2 normalizes the unbridled process of plaque neovessel formation and induces maturation of nascent vessels resulting in prevention of intraplaque haemorrhage and influx of inflammatory cells into the plaque and subsequently increases plaque stability. METHODS AND RESULTS: In human carotid and vein graft atherosclerotic lesions, leaky plaque neovessels and intraplaque haemorrhage co-localize with VEGF/VEGFR2 and angiopoietins. Using hypercholesterolaemic ApoE3*Leiden mice that received a donor caval vein interposition in the carotid artery, we demonstrate that atherosclerotic vein graft lesions at t28 are associated with hypoxia, Hif1α and Sdf1 up-regulation. Local VEGF administration results in increased plaque angiogenesis. VEGFR2 blockade in this model results in a significant 44% decrease in intraplaque haemorrhage and 80% less extravasated erythrocytes compared to controls. VEGFR2 blockade in vivo results in a 32% of reduction in vein graft size and more stable lesions with significantly reduced macrophage content (30%), and increased collagen (54%) and smooth muscle cell content (123%). Significant decreased VEGF, angiopoietin-2 and increased Connexin 40 expression levels demonstrate increased plaque neovessel maturation in the vein grafts. VEGFR2 blockade in an aortic ring assay showed increased pericyte coverage of the capillary sprouts. CONCLUSION: Inhibition of intraplaque haemorrhage by controlling neovessels maturation holds promise to improve plaque stability.
Assuntos
Hemorragia/prevenção & controle , Neovascularização Patológica/prevenção & controle , Placa Aterosclerótica/tratamento farmacológico , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Angiopoietina-2/sangue , Animais , Biomarcadores/sangue , Conexinas/sangue , Modelos Animais de Doenças , Humanos , Camundongos , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/farmacologia , Proteína alfa-5 de Junções ComunicantesRESUMO
BACKGROUND: Endovascular aneurysm repair (EVAR) has become the preferred strategy for elective repair of abdominal aortic aneurysm (AAA) for many patients. However, the superiority of the endovascular procedure has recently been challenged by reports of impaired long-term survival in patients who underwent EVAR. A systematic review of long-term survival following AAA repair was therefore undertaken. METHODS: A systematic review was performed according to PRISMA guidelines. Articles reporting short- and/or long-term mortality of EVAR and open surgical repair (OSR) of AAA were identified. Pooled overall survival estimates (hazard ratios (HRs) with corresponding 95 per cent c.i. for EVAR versus OSR) were calculated using a random-effects model. Possible confounding owing to age differences between patients receiving EVAR or OSR was addressed by estimating relative survival. RESULTS: Some 53 studies were identified. The 30-day mortality rate was lower for EVAR compared with OSR: 1·16 (95 per cent c.i. 0·92 to 1·39) versus 3·27 (2·71 to 3·83) per cent. Long-term survival rates were similar for EVAR versus OSR (HRs 1·01, 1·00 and 0·98 for 3, 5 and 10 years respectively; P = 0·721, P = 0·912 and P = 0·777). Correction of age inequality by means of relative survival analysis showed equal long-term survival: 0·94, 0·91 and 0·76 at 3, 5 and 10 years for EVAR, and 0·96, 0·91 and 0·76 respectively for OSR. CONCLUSION: Long-term overall survival rates were similar for EVAR and OSR. Available data do not allow extension beyond the 10-year survival window or analysis of specific subgroups.
Assuntos
Aneurisma da Aorta Abdominal/mortalidade , Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Cirúrgicos Eletivos/métodos , Procedimentos Endovasculares/métodos , Humanos , Análise de Sobrevida , Taxa de SobrevidaRESUMO
BACKGROUND: Venous grafts are commonly used as conduits to bypass occluded arteries. Unfortunately, patency rates are limited by vein graft disease (VGD). Toll like receptors (TLRs) can be activated in vein grafts by endogenous ligands. This study aims to investigate the role of TLR3 in VGD. METHODS: Vein graft surgery was performed by donor caval vein interpositioning in the carotid artery of recipient Tlr2-/-, Tlr3-/-, Tlr4-/- and control mice. Vein grafts were harvested 7, 14 and 28d after surgery to perform immunohistochemical analysis. Expression of TLR-responsive genes in vein grafts was analysed using a RT2-profiler PCR Array. mRNA expression of type-I IFN inducible genes was measured with qPCR in bone marrow-derived macrophages (BMM). RESULTS: TLR2, TLR3 and TLR4 were observed on vein graft endothelial cells, smooth muscle cells and macrophages. Tlr3-/- vein grafts demonstrated no differences in vessel wall thickening after 7d, but after 14d a 2.0-fold increase (pâ¯=â¯0.02) and 28d a 1.8-fold increase (pâ¯=â¯0.009) compared to control vein grafts was observed, with an increased number of macrophages (pâ¯=â¯0.002) in the vein graft. Vessel wall thickening in Tlr4-/- decreased 0.6-fold (pâ¯=â¯0.04) and showed no differences in Tlr2-/- compared to control vein grafts. RT2-profiler array revealed a down-regulation of type-I IFN inducible genes in Tlr3-/- vein grafts. PolyI:C stimulated BMM of Tlr3-/- mice showed a reduction of Ifit1 (pâ¯=â¯0.003) and Mx1 (pâ¯<â¯0.0001) mRNA compared to control. CONCLUSIONS: We here demonstrate that TLR3 can play a protective role in VGD development, possibly regulated via type-I IFNs and a reduced inflammatory response.
Assuntos
Proteínas de Transporte/genética , Receptor 3 Toll-Like/genética , Transplantes/metabolismo , Veias/crescimento & desenvolvimento , Proteínas Adaptadoras de Transdução de Sinal , Animais , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Artérias Carótidas/crescimento & desenvolvimento , Artérias Carótidas/metabolismo , Diferenciação Celular/genética , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Regulação da Expressão Gênica/genética , Humanos , Interferon Tipo I/genética , Ligantes , Macrófagos/metabolismo , Camundongos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Proteínas de Ligação a RNA , Transdução de Sinais/genética , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Transplantes/crescimento & desenvolvimento , Transplantes/patologia , Veias/metabolismoRESUMO
BACKGROUND: The introduction of endovascular aneurysm repair (EVAR) has reduced perioperative mortality after abdominal aortic aneurysm (AAA) surgery. The objective of this systematic review was to assess existing mortality risk prediction models, and identify which are most useful for patients undergoing AAA repair by either EVAR or open surgical repair. METHODS: A systematic search of the literature was conducted for perioperative mortality risk prediction models for patients with AAA published since 2006. PRISMA guidelines were used; quality was appraised, and data were extracted and interpreted following the CHARMS guidelines. RESULTS: Some 3903 studies were identified, of which 27 were selected. A total of 13 risk prediction models have been developed and directly validated. Most models were based on a UK or US population. The best performing models regarding both applicability and discrimination were the perioperative British Aneurysm Repair score (C-statistic 0·83) and the preoperative Vascular Biochemistry and Haematology Outcome Model (C-statistic 0·85), but both lacked substantial external validation. CONCLUSION: Mortality risk prediction in AAA surgery has been modelled extensively, but many of these models are weak methodologically and have highly variable performance across different populations. New models are unlikely to be helpful; instead case-mix correction should be modelled and adapted to the population of interest using the relevant mortality predictors.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Endovasculares/mortalidade , Aneurisma da Aorta Abdominal/mortalidade , Procedimentos Cirúrgicos Eletivos/mortalidade , Tratamento de Emergência/mortalidade , Mortalidade Hospitalar , Humanos , Modelos Teóricos , Medição de Risco/métodos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: The reported 54 mm median intervention diameter for endovascular aneurysm repair (EVAR) in the Vascular Quality Initiative and European data from the Pharmaceutical Aneurysm Stabilisation Trial (PHAST) implies that in real life the majority of abdominal aortic aneurysm (AAA) repairs occur at diameters smaller than the consensus intervention threshold of 55 mm. This study explores the potential consequences of this practice. METHODS: The differences between real life AAA repair and consensus based intervention threshold were explored in reported data from vascular quality initiatives and PHAST. The subsequent consequences of advancement of endovascular aneurysm repair (EVAR) were estimated using a multistate model based on life tables for the EVAR Medicare population. RESULTS: There appears an approximate 5 mm difference in AAA diameter between real life practice and consensus intervention threshold. Assuming a 2.5 mm annual growth rate, this results in an approximately 2 year advancement of AAA repair. According to the model used, early repair reduces overall small aneurysm patient mortality by 2.3%, it results in 21.9% more EVAR procedures, more EVAR related deaths, and 42.3% and 36.8% more open and endovascular re-interventions, respectively. Cost-benefit estimates imply 482 fewer AAA related deaths, but 140 extra EVAR related deaths for a population of more than 30,000 AAA patients, and a 300 million USD increase in health costs for the 8 year observation period in the Medicare population. CONCLUSIONS: In the real life situation a large proportion of EVAR procedures appear to occur before reaching the consensus threshold. Although this reduces mortality, it comes at a cost of approximately 1 million USD per prevented rupture related death.
Assuntos
Aneurisma da Aorta Abdominal/economia , Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/economia , Intervenção Médica Precoce/economia , Procedimentos Endovasculares/economia , Custos de Cuidados de Saúde , Avaliação de Processos em Cuidados de Saúde/economia , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/mortalidade , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Simulação por Computador , Análise Custo-Benefício , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Humanos , Medicare/economia , Modelos Econômicos , Sistema de Registros , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
OBJECTIVE/BACKGROUND: The Dutch Surgical Aneurysm Audit (DSAA) is mandatory for all patients with primary abdominal aortic aneurysms (AAAs) in the Netherlands. The aims are to present the observed outcomes of AAA surgery against the predicted outcomes by means of V-POSSUM (Vascular-Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity). Adjusted mortality was calculated by the original and re-estimated V(physiology)-POSSUM for hospital comparisons. METHODS: All patients operated on from January 2013 to December 2014 were included for analysis. Calibration and discrimination of V-POSSUM and V(p)-POSSUM was analysed. Mortality was benchmarked by means of the original V(p)-POSSUM formula and risk-adjusted by the re-estimated V(p)-POSSUM on the DSAA. RESULTS: In total, 5898 patients were included for analysis: 4579 with elective AAA (EAAA) and 1319 with acute abdominal aortic aneurysm (AAAA), acute symptomatic (SAAA; n = 371) or ruptured (RAAA; n = 948). The percentage of endovascular aneurysm repair (EVAR) varied between hospitals but showed no relation to hospital volume (EAAA: p = .12; AAAA: p = .07). EAAA, SAAA, and RAAA mortality was, respectively, 1.9%, 7.5%, and 28.7%. Elective mortality was 0.9% after EVAR and 5.0% after open surgical repair versus 15.6% and 27.4%, respectively, after AAAA. V-POSSUM overestimated mortality in most EAAA risk groups (p < .01). The discriminative ability of V-POSSUM in EAAA was moderate (C-statistic: .719) and poor for V(p)-POSSUM (C-statistic: .665). V-POSSUM in AAAA repair overestimated in high risk groups, and underestimated in low risk groups (p < .01). The discriminative ability in AAAA of V-POSSUM was moderate (.713) and of V(p)-POSSUM poor (.688). Risk adjustment by the re-estimated V(p)-POSSUM did not have any effect on hospital variation in EAAA but did in AAAA. CONCLUSION: Mortality in the DSAA was in line with the literature but is not discriminative for hospital comparisons in EAAA. Adjusting for V(p)-POSSUM, revealed no association between hospital volume and treatment or outcome. Risk adjustment for case mix by V(p)-POSSUM in patients with AAAA has been shown to be important.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Ruptura Aórtica/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Hospitais , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/mortalidade , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/mortalidade , Benchmarking , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Procedimentos Cirúrgicos Eletivos , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Auditoria Médica , Países Baixos , Indicadores de Qualidade em Assistência à Saúde , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Management of abdominal aortic aneurysms (AAAs) relies on surgical repair of larger AAAs. Consequently medical interventions inhibiting AAA progression could greatly reduce the need for surgical repair. A spectrum of pharmaceutical strategies has been reported, albeit conclusions often appear contradictory. Given the longstanding interest in pharmaceutical AAA stabilization, a systematic review of the available literature is relevant. OBJECTIVES: The aim is to provide an up to date systematic review of the available data on pharmaceutical therapies for stabilizing or impeding AAA growth. METHODS: A search using Pubmed, Embase, Web of science, Cochrane, CINAHL, Academic Search Premier, and Science Direct identified 27 eligible papers that studied the clinical effect of the pharmaceutical therapy on AAA diameter growth. RESULTS: This review shows that there is currently no pharmaceutical strategy that reduces AAA growth. Most studies are of poor methodological quality. Initial promising reports are often not confirmed in subsequent larger studies, raising the possibility of selective reporting. CONCLUSION: There is currently no pharmaceutical means that halts AAA growth.
Assuntos
Aneurisma da Aorta Abdominal/tratamento farmacológico , Fármacos Cardiovasculares/uso terapêutico , Aneurisma da Aorta Abdominal/diagnóstico , Aneurisma da Aorta Abdominal/mortalidade , Ruptura Aórtica/mortalidade , Ruptura Aórtica/prevenção & controle , Fármacos Cardiovasculares/efeitos adversos , Progressão da Doença , Humanos , Medição de Risco , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVES: Maturation failure is the major limitation of arteriovenous fistulas (AVFs) as hemodialysis access conduits. Indeed, 30-50% of AVFs fail to mature due to intimal hyperplasia and insufficient outward remodeling. Elastin has emerged as an important determinant of vascular remodeling. Here the role of elastin in AVF remodeling in elastin haplodeficient (eln(+/-)) mice undergoing AVF surgery has been studied. METHODS: Unilateral AVFs between the branch of the jugular vein and carotid artery in an end to side manner were created in wild-type (WT) C57BL/6 (n = 11) and in eln(+/-) mice (n = 9). Animals were killed at day 21 and the AVFs were analyzed histologically and at an mRNA level using real-time quantitative polymerase chain reaction. RESULTS: Before AVF surgery, a marked reduction in elastin density in the internal elastic lamina (IEL) of eln(+/-) mice was observed. AVF surgery resulted in fragmentation of the venous internal elastic lamina in both groups while the expression of the tropoelastin mRNA was 53% lower in the eln(+/-) mice than in WT mice (p < .001). At 21 days after AVF surgery, the circumference of the venous outflow tract of the AVF was 21% larger in the eln(+/-) mice than in the WT mice (p = .037), indicating enhanced outward remodeling in the eln(+/-) mice. No significant difference in intimal hyperplasia was observed. The venous lumen of the AVF in the eln(+/-) mice was 53% larger than in the WT mice, although this difference was not statistically significant (eln(+/-), 350,116 ± 45,073 µm(2); WT, 229,405 ± 40,453 µm(2); p = .064). CONCLUSIONS: In a murine model, elastin has an important role in vascular remodeling following AVF creation, in which a lower amount of elastin results in enhanced outward remodeling. Interventions targeting elastin degradation might be a viable option in order to improve AVF maturation.
Assuntos
Fístula Arteriovenosa/metabolismo , Elastina/metabolismo , Remodelação Vascular/fisiologia , Animais , Fístula Arteriovenosa/cirurgia , Derivação Arteriovenosa Cirúrgica/métodos , Artéria Carótida Primitiva/metabolismo , Artéria Carótida Primitiva/cirurgia , Hiperplasia/metabolismo , Veias Jugulares/metabolismo , Veias Jugulares/cirurgia , Masculino , Camundongos Endogâmicos C57BL , Grau de Desobstrução Vascular/fisiologiaRESUMO
OBJECTIVE: NK cells are known to be involved in cardiovascular disease processes. One of these processes, vascular remodeling, may strongly differ between individuals and mouse strains such as the C57BL/6 and BALB/c. Moreover, C57BL/6 and BALB/c mice vary in immune responses and in the composition of their Natural Killer gene Complex (NKC). Here we study the role of NK cells, and in particular the C57BL/6 NKC in vascular remodeling and intimal hyperplasia formation. METHODS AND RESULTS: C57BL/6, BALB/c and CMV1(r) mice, a BALB/c strain congenic for the C57BL/6 NKC, were used in an injury induced cuff model and a vein graft model. NK cell depleted C57BL/6 mice demonstrated a 43% reduction in intimal hyperplasia after femoral artery cuff placement compared to control C57BL/6 mice (p<0.05). Cuff placement and vein grafting resulted in profound intimal hyperplasia in C57BL/6 mice, but also in CMV1(r) mice, whereas this was significantly less in BALB/c mice. Significant more leukocyte infiltrations and IFN-γ staining were seen in both C57BL/6 and CMV1(r) vein grafts compared to BALB/c vein grafts. CONCLUSIONS: These data demonstrate an important role for NK cells in intimal hyperplasia and vascular remodeling. Furthermore, the C57BL/6 NKC in CMV1(r) mice stimulates vascular remodeling most likely through the activation of (IFN-γ-secreting) NK-cells that modulate the outcome of vascular remodeling.
Assuntos
Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patologia , Regulação da Expressão Gênica , Células Matadoras Naturais/metabolismo , Túnica Íntima/metabolismo , Túnica Íntima/patologia , Animais , Artérias/imunologia , Artérias/metabolismo , Artérias/patologia , Vasos Sanguíneos/imunologia , Modelos Animais de Doenças , Hiperplasia , Inflamação/genética , Inflamação/imunologia , Células Matadoras Naturais/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Túnica Íntima/imunologia , Veias/imunologia , Veias/metabolismo , Veias/patologiaRESUMO
OBJECTIVES: To evaluate results after carotid body tumor (CBT) surgery using a novel dissection technique. METHODS: A retrospective analysis of all operated CBT in the last 6 years was carried out and results were compared with the current literature and our previous series, which reported another 111 cases operated on until 2005. RESULTS: Forty-five CBTs were removed in 41 (56% hereditary cases) patients (seven Shamblin I, 22 II, and 16 III). There were no cases of permanent cranial nerve injury or stroke. These pre- and postoperative results compare favorably with our previous series and are superior to, generally smaller, studies reported in the contemporary literature. CONCLUSIONS: This large series of surgically-treated CBTs supports craniocaudal dissection as the surgical technique of choice as it limits blood loss and facilitates safe CBT resection.
Assuntos
Artéria Carótida Primitiva/cirurgia , Tumor do Corpo Carotídeo/cirurgia , Dissecação/métodos , Procedimentos Neurocirúrgicos/métodos , Procedimentos Cirúrgicos Vasculares/métodos , Adolescente , Adulto , Perda Sanguínea Cirúrgica/prevenção & controle , Tumor do Corpo Carotídeo/classificação , Traumatismos dos Nervos Cranianos/etiologia , Doenças do Nervo Facial/etiologia , Feminino , Seguimentos , Humanos , Doenças do Nervo Hipoglosso/etiologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Procedimentos Neurocirúrgicos/efeitos adversos , Paresia/etiologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Adulto JovemRESUMO
Recently, it was demonstrated that arteriogenesis is enhanced in mice deficient in regulatory T cells (CD4(+) CD25(+) FoxP3(+) T cell), which can suppress effector T cell responses. The present study investigates the effects of these regulatory T cells on arteriogenesis in more detail by either specific expanding or depleting regulatory T cells. Hind limb ischemia was induced by electro-coagulation of the femoral artery in mice. Regulatory T cells were either expanded by injecting mice with a complex of interleukin (IL)-2 with the IL-2 monoclonal antibody JES6-1, or depleted by anti-CD25 antibody or diphtheria toxin injections in DEREG mice (depletion of regulatory T cells). Blood flow restoration was monitored using laser Doppler perfusion imaging. Collateral arteries were visualized by immunohistochemistry. Regulatory T cell expansion led to a moderate though significant suppression of blood flow restoration after ischemia induction. Surprisingly, depletion of regulatory T cells resulted in minor increase on blood flow recovery. However, collateral and capillary densities in the post-ischemic skeletal muscle were significantly increased in DEREG mice depleted for regulatory T cells. The presence of regulatory T cells after ischemia induction when analysed in non-depleted DEREG mice could be demonstrated by green fluorescent protein staining only in lymph nodes in the ischemic area, and not in the ischemic muscle tissue. The current study demonstrates that, even under conditions of major changes in regulatory T cell content, the contribution of regulatory T cells to the regulation of the arteriogenic response is only moderate.
Assuntos
Membro Posterior/irrigação sanguínea , Isquemia/fisiopatologia , Neovascularização Patológica/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/farmacologia , Toxina Diftérica/administração & dosagem , Toxina Diftérica/farmacologia , Artéria Femoral/patologia , Artéria Femoral/fisiopatologia , Membro Posterior/fisiopatologia , Interleucina-2/administração & dosagem , Interleucina-2/imunologia , Interleucina-2/farmacologia , Subunidade alfa de Receptor de Interleucina-2/imunologia , Isquemia/sangue , Isquemia/imunologia , Linfonodos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/fisiopatologiaRESUMO
OBJECTIVES: It is currently unclear whether the parallels between abdominal aortic aneurysms (AAAs) and chronic obstructive pulmonary disease (COPD) are explained by common risk factors alone, such as cigarette smoking, or by a predetermined cause. Given the persistent controversy with regard to the association between AAA and COPD, we studied this association in depth. METHODS: We conducted a case-control study comparing patients with a small AAA (maximum infrarenal diameter 35-50 mm, n = 221) with controls diagnosed with peripheral artery disease (PAD, n = 87). The controls were matched to the cases for lifetime cigarette smoking. Pulmonary function was measured by spirometry, and all subjects completed a questionnaire on medical history and smoking habits (current, former and never smokers). RESULTS: Aneurysm patients were similar to controls with respect to gender (p = 0.71), lifetime cigarette smoking (39 vs. 34 pack years, p = 0.23) and history of cardiovascular disease (45% vs. 55%, p = 0.12). Aneurysm patients had more airway obstruction (forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) (0.69 ± 0.12 vs. 0.78 ± 0.11, p < 0.001)), which was most pronounced in never smokers (0.73 ± 0.07 vs. 0.86 ± 0.07, p < 0.001). COPD was more prevalent in aneurysm patients (44%; 98/221) than in controls (20%; 17/87) (adjusted odds ratio (OR) 3.0; 95% confidence interval (95%CI) 1.6-5.5, p < 0.001). In particular, a major proportion of AAA patients was newly diagnosed with COPD; only 40 of 98 patients (41%) with COPD (mild, moderate or severe/very severe) were known before with obstructive pulmonary defects and received treatment. CONCLUSIONS: This study confirms an association between AAA and COPD and shows that this association is independent from smoking. Findings also demonstrate that COPD is under-diagnosed in AAA patients.
Assuntos
Aneurisma da Aorta Abdominal/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fumar/epidemiologia , Idoso , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/tratamento farmacológico , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Doxiciclina/uso terapêutico , Feminino , Volume Expiratório Forçado , Humanos , Modelos Lineares , Modelos Logísticos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Países Baixos/epidemiologia , Razão de Chances , Prevalência , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Medição de Risco , Fatores de Risco , Espirometria , Inquéritos e Questionários , Ultrassonografia , Capacidade VitalRESUMO
AIM: Monocytes play a significant role in neovascularisation. The stimuli that differentiate monocytes along a pro-angio-/arteriogenic-supporting pathway are currently unclear. We investigated whether pre-stimulation of human monocytes with soluble T-cell-derived factors improves revascularisation in murine hind limb ischaemia as a new option for therapeutic angio- and arteriogenesis. DESIGN: Human monocytes were cultured with or without soluble T-cell-derived factors. Unstimulated and pre-stimulated monocytes were transfused after induction of hind limb ischaemia in nude mice. METHODS: Blood flow was measured with laser Doppler perfusion imaging. Collaterals were visualised by immunohistochemistry and angiography. Monocytes were characterised by flowcytometry and Bio-Plex assays. RESULTS: Transfusion of T-cell-pre-stimulated monocytes significantly improved blood flow recovery after hind limb ischaemia and increased collateral size and collateral and capillary number in the post-ischaemic paw. Pre-stimulated monocytes produced a wide variety of factors that support neovascularisation such as platelet-derived growth factor-BB, vascular-endothelial growth factor, interleukin-4 and tumour necrosis factor-α. Few transfused human cells were detected in the muscle tissue, suggesting that paracrine rather than direct effects appear responsible for the enhanced recovery of blood flow observed. CONCLUSION: These results show a beneficial role for T-cell-pre-stimulated monocytes in neovascularisation, rendering the monocyte a potential candidate for regenerative cell therapy that promotes revascularisation in peripheral arterial disease patients.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Isquemia/cirurgia , Monócitos/transplante , Músculo Esquelético/irrigação sanguínea , Neovascularização Fisiológica , Proteínas Angiogênicas/metabolismo , Animais , Velocidade do Fluxo Sanguíneo , Capilares/imunologia , Capilares/fisiopatologia , Células Cultivadas , Circulação Colateral , Modelos Animais de Doenças , Citometria de Fluxo , Membro Posterior , Humanos , Imuno-Histoquímica , Isquemia/diagnóstico por imagem , Isquemia/imunologia , Isquemia/fisiopatologia , Fluxometria por Laser-Doppler , Receptores de Lipopolissacarídeos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Monócitos/imunologia , Comunicação Parácrina , Radiografia , Fluxo Sanguíneo Regional , Fatores de TempoRESUMO
PURPOSE: Ruptured aneurysm of the abdominal aorta (RAAA) is a condition associated with high mortality rate. If Cardiopulmonary Resuscitation (CPR) is required, outcome is considered even worse. The aim of this study was to assess the effect of CPR on 30-day mortality of RAAA patients. Furthermore the Hardman index was evaluated. METHODS: 109 patients with RAAA during a 5 year period (2001-2005) were analysed retrospectively. 30-day mortality, the presence of CPR and Hardman risk factors were recorded. The presence of CPR and the Hardman index were related to clinical outcome. RESULTS: 104 patients were included in our analysis. Eighteen patients received CPR. Overall 30-day mortality was 40%. Patients receiving CPR had a higher mortality rate than patients who did not (89% vs. 30%, p <0.0001). Patients receiving CPR prior to surgery had a mortality rate of 100% (n = 12). In patients with a Hardman Index of < or = 1, 2 and > or = 3 the 30-day mortality was respectively 15%, 47% and 81%. CONCLUSION: Requirement of CPR has a detrimental effect on RAAA-patient outcome. Patients receiving CPR prior to surgery have no survival chance. We advocate that surgery in these patients should not be undertaken. Hardman Index has a predictive value concerning 30-day mortality.
Assuntos
Aneurisma Roto/mortalidade , Aneurisma da Aorta Abdominal/mortalidade , Reanimação Cardiopulmonar , Idoso , Aneurisma Roto/epidemiologia , Aneurisma Roto/cirurgia , Aneurisma da Aorta Abdominal/epidemiologia , Aneurisma da Aorta Abdominal/cirurgia , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores Sexuais , Análise de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Increased use of endovascular aneurysm repair (EVAR) and reduced open surgical repair (OSR), has decreased postoperative mortality after elective repair of abdominal aortic aneurysms (AAAs). The choice between EVAR or OSR depends on aneurysm anatomy, and the experience and preference of the vascular surgeon, and therefore differs between hospitals. The aim of this study was to investigate the current mortality risk difference (RD) between EVAR and OSR, and the effect of hospital preference for EVAR on overall mortality. METHODS: Primary elective infrarenal or juxtarenal aneurysm repairs registered in the Dutch Surgical Aneurysm Audit (2013-2017) were analysed. First, mortality in hospitals with a higher preference for EVAR (high-EVAR group) was compared with that in hospitals with a lower EVAR preference (low-EVAR group), divided by the median percentage of EVAR. Second, the mortality RD between EVAR and OSR was determined by unadjusted and adjusted linear regression and propensity-score (PS) analysis and then by instrumental-variable (IV) analysis, adjusting for unobserved confounders; percentage EVAR by hospital was used as the IV. RESULTS: A total of 11 997 patients were included. The median hospital rate of EVAR was 76.6 per cent. The overall mortality RD between high- and low-EVAR hospitals was 0.1 (95 per cent -0.5 to 0.4) per cent. The OSR mortality rate was significantly higher among high-EVAR hospitals than low-EVAR hospitals: 7.3 versus 4.0 per cent (RD 3.3 (1.4 to 5.3) per cent). The EVAR mortality rate was also higher in high-EVAR hospitals: 0.9 versus 0.7 per cent (RD 0.2 (-0.0 to 0.6) per cent). The RD following unadjusted, adjusted, and PS analysis was 4.2 (3.7 to 4.8), 4.4 (3.8 to 5.0), and 4.7 (4.1 to 5.3) per cent in favour of EVAR over OSR. However, the RD after IV analysis was not significant: 1.3 (-0.9 to 3.6) per cent. CONCLUSION: Even though EVAR has a lower mortality rate than OSR, the overall effect is offset by the high mortality rate after OSR in hospitals with a strong focus on EVAR.
Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/efeitos adversos , Hospitais com Alto Volume de Atendimentos , Humanos , Complicações Pós-Operatórias , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The management of abdominal aortic aneurysm (AAA) is fully dictated by AAA size, but there are no uniform measurement guidelines, and systematic differences exist between ultrasound- and CT-based size estimation. The aim of this study was to devise a uniform ultrasound acquisition and measurement protocol, and to test whether harmonization of ultrasound and CT readings is feasible. METHODS: A literature review was undertaken to evaluate evidence for ultrasound-based measurement of AAA. A protocol for measuring AAA was then developed, and intraobserver and interobserver reproducibility was tested. Finally, agreement between ultrasound readings and CT-based AAA diameters was evaluated. This was an observational study of patients with a small AAA who participated in two pharmaceutical intervention trials. RESULTS: Based on a literature review, an ultrasound acquisition and reading protocol was devised. Evaluation of the protocol showed an intraobserver repeatability of 1.6 mm (2s.d.) and an interobserver intraclass correlation coefficient (ICC) of 0.97. Comparison of protocolled ultrasound readings and local CT readings indicated a good correlation (r = 0.81), but a systematic +4.1-mm difference for CT. Harmonized size readings for ultrasound imaging and CT increased the correlation (r = 0.91) and reduced the systematic difference to +1.8 mm by CT. Interobserver reproducibility of protocolized CT measurements showed an ICC of 0.94 for the inner-to-inner method and 0.96 for the outer-to-outer method. CONCLUSION: The absence of harmonized size acquisition and reading guidelines results in overtreatment and undertreatment of patients with AAA. This can be avoided by the implementation of standardized ultrasound acquisition and a harmonized reading protocol for ultrasound- and CT-based readings.
Assuntos
Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/diagnóstico por imagem , Ensaios Clínicos como Assunto , Humanos , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
BACKGROUND: Lower extremity arterial revascularization (LEAR) is the gold-standard for critical lower limb ischemia (CLI). The goal of this study was twofold. First, we evaluated the long-term functional status of patients undergoing primary LEAR for CLI. Second, prognostic factors of long-term functional status and survival after primary LEAR for CLI were assessed. METHODS: All primary LEAR procedures were analyzed. Patients were stratified by preoperative functional status: ambulatory (group I) vs nonambulatory (group II). Patients were followed-up after 3 and 6 years. Adverse events (AEs) were categorized according to predefined standards: minor, surgical, failed revascularization, and systemic. Associated patient demographic/clinical data were analyzed using univariate and multivariate methods. RESULTS: There were 106 LEAR patients (group I: n = 42, 40% vs group II: n = 64, 60%). Group II patients were significantly older (75 vs 62 years; P = .00), were classified ASA 3-4 more frequently (78% vs 52%; P < .02), had more cardiac disease (n = 42, 66% vs n = 10, 24%; P = .00), renal disease (n = 26, 41% vs n = 7, 17%; P = .00), diabetes (n = 36, 56% vs n = 8, 19%; P = .00), hypertension (n = 47, 73% vs n = 13, 31%; P = .00) and severe CLI (n = 42, 66% vs n = 18, 38%; P < .01). Group II patients had a higher incidence of death (65.6% vs 14.3%; P = .00), minor AEs (n = 38, 26% vs n = 10, 22%; P = .00), surgical AEs (n = 48, 33% vs n = 12, 26%; P < .02) and systemic AEs (n = 24, 86% vs n = 4, 9%; P < .02). Also more unplanned reinterventions occurred in group II (n = 148, 76% vs n = 47, 24%; P = .00). Nonambulatory status was a multivariate independent predictor of nonambulatory status after LEAR during 6 years follow-up (odds ration [OR[: 21.47; 95% confidence interval [CI]: 2.76-166.77; P = .00). Pulmonary disease (OR: 7.49; 95% CI: 2.17-25.80; P = .00), not prescribing beta-blockers (OR: 4.67; 95% CI: 1.28-17.03; P < .02), nonambulatory status (OR: 22.99; 95% CI: 6.27-84.24; P = .00), and systemic AEs (OR: 9.66; 95% CI: 1.84-50.57; P < .01) were independent predictors of death. Functional status was not improved in group II after long-term follow-up. CONCLUSION: Nonambulatory patients suffer from extensive comorbid conditions. They are accompanied with an increased occurrence of AEs, unplanned reinterventions, and poor long-term survival rates. Successful LEAR did not improve their functional status after 6 years. This emphasizes that attempts for limb salvage must be carefully considered in these patients.
Assuntos
Indicadores Básicos de Saúde , Claudicação Intermitente/cirurgia , Isquemia/cirurgia , Extremidade Inferior/irrigação sanguínea , Procedimentos Cirúrgicos Vasculares , Antagonistas Adrenérgicos beta/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estado Terminal , Complicações do Diabetes/mortalidade , Complicações do Diabetes/cirurgia , Feminino , Cardiopatias/complicações , Humanos , Hipertensão/complicações , Claudicação Intermitente/etiologia , Claudicação Intermitente/mortalidade , Isquemia/complicações , Isquemia/mortalidade , Estimativa de Kaplan-Meier , Salvamento de Membro , Modelos Logísticos , Pneumopatias/complicações , Masculino , Pessoa de Meia-Idade , Limitação da Mobilidade , Razão de Chances , Seleção de Pacientes , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Recuperação de Função Fisiológica , Sistema de Registros , Reoperação , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidadeRESUMO
OBJECTIVES: This study presents a review of studies reporting on quality of care in vascular surgery. The aim of this study was to provide insight in quality improvement initiatives in vascular surgery. DESIGN: Original data were collected from MEDLINE and EMBASE databases. Inclusion criteria were: description of one of the three factors of quality of care, e.g. process, outcome or structure and prospectively described. All articles identified were ascribed to a domain of quality of care. RESULTS: 57 prospective articles were included, drawn from 859 eligible reports. Structure as an indicator of quality of care was described in 19 reports, process in 7 reports and outcome in 31 reports. Most studies based on structural measures considered the introduction of a clinical pathway or a registration system. Reports based on process measures showed promising results. Outcome as clinical indicator mainly focussed on identifying risk factors for morbidity, mortality or failure of treatment. CONCLUSIONS: Structure and process indicators are evaluated scarcely in vascular surgery. Many studies in vascular surgery have been focussed on outcomes as indicator of quality of care, but a shift towards process measures should be considered as focus of attention in the future.
Assuntos
Pesquisa sobre Serviços de Saúde/normas , Avaliação de Processos e Resultados em Cuidados de Saúde/normas , Indicadores de Qualidade em Assistência à Saúde/normas , Procedimentos Cirúrgicos Vasculares/normas , Procedimentos Clínicos/normas , Humanos , Estudos Prospectivos , Projetos de Pesquisa , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidadeRESUMO
OBJECTIVE: Since patients with peripheral arterial occlusive disease (PAOD) are at high-risk for cardiovascular morbidity and mortality, preventive measures aimed to reduce cardiovascular adverse events are advocated in the current guidelines. We conducted a systematic review to assess the implementation of secondary prevention (SP) measures in PAOD patients. METHODS: PubMed, Cochrane Library, EMBASE and Web of Science databases were searched to perform a systematic review of the literature from 1999 till June 2008 on SP for PAOD patients. Assessment of study quality was done following the Cochrane Library review system. The record outcomes were antiplatelet agents, heart rate lowering agents, blood pressure lowering agents, lipid lowering agents, glucose lowering agents, smoking cessation and walking exercise. RESULTS: From a total of 2137 identified studies, 83 observational studies met the inclusion criteria, of which 24 were included in the systematic review comprising 34 157 patients. These patients suffered from coronary artery disease (n=3516, 41%), myocardial infraction (n=2647, 38%), angina pectoris (n=1790, 31%), congestive heart failure (n=2052, 14%), diabetes mellitus (n=10 690, 31%),hypertension (n=20 823, 73%) and hyperlipidaemia (n=15 067, 64%). Contrary to what the guidelines prescribe, antiplatelet agents, heart rate lowering agents, blood pressure lowering agents and lipid lowering agents were prescribed in 63%, 34%, 46% and 45% of the patients, respectively. Glucose lowering agents were prescribed in 81% and smoking cessation in 39% of the patients. CONCLUSION: The majority of patients suffering from PAOD do not receive the entire approach of SP measures as suggested by the current guidelines. To our knowledge, the cause of this undertreatment is multifactorial: patient, physician or health-care-related.