RESUMO
PURPOSE: The purpose of the study was to provide a consensus definition of the infrarenal sealing zone and develop an algorithm to determine when and if adjunctive procedure(s) or reintervention should be considered in managing patients undergoing endovascular aortic repair (EVAR) for infrarenal abdominal aortic aneurysm (AAA). METHODS: A European Advisory Board (AB), made up of 11 vascular surgeons with expertise in EVAR for AAA, was assembled to share their opinion regarding the definition of preoperative and postoperative infrarenal sealing zone. Information on their current clinical practice and level of agreement on proposed reintervention paths was used to develop an algorithm. The process included 2 virtual meetings and 2 rounds of online surveys completed by the AB (Delphi method). Consensus was defined as reached when ≥ 8 of 11 (73%) respondents agreed or were neutral. RESULTS: The AB reached complete consensus on definitions and measurement of the pre-EVAR target anticipated sealing zone (TASZ) and the post-EVAR real achieved sealing zone (RASZ), namely, the shortest length between the proximal and distal reference points as defined by the AB, in case of patients with challenging anatomies. Also, agreement was achieved on a list of 4 anatomic parameters and 3 prosthesis-/procedure-related parameters, considered to have the most significant impact on preoperative and postoperative sealing zones. Furthermore, the agreement was reached that in the presence of visible neck-related complications, both adjunctive procedure(s) and reintervention should be contemplated (100% consensus). In addition, adjunctive procedure(s) or reintervention can be considered in the following cases (% consensus): insufficient sealing zone on completion imaging (91%) or on the first postoperative computed tomography (CT) scan (91%), suboptimal sealing zone on completion imaging (73%) or postoperative CT scan (82%), and negative evolution of the actual sealing zone over time (91%), even in the absence of visible complications. CONCLUSIONS: AB members agreed on definitions of the pre- and post-EVAR infrarenal sealing zone, as well as factors of influence. Furthermore, a clinical decision algorithm was proposed to determine the timing and necessity of adjunctive procedure(s) and reinterventions.
Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/métodos , Correção Endovascular de Aneurisma , Técnica Delphi , Consenso , Prova Pericial , Resultado do Tratamento , Procedimentos Endovasculares/efeitos adversos , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Fatores de Risco , Estudos Retrospectivos , Prótese VascularRESUMO
BACKGROUND: Biological xenografts using tubulized porcine pericardium are an alternative to replace infected prosthetic graft. We recently reported an innovative technique using a stapled porcine pericardial bioconduit for immediate vascular reconstruction in emergency. The objective of this study is to compare the growth and adherence to grafts of bacteria and yeast incubated with stapled porcine pericardium, sutured or naked pericardium. MATERIAL AND METHODS: One square centimeter of porcine pericardial patches, with or without staples or sutures, was incubated with 105 colony forming units of Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Candida albicans for 1, 6, and 24 h. The medium was collected to quantify planktonic microorganisms, while grafts were sonicated to quantify adherent microorganisms. Dacron and Dacron Silver were analyzed in parallel as synthetic reference prostheses. RESULTS: Stapled porcine pericardium reduced the growth and the adherence of E coli (2- to 30-fold; P < 0.0005), S aureus (11- to 1000-fold; P < 0.0006), S epidermidis (>500-fold; P < 0.0001), and C albicans (12- to 50-fold; P < 0.0001) when compared to medium alone (growth) and pericardium or Dacron (adherence). Native and sutured porcine pericardium interfered with the growth and the adherence of E coli and C albicans, and Dacron with that of S epidermidis. As expected, Dacron Silver was robustly bactericidal. CONCLUSIONS: Stapled porcine pericardium exhibited a lower susceptibility to infection by bacteria and yeasts in vitro when compared to the native and sutured porcine pericardium. Stapled porcine pericardium might be a good option for rapid vascular grafting without increasing infectivity.
Assuntos
Prótese Vascular , Polietilenotereftalatos , Animais , Escherichia coli , Humanos , Pericárdio , Prata , Staphylococcus aureus , Staphylococcus epidermidis , SuínosRESUMO
OBJECTIVE/BACKGROUND: In critical limb ischaemia (CLI), current guidelines recommend revascularisation whenever possible, preferentially through endovascular means. However, in the case of long occlusions or failed endovascular attempts, distal bypasses still have a place. Single segment great saphenous vein (GSV), which provides the best conduit, is often not available and currently there is no consensus about the best alternative graft. METHODS: From January 2006 to December 2015, 42 cryopreserved arterial allografts were used for a distal bypass. Autologous GSVs or alternative autologous conduits were unavailable for all patients. The patients were observed for survival, limb salvage, and allograft patency. The results were analysed with Kaplan-Meier graphs. RESULTS: Estimates of secondary patency at one, two and five years were 81%, 73%, and 57%, respectively. Estimates of primary patency rates at one, two and five years were 60%, 56%, and 26%, respectively. Estimates of limb salvage rates at one, two and five years were 89%, 89%, and 82%, respectively. Estimates of survival rates at one, two and five years were 92%, 76% and 34%, respectively. At 30 days, major amputations and major adverse cardiac events were one and zero, respectively. Six major amputations occurred during the long-term follow up. CONCLUSION: Despite a low primary patency rate at two years, the secondary patency of arterial allografts is acceptable for distal bypasses. This suggests that cryopreserved arterial allografts are a suitable alternative for limb saving distal bypasses in the absence of venous conduits, improving limb salvage rates and, possibly, quality of life.
Assuntos
Artérias/transplante , Criopreservação , Isquemia/cirurgia , Extremidade Inferior/irrigação sanguínea , Enxerto Vascular/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Amputação Cirúrgica , Estado Terminal , Feminino , Oclusão de Enxerto Vascular/etiologia , Oclusão de Enxerto Vascular/fisiopatologia , Oclusão de Enxerto Vascular/cirurgia , Humanos , Isquemia/diagnóstico por imagem , Isquemia/fisiopatologia , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Enxerto Vascular/efeitos adversos , Grau de Desobstrução VascularRESUMO
OBJECTIVES: Recanalization of peripheral chronic total occlusions (CTO) is technically challenging especially in cases of in-stent and/or pre-stent and heavily calcified lesions. A high-frequency vibrational device (HFVD) was first used as a secondary-intention device in CTO recanalizations when they were refractory to a guidewire. The aim of this study was to assess the safety and efficacy of the HFVD as a first-line treatment for challenging CTOs and thus to define the percutaneous intentional intraluminal-assisted recanalization (PILAR) technique. METHODS: Fifty-two patients were treated with the HFVD. Only challenging CTOs were included: 7 pre-stent, 7 in-stent, and 38 highly calcified CTOs. Technical success was defined as the ability to cross the CTO using the HFVD. Secondary outcome was defined as successful intraluminal crossing. Safety endpoints were procedure-related thromboembolism or perforation. Patients were followed up at 3 months and 1 year. RESULTS: The technical success rate for recanalization was 90%, of which 83% were intraluminal. The mean recanalized length was 91 ± 44 mm. One thromboembolic complication occurred, which was subsequently treated with thromboaspiration. Three-month and 1-year primary patency rates were 92% and 79%, respectively. CONCLUSIONS: HFVD-based PILAR is a safe and effective technique for in-stent or pre-stent CTO recanalization of long and calcified lesions. KEY POINTS: ⢠Intraluminal recanalization is the preferred procedure in heavily calcified or pre-/in-stent CTO. ⢠First-line use of assisted intraluminal recanalization for CTO defines the PILAR technique. ⢠HFVD-based PILAR is safe and provides a high success rate for challenging CTO recanalization.
Assuntos
Cateterismo/métodos , Claudicação Intermitente/terapia , Perna (Membro)/irrigação sanguínea , Vibração/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia , Doença Crônica , Feminino , Humanos , Claudicação Intermitente/diagnóstico , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Mortality with ruptured abdominal aortic aneurysms (rAAAs) is 80% overall, 50% when operated, and 100% when not operated. Distinguishing in emergency patients who should be operated versus being offered palliative treatment is difficult. We sought to identify key factors to consider in this decision-making. METHODS: Between 2001 and 2014, we selected all consecutive patients with rAAA treated by open or endovascular procedures in a tertiary hospital for inclusion in this retrospective, single-center study. Symptomatic aneurysms and isolated ruptured iliac aneurysms were excluded. The primary outcome was in-hospital mortality, and secondary outcomes were institutionalization rate and long-term mortality. Associations between predictive factors and in-hospital mortality were evaluated using univariate logistic regression. The local ethics committee approved this study. RESULTS: The mean age (±standard deviation) of the 72 included patients was 73 years (±9.0) and 88% were men. Among the 65 open (90%) and 7 endovascular procedures (10%), overall in-hospital mortality was 21%, 1- and 2-year mortalities were both 26%, and the institutionalization rate was 5%. Mean follow-up was 43 months (Kaplan-Meier estimate). Univariate analysis identified age as associated with a 20% per year increased risk of in-hospital mortality (correlation, P < 0.0001). Female sex was the other main preoperative risk factor correlated with in-hospital mortality (P = 0.006). Significant perioperative risk factors were suprarenal clamping (P = 0.038), amount of fresh frozen plasma transfused (P = 0.018), and number of blood transfusions (P < 0.0001). CONCLUSIONS: The most significant preoperative mortality-related factors were age and female sex. Our study also showed that institutionalization and long-term mortality are not factors to consider in the decision-making process.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Ruptura Aórtica/cirurgia , Tomada de Decisão Clínica , Seleção de Pacientes , Centros de Atenção Terciária , Procedimentos Cirúrgicos Vasculares , Fatores Etários , 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 , Técnicas de Apoio para a Decisão , Feminino , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Suíça , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidadeRESUMO
BACKGROUND: The aim of this study is to evaluate the short- and mid-term results of the Zenith bifurcated iliac side branch device (ZBIS) in the treatment of common iliac artery (CIA) aneurysms, and to assess risk factors for intraoperative internal iliac artery (IIA) thrombosis. METHODS: All patients who underwent endovascular treatment of either an isolated CIA aneurysm or an aortoiliac aneurysm using the ZBIS device in the departments of vascular surgery of Strasbourg (France) and Lausanne (Switzerland) between January 2010 and December 2014 were retrospectively collected. RESULTS: Thirty-one implantations were performed: 30 patients underwent 31 endovascular CIA aneurysm treatments with the ZBIS device. Mean operative time was 188 min. Technical success was obtained in 26 implantations (84%). In 5 implantations (16%), the final angiogram revealed an IIA thrombosis. Thirty-day mortality was 3.2%. Thirty-day morbidity was 13.3%. Mean follow-up was 15 months. Overall survival was 96% at 1 year and 89% at 2 years. In intention-to-treat analysis, primary patency of the internal iliac side branch was 84% at 1 year and 76% at 2 years (5 peroperative IIA occlusions and 1 late occlusion). Freedom from reintervention was 89% at 1 and 2 years. One case of type III endoleak and 2 cases of type II endoleaks were identified. Only type III endoleak required an additional intervention with a covered stent. Aneurysm diameter decreased in 15 implantations (48%) and remained stable in 16 implantations (52%). Clinical, radiological, and peroperative parameters were analyzed to identify risk factor for intraoperative thrombosis of the internal iliac side branch. Notion of intraoperative difficulties (any additional procedure that was not initially planned and increasing the operating time) appeared as a risk factor in multivariate analysis (P < 0.01, standard deviation 1.27, odds ratio 30.6). CONCLUSIONS: The main findings of our study is that the procedure can be difficult to perform in particular conditions and can lead to peroperative failure in these cases, highlighting the need for adequate patients screening. When technical success is obtained, outcomes can be considered as satisfactory.
Assuntos
Arteriopatias Oclusivas/etiologia , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Aneurisma Ilíaco/cirurgia , Artéria Ilíaca/cirurgia , Trombose/etiologia , Idoso , Idoso de 80 Anos ou mais , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/mortalidade , Arteriopatias Oclusivas/fisiopatologia , Implante de Prótese Vascular/mortalidade , Endoleak/etiologia , Feminino , França , Oclusão de Enxerto Vascular/etiologia , Humanos , Aneurisma Ilíaco/diagnóstico por imagem , Aneurisma Ilíaco/mortalidade , Aneurisma Ilíaco/fisiopatologia , Artéria Ilíaca/diagnóstico por imagem , Artéria Ilíaca/fisiopatologia , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Duração da Cirurgia , Desenho de Prótese , Estudos Retrospectivos , Fatores de Risco , Suíça , Trombose/diagnóstico por imagem , Trombose/mortalidade , Trombose/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
Rare Vascular Diseases (RVD) encompass different types of vessel involvement. Some cause a dilation, others a weakening or tortuosity of the arterial wall, others an obstruction or excessive calcification of arterial walls. Clinical pathway of patients with RVD to diagnosis is often long and complex. Thus, in order to allow early diagnosis and coordinated multidisciplinary management and follow-up, a specialized RVD centre has been set-up at the CHUV, following the framework of the national concept of rare diseases.
Les maladies vasculaires rares (MVR) englobent différents types d'atteintes des vaisseaux. Certaines engendrent une dilatation ou une tortuosité de la paroi artérielle, d'autres une fragilisation de la paroi, d'autres encore entraînent une obstruction du vaisseau, une calcification excessive des parois, ou des malformations vasculaires. Comme pour toutes les maladies rares, le parcours des patients vers un diagnostic est souvent long et complexe. Afin de permettre un diagnostic le plus précoce possible, ainsi qu'un suivi coordonné et une prise en charge multidisciplinaire médicale et sociale, un centre des MVR a été mis en place au CHUV, dans le cadre du concept national des maladies rares.
Assuntos
Doenças Raras , Doenças Vasculares , Calcinose , Humanos , Equipe de Assistência ao Paciente , Doenças Raras/diagnóstico , Doenças Raras/terapia , Doenças Vasculares/diagnóstico , Doenças Vasculares/terapiaRESUMO
BACKGROUND: Multilevel peripheral arterial disease is frequently observed in patients with intermittent claudication or critical limb ischemia. This report evaluates the efficacy of one-stage hybrid revascularization in patients with multilevel arterial peripheral disease. PATIENTS AND METHODS: A retrospective analysis of a prospective database included all consecutive patients treated by a hybrid approach for a multilevel arterial peripheral disease. The primary outcome was the patency rate at 6 months and 1 year. Secondary outcomes were early and midterm complication rate, limb salvage and mortality rate. Statistical analysis, including a Kaplan-Meier estimate and univariate and multivariate Cox regression analyses were carried out with the primary, primary assisted and secondary patency, comparing the impact of various risk factors in pre- and post-operative treatments. RESULTS: 64 patients were included in the study, with a mean follow-up time of 428 days (range: 4 - 1140). The technical success rate was 100 %. The primary, primary assisted and secondary patency rates at 1 year were 39 %, 66 % and 81 %, respectively. The limb-salvage rate was 94 %. The early mortality rate was 3.1 %. Early and midterm complication rates were 15.4 % and 6.4 %, respectively. The early mortality rate was 3.1 %. CONCLUSIONS: The hybrid approach is a major alternative in the treatment of peripheral arterial disease in multilevel disease and comorbid patients, with low complication and mortality rates and a high limb-salvage rate.
Assuntos
Endarterectomia , Procedimentos Endovasculares , Claudicação Intermitente/terapia , Isquemia/terapia , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/terapia , Enxerto Vascular , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Estado Terminal , Bases de Dados Factuais , Endarterectomia/efeitos adversos , Endarterectomia/mortalidade , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Claudicação Intermitente/mortalidade , Claudicação Intermitente/fisiopatologia , Claudicação Intermitente/cirurgia , Isquemia/mortalidade , Isquemia/fisiopatologia , Isquemia/cirurgia , Estimativa de Kaplan-Meier , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Doença Arterial Periférica/cirurgia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Suíça , Fatores de Tempo , Resultado do Tratamento , Enxerto Vascular/efeitos adversos , Enxerto Vascular/mortalidade , Grau de Desobstrução VascularRESUMO
Sarcomas are rare diseases, the treatment of which requires an appropriate technical plateform and a broad spectrum of multidisciplinary specialists. Many are initially treated by unplanned excision, and then referred to specialized centres. Secondary treatments may lead to higher complication rates and local recurrence, with lower functional outcome, life quality and possibly overall survival. In order to improve the accessibility for referral to a specialist centre, the coordination of clinical and research activities, and the quality of the management of sarcomas in general, Lausanne University Hospital (CHUV) has opened a Sarcoma centre on October 1st 2016. The objective of the present paper is to illustrate the concept and provide useful clinical recommendations.
Les sarcomes sont des maladies rares, dont la prise en charge multidisciplinaire nécessite un plateau technique important. Ils font souvent l'objet d'une excision initiale accidentelle, nécessitant une reprise en milieu spécialisé, avec un risque majoré de complications et de récidive locale, un impact sur la fonction, voire la survie. La prise en charge des sarcomes est réservée aux centres de référence, où il est souvent difficile pour le praticien de trouver un interlocuteur à qui adresser un patient ou demander un avis. Pour les cliniciens et les chercheurs, il est souvent compliqué de coordonner les activités. Pour en améliorer la prise en charge globale, le CHUV a donc créé un centre des sarcomes, inauguré le 1er octobre 2016. Le présent article a pour but d'illustrer cette problématique et de rappeler quelques données cliniques utiles.
Assuntos
Pesquisa Biomédica/organização & administração , Institutos de Câncer/organização & administração , Sarcoma/terapia , Humanos , Qualidade de Vida , Encaminhamento e Consulta , Sobrevida , SuíçaAssuntos
Prótese Vascular/microbiologia , Procedimentos de Cirurgia Plástica/métodos , Infecções Relacionadas à Prótese/cirurgia , Ruptura Espontânea/cirurgia , Grampeamento Cirúrgico/métodos , Idoso , Bioprótese , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Artéria Femoral/cirurgia , Humanos , Masculino , Artéria Poplítea/cirurgia , Infecções Relacionadas à Prótese/complicações , Procedimentos de Cirurgia Plástica/instrumentação , Ruptura Espontânea/etiologia , Grampeamento Cirúrgico/instrumentação , Resultado do TratamentoRESUMO
Background: The aim of this study was to assess the prognostic role of frailty and sarcopenia on the survival of patients with AAA undergoing elective endovascular repair (EVAR). Methods: A systematic review of the literature was conducted in accordance with Meta-analysis of Observational Studies in Epidemiology (MOOSE). The association of frailty or sarcopenia with 30-day mortality and late survival was expressed as odds ratios (ORs) or hazard ratios (HRs) with a 95% confidence interval (CI). Meta-analysis random effects models were applied. The five-factor modified frailty index (mFI-5) was used as a frailty metric and sarcopenia was determined using computed tomography angiography (CTA) with measurements of the total psoas muscle area. Frailty was defined as patients with mFI-5 ≥ 0.6 and sarcopenia was defined as the total psoas muscle area (TPA) within the lowest tertile. Results: Thirteen observational cohorts reporting a total of 56,756 patient records were eligible for analysis. Patients with frailty (mFI-5 ≥ 0.6) had significantly increased 30-day mortality than those without frailty (random effects method: OR, 4.84, 95% CI 3.34-7.00, p < 0.001). Patients with sarcopenia (lowest TPA tertile) had significantly increased 30-day mortality according to the fixed effects method (OR, 3.30, 95% CI 2.17-5.02, p < 0.001), but not the random effects method (OR, 2.64, 95% CI 0.83-8.39, p = 0.098). Patients with sarcopenia or frailty had a significantly increased hazard ratio (HR) for late mortality than those without frailty or sarcopenia according to the random effects method (HR, 2.39, 95% CI 1.66-3.43, p < 0.001). The heterogeneity of the studies was low (I2: 0.00%, p = 0.86). The relation of frailty to age extracted from four studies demonstrates that the risk of frailty increases with age according to the random effects method (standard mean differences, SMD, 0.52, 95% CI 0.44-0.61, p < 0.001). The heterogeneity of the studies was low (I2: 0.00%, p = 0.64). Conclusions: Patients with sarcopenia or frailty have a significantly increased risk of mortality following elective EVAR. Prospective studies validating the use of frailty and sarcopenia for risk prediction after EVAR are needed before these tools can be used to support decision making.
RESUMO
Intimal hyperplasia (IH) is the major cause of stenosis of vein grafts. Drugs such as statins prevent stenosis, but their systemic administration has limited effects. We developed a hyaluronic acid hydrogel matrix, which ensures a controlled release of atorvastatin (ATV) at the site of injury. The release kinetics demonstrated that 100% of ATV was released over 10 hours, independent of the loading concentration of the hydrogel. We investigated the effects of such a delivery on primary vascular smooth muscle cells isolated from human veins. ATV decreased the proliferation, migration, and passage of human smooth muscle cells (HSMCs) across a matrix barrier in a similar dose-dependent (5-10 µM) and time-dependent manner (24-72 hours), whether the drug was directly added to the culture medium or released from the hydrogel. Expression analysis of genes known to be involved in the development of IH demonstrated that the transcripts of both the gap junction protein connexin43 (Cx43) and plasminogen activator inhibitor-1 (PAI-1) were decreased after a 24-48-hour exposure to the hydrogel loaded with ATV, whereas the transcripts of the heme oxygenase (HO-1) and the inhibitor of tissue plasminogen activator were increased. At the protein level, Cx43, PAI-1, and metalloproteinase-9 expression were decreased, whereas HO-1 was upregulated in the presence of ATV. The data demonstrate that ATV released from a hydrogel has effects on HSMCs similar to the drug being freely dissolved in the environment.
Assuntos
Ácidos Heptanoicos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Miócitos de Músculo Liso/efeitos dos fármacos , Pirróis/farmacologia , Veias/citologia , Atorvastatina , Western Blotting , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Primers do DNA , Relação Dose-Resposta a Droga , Ácidos Heptanoicos/administração & dosagem , Humanos , Hidrogéis , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Imuno-Histoquímica , Cultura Primária de Células , Pirróis/administração & dosagem , Transcrição Gênica/efeitos dos fármacos , Veias/efeitos dos fármacosRESUMO
BACKGROUND: Human saphenous vein grafts are one of the salvage bypass conduits when endovascular procedures are not feasible or fail. Understanding the remodeling process that venous grafts undergo during exposure to arterial conditions is crucial to improve their patency, which is often compromised by intimal hyperplasia. The precise role of hemodynamic forces such as shear stress and arterial pressure in this remodeling is not fully characterized. The aim of this study was to determine the involvement of arterial shear stress and pressure on vein wall remodeling and to unravel the underlying molecular mechanisms. METHODS: An ex vivo vein support system was modified for chronic (up to 1 week), pulsatile perfusion of human saphenous veins under controlled conditions that permitted the separate control of arterial shear stress and different arterial pressure (7 mm Hg or 70 mm Hg). RESULTS: Veins perfused for 7 days under high pressure (70 mm Hg) underwent significant development of a neointima compared with veins exposed to low pressure (7 mm Hg). These structural changes were associated with altered expression of several molecular markers. Exposure to an arterial shear stress under low pressure increased the expression of matrix metalloproteinase (MMP)-2 and MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 at the transcript, protein, and activity levels. This increase was enhanced by high pressure, which also increased TIMP-2 protein expression despite decreased levels of the cognate transcript. In contrast, the expression of plasminogen activator inhibitor-1 increased with shear stress but was not modified by pressure. Levels of the venous marker Eph-B4 were decreased under arterial shear stress, and levels of the arterial marker Ephrin-B2 were downregulated under high-pressure conditions. CONCLUSIONS: This model is a valuable tool to identify the role of hemodynamic forces and to decipher the molecular mechanisms leading to failure of human saphenous vein grafts. Under ex vivo conditions, arterial perfusion is sufficient to activate the remodeling of human veins, a change that is associated with the loss of specific vein markers. Elevation of pressure generates intimal hyperplasia, even though veins do not acquire arterial markers. CLINICAL RELEVANCE: The pathological remodeling of the venous wall, which leads to stenosis and ultimately graft failure, is the main limiting factor of human saphenous vein graft bypass. This remodeling is due to the hemodynamic adaptation of the vein to the arterial environment and cannot be prevented by conventional therapy. To develop a more targeted therapy, a better understanding of the molecular mechanisms involved in intimal hyperplasia is essential, which requires the development of ex vivo models of chronic perfusion of human veins.
Assuntos
Hemodinâmica , Veia Safena/patologia , Veia Safena/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Pressão Arterial , Fenômenos Biomecânicos , Proliferação de Células , Efrina-B2/genética , Efrina-B2/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Hiperplasia , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Neointima , Perfusão , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Fluxo Pulsátil , RNA Mensageiro/metabolismo , Receptor EphB4/genética , Receptor EphB4/metabolismo , Veia Safena/metabolismo , Estresse Mecânico , Fatores de Tempo , Técnicas de Cultura de Tecidos , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Grau de Desobstrução VascularRESUMO
Although rare, popliteal artery aneurysms are the most common peripheral aneurysms and are frequently associated with abdominal aorta aneurysms. They are often bilateral. One third of patients are asymptomatic at diagnosis, with an insidious evolution. Symptomatic patients may present with symptoms of either acute ischemia or chronic ischemia, or rarely compression or rupture. Surgical exclusion of aneurysm followed by venous bypass remains the treatment of choice. Endovascular treatment is an attractive alternative currently reserved for patients at high risk, with good anatomical criteria. Elective treatment before symptoms onset is preferable given the best results in terms of patency and complications. A conservative approach is allowed for small aneurysms without major embolic risk provided careful monitoring by ultrasound.
Assuntos
Aneurisma/diagnóstico , Aneurisma/terapia , Algoritmos , Procedimentos Endovasculares , Humanos , Artéria Poplítea/cirurgiaRESUMO
In the western world, the carotid-artery stenosis is one of the major causes of ischemic stroke in elderly people. The principal therapeutic indication is a symptomatic stenosis > 50% in the first two weeks and the surgical approach has shown the best results. Despite inferior results to carotid endarterectomy in terms of post-operative rate of stroke and/or death, except for young patients, carotid stenting remains the best choice in patients at high surgical risk. The best medical treatment, consisting in correction of cardiovascular risk factors, statin therapy and anti-aggregation led to a drastic reduction in the annual rate of stroke associated to carotid stenosis and thus limited the surgical intervention in asymptomatic patient to men with a life expectancy of at least 5 years and a stenosis > 70%.
Assuntos
Estenose das Carótidas/terapia , Estenose das Carótidas/diagnóstico , Tomada de Decisões , Endarterectomia das Carótidas , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Acidente Vascular Cerebral/prevenção & controleRESUMO
Management of musculoskeletal tumours usually begins with the appearance of a lump or bump, or the onset of unspecific symptoms. A poor initial work-up, a faulty biopsy or an inadequate resection may have a severe impact on the prognosis, including re-interventions, amputation, local recurrence or systemic spread of the disease. The patient with a suspicious lesion should be referred to a "sarcoma centers" where a planned and well-performed diagnostic work-up will allow a precise diagnosis in terms of histology and staging. After a multidisciplinary discussion of the case, an accurate treatment plan is established. Such an approach allows an adequate patient management, often with a positive impact on the survival and functional outcome.
Assuntos
Neoplasias Ósseas/diagnóstico , Neoplasias Musculares/diagnóstico , Equipe de Assistência ao Paciente , Biópsia , Neoplasias Ósseas/terapia , Diagnóstico por Imagem , Humanos , Neoplasias Musculares/terapia , Gradação de Tumores , Estadiamento de NeoplasiasRESUMO
Intimal hyperplasia (IH) is an undesirable pathology occurring after peripheral or coronary bypass surgery. It involves the proliferation and migration of vascular smooth muscle cells, leading to a reduction in the diameter of the vascular lumen, which can lead to stenosis and graft failure. Topically applied atorvastatin (ATV) has been shown to slow down this process. To be effective, the drug delivery system should remain at the perivascular site for 5-8 weeks, corresponding to the progression of IH, and be capable of releasing an initial dose of the drug followed by a sustained release. Ideally, bioadhesion would anchor the gel to the application site. To meet these needs, we encapsulated ATV in a 2-component system: a hyaluronic acid-dopamine bioadhesive gel for rapid release and biodegradable microparticles for sustained release. The system was characterized by scanning electron microscopy, rheology, bioadhesion on porcine arteries, and a release profile. The rheological properties were adequate for perivascular application, and we demonstrated superior bioadhesion and cohesion compared to the control HA formulations. The release profile showed a burst, generated by free ATV, followed by sustained release over 8 weeks. A preliminary evaluation of subcutaneous biocompatibility in rats showed good tolerance of the gel. These results offer new perspectives on the perivascular application towards an effective solution for the prevention of IH.
RESUMO
Intimal hyperplasia (IH) occurs in a considerable number of cases of blood vessel reconstruction by stenting or balloon angioplasty, venous bypass grafting, and arteriovenous dialysis accesses. It is triggered by endothelial injury during the vascular intervention and leads to vessel restenosis with life-threatening consequences for patients. To date, the drugs used for IH prevention in clinics-paclitaxel and rapalog drugs-have been focusing primarily on the vascular smooth muscle cell (VSMC) proliferation pathway of IH development. Limitations, such as endothelial toxicity and inappropriate drug administration timing, have spurred the search for new and efficient pharmacological approaches to control IH. In this state-of-the-art review, we present the pathways of IH development, focusing on the key events and actors involved in IH. Subsequently, we discuss different drugs and drug combinations interfering with these pathways based on their effect on peripheral circulation IH models in animal studies, or on clinical reports. The reports were obtained through an extensive search of peer-reviewed publications in Pubmed, Embase, and Google Scholar, with search equations composed based on five concepts around IH and their various combinations. To improve vascular intervention outcomes, rethinking of conventional therapeutic approaches to IH prevention is needed. Exploring local application of drugs and drug combinations acting on different pathophysiological pathways of IH development has the potential to provide effective and safe restenosis prevention.
Assuntos
Túnica Íntima , Animais , Humanos , Hiperplasia/metabolismo , Hiperplasia/patologia , Hiperplasia/prevenção & controle , Túnica Íntima/metabolismo , Túnica Íntima/patologiaRESUMO
Background: Aneurysm shrinkage has been proposed as a marker of successful endovascular aneurysm repair (EVAR). We evaluated the impact of sac shrinkage on secondary interventions, on survival and its association with endoleaks, and on compliance with instructions for use (IFU). Methods: This observational retrospective study was conducted on all consecutive patients receiving EVAR for an infrarenal abdominal aortic aneurysm (AAA) using exclusively Endurant II/IIs endograft from 2014 to 2018. Sixty patients were entered in the study. Aneurysm sac shrinkage was defined as decrease ≥5 mm of the maximum aortic diameter. Univariate methods and Kaplan-Meier plots assessed the potential impact of shrinkage. Results: Twenty-six patients (43.3%) experienced shrinkage at one year, and thirty-four (56.7%) had no shrinkage. Shrinkage was not significantly associated with any demographics or morbidity, except hypertension (p = 0.01). No aneurysm characteristics were associated with shrinkage. Non-compliance with instructions for use (IFU) in 13 patients (21.6%) was not associated with shrinkage. Three years after EVAR, freedom from secondary intervention was 85 ± 2% for the entire series, 92.3 ± 5.0% for the shrinkage group and 83.3 ± 9% for the no-shrinkage group (Logrank: p = 0.49). Survival at 3 years was not significantly different between the two groups (85.9 ± 7.0% vs. 79.0 ± 9.0%, Logrank; p = 0.59). Strict compliance with IFU was associated with less reinterventions at 3 years (92.1 ± 5.9% vs. 73.8 ± 15%, Logrank: p = 0.03). Similarly, survival at 3 years did not significantly differ between strict compliance with IFU and non-compliance (81.8 ± 7.0% vs. 78.6 ± 13.0%, Logrank; p = 0.32). Conclusion: This study suggests that shrinkage ≥5 mm at 1-year is not significantly associated with a better survival rate or a lower risk of secondary intervention than no-shrinkage. In this series, the risk of secondary intervention regardless of shrinkage seems to be linked more to non-compliance with IFU. Considering the small number of patients, these results must be confirmed by extensive prospective studies.