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Importance: The increase in minimally invasive surgical procedures has eroded exposure of general surgery residents to open operations. High-fidelity simulation, together with deliberate instruction, is needed for advanced open surgical skill (AOSS) development. Objective: To collect validity evidence for AOSS tools to support a shared model for instruction. Design, Setting, and Participants: This prospective cohort study included postresidency surgeons (PRSs) and second-year general surgery residents (R2s) at a single academic medical center who completed simulated tasks taught within the AOSS curriculum between June 1 and October 31, 2021. Exposures: The AOSS curriculum includes 6 fine-suture and needle handling tasks, including deep suture tying (with and without needles) and continuous suturing using the pitch-and-catch and push-push-pull techniques (both superficial and deep). Teaching and assessment are based on specific microskills using a 3-dimensional printed iliac fossa model. Main Outcomes and Measures: The PRS group was timed and scored (5-point Likert scale) on 10 repetitions of each task. Six months after receiving instruction on the AOSS tasks, the R2 group was similarly timed and scored. Results: The PRS group included 14 surgeons (11 male [79%]; 8 [57%] attending surgeons) who completed the simulation; the R2 group, 9 surgeons (5 female [55%]) who completed the simulation. Score and time variability were greater for the R2s compared with the PRSs for all tasks. The R2s scored lower and took longer on (1) deep pitch-and-catch suturing (69% of maximum points for a mean [SD] of 142.0 [31.7] seconds vs 77% for a mean [SD] of 95.9 [29.4] seconds) and deep push-push-pull suturing (63% of maximum points for a mean [SD] of 284.0 [72.9] seconds vs 85% for a mean [SD] of 141.4 [29.1] seconds) relative to the corresponding superficial tasks; (2) suture tying with a needle vs suture tying without a needle (74% of maximum points for a mean [SD] of 64.6 [19.8] seconds vs 90% for a mean [SD] of 54.4 [15.6] seconds); and (3) the deep push-push-pull vs pitch-and-catch techniques (63% of maximum points for a mean [SD] of 284.0 [72.9] seconds vs 69% of maximum points for a mean [SD] of 142.0 [31.7] seconds). For the PRS group, time was negatively associated with score for the 3 hardest tasks: superficial push-push-pull (ρ = 0.60; P = .02), deep pitch-and-catch (ρ = 0.73; P = .003), and deep push-push-pull (ρ = 0.81; P < .001). For the R2 group, time was negatively associated with score for the 2 easiest tasks: suture tying without a needle (ρ = 0.78; P = .01) and superficial pitch-and-catch (ρ = 0.79; P = .01). Conclusions and Relevance: The findings of this cohort study offer validity evidence for a novel AOSS curriculum; reveal differential difficulty of tasks that can be attributed to specific microskills; and suggest that position on the surgical learning curve may dictate the association between competency and speed. Together these findings suggest specific, actionable opportunities to guide instruction of AOSS, including which microskills to focus on, when individual rehearsal vs guided instruction is more appropriate, and when to focus on speed.
Assuntos
Internato e Residência , Cirurgiões , Competência Clínica , Estudos de Coortes , Currículo , Feminino , Humanos , Masculino , Estudos Prospectivos , Técnicas de Sutura/educaçãoRESUMO
BACKGROUND: Prophylactic carotid artery stenting (CAS) is an effective strategy to reduce perioperative stroke in patients with severe carotid stenosis who require cardiothoracic surgery (CTS). Staging both procedures (CAS-CTS) during a single hospitalization presents conflicting demands for antiplatelet therapy and the optimal pharmacologic strategy between procedures is not established. The purpose of this study is to present our initial experience with a "bridging" protocol for staged CAS-CTS. METHODS: A retrospective review of staged CAS-CTS procedures at a single referral center was performed. All patients had multivessel coronary and/or valvular disease and severe carotid stenosis (>70%). Patients not previously on aspirin were also started on aspirin prior to surgery, followed by eptifibatide during CAS (intraprocedural bolus followed by post-procedural infusion which was continued until the morning of surgery). Pre- and perioperative (30 days) neurologic morbidity and mortality was the primary endpoint. RESULTS: 11 CAS procedures were performed in 10 patients using the protocol. The median duration of eptifibatide bridge therapy was 36 h (range 24-288 h). There was one minor bleeding complication (1/11, 9.1%) and no major bleeding complications during the bridging and post-operative period. There was one post-operative, non-neurologic death and zero perioperative ischemic strokes. CONCLUSIONS: For patients undergoing staged CAS-CTS, Eptifibatide bridging therapy is a viable temporary antiplatelet strategy with a favorable safety profile. This strategy enables a flexible range of time-intervals between procedures.
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BACKGROUND: Plasma 25 hydroxycholecalciferol (vitamin D) deficiency has been associated with adverse cardiovascular outcomes in epidemiologic studies. Chronic kidney disease is associated with loss of 1α-hydroxylase and consequently vitamin D deficiency. We hypothesized that vitamin D deficiency was associated with increased mortality and increased vascular access failure in patients undergoing permanent vascular access for end-stage renal disease. METHODS: This retrospective cohort study analyzed 128 patients undergoing permanent vascular access surgery between 2003 and 2012 for whom concurrent plasma vitamin D levels were also available. Levels were considered deficient at <20 ng/mL. Multivariable analysis was used to determine the association between vitamin D and mortality and vascular access outcomes. RESULTS: The mean age was 66.7 years, 96.8% were male, 32.0% were African American, and 60.9% had diabetes mellitus. In the entire cohort, 55.5% were vitamin D-deficient, despite similar rates of repletion among the vitamin D-deficient and nondeficient groups. During a median follow-up of 2.73 years, there were 40 deaths (31%). Vitamin D-deficient patients tended to be younger (P = .01) and to have higher total cholesterol (P = .001) and lower albumin (P = .017) and calcium (P = .007) levels. Despite their younger age, mortality was significantly higher (P = .026) and vascular access failure was increased (P = .008) in the vitamin D-deficient group. Multivariate logistic regression analysis found vitamin D deficiency (odds ratio [OR], 3.64; 95% confidence interval [CI], 1.12-11.79; P = .031), hemodialysis through a central catheter (OR, 3.08; 95% CI, 1.04-9.12; P = .042), coronary artery disease (OR, 3.08; 95% CI, 1.06-8.94; P = .039), increased age (OR, 1.09; 95% CI, 1.03-1.15; P = .001), and albumin (OR, 0.27; 95% CI, 0.09-0.83; P = .023) remained independent predictors of mortality. Vitamin D deficiency (hazard ratio [HR], 2.34; 95% CI, 1.17-4.71; P = .02), a synthetic graft (HR, 3.50; 95% CI, 1.38-8.89; P = .009), and hyperlipidemia (HR, 0.42; 95% CI, 0.22-0.81; P = .01) were independent predictors of vascular access failure in a Cox proportional hazard model. CONCLUSIONS: Vitamin D deficiency is highly prevalent in patients undergoing vascular access procedures. Patients who are deficient in vitamin D have worse survival and worse vascular access outcomes. Further study is warranted to assess whether aggressive vitamin D repletion will improve outcomes in this population.
Assuntos
Derivação Arteriovenosa Cirúrgica/efeitos adversos , Calcifediol/deficiência , Falência Renal Crônica/mortalidade , Deficiência de Vitamina D/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Prótese Vascular/efeitos adversos , Calcifediol/sangue , Cálcio/sangue , Cateterismo Venoso Central , Colesterol/sangue , Doença das Coronárias/epidemiologia , Seguimentos , Humanos , Hiperlipidemias/epidemiologia , Estimativa de Kaplan-Meier , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/metabolismo , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicaçõesRESUMO
OBJECTIVE: To study atherosclerosis regression in mice after plasma lipid reduction to moderately elevated apolipoprotein B (apoB)-lipoprotein levels. APPROACH AND RESULTS: Chow-fed hypomorphic Apoe mice deficient in low-density lipoprotein receptor expression (Apoe(h/h)Ldlr(-/-)Mx1-cre mice) develop hyperlipidemia and atherosclerosis. These mice were studied before and after inducible cre-mediated Apoe gene repair. By 1 week, induced mice displayed a 2-fold reduction in plasma cholesterol and triglyceride levels and a decrease in the non-high-density lipoprotein:high-density lipoprotein-cholesterol ratio from 87%:13% to 60%:40%. This halted atherosclerotic lesion growth and promoted macrophage loss and accumulation of thick collagen fibers for up to 8 weeks. Concomitantly, blood Ly-6C(high) monocytes were decreased by 2-fold but lesional macrophage apoptosis was unchanged. The expression of several genes involved in extracellular matrix remodeling and cell migration was changed in lesional macrophages 1 week after Apoe gene repair. However, mRNA levels of numerous genes involved in cholesterol efflux and inflammation were not significantly changed at this time point. CONCLUSIONS: Restoring apoE expression in Apoe(h/h)Ldlr(-/-)Mx1-cre mice resulted in lesion stabilization in the context of a human-like ratio of non-high-density lipoprotein:high-density lipoprotein-cholesterol. Our data suggest that macrophage loss derived in part from reduced blood Ly-6C(high) monocytes levels and genetic reprogramming of lesional macrophages.
Assuntos
Apolipoproteínas E/genética , Terapia Genética/métodos , Placa Aterosclerótica/genética , Placa Aterosclerótica/terapia , Receptores de LDL/genética , Animais , Apolipoproteína B-100 , Apolipoproteínas B/sangue , Apolipoproteínas B/genética , Apolipoproteínas E/sangue , Apolipoproteínas E/deficiência , Apoptose/fisiologia , Colesterol/sangue , HDL-Colesterol/sangue , Modelos Animais de Doenças , Progressão da Doença , Regulação da Expressão Gênica/fisiologia , Humanos , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Hiperlipidemias/terapia , Macrófagos/citologia , Camundongos , Camundongos Knockout , Monócitos/citologia , Placa Aterosclerótica/metabolismo , Receptores de LDL/deficiência , Triglicerídeos/sangueRESUMO
BACKGROUND: Multibranched endovascular aneurysm repair (MBEVAR) has the potential to lower the morbidity and mortality rates of thoracoabdominal aneurysm repair, but the applicability of the technique is unknown. Our aim was to estimate the prevalence of anatomic suitability for MBEVAR. METHODS: Retrospective review of patients referred for a prospective trial of MBEVAR between November 2005 and July 2012. Anatomic suitability was assessed on three-dimensional computed tomography scan reconstructions according to the current criteria for a custom-made stent graft or a fixed, off-the-shelf stent graft in both standard (22F) and low-profile (18F) delivery systems. RESULTS: A total of 250 contrast-enhanced computed tomography scans were reviewed, 49 of which were excluded due to inadequate aneurysm size. Of 201 candidates for repair, 149 (74%) were men and 86 (43%) had Crawford classification type IV/paravisceral aneurysms; 109 (58%) were anatomically suitable for a single-stage repair with a custom-made, low-profile stent graft. Another 58 (29%) could have been made suitable for MBEVAR with an adjunct procedure, including angiogram with visceral or renal artery stenting (n = 23), carotid-subclavian bypass (n = 5), or iliac bypass for device insertion (n = 17), or to preserve internal iliac artery flow because of an iliac aneurysm (n = 9), or dissection (n = 8). There was no association between suitability and gender, aneurysm diameter, or type. However, women were significantly more likely to need a conduit or low-profile device (P = .003). Patients with type B aortic dissections were significantly less likely to have anatomy suitable for repair (P = .035) and more likely to require a multistage repair. Thirty-four patients would have been unsuitable for repair because of renal artery anatomy (n = 14), visceral artery anatomy (n = 4), lack of a proximal landing zone due to an arch aneurysm (n = 7), or inadequate access arteries (n = 9). The low-profile device increased the number of patients who would have been suitable for a single-stage repair by 16. The off-the-shelf graft has the advantage of a faster assessment-to-treatment time, but only 64 patients would have been suitable for a single-stage repair and another 30 could have been made suitable with an adjunct procedure. CONCLUSIONS: Most patients would have been suitable or could have been made suitable for a thoracoabdominal stent graft using current anatomic criteria. The applicability of MBEVAR will continue to change as the experience with the technique grows and devices evolve, as evidenced by the potential reduction in iliac bypasses after the introduction of a low-profile device and the ability to treat symptomatic or urgent patients with the off-the-shelf device.
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Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Procedimentos Endovasculares/métodos , Stents , Feminino , Humanos , Imageamento Tridimensional , Masculino , Desenho de Prótese , Ajuste de Prótese , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: This study determined early and intermediate results of multibranched endovascular thoracoabdominal (TAAA) and pararenal aortic aneurysm (PRAA) repair using a uniform operative technique. METHODS: Eighty-one patients (mean age, 73 ± 8 years, 19 [23.5%] women) underwent endovascular TAAA repair in a prospective trial using self-expanding covered stents connecting axially oriented, caudally directed cuffs to target aortic branches. Mean aneurysm diameter was 67 ± 10 mm. Thirty-nine TAAA (48.1%) were Crawford type II, III, or V; 42 (51.9%) were type IV or pararenal. Thirty-three procedures (40.7%) were staged. The insertion approach was femoral for aortic components and brachial for branch components. Follow-up assessments were performed at 1, 6, and 12 months, and yearly thereafter. RESULTS: All devices (n = 81) and branches (n = 306) were successfully inserted and deployed, with no conversions to open repair. Overall mortality was 6.2% (n = 5), including three perioperative (3.7%) and two late treatment-related deaths (2.5%). Permanent paraplegia occurred in three patients (3.7%), and transient paraplegia/paraparesis occurred in 16 (19.8%). Four patients (4.9%) required dialysis postoperatively, three permanently and one transiently. Women accounted for 67% of the paraplegia, 75% of the perioperative dialysis, and 60% of the perioperative or treatment-related deaths. During a mean follow-up of 21.2 months, no aneurysms ruptured, but four (4.9%) enlarged: two were successfully treated, one was unsuccessfully treated, and one was not treated. No late onset spinal cord ischemia symptoms developed. Of the five patients starting dialysis during follow-up, two resulted from renal branch occlusion. Sixteen branches occluded (nine renal, two celiac) or developed stenoses (four renal, one superior mesenteric artery), requiring stenting. Primary patency was 94.8%, and primary-assisted patency was 95.1%. Thirty-two patients (39.5%) underwent 42 reinterventions. Of 25 early reinterventions (≤ 45 days), 10 were to treat access or insertion complications, and 5 were for endoleak. Of 17 late reinterventions, eight were for endoleak and five were for branch stenosis/occlusion. New endoleaks developed in two patients during follow-up. Overall, 73 of 81 patients (90.1%) were treated without procedure-related death, dialysis, paralysis, aneurysm rupture, or conversion to open repair. CONCLUSIONS: Total endovascular TAAA/PRAA repair using caudally directed cuffs is safe, effective, and durable in the intermediate term. The most common form of late failure, renal artery occlusion, rarely had a clinically significant consequence (dialysis). The trend toward worse outcome in women needs further study.
Assuntos
Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/métodos , Prótese Vascular , Stents , Idoso , Análise de Variância , Aneurisma da Aorta Torácica/mortalidade , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/terapia , Estudos Prospectivos , Desenho de Prótese , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Apolipoprotein (apo) E is best known for its ability to lower plasma cholesterol and protect against atherosclerosis. Although the liver is the major source of plasma apoE, extra-hepatic sources of apoE, including from macrophages, account for up to 10% of plasma apoE levels. This study examined the contribution of macrophage-derived apoE expression levels in diet-induced hyperlipidemia and atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: Hypomorphic apoE (Apoe(h/h)) mice expressing wildtype mouse apoE at â¼2-5% of physiological levels in all tissues were derived by gene targeting in embryonic stem cells. Cre-mediated gene repair of the Apoe(h/h) allele in Apoe(h/h)LysM-Cre mice raised apoE expression levels by 26 fold in freshly isolated peritoneal macrophages, restoring it to 37% of levels seen in wildtype mice. Chow-fed Apoe(h/h)LysM-Cre and Apoe(h/h) mice displayed similar plasma apoE and cholesterol levels (55.53±2.90 mg/dl versus 62.70±2.77 mg/dl, nâ=â12). When fed a high-cholesterol diet (HCD) for 16 weeks, Apoe(h/h)LysM-Cre mice displayed a 3-fold increase in plasma apoE and a concomitant 32% decrease in plasma cholesterol when compared to Apoe(h/h) mice (602.20±22.30 mg/dl versus 888.80±24.99 mg/dl, nâ=â7). On HCD, Apoe(h/h)LysM-Cre mice showed increased apoE immunoreactivity in lesional macrophages and liver-associated Kupffer cells but not hepatocytes. In addition, Apoe(h/h)LysM-Cre mice developed 35% less atherosclerotic lesions in the aortic root than Apoe(h/h) mice (167×10(3)±16×10(3) µm(2) versus 259×10(3)±56×10(3) µm(2), nâ=â7). This difference in atherosclerosis lesions size was proportional to the observed reduction in plasma cholesterol. CONCLUSIONS/SIGNIFICANCE: Macrophage-derived apoE raises plasma apoE levels in response to diet-induced hyperlipidemia and by such reduces atherosclerosis proportionally to the extent to which it lowers plasma cholesterol levels.
Assuntos
Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Aterosclerose/prevenção & controle , Hiperlipidemias/prevenção & controle , Macrófagos/metabolismo , Animais , Apolipoproteínas E/sangue , Aterosclerose/sangue , Aterosclerose/etiologia , Aterosclerose/terapia , Colesterol/sangue , Dieta Aterogênica , Expressão Gênica , Terapia Genética , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Hiperlipidemias/terapia , Células de Kupffer/metabolismo , Camundongos , Camundongos Knockout , Camundongos Transgênicos , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
OBJECTIVE: Apolipoprotein (apo) E4 is an established risk factor for atherosclerosis, but the structural components underlying this association remain unclear. ApoE4 is characterized by 2 biophysical properties: domain interaction and molten globule state. Substituting Arg-61 for Thr-61 in mouse apoE introduces domain interaction without molten globule state, allowing us to delineate potential proatherogenic effects of domain interaction in vivo. METHODS AND RESULTS: We studied atherosclerosis susceptibility of hypomorphic Apoe mice expressing either Thr-61 or Arg-61 apoE (ApoeT(h/h) or ApoeR(h/h)mice). On a chow diet, both mouse models were normolipidemic with similar levels of plasma apoE and lipoproteins. However, on a high-cholesterol diet, ApoeR(h/h) mice displayed increased levels of total plasma cholesterol and very-low-density lipoprotein as well as larger atherosclerotic plaques in the aortic root, arch, and descending aorta compared with ApoeT(h/h) mice. In addition, evidence of cellular dysfunction was identified in peritoneal ApoeR(h/h) macrophages which released lower amounts of apoE in culture medium and displayed increased expression of major histocompatibility complex class II molecules. CONCLUSIONS: These data indicate that domain interaction mediates proatherogenic effects of apoE4 in part by modulating lipoprotein metabolism and macrophage biology. Pharmaceutical targeting of domain interaction could lead to new treatments for atherosclerosis in apoE4 individuals.
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Apolipoproteína E4/genética , Aterosclerose/genética , DNA/genética , Regulação da Expressão Gênica , Predisposição Genética para Doença , Animais , Apolipoproteína E4/biossíntese , Aterosclerose/etiologia , Aterosclerose/metabolismo , Dieta Aterogênica/efeitos adversos , Modelos Animais de Doenças , Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
BACKGROUND: As they are "end arteries," microembolic obstruction of brain penetrating arteries would be expected to create ischemia. Yet the mammalian brain appears to have an impressive tolerance to experimental microembolization with ischemia occurring only after the injection of large numbers of particulates. Potential explanations could be that the majority of these particulates marginate along the pial vasculature or escape the cerebral circulation via arteriovenous (AV) fistulae. METHODS: To test these theories, we first established the level of injury created by the injection of 20, 45, and 90 µm fluorescent microspheres in Sprague-Dawley rats. Brains were examined by immunohistochemistry for injury and for infarction. We then injected 1000 size 20 µm, 500 size 45 µm, and 150 size 90 µm and harvested the brains and lungs for assays of fluorescence. The location of microemboli within the brain was established by determining the percent of 20 and 45 µm fluorescent microspheres entering the superficial versus deeper layers of the brain. The location of larger microemboli was established by 2T-MRI after injection of 60-100 µm microthrombi labeled with supraparamagnetic iron oxide (SPIO) particles. RESULTS: With 20 µm microspheres there were no areas of injury or infarction after injection of 500 and rare areas of injury and no infarctions after injection of 1000 microspheres. With either 250 or 500 size 45 µm microspheres there were a few (≤ 6) small areas of injury per animal with ≤ 2 areas of infarction. After injection, 93%-96% of injected microspheres remained in the brain. Approximately 40% of either fluorescent or SPIO labeled microthrombi were found on the brain surface. CONCLUSIONS: As in humans, the rat brain has an impressive tolerance to microemboli, although this clearly varies with emboli size and number. Wash out of particulates through AV connections is not a major factor in brain tolerance in this model. Approximately 40% of microemboli remain in the larger pial vasculature where the more extensive collateralization may limit their effects on distal perfusion. However, the remaining 60% enter penetrating arteries but few create ischemia.
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Infarto Encefálico/fisiopatologia , Isquemia Encefálica/fisiopatologia , Artérias Cerebrais/fisiologia , Embolia Intracraniana/fisiopatologia , Microesferas , Animais , Infarto Encefálico/patologia , Isquemia Encefálica/patologia , Modelos Animais de Doenças , Fluorescência , Embolia Intracraniana/patologia , Imageamento por Ressonância Magnética , Embolia Pulmonar/patologia , Embolia Pulmonar/fisiopatologia , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: We investigated atheroprotective properties of apolipoprotein (apo) E beyond its ability to lower plasma cholesterol. We hypothesized that apoE reduces atherosclerosis by decreasing lipid accumulation in circulating monocytes and the inflammatory state of monocytes and the vascular endothelium. METHODS AND RESULTS: We developed mice with spontaneous hyperlipidemia with and without plasma apoE. Hypomorphic apoE mice deficient in low-density lipoprotein receptor (Apoe(h/h)Ldlr(-/-)) were compared to Apoe(-/-)Ldlr(-/-) mice. Despite 4-fold more plasma apoE than WT mice, Apoe(h/h)Ldlr(-/-) mice displayed similar plasma cholesterol as Apoe(-/-) Ldlr(-/-) mice but developed 4-fold less atherosclerotic lesions by 5 months of age. The aortic arch of Apoe(h/h)Ldlr(-/-) mice showed decreased endothelial expression of ICAM-1, PECAM-1, and JAM-A. In addition, Apoe(h/h)Ldlr(-/-) mice had less circulating leukocytes and proinflammatory Ly6C(high) monocytes. These monocytes had decreased neutral lipid content and reduced surface expression of ICAM-1, VLA-4, and L-Selectin. Apoe(h/h)Ldlr(-/-) mice displayed increased levels of apoA1-rich HDL that were potent in promoting cellular cholesterol efflux. CONCLUSIONS: Our findings suggest that apoE reduces atherosclerosis in the setting of hyperlipidemia by increasing plasma apoA1-HDL that likely contribute to reduce intracellular lipid accumulation and thereby the activation of circulating leukocytes and the vascular endothelium.
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Apolipoproteínas E/metabolismo , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Endotélio Vascular/metabolismo , Mediadores da Inflamação/metabolismo , Metabolismo dos Lipídeos , Monócitos/metabolismo , Animais , Apolipoproteínas E/deficiência , Moléculas de Adesão Celular/metabolismo , Colesterol/metabolismo , Modelos Animais de Doenças , Integrina alfa4beta1/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Selectina L/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores de LDL/deficiência , Receptores de LDL/metabolismoRESUMO
BACKGROUND: Much of the brain is perfused by penetrating arteries that are the "single source" of blood to their surrounding tissues. These tissues should be equally vulnerable to ischemia from embolic occlusion, but there are questions about whether emboli have access to the penetrating arteries serving the deep brain tissues. To examine this issue in humans we recorded the number and distribution of new ischemic lesions on diffusion-weighted magnetic resonance imaging (DWMRI) after carotid artery stenting (CAS), a procedure producing showers of numerous small atheroemboli. METHODS: Twenty-nine men (aged 62-81) underwent 30 CAS procedures with distal protection in place, and DWMRI 48 hours after the procedure documented new lesions had developed. Thirteen patients were asymptomatic, and 16 had experienced recent symptoms ipsilateral to the treated carotid stenosis. A DWMRI study was done in each patient ≤72 hours before the procedure. All MRI studies were read by the same neuroradiologist. RESULTS: One patient sustained a minor stroke, which resolved. DWNRI found 131 new lesions (median, 3; range, 1-17; interquartile range, 2-4). Lesion size was <5 mm in 96.6% and 5 to 10 mm in 3.1%. Lesions were ipsilateral in 83.1% and contralateral in 16.9%. Lesions were in the distribution of the middle cerebral artery (91.6%), posterior cerebral artery (6.1%), and superior cerebellar artery subclavian artery (2.0%). Most lesions were in the cortex but at a depth where they were best described as cortical/subcortical (90.8%). The rest were in the periventricular white matter (6.1%) and deep gray matter (3.0%). CONCLUSIONS: The ischemic areas developing after CAS were predominately in the deeper layers of the cortex in the distribution of the middle cerebral artery, but lesions were seen throughout the brain. The distribution of lesions caused by CAS-induced embolization coincided with estimates of blood flow to the respective areas of the brain. These data add to the evidence implicating microemboli in ischemic pathologies throughout the brain.
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Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/instrumentação , Isquemia Encefálica/etiologia , Estenose das Carótidas/terapia , Embolia Intracraniana/etiologia , Stents , Acidente Vascular Cerebral/etiologia , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Estenose das Carótidas/complicações , Estenose das Carótidas/patologia , Circulação Cerebrovascular , Imagem de Difusão por Ressonância Magnética , Humanos , Embolia Intracraniana/patologia , Embolia Intracraniana/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , São Francisco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: This study determined the rate, extent, and clinical significance of neck dilatation after endovascular aneurysm repair (EVAR). METHODS: The study included 46 patients who underwent elective EVAR using bifurcated Zenith stent grafts (Cook, Bloomington, Ind) and had at least 48 months of clinical and radiographic follow-up. Computed tomography images were analyzed on a 3-dimensional workstation (TeraRecon, San Mateo, Calif). Neck diameter was measured 10 mm below the most inferior renal artery in planes orthogonal to the aorta. Nominal stent graft diameter was obtained from implantation records. RESULTS: Median follow-up was 59 months (range, 48-120 months). Neck dilation occurred in all 46 patients. The rate of neck dilation was greatest at early follow-up intervals. At 48 months, median neck dilation was 5.3 mm (range, 2.3-9.8 mm). The extent of neck dilation at 48 months correlated with percentage of stent graft oversizing (Spearman rho = 0.61, P < .001). No type I endoleak or migration >5 mm occurred. CONCLUSIONS: After EVAR with the Zenith stent graft, the neck dilates until its diameter approximates the diameter of the stent graft. Neck dilation was not associated with type I endoleak or migration of the stent graft.
Assuntos
Aneurisma Aórtico/cirurgia , Implante de Prótese Vascular , Idoso , Idoso de 80 Anos ou mais , Aneurisma Aórtico/diagnóstico por imagem , Aortografia/métodos , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Dilatação Patológica , Feminino , Humanos , Masculino , Desenho de Prótese , São Francisco , Stents , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
None of the commercially available stent grafts are supplied in a tapered configuration suitable for the endovascular repair of common iliac artery aneurysms. We describe a simple technique for reversing the proximal and distal orientation of a standard flared bell-bottom stent graft limb from the Zenith system of abdominal aortic aneurym repair. When reloaded in this fashion, the stent graft is deployed just like any other Zenith (Cook, Inc., Bloomington, IN) stent graft limb. However, we caution that this departure from standard use introduces new sources of potential device failure, requires several additional precautions, and should not be attempted by those unfamiliar with the routine use of the unmodified device.
Assuntos
Aneurisma/cirurgia , Artéria Ilíaca/cirurgia , Stents , Implante de Prótese Vascular/instrumentação , Implante de Prótese Vascular/métodos , Desenho de Equipamento , HumanosRESUMO
OBJECTIVES: Choices for embolic protection during carotid stent procedures include distal filtration (DF) and proximal occlusion with flow reversal (POFR). DF devices are widely used but have produced only modest improvements in clinical outcomes. There is less experience with POFR devices but single center reports suggest reduced emboli detected by transcranial Doppler (TCD). To determine if POFR offers a significant improvement in embolic protection, we tested five DF devices and two POFR devices with 8F and 10F sheath design in an ex vivo angioplasty system using human carotid plaques excised en bloc. Physiologic pressures and flows were used and the efficiency of plaque fragment removal by these devices compared. METHODS: Thirty-three human carotid plaques removed en bloc were secured in tailored polytetrafluoroethylene (PTFE) grafts. The distal PTFE was either 6 mm or 5 mm inner diameter (ID). Saline was delivered through the excised carotid plaque as follows: a cleaning 50 mL flush was done prior to the angioplasty procedure and discarded; further flushes of forward flow were done with five pressurized "pulsations" of 10 mL each (50 mL), peak pressure 140 mm Hg. Balloon angioplasty was done with a 4 mm and then a 6 mm balloon. DF flushes were applied after each angioplasty and "postprocedure" after the device was removed. With POFR, 50 mL were collected through the sheath after balloon angioplasty by either back-pressure of 20 mm Hg, 40 mm Hg or 60 mm Hg, or by aspiration. Postangioplasty pressurized forward flush of 50 or 100 mL was done as described. Each flush was collected, centrifuged, and examined for plaque fragments. Fragments greater than 60 microns were sized and counted on a 100 micron grid. RESULTS: When DF devices were used in 6 mm lumen PTFE, the percent of fragments trapped was poor (13.7% to 27.8%). There were no statistically significant differences between the devices. The capture of fragments improved (22% vs 51.4%, P < .001) when devices appropriate for a 6 mm lumen were used in a 5 mm PTFE "ICA", functionally over-sizing the devices. POFR efficiency improved with increasing back-pressures and with repeated aspirations. Postprocedure, successive flushes of pressurized forward flow yielded additional plaque fragments and when the efficiency of POFR was assessed with forward flushing volumes similar to those used for DF, the efficiencies were similar, although larger fragments were more efficiently removed with POFR. CONCLUSION: In our model, both protection strategies were less than ideal. For POFR, high back pressures or multiple aspirations improve the efficiency of cerebral protection but additional fragments were released by pressurized flow even after aspiration of 150 mL of saline. DF devices create a pressure gradient and fragments apparently went around the device with pressurized flow in our PTFE lumen. Over-sizing of DF devices partially corrected this problem and increased over all DF efficiency to be comparable to POFR for smaller fragments but not for larger fragments.
Assuntos
Angioplastia com Balão/efeitos adversos , Oclusão com Balão/instrumentação , Estenose das Carótidas/terapia , Embolia/prevenção & controle , Filtração/instrumentação , Hemodinâmica , Stents , Angioplastia com Balão/instrumentação , Pressão Sanguínea , Prótese Vascular , Estenose das Carótidas/fisiopatologia , Endarterectomia das Carótidas , Desenho de Equipamento , Humanos , Teste de Materiais , Politetrafluoretileno , Desenho de Prótese , Fluxo Pulsátil , Fluxo Sanguíneo Regional , SucçãoRESUMO
OBJECTIVE: This study was conducted to determine the outcome of adjunctive renal artery stenting for renal artery coverage at the time of endovascular abdominal aortic aneurysm repair (EVAR). METHODS: Between August 2000 and August 2008, 29 patients underwent elective EVAR using bifurcated Zenith stent grafts (Cook, Indianapolis, Ind) and simultaneous renal artery stenting. Renal artery stenting during EVAR was performed with endograft "encroachment" on the renal artery ostium (n = 23) or placement of a renal stent parallel to the main body of the endograft ("snorkel," n = 8). Follow-up included routine contrast-enhanced computed tomography (CT), multiview abdominal radiographs, and serum creatinine measurement at 1, 6, and 12 months, and then yearly thereafter. RESULTS: Thirty-one renal arteries were stented successfully in 29 patients. The 18 patients with planned renal artery stent placement had a proximal neck length <15 mm. Mean proximal neck length was shorter in patients who underwent the "snorkel" technique (6.9 +/- 3.1 mm) compared with those with planned endograft encroachment (9.9 +/- 2.6 mm). None of the patients with unplanned endograft encroachment had neck lengths <15 mm (mean length, 26.3 +/- 10.2 mm). Mean proximal neck angulation was 42.8 degrees +/- 24.0 degrees and did not differ between the groups. One patient had a type I endoleak on completion angiography, and two additional patients had a type I endoleak on the first postoperative CT scan. All type I endoleaks resolved by the 1-month postoperative CT scan. The primary assisted patency of renal artery stents was 100% at a median follow-up of 12.5 months (range, 2 days-77.4 months). In one patient near occlusion of a renal artery stent was noted on follow-up CT scan at 9 months; patency was restored by placement of an additional stent. One patient required dialysis after sustained hypotension from a right external iliac artery injury that resulted in prolonged postoperative bleeding. Mean serum creatinine was 1.1 +/- 0.3 mg/dL at baseline, 1.2 +/- 0.5 mg/dL at 1 month of follow-up, and 1.2 +/- 0.5 mg/dL at 2 years of follow-up. There were no late type I endoleaks (>1 month postoperatively) or stent graft migrations. CONCLUSIONS: Adjunctive renal artery stenting during endovascular AAA repair using the "encroachment" and "snorkel" techniques is safe and effective. Short- and medium-term primary patency rates are excellent, but careful follow-up is needed to determine the durability of these techniques.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Artéria Renal/cirurgia , Stents , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aortografia/métodos , Implante de Prótese Vascular/efeitos adversos , Creatinina/sangue , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Desenho de Prótese , Artéria Renal/diagnóstico por imagem , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
During the past 15 years, endovascular methods of repair have assumed an ever more prominent role in the management of aortic aneurysms because they do not require direct exposure of the aneurysm and do not interrupt flow through the aneurysm. However, one cannot use endovascular techniques to exclude aneurysms that have branches to vital organs without first providing those branches with an alternative source of blood flow. One approach involves conventional surgical bypass to effectively "debranch" the affected segment. This approach has gained popularity because the endovascular part of the procedure is relatively simple and the surgical part does not necessarily require exposure of the aneurysm itself. The other approach involves endovascular bypass to the branches of the aorta through branches of the stent-graft. The relative merits of the two approaches depend largely on the morbidity of surgical debranching, which varies from segment to segment depending on the surgical accessibility of the branch arteries and the consequences of downstream ischemia. The authors generally favor the use of branched stent-grafts in the thoracoabdominal aorta and a combined approach in the aortic arch.
Assuntos
Aneurisma Aórtico/terapia , Implante de Prótese Vascular/métodos , Desenho de Prótese , Stents/normas , HumanosRESUMO
BACKGROUND AND PURPOSE: Microemboli occur frequently in patients with asymptomatic carotid atherosclerosis. In other vascular beds, microemboli are known to initiate an inflammatory response, causing organ dysfunction. In the current study, we investigated whether emboli composed of cholesterol crystals, a component of human atherosclerotic plaque, could also cause inflammation and brain dysfunction demonstrated by cognitive impairment. METHODS: Cholesterol crystals of 60 to 100 microm were injected via the rat internal carotid artery. T2-weighted magnetic resonance imaging was conducted after 3 days to estimate infarct volume. Brains were examined for matrix metalloproteinase activation at 24 hours and for albumin leakage and microglia and astrocyte activation at 4 days and 1, 2, and 4 weeks after embolization. To determine changes in cognition, behavioral tests including open field, motor learning, and Barnes Maze tests were conducted on young adult and middle-aged rats 4 weeks after either a single injection or after repeated, bilateral injections given at an interval of 2 weeks. RESULTS: Matrix metalloproteinase activation was detected in 50% of the animals examined. Perivascular albumin staining was found at 4 days but rarely persisted beyond 1 week. Activation of microglia and astrocytes occurred in all animals and persisted for up to 8 weeks. Cognitive impairment was observed in middle-aged rats after repeated, bilateral injections but not after single injections. In these animals, areas of inflammation were small and scattered but often involved the striatum and hippocampus. CONCLUSIONS: Cholesterol embolization caused an inflammatory response in the brain with persistent activation of microglia and astrocytes and led to cognitive impairment after repeated injections in middle-aged animals with only small foci of neural injury. These data indicate that microembolization causes inflammation and that minimal neuronal injury can cause cognitive impairment in older animals.
Assuntos
Barreira Hematoencefálica/metabolismo , Colesterol/farmacocinética , Transtornos Cognitivos/metabolismo , Embolia Intracraniana/metabolismo , Acidente Vascular Cerebral/metabolismo , Fatores Etários , Animais , Comportamento Animal , Barreira Hematoencefálica/patologia , Doenças das Artérias Carótidas/imunologia , Doenças das Artérias Carótidas/metabolismo , Doenças das Artérias Carótidas/patologia , Artéria Carótida Interna , Colesterol/química , Transtornos Cognitivos/imunologia , Transtornos Cognitivos/patologia , Corpo Estriado/patologia , Cristalização , Modelos Animais de Doenças , Encefalite/metabolismo , Encefalite/patologia , Hipocampo/patologia , Embolia Intracraniana/imunologia , Embolia Intracraniana/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/patologiaRESUMO
OBJECTIVES: Microthrombi are undoubtedly the most common embolic material in the cerebral circulation, originating from even minor irregularities of the arterial wall, fibrillating atria, cardiac valves, and patent foramen ovale. Thrombus fragments are globular and likely to completely obstruct terminal vessels. In contrast, previous work with "atheroemboli" of needle-like cholesterol crystals rarely cause occlusions or infarctions instead creating small foci of inflammation. In this work, we asked if microthrombi would occlude terminal vessels and create lacunar type infarctions in the subcortical tissues of the rat brain where, as in human brain, collateral flow is limited relative to the cortex. METHODS: Three treatment groups of adult male Sprague-Dawley rats were studied. All groups underwent general anesthesia with monitoring of temperature and blood pressure during cannulation of the right internal carotid artery. In the group embolized with thrombus fragments (n = 12), animals had injections of 300 fragments of thrombus size 60 to 100 microns, the cholesterol group (n = 6) had injections of 300 cholesterol crystals of similar size, and the control group (n = 4) had injections of saline. Brains were harvested at 4 days with perfusion fixation and were examined by immunohistochemical staining for breaks in the blood brain barrier (BBB) (albumin), microglial activation (CD11b), astrocyte activation (GFAP), and infarction (loss of NeuN staining). Size and location of the areas of injury and infarction were recorded. RESULTS: Clot fragments caused discreet infarcts in 10/12 animals that were 0.1-1.7 mm in diameter and coincided with activation of microglia and astrocytes. In some areas, necrosis was already underway at this early time point. Consistent with our previous work, the infarcts caused by cholesterol crystals were smaller (P = .014). Foci of BBB disruption and microglial activation were distributed throughout the brain whereas areas of infarction were found almost exclusively in subcortical tissues (P = .029). CONCLUSIONS: Injecting microthrombi reproducibly caused areas of necrosis resembling lacunar type infarctions. These were primarily located in the striatum and thalamus presumably because these areas lack the branching, collateral network seen in the cortex. In addition, these data give further evidence that the extent of brain injury from emboli depends upon composition and shape as well as size.
Assuntos
Infarto Encefálico/etiologia , Animais , Astrócitos/metabolismo , Barreira Hematoencefálica/metabolismo , Infarto Encefálico/metabolismo , Infarto Encefálico/patologia , Corpo Estriado/patologia , Modelos Animais de Doenças , Embolia de Colesterol/complicações , Imuno-Histoquímica , Masculino , Microglia/metabolismo , Necrose , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Tálamo/patologiaRESUMO
OBJECTIVE: This study assessed the role of multibranched stent grafts for thoracoabdominal aortic aneurysm (TAAA) repair. METHODS: Self-expanding covered stents were used to connect the caudally directed cuffs of an aortic stent graft with the visceral branches of a TAAA in 22 patients (16 men, 6 women) with a mean age of 76 +/- 7 years. All patients were unfit for open repair, and nine had undergone prior aortic surgery. Customized aortic stent grafts were inserted through surgically exposed femoral (n = 16) or iliac (n = 6) arteries. Covered stents were inserted through surgically exposed brachial arteries. Spinal catheters were used for cerebrospinal fluid pressure drainage in 22 patients and for and spinal anesthesia in 11. RESULTS: All 22 stent grafts and all 81 branches were deployed successfully. Aortic coverage as a percentage of subclavian-to-bifurcation distance was 69% +/- 20%. Mean contrast volume was 203 mL, mean blood loss was 714 mL, and mean hospital stay was 10.9 days. Two patients (9.1%) died perioperatively: one from guidewire injury to a renal arterial branch and the other from a medication error. Serious or potentially serious complications occurred in 9 of 22 patients (41%). There was no paraplegia, renal failure, stroke, or myocardial infarction among the 20 surviving patients. Two patients (9.1%) underwent successful reintervention: one for localized intimal disruption and the other for aortic dissection, type I endoleak, and stenosis of the superior mesenteric artery. One patient has a type II endoleak. Follow-up is >1 month in 19 patients, >6 months in 12, and >12 months in 8. One branch (renal artery) occluded for a 98.75% branch patency rate at 1 month. The other 80 branches remain patent. There are no signs of stent graft migration, component separation, or fracture. CONCLUSIONS: Multibranched stent graft implantation eliminates aneurysm flow, preserves visceral perfusion, and avoids many of the physiologic stresses associated with other forms of repair. The results support an expanded role for this technique in the treatment of TAAA.