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1.
Ann Surg ; 278(2): 172-178, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-36728522

RESUMEN

OBJECTIVE: The aim was to analyze the risk of progression to chronic limb-threatening ischemia (CLTI), amputation and subsequent interventions after revascularization versus noninvasive therapy in patients with intermittent claudication (IC). BACKGROUND: Conflicting evidence exists regarding adverse limb outcomes after each treatment strategy. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. MEDLINE, Web of Science, and Google Scholar were searched aided by a health sciences librarian through August 16, 2022. Randomized control trials (RCTs) comparing invasive (endovascular or surgical revascularization) and noninvasive treatment (exercise and/or medical treatment) were included. PROSPERO registration was completed (CRD42022352831). RESULTS: A total of 9 RCTs comprising 1477 patients (invasive, 765 patients; noninvasive, 712 patients) were eligible. During a mean of 3.6-year follow-up, progression to CLTI after invasive [5 (2-8) per 1000 person-years] and noninvasive treatment [6 (3-10) per 1000 person-years] were not statistically different [rate ratio (RR): 0.77; 95% CI, 0.35-1.69; P =0.51, I2 =0%]. Incidence of amputation (RR: 1.69; 95% CI, 0.54-5.26; P =0.36, I2 =0%) and all-cause mortality (hazard ratio: 1.26; 95% CI, 0.91-1.74; P =0.16, I2 =0%) also did not differ between the groups. However, the invasive treatment group underwent significantly more revascularizations (RR: 4.15; 95% CI, 2.80-6.16; P <0.00001, I2 =83%). The results were not changed by fixed effect or random-effects models, nor by sensitivity analysis. CONCLUSIONS: Although there is equivalent risk of progression to CLTI, major amputation and all-cause mortality compared with noninvasive treatment, invasive treatment for patients with IC led to significantly more revascularization procedures and should be used selectively in patients with major lifestyle limitation. Guideline recommendation of noninvasive treatment for first-line IC therapy is supported.


Asunto(s)
Procedimientos Endovasculares , Enfermedad Arterial Periférica , Humanos , Procedimientos Endovasculares/efectos adversos , Terapia por Ejercicio , Claudicación Intermitente/cirugía , Claudicación Intermitente/etiología , Isquemia/etiología , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/cirugía , Factores de Riesgo , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto
2.
J Vasc Surg ; 75(1): 348-355.e10, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34500028

RESUMEN

OBJECTIVE: Controversy has continued regarding the use of endovascular aneurysm repair (EVAR) vs open aneurysm repair (OAR) for infected abdominal aortic aneurysms (AAAs). In the present study, we investigated the comparative outcomes of EVAR and OAR for the treatment of infected AAAs. METHODS: We conducted a systematic review and meta-analysis using the MEDLINE and EMBASE databases through May 2021. We included studies that had described both EVAR and OAR for the treatment of infected AAAs. The primary endpoints were the rates of recurrent infection and related rupture and/or death. Perioperative and 1-year mortality and readmissions and reinterventions were also analyzed. RESULTS: Fourteen observational studies describing a total of 1203 patients (EVAR, 359 [29.8%]; OAR, 844 [70.2%]) were eligible for qualitative analysis. The baseline characteristics included diabetes mellitus (33.2%), fever at presentation (71.6%), rupture at diagnosis (26.1%), and positive blood cultures (52.5%). The mean follow-up period ranged from 12 to 40 months. The use of EVAR became more prevalent in recent years (2016-2020, 32.4%) compared with the former period (2010-2015, 13.8%; P < .0001). Fenestrated, branched, or concomitant visceral debranching EVAR was performed in 6.1% of cases. In OAR, surgical debridement was consistently performed, and in situ reconstruction was applied in 82.2% and an omental flap in 51.5%. In nine studies considered for quantitative analysis, the patients' background (EVAR, n = 264; OAR, n = 274) were statistically balanced. The crude rates of recurrent infection and related rupture or death were 13.6% (95% confidence interval [CI], 8.8%-18.5%) and 4.9% (95% CI 1.8%-8.0%), respectively. The pooled analyses depicted significantly higher rates of recurrent infection after EVAR than after OAR (relative risk [RR], 2.42; 95% CI, 1.80-3.27; P < .0001; I2 = 0%). Recurrent infection-related rupture or death (RR, 1.51; 95% CI, 0.70-3.23; P = .29; I2 = 0%), perioperative death (RR, 0.80; 95% CI, 0.39-1.65; P = .55; I2 = 35%), 1-year mortality (hazard ratio, 1.12; 95% CI, 0.97-1.28; P =.13; I2 = 0%), and readmission or reintervention (RR, 1.16; 95% CI, 0.74-1.82; P =.52; I2 = 0%) were not significantly different statistically between the two groups. Funnel plots showed no evidence of publication bias. Sensitivity analyses of leave-one-out meta-analysis confirmed higher rates of recurrent infection after EVAR. CONCLUSIONS: EVAR has become more prevalent as the initial treatment of infected AAAs. Although operative and 1-year survival were similar between OAR and EVAR groups, recurrent infection was more frequent after EVAR. This limitation should be weighed in selecting patients for EVAR in infected AAAs. Postoperative graft and infection surveillance are critical, especially after EVAR.


Asunto(s)
Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular/efectos adversos , Procedimientos Endovasculares/efectos adversos , Reinfección/epidemiología , Aneurisma de la Aorta Abdominal/microbiología , Aneurisma de la Aorta Abdominal/mortalidad , Implantación de Prótesis Vascular/estadística & datos numéricos , Desbridamiento/estadística & datos numéricos , Procedimientos Endovasculares/estadística & datos numéricos , Estudios de Seguimiento , Humanos , Readmisión del Paciente/estadística & datos numéricos , Reinfección/microbiología , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Resultado del Tratamiento
3.
Eur J Vasc Endovasc Surg ; 64(1): 32-40, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35472449

RESUMEN

OBJECTIVE: The newly proposed Global Limb Anatomic Staging System (GLASS), a categorical staging of infrainguinal artery disease complexity, is expected to correlate with clinical outcomes in patients with chronic limb threatening ischaemia (CLTI). This study aimed to verify the relationship between GLASS stages and clinical outcomes after endovascular treatment (EVT) and bypass surgery (BS). DATA SOURCES: MEDLINE, Web of Science Core Collection, and Google Scholar were searched in consultation with a health sciences librarian through June 2021. REVIEW METHODS: This systematic review and meta-analysis was carried out according to the PRISMA guidelines. All studies comparing the outcomes of patients with CLTI stratified by GLASS staging were eligible. Amputation free survival (AFS), limb salvage rate (LSR), major adverse limb event (MALE), overall survival, immediate technical failure (ITF), and limb based patency (LBP) were analysed. Data were pooled and synthesised with a random effects model. RESULTS: Datasets from seven retrospective cohort studies and one randomised control trial with a total of 2 204 patients (2 483 limbs) were identified. Pooled estimates demonstrated statistical differences between GLASS 1+2 and GLASS 3 in LSR (HR 0.61; 95% CI 0.47 - 0.80, p < .001) and MALE (HR 0.66; 95% CI 0.53 - 0.83, p < .001). After stratification, there were statistical differences in AFS, LSR, and MALE between GLASS 1+2 and GLASS 3 in the EVT subgroup but not in BS. In GLASS 2 and 3, MALE was significantly worse after EVT. In GLASS stages 1, 2, and 3, ITF after EVT was 3.9%, 5.3%, and 27.9%, respectively. LBP after EVT was significantly different between GLASS 1+2 and GLASS 3 (HR 0.83; 95% CI 0.71 - 0.97, p = .020). CONCLUSION: GLASS is predictive of LSR and MALE as well as ITF and LBP after EVT. The current meta-analysis suggests advanced GLASS stages favour BS over EVT.


Asunto(s)
Procedimientos Endovasculares , Enfermedad Arterial Periférica , Humanos , Isquemia , Recuperación del Miembro , Extremidad Inferior , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
4.
Vasc Med ; 27(3): 261-268, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34930052

RESUMEN

Background: Pharmacotherapy for undersized abdominal aortic aneurysm (AAA) is a clinical unmet need. Randomized controlled trials (RCTs) have failed to show effectiveness despite countless promising data in preclinical studies. We aimed to identify the population with undersized AAAs (30-54 mm) who potentially benefit from pharmacotherapy. Methods: In accordance with the PRISMA statement, we conducted a systematic review and meta-analysis of placebo-controlled RCTs. The primary outcome was mean difference (MD) in annual growth rate (< 0 favors pharmacotherapy), and the secondary outcome was aneurysm-related events (diameters ⩾ 55 mm, ruptures, or referral to surgery). Results: Our search strategy identified eight RCTs (six trials on antibiotics [ABx], two on renin-angiotensin system inhibitors [RAS-I]) with a total of 1325 patients. The mean of baseline diameters ranged from 33.1 mm to 43.1 mm. Neither ABx nor RAS-I showed significant differences in MD. Multivariable random-effects restricted maximum likelihood meta-regression revealed a statistically significant linear relationship between baseline diameter and MD (coefficient 0.15 [95% CI 0.0011, 0.30], p = 0.049) but not for the follow-up period (p = 0.28) and duration of treatment (p = 0.11). In line with this result, ABx with baseline diameter < 40 mm significantly reduced MD (-1.03 mm/year [95% CI -1.64, -0.42], p = 0.001) and a borderline significant difference in aneurysm-related events (HR 0.53 [95% CI 0.28, 1.00], p = 0.05), whereas the other groups ⩾ 40 mm never demonstrated effectiveness. Fixed-effect models did not change the results. No evidence of publication bias was detected. Conclusion: Undersized AAAs < 40 mm can potentially benefit from pharmacotherapy. Future RCTs should consider preferentially including undersized AAA with smaller diameters.


Asunto(s)
Aneurisma de la Aorta Abdominal , Antibacterianos/uso terapéutico , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/tratamiento farmacológico , Aneurisma de la Aorta Abdominal/cirugía , Humanos
5.
J Surg Res ; 257: 294-305, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32871430

RESUMEN

BACKGROUND: Drug-eluting stents impair post-angioplasty re-endothelialization thus compromising restenosis prevention while heightening thrombotic risks. We recently found that inhibition of protein kinase RNA-like endoplasmic reticulum kinase (PERK) effectively mitigated both restenosis and thrombosis in rodent models. This motivated us to determine how PERK inhibition impacts re-endothelialization. METHODS: Re-endothelialization was evaluated in endothelial-denuded rat carotid arteries after balloon angioplasty and periadventitial administration of PERK inhibitor in a hydrogel. To study whether PERK in smooth muscle cells (SMCs) regulates re-endothelialization by paracrinally influencing endothelial cells (ECs), denuded arteries exposing SMCs were lentiviral-infected to silence PERK; in vitro, the extracellular vesicles isolated from the medium of PDGF-activated, PERK-upregulating human primary SMCs were transferred to human primary ECs. RESULTS: Treatment with PERK inhibitor versus vehicle control accelerated re-endothelialization in denuded arteries. PERK-specific silencing in the denuded arterial wall (mainly SMCs) also enhanced re-endothelialization compared to scrambled shRNA control. In vitro, while medium transfer from PDGF-activated SMCs impaired EC viability and increased the mRNA levels of dysfunctional EC markers, either PERK inhibition or silencing in donor SMCs mitigated these EC changes. Furthermore, CXCL10, a paracrine cytokine detrimental to ECs, was increased by PDGF activation and decreased after PERK inhibition or silencing in SMCs. CONCLUSIONS: Attenuating PERK activity pharmacologically or genetically provides an approach to accelerating post-angioplasty re-endothelialization in rats. The mechanism may involve paracrine factors regulated by PERK in SMCs that impact neighboring ECs. This study rationalizes future development of PERK-targeted endothelium-friendly vascular interventions.


Asunto(s)
Angioplastia de Balón/efectos adversos , Reestenosis Coronaria/prevención & control , Miocitos del Músculo Liso/efectos de los fármacos , Inhibidores de Proteínas Quinasas/administración & dosificación , Repitelización/efectos de los fármacos , eIF-2 Quinasa/antagonistas & inhibidores , Angioplastia de Balón/instrumentación , Animales , Arterias Carótidas/efectos de los fármacos , Arterias Carótidas/patología , Arterias Carótidas/cirugía , Reestenosis Coronaria/etiología , Modelos Animales de Enfermedad , Stents Liberadores de Fármacos/efectos adversos , Células Endoteliales/efectos de los fármacos , Células Endoteliales/patología , Endotelio Vascular/citología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/patología , Humanos , Masculino , Músculo Liso Vascular/citología , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Comunicación Paracrina/efectos de los fármacos , Comunicación Paracrina/genética , ARN Interferente Pequeño/metabolismo , Ratas , Repitelización/genética , eIF-2 Quinasa/genética
6.
Ann Vasc Surg ; 66: 282-288, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32027989

RESUMEN

BACKGROUND: Concern regarding the adequacy of the vascular surgery workforce persists. We aimed to predict future vascular surgery workforce size and capacity using contemporary data on the US population and number, productivity, and practice patterns of vascular surgeons. METHODS: The workforce size needed to maintain current levels of access was estimated to be 1.4 vascular surgeons/100,000 population. Updated population estimates were obtained from the US Census Bureau. We calculated future vascular surgery workforce needs based on the estimated population for every 10 years from 2020 to 2050. American Medical Association Physician Masterfile data from 1997 to 2017 were used to establish the existing vascular surgery workforce size and predict future workforce size, accounting for annual rates of new certificates (increased to an average of 133/year since 2013), retirement (17%/year), and the effects of burnout, reduced work hours, transitions to nonclinical jobs, or early retirement. Based on Medical Group Management Association data that estimate median vascular surgeon productivity to be 8,481 work relative value units (wRVUs)/year, excess/deficits in wRVU capacity were calculated based on the number of anticipated practicing vascular surgeons. RESULTS: Our model predicts declining shortages of vascular surgeons through 2040, with workforce size meeting demand by 2050. In 2030, each surgeon would need to increase yearly wRVU production by 22%, and in 2040 by 8%, to accommodate the workload volume. CONCLUSIONS: Our model predicts a shortage of vascular surgeons in the coming decades, with workforce size meeting demand by 2050. Congruence between workforce and demand for services in 2050 may be related to increases in the number of trainees from integrated residencies combined with decreases in population estimates. Until then, vascular surgeons will be required to work harder to accommodate the workload. Burnout, changing practice patterns, geographic maldistribution, and expansion of health care coverage and utilization may adversely affect the ability of the future workforce to accommodate population needs.


Asunto(s)
Necesidades y Demandas de Servicios de Salud/tendencias , Fuerza Laboral en Salud/tendencias , Evaluación de Necesidades/tendencias , Cirujanos/provisión & distribución , Cirujanos/tendencias , Procedimientos Quirúrgicos Vasculares/tendencias , Censos , Predicción , Humanos , Modelos Teóricos , Factores de Tiempo , Estados Unidos , Carga de Trabajo
7.
J Proteome Res ; 18(4): 1669-1678, 2019 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-30784274

RESUMEN

Restenosis, or renarrowing of the arterial lumen, is a common recurrent disease following balloon angioplasty and stenting treatments for cardiovascular disease. A major technical barrier for deciphering restenotic mechanisms is the dynamic, spatial profiling of bioactive lipids in the arterial wall, especially in small animals. Here, applying matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI), we conducted the first lipidomic study of temporal-spatial profiling in a small animal model of angioplasty-induced restenosis. Cross sections were collected 3, 7, and 14 days after balloon angioplasty of rat carotid arteries. MALDI-MSI analyses showed that diacylglycerols (DAGs), signaling lipids associated with restenosis, and lysophosphatidylcholines (LysoPCs), whose function was uncharacterized in restenosis, dramatically increased at postangioplasty day 7 and day 14 in the neointimal layer of balloon-injured arteries compared to uninjured controls. In contrast, sphingomyelins (SMs) did not increase, but rather decreased at day 3, day 7, and day 14 in injured arteries versus the uninjured control arteries. These results revealed previously unexplored distinct temporal-spatial lipid dynamics in the restenotic arterial wall. Additionally, we employed time-of-flight secondary ion mass spectrometry (TOF-SIMS) tandem MS imaging for both molecular identification and imaging at high spatial resolution. These imaging modalities provide powerful tools for unraveling novel mechanisms of restenosis involving lipids or small signaling molecules.


Asunto(s)
Arterias Carótidas , Estenosis Carotídea , Lípidos/análisis , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Animales , Arterias Carótidas/química , Arterias Carótidas/metabolismo , Arterias Carótidas/patología , Estenosis Carotídea/metabolismo , Estenosis Carotídea/patología , Masculino , Ratas , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem
9.
J Surg Res ; 221: 196-203, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29229128

RESUMEN

BACKGROUND: Readmission within 30 d of an acute hospital stay is frequent, costly, and increasingly subject to penalties. Early readmission is most common after vascular surgery; these patients are often discharged to skilled nursing facilities (SNFs), making postacute care an essential partner in reducing readmissions. We characterize 30-day readmissions among vascular surgery patients discharged to SNF to provide evidence for this understudied segment of readmission after specialty surgery. METHODS: We utilize the Centers for Medicare & Medicaid Services Chronic Conditions Warehouse, a longitudinal 5% national random sample of Medicare beneficiaries to study 30-day readmission or death after discharge to SNF following abdominal aortic aneurysm repair or lower extremity revascularization from 2005-2009. Descriptive statistics and logistic regression with Least Adaptive Shrinkage and Selection Operator were used for analysis. RESULTS: Two thousand one hundred ninety-seven patients underwent an abdominal aortic aneurysm procedure or lower extremity revascularization at 686 hospitals and discharged to 1714 SNFs. Eight hundred (36%) were readmitted or had died at 30 d. In adjusted analysis, predictors of readmission or death at 30 d included SNF for-profit status (OR [odds ratio] = 1.2; P = 0.032), number of hospitalizations in the previous year (OR = 1.06; P = 0.011), number of comorbidities (OR = 1.06; P = 0.004), emergent procedure (OR = 1.69; P < 0.001), renal complication (OR = 1.38; P = 0.003), respiratory complication (OR = 1.45; P < 0.001), thromboembolic complication (OR = 1.57; P = 0.019), and wound complication (OR = 0.70; P = 0.017). CONCLUSIONS: Patients discharged to SNF following vascular surgery have exceptionally high rates of readmission or death at 30 d. Many factors predicting readmission or death potentially modify decision-making around discharge, making early detection, discharge planning, and matching patient needs to SNF capabilities essential to improving outcomes.


Asunto(s)
Alta del Paciente , Readmisión del Paciente/estadística & datos numéricos , Instituciones de Cuidados Especializados de Enfermería , Procedimientos Quirúrgicos Vasculares/mortalidad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Estados Unidos/epidemiología
10.
Ann Surg ; 265(2): 424-430, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-28059972

RESUMEN

OBJECTIVE: The aim of this study was to determine whether endovascular or open revascularization provides an advantageous approach to symptomatic peripheral arterial disease (PAD) over the longer term. SUMMARY OF BACKGROUND DATA: The optimal revascularization strategy for symptomatic lower extremity PAD is not established. METHODS: We evaluated amputation-free survival, overall survival, and relative rate of subsequent vascular intervention after endovascular or open lower extremity revascularization for propensity-score matched cohorts of Medicare beneficiaries with PAD from 2006 through 2009. RESULTS: Among 14,685 eligible patients, 5928 endovascular and 5928 open revascularization patients were included in matched analysis. Patients undergoing endovascular repair had improved amputation-free survival compared with open repair at 30 days (7.4 vs 8.9%, P = 0.002). This benefit persisted over the long term: At 4 years, 49% of endovascular patients had died or received major amputation compared with 54% of open patients (P < 0.001). An endovascular procedure was associated with a risk-adjusted 16% decreased risk of amputation or death compared with open over the study period (hazard ratio: 0.84; 95% confidence interval, 0.79-0.89; P < 0.001). The amputation-free survival benefit associated with an endovascular revascularization was more pronounced in patients with congestive heart failure or ischemic heart disease than in those without (P = 0.021 for interaction term). The rate of subsequent intervention at 30 days was 7.4% greater for the endovascular vs the open revascularization cohort. At 4 years, this difference remained stable at 8.6%. CONCLUSIONS: Using population-based data, we demonstrate that an endovascular approach is associated with improved amputation-free survival over the long term with only a modest relative increased risk of subsequent intervention.


Asunto(s)
Procedimientos Endovasculares , Enfermedad Arterial Periférica/cirugía , Adulto , Anciano , Amputación Quirúrgica/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Análisis por Apareamiento , Persona de Mediana Edad , Enfermedad Arterial Periférica/mortalidad , Puntaje de Propensión , Reoperación/estadística & datos numéricos , Análisis de Supervivencia , Resultado del Tratamiento
11.
J Vasc Surg ; 65(3): 793-803, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28236921

RESUMEN

OBJECTIVE: This study was conducted to identify the most clinically relevant and costly perioperative complications occurring in vascular surgery patients. METHODS: The analysis included patients in the 2012 to 2014 National Surgical Quality Improvement Program database undergoing one of four high-risk vascular procedures. The procedures-aortic reconstruction, lower extremity bypass, lower extremity amputation, and carotid endarterectomy (CEA)-were selected because they have been established as high risk in the literature, rendering them natural targets for quality improvement initiatives. Population-attributable fractions (PAFs) were used to estimate the impact of seven prespecified complications on 30-day outcomes in the study population. The PAF predicts the reduction in outcome anticipated if a particular complication were to be prevented across the study population. Unadjusted and adjusted PAFs were reported. CEA was analyzed separately from the other procedures. RESULTS: The analysis included 72,805 National Surgical Quality Improvement Program patients. Pneumonia had the largest impact on the incidence of end-organ dysfunction in CEA patients (adjusted PAF, 24.4%; 95% confidence interval, 20.6-28.1), and cerebrovascular accident had the largest impact on mortality in these patients (adjusted PAF, 23.1%; 95% confidence interval, 18.5-27.3). In patients undergoing abdominal or lower extremity vascular surgery, bleeding and pneumonia had the largest impact on clinical outcomes and need for prolonged hospitalization, and surgical site infection had the largest impact on hospital readmission. In contrast, prevention of venous thromboembolism, urinary tract infection, and myocardial infarction do not demonstrate substantial impact on patient outcomes or resource utilization in either group of vascular surgery patients. CONCLUSIONS: Quality initiatives that can successfully reduce the occurrence of postoperative stroke, bleeding, and pneumonia will have the greatest clinical impact on the outcomes of vascular surgery patients. Initiatives that target complications such as venous thromboembolism, urinary tract infection, or myocardial infarction will have little impact on this patient population.


Asunto(s)
Complicaciones Posoperatorias/epidemiología , Procedimientos Quirúrgicos Vasculares/efectos adversos , Anciano , Anciano de 80 o más Años , Amputación Quirúrgica/efectos adversos , Aorta/cirugía , Ahorro de Costo , Bases de Datos Factuales , Endarterectomía Carotidea/efectos adversos , Femenino , Costos de la Atención en Salud , Humanos , Incidencia , Extremidad Inferior/irrigación sanguínea , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/cirugía , Complicaciones Posoperatorias/economía , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/prevención & control , Mejoramiento de la Calidad , Indicadores de Calidad de la Atención de Salud , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiología , Injerto Vascular/efectos adversos , Procedimientos Quirúrgicos Vasculares/economía , Procedimientos Quirúrgicos Vasculares/mortalidad , Procedimientos Quirúrgicos Vasculares/tendencias
12.
Stem Cells ; 34(11): 2744-2757, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27340942

RESUMEN

CXCR4 is a stem/progenitor cell surface receptor specific for the cytokine stromal cell-derived factor-1 (SDF-1α). There is evidence that bone marrow-derived CXCR4-expressing cells contribute to intimal hyperplasia (IH) by homing to the arterial subintima which is enriched with SDF-1α. We have previously found that transforming growth factor-ß (TGFß) and its signaling protein Smad3 are both upregulated following arterial injury and that TGFß/Smad3 enhances the expression of CXCR4 in vascular smooth muscle cells (SMCs). It remains unknown, however, whether locally induced CXCR4 expression in SM22 expressing vascular SMCs plays a role in neointima formation. Here, we investigated whether elevated TGFß/Smad3 signaling leads to the induction of CXCR4 expression locally in the injured arterial wall, thereby contributing to IH. We found prominent CXCR4 upregulation (mRNA, 60-fold; protein, 4-fold) in TGFß-treated, Smad3-expressing SMCs. Chromatin immunoprecipitation assays revealed a specific association of the transcription factor Smad3 with the CXCR4 promoter. TGFß/Smad3 treatment also markedly enhanced SDF-1α-induced ERK1/2 phosphorylation as well as SMC migration in a CXCR4-dependent manner. Adenoviral expression of Smad3 in balloon-injured rat carotid arteries increased local CXCR4 levels and enhanced IH, whereas SMC-specific depletion of CXCR4 in the wire-injured mouse femoral arterial wall produced a 60% reduction in IH. Our results provide the first evidence that upregulation of TGFß/Smad3 in injured arteries induces local SMC CXCR4 expression and cell migration, and consequently IH. The Smad3/CXCR4 pathway may provide a potential target for therapeutic interventions to prevent restenosis. Stem Cells 2016;34:2744-2757.


Asunto(s)
Traumatismos de las Arterias Carótidas/genética , Neointima/genética , Receptores CXCR4/genética , Proteína smad3/genética , Factor de Crecimiento Transformador beta/metabolismo , Túnica Íntima/metabolismo , Animales , Arterias Carótidas/metabolismo , Traumatismos de las Arterias Carótidas/metabolismo , Traumatismos de las Arterias Carótidas/patología , Movimiento Celular , Regulación de la Expresión Génica , Masculino , Ratones , Ratones Noqueados , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Neointima/metabolismo , Neointima/patología , Fosforilación , Cultivo Primario de Células , Regiones Promotoras Genéticas , Ratas , Ratas Sprague-Dawley , Receptores CXCR4/deficiencia , Transducción de Señal , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta/farmacología , Túnica Íntima/lesiones
13.
Biomacromolecules ; 18(7): 2205-2213, 2017 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-28613846

RESUMEN

At present, there are no clinical options for preventing neointima-caused (re)stenosis after open surgery such as bypass surgery for treating flow-limiting vascular disease. Perivascular drug delivery is a promising strategy, but in translational research, it remains a major challenge to achieve long-term (e.g., > 3 months) anti(re)stenotic efficacy. In this study, we engineered a unique drug delivery system consisting of durable unimolecular micelles, formed by single multiarm star amphiphilic block copolymers with only covalent bonds, and a thermosensitive hydrogel formed by a poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) triblock copolymer (abbreviated as triblock gel) that is stable for about 4 weeks in vitro. The drug-containing unimolecular micelles (UMs) suspended in Triblock gel were able to sustain rapamycin release for over 4 months. Remarkably, even 3 months after perivascular application of the rapamycin-loaded micelles in Triblock gel in the rat model, the intimal/medial area ratio (a restenosis measure) was still 80% inhibited compared to the control treated with empty micelle/gel (no drug). This could not be achieved by applying rapamycin in Triblock gel alone, which reduced the intimal/medial ratio only by 27%. In summary, we created a new UM/Triblock gel hybrid system for perivascular drug delivery, which produced a rare feat of 3-month restenosis inhibition in animal tests. This system exhibits a real potential for further translation into an anti(re)stenotic application with open surgery.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Hidrogeles , Micelas , Neointima/metabolismo , Sirolimus , Animales , Hidrogeles/química , Hidrogeles/farmacología , Masculino , Neointima/patología , Ratas , Ratas Sprague-Dawley , Sirolimus/química , Sirolimus/farmacología
14.
Arterioscler Thromb Vasc Biol ; 36(9): 1962-71, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27386936

RESUMEN

OBJECTIVE: Arterial calcification is common and contributes to the pathogenesis of occlusive vascular disease. Similar to the dynamics of bone, it is a tightly controlled process that maintains a balance between osteogenesis and osteolysis. However, whether calcium homeostasis plays a role in the development of aneurysms has not been explored. We hypothesized that macrophages differentiate into osteoclasts in aneurysmal arteries and that protease byproducts contribute to aneurysm pathophysiology. APPROACH AND RESULTS: We performed histological and immunohistochemical analyses and showed that macrophages positive for several osteoclast markers, including tartrate acid phosphatase, occur in great numbers in the human aneurysmal aorta, but very few occur in the human stenotic aorta and none in the nondiseased human aorta. Moreover, in situ zymography showed elevated protease activity in these cells compared with undifferentiated macrophages. Tumor necrosis factor-α and calcium phosphate stimulated this osteoclastogenic differentiation process through nuclear factor-κB, mitogen-activated protein kinases, and intracellular calcium signaling but not the receptor activator of the nuclear factor-κB ligand. Inhibition of osteoclastogenic differentiation by bisphosphonate inhibits aneurysm development in a mouse model. CONCLUSIONS: These results suggest that differentiation of macrophages into osteoclasts contributes to the pathophysiology of aneurysmal disease.


Asunto(s)
Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/metabolismo , Transdiferenciación Celular , Macrófagos/metabolismo , Osteoclastos/metabolismo , Osteogénesis , Calcificación Vascular/metabolismo , Angiotensina II , Animales , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/inducido químicamente , Aneurisma de la Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/prevención & control , Cloruro de Calcio , Fosfatos de Calcio/farmacología , Señalización del Calcio , Transdiferenciación Celular/efectos de los fármacos , Difosfonatos/farmacología , Modelos Animales de Enfermedad , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/patología , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Osteoclastos/patología , Osteogénesis/efectos de los fármacos , Células RAW 264.7 , Fosfatasa Ácida Tartratorresistente/metabolismo , Factores de Tiempo , Factor de Necrosis Tumoral alfa/farmacología , Calcificación Vascular/patología
15.
J Proteome Res ; 15(9): 3420-31, 2016 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-27457343

RESUMEN

Isobaric labeling has become a widespread tool for quantitative proteomic studies. Here, we report the development and evaluation of several dimethylated amino acids as novel isobaric tags for quantitative proteomics. Four-plex dimethylated alanine (DiAla), valine (DiVal), and leucine (DiLeu) have been synthesized, sharing common features of peptide tagging and reporter ion production. DiAla and DiLeu are shown to achieve complete labeling. These two tags' impacts on peptide fragmentation and quantitation are further evaluated using HEK293 cell lysate. DiAla labeling generates more abundant backbone fragmentation whereas DiLeu labeling produces more intense reporter ions. Nonetheless, both tags enable accurate quantitative analysis of HEK293 cell proteomes. DiAla and DiLeu tags are then applied to study the TGF-ß/Smad3 pathway with four differentially treated mouse vascular smooth muscle (MOVAS) cells. Our MS data reveal proteome-wide changes of AdSmad3 as compared to the GFP control, consistent with previous findings of causing smooth muscle cell (SMC) dedifferentiation.1 Additionally, the other two novel mutations on the hub protein Smad3, Y226A, and D408H, show compromised TGF-ß/Smad3-dependent gene transcription and reversed phenotypic switch. These results are further corroborated with Western blotting and demonstrate that the novel DiAla and DiLeu isobaric tagging reagents provide useful tools for multiplex quantitative proteomics.


Asunto(s)
Proteómica/métodos , Transducción de Señal , Proteína smad3/metabolismo , Coloración y Etiquetado/métodos , Factor de Crecimiento Transformador beta/metabolismo , Alanina/análogos & derivados , Aminoácidos/síntesis química , Aminoácidos/química , Animales , Células HEK293 , Humanos , Leucina/análogos & derivados , Metilación , Ratones , Músculo Liso Vascular/citología , Valina/análogos & derivados
16.
J Pharmacol Exp Ther ; 356(1): 137-47, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26483397

RESUMEN

Abdominal aortic aneurysm (AAA), characterized by exuberant inflammation and tissue deterioration, is a common aortic disease associated with a high mortality rate. There is currently no established pharmacological therapy to treat this progressive disease. Andrographolide (Andro), a major bioactive component of the herbaceous plant Andrographis paniculata, has been found to exhibit potent anti-inflammatory properties by inhibiting nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activity in several disease models. In this study, we investigated the ability of Andro to suppress inflammation associated with aneurysms, and whether it may be used to block the progression of AAA. Whereas diseased aortae continued to expand in the solvent-treated group, daily administration of Andro to mice with small aneurysms significantly attenuated aneurysm growth, as measured by the diminished expansion of aortic diameter (165.68 ± 15.85% vs. 90.62 ± 22.91%, P < 0.05). Immunohistochemistry analyses revealed that Andro decreased infiltration of monocytes/macrophages and T cells. Mechanistically, Andro inhibited arterial NF-κB activation and reduced the production of proinflammatory cytokines [CCL2, CXCL10, tumor necrosis factor α, and interferon-γ] in the treated aortae. Furthermore, Andro suppressed α4 integrin expression and attenuated the ability of monocytes/macrophages to adhere to activated endothelial cells. These results indicate that Andro suppresses progression of AAA, likely through inhibition of inflammatory cell infiltration via downregulation of NF-κB-mediated cytokine production and α4 integrin expression. Thus, Andro may offer a pharmacological therapy to slow disease progression in patients with small aneurysms.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Aneurisma de la Aorta Abdominal/tratamiento farmacológico , Citocinas/antagonistas & inhibidores , Diterpenos/uso terapéutico , Integrinas/antagonistas & inhibidores , Animales , Aorta Torácica/efectos de los fármacos , Citocinas/biosíntesis , Progresión de la Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Integrinas/biosíntesis , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , FN-kappa B/efectos de los fármacos , Cultivo Primario de Células , Linfocitos T/efectos de los fármacos
17.
J Biol Chem ; 289(13): 9013-26, 2014 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-24519937

RESUMEN

Proinflammatory chemokines released by vascular smooth muscle cells (VSMCs) play a critical role in vascular inflammation. Protein kinase C-δ (PKCδ) has been shown to be up-regulated in VSMCs of injured arteries. PKCδ knock-out (Prkcd(-/-)) mice are resistant to inflammation as well as apoptosis in models of abdominal aortic aneurysm. However, the precise mechanism by which PKCδ modulates inflammation remains incompletely understood. In this study, we identified four inflammatory chemokines (Ccl2/Mcp-1, Ccl7, Cxcl16, and Cx3cl1) of over 45 PKCδ-regulated genes associated with inflammatory response by microarray analysis. Using CCL2 as a prototype, we demonstrated that PKCδ stimulated chemokine expression at the transcriptional level. Inhibition of the NF-κB pathway or siRNA knockdown of subunit p65, but not p50, eliminated the effect of PKCδ on Ccl2 expression. Overexpressing PKCδ followed by incubation with phorbol 12-myristate 13-acetate resulted in an increase in p65 Ser-536 phosphorylation and enhanced DNA binding affinity without affecting IκB degradation or p65 nuclear translocation. Prkcd gene deficiency impaired p65 Ser-536 phosphorylation and DNA binding affinity in response to TNFα. Results from in situ proximity ligation analysis and co-immunoprecipitation performed on cultured VSMCs and aneurysmal aorta demonstrated physical interaction between PKCδ and p65 that took place largely outside the nucleus. Promoting nuclear translocation of PKCδ with peptide ψδRACK diminished Ccl2 production, whereas inhibition of PKCδ translocation with peptide δV1-1 enhanced Ccl2 expression. Together, these results suggest that PKCδ modulates inflammation at least in part through the NF-κB-mediated chemokines. Mechanistically, PKCδ activates NF-κB through an IκB-independent cytosolic interaction, which subsequently leads to enhanced p65 phosphorylation and DNA binding affinity.


Asunto(s)
Quimiocinas/genética , Citosol/metabolismo , Regulación de la Expresión Génica , Músculo Liso Vascular/citología , Proteína Quinasa C-delta/metabolismo , Factor de Transcripción ReIA/metabolismo , Animales , Aneurisma de la Aorta Abdominal/patología , ADN/metabolismo , Activación Enzimática , Inflamación/metabolismo , Masculino , Ratones , Músculo Liso Vascular/patología , Fosforilación , Unión Proteica , Ratas , Transcripción Genética , Regulación hacia Arriba
18.
J Vasc Surg ; 62(1): 22-6, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25935276

RESUMEN

OBJECTIVE: Although placement of an open iliac conduit for endovascular aortic aneurysm repair (EVAR) is generally felt to result in higher morbidity and mortality, published literature is scarce. Our objective was to assess 30-day outcomes after elective EVAR with an open iliac conduit using a multi-institutional database. METHODS: Patients who underwent elective EVAR (n = 14,339) for abdominal aortic aneurysm were identified from the American College of Surgeons National Surgical Quality Improvement Program 2005 to 2011 database. Univariable and multivariable logistic regression analyses were performed. RESULTS: An open iliac conduit was used in 231 patients (1.6%), and the remainder had femoral exposure or percutaneous EVAR. Women comprised 32% of patients with iliac conduits in contrast to 17% of those without iliac conduits. Patients with iliac conduits were older and had a lower body mass index. Univariable analysis showed patients with open iliac conduits had a higher incidence of postoperative pneumonia (3.0% vs 1.1%), ventilator dependence (4.8% vs 1.0%), renal failure (3.0% vs 0.7%), cardiac arrest or myocardial infarction (5.2% vs 1.1%), return to the operating room (9.1% vs 3.7%), major morbidity (16.0 vs 6.6%), and death (3.0% vs 0.9%). On multivariable analysis, the use of open iliac conduits was associated with higher risk of 30-day mortality (odds ratio, 2.7; 95% confidence interval, 1.2-6.0) and 30-day major morbidity (odds ratio, 2.3; 95% confidence interval, 1.6-3.3). CONCLUSIONS: Patients with open iliac conduits for EVAR are more likely to be female and have higher postoperative morbidity and mortality. For patients with complex iliac artery disease, conduits are a viable alternative after EVAR to be performed, albeit at an increased risk. These data do suggest the need for lower-profile grafts and other alternative strategies for navigating complex iliac artery disease.


Asunto(s)
Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular , Prótesis Vascular , Procedimientos Endovasculares , Arteria Ilíaca/cirugía , Aneurisma de la Aorta Abdominal/diagnóstico , Aneurisma de la Aorta Abdominal/mortalidad , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/instrumentación , Implantación de Prótesis Vascular/mortalidad , Distribución de Chi-Cuadrado , Bases de Datos Factuales , Procedimientos Quirúrgicos Electivos , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/instrumentación , Procedimientos Endovasculares/mortalidad , Femenino , Humanos , Modelos Logísticos , Masculino , Análisis Multivariante , Oportunidad Relativa , Selección de Paciente , Diseño de Prótesis , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos
19.
J Vasc Surg ; 62(4): 1023-1031.e5, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26143662

RESUMEN

OBJECTIVE: Surgical site infection (SSI) is one of the most common postoperative complications after vascular reconstruction, producing significant morbidity and hospital readmission. In contrast to SSI that develops while patients are still hospitalized, little is known about the cohort of patients who develop SSI after discharge. In this study, we explore the factors that lead to postdischarge SSI, investigate the differences between risk factors for in-hospital vs postdischarge SSI, and develop a scoring system to identify patients who might benefit from postdischarge monitoring of their wounds. METHODS: Patients who underwent major vascular surgery from 2005 to 2012 for aneurysm and lower extremity occlusive disease were identified from the American College of Surgeons National Surgical Quality Improvement Program Participant Use Files. Patients were categorized as having no SSI, in-hospital SSI, or SSI after hospital discharge. Predictors of postdischarge SSI were determined by multivariable logistic regression and internally validated by bootstrap resampling. Risk scores were assigned to all significant variables in the model. Summative risk scores were collapsed into quartile-based ordinal categories and defined as low, low/moderate, moderate/high, and high risk. Multivariable logistic regression was used to determine predictors of in-hospital SSI. RESULTS: Of the 49,817 patients who underwent major vascular surgery, 4449 (8.9%) were diagnosed with SSI (2.1% in-hospital SSI; 6.9% postdischarge SSI). By multivariable analysis, factors significantly associated with increased odds of postdischarge SSI include female gender, obesity, diabetes, smoking, hypertension, coronary artery disease, critical limb ischemia, chronic obstructive pulmonary disease, dyspnea, neurologic disease, prolonged operative time >4 hours, American Society of Anesthesiology class 4 or 5, lower extremity revascularization or aortoiliac procedure, and groin anastomosis. The model exhibited moderate discrimination (bias-corrected C statistic, 0.691) and excellent internal calibration. The postdischarge SSI rate was 2.1% for low-risk patients, 5.1% for low/moderate-risk patients, 7.8% for moderate/high-risk patients, and 14% for high-risk patients. In a comparative analysis, comorbidities were the primary driver of postdischarge SSI, whereas in-hospital factors (operative time, emergency case status) and complications predicted in-hospital SSI. CONCLUSIONS: The majority of SSIs after major vascular surgery develop following hospital discharge. We have created a scoring system that can select a cohort of patients at high risk for SSI after discharge. These patients can be targeted for transitional care efforts focused on early detection and treatment with the goal of reducing morbidity and preventing readmission secondary to SSI.


Asunto(s)
Infección de la Herida Quirúrgica , Procedimientos Quirúrgicos Vasculares , Anciano , Análisis de Varianza , Aneurisma/cirugía , Arteriopatías Oclusivas/cirugía , Estudios de Cohortes , Femenino , Predicción , Humanos , Masculino , Monitoreo Fisiológico , Alta del Paciente , Factores de Riesgo
20.
J Surg Res ; 198(1): 245-51, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26025626

RESUMEN

BACKGROUND: Information technology is transforming health care communication. Using smartphones to remotely monitor incisional wounds via digital photos as well as collect postoperative symptom information has the potential to improve patient outcomes and transitional care. We surveyed a vulnerable patient population to evaluate smartphone capability and willingness to adopt this technology. METHODS: We surveyed 53 patients over a 9-mo period on the vascular surgery service at a tertiary care institution. Descriptive statistics were calculated to describe survey item response. RESULTS: A total of 94% of recruited patients (50 of 53) participated. The cohort was 50% female, and the mean age was age 70 y (range: 41-87). The majority of patients owned cell phones (80%) and 23% of these cell phones were smartphones. Ninety percent of patients had a friend or family member that could help take and send photos with a smartphone. Ninety-two percent of patients reported they would be willing to take a digital photo of their wound via a smartphone (68% daily, 22% every other day, 2% less than every other day, and 8% not at all). All patients reported they would be willing to answer questions related to their health via a smartphone. Patients identified several potential difficulties with regard to adopting a smartphone wound-monitoring protocol including logistics related to taking photos, health-related questions, and coordination with caretakers. CONCLUSIONS: Our survey demonstrates that an older patient cohort with significant comorbidity is able and willing to adopt a smartphone-based postoperative monitoring program. Patient training and caregiver participation will be essential to the success of this intervention.


Asunto(s)
Cuidadores , Teléfono Celular , Complicaciones Posoperatorias/diagnóstico , Infección de la Herida Quirúrgica/diagnóstico , Telemedicina , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios
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