RESUMO
Embryonic stem cell (ESC)-derived embryoid body (EB) is a unique model for studying vascular development, in that it provides a three-dimensional microenvironment that mimics an in vivo milieu. When using gene-targeting EBs to study certain defects in vascular morphogenesis, it is necessary to determine whether the defect is due to the intrinsic loss of the gene in endothelial cells (EC) or rather due to the lack of surrounding factors that would typically promote vascular development. Here we describe a chimeric EB vessel development model, in which the utilization of the PECAM-GFP reporter gene in wild-type ESCs allows for the introduction of "normal" extracellular factors formed by its parallel differentiation to the gene-deletion EC that might otherwise be devoid of these factors.
Assuntos
Vasos Sanguíneos/embriologia , Corpos Embrioides/citologia , Marcação de Genes/métodos , Morfogênese , Animais , Técnicas de Cultura de Células , Diferenciação Celular , Corpos Embrioides/metabolismo , Células Endoteliais/citologia , Inativação Gênica , Proteínas de Fluorescência Verde/genética , Camundongos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Transfecção , Proteína cdc42 de Ligação ao GTP/deficiência , Proteína cdc42 de Ligação ao GTP/genéticaRESUMO
OBJECTIVE: The management of popliteal artery aneurysms (PAAs) has undergone significant transition from open surgery to endovascular graft placement with few longitudinal data evaluating outcomes. METHODS: The Centers of Medicare & Medicaid Services Inpatient claims (2005-2007) were queried with a diagnosis of lower extremity artery aneurysm in association with elective Current Procedural Terminology codes for open (OPEN group) and endovascular (ENDO group) repair. RESULTS: A total of 2962 patients were identified. Endovascular interventions significantly increased over the time of the study (11.7% vs 23.6%, P < .0001). Overall complication rates for OPEN and ENDO groups did not differ significantly (11.3% vs 9.3%; P = .017). No differences in the 30- and 90-day mortality rates were found between OPEN versus ENDO groups. The ENDO group had greater 30- and 90-day reinterventions (4.6% vs 2.1%, P = .001 and 11.8% vs 7.4%, P = .0007, respectively). Length of stay (4.5 days vs 2.5 days, P < .0001) and charges ($43 180 vs $35 540, P < .0001) were greater for OPEN group. CONCLUSION: Despite a significant increase in the utilization of endovascular repair of PAAs, endovascular repair was associated with greater reinterventions over time and did not offer a mortality or cost benefit.
Assuntos
Aneurisma/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Medicare , Artéria Poplítea/cirurgia , Idoso , Idoso de 80 Anos ou mais , Aneurisma/economia , Aneurisma/mortalidade , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/economia , Implante de Prótese Vascular/mortalidade , Centers for Medicare and Medicaid Services, U.S. , Distribuição de Qui-Quadrado , Análise Custo-Benefício , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/economia , Procedimentos Endovasculares/mortalidade , Feminino , Custos de Cuidados de Saúde , Humanos , Tempo de Internação , Modelos Logísticos , Masculino , Medicare/economia , Análise Multivariada , Razão de Chances , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/terapia , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
GATA-6 is a zinc-finger transcription factor essential for early embryogenesis. Ablation of GATA-6 in mice impairs endoderm differentiation and causes apoptosis of epiblast cells. The endoderm defects have been attributed to the loss of HNF4, disabled-2, and GATA-4. However, the mechanisms underlying epiblast apoptosis are unclear. In this study we used mouse embryonic stem cell-derived embryoid bodies (EBs) as a model for peri-implantation development and found that ablation of GATA-6 causes massive apoptosis during EB differentiation. Endoderm grafting experiments and ectopic basement membrane (BM) assembly suggest that both BM and non-BM factors contribute to cell survival. Furthermore, the increased cell death in mutant EBs is accompanied by reduced expression of bone morphogenetic protein 2 (BMP-2). Chromatin immunoprecipitation reveals direct binding of GATA-6 to the Bmp2 promoter. Treatment of the mutant EBs with BMP-2 markedly suppresses apoptosis, whereas stable overexpression of the BMP antagonist noggin or a dominant-negative BMP receptor in normal EBs leads to increased apoptosis. Last, activation of SMAD1/5 by phosphorylation is significantly inhibited in the absence of GATA-6, and this is reversed by exogenous BMP-2. Treatment of normal EBs with SMAD phosphorylation inhibitor increases apoptosis. Collectively these results suggest that GATA-6 promotes cell survival by regulating endoderm expression of BMP-2 and BM during embryonic epithelial morphogenesis.
Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Diferenciação Celular , Células-Tronco Embrionárias/metabolismo , Fator de Transcrição GATA6/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/farmacologia , Linhagem Celular , Sobrevivência Celular , Corpos Embrioides/citologia , Corpos Embrioides/metabolismo , Células-Tronco Embrionárias/citologia , Endoderma/metabolismo , Endoderma/ultraestrutura , Fator de Transcrição GATA6/genética , Perfilação da Expressão Gênica , Camadas Germinativas/metabolismo , Immunoblotting , Camundongos , Microscopia Eletrônica , Microscopia de Fluorescência , Mutação , Fosforilação , Regiões Promotoras Genéticas/genética , Ligação Proteica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Smad/genética , Proteínas Smad/metabolismo , Fatores de Tempo , Regulação para CimaRESUMO
Apoptosis is an essential step in cavitation during embryonic epithelial morphogenesis, but its mechanisms are largely unknown. In this paper, we used embryonic stem cell-differentiated embryoid bodies (EBs) as a model and found that Bnip3 (Bcl-2/adenovirus E1B 19-kD interacting protein), a BH3-only proapoptotic protein, was highly up-regulated during cavitation in a hypoxia-dependent manner. Short hairpin RNA silencing of Bnip3 inhibited apoptosis of the core cells and delayed cavitation. We show that the Bnip3 up-regulation was mediated mainly by hypoxia-inducible factor (HIF)-2. Ablation of HIF-2α or HIF-1ß, the common ß subunit of HIF-1 and -2, suppressed Bnip3 up-regulation and inhibited apoptosis and cavitation. We further show that apoptosis-inducing factor (AIF) cooperated with Bnip3 to promote lumen clearance. Bnip3 silencing in AIF-null EBs nearly blocked apoptosis and cavitation. Moreover, AIF also regulated Bnip3 expression through mitochondrial production of reactive oxygen species and consequent HIF-2α stabilization. These results uncover a mechanism of cavitation through hypoxia-induced apoptosis of the core cells mediated by HIFs, Bnip3, and AIF.
Assuntos
Fator de Indução de Apoptose/fisiologia , Apoptose , Células-Tronco Embrionárias/fisiologia , Células Epiteliais/fisiologia , Proteínas de Membrana/fisiologia , Proteínas Mitocondriais/fisiologia , Morfogênese/fisiologia , Animais , Fator de Indução de Apoptose/genética , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Células Cultivadas , Células-Tronco Embrionárias/citologia , Células Epiteliais/citologia , Inativação Gênica/fisiologia , Proteínas de Membrana/genética , Camundongos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Regulação para CimaRESUMO
BACKGROUND: Improving patient safety has become a national priority. Patient safety indicators (PSIs) are validated tools to identify potentially preventable adverse events. No studies currently exist for evaluating lower extremity (LE) vascular procedures and the occurrence of PSIs. METHODS: The Nationwide Inpatient Sample (2003-2007) was queried for elective LE angioplasty (endo) and bypass (open). PSIs appropriate to surgery were analyzed by χ(2) and logistic regression analyses. RESULTS: A total of 226,501 LE interventions (104,491 endo; 122,010 open) were evaluated. The rate of developing any PSI was 7.74% (open) and 8.51% (endo), P < .0001. In the latter group, PSI9 (postoperative hemorrhage or hematoma) with the rate 4.74% was a predominant indicator that was associated with an almost three times greater likelihood of death in this group. PSI predictors included advanced age (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.55-1.75 for oldest vs youngest patients), females (OR, 1.18; 95% CI, 1.13-1.22), blacks (OR, 1.10; 95% CI, 1.04-1.17), congestive heart failure (OR, 1.83; 95% CI, 1.72-1.96), diabetes mellitus (OR, 1.20; 95% CI, 1.12-1.28), renal failure (OR, 2.31; 95% CI, 2.14-2.50), hospital teaching status (OR, 1.21; 95% CI, 1.17-1.26), and larger hospitals (OR, 1.11; 95% CI, 1.05-1.17). PSI occurrence was associated with increased cost ($28,387 vs $13,278; P < .0001). CONCLUSIONS: Endovascular procedures were found to have lower mortality rates overall, but were found to have a greater number of safety events occur primarily due to bleeding complications in women and the elderly. PSIs were associated with advanced age, black race, and comorbidities. Adverse events added significant cost, occurred more frequently in teaching and large hospitals, and future organizational analysis may improve safety and reduce cost.
Assuntos
Angioplastia/efeitos adversos , Hospitais , Extremidade Inferior/irrigação sanguínea , Doenças Vasculares Periféricas/terapia , Complicações Pós-Operatórias/prevenção & controle , Melhoria de Qualidade , Indicadores de Qualidade em Assistência à Saúde , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Adolescente , Adulto , Negro ou Afro-Americano , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Angioplastia/economia , Angioplastia/mortalidade , Distribuição de Qui-Quadrado , Comorbidade , Bases de Dados como Assunto , Feminino , Hematoma/etiologia , Hematoma/prevenção & controle , Custos Hospitalares , Hospitais/estatística & dados numéricos , Hospitais de Ensino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Doenças Vasculares Periféricas/economia , Doenças Vasculares Periféricas/mortalidade , Doenças Vasculares Periféricas/cirurgia , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/mortalidade , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/prevenção & controle , Melhoria de Qualidade/economia , Melhoria de Qualidade/estatística & dados numéricos , Indicadores de Qualidade em Assistência à Saúde/economia , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Resultado do Tratamento , Estados Unidos , Procedimentos Cirúrgicos Vasculares/economia , Procedimentos Cirúrgicos Vasculares/mortalidade , Adulto JovemRESUMO
OBJECTIVE: A relationship exists between higher hospital volume and lower mortality, yet the impact of hospital volume on infectious complications after elective abdominal aortic aneurysm (AAA) repair is unknown. METHODS: The Medicare database (2005-2007) was utilized. Top 10% for volume were categorized as high-volume (HV) and compared to low-volume (LV) centers for infectious complications and utilization. RESULTS: A total of 42 155 endovascular aneurysm repair (EVAR) and 17 210 open AAA were identified. Mortality in HV was significantly lower than in LV after EVAR and open AAA. After EVAR, HV had lower than LV rates of overall infection (3.10% vs 3.51%; P = .021), PNA (0.94% vs 1.27%, P = .002), and sepsis (0.31% vs 0.45%; P = .03). Length of stay (LOS) and total hospital charges were significantly lower at HV compared to LV after both EVAR and open AAA. CONCLUSION: For Medicare beneficiaries, undergoing elective AAA repair at hospitals performing higher volume significantly reduced postoperative infectious complications and hospital resource utilization. Further analysis identifying systematic reasons for disparities may offer cost savings and improve outcomes.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Endovasculares/efeitos adversos , Hospitais , Medicare , Avaliação de Processos e Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/economia , Aneurisma da Aorta Abdominal/mortalidade , Distribuição de Qui-Quadrado , Redução de Custos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Procedimentos Endovasculares/economia , Procedimentos Endovasculares/mortalidade , Feminino , Custos Hospitalares , Hospitais/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Medicare/economia , Medicare/estatística & dados numéricos , Razão de Chances , Avaliação de Processos e Resultados em Cuidados de Saúde/economia , Avaliação de Processos e Resultados em Cuidados de Saúde/estatística & dados numéricos , Pneumonia/etiologia , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Sepse/etiologia , Infecção da Ferida Cirúrgica/etiologia , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Infecções Urinárias/etiologia , Procedimentos Cirúrgicos Vasculares/economia , Procedimentos Cirúrgicos Vasculares/mortalidadeRESUMO
OBJECTIVE: The goal of this study was to determine the role of Cdc42 in embryonic vasculogenesis and the underlying mechanisms. METHODS AND RESULTS: By using genetically modified mouse embryonic stem (ES) cells, we demonstrate that ablation of the Rho GTPase Cdc42 blocks vascular network assembly during embryoid body (EB) vasculogenesis without affecting endothelial lineage differentiation. Reexpression of Cdc42 in mutant EBs rescues the mutant phenotype, establishing an essential role for Cdc42 in vasculogenesis. Chimeric analysis revealed that the vascular phenotype is caused by inactivation of Cdc42 in endothelial cells rather than surrounding cells. Endothelial cells isolated from Cdc42-null EBs are defective in directional migration and network assembly. In addition, activation of atypical protein kinase Cι (PKCι) is abolished in Cdc42-null endothelial cells, and PKCι ablation phenocopies the vascular abnormalities of the Cdc42-null EBs. Moreover, the inhibitory phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) at Ser9 depends on Cdc42 and PKCι, and expression of kinase-dead GSK-3ß in Cdc42-null EBs promotes the formation of linear endothelial segments without branches. These results suggest that PKCι and GSK-3ß are downstream effectors of Cdc42 during vascular morphogenesis. CONCLUSIONS: Cdc42 controls vascular network assembly but not endothelial lineage differentiation by activating PKCι during embryonic vasculogenesis.
Assuntos
Vasos Sanguíneos/embriologia , Isoenzimas/metabolismo , Neovascularização Fisiológica , Proteína Quinase C/metabolismo , Proteína cdc42 de Ligação ao GTP/metabolismo , Junções Aderentes/metabolismo , Animais , Vasos Sanguíneos/citologia , Vasos Sanguíneos/metabolismo , Diferenciação Celular , Linhagem Celular , Movimento Celular , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Isoenzimas/deficiência , Isoenzimas/genética , Camundongos , Proteína Quinase C/deficiência , Proteína Quinase C/genética , Transdução de Sinais , Proteína cdc42 de Ligação ao GTP/deficiência , Proteína cdc42 de Ligação ao GTP/genéticaRESUMO
Talin is a cytoskeletal protein that binds to integrin ß cytoplasmic tails and regulates integrin activation. Talin1 ablation in mice disrupts gastrulation and causes embryonic lethality. However, the role of talin in mammalian epithelial morphogenesis is poorly understood. Here we demonstrate that embryoid bodies (EBs) differentiated from talin1-null embryonic stem cells are defective in integrin adhesion complex assembly, epiblast elongation, and lineage differentiation. These defects are accompanied by a significant reduction in integrin ß1 protein levels due to accelerated degradation through an MG-132-sensitive proteasomal pathway. Overexpression of integrin ß1 or MG-132 treatment in mutant EBs largely rescues the phenotype. In addition, epiblast cells isolated from talin1-null EBs exhibit impaired cell spreading and focal adhesion formation. Transfection of the mutant cells with green fluorescent protein (GFP)-tagged wild-type but not mutant talin1 that is defective in integrin binding normalizes integrin ß1 protein levels and restores focal adhesion formation. Significantly, cell adhesion and spreading are also improved by overexpression of integrin ß1. All together, these results suggest that talin1 binding to integrin promotes epiblast adhesion and morphogenesis in part by preventing integrin ß1 degradation.
Assuntos
Integrinas/metabolismo , Morfogênese , Talina/fisiologia , Animais , Adesão Celular , Células Cultivadas , Corpos Embrioides , Células-Tronco Embrionárias , Epitélio/embriologia , Adesões Focais , Integrina beta1/genética , Integrina beta1/metabolismo , Camundongos , Estabilidade ProteicaRESUMO
OBJECTIVES: Catheter-based revascularization has emerged as an alternative to surgical bypass for the tibioperoneal vessels. The purpose of this analysis was to describe the outcomes of tibial angioplasty interventions for critical limb ischemia (CLI) in the hospitalized Medicare population, to examine in-hospital complications, to define the 30-day readmission and mortality rates, and to assess secondary procedures performed in this population. METHODS: In-patients with CLI undergoing tibioperoneal angioplasty were identified using The Centers for Medicare & Medicaid Services in-patient claims for 2005 to 2007. In-hospital complications, mortality, 30-day secondary procedures, and 30-day rehospitalization after discharge were described. RESULTS: A total of 13,258 in-patients underwent tibioperoneal angioplasty (54.2% men; 75.7% white, 17.1% African American; 42.8% gangrene, 46.7% rest pain, 10.5% claudication) and 29.3% had a stent, 47.3% had femoral-popliteal angioplasty, and 20.1% had atherectomy during their initial procedure. Initial hospital complications included renal complications (8.1%), respiratory complications and pneumonia (5.1%), and cardiac complications with acute myocardial infarction (3.2%). Mortality in-hospital was 2.8% and at 30 days was 6.7%. Thirty-day rehospitalization rate was 29.6%. Thirty-day reinterventions included repeat angiogram (8.5%), repeat tibioperoneal angioplasty (3.2%), open bypass (2.1%), and lower extremity amputations (23.8%). Gangrene was the most frequent diagnosis at rehospitalization (13.5%). Patients with gangrene as an indication for tibioperoneal angioplasty were 1.8 times (95% confidence interval [CI], 1.56-2.10) as likely as patients with rest pain to be rehospitalized during 30 days after discharge. Among comorbidities, predictors of 30-day rehospitalization included chronic renal failure (odds ratio [OR], 1.4; 95% CI, 1.27-1.52), chronic pulmonary disease (OR, 1.1; 95% CI, 1.01-1.25), and congestive heart failure (CHF; OR, 1.1; 95% CI, 1.01-1.22). About one-quarter of patients (23.8%) within 30 days after their initial procedure underwent amputation at any level of the lower limb. CONCLUSION: Tibioperoneal angioplasty is associated with frequent in-hospital complications, an overall 30-day amputation rate of 23.8% for all procedures and indications, and a 30-day rehospitalization rate of almost 30%. Further detailed analysis of tibioperoneal intervention is essential to define best treatment strategies and to minimize complications and readmission rates.
Assuntos
Angioplastia , Isquemia/terapia , Extremidade Inferior/irrigação sanguínea , Medicare , Artérias da Tíbia , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Angioplastia/efeitos adversos , Angioplastia/instrumentação , Angioplastia/mortalidade , Distribuição de Qui-Quadrado , Estado Terminal , Feminino , Humanos , Isquemia/mortalidade , Isquemia/cirurgia , Salvamento de Membro , Modelos Logísticos , Masculino , Razão de Chances , Readmissão do Paciente , Retratamento , Medição de Risco , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
Acute radiation syndrome or radiation sickness is a serious illness that occurs after the body receives a high dose of radiation, typically over a short period of time. This condition may be underrecognized by interventionalists and must be considered whenever performing complex endovascular procedures.
Assuntos
Síndrome Aguda da Radiação/etiologia , Aneurisma da Aorta Abdominal/cirurgia , Aortografia/efeitos adversos , Implante de Prótese Vascular , Procedimentos Endovasculares , Radiografia Intervencionista/efeitos adversos , Idoso , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Fluoroscopia , Humanos , Masculino , Doses de Radiação , Radiodermite/etiologia , Medição de RiscoRESUMO
Thoracic endovascular aortic repair (TEVAR) has evolved as a treatment option for the management of thoracic aortic trauma as an alternative to open thoracic aortic repair (OTAR). Population-level outcomes are not known and were evaluated. Secondary data analysis of the 2005-2006 Nationwide Inpatient Sample data was performed, and 1,561 patients with thoracic aortic injury (mean age 44.8 +/- 18.8 years; men 77.2%) were identified. Of these, 510 underwent emergent surgical intervention: 240 OTAR (47%) and 270 TEVAR (53%). Males were more likely to undergo any surgery (77.2% vs 22.8%; p = .03). Hospital mortality after OTAR was greater compared to TEVAR (14.61% vs 7.43%; p = .009). OTAR patients were more likely to have pulmonary complications (37.8% vs 21.65; p < .0001) but were less likely to have stroke (2.1% vs 5.8%; p = .03) compared to TEVAR patients. After adjustment, OTAR patients remained more likely to die compared to TEVAR patients (OR 11.5; 95% CI 4.0-33.2). Hospital length of stay and hospital cost were significantly greater for OTAR than for TEVAR. An increase in patients with thoracic aortic injury undergoing repair was found (23.0% vs 40.3%; p < .0002). In trauma, TEVAR was associated with decreased hospital mortality, hospital use, and pulmonary complications but increased rates of stroke. Further implementation of TEVAR for management of thoracic aortic trauma may improve future outcomes and reduce hospital resource use.
Assuntos
Aorta Torácica/cirurgia , Procedimentos Endovasculares/economia , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Custos Hospitalares , Avaliação de Processos e Resultados em Cuidados de Saúde/economia , Procedimentos Cirúrgicos Vasculares/economia , Ferimentos e Lesões/cirurgia , Adolescente , Adulto , Idoso , Aorta Torácica/lesões , Distribuição de Qui-Quadrado , Bases de Dados como Assunto , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Pacientes Internados , Tempo de Internação/economia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Estados Unidos , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidade , Ferimentos e Lesões/economia , Ferimentos e Lesões/mortalidade , Adulto JovemRESUMO
OBJECTIVES: To evaluate the incidence of postoperative sepsis after elective procedures, to define surgical procedures with the greatest risk for developing sepsis, and to evaluate patient and hospital confounders. BACKGROUND DATA: The development of sepsis after elective surgical procedures imposes a significant clinical and resource utilization burden in the United States. We evaluated the development of sepsis after elective procedures in a nationally representative patient cohort and assessed the effect of sociodemographic and hospital characteristics on the development of postoperative sepsis. METHODS: The Nationwide inpatient sample was queried between 2002 and 2006 and patients developing sepsis after elective procedures were identified using the patient safety indicator "Postoperative Sepsis" (PSI-13). Case-mix adjusted rates were calculated by using a multivariate logistic regression model for sepsis risk and an indirect standardization method. RESULTS: A total of 6,512,921 weighted elective surgical cases met the inclusion criteria and 78,669 cases (1.21%) developed postoperative sepsis. Case-mix adjustment for age, race, gender, hospital bed size, hospital location, hospital teaching status, and patient income demonstrated esophageal, pancreatic, and gastric procedures represented the greatest risk for the development of postoperative sepsis. Thoracic, adrenal, and hepatic operations accounted for the greatest mortality rates if sepsis developed. Increasing age, Blacks, Hispanics, and men were more likely to develop sepsis. Decreased median household income, larger hospital bed size, urban hospital location, and nonteaching status were associated with greater rates of postoperative sepsis. CONCLUSIONS: The development of postoperative sepsis is multifactorial and procedures, most likely to develop sepsis, did not demonstrate the greatest mortality after sepsis developed. Factors associated with the development of sepsis included race, age, hospital size, hospital location, and patient income. Further evaluation of high-risk procedures, populations, and environments may assist in reducing this costly complication.
Assuntos
Procedimentos Cirúrgicos Eletivos/efeitos adversos , Sepse/epidemiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sepse/etiologia , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Iliac artery tortuosity can be a limiting factor in treating abdominal aortic aneurysms by endovascular means. In this case, a 6F catheter guiding sheath was used to allow tracking of the superstiff wire to straighten the iliac artery on the left. This allowed for tracking of the larger sheath so that a bifurcated device could be completed. This technique may be useful in dealing with extreme iliac tortuosity if one is unable to advance the superstiff wire.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Artéria Ilíaca/patologia , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aortografia/métodos , Humanos , Artéria Ilíaca/diagnóstico por imagem , Masculino , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
During murine peri-implantation development, the egg cylinder forms from a solid cell mass by the apoptotic removal of inner cells that do not contact the basement membrane (BM) and the selective survival of the epiblast epithelium, which does. The signaling pathways that mediate this fundamental biological process are largely unknown. Here we demonstrate that Rac1 ablation in embryonic stem cell-derived embryoid bodies (EBs) leads to massive apoptosis of epiblast cells in contact with the BM. Expression of wild-type Rac1 in the mutant EBs rescues the BM-contacting epiblast, while expression of a constitutively active Rac1 additionally blocks the apoptosis of inner cells and cavitation, indicating that the spatially regulated activation of Rac1 is required for epithelial cyst formation. We further show that Rac1 is activated through integrin-mediated recruitment of the Crk-DOCK180 complex and mediates BM-dependent epiblast survival through activating the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway. Our results reveal a signaling cascade triggered by cell-BM interactions essential for epithelial morphogenesis.
Assuntos
Membrana Basal/metabolismo , Camadas Germinativas/citologia , Camadas Germinativas/metabolismo , Neuropeptídeos/metabolismo , Proteínas rac de Ligação ao GTP/metabolismo , Animais , Apoptose/fisiologia , Linhagem Celular , Sobrevivência Celular/fisiologia , Desenvolvimento Embrionário/fisiologia , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Epitélio/embriologia , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Integrina beta1/metabolismo , Camundongos , Neuropeptídeos/deficiência , Neuropeptídeos/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-crk/genética , Proteínas Proto-Oncogênicas c-crk/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transdução de Sinais , Proteínas rac de Ligação ao GTP/deficiência , Proteínas rac de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTPRESUMO
OBJECTIVE: This study was conducted to evaluate and compare the rates of postoperative infectious complications and death after elective vascular surgery, define vascular procedures with the greatest risk of developing nosocomial infections, and assess the effect of infection on health care resource utilization. METHODS: The Nationwide Inpatient Sample (2002-2006) was used to identify major vascular procedures by International Classification of Diseases, 9th Clinical Modification (ICD-9-CM) codes. Infectious complications identified included pneumonia, urinary tract infections (UTI), postoperative sepsis, and surgical site infections (SSI). Case-mix-adjusted rates were calculated using a multivariate logistic regression model for infectious complication or death as an outcome and indirect standardization. RESULTS: A total of 870,778 elective vascular surgical procedures were estimated and evaluated with an overall postoperative infection rate of 3.70%. Open abdominal aortic surgery had the greatest rate of postoperative infections, followed by open thoracic procedures and aorta-iliac-femoral bypass. Thoracic endovascular aneurysm repair (TEVAR) infectious complication rates were two times greater than after EVAR (P < .0001). Pneumonia was the most common infectious complication after open aortic surgery (6.63%). UTI was the most common after TEVAR (2.86%) and EVAR (1.31%). Infectious complications were greater in octogenarians (P < .0002), women (P < .0001), and blacks (P < .0001 vs whites and Hispanics). Nosocomial infections after elective vascular surgery significantly increased hospital length of stay (13.8 +/- 15.4 vs 3.5 +/- 4.2 days; P < .001) and reported total hospital cost ($37,834 +/- $42,905 vs $11,851 +/- $11,816; P < .001). CONCLUSIONS: Elective vascular surgical procedures vary widely in the estimated risk of postoperative infection. Open aortic surgery and endarterectomy of the head and neck vessels have, respectively, the greatest and the lowest reported incidence for postoperative infectious complications. Women, octogenarians, and blacks have the highest risk of infectious complications after elective vascular surgery. Disparities in the development of infectious complications on a systems level were also found in larger hospitals and teaching hospitals. Hospital infectious complications were found to significantly increase health care resource utilization. Strategies that reduce nosocomial complications and target high-risk procedures may offer significant future cost savings.
Assuntos
Infecção Hospitalar/etiologia , Infecção da Ferida Cirúrgica/etiologia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Adolescente , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Redução de Custos , Análise Custo-Benefício , Infecção Hospitalar/economia , Infecção Hospitalar/etnologia , Infecção Hospitalar/mortalidade , Infecção Hospitalar/prevenção & controle , Bases de Dados como Assunto , Procedimentos Cirúrgicos Eletivos , Feminino , Custos de Cuidados de Saúde , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde , Hispânico ou Latino/estatística & dados numéricos , Humanos , Controle de Infecções/economia , Tempo de Internação/economia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Medição de Risco , Fatores de Risco , Fatores Sexuais , Infecção da Ferida Cirúrgica/economia , Infecção da Ferida Cirúrgica/etnologia , Infecção da Ferida Cirúrgica/mortalidade , Infecção da Ferida Cirúrgica/prevenção & controle , Resultado do Tratamento , Estados Unidos/epidemiologia , Procedimentos Cirúrgicos Vasculares/economia , Procedimentos Cirúrgicos Vasculares/mortalidade , População Branca/estatística & dados numéricos , Adulto JovemRESUMO
OBJECTIVES: To assess national outcomes of carotid artery stenting (CAS) with respect to hospital and practitioner volume. METHODS: The 2005 to 2006 Nationwide Inpatient Sample (NIS) was used to assess CAS with respect to hospital volume, physician volume, and associated complications. RESULTS: Eighteen thousand five hundred ninety-nine CAS interventions were identified. The top 25% was used to define high-volume hospitals (>60 CAS/2 years) and practitioners (>30 CAS/2 years). The stroke rate after CAS was significantly different between low- and high-volume hospitals (2.35% vs 1.78%, respectively; P = .0206). The stroke rate after CAS was also significantly different between low- and high-volume practitioners (2.19% vs 1.51%, P = .0243). Hospital resource use varied significantly between low- and high-volume hospitals (length of stay [LOS]: 1.64 +/- 2.10 vs 1.45 +/- 11.21, P = .0006; total charges: $32 261 +/- 20 562 vs $30 131 +/- 19 592, P = .0047) and practitioners (LOS: 1.70 +/- 2.14 vs 1.36 +/- 1.36; P < .0001; total charges: $33 762 +/- 21 081 vs $23 957 +/- 19 713; P < .0001). CONCLUSIONS: This analysis demonstrates that hospital and physician volume are associated with outcomes and utilization after CAS. High-volume hospitals and practitioners were associated with lower procedure stroke rates and decreased hospital resource utilization.
Assuntos
Angioplastia/instrumentação , Doenças das Artérias Carótidas/terapia , Competência Clínica , Hospitais , Avaliação de Processos e Resultados em Cuidados de Saúde , Stents , Idoso , Idoso de 80 Anos ou mais , Angioplastia/efeitos adversos , Angioplastia/economia , Angioplastia/estatística & dados numéricos , Doenças das Artérias Carótidas/economia , Doenças das Artérias Carótidas/epidemiologia , Competência Clínica/estatística & dados numéricos , Feminino , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Custos Hospitalares , Hospitais/estatística & dados numéricos , Humanos , Tempo de Internação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Avaliação de Processos e Resultados em Cuidados de Saúde/estatística & dados numéricos , Medição de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
Isolated dissection of the origin of both celiac and superior mesenteric arteries is a rare vascular pathology with limited management guidelines. The presentation is generally nonspecific, most often manifesting with epigastric pain radiating to the back. A high diagnostic index of suspicion and stepwise management are essential for a successful outcome. This case report details the clinical course of a 57-year-male who presented with a 2-week history of epigastric discomfort with back pain and was found to have focal celiac artery dissection with aneurysmal dilation of 1.2 cm. His vital signs were stable, and the physical examination was unremarkable. At this time, he was placed on antiplatelet medication and was scheduled for endovascular repair of his celiac aneurysm with a covered stent graft. Two weeks later, recurrent abdominal pain prompted a repeat computed tomographic scan that revealed sequential superior mesenteric artery (SMA) dissection. The patient was admitted and anticoagulated. A complete workup ruled out underlying collagen vascular and autoimmune pathology. He remained stable, with significant symptomatic improvement. After 6 months, anticoagulation was discontinued and antiplatelet therapy was instituted for long-term management. Subsequent operative or endovascular intervention was not required. The patient was continuing to do well on his 18-month clinical follow-up. There are 71 cases of SMA and 12 cases of celiac artery dissection in the literature. This report outlines this rare presentation of isolated, proximal sequential celiac artery and SMA dissection. This case illustrates that conservative management may be warranted in uncomplicated, isolated visceral arterial dissection.
Assuntos
Anticoagulantes/administração & dosagem , Dissecção Aórtica/tratamento farmacológico , Artéria Celíaca , Artéria Mesentérica Superior , Inibidores da Agregação Plaquetária/administração & dosagem , Dor Abdominal/etiologia , Dissecção Aórtica/complicações , Dissecção Aórtica/diagnóstico , Dor nas Costas/etiologia , Artéria Celíaca/diagnóstico por imagem , Esquema de Medicação , Humanos , Masculino , Artéria Mesentérica Superior/diagnóstico por imagem , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Resultado do Tratamento , UltrassonografiaRESUMO
OBJECTIVES: Lower extremity percutaneous transluminal angioplasty (LE PTA) is currently performed by a variety of endovascular specialists. We hypothesized that cardiologists (CRD) and vascular surgeons (VAS) may have different practice patterns, indications for intervention, and hospital resource utilization. METHODS: Using the State Inpatient Databases for New Jersey (2003-2007), patients with elective admission undergoing PTA procedures with indications of claudication, rest pain, and gangrene/ulceration were examined. Physician specialty was determined based on all procedures performed. We contrasted by specialty, the indication for LE PTA for the procedure, volume, and hospital resource utilization. RESULTS: Of the 1887 cases of LE PTA, VAS performed 866 (45.9%) and CRD 1021 (54.1%) procedures. The mean patient age was 68.0 years (CRD) vs 70.7 years (VAS), P = .0163. Indications for intervention were compared for CRD vs VAS: claudication 80.7% vs 60.7%, (P < .002); rest pain 6.2% vs 16.0%, (P < .002); gangrene/ulceration 13.1% vs 23.3%, (P < .002). Stents (64.8% of cases) were utilized similarly among physicians (P = .18), and mean hospital length of stay were similar (2.38 days vs 2.41 days, P = .85). Hospital charges by indication varied between CRD vs VAS (all procedures: $49,748 vs $42,158 [P < .0001]). Revenue center charges were different between CRD vs VAS: medical surgical supply $19,128 vs $12,737, (P < .0001); pharmacy $1,959 vs $1,115, (P < .0001). Only 10.7% of CRD were high volume practitioners, compared with 36.8% among VAS (P < .05). High volume practitioners had significantly lower hospital charges ($41,730 vs $51,014, P < .001). CONCLUSIONS: Cardiologists performing lower extremity angioplasty were more likely to treat patients with claudication than those with rest pain or gangrene/ulceration. Despite treating younger patients with less severe peripheral vascular disease, cardiologists used significantly greater hospital resources. High practitioner volume, regardless of specialty, was associated with lower hospital resource utilization. Reducing variations in indication and practitioner volume may offer substantial cost savings for lower extremity endovascular interventions.
Assuntos
Angioplastia com Balão/estatística & dados numéricos , Cardiologia , Recursos em Saúde/estatística & dados numéricos , Claudicação Intermitente/terapia , Extremidade Inferior/irrigação sanguínea , Avaliação de Processos e Resultados em Cuidados de Saúde , Doenças Vasculares Periféricas/terapia , Padrões de Prática Médica , Procedimentos Cirúrgicos Vasculares , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Angioplastia com Balão/economia , Cardiologia/economia , Competência Clínica , Redução de Custos , Bases de Dados como Assunto , Feminino , Gangrena , Recursos em Saúde/economia , Custos Hospitalares , Humanos , Claudicação Intermitente/economia , Claudicação Intermitente/etiologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , New Jersey , Razão de Chances , Seleção de Pacientes , Doenças Vasculares Periféricas/complicações , Doenças Vasculares Periféricas/economia , Padrões de Prática Médica/economia , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/economia , Adulto JovemRESUMO
BACKGROUND: There has been a dramatic increase in the use of endovascular technology for treatment of abdominal aortic aneurysms (AAA), but practice patterns have not been well-evaluated. Hospital resource use and outcomes after elective endovascular abdominal aortic repair (EVAR) and open surgical repair were assessed by hospital type, ie, major teaching (MT), teaching affiliate, and nonteaching (NT). STUDY DESIGN: Elective, nonruptured AAA repairs were identified in the State Inpatient Databases for New Jersey (2001 to 2006). Descriptive statistics, univariate, multivariable, trend, and case-mix-adjustment analyses were employed. RESULTS: A total of 6,227 subjects were identified; 4,698 patients (mean age 73.0 +/- 8.01 years; 79.2% men) underwent elective repair of AAA. EVAR was performed 2.6 times more often in MT compared with NT (p < 0.0001) institutions. Univariate evaluation demonstrated that women had a predominance of EVAR performed (p < 0 .0002) in MT hospitals and that minorities in NT hospitals were more likely to be treated with open operations (p = 0.0148). Case-mix-adjusted mortality rates for EVAR were higher at NT (1.95%; 95% CI, 1.81 to 2.09) compared with MT (0.73%; 95% CI, 0.69 to 0.77) hospitals. After adjustment, MT hospitals were more likely to use EVAR (odds ratio = 2.4; 95% CI, 2.11 to 2.83) and less likely to have increased length of stay (odds ratio = 0.38; 95% CI, 0.32 to 0.44) compared with NT. CONCLUSIONS: Hospital teaching status was significantly associated with repair type, overall mortality, and hospital resource use. MT hospitals were considerably more likely to use EVAR for elective AAA repair, offered an improvement in survival, were more likely to treat women and minorities with EVAR, and demonstrated decreased length of stay and cost.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Cirúrgicos Eletivos/normas , Hospitais de Ensino , Idoso , Competência Clínica , Grupos Diagnósticos Relacionados , Feminino , Hospitais , Humanos , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , New Jersey , Complicações Pós-Operatórias , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the impact of carotid reconstruction (REC) and pre-operative embolization (EMB) for Carotid Body Tumor (CBT) surgery. METHODS: Retrospective study utilizing the Nationwide Inpatient Sample (2002-2006). RESULTS: 2117 patients (mean age 56.5 +/- 17.2 years) underwent CBT surgery: 1686 excision alone (EX); 129 excision with embolization (EX+EMB); and 302 excision with carotid artery reconstruction (EX+REC). EX+REC compared to EX had greater rates of mortality (1.61%vs.0.59%; P =.0495), stroke (17.7% vs. 3.5%; P < .0002), and postoperative hemorrhage (43.1% vs. 2.4%; P < 0.002). EX+EMB did not demonstrate increased mortality or stroke compared to EX and the rate of postoperative hematoma was similar between groups (P = .3144). CONCLUSIONS: CBT resection is a relatively rare procedure and when combined with EMB was more expensive, but was associated with significantly fewer complications and decreased blood product utilization. These data suggest that CBT surgery requiring carotid reconstruction carries significant morbidity and that EMB as an adjunctive tool was beneficial for CBT surgery outcomes.