RESUMEN
BACKGROUND: Clostridium difficile infection (CDI) is an increasing nosocomial problem. New, more-virulent strains of C. difficile have spread across North America and Europe. Health care institutions now face a greater incidence of disease, often with greater severity. A need for surgical management for control of infection is on the increase. The clinical appearance of CDI is changed. METHODS: We report four unusual and severe cases of CDI in surgical patients with a review of the relevant literature. RESULTS: One patient developed CDI and required a colectomy for a perforated viscus. He developed C. difficile ileitis 12 days later that responded to medical therapy. Another patient who underwent a colectomy for infrarenal aortic occlusion, later in his hospital course, developed C. difficile ileitis and died. The third patient was hospitalized for several months for hypertension and associated morbidities. Eventually he developed severe abdominal pain and was found to have a small bowel mural abscess that grew C. difficile on culture. A fourth patient, taking long-term antibiotics for a surgical site infection of the knee, developed unexplained leukocytosis without diarrhea. Colonoscopy revealed pseudomembranous colitis that advanced to toxic megacolon. She required a colectomy and ultimately died from the disease. CONCLUSIONS: Patients are at high risk from CDI in this modern era. Disease manifestations may differ from the typical presentation. A heightened awareness for diagnosing this dangerous, evolving disease is paramount.
Asunto(s)
Clostridioides difficile/aislamiento & purificación , Infección Hospitalaria/patología , Enterocolitis Seudomembranosa/patología , Complicaciones Posoperatorias/patología , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Colectomía , Infección Hospitalaria/microbiología , Infección Hospitalaria/cirugía , Enterocolitis Seudomembranosa/microbiología , Enterocolitis Seudomembranosa/cirugía , Europa (Continente) , Resultado Fatal , Femenino , Humanos , Masculino , Persona de Mediana Edad , América del Norte , Complicaciones Posoperatorias/microbiología , Complicaciones Posoperatorias/cirugíaRESUMEN
OBJECTIVE: Older patients are thought to tolerate acute ischemia more poorly than younger patients. Since aging may depress both angiogenesis and arteriogenesis, we determined the effects of age on both angiogenesis and arteriogenesis in a model of severe acute limb ischemia. METHODS: Young adult (3-months-old) and aged (18-months-old) C57BL/6 mice underwent right common iliac artery and vein ligation and transection. Data were collected on days 0, 7, and 14. Perfusion was measured with a laser Doppler scan and compared to the contralateral limb. Functional deficits were evaluated with the Tarlov scale. Capillary density and endothelial progenitor cell (EPC) number were determined by direct counting lectin-positive/alpha-actin-negative cells and VEGFR2/CXCR4 dually-positive cells, respectively; angiography was performed to directly assess arteriogenesis. RESULTS: Young adult and aged mice had a similar degree of decreased perfusion after iliac ligation (young, n = 15: 20.4 +/- 1.9%, vs aged, n = 20: 19.6 +/- 1.3%; P = .72, analysis of variance [ANOVA]); however, young mice recovered faster and to a greater degree than aged mice (day 7, 35 +/- 6% vs 17 +/- 4%, P = .046; day 14, 60 +/- 5% vs 27 +/- 7%, P = .0014). Aged mice had worse functional recovery by day 14 compared to young mice (2.3 +/- 0.3 vs 4.3 +/- 0.4; P = .0021). Aged mice had increased capillary density (day 7, 12.9 +/- 4.4 vs 2.8 +/- 0.3 capillaries/hpf; P = .02) and increased number of EPC incorporated into the ischemic muscle (day 7, 8.1 +/- 0.9 vs 2.5 +/- 1.9 cells; P = .007) compared to young mice, but diminished numbers of collateral vessels to the ischemic limb (1 vs 9; P = .01), as seen on angiography. CONCLUSION: After severe hind limb ischemia, aged animals become ischemic to a similar degree as young animals, but aged animals have significantly impaired arteriogenesis and functional recovery compared to younger animals. These results suggest that strategies to stimulate arteriogenesis may complement those that increase angiogenesis, and may result in improved relief of ischemia.
Asunto(s)
Isquemia/fisiopatología , Músculo Esquelético/irrigación sanguínea , Neovascularización Fisiológica , Enfermedad Aguda , Factores de Edad , Animales , Arterias/fisiopatología , Velocidad del Flujo Sanguíneo , Capilares/fisiopatología , Circulación Colateral , Modelos Animales de Enfermedad , Células Endoteliales/patología , Miembro Posterior , Arteria Ilíaca/cirugía , Vena Ilíaca/cirugía , Isquemia/patología , Flujometría por Láser-Doppler , Ligadura , Masculino , Ratones , Ratones Endogámicos C57BL , Microcirculación , Recuperación de la Función , Flujo Sanguíneo Regional , Índice de Severidad de la Enfermedad , Células Madre/patología , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
Vascular smooth muscle cells (SMC) may be directly exposed to blood flow after an endothelial-denuding injury. It is not known whether direct exposure of SMC to shear stress reduces SMC turnover and contributes to the low rate of restenosis after most vascular interventions. This study examines if laminar shear stress inhibits SMC proliferation or stimulates apoptosis. Bovine aortic SMC were exposed to arterial magnitudes of laminar shear stress (11 dynes/cm(2)) for up to 24 h and compared to control SMC (0 dynes/cm(2)). SMC density was assessed by cell counting, DNA synthesis by (3)[H]-thymidine incorporation, and apoptosis by TUNEL staining. Akt, caspase, bax, and bcl-2 phosphorylation were assessed by Western blotting; caspase activity was also measured with an in vitro assay. Analysis of variance was used to compare groups. SMC exposed to laminar shear stress had a 38% decrease in cell number (n = 4, P = 0.03), 54% reduction in (3)[H]-thymidine incorporation (n = 3, P = 0.003), and 15-fold increase in TUNEL staining (n = 4, P < 0.0001). Akt phosphorylation was reduced by 67% (n = 3, P < 0.0001), whereas bax/bcl-2 phosphorylation was increased by 1.8-fold (n = 3, P = 0.01). Caspase-3 activity was increased threefold (n = 5, P = 0.03). Pretreatment of cells with ZVAD-fmk or wortmannin resulted in 42% increased cell retention (n = 3, P < 0.01) and a fourfold increase in apoptosis (n = 3, P < 0.04), respectively. Cells transduced with constitutively-active Akt had twofold decreased apoptosis (n = 3, P < 0.002). SMC exposed to laminar shear stress have decreased proliferation and increased apoptosis, mediated by the Akt pathway. These results suggest that augmentation of SMC apoptosis may be an alternative strategy to inhibit restenosis after vascular injury.
Asunto(s)
Apoptosis/fisiología , Músculo Liso Vascular/citología , Miocitos del Músculo Liso/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/fisiología , Animales , Bovinos , Proliferación Celular , Células Cultivadas , Hemodinámica , Humanos , Etiquetado Corte-Fin in Situ , Miocitos del Músculo Liso/citología , Proteínas Proto-Oncogénicas c-akt/genética , Resistencia al Corte , Estrés MecánicoRESUMEN
BACKGROUND/AIMS: Age-associated changes in endothelial nitric oxide synthase (eNOS) expression have not been definitively linked to the pathophysiology of aortic aneurysms. We examined the role of eNOS in human patients and an age-appropriate mouse model. METHODS: eNOS transcripts and immunodetectable protein were assessed by quantitative PCR and immunohistochemistry in human ascending thoracic aneurysms (n = 29) and referent aortae (n = 31). Carotid aneurysms were induced with CaCl2 in young adult (3 months) and aged (18 months) C57BL/6 and eNOS-knockout (eNOS-KO) mice. RESULTS: eNOS transcripts and protein were reduced in human aneurysms compared with controls, although aortic eNOS expression also decreased with patient age. Aged wild-type mice had significantly larger aneurysm diameter than young adult mice. Aged wild-type mice had reduced eNOS transcripts and protein compared with young adult mice. Aged eNOS-KO mice had smaller aneurysms compared with aged wild-type mice but similar size aneurysms compared with young eNOS-KO and young wild-type mice. CONCLUSION: eNOS expression is reduced in both aged human and aged mouse endothelium and eNOS expression is linked to aneurysm expansion in aged but not young adult mice. These findings support the relevance of age-associated changes in eNOS expression in clinical aneurysmal disease.
Asunto(s)
Envejecimiento/metabolismo , Enfermedades de las Arterias Carótidas/etiología , Aneurisma Intracraneal/etiología , Óxido Nítrico Sintasa de Tipo III/metabolismo , Adulto , Animales , Aorta/enzimología , Aorta/metabolismo , Aneurisma de la Aorta/enzimología , Enfermedades de las Arterias Carótidas/enzimología , Enfermedades de las Arterias Carótidas/patología , Enfermedades de las Arterias Carótidas/fisiopatología , Progresión de la Enfermedad , Humanos , Aneurisma Intracraneal/enzimología , Aneurisma Intracraneal/patología , Aneurisma Intracraneal/fisiopatología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Óxido Nítrico Sintasa de Tipo III/deficiencia , Óxido Nítrico Sintasa de Tipo III/genética , ARN Mensajero/metabolismoRESUMEN
Vascular smooth muscle cells exhibit varied responses after vessel injury and surgical interventions, including phenotypic switching, migration, proliferation, protein synthesis, and apoptosis. Although the source of the smooth muscle cells that accumulate in the vascular wall is controversial, possibly reflecting migration from the adventitia, from the circulating blood, or in situ differentiation, the intracellular signal transduction pathways that control these processes are being defined. Some of these pathways include the Ras-mitogen-activated protein kinase, phosphatidylinositol 3-kinase-Akt, Rho, death receptor-caspase, and nitric oxide pathways. Signal transduction pathways provide amplification, redundancy, and control points within the cell and culminate in biologic responses. We review some of the signaling pathways activated within smooth muscle cells that contribute to smooth muscle cell heterogeneity and development of pathology such as restenosis and neointimal hyperplasia.
Asunto(s)
Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Transducción de Señal , Procedimientos Quirúrgicos Vasculares , Animales , Apoptosis , Células de la Médula Ósea/metabolismo , Diferenciación Celular , Movimiento Celular , Proliferación Celular , Constricción Patológica/metabolismo , Constricción Patológica/patología , Matriz Extracelular/metabolismo , Humanos , Hiperplasia/metabolismo , Hiperplasia/patología , Músculo Liso Vascular/lesiones , Músculo Liso Vascular/patología , Músculo Liso Vascular/fisiopatología , Músculo Liso Vascular/cirugía , Miocitos del Músculo Liso/patología , Fenotipo , Proteínas Quinasas/metabolismo , Células Madre/metabolismo , Procedimientos Quirúrgicos Vasculares/efectos adversosRESUMEN
OBJECTIVES: Ephrin ligands and Eph receptors are signaling molecules that are differentially expressed on arteries and veins during development. We examined whether Eph-B4, a venous marker, and Ephrin-B2, an arterial marker, are regulated during vein graft adaptation in humans and aged rats. METHODS AND RESULTS: Eph-B4 transcripts and immunodetectable protein are downregulated in endothelial and smooth muscle cells of patent vein grafts in both humans and in aged rats, whereas Ephrin-B2 transcripts and protein are not strongly induced. Other markers of arterial identity, including dll4 and notch-4, are also not induced during vein graft adaptation in aged rats. Because VEGF-A is upstream of the Ephrin-Eph pathway, and expression of VEGF-A is induced only at early time points after exposure of the vein to the arterial environment, we inhibited VEGF-A in vein grafts using an siRNA-based approach. Vein grafts treated with siRNA directed against VEGF-A demonstrated a thicker intima-media containing alpha-actin, consistent with arterialization, but did not contain Eph-B4 or Ephrin-B2. CONCLUSIONS: Venous identity is preserved in the veins of aged animals, but is lost during adaptation to the arterial circulation; arterial markers are not induced. Markers of vessel identity are plastic in adults and their selective regulation may mediate vein graft adaptation to the arterial environment in aged animals and humans.
Asunto(s)
Adaptación Fisiológica/fisiología , Arterias Carótidas/trasplante , Efrina-B2/metabolismo , Receptor EphA4/metabolismo , Vena Safena/trasplante , Factores de Edad , Anastomosis Quirúrgica , Animales , Biomarcadores/análisis , Arterias Carótidas/patología , Modelos Animales de Enfermedad , Efrina-B2/análisis , Femenino , Técnica del Anticuerpo Fluorescente , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Inmunohistoquímica , Masculino , Neovascularización Fisiológica , Probabilidad , Ratas , Ratas Endogámicas F344 , Receptor EphA4/análisis , Factores de Riesgo , Vena Safena/patología , Sensibilidad y Especificidad , Procedimientos Quirúrgicos Vasculares/métodosRESUMEN
Both neointimal hyperplasia and inward remodeling contribute to restenosis and lumen loss. Nogo-B has been recently described as an inhibitor of vascular injury and neointimal hyperplasia. To determine whether Nogo-B expression may be a mediator of inward remodeling, we examine the localization of expression of Nogo-B in an in vivo model that examines both neointimal hyperplasia and inward remodeling. The rabbit carotid artery was subjected to balloon injury, outflow branch ligation to reduce flow, or both balloon injury and reduction in flow. In balloon injury-induced neointimal hyperplasia Nogo-B expression was reduced in the intima and media but stimulated in the adventitia. In low flow-induced inward remodeling medial Nogo-B expression was not reduced and adventitial Nogo-B expression was not stimulated. Low flow significantly augmented balloon injury-induced neointimal hyperplasia and was accompanied by reduced intimal and medial Nogo-B expression, and increased adventitial Nogo-B expression in both smooth muscle cells and macrophages. Low flow-induced inward remodeling is not associated with changes in medial Nogo-B expression and is distinct from injury-induced neointimal hyperplasia. Pharmacological strategies to inhibit neointimal hyperplasia and restenosis using normal flow models may only partially account for lumen loss and therefore may not accurately predict responses in patients with extensive outflow disease.
Asunto(s)
Arterias Carótidas/patología , Estenosis Carotídea/patología , Proteínas de la Mielina/análisis , Túnica Íntima/patología , Túnica Media/patología , Animales , Apoptosis , Biomarcadores/análisis , Velocidad del Flujo Sanguíneo , Arterias Carótidas/química , Arterias Carótidas/fisiopatología , Arterias Carótidas/cirugía , Estenosis Carotídea/metabolismo , Estenosis Carotídea/fisiopatología , Cateterismo , Proliferación Celular , Tejido Conectivo/metabolismo , Tejido Conectivo/patología , Modelos Animales de Enfermedad , Hiperplasia , Ligadura , Masculino , Proteínas Nogo , Conejos , Estrés Mecánico , Resistencia a la Tracción , Túnica Íntima/química , Túnica Media/químicaRESUMEN
BACKGROUND: The deleterious effects of perioperative malnutrition on recovery after general surgery are established. Since the effects of perioperative malnutrition on recovery after vascular surgery are not known, we examined the effects of nutritional status, and risk factors predictive of malnutrition, on outcome after vascular surgery. METHODS: The records of all open index vascular cases (abdominal aortic aneurysm [AAA] repair, carotid endarterectomy [CEA], lower extremity bypass) performed at the Veterans Affairs (VA) Connecticut between July 2004 and June 2005 were reviewed. The primary outcome was mortality; secondary outcomes included infection and nutritional risk index (NRI) scores. RESULTS: Sixty-eight open vascular cases were performed during the study period. Nutritional depletion developed in 55% of patients and was more likely in patients undergoing AAA (85%) or bypass (77%) than CEA (30%; P = .0005). Patients who developed malnutrition had similar mortality as patients who did not develop postoperative malnutrition (6.1% vs. 3.7%; P = .68); however, malnourished patients had higher rates of postoperative infection (24.2% vs. 3.7%; P = .03). Chronic renal failure was the only patient-associated risk factor predictive of postoperative nutritional depletion (odds ratio 5.9, confidence interval 1.0 to 33.6; P = .04). CONCLUSIONS: Patients undergoing major open vascular surgery have high rates of postoperative malnutrition, with patients undergoing AAA repair having the highest rates of postoperative malnutrition and infection. Patients with chronic renal failure undergoing vascular surgery are associated with increased risk for postoperative malnutrition and may be a group to target for perioperative risk factor modification and nutritional supplementation.
Asunto(s)
Fallo Renal Crónico/epidemiología , Desnutrición/etiología , Enfermedades Vasculares/epidemiología , Procedimientos Quirúrgicos Vasculares/efectos adversos , Aneurisma de la Aorta Abdominal/cirugía , Comorbilidad , Angiopatías Diabéticas/cirugía , Endarterectomía Carotidea/efectos adversos , Humanos , Desnutrición/epidemiología , Análisis Multivariante , Evaluación Nutricional , Estado Nutricional , Nutrición Parenteral , Proyectos Piloto , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
OBJECTIVE: Patient, hospital, and surgeon factors affect outcome after carotid endarterectomy (CEA). The nature and importance of hospital-specific factors, especially those unrelated to procedural volume, that affect post-CEA outcome remains poorly defined. We used a statewide database to determine the impact of several hospital-associated factors on outcome after CEA. METHODS: Hospital factors were established by telephone survey and validated by repeated survey as well as by the Connecticut Hospital Association, Connecticut state, and individual hospital internet Websites. All CEA in Connecticut non-federal hospitals between 1991 and 2002 were examined, including perioperative mortality, stroke, and cardiac complications. Multivariable logistic regression was used to analyze data. RESULTS: There were 14,288 CEAs performed with 0.5% mortality, 1.3% stroke, and 2.4% cardiac complications. The only hospital factor independently predictive of perioperative mortality was few number of hospital beds (less than 132 beds; odds ratio (OR) 2.78, P = 0.032). Factors predictive of perioperative stroke included few number of beds (OR 1.96, P = 0.001) and absence of a critical pathway (OR 1.39, P = 0.038). Factors predictive of perioperative cardiac complications included few number of beds (OR 3.01, P = 0.003), absence of a critical pathway (OR 1.50, P = 0.001), and absence of dedicated vascular recovery beds (OR 1.35, P = 0.03). Combined mortality, stroke, or cardiac complications were independently predicted by few hospital beds (OR 4.58, P = 0.002), absence of a critical pathway (OR 1.81, P < or = 0.0001), or inability to perform cardiac angiography (OR 3.92, P = 0.024). CONCLUSIONS: Hospital-based factors, such as greater bed capacity, use of critical pathways, ability to perform cardiac angiography, or presence of a dedicated vascular recovery unit predict reduced perioperative mortality, stroke and cardiac complications from CEA. These results suggest that hospital-associated factors do impact surgical outcome and that surgeons need to optimize these factors, extrinsic to the patient and surgeon, to provide maximal quality of care.