RESUMEN
BACKGROUND: Intra-abdominal adhesions are the most frequent postoperative complication after abdominopelvic surgery. Our laboratory has previously shown that an intraoperative peritoneal lavage containing either the histone deacetylase inhibitor valproic acid (VPA) or a neurokinin-1 receptor antagonist (NK-1RA) reduced adhesions by approximately 50% in a rat model. The objective of this study was to determine whether the combination of these 2 drugs was more effective in reducing adhesions than either alone. METHODS: Rats underwent laparotomy with creation of peritoneal ischemic buttons to induce adhesions. A single dose of VPA (25 mg/kg), NK-1RA (50 mg/kg), a combination of both, or 0.9% saline was lavaged intraperitoneally just before wound closure. On postoperative day 7, adhesions were quantified. To investigate early mechanisms of adhesiogenesis, adhesions were created as described and adhesive button tissue was harvested at 30 minutes and 3 hours postoperatively and fibrinogen and vascular endothelial growth factor (VEGF) protein levels, both indices of peritoneal extravasations, were determined by Western blot analysis. Peritoneal fluid was collected in similar experiments at 30 minutes, and 3 and 6 hours to measure fibrinolytic activity, an index of the ability of the peritoneum to degrade fibrinous adhesions. RESULTS: The coadministration of VPA plus NK-1RA reduces adhesions by 72.6% relative to saline (P < .001); this reduction was greater than either compound alone (P < .001). Peritoneal fibrinolytic activity was significantly increased at 3 and 6 hours postoperatively in animals administered the combination therapy versus saline (P = .01). VPA plus NK-1RA significantly decreased fibrinogen and VEGF protein levels at 3 and 6 hours compared with saline controls. CONCLUSION: These results suggest that a combined pharmacologic approach targeting multiple adhesiogenic pathways provides optimal adhesion prevention.
Asunto(s)
Inhibidores de Histona Desacetilasas/administración & dosificación , Antagonistas del Receptor de Neuroquinina-1/administración & dosificación , Adherencias Tisulares/prevención & control , Abdomen , Animales , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Fibrinógeno/análisis , Cuidados Intraoperatorios , Masculino , Ratas , Ratas Wistar , Ácido Valproico/administración & dosificación , Factor A de Crecimiento Endotelial Vascular/análisis , Cicatrización de Heridas/efectos de los fármacosRESUMEN
We describe an endovascular technique using in situ stent graft fenestration and pump assist to repair a pseudoaneurysm of the transverse arch following previous ascending aortic and transverse arch replacements.
Asunto(s)
Aneurisma Falso/cirugía , Aorta Torácica/cirugía , Implantación de Prótesis Vascular/métodos , Procedimientos Endovasculares/métodos , Stents , Aorta/cirugía , Aneurisma de la Aorta Torácica/cirugía , Puente Cardiopulmonar , Femenino , Humanos , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: We previously demonstrated that postoperative peritoneal injury and inflammation contribute to adhesiogenesis. Recent evidence suggests that in addition to their role of interfering with the acetylation status of nuclear histone proteins, histone deacetylase inhibitors (HDACIs) including valproic acid (VPA) can target nonhistone proteins to resolve inflammation and modulate immune cells. We hypothesized that HDACIs could reduce adhesions. METHODS: Seventy-two rats underwent laparotomy with creation of 6 peritoneal ischemic buttons to induce adhesions. A single intraperitoneal (IP) dose of 50 mg/kg VPA was administered intraoperatively, whereas controls received vehicle. To evaluate the timing, 25 rats underwent ischemic button creation with either an intraoperative or a delayed IP dose of VPA at 1, 3, or 6 hours postoperatively. On postoperative day 7, adhesions were quantified. To investigate mechanisms, ischemic buttons were created in 24 rats and either VPA or saline was administered in 1 intraoperative dose. At 3 or 24 hours later, peritoneal fluid was collected and fibrinolytic activity measured. Alternatively, button tissue was collected 30 minutes postoperatively to measure tissue factor, fibrinogen, and vascular endothelial growth factor (VEGF) by real-time polymerase chain reaction or Western blot. RESULTS: A single intraoperative dose of VPA reduced adhesions by 50% relative to controls (P < .001). Delayed dosing did not reduce adhesions. In operated animals, peritoneal fibrinolytic activity was not different between groups. Tissue factor mRNA was downregulated by 50% (P = .02) and protein by 34% (P < .01) in animals administered VPA versus saline. VPA decreased fibrinogen protein by 56% and VEGF protein by 25% compared with saline (P = .03). CONCLUSION: These findings suggest that VPA rapidly reduces the extravasation of key adhesiogenic substrates into the peritoneum. A single, intraoperative intervention provides an ideal dosing strategy and indicates an exciting new role for HDACIs in adhesion prevention.
Asunto(s)
Fibrinógeno/metabolismo , Inhibidores de Histona Desacetilasas/administración & dosificación , Peritoneo/metabolismo , Adherencias Tisulares/prevención & control , Ácido Valproico/administración & dosificación , Animales , Benzamidas/administración & dosificación , Fibrina/metabolismo , Ácidos Hidroxámicos/administración & dosificación , Intestinos/cirugía , Cuidados Intraoperatorios , Masculino , Peritoneo/efectos de los fármacos , Piridinas/administración & dosificación , Ratas , Ratas Wistar , Tromboplastina/metabolismo , Adherencias Tisulares/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Vorinostat , Cicatrización de Heridas/efectos de los fármacosRESUMEN
BACKGROUND: We hypothesized that trauma patient evaluations using evidence-based treatment guidelines (evidence-based group [EBG]), which include serial examinations and limited computed tomography (CT) scans in an established trauma center, would be associated with equivalent outcomes but with decreased CT scan usage, decreased cost, and less radiation exposure compared with a liberal CT scan approach (conventional group [CONV]). METHODS: Fifteen evidence-based treatment guidelines were developed using published literature and in collaboration with other institutional departments. These were implemented on July 1, 2010. Prospectively collected data during a 4-month period were compared with a similar period in 2008 when CONV was used. RESULTS: In 2010 (EBG), there were 611 patients compared with 612 in 2008 (CONV). Their average Injury Severity Score was 11.93 versus 8.77 (p < 0.0001), and the total CT scans were 757 and 1194, respectively (p < 0.001). The average APACHE II and hospital length of stay did not significantly vary. No missed or delayed injuries were identified. Estimated CT scan charges were $1,842,534 versus $2,935,024. The average number of scans per patient were 1.2 (EBG) versus 1.9 (CONV). Regarding radiation dosimetry, the estimated average computed tomography dose index (CTDI) per patient were 36.7 versus 53.31 mGy, and the estimated average dose-length product per patient were 889.91 versus 1364.11 mGy·cm. CONCLUSION: EBG, including serial examinations, provided equivalent diagnostic data to CONV for initial workup but reduced CT scan usage, CT scan charges, and average radiation exposure per patient. This strategy may be beneficial in institutions where serial monitoring can be assiduously provided. LEVEL OF EVIDENCE: Case management study, level IV.
Asunto(s)
Ahorro de Costo , Guías de Práctica Clínica como Asunto/normas , Tomografía Computarizada por Rayos X/economía , Tomografía Computarizada por Rayos X/normas , Heridas y Lesiones/diagnóstico por imagen , Adulto , Anciano , Estudios de Cohortes , Análisis Costo-Beneficio , Pruebas Diagnósticas de Rutina/normas , Medicina Basada en la Evidencia , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Control de Calidad , Dosis de Radiación , Efectos de la Radiación , Radiometría/métodos , Medición de Riesgo , Tomografía Computarizada por Rayos X/efectos adversos , Centros Traumatológicos/economía , Centros Traumatológicos/normas , Estados Unidos , Heridas y Lesiones/economía , Adulto JovenRESUMEN
BACKGROUND: The hepatic acute phase response(APR) is an organ-specific response to a diverse array of insults and is largely under transcriptional control. Liver-specific transcription factors, hepatic nuclear factors (HNFs)-1α and 4α play important roles in maintenance of liver phenotype and function and their binding activity changes early after injury. However, their roles in modulation of the liver's response over time are not defined. MATERIALS AND METHODS: C57/BL6 mice were anesthetized and exposed to 95°C water for 10 s to create a 15% body surface area full-thickness burn. At specific time points, the mice were sacrificed. An ELISA for IL-6 was performed on serum and hepatic mRNA levels for fibrinogen-γ and serum amyloid A(SAA)-3 were obtained through polymerase chain reaction (PCR). Transcriptional factor binding activity was assessed with electrophoretic mobility shift assays. RESULTS: Serum IL-6 levels peaked at 3 h and fibrinogen-γ and SAA mRNA levels increased more than 6-fold at 12 h before returning to control levels at 48 h. The binding activity of HNF-4α and HNF-1α rapidly declined after injury (1.5 h) but recovered to near control level at 24 and 6 h, respectively. CONCLUSIONS: Changes in HNF-4α and HNF-1α binding occurred before changes in acute phase protein mRNA levels and were preceded by the peak in IL-6 levels. The rapid suppression and reconstitution of liver-specific transcription factor binding after injury may represent a mechanism that allows the normal liver phenotype to change and an injury-response phenotype to prevail. This mechanism in the liver's adaptive response to injury suggests a central role for both HNF-4α and HNF-1α in transcriptional regulation of the hepatic APR.