Factor VIIa administration in traumatic brain injury: an AAST-MITC propensity score analysis.

Background:Recombinant factor VIIa (rFVIIa) has been used off-label as an adjunct in the reversal of warfarin therapy and management of hemorrhage after trauma. Only a handful of these reports are rigorous studies, from which results regarding safety and effectiveness have been mixed. There remains no clear consensus as to the role of rFVIIa in traumatic brain injury (TBI). Methods:Eleven level 1 trauma centers provided clinical data and head CT scans of patients with a Glasgow Coma Scale (GCS) score of ≤13 and radiographic evidence of TBI. A propensity score (PS) to receive rFVIIa in those surviving ≥2 days was calculated for each patient based on patient demographics, comorbidities, physiology, Injury Severity Score, admission GCS score, and treatment center. Patients receiving rFVIIa within 24 hours of admission were matched to patients who did not receive rFVIIa for outcomes assessment. Subgroup analysis evaluated patients with primary head injury with PS matching. Results:There were 4284 patient observations; 129 received rFVIIa. Groups were comparable after matching. No differences in mortality or morbidity were found. Improvement in GCS score from admission to discharge was less among those receiving rFVIIa (5.5 vs. 2.4; P value 0.001); however, there was no difference in average GCS score at discharge. No significant differences in outcomes were identified in patients with isolated TBI receiving rFVIIa. Discussion:rFVIIa in early management of TBI is not associated with a decreased risk of mortality or morbidity, and may negatively impact recovery and functional status at discharge in the severely injured patient with polytrauma. Level of evidence:Level III. Study type:Therapeutic/care management

A Comprehensive review of abdominal infections

AbstractIntra-abdominal infection (IAI) is an important cause of morbidity and mortality. It is the second most commonly identified cause of severe sepsis in the intensive care unit and it has been associated with a high mortality rate. Most IAI are the result of inflammation and perforations of the gastrointestinal tract, such as appendicitis, peptic ulcer disease, and diverticulitis. Successful treatment of IAI is based on early and appropriate source recognition, containment and antimicrobial coverage. We will review the pathophysiology of IAI and provide clinical guidelines for its management

Insights into the regulation of TNF-a production in human mononuclear cells: the effects of non-specific phosphodiesterase inhibition

OBJECTIVE: The objective of this study was to determine the effect of nonspecific phosphodiesterase inhibition on transcription factor activation and tumor necrosis factor-alpha (TNF-a) production in lipopolysaccharide (LPS)-stimulated human mononuclear cells. INTRODUCTION: The production of TNF-a following LPS stimulation is one of the key steps in bacterial sepsis and inflammation. The mechanism by which phosphodiesterase inhibition alters TNF-a production in the presence of LPS remains unclear. METHODS: Human mononuclear cells were stimulated with LPS (1 µg/mL), in the presence and absence of Pentoxifylline (PTX; 20 mM), a nonspecific phosphodiesterase inhibitor. Western blotting of phosphorylated cytoplasmic I-kBa, nuclear factor-kB p65 (NF-kB), and nuclear cAMP-response element binding protein (CREB) was performed. DNA binding of NF-kB and CREB was verified by electrophoretic mobility shift assay. TNF-a levels were determined in the supernatant of stimulated cells in the presence and absence Protein kinase A inhibition by an enzyme-linked immunosorbent assay (ELISA). RESULTS: PTX was demonstrated to significantly reduce cytoplasmic I-kBa phosphorylation, nuclear p65 phosphorylation, and the DNA binding activity of NF-kB. In contrast, PTX markedly enhanced the phosphorylation and DNA binding activity of CREB. Cells concomitantly treated with PTX and LPS secreted similar levels of TNF-a in the presence and absence Protein kinase A inhibition. DISCUSSION: The increased level of cAMP that results from phosphodiesterase inhibition affects cytoplasmic and nuclear events, resulting in the attenuation of NF-kB and the activation of CREB transcriptional DNA binding through pathways that are partially Protein kinase A-independent. CONCLUSION: PTX-mediated phosphodiesterase inhibition occurs partially through a Protein kinase A-independent pathway and may serve as a useful tool in the attenuation of LPS-induced inflammation

Insights into the Regulation of TNF-α Production in Human Mononuclear Cells: The Effects of Non-Specific Phosphodiesterase Inhibition

OBJECTIVE: The objective of this study was to determine the effect of nonspecific phosphodiesterase inhibition on transcription factor activation and tumor necrosis factor-alpha (TNF-a) production in lipopolysaccharide (LPS)-stimulated human mononuclear cells. INTRODUCTION: The production of TNF-a following LPS stimulation is one of the key steps in bacterial sepsis and inflammation. The mechanism by which phosphodiesterase inhibition alters TNF-a production in the presence of LPS remains unclear. METHODS: Human mononuclear cells were stimulated with LPS (1 µg/mL), in the presence and absence of Pentoxifylline (PTX; 20 mM), a nonspecific phosphodiesterase inhibitor. Western blotting of phosphorylated cytoplasmic I-kBa, nuclear factor-kB p65 (NF-kB), and nuclear cAMP-response element binding protein (CREB) was performed. DNA binding of NF-kB and CREB was verified by electrophoretic mobility shift assay. TNF-a levels were determined in the supernatant of stimulated cells in the presence and absence Protein kinase A inhibition by an enzyme-linked immunosorbent assay (ELISA). RESULTS: PTX was demonstrated to significantly reduce cytoplasmic I-kBa phosphorylation, nuclear p65 phosphorylation, and the DNA binding activity of NF-kB. In contrast, PTX markedly enhanced the phosphorylation and DNA binding activity of CREB. Cells concomitantly treated with PTX and LPS secreted similar levels of TNF-a in the presence and absence Protein kinase A inhibition. DISCUSSION: The increased level of cAMP that results from phosphodiesterase inhibition affects cytoplasmic and nuclear events, resulting in the attenuation of NF-kB and the activation of CREB transcriptional DNA binding through pathways that are partially Protein kinase A-independent. CONCLUSION: PTX-mediated phosphodiesterase inhibition occurs partially through a Protein kinase A-independent pathway and may serve as a useful tool in the attenuation of LPS-induced inflammation

Gastric Trichobezoar Causing Intermittent Small Bowel Obstruction: Report of a Case and Review of the Literature

We report the unusual case of a 45-year-old woman who presented with multiple episodes of small bowel obstruction. Initial exploratory lap-roscopy did not reveal an etiology of the obstruction. Subsequent upper endoscopy identified a non-obstructing gastric trichobezoar which could not be removed endoscopically but was not thought to be responsible for the small bowel obstruction given its location. One week postoperatively, the patient experienced recurrence of small bowel obstruction. Repeat endoscopy disclosed that the trichobezoar was no longer located in the stomach and upon repeat laparotomy was extracted from the mid-jejunum. In the following 8 months, the patient had no further episodes of small bowel obstruction. Consequently, gastric bezoars should be included in the differential diagnosis of recurrent small bowel obstruction

A Novel Fluid Resuscitation Strategy Modulates Pulmonary Transcription Factor Activation in a Murine Model of Hemorrhagic Shock

INTRODUCTION: Combining the hemodynamic and immune benefits of hypertonic saline with the anti-inflammatory effects of the phosphodiesterase inhibitor pentoxifylline (HSPTX) as a hemorrhagic shock resuscitation strategy reduces lung injury when compared with the effects of Ringer's lactate (RL). We hypothesized that HSPTX exerts its anti-inflammatory effects by interfering with nuclear factor kappa B/cAMP response element-binding protein (NF-κB-CREB) competition for the coactivator CREB-binding protein (CBP) in lung tissue, thus affecting pro-inflammatory mediator production. METHODS: Male Sprague-Dawley rats underwent 60 minutes of hemorrhagic shock to reach a mean arterial blood pressure of 35 mmHg followed by resuscitation with either RL or HSPTX (7.5% HS + 25 mg/kg PTX). After four hours, lung samples were collected. NF-κB activation was assessed by measuring the levels of phosphorylated cytoplasmic inhibitor of kappa B (I-κB) and nuclear NF-κB p65 by western blot. NF-κB and CREB DNA-binding activity were measured by electrophoretic mobility shift assay (EMSA). Competition between NF-κB and CREB for the coactivator CBP was determined by immunoprecipitation. Interleukin-8 (IL-8) levels in the lung were measured by ELISA. RESULTS: RL resuscitation produced significantly higher levels of lung IL-8 levels, I-κB phosphorylation, p65 phosphorylation, and NF-κB DNA binding compared with HSPTX. NF-κB-CBP-binding activity was similar in both groups, whereas CREB-CBP-binding activity was significantly increased with HSPTX. CREB-DNA binding-activity increased to a greater level with HSPTX compared with RL. DISCUSSION: HSPTX decreases lung inflammation following hemorrhagic shock compared with conventional resuscitation using RL through attenuation of NF-κB signaling and increased CREB-DNA binding activity. HSPTX may have therapeutic potential in the attenuation of ischemia-reperfusion injury observed after severe hemorrhagic shock

Abdominal damage control surgery and reconstruction: world society of emergency surgery position paper

Abstract Damage control laparotomy was first described by Dr. Harlan Stone in 1983 when he suggested that patients with severe trauma should have their primary procedures abbreviated when coagulopathy was encountered. He recommended temporizing patients with abdominal packing and temporary closure to allow restoration of normal physiology prior to returning to the operating room for definitive repair. The term damage control in the trauma setting was coined by Rotondo et al., in 1993. Studies in subsequent years have validated this technique by demonstrating decreased mortality and immediate post-operative complications. The indications for damage control laparotomy have evolved to encompass abdominal compartment syndrome, abdominal sepsis, vascular and acute care surgery cases. The perioperative critical care provided to these patients, including sedation, paralysis, nutrition, and fluid management strategies may improve closure rates and recovery. In the rare cases of inability to primarily close the abdomen, there are a number of reconstructive strategies that may be used in the acute and chronic phases of abdominal closure

Vena cava filters : a decade of experience in a level I trauma center

OBJETIVO: Avaliar os dados relativos à utilização de filtro de veia cava na Divisão de Trauma do Centro Médico da UCSD San Diego, CA/EUA. MÉTODOS: Estudo descritivo realizado na Divisão de Trauma visando avaliar a experiência acumulada e a conduta terapêutica nos doentes atendidos pela equipe da Divisão de Trauma e submetidos à colocação de filtro de veia cava como método de prevenção ou tratamento do TEP no período de janeiro de 1999 a dezembro de 2008. RESULTADOS: O estudo compreendeu 512 doentes, destacando-se o sexo masculino (73%). Quanto à causa do traumatismo predominou o acidente automobilístico, seguido por lesões provocadas por quedas. A relação homem/mulher foi 3:1. A faixa etária mais atingida foi 21 a 40 anos, representando 36% dos doentes. O percentual de filtros de cava profiláticos foi de 82% contra 18% de filtros terapêuticos. O traumatismo craniano foi a principal causa para indicação de filtros profiláticos seguido dos traumas raquimedulares. O índice de TVP pós-filtro foi 11%. CONCLUSÃO: Na presença de contraindicação ao uso de anticoagulantes em doentes vítimas de trauma grave, os filtros de veia cava inferior demonstraram ser uma opção efetiva e segura. Entretanto, deve-se aplicar rigor ao julgamento clínico para todas as indicações, mesmo após o advento de filtros "recuperáveis".OBJECTIVE: To evaluate the data on the use of vena cava filter in the Division of Trauma, UCSD Medical Center - San Diego, CA / USA. METHODS: A descriptive study was conducted at the Division of Trauma to evaluate the cumulated experience and the therapeutic approach in patients attended by the staff of the Division of Trauma and submitted to placement of a vena cava filter as a method of prevention or treatment of Pulmonary Thromboembolism (PTE) from January 1999 to December 2008. RESULTS: The study comprised 512 patients, mostly males (73%). As to the cause, automobile accident injuries predominated, followed by injuries caused by falls. The male / female ratio was 3:1. The most affected age group was the one between 21 to 40 years, representing 36% of patients. The percentage of prophylactic vena cava filters was 82%, whilst 18% had treatment purposes. Head trauma was the main cause for the indication of prophylactic filters followed by spinal cord trauma. The rate of pos-filter deep vein thrombosis (DVT) was 11%. CONCLUSION: In the presence of contraindications to the use of anticoagulants in patients who suffered severe trauma, the inferior vena cava filters have proven to be an effective and safe optio n. However, one should apply rigorous clinical judgment to all indications, even after the advent of retrievable filters