Efficacy of Mepliex® Ag Versus Xeroform® As A Split-Thickness Skin Graft Donor Site Dressing: Bad Habits Die Hard.

Autografting with split-thickness skin grafts (STSG) remains an essential procedure in burn and reconstructive surgery. The process of harvesting STSG, however, leaves behind a donor site, an exposed area of partial-thickness dermis left to heal by secondary intention. There has yet to be a consensus amongst surgeons regarding optimal management of the donor site. The ideal donor site dressing is one that allows for expeditious healing while minimizing pain and infection. Despite numerous studies demonstrating the superiority of moist wound healing, many surgeons continue to treat STSG donor sites dry, with petroleum-based gauze. In this study, two burn centers performed a retrospective review of burn patients whose STSG donor sites were treated with either Xeroform® or Mepilex® Ag dressings. Infections were documented and in a subgroup analysis of patients, postoperative pain scores were noted and total opiate usage during hospitalization was calculated. Analysis revealed an overall infection rate of 1.2% in the Mepilex® Ag group and 11.4% in the Xeroform® group (p<0.0001). Patients with Xeroform® donor site dressings had increased odds of donor site infection (OR=10.8, p=0.002). In subgroup analysis, there were no significant differences in maximum pain scores between Mepilex® Ag and Xeroform® groups, nor were there differences in opiate usage. STSG donor sites dressed with silver foam dressings have a lower rate of donor site infection relative to those dressed with petroleum-based gauze. Moist donor site dressings such as foam dressings (including Mepilex® Ag) should be the standard of care in STSG donor site wound care.

La greffes de peau mince (GPM) demeure une procédure essentielle dans la chirurgie de brûlure et de reconstruction. La zone donneuse de greffe (ZDG) représente une perte de substance cutanée superficielle, cicatrisant spontanément. Il n'y a pas de consensus concernant la prise en charge optimale de la ZDG. Le pansement idéal de la ZDG doit promouvoir la cicatrisation et réduire la douleur ainsi que le risque infectieux. Malgré les nombreuses publications montrant l'intérêt d'un environnement humide pour la cicatrisation, de nombreux chirurgiens réalisent des pansements secs vaselinés. Cette étude rétrospective effectuée dans 2 CTB compare les pansements de ZDG réalisés au Xéroform® ou au Mepilex Ag®. Les infections ont été documentées et, dans un sous-groupe, les scores de douleur et la consommation d'opiacés au long de l'hospitalisation ont été notés. Les taux d'infection sont de 1,2% dans le groupe Mepilex Ag® et 11,4% avec Xéroform® (p<0,0001). Le risque d'infection de la ZDG est augmenté (OR 10,8 ; p = 0,002) en cas d'utilisation de Xéroform®. Il n'y avait pas de différence de douleur et de consommation d'opiacés entre les 2 groupes. Les ZDG recouvertes d'un pansement hydrocellulaire imprégné d'argent s'infectent moins que celles traitées avec une gaze imprégnée de vaseline. L'utilisation sur les ZDG d'un pansement humide comme une mousse hydrocellulaire (par exemple Mepilex Ag®) devrait devenir la norme.

Electroporation-mediated delivery of the FER gene in the resolution of trauma-related fatal pneumonia.

Injured patients with lung contusion (LC) are at risk of developing bacterial pneumonia (PNA) followed by sepsis and death. A recent genome-wide association study (GWAS) showed FER gene expression positively correlating with survival rates among individuals with above conditions. We sought to determine whether electroporation (EP)-mediated delivery of FER gene could indeed improve survival, in a lethal model of combined LC and PNA. C57BL/6 mice sustained unilateral LC, which preceded a 500 Klebsiella colony forming unit (CFU) inoculation by 6 h. In-between these insults, human FER plasmid (pFER) was introduced into the lungs followed by eight EP pulses applied externally (10 ms at 200 V cm-1). Control groups included EP of empty vector (pcDNA3) or Na+/K+-ATPase genes (pPump) and no treatment (LC+PNA). We recorded survival, histology, lung mechanics, bronchial alveolar lavage (BAL) fluid, FER and inflammatory gene expression and bacteriology. The data show that 7-day survival was significantly improved by pFER compared with control groups. pFER increased BAL monocytes and activated antibacterial response genes (nitric oxide synthase (NOS), Fizz). pFER treatment showed decreased lung and blood Klebsiella counts reaching, in some cases, complete sterilization. In conclusion, FER gene delivery promoted survival in LC+PNA mice via recruitment of activated immune cells, improving efficiency of bacterial clearance within contused lung.

Lipopolysaccharide binding protein inhibitory peptide protects against acetaminophen-induced hepatotoxicity.

Acetaminophen (APAP)-induced liver injury remains the main cause of acute liver failure in the United States. Our previous work demonstrated that LPS binding protein (LBP) knockout mice are protected from APAP-induced hepatotoxicity. LBP is known to bind avidly to LPS, facilitating cellular activation. In this study, we sought to specifically inhibit the interaction between LBP and LPS to define the role of this interaction in APAP-induced liver injury. The peptide LBPK95A was able to inhibit LBP-mediated LPS activation of RAW 267.4 cells in a dose-dependent manner in vitro. In vivo, C57Bl/6 mice were treated with either LBPK95A or vehicle control concurrently with the administration of APAP (350 mg/kg). Mice treated with LBPK95A had significantly lower serum aspartate aminotransferase and alanine aminotransferase levels. Morphometric analysis of the liver tissue showed significantly less liver injury in mice treated with LBPK95A. To assess whether the LBPK95A altered glutathione depletion and APAP metabolism, we measured total glutathione levels in the liver after APAP. We found no difference in the glutathione levels and APAP-adduct formation between LBPK95A vs. vehicle control both at baseline and after APAP. In conclusion, our results support the hypothesis that LBP-induced liver injury after APAP is due to its ability to mediate activation by endogenous LPS. Our results suggest that blocking LBP-LPS interactions is a potential therapeutic avenue for the treatment of APAP-induced liver injury.

A novel stable reproducible model of hepatic failure in canines.

BACKGROUND: Stable and reproducible large animal models of hepatic failure, which allow the assessment of liver-assist devices, are not available. Our objective was to develop a physiologically stable animal model of hepatic failure on which the safety and efficacy of an extracorporeal liver-assist device can be tested. We hypothesized that a surgical model which consists of an end-to-side portocaval shunt combined with common bile duct ligation and transection would create hepatic failure with: (1) elevations in amino transferases, total bilirubin, and ammonia; (2) a decrease in the ratio of branched chain to aromatic amino acids; and (3) histologic evidence of hepatic injury. METHODS: Eleven mongrel dogs underwent common bile duct transection and an end-to-side portocaval shunt. Aminotransferases (AST, ALT), total bilirubin, ammonia, and branched chain and aromatic amino acids were measured prior to operation (baseline) and after 9 days. A necropsy was performed on Postoperative Day 9 and liver biopsies were obtained for histology. RESULTS: By Postoperative Day 9, AST, ALT, total bilirubin, and ammonia values were significantly elevated compared to baseline (P < 0.02). The ratio of branched chain to aromatic amino acids was significantly reduced compared to baseline (P < 0.003). There was histologic evidence of cholestasis and inflammation. CONCLUSION: Portocaval shunt with common bile duct transection produces liver failure with elevations in aminotransferases, total bilirubin, and ammonia, a decreased branched chain to aromatic amino acid ratio, and histologic inflammation. Unlike ischemic or chemically induced models of liver failure, the dogs were hemodynamically and neurologically stable. This model can be used to test the safety and efficacy of liver-assist devices aimed at temporizing the detoxification functions of the failing liver.

The response to splenectomy in pediatric patients with idiopathic thrombocytopenic purpura who fail high-dose intravenous immune globulin.

BACKGROUND: A recent article by Law et al concluded that patients with idiopathic thrombocytopenic purpura (ITP) who have a poor response to intravenous immune globulin (IgG) are unlikely to have a good or excellent response to surgical splenectomy. METHODS: The authors studied retrospectively 23 pediatric patients age 11.7 +/- 1.0 years with ITP who had been treated with IgG before undergoing splenectomy. As in the aforementioned article, the responses to the 2 treatments were classified on the basis of the platelet count as poor (<50,000/mm3), good (50,000 to 150,000/mm3), or excellent (>150,000/mm3). For patients who received multiple IgG treatments, both initial and final treatment responses were analyzed. RESULTS: Sixteen patients had an excellent or good initial response to IgG. Of these 16 patients, 14 had an excellent or good response to splenectomy. Among the 7 patients who had a poor response to IgG there were 3 who had an excellent or good response to splenectomy (43%), and 4 patients who had a poor response to splenectomy. A good or excellent response to initial treatment with IgG was associated with a significant probability of a good or excellent response to splenectomy (P = .045). CONCLUSIONS: A good or excellent response to IgG may be predictive of a favorable response to splenectomy. However, a poor response to IgG does not preclude a satisfactory response to splenectomy in pediatric patients with ITP.

Advances in ventilatory support of the pediatric surgical patient.

Severe respiratory failure in newborn and pediatric patients is associated with significant morbidity and mortality. Basic science laboratory investigation has led to advances both in our understanding of ventilator-induced lung injury and in optimizing the supportive use of conventional ventilation strategies. Over the past few years, progress has been made in alternative therapies for ventilating both children and adults with severe respiratory failure. This review focuses on recent laboratory and clinical data detailing the techniques of permissive hypercapnia, high frequency oscillatory ventilation, inhaled nitric oxide, intratracheal pulmonary ventilation, and liquid ventilation. Some of these modalities are becoming commonplace, and others may have much to offer the clinician if their benefit is clearly demonstrated in future clinical trials.

Clinical implications of the new biology in the development of melanoma vaccines.

There has been a resurgence in clinical research of vaccine therapies, particularly for the treatment of melanoma. The renewed interest in this field is attributable to an increased understanding regarding the immune response to tumors and the immunobiology of melanoma. Molecular biology techniques have enabled investigators to develop genetically engineered tumor vaccines that are intended to favor the type 1 immune response over the type 2 response. Melanoma-associated antigens have been characterized at the molecular level and are currently being investigated in clinical trials. Dendritic cell biology has also provided a potent method to present antigens to the host for immunization. Lastly, vaccines are being explored as a method to generate immune T-cells for adoptive immunotherapy. These new areas of clinical investigation will be reviewed in the context of the historical developments that have laid the foundations of this field.

Laparoscopic splenectomy in patients with hematologic malignancies.

BACKGROUND: Although laparoscopic splenectomy (LS) for benign hematologic disease is well accepted, its role in hematologic malignancies is not clearly defined. This study examined the efficacy and feasibility of LS for hematologic malignancies. METHODS: Records were reviewed from patients who underwent LS at two university hospitals. Charts from 77 open splenectomies for malignancy (OM) during the same period were also reviewed. RESULTS: Fifty-three patients underwent LS, 22 for hematologic malignancies (LM) and 31 for benign hematologic disorders (LB). Median splenic weight was greater in the LM group (930 g) than in the LB group (164 g, P = 0.001). LM was associated with longer operations and greater blood loss than was LB. LM had a 41% conversion rate. Morbidity, mortality, and transfusion rates were similar. Median hospital stay was shorter for LM (4 days) than for OM (6 days, P = 0.001). CONCLUSIONS: LS is feasible in hematologic malignancies but is associated with increased operative time and blood loss and a high conversion rate. Morbidity and mortality, however, was similar. Shorter hospital stays for LM compared with OM may translate into earlier recovery and initiation of antineoplastic therapy.

Postischemic hyperglycemia worsens neurologic outcome after spinal cord ischemia.

PURPOSE: The neurologic effect of induced hyperglycemia in the postischemic period was investigated with a rat aortic occlusion model. METHODS: Sprague-Dawley rats weighing 200 to 350 gm were anesthetized, intubated, and ventilated with 1% to 1.5% halothane. Temperature was continuously monitored and maintained at 37 degrees +/- 0.5 degrees C. The chest was opened, the thymus excised, and the aortic arch exposed. Snares were placed around the aorta distal to the left subclavian artery and the right and left subclavian arteries. The three vessels thus isolated were occluded for 8 minutes. With snare release and withdrawal, the rats received an intraperitoneal injection of 5% dextrose in water (2 gm/kg) or an equivalent volume of 0.9% saline solution. In a second group of rats the administration of glucose or saline solution was delayed until 30 minutes after snare release. Blood samples for blood glucose determination were obtained before operation, before occlusion, immediately after occlusion, and 15, 30, 45, 60, and 240 minutes after occlusion. A neurologic deficit score was assigned at 1, 4, 18, and 24 hours after occlusion to quantify hindlimb neurologic deficit based on 15-point scale (0 = normal, 15 = severe deficit). Sham-operated rats received the same operation and injection, but the snares were only manipulated and not made occlusive. RESULTS: The rats that were administered glucose immediately after snare release showed a statistically significant exacerbation of lower extremity neurologic deficit at 24 hours after occlusion (p < or = 0.05, Mann-Whitney U test). The sham-operated rats were normal (0 score) at 24 hours. Significant elevation of blood glucose (321 +/- 33 mg/dl) was seen in the glucose-injected rats at 15 minutes and continued for up to 4 hours after occlusion (p = 0.040 and 0.014, respectively; Student's t test). CONCLUSION: Postischemic hyperglycemia immediately after a standard spinal cord ischemic stress worsens neurologic outcome.