Lee D. Faucher

Prospective analysis of nosocomial infection rates, antibiotic use, and patterns of resistance in a burn population.

Despite significant advances in burn care, infection remains a major cause of morbidity and mortality in burn patients. We sought to determine accurate infection rates, risk factors for infection, and the percentage of infections caused by resistant organisms. In addition, we attempted to identify interventions to decrease the use of antimicrobial drugs. Data were collected prospectively from 157 burn patients admitted to the University of Iowa Carver College of Medicine burn treatment center from October 2001 to October 2002. A research assistant reviewed the medical record for each patient identified by burn surgeons as being infected to determine whether these episodes met the infection control criteria for nosocomial infections. The infection control assessment agreed with the surgeon′s assessment for 16.7% of the pneumonias, 70.0% of the burn wound infections, 57.1% of the urinary tract infections, and 70.0% of the bloodstream infections. By multiple logistic regression analysis, body surface area burned, comorbidities, and use of invasive devices were significantly related to acquisition of nosocomial infections as identified by both the burn surgeons and the infection control criteria. Staphylococcus aureus and Pseudomonas were the most common resistant organisms identified. In our population, surgeons could decrease antimicrobial use by using explicit criteria for identifying patients with hospital-acquired infections, limiting perioperative prophylaxis to patients at highest risk of infection, and decreasing the incidence of nosocomial infection with reduced use of devices and strict adherence to aseptic technique.

Phase I/II Clinical Evaluation of StrataGraft: A Consistent, Pathogen-Free Human Skin Substitute

BACKGROUND Large wounds often require temporary allograft placement to optimize the wound bed and prevent infection until permanent closure is feasible. We developed and clinically tested a second-generation living human skin substitute (StrataGraft). StrataGraft provides both a dermis and a fully-stratified, biologically-functional epidermis generated from a pathogen-free, long-lived human keratinocyte progenitor cell line, Neonatal Immortalized KeratinocyteS (NIKS). METHODS Histology, electron microscopy, quantitative polymerase chain reaction, and bacterial growth in vitro were used to analyze human skin substitutes generated from primary human keratinocytes or NIKS cells. A phase I/II, National Institute of Health-funded, randomized, safety, and dose escalation trial was performed to assess autograft take in 15 patients 2 weeks after coverage with StrataGraft skin substitute or cryopreserved cadaver allograft. RESULTS StrataGraft skin substitute exhibited a fully stratified epidermis with multilamellar lipid sheets and barrier function as well as robust human beta defensin-3 mRNA levels. Analysis of the primary endpoint in the clinical study revealed no differences in autograft take between wound sites pretreated with StrataGraft skin substitute or cadaver allograft. No StrataGraft-related adverse events or serious adverse events were observed. CONCLUSIONS The major finding of this phase I/II clinical study is that performance of StrataGraft skin substitute was comparable to cadaver allograft for the temporary management of complex skin defects. StrataGraft skin substitute may also eliminate the risk for disease transmission associated with allograft tissue and offer additional protection to the wound bed through inherent antimicrobial properties. StrataGraft is a pathogen-free human skin substitute that is ideal for the management of severe skin wounds before autografting.

Practice guidelines for the management of pain

OPTIONS 1. Control of burn pain must begin upon initiation of medical care. Once intravenous access is gained and resuscitation started, intravenous opioids should be administered. The opioid dose occasionally exceeds the standard weight-based recommendations and is necessary to achieve adequate pain control. 2. Opioids, along with other adjuncts such as benzodiazepines, are used to control background pain and are supplemented to achieve procedural and breakthrough pain control. 3. Standardized metrics should be regularly used to quantify patient pain and anxiety levels

Stratagraft Skin Substitute Is Well-tolerated and Is Not Acutely Immunogenic in Patients With Traumatic Wounds: Results From a Prospective, Randomized, Controlled Dose Escalation Trial

Objective:The goal of this study was to assess the immunogenicity and antigenicity of StrataGraft skin tissue in a randomized phase I/II clinical trial for the temporary management of full-thickness skin loss. Background:StrataGraft skin tissue consists of a dermal equivalent containing human dermal fibroblasts and a fully stratified, biologically active epidermis derived from Near-diploid Immortalized Keratinocyte S (NIKS) cells, a pathogen-free, long-lived, consistent, human keratinocyte progenitor. Methods:Traumatic skin wounds often require temporary allograft coverage to stabilize the wound bed until autografting is possible. StrataGraft and cadaveric allograft were placed side by side on 15 patients with full-thickness skin defects for 1 week before autografting. Allografts were removed from the wound bed and examined for allogeneic immune responses. Immunohistochemistry and indirect immunofluorescence were used to assess tissue structure and cellular composition of allografts. In vitro lymphocyte proliferation assays, chromium-release assays, and development of antibodies were used to examine allogeneic responses. Results:One week after patient exposure to allografts, there were no differences in the numbers of T or B lymphocytes or Langerhans cells present in StrataGraft skin substitute compared to cadaver allograft, the standard of care. Importantly, exposure to StrataGraft skin substitute did not induce the proliferation of patient peripheral blood mononuclear cells to NIKS keratinocytes or enhance cell-mediated lysis of NIKS keratinocytes in vitro. Similarly, no evidence of antibody generation targeted to the NIKS keratinocytes was seen. Conclusions:These findings indicate that StrataGraft tissue is well-tolerated and not acutely immunogenic in patients with traumatic skin wounds. Notably, exposure to StrataGraft did not increase patient sensitivity toward or elicit immune responses against the NIKS keratinocytes. We envision that this novel skin tissue technology will be widely used to facilitate the healing of traumatic cutaneous wounds.This study was registered at www.clinicaltrials.gov (NCT00618839).

Phenotyping Clostridium septicum Infection: A Surgeon's Infectious Disease

BACKGROUND Clostridium septicum infection is associated with malignancy. Whether disease phenotype is affected by malignant status is not known. Surgical treatment is used frequently but its impact on survival has not been examined in a cohort >30 patients. METHODS A PubMed search of English language journal articles yielded 320 cases. Full information (infection location, cancer type, operative intervention, and survival) was available for 224 cases + 7 at our institution not previously reported. RESULTS Seventy-two percent of patients had malignancy or malady of the gastrointestinal (GI) or hematologic (HEME) organ systems. HEME survival was inferior to GI survival (35% versus 55%, P = 0.03). Overall, patients who underwent operation had improved survival (57% versus 26%; P < 0.0001) and this association was maintained within GI and HEME cohorts (P = 0.002 and 0.005, respectively). More GI than HEME patients underwent operation (81% versus 51%, P < 0.001). GI patients were more likely than HEME patients to experience infection of skin and soft tissues (SSTI, P = 0.006). Diabetics were more likely to experience SSTI than nondiabetics (77% versus 45%, P < 0.001). CONCLUSIONS C. septicum infectious phenotype varies with host milieu. The SSTI phenotype is more common in GI and diabetic patients. This recognition may aid in directing the search for occult malignancy, which must be performed given the >70% incidence of concomitant cancer. This infection is more fatal in HEME versus GI patients, perhaps due in part to less HEME group operative intervention. Primary surgical therapy should be considered in GI or HEME patients as operative intervention benefits both groups.

Practice guidelines for deep venous thrombosis prophylaxis in burns.

Measures to prevent deep venous thrombosis (DVT), including low-dose subcutaneous heparin, low molecular weight heparin, or sequential compression devices, may be considered in high-risk patients, specifically those with a previous history of thromboembolic disease, and in patients with significant burns of the lower extremities. The purpose of this guideline is to review the principles of prophylaxis for DVT in burn patients and to present a reasonable approach for the treatment of patients during burn resuscitation. This guideline is designed to aid those physicians who are responsible for the triage and initial management of burn patients. DVT in the burn patient is a more common event than previously reported, with incidence ranging from 1% to 23% in the few available series. The suspected risk of bleeding using low-dose heparin has deterred most burn surgeons from using heparin routinely in all burn patients. Much remains unknown, however, regarding the real risks and benefits of this complication and its treatment. A Medline search of all English language citations from 1966 through 2006 was undertaken using the key words “deep vein thrombosis” and “deep venous thrombosis” with “burns.” This produced 18 references. The addition of the key words “pulmonary embolism” with “burns” produced a total of 82 references, of which 7 were felt to be relevant to this topic based on evidentiary classification of the data. There are no prospective, randomized, controlled studies evaluating the effectiveness of any prophylactic preventive measures against DVT in burn patients. The apparently low incidence of this condition in burn patients would appear to preclude its evaluation in a single-center study, and no multicenter studies have been conducted.

Are we headed for a shortage of burn surgeons

Newly trained burn surgeons are in high demand but low supply. The purpose of this study was to quantitate the current need for burn surgeons and to identify the need in the future. A questionnaire was sent to the 159 burn care facilities in North America listed in the 1999 to 2000 American Burn Association Directory. Of the 159 centers, 9 surveys were returned stating the center did not exist. Eighty-four (56%) of the remaining 150 centers responded. Twenty-nine percent of responding burn centers are currently attempting to recruit another burn surgeon, and an additional 38% anticipate needing to recruit one within the next 5 years. Of these, 89% anticipate difficulty finding another burn surgeon. This survey identifies a need for burn surgeons now and warns of a severe shortage in the immediate future. Current burn surgeons need to ensure that any interested trainee be mentored appropriately toward a career in burn surgery.

Local delivery of allogeneic bone marrow and adipose tissue-derived mesenchymal stromal cells for cutaneous wound healing in a porcine model.

Wound healing remains a major challenge in modern medicine. Bone marrow‐ (BM) and adipose tissue‐ (AT) derived mesenchymal stromal/stem cells (MSCs) are of great interest for tissue reconstruction due to their unique immunological properties and regenerative potential. The purpose of this study was to characterize BM and AT‐MSCs and evaluate their effect when administered in a porcine wound model. MSCs were derived from male Göttingen Minipigs and characterized according to established criteria. Allogeneic BM‐ or AT‐MSCs were administered intradermally (1 x 106 cells) into partial‐thickness wounds created on female animals, and covered with Vaseline® gauze or fibrin in a randomized pattern. Animals were euthanized at 7, 10, 14 and 21 days. Tissues were analyzed visually for healing and by microscopic examination for epidermal development and remodelling. Polymerase chain reaction (PCR) was used to detect the presence of male DNA in the specimens. All wounds were healed by 14 days. MSC‐injected wounds were associated with improved appearance and faster re‐epithelialization compared to saline controls. Evaluation of rete ridge depth and architecture showed that MSC treatment promoted a faster rate of epidermal maturation. Male DNA was detected in all samples at days 7 and 10, suggesting the presence of MSCs. We showed the safety, feasibility and potential efficacy of local injection of allogeneic BM‐ and AT‐MSCs for treatment of wounds in a preclinical model. Our data in this large animal model support the potential use of BM‐ and AT‐MSC for treatment of cutaneous wounds through modulation of healing and epithelialization. Copyright

Effect of a fish oil and arginine-fortified diet in thermally injured patients.

Burn injury induces a hypercatabolic inflammatory state, predisposing burn patients to malnutrition, poor wound healing, and infectious complications. We conducted this study to determine what effect a diet fortified with fish oil and arginine (FAD) would have on wound healing in a thermally injured population. Twenty-three thermally injured patients were enrolled in this randomized double blind enteral feeding study from July 2002 to August 2004. All study patients received isonitrogenous enteral intragastric feeding within 48 hours of admission. Patients were randomized to our standard diet (STD, ProBalance with Promix, Probalance from Nestlé, Glendale, CA; ProMix R.D., Navaco Laboratories, Phoenix, AZ) or a diet fortified with fish oil and arginine (FAD, Crucial, Nestlé Nutrition Glendale, CA) Diets were advanced as tolerated to meet 100% of estimated needs. The primary endpoint of the study was time to heal the first donor site. There were no statistical differences between the study groups with respect to baseline characteristics. Both diets were well tolerated, and there were no differences in the daily total kilocalories or protein intake per kilogram between the two diet groups throughout the study. Although nonsignificant, the patients in the FAD group showed a slightly faster healing time than those in the STD group (10.8 ± 2.7 days vs 12.3 ± 5.2 days, respectively). This trend was further accelerated when those with body surface area burns less than 30% were examined (patients with body surface area burns <30% in the FAD healed in 9.0 ± 1.7 vs corresponding patients in the standard group who healed in 12.2 ± 6.2, P = .63). Patients in the FAD group trended to more infections and more adverse complications. The adverse complications were predominantly associated with inhalation injuries. The role of fortified enteral diets in the outcomes of thermally injured patients deserves further study. Such a future study should be conducted in a multicenter trial and involve inhalation injury stratification systems to accurately score and randomize patients for inhalation injury. Finally, the frequency and pattern of infections in patients receiving fortified enteral diets deserves further evaluation.

Injury stimulates an innate respiratory immunoglobulin a immune response in humans.

BACKGROUND Secretory immunoglobulin A (SIgA) is the specific immune antibacterial defense. Since pneumonia frequently complicates the course of trauma patients, we studied early airway immune responses after injury. METHODS Twelve severely injured, intubated (expected for >/=5 d) patients had tracheal and bilateral lung lavage (BAL) within 30 hours of injury (n = 12). Epithelial lining fluid (ELF) volume and SIgA were measured by urea dilution and enzyme-linked immunosorbent assay (ELISA), respectively. Control BAL specimens were obtained from eight healthy elective surgical patients. Anatomically based comparisons were made between groups with Welchs unpaired t test. To verify human data, 30 male mice received no injury (time 0, n = 7) or injury with abdominal and neck incisions and were killed for airway IgA at 4 (n = 7), 8 (n = 8), and 24 (n = 8) hours. Analysis of variance (ANOVA) and Fishers protected least significant difference testing was used to analyze animal data. RESULTS Initial trauma patient SIgA concentration (SIgA/mL ELF) increased compared with control in the lungs bilaterally (p < 0.05 both right and left). ELF volume was significantly higher in the right lung (p = 0.02) and just missed statistical significance (p = 0.07) on the left. Mouse IgA increased 8 hours after stress (p < 0.05 versus 0, 4, and 24 hours) and returned to normal by 24 hours. CONCLUSION A previously unrecognized innate human airway mucosal immune response with increased airway SIgA and ELF occurs after severe injury and is reproducible experimentally. This accessible, quantifiable human response allows study of clinical strategies to reduce infections via mucosal immune therapies.