The use of closed incision negative pressure therapy for incision and surrounding soft tissue management: Expert panel consensus recommendations.

As the use of closed incision negative pressure therapy (ciNPT) becomes more widespread, dressing designs have evolved to address implementation challenges and meet surgeon demand. While traditional application of ciNPT was limited to the immediate suture line, a novel dressing that covers the incision and additional surrounding tissues has become available. To expand upon previous ciNPT recommendations and provide guidance on this new dressing, an expert panel of plastic surgeons convened to review the current literature, identify challenges to the implementation and sustainability of ciNPT, and use a modified Delphi technique to form a consensus on the appropriate use of ciNPT with full-coverage dressings. After three rounds of collecting expert opinion via the Delphi method, consensus was reached if 80% of the panel agreed upon a statement. This manuscript establishes 10 consensus statements regarding when ciNPT with full-coverage foam dressings should be considered or recommended in the presence of patient or incision risk factors, effective therapeutic settings and duration, precautions for use, and tools and techniques to support application. The panel also discussed areas of interest for future study of ciNPT with full-coverage dressings. High-quality, controlled studies are needed to expand the understanding of the benefits of ciNPT over the incision and surrounding tissues.

Factors Associated With Adherence to Nasoalveolar Molding (NAM) by Caregivers of Infants Born With Cleft Lip and Palate.

OBJECTIVE: Identify factors associated with adherence to nasoalveolar molding (NAM) therapy. DESIGN: Retrospective case-control study. SETTING: Tertiary referral center. PATIENTS, PARTICIPANTS: Infants with cleft lip, with or without cleft palate, referred for NAM. One hundred thirty-five patients met criteria. MAIN OUTCOME MEASURE(S): Adherence to NAM therapy, defined as continuous use of the appliance and attendance of NAM adjustment visits. RESULTS: Female sex (OR = 2.85, 95% CI 1.21-6.74), bilateral cleft (OR = 2.88, 95% CI 1.29-6.46), and travel distance (OR = 1.01, 95% CI 1.00-1.01) were independent predictors of nonadherence. Bilateral clefts (OR = 8.35, 95% CI 2.72-25.64) and public-payer insurance (OR = 3.67, 95% CI 1.13-11.91) for male patients were significantly associated with nonadherence, in our sex-stratified multivariate model. The majority of the families (58%) had public health insurance. Males comprised 77.0% of the cohort. CONCLUSIONS: NAM treatment adherence is impaired by bilateral clefts, female sex, increased travel distance, and public insurance. Further studies are warranted to investigate how these factors affect adherence, and to develop interventions to improve adherence in families at risk due to economic or psychosocial barriers.

Implementation of a Tranexamic Acid Protocol to Reduce Blood Loss During Cranial Vault Remodeling for Craniosynostosis.

OBJECTIVE: Pediatric cranial vault remodeling for repair of craniosynostosis is associated with significant blood loss and transfusion requirements. Beginning in 2011, the authors evaluated the impact tranexamic acid (TXA) on blood loss and blood product transfusion for children less than 15 months of age undergoing primary surgical repair of nonsyndromic single suture craniosynostosis. METHODS: Following institutional review board approval, the authors performed a retrospective study of all children undergoing surgical correction of craniosynostosis at Oregon Health & Science University from 2005 to 2015. All available records were reviewed, and patient data were collected from the time of preoperative evaluation until discharge, comparing patient and clinical variables before and after the implementation of perioperative TXA. RESULTS: Of a total of 259 patients with craniosynostosis, 187 had nonsyndromic single-suture involvement; 69 of these patients (36.9%) received TXA. A single surgical team (AAK and NRS) performed all operations. Median age at the time of surgery was 8.1 months (interquartile range [IQR] of 6.0-9.8 months). The TXA group had a significant reduction in estimated intraoperative blood loss (26 mL/kg versus 36 mL/kg, P <0.001), cell saver volume transfused 6 mL/kg versus 10 mL/kg, P <0.001), red cell transfusion volume (32 mL/kg versus 42 mL/kg, P <0.001), exposure to plasma transfusion (0% versus 24% P <0.001), exposure to cryoprecipitate transfusion (0% versus 16%, P <0.001), and exposure to platelet transfusion (0% versus 7.6% P = 0.03). Despite reduced red cell transfusion, the TXA-treated patients exhibited similar postoperative hematocrits (30.4 versus 30.3 P = 0.906) to those not treated with TXA. Use of TXA was associated with reduced length of stay (4 days IQR 3-4 versus 4 days IQR 4-5, P <0.001) and reduced postoperative output from surgically placed drains (181 mL versus 311 mL P <0.001). There was no difference in postoperative complications between groups and no deaths in either group. CONCLUSIONS: The introduction of TXA for nonsyndromic single-suture synostosis repair at our institution has significantly reduced blood loss and blood product and plasma transfusion during and following primary cranial vault remodeling for single suture craniosynostosis. Postoperative hematocrit was similar in the TXA-treated and untreated groups despite reduced red cell transfusion in the treated group. In addition, TXA use in this population has eliminated the need for plasma transfusion, and is associated with a shorter hospital stay. No difference in postoperative complications was observed. Our data provide support for further investigation of TXA treatment to improve clinical outcomes in children undergoing pediatric cranial vault remodeling.

Computed tomography-generated anthropometric measurements of orbital relationships in normal infants and children.

OBJECTIVE The aim of this study was to develop soft-tissue and bony anthropometric orbital measurements in a normal pediatric population based upon CT scans. METHODS This was a retrospective stratified study of children with ages ranging from birth to 36 months. Head CT images for 204 children were available and obtained with 0.625-1-mm slice widths. Soft-tissue and bone windows were reviewed. Images were oriented in the Frankfort horizontal plane, and the intercanthal (IC), bony interorbital (IO), and bony lateral orbital (LO) distances were measured. Age group stratifications were 0-3, > 3-6, > 6-9, > 9-12, > 12-18, > 18-24, > 24-30, and > 30-36 months. Patients with known syndromes or craniofacial abnormalities were excluded. Statistical analysis included the mean, SD, SEM, 95% CI, and an evaluation of IO:LO ratio. RESULTS There was an average of 25.5 patients in each age group (range 25-27 patients). All soft-tissue and bony measurements consistently showed rapid increase from 0-6 months of age, which tapered after age > 12 months. The mean IC, bony IO, and bony LO distances started at 22.22 ± 1.13 mm, 14.16 ± 0.74 mm, and 65.56 ± 1.76 mm, and at 12 months were 27.74 ± 1.01 mm, 16.21 ± 0.75 mm, and 77.98 ± 1.57 mm, respectively. The bony LO position was equivalent to the lateral canthal position and measurements. The IC distance was approximately one-third the lateral canthal distance for all age groups. CONCLUSIONS This study established and reported normal anthropometric orbital measurements in a pediatric population using fine-cut craniofacial CT. These measurements are essential when evaluating children with craniofacial anomalies.

Age at the Time of Surgery and Maintenance of Head Size in Nonsyndromic Sagittal Craniosynostosis.

BACKGROUND: Repair of nonsyndromic sagittal craniosynostosis should durably improve intracranial volume and cranial index. The optimal timing of surgery is not known. The authors previously reported reoperation in patients aged younger than 6 months at primary repair. METHODS: Patients undergoing primary reconstruction for sagittal craniosynostosis before age 1 year between 2005 and 2013 at Oregon Health & Science University underwent retrospective computed tomographic determination of cranial index and intracranial volume preoperatively and 2 years postoperatively and head circumference measurements until age 6 years. RESULTS: Fifty-six patients undergoing operation before their first birthday were studied in two groups: those younger than 6 months [34 (61 percent)] and those aged 6 months or older at the time of operation. Head circumference percentile increased immediately after surgery but decreased at 1 and 2 years after surgery, significantly more so in patients younger than 6 months (p < 0.015 at 1 year; p < 0.011 at 2-year follow-up). Mean 2-year postoperative cranial index was significantly increased in both groups (p < 0.001), which did not differ preoperatively (younger than 6 months, 76.5; 6 months or older, 78.0) or 2 years postoperatively (younger than 6 months, 88.4; 6 months or older, 87.1; p = not significant). Intracranial volume increased in all patients from before surgery to 2 years postoperatively and was higher in the patients aged 6 months or older (p < 0.001). CONCLUSION: Cranial reconstruction for nonsyndromic sagittal craniosynostosis improved cranial index equally in all patients but increased head circumference and intracranial volume significantly more in patients who underwent surgical reconstruction at age 6 months or older. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

A Reduction in Radiation Exposure During Pediatric Craniofacial Computed Tomography.

BACKGROUND: Radiation exposure during computed tomography (CT) evaluation in children is the subject of growing professional and public concern. The authors previously demonstrated an 18% reduction in effective radiation dose during craniofacial CT imaging using a modified head position ("exaggerated sniff"), without any compromise of image diagnostic quality. The current study reports additional reduction of radiation exposure using a commercially available iterative reconstruction CT technique. METHODS: This single-institution, retrospective cohort study compared the overall effective radiation dose received during elective pediatric craniofacial CT imaging. Patients imaged using the iterative reconstruction and exaggerated sniff protocol combined (January 2010 through December 2013) were compared with those undergoing imaging with the exaggerated sniff position alone, between October 2008 and January 2010. RESULTS: A total of 325 patients who underwent CT imaging with the exaggerated sniff position, decreased dose and iterative reconstruction protocol experienced an average effective radiation dose of 1.22 mSv (47% reduction), compared with 2.32 mSv for the sniff-position alone group. Age-matched reference patients not treated using either protocol received an average of 2.82 mSv. This represents a 56.7% average radiation dose reduction for combined sniff position and iterative reconstruction patients compared with reference patients and 47.4% reduction compared with the sniff-position alone group. Image quality of both bone and brain windows was equivalent. CONCLUSIONS: Altering head position and use of iterative reconstruction technique with a reduced radiation protocol diminishes CT imaging-related effective radiation dose by approximately 50% in children undergoing elective cranial CT imaging for craniofacial disorders.

The American Society of Maxillofacial Surgery Preceptorship Program: A Product of the 2013 American Society of Maxillofacial Surgery Executive Board Strategy Session and Survey.

One of the main goals of the American Society of Maxillofacial Surgery (ASMS) is to develop educational programs that increase expertise in maxillofacial surgery. We describe the outline of the new ASMS Preceptorship Program, a collective effort by ASMS members to increase access to all areas of maxillofacial surgery. Furthermore, we discuss the original survey pertinent to the development of this program, the results of the survey, and specifics regarding the structure of the program. We hope for the preceptorship program to be an excellent resource for members to mentor one another, develop intellectual and academic curiosity, provide avenues for collaboration, and further the ASMS's role in shaping maxillofacial surgery into the future.

Local Wound Care for Primary Cleft Lip Repair: Treatment and Outcomes With use of Topical Hydrogen Peroxide.

OBJECTIVES: This study highlights and validates a peroxide-based wound healing strategy for treatment of surgically closed facial wounds in a pediatric population. The authors identified pediatric patients undergoing primary cleft lip repair as a specific population to evaluate the outcomes of such a protocol. Through analysis of defined outcome measures, a reliable and reproducible protocol for postoperative wound care following primary cleft lip repair with favorable results is described. METHODS: This retrospective study analyzes wound healing outcomes in pediatric patients undergoing primary cleft lip repair from 2006 to 2011 at a tertiary academic center. The wound healing protocol was used in both primary unilateral and bilateral repairs. One hundred fortysix patients between the ages of 0 and 4 years underwent primary cleft lip repair and cleft rhinoplasty by a single, fellowship-trained craniofacial surgeon. Postoperatively, wounds were treated with half-strength hydrogen peroxide and bacitracin, as well as scar massage. Incisional dehiscence, hypertrophic scar formation, discoloration, infection, and reoperation were studied. Outcomes were evaluated in light of parent compliance, demographics, preoperative nasoalveolar molding (PNAM), and diagnosis. RESULTS: The authors identified 146 patients for inclusion in this study. There was no wound or incisional dehiscence. One hundred twenty-four patients demonstrated favorable cosmetic outcome. Only 3 (2%) of patients who developed suboptimal outcomes underwent secondary surgical revision (> 1 year after surgery). Demographic differences were not statistically significant, and PNAM treatment did not influence outcomes. CONCLUSION: These data validate the use of halfstrength hydrogen peroxide and bacitracin as part of a wound healing strategy in pediatric incisional wounds. The use of hydrogen peroxide produced comparable outcomes to previously published studies utilizing other wound healing strategies and, therefore, these study findings support the further use of this regimen for this particular population.

Transcriptional profiling of rapamycin-treated fibroblasts from hypertrophic and keloid scars.

Excess scar formation after cutaneous injury can result in hypertrophic scar (HTS) or keloid formation. Modern strategies to treat pathologic scarring represent nontargeted approaches that produce suboptimal results. Mammalian target of rapamycin (mTOR), a central mediator of inflammation, has been proposed as a novel target to block fibroproliferation. To examine its mechanism of action, we performed genomewide microarray on human fibroblasts (from normal skin, HTS, and keloid scars) treated with the mTOR inhibitor, rapamycin. Hypertrophic scar and keloid fibroblasts demonstrated overexpression of collagen I and III that was effectively abrogated with rapamycin. Blockade of mTOR specifically impaired fibroblast expression of the collagen biosynthesis genes PLOD, PCOLCE, and P4HA, targets significantly overexpressed in HTS and keloid scars. These data suggest that pathologic scarring can be abrogated via modulation of mTOR pathways in procollagen and collagen processing.

Effectiveness and safety of independent pediatric nurse practitioners in evaluating plagiocephaly.

BACKGROUND: The American Academy of Pediatrics Back to Sleep program in 1992 dramatically increased the incidence of posterior plagiocephaly in infants. In 2000, the craniofacial disorders program at Oregon Health & Science University established a plagiocephaly screening clinic staffed by pediatric nurse practitioners. METHODS: Electronic medical records of patients seen in a single accredited craniofacial disorders clinic from 2005 to 2011 were reviewed retrospectively to identify patients screened independently by pediatric nurse practitioners for positional plagiocephaly versus synostosis. RESULTS: Over a 7-year period, 1228 patients were independently screened. Over half [638 patients (52 percent)] were followed through subsequent visits for craniofacial disorders without any direct surgeon input. Of these, 169 (26 percent) were treated with orthotic consultation for a molding helmet, 385 (60 percent) received a combination of counseling and/or physical therapy for torticollis, and 84 (13 percent) were lost to follow-up. No patient managed by pediatric nurse practitioners was identified to have cranial synostosis and no patient underwent early or delayed surgery. All returning patients [n=554 (86 percent)] showed improvement in, or resolution of, their presenting deformity. The remaining 590 patients (48 percent) were referred by the pediatric nurse practitioner for surgical consultation. Computed tomographic imaging revealed synostosis in 121 patients. CONCLUSIONS: Pediatric nurse practitioners accurately screened over half of patients referred to a high-volume craniofacial disorders program for positional plagiocephaly versus synostosis, without surgeon input. Based on available information, no synostosis diagnosis was overlooked using this approach. With specific training, pediatric nurse practitioners working in a craniofacial disorders program can safely and independently screen for positional versus synostotic plagiocephaly. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, III.

Tacrolimus fails to regulate collagen expression in dermal fibroblasts.

BACKGROUND: The purpose of this study was to investigate the effects of tacrolimus on human fibroblasts derived from unwounded skin, hypertrophic scars (HTS), and keloids. We hypothesized that tacrolimus, a potent anti-inflammatory and immunosuppressant drug known to attenuate solid organ transplant fibrosis, would block collagen expression in human dermal fibroblasts. METHODS: We performed genomewide microarray analysis on human dermal fibroblasts treated with tacrolimus in vitro. We used principal component analysis and hierarchical clustering to identify targets regulated by tacrolimus. We performed quantitative polymerase chain reaction to validate the effect of tacrolimus on collagen 1 and 3 expression. RESULTS: We identified 62, 136, and 185 gene probes on microarray analysis that were significantly regulated (P < 0.05) by tacrolimus in normal, HTS, and keloid fibroblasts, respectively. Collagen pathways were not blocked after tacrolimus exposure in any of the fibroblast groups; we validated these findings using quantitative polymerase chain reaction for collagen 1 and 3. Microarray gene expression of NME/NM23 nucleoside diphosphate kinase 1 and heterogeneous nuclear ribonucleoprotein H3-2H9 were significantly downregulated (P < 0.05) by tacrolimus in both HTS and keloid fibroblast populations but not normal fibroblasts. CONCLUSIONS: Tacrolimus does not modulate the expression of collagen 1 or 3 in human dermal fibroblasts in vitro. Microarray gene expression of NME/NM23 nucleoside diphosphate kinase 1 and heterogeneous nuclear ribonucleoprotein H3-2H9 are blocked by tacrolimus in pathologic fibroblasts but not normal fibroblasts, and may represent novel genes underlying HTS and keloid pathogenesis. Tacrolimus-based anti-fibrotics might prove more effective if non-fibroblast populations such as inflammatory cells and keratinocytes are targeted.

Benign radiographic coronal synostosis after sagittal synostosis repair.

Whether cranial vault remodeling surgery for nonsyndromic, isolated sagittal suture synostosis affects the patency of initially normal, unaffected sutures is unknown. The influence of coronal and lambdoidal suture patency after cranial vault remodeling on the trajectory of subsequent cranial growth is also unknown. Disruption of normal sutural anatomy during cranial vault reconstruction could influence the incidence of secondary craniosynostosis and need for reoperation in a small proportion of these patients.We performed a retrospective review of patients younger than 1 year with nonsyndromic sagittal synostosis treated at a single tertiary referral pediatric hospital from September 2005 to January 2010 by an interdisciplinary team. Computed tomographic images obtained preoperatively, immediately postoperatively, and 2 years postoperatively were evaluated for the occurrence of secondary synostosis of initially nonsynostotic sutures. Craniofacial disorders clinic and ophthalmologic follow-up records were also analyzed for the occurrence of radiographic cranial restenosis, clinical or ophthalmologic signs of intracranial hypertension (ICH), and reoperation.Fifty-one patients younger than 1 year underwent primary surgical repair of isolated, nonsyndromic sagittal suture synostosis during the study period. Thirty-seven of these patients (71%) had completed 2-year clinical and radiographic follow-up by the time of analysis, constituting the study population. The average age at surgery was 5.4 months (range, 3.1-11.5 months). Thirty-three (89%) of the 37 study patients showed radiographic evidence of bilateral secondary coronal synostosis (SCS). Five patients (15%) additionally showed partial lambdoid synostosis. One patient with radiographic SCS (3%) required reoperation for radiographic cranial restenosis, clinical signs and symptoms of ICH, and papilledema first noted 1 year after primary cranial vault reconstruction.There is a high incidence of secondary coronal suture synostosis following cranial vault remodeling for isolated, nonsyndromic sagittal synostosis. Postoperative SCS was only rarely associated with secondary radiographic cranial stenosis, clinical or ophthalmologic signs of ICH, and the need for reoperation.

Delayed intracranial hypertension after cranial vault remodeling for nonsyndromic single-suture synostosis.

OBJECT: Delayed intracranial hypertension may occur after cranial vault remodeling for synostosis and may result in visual loss and developmental delay. Delayed intracranial hypertension is relatively common in children with syndromic, multisuture synostosis, but the incidence is poorly defined in children with single-suture nonsyndromic synostosis. This study evaluates the frequency of reoperation for delayed intracranial hypertension after single-suture synostosis repair. METHODS: Patients who had undergone cranial vault remodeling for nonsyndromic single-suture synostosis and were treated at a single tertiary pediatric hospital between July 2000 and December 2010 were analyzed for the occurrence of delayed intracranial hypertension and reoperation for cranial vault remodeling. RESULTS: Eighty-one patients with clinical follow-up of at least 3 years were analyzed from a total of 156 consecutive patients. The average patient age at the initial operation was 9.1 months. Five (6.2%) of 81 patients presented with delayed clinical and ophthalmological signs and symptoms of intracranial hypertension following initial cranial vault reconstruction, confirmed indirectly in each case by CT findings and directly by intracranial pressure monitoring. These 5 patients underwent repeat cranial vault reconstruction. CONCLUSIONS: Calvarial growth restriction and intracranial hypertension occur sporadically following primary cranial vault reconstruction for single-suture nonsyndromic cranial synostosis. In this series, delayed intracranial hypertension occurred only in male patients who underwent primary repair of isolated sagittal synostoses at an age less than or equal to 5 months.

Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling.

Exuberant fibroproliferation is a common complication after injury for reasons that are not well understood. One key component of wound repair that is often overlooked is mechanical force, which regulates cell-matrix interactions through intracellular focal adhesion components, including focal adhesion kinase (FAK). Here we report that FAK is activated after cutaneous injury and that this process is potentiated by mechanical loading. Fibroblast-specific FAK knockout mice have substantially less inflammation and fibrosis than control mice in a model of hypertrophic scar formation. We show that FAK acts through extracellular-related kinase (ERK) to mechanically trigger the secretion of monocyte chemoattractant protein-1 (MCP-1, also known as CCL2), a potent chemokine that is linked to human fibrotic disorders. Similarly, MCP-1 knockout mice form minimal scars, indicating that inflammatory chemokine pathways are a major mechanism by which FAK mechanotransduction induces fibrosis. Small-molecule inhibition of FAK blocks these effects in human cells and reduces scar formation in vivo through attenuated MCP-1 signaling and inflammatory cell recruitment. These findings collectively indicate that physical force regulates fibrosis through inflammatory FAK-ERK-MCP-1 pathways and that molecular strategies targeting FAK can effectively uncouple mechanical force from pathologic scar formation.

Novel use of osmotic tissue expanders to treat difficult anterior palatal fistulas.

OBJECTIVE: Novel use of osmotic tissue expanders to recruit local palatal mucoperiosteum for the treatment of difficult anterior palatal fistulas. DESIGN: This is a retrospective review of our experience with osmotic tissue expanders for closure of secondary palatal fistulas. SETTING: The study occurred at Oregon Health and Science University, a tertiary care level academic hospital. PATIENTS, PARTICIPANTS: All patients were treated for combined cleft lip and palate by the Oregon Health and Science University Craniofacial Disorders multidisciplinary team. They were determined to be appropriate candidates due to the anterior location of the fistula and symptomatic nature. Patients complained of significant nasal regurgitation of liquid and solids. INTERVENTIONS: All patients underwent a two-stage procedure under general anesthesia. The first stage was placement of the expanders. The second stage was 1 week later, with removal of the expanders, palatal revision, and closure of the oronasal fistula. MAIN OUTCOME MEASURE: The primary outcome measures determined before data collection were treatment of symptoms and decreased size of fistula. RESULTS: Seven patients with palatal fistulas were treated with osmotic tissue expanders. Five patients had complete closure of the fistula. Two patients demonstrated slit-like fistulas that were no longer symptomatic and were amenable to closure at time of alveolar bone grafting. No complications were observed. CONCLUSIONS: The use of osmotic tissue expanders is a viable alternative for repair of large anterior palatal fistulas, especially in a scarred or previously operated palate. Patients were also no longer symptomatic.

Decreasing the effective radiation dose in pediatric craniofacial CT by changing head position.

BACKGROUND: Children are exposed to ionizing radiation during pre- and post-operative evaluation for craniofacial surgery. OBJECTIVE: The primary purpose of the study was to decrease effective radiation dose while preserving the diagnostic quality of the study. MATERIALS AND METHODS: In this prospective study 49 children were positioned during craniofacial CT (CFCT) imaging with their neck fully extended into an exaggerated sniff position, parallel to the CT gantry, to eliminate the majority of the cervical spine and the thyroid gland from radiation exposure. Image-quality and effective radiation dose comparisons were made retrospectively in age-matched controls (n = 49). RESULTS: When compared to CT scans reviewed retrospectively, the prospective examinations showed a statistically significant decrease in z-axis length by 16% (P < 0.0001) and delivered a reduced effective radiation dose by 18% (P < 0.0001). The subjective diagnostic quality of the exams performed in the prospective arm was maintained despite a slight decrease in the quality of the brain windows. There was statistically significant improvement in the quality of the bone windows and three-dimensional reconstructed images. CONCLUSION: Altering the position of the head by extending the neck during pediatric craniofacial CT imaging statistically reduces the effective radiation dose while maintaining the diagnostic quality of the images.

Application of the vacuum-assisted closure in pediatric patients with orthopedic sequelae of meningococcemia: report of a case successfully treated.

Patients who survive the initial acute phase of fulminant meningococcemia are at an increased risk for serious complications as a result of poor tissue perfusion. It is rare that early surgical intervention is required, as it is relatively difficult to determine the degree of tissue loss early on. Once the patient is stable, debridement of all necrotic tissue is essential and may necessitate extensive removal of skin, subcutaneous tissue, and muscle. Widespread use of the vacuum-assisted closure for complex soft tissue injuries has generally showed accelerated wound healing compared with traditional methods. We report a new possible application of the vacuum-assisted closure system in very young patients with loss of tissue as a result of purpura fulminans secondary to meningococcemia.

TRAIL-R as a negative regulator of innate immune cell responses.

TRAIL receptor (TRAIL-R) signaling has been implicated in inducing apoptosis in tumor cells, but little is understood about its physiological function. Here, we report the generation and characterization of TRAIL-R(-/-) mice, which develop normal lymphocyte populations but possess enhanced innate immune responses. TRAIL-R(-/-) mice exhibited increased clearance of murine cytomegalovirus that correlated with increased levels of IL-12, IFN-alpha, and IFN-gamma. Stimulation of macrophages with Mycobacterium and Toll-like receptor (TLR)-2, -3, and -4, but not TLR9, ligands resulted in high levels of TRAIL upregulation and enhanced cytokine production in TRAIL-R(-/-) cells. The immediate-early TLR signaling events in TRAIL-R(-/-) macrophages and dendritic cells are normal, but I kappa B-alpha homeostatic regulation and NF-kappa B activity at later time points is perturbed. These data suggest that TRAIL-R negatively regulates innate immune responses.