Perioperative support, not volume, is necessary to optimize outcomes in surgical management of necrotizing enterocolitis.

BACKGROUND: This study examines the relationship between hospital volume of surgical cases for necrotizing enterocolitis (NEC) and patient outcomes. METHODS: A retrospective cross-sectional review was performed using the HCUP SID for California from 2007 to 2011. Patients with NEC who underwent surgery were identified using ICD-9CM codes. Risk-adjusted models were constructed with mixed-effects logistic regression using patient and demographic covariates. RESULTS: 23 hospitals with 618 patients undergoing NEC-related surgical intervention were included. Overall mortality rate was 22.5%. There were no significant differences in the number of NICU beds (p = 0.135) or NICU intensivists (p = 0.469) between high and low volume hospitals. Following risk adjustment, no difference in mortality rate was observed between high and low volume hospitals respectively (24.0% vs. 20.3%, p = 0.555). CONCLUSIONS: Our observation that neonates with NEC treated at low-volume centers have no increased risk of mortality may be explained by similar availability of NICU and intensivists resources across hospitals.

Heparin-binding epidermal growth factor-like growth factor gene disruption is associated with delayed intestinal restitution, impaired angiogenesis, and poor survival after intestinal ischemia in mice.

PURPOSE: We have demonstrated that administration of heparin-binding epidermal growth factor-like growth factor (HB-EGF) protects the intestines from injury. The aim of the current study was to evaluate the effect of HB-EGF gene disruption on intestinal restitution, angiogenesis, and long-term survival after intestinal ischemia/reperfusion (I/R) injury. METHODS: HB-EGF (-/-) and wild-type HB-EGF (+/+) littermate mice were subjected to 45 minutes of superior mesenteric artery occlusion followed by reperfusion. Functional recovery of the gut permeability barrier was evaluated with Ussing chamber studies, and microvessel density was evaluated immunohistochemically. Animal survival was evaluated using the Kaplan-Meier method. RESULTS: Histologic damage after ischemia was significantly higher in HB-EGF (-/-) mice compared with HB-EGF (+/+) mice, associated with a significantly higher number of incompetent (nonhealed, nonresurfaced) villi indicative of delayed structural healing by restitution. HB-EGF (-/-) mice had increased intestinal permeability after intestinal I/R. HB-EGF (-/-) mice had significantly lower microvessel density at 3 and 7 days after I/R, indicating that HB-EGF gene deletion resulted in delayed onset of angiogenesis. Two-week mortality rates were significantly higher in HB-EGF (-/-) mice. CONCLUSIONS: Endogenous HB-EGF significantly enhances healing by restitution, prolongs survival, and enhances angiogenesis in mice subjected to intestinal I/R injury. These findings support our hypothesis that HB-EGF administration may improve outcome in patients with intestinal I/R injury, including necrotizing enterocolitis.

A silver impregnated antimicrobial dressing reduces hospital length of stay for pediatric patients with burns.

We sought to study whether the application of a novel silver impregnated antimicrobial dressing (Aquacel Ag, ConvaTec, Princeton, NJ) affects the hospital length of stay in pediatric patients with partial-thickness burns. A retrospective review of Burn Registry Data from a large children's hospital burn unit was conducted to answer this question. Pediatric patients admitted with partial-thickness burns treated with Aquacel Ag from January 2005 through August 2005 were included in the study (n = 39). The comparison group of patients treated with silver sulfadiazine (SSD; Par Pharmeceuticals, Woodcliff, NJ) cream was matched for age and %TBSA burned from the same time period the previous year (n = 40). Analysis was conducted for intent to treat. Mean length of stay for control patients treated with SSD was significantly longer (8.36 days) compared with Aquacel Ag-treated patients (4.48 days; p = .002, t-test for unequal variances). Length of stay for both groups was significantly associated with %TBSA burned (p < .001, r2 = .38). Post-hoc analysis controlling for %TBSA burned revealed an adjusted mean length of stay for the control group that was longer than that of the Aquacel Ag group (5.9 days vs. 3.8 days, respectively). These data confirm that application of a new burn dressing (Aquacel Ag) reduces hospital length of stay. Reduction in the complexity and number of dressing changes needed with use of Aquacel Ag, in combination with significantly reduced length of stay, should result in a significant cost savings in the care of this patient population.

A silver-impregnated antimicrobial dressing reduces hospital costs for pediatric burn patients.

PURPOSE: Since using a novel silver-impregnated antimicrobial dressing (Aquacel Ag, ConvaTec, Princeton, NJ) in our pediatric patients with partial-thickness burns, hospital LOS has been significantly reduced. Here we investigated whether there was concomitant cost-effectiveness of this approach. METHODS: We retrospectively reviewed Burn Registry Data from a large Children's Hospital Burn Unit from January 2005 through August 2005 for inpatients with partial-thickness burns treated with Aquacel Ag. A comparison group was composed of patients from the same period the previous year treated with silver sulfadiazine cream (SSD, Par Pharmaceuticals, Woodcliff, NJ) and matched for age and %TBSA burned. Patients with inhalation injury or full-thickness burns were excluded. Intent-to-treat analysis was limited to patients with less than 22% TBSA burn. Direct costs and total charges were compared statistically after log transformation due to the skewedness of the data. RESULTS: Total charges and direct costs were significantly lower for Aquacel Ag-treated patients (n = 38) than for SSD-treated patients (n = 39) (P = .004 and P < .001, respectively). In addition, Aquacel Ag-treated patients had a shorter LOS than SSD-treated patients. DISCUSSION: These data strongly support our findings that the application of Aquacel Ag reduces hospital LOS which results in a significant cost savings in the care of pediatric patients with partial-thickness burns.

Functional genomics and gene expression profiling in sepsis: beyond class prediction.

Functional genomics involving genome-wide expression analyses is rapidly finding applications in clinical medicine. New technologies now permit the simultaneous analysis of mRNA levels for the entire human transcriptome from as few as 1000 cells. This approach is dramatically changing the way we define health and disease, allowing, for the first time, an unbiased view of the global changes in gene expression that are occurring. For the study of trauma biology and sepsis, this technology offers a powerful tool to develop molecular signatures for inflamed tissues and specific cell populations. At present, functional genomics is being used to classify the progress of disease and survival in response to traumatic and burn injury, sepsis and visceral ischemia, and reperfusion injury, as well as to describe patterns of gene expression in response to varying microbial pathogens. As the number of bioinformatics tools increases, functional genomics is beginning to reveal the underlying complexity of the biological response to a variety of inflammatory diseases and is providing new approaches for their exploration. Functional genomics is becoming a standard tool in inflammation research as a means to unravel the basic biological processes.

Administration of prenatal betamethasone suppresses the adrenal-hypophyseal axis in newborns with congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a condition that is characterized by pulmonary hypoplasia and pulmonary hypertension. Prenatal betamethasone often is administered to fetuses with CDH to improve pulmonary function. In this study, the authors investigate the possible role of the adrenal-hypophyseal axis in CDH in an animal model and subsequently in human infants with CDH. METHODS: Twin fetal sheep underwent creation of DH or a sham thoracotomy, and levels of plasma and lung ACTH and plasma cortisol were compared. For the human studies, plasma levels of ACTH, cortisol, and DHEA were measured in cord blood samples collected from 9 CDH (5 that received prenatal betamethasone) and compared with those of 14 normal newborns. In both studies, ACTH and cortisol levels were determined by radioimmunoassay (RIA). Human (DHEA) levels were determined by ELISA. RESULTS: Plasma ACTH and cortisol levels were elevated in fetal DH sheep compared with sham-operated controls; however, levels of ACTH in lung tissues were not different. Human newborns with CDH who have been exposed to prenatal steroids have significantly lower plasma ACTH, cortisol, and DHEA levels than normal newborns and CDH newborns not exposed to prenatal betamethasone. CONCLUSIONS: In an ovine model of CDH, the adrenal-hypophyseal axis appears up-regulated in DH fetuses compared with sham-operated animals. Conversely, the adrenal-hypophyseal axis in human CDH newborns appears normal but is suppressed by the administration of prenatal betamethasone.

Temporal patterns of gene expression in murine cutaneous burn wound healing.

The global changes in gene expression in injured murine skin were characterized following a second-degree scald burn. Dorsal skin was harvested from uninjured and from burned mice at 2 h and at 3 and 14 days following immersion in 65 degrees C water for 45 s. Gene expression was surveyed using an Affymetrix U74Av2 GeneChip, and patterns of gene expression were analyzed using hierarchical clustering and supervised analysis. Burn injury produced significant alterations in the expression of a number of genes, with the greatest changes seen 3 and 14 days after the scald burn. Using a supervised analysis with a false discovery rate of 1% or 5%, differences in the expression of 192 or 1,116 genes, respectively, discriminated among the unburned skin and the three time points after the burn injury. Gene expression was primarily a transient and time-dependent upregulation. The expression of only 24 of the 192 discriminating genes was downregulated after the burn injury. No gene exhibited a sustained increase in expression over the entire 14 days following the burn injury. Gene ontologies revealed an integrated upregulation of inflammatory and protease genes at acute time intervals, and a diminution of cytoskeletal and muscle contractile genes at 3 or 14 days after the injury. Following a second-degree scald burn, global patterns of gene expression in the burn wound change dramatically over several weeks in a time-dependent manner, and these changes can be categorized based on the biological relevance of the genes.

Management of blunt pediatric hepatic and splenic injury: similar process, different outcome.

Though nonoperative management of stable children with blunt solid organ injury has been shown to be effective, we hypothesize that hepatic injuries represent a higher mortality risk than splenic injuries and that combination hepatosplenic injury is a marker of even greater mortality potential. A multi-institutional pediatric trauma registry was queried for all children with blunt injuries to the liver (H) or spleen (S), excluding those with severe brain injury. Incidence and mortality of H, S, and all combinations of H/S were compared. The mortality rate for patients with H was significantly higher (2.5%) than in patients with S (0.7%), and the overall mortality of H/S (8.6%) was significantly higher than both. Furthermore, the mortality of H/S injuries was associated with increasing severity of either the hepatic or splenic injury. In childhood injury, H and S occur with almost equal frequency but with different mortality, and H/S is less common but associated with increased mortality.

Analysis of gene expression patterns in human postburn hypertrophic scars.

Hypertrophic scars cause cosmetic disfigurement and limited mobility in burn patients. To better understand the molecular pathophysiology of hypertrophic scar formation, microarray analyses were performed on normal skin and hypertrophic scars from four burn patients. Microarray analyses were determined in an effort to identify genes whose expression discriminated between normal skin and mature, hypertrophic scars. Surgical biopsies were obtained from two pediatric and two adult patients 6 to 15 months after burn injury. Total RNA was isolated from the samples and subjected to microarray analysis using the Affymetrix U95Av2 GeneChip. Results from this analysis revealed 31 probe sets representing genes that were consistently up-regulated at least two-fold in hypertrophic scar specimens from all four patients and four probe sets that were down-regulated. The significance analysis of microarrays algorithm also identified 35 probe sets whose increased expression resulted in the hierarchal clustering of the hypertrophic scar and normal tissue, seven of which were identical to the six genes identified by paired analyses. These six genes all displayed elevated levels of expression in the scar tissue. Proteins encoded by the genes identified included germline oligometric matrix protein, matrix metalloproteinase-16, collagen type 1alpha, pleiotrophin, and thrombospondin-4. Although the results presented here suggest that there may be unique patterns of gene expression in hypertrophic scars that may be important in the evaluation and treatment of hypertrophic scarring, the results must be confirmed with larger datasets.