Negative Pressure Wound Therapy for a Giant Wound Secondary to Malignancy-induced Necrotizing Fasciitis: Case Report and Review of the Literature.

BACKGROUND: Necrotizing fasciitis (NF) is a life-threatening condition in which rapid diagnosis, debridement of nonviable tissue, and broad-spectrum antibiotics are critical to effective treatment. The debridement required can be extensive, resulting in large wounds that can sometimes be covered with split-thickness skin grafts (STSGs) with the help of negative pressure wound therapy (NPWT), or vacuum-assisted closure, to decrease the wound size. CASE REPORT: The authors report a rare case of NF due to malignancy-associated bowel perforation with a giant lower extremity wound secondary to debridement that involved 20% of the total body surface area (TBSA) in a 64-year-old, previously healthy, nonsmoking man. The wound was surgically debrided twice and packed before NPWT was applied. Based on the authors' literature search, this case is 1 of the single largest wounds successfully managed with a STSG and NPWT. CONCLUSIONS: Rapid diagnosis of NF is critical to guide surgical management and administration of antibiotics. It is important to be mindful of the origin of certain necrotizing infections, and clinicians should have a greater index of suspicion for NF when assessing skin infections in unwell patients with concomitant bowel perforation secondary to gastrointestinal malignancy.

Obstetrical brachial plexus injury: burden in a publicly funded, universal healthcare system.

OBJECT The aim of this study was to determine the volume and timing of referrals for obstetrical brachial plexus injury (OBPI) to multidisciplinary centers in a national demographic sample. Secondarily, we aimed to measure the incidence and risk factors for OBPI in the sample. The burden of OBPI has not been investigated in a publicly funded system, and the timing and volume of referrals to multidisciplinary centers are unknown. The incidence and risk factors for OBPI have not been established in Canada. METHODS This is a retrospective cohort study. The authors used a demographic sample of all infants born in Canada, capturing all children born in a publicly funded, universal healthcare system. OBPI diagnoses and corresponding risk factors from 2004 to 2012 were identified and correlated with referrals to Canada's 10 multidisciplinary OBPI centers. Quality indicators were approved by the Canadian OBPI Working Group's guideline consensus group. The primary outcome was the timing of initial assessment at a multidisciplinary center, "good" if assessed by the time the patient was 1 month of age, "satisfactory" if by 3 months of age, and "poor" if thereafter. Joinpoint regression analysis was used to determine the OBPI incidence over the study period. Odds ratios were calculated to determine the strength of association for risk factors. RESULTS OBPI incidence was 1.24 per 1000 live births, and was consistent from 2004 to 2012. Potential biases underestimate the level of injury identification. The factors associated with a very strong risk for OBPI were humerus fracture, shoulder dystocia, and clavicle fracture. The majority (55%-60%) of OBPI patients identified at birth were not referred. Among those who were referred, the timing of assessment was "good" in 28%, "satisfactory" in 66%, and "poor" in 34%. CONCLUSIONS Shoulder dystocia was the strongest modifiable risk factor for OBPI. Most children with OBPI were not referred to multidisciplinary care. Of those who were referred, 72% were assessed later than the target quality indicator of 1 month that was established by the national guideline consensus group. A referral gap has been identified using quality indicators at clinically relevant time points; this gap should be addressed with the use of knowledge tools (e.g., a clinical practice guideline) to target variations in referral rates and clinical practice. Interventions should guide the referral process.

Morphologic and Histologic Comparison of Hypertrophic Scar in Nude Mice, T-Cell Receptor, and Recombination Activating Gene Knockout Mice.

BACKGROUND: Proliferative scars in nude mice have demonstrated morphologic and histologic similarities to human hypertrophic scar. Gene knockout technology provides the opportunity to study the effect of deleting immune cells in various disease processes. The authors' objective was to test whether grafting human skin onto T-cell receptor (TCR) αß-/-γδ-/-, recombination activating gene (RAG)-1-/-, and RAG-2γ-/-c-/- mice results in proliferative scars consistent with human hypertrophic scar and to characterize the morphologic, histologic, and cellular changes that occur after removing immune cells. METHODS: Nude TCRαß-/-γδ-/-, RAG-1-/-, and RAG-2-/-γc-/- mice (n = 20 per strain) were grafted with human skin and euthanized at 30, 60, 120, and 180 days. Controls (n = 5 per strain) were autografted with mouse skin. Scars and normal skin were harvested at each time point. Sections were stained with hematoxylin and eosin, Masson's trichrome, and immunohistochemistry for anti-human leukocyte antigen-ABC, α-smooth muscle actin, decorin, and biglycan. RESULTS: TCRαß-/-γδ-/-, RAG-1-/-, and RAG-2-/-γc-/- mice grafted with human skin developed firm, elevated scars with histologic and immunohistochemical similarities to human hypertrophic scar. Autografted controls showed no evidence of pathologic scarring. Knockout animals demonstrated a capacity for scar remodeling not observed in nude mice where reductions in α-smooth muscle actin staining pattern and scar thickness occurred over time. CONCLUSIONS: Human skin transplanted onto TCRαß-/-γδ-/-, RAG-1-/-, and RAG-2-/-γc-/- mice results in proliferative scars with morphologic and histologic features of human hypertrophic scar. Remodeling of proliferative scars generated in knockout animals is analogous to changes in human hypertrophic scar. These animal models may better represent the natural history of human hypertrophic scar.

Primary Nerve Repair for Obstetrical Brachial Plexus Injury: A Meta-Analysis.

BACKGROUND: Nerve repair may be effective in improving function following obstetrical brachial plexus injury. No previous review has directly compared nerve repair to nonoperative management for similar patients, and no previous analysis has been adequately powered to determine whether nerve repair reduces impairment. METHODS: Electronic databases were searched (MEDLINE, Embase, CINAHL, and Cochrane Central). Eligible studies were randomized controlled trials, observational studies, and case series (n > 9); included patients younger than 2 years undergoing nerve repair or nonoperative management of obstetrical brachial plexus injury; and reported functional impairment. Two reviewers independently screened articles using objective a priori criteria. Bias was assessed for each study. Overall quality of evidence was evaluated for each outcome. RESULTS: Among nine cohort studies including 222 patients, nerve repair significantly reduced functional impairment compared with nonoperative management (relative risk, 0.58; 95 percent CI, 0.43 to 0.79; p < 0.001; I = 0 percent; absolute risk reduction, 19 percent; number needed to treat, six). Findings are consistent with comparison of similar patients from case series. With operative management, no deaths were reported; major adverse events were reported in 1.5 percent, and minor adverse events were reported in 5.0 percent of cases. Among demographic (all severities) samples managed nonoperatively, residual impairment remains in 27 percent (19 to 36 percent). CONCLUSIONS: Nerve repair reduces functional impairment in obstetrical brachial plexus injury. Nonoperative management in patients with a deficit at 3 months of age leads to a high proportion of functional impairment. Mortality is not a common risk of modern pediatric microsurgical nerve repair. Residual impairment with nonoperative management is underestimated in the reported literature. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

A nude mouse model of hypertrophic scar shows morphologic and histologic characteristics of human hypertrophic scar.

Hypertrophic scar (HSc) is a fibroproliferative disorder that occurs following deep dermal injury. Lack of a relevant animal model is one barrier toward better understanding its pathophysiology. Our objective is to demonstrate that grafting split-thickness human skin onto nude mice results in survival of engrafted human skin and murine scars that are morphologically, histologically, and immunohistochemically consistent with human HSc. Twenty nude mice were xenografted with split-thickness human skin. Animals were euthanized at 30, 60, 120, and 180 days postoperatively. Eighteen controls were autografted with full-thickness nude mouse skin and euthanized at 30 and 60 days postoperatively. Scar biopsies were harvested at each time point. Blinded scar assessment was performed using a modified Manchester Scar Scale. Histologic analysis included hematoxylin and eosin, Masson's trichrome, toluidine blue, and picrosirius red staining. Immunohistochemistry included anti-human human leukocyte antigen-ABC, α-smooth muscle actin, decorin, and biglycan staining. Xenografted mice developed red, shiny, elevated scars similar to human HSc and supported by blinded scar assessment. Autograft controls appeared morphologically and histologically similar to normal skin. Xenografts survived up to 180 days and showed increased thickness, loss of hair follicles, adnexal structures and rete pegs, hypercellularity, whorled collagen fibers parallel to the surface, myofibroblasts, decreased decorin and increased biglycan expression, and increased mast cell density. Grafting split-thickness human skin onto nude mice results in persistent scars that show morphologic, histologic, and immunohistochemical consistency with human HSc. Therefore, this model provides a promising technique to study HSc formation and to test novel treatment options.

Antagonistic effects of the SRp30c protein and cryptic 5' splice sites on the alternative splicing of the apoptotic regulator Bcl-x.

Alternative 5' splice site selection allows Bcl-x to produce two isoforms with opposite effects on apoptosis. The pro-apoptotic Bcl-x(S) variant is up-regulated by ceramide and down-regulated by protein kinase C through specific cis-acting exonic elements, one of which is bound by SAP155. Splicing to the Bcl-x(S) 5' splice site is also enforced by heterogeneous nuclear ribonucleoprotein (hnRNP) F/H proteins and by Sam68 in cooperation with hnRNP A1. Here, we have characterized exon elements that influence splicing to the 5' splice site of the anti-apoptotic Bcl-x(L) isoform. Within a 86-nucleotide region (B3) located immediately upstream of the Bcl-x(L) donor site we have identified two elements (ML2 and AM2) that stimulate splicing to the Bcl-x(L) 5' splice site. SRp30c binds to these elements and can shift splicing to the 5' splice site of Bcl-x(L) in an ML2/AM2-dependent manner in vitro and in vivo. The B3 region also contains an element that represses the use of Bcl-x(L). This element is bound by U1 small nuclear ribonucleoprotein and contains two 5' splice sites that can be used when the Bcl-x(L) 5' splice site is mutated or the ML2/AM2 elements are deleted. Conversely, mutating the cryptic 5' splice sites stimulates splicing to the Bcl-x(L) site. Thus, SRp30c stimulates splicing to the downstream 5' splice site of Bcl-x(L), thereby attenuating the repressive effect of upstream U1 snRNP binding sites.