Serum Amyloid P Attenuates Hypertrophic Scarring in Large Animal Models.

INTRODUCTION: This study's purpose was to (1)determine the effect of locally administered serum amyloid P (SAP) on the development of hypertrophic scars (HTS) in porcine and rabbit HTS models and (2)determine the pharmacokinetics of systemically administered SAP and its effect on circulating fibrocyte quantities. METHODS: Two large animal (New Zealand White Rabbit and Female Red Duroc Pigs) HTS models were utilized to study the effects of daily local injections of SAP immediately post wounding (x5 d in rabbits; x7 d in pigs) on HTS development as measured by scar elevation index , scar area, wound closure, and molecular expression studies of scar components. For SAP pharmacokinetics, total and human SAP levels in porcine blood were measured at regular intervals following intravenous administration of human SAP. Fibrocyte quantities were determined prior to and 1 h following human SAP intravenous administration. RESULTS: In the rabbit model, local SAP significantly decreased the level of tissue inhibitor of metalloproteinases-1 mRNA expression and maintained matrix mettaloproteinase-9 expression, while control and vehicle groups significantly declined. In the pig model, there was a significant decrease in the trend of scar elevation indexes treated with local SAP versus controls over the study period. This decrease was statistically significant at days 14 and 84. Human SAP administered intravenously is degraded within 24 h and does not influence circulating fibrocyte quantities. CONCLUSIONS: This is the first study to demonstrate attenuation of HTS formation using locally administered SAP in large animal HTS models. Local SAP administration reduces HTS formation by maintaining matrix mettaloproteinase-9 and decreasing tissue inhibitor of metalloproteinases-1. Intravenous administration of SAP is not as effective.

Thin and Ultra-Thin Split-Thickness Skin Grafts Are Safe and Efficacious in the Burn Population.

Split-thickness skin-grafts are a mainstay of burn management. Studies suggest no benefit to using thick (0.025 inch) over standard (0.012-0.020 inch) grafts, and some support the use of thin (0.008 inch) over standard thickness. Data on the use of even thinner grafts is scarce. This study reviewed outcomes of burn patients treated with thin (0.008-0.011 inch) and ultra-thin (≤0.007 inch) grafts. Retrospective review of records from July 2012 to June 2016 included patients who sustained operative burns treated by a single surgeon. Patients were excluded for nonoperative injuries, inhalational injuries, or prolonged hospitalizations. Outcome measures were compared between thin and ultra-thin groups. One-hundred twenty-eight patients met inclusion criteria; 35 received thin split-thickness skin-grafts while 93 received ultra-thin. Cohort analysis demonstrated equivalent graft-take, time to reepithelialization, and functional outcomes. Time to donor-site healing was significantly faster in the ultra-thin cohort (P = .04). Of those with functional outcomes recorded, 88.1% had good-excellent function and 11.9% retained a limitation in function as designated in physical therapy notes. There were fewer complications overall (P = .004) and a lower incidence of hypertrophic scarring (P = .025) in the ultra-thin cohort. This study presents a single-surgeon experience with thin and ultra-thin split-thickness skin-grafts. These grafts are exhibit excellent graft-take and few complications. There was no correlation between thickness and functional outcome at the time of physical therapy discharge. Donor-site reepithelialization was faster with ultra-thin grafts, which may be important in patients with large burns and limited donor sites.

Self-inflicted burn injuries: Etiologies, risk factors and impact on institutional resources.

INTRODUCTION: Self-inflicted burns are a rare cause of injury, accounting for only 1.0% of burns in the United States. While rare, the physical and psychosocial ramifications of these injuries are lasting. The goal of this study was to examine the etiologies, risk factors and outcomes of self-inflected burns in an urban setting. METHODS: Records of all patients presented to a regional burn center from July 2011 to June 2015 were reviewed. Those who sustained a self-inflected burn were identified and included in this study. Demographic data, psychiatric history, previous self-harm records, insurance status, injury circumstance, burn characteristic [location and total body surface area (TBSA)], need for excision and grafting, graft-take and duration of hospital stay and costs were reviewed. This group was then compared to a cohort of 166 patients with non-intentional burn during the same time frame matched for age and TBSA%. RESULTS: There were 34 patients with a mean (SD) age of 31 (15.2) who sustained a self-inflicted burn during the study period. The mean TBSA% was 2.8 (SD=5.1), with most injuries in the upper and lower extremities. Fifty three percent of the patients presented with altered mental status secondary to either psychiatric illness or intoxication. Twenty-four percent of incidents were claimed as suicide attempts and suicidal ideation was present in 47% of cases. Twenty-six percent of patients with a previous psychiatric diagnosis were not on a psychiatric medication prior to incident. There was record of previous self-harm in 26% of patients. When compared to control group of 166 patient with non-intentional burn, patients with self-inflicted burn had higher rates of substance abuse (35% vs. 13%, p<0.05), longer stay in the hospital (11.3 vs. 5.3 days, p<0.01), longer stay in the intensive care unit (1.8 vs. 0.2 days, p<0.01), and lower rates of insurance (15% vs. 42%, p<0.001). These patients also exhibited a higher need for excision and grafting (41% vs. 20%, p<0.01). CONCLUSIONS: Patients with self-inflected burn have a higher rate of previous self-harm behavior, psychiatric comorbidities and substance abuse. These patients are more likely to require surgical excision and grafting and expanded institutional resources compared to those with non-intentional burn with similar degree and size of burn. Increased counseling of at-risk populations may help to decrease this potentially preventable method of injury.

Epidemiology and Outcomes of Auricular Burn Injuries.

Auricular burns represent a unique type of injury. The acute management and clinical course of these injuries can be different from other facial burns. There is a paucity of literature pertaining to the epidemiology and acute management of auricular burns. Most studies focus on deformity reconstruction. The aim of this study was to characterize the epidemiology, treatment, and outcomes of auricular burns. Data from all patients presenting to a regional burn center in a 4-year period were reviewed and those with auricular burns were identified. Demographic data, burn mechanism, insurance status, method of treatment, need for skin grafting, percentage graft-take, time to reepithelialization and incidence of deformity were reviewed. During the study period, 593 facial burns were evaluated and 132 (22%) sustained burns to the auricle. The most common mechanisms of injury were flame (65.1%) and scalding (22.5%). Auricular burns were mostly second degree (88%), involved both ears in 44%, and involved only the ventral aspect of the ear in 57%. The majority of patients healed well with conservative management; none suffered from chondritis. Of the 89 patients followed to healing, 1 patient (1.1%) received full-thickness skin grafts to the auricle, resulting in excellent graft-take. All other patients were managed nonoperatively, and none suffered from ear deformities. Auricular burns occur with surprising frequency in patients presenting to burn centers. Careful acute management of these injuries can eliminate development of chondritis and minimize the rate of deformity and need for reconstruction. The majority of wounds heal with conservative management, but time to reepithelialization can be prolonged.

Indications and Controversies for Complete and Implant-Enhanced Latissimus Dorsi Breast Reconstructions.

This article describes the use of implant-enhanced and total-autologous latissimus dorsi myocutaneous flaps in breast reconstruction. It addresses the indications for use of this reconstruction alternative, which have recently been expanded thanks to the advent of high-volume fat grafting. Given its straightforward dissection, reliable vascular pedicle, variety of approaches, and potential for excellent aesthetic results, use of latissimus dorsi flaps may be considered among first-line options in selected patients.

The Impact of Body Contouring Procedures on Urologic Outcomes in Massive Weight Loss Patients.

BACKGROUND: Post-massive weight loss body contouring is a growing area of plastic surgery. Studies have shown preexisting urinary incontinence amelioration in patients undergoing abdominal body-contouring procedures. These studies are small, focus on cosmetic abdominoplasties, and lack use of standardized surveys. The purpose of this study was to evaluate urinary incontinence endpoints in massive weight loss patients undergoing body-contouring procedures. METHODS: A retrospective review was conducted over a 6-year period. Patients excluded had previous body-contouring procedures or previously treated urinary incontinence. Participants completed validated surveys to catalogue preoperative and postoperative urinary habits. Patients were then subdivided based on presence of preoperative incontinence. Outcomes were compared within and between cohorts using the t test and chi-square test. RESULTS: A total of 102 patients completed the survey. Of those, 44 had preoperative urinary incontinence. Patients with incontinence were found to be significantly older than those who did not. Postoperatively, patients with preoperative incontinence had significant decreases in incidence and severity of symptoms (p < 0.01, respectively), and significantly improved their quality of life (p < 0.02). Over 20 percent noted symptom resolution, and 67 percent were mostly or completely satisfied with the outcome. CONCLUSIONS: This study is the first to document amelioration of urinary incontinence symptoms in massive weight loss patients undergoing body-contouring procedures. It adds to the literature suggesting that abdominoplasties in select patients may improve incontinence symptoms. Future work will focus on evaluating the mechanism of this outcome and documenting improvement in an objective, prospective manner. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Use of a home vacuum-assisted closure device in the burn population is both cost-effective and efficacious.

INTRODUCTION: The vacuum assisted closure device (VAC) improves wound-healing when utilized as a bolster to secure split thickness skin grafts (STSG). Patients typically remain hospitalized for VAC therapy; however, home VACs (hVAC) are now available. Limited studies examine burns treated with hVAC as a STSG bolster. METHOD: A retrospective study of records from an ABA verified regional burn center was conducted over 23 months. Patients included STSGs for burn. Data points included demographics, burn mechanism and location, graft characteristics, hospital length of stay (LOS), and time to heal. RESULTS AND DISCUSSION: Fifty patients were included, with average age of 39 years (range <1-83years). Average burn TBSA was 1.27±1.42 (range 0.05-8.18). Grafted area average was 102.9±128.1cm2. The most commonly treated areas were the leg/foot, thigh, and torso (53%, 16%, and 16%, respectively). Average LOS was 1.1±1.2 days. Mean graft-take was 99.2±2.8% with one patient undergoing repeat STSG. Average post-operative time to heal was 16±6 days. A 5-day inpatient stay with a VAC costs an average of $34,635, compared to $9134 for an hVAC over the same period. CONCLUSIONS: The hVAC is a cost-effective STSG bolster in the burn population for appropriate candidates. Excellent graft-take and low morbidity rates imply that this is an efficacious alternative for STSG bolster.

Jewelry Ring-Associated Electrothermal Burn Injuries: A Nine-Patient Case Series.

Ring-associated burns are infrequent, comprising only a small fraction of burn consults and admissions. However, because of the location of these burns and the propensity for circumferential wounds, small burn size may belie the severity of resultant injuries. Herein, the authors present their experience with this potentially severe type of burn. Records from a regional burn center were retrospectively analyzed during a 36-month period. All patients who sustained ring burns were included. Data points included demographics, burn location, need for surgical intervention, grafted area, hospital days (length of stay), percent graft take, complications, and time to re-epithelialization. Nine patients sustained ring-associated burns during the study period, accounting for 1.4% of all patients with burns seen during the same period. Average age was 41 years (range: 29-52 years). Seven (77%) ring-associated burns involved contact with a battery. All injuries were circumferential. Average burn TBSA was 0.07%. Two patients (22%) had third-degree injuries, both of which received split-thickness skin grafts. Grafted area was 4 and 5 cm, respectively. Average length of stay was 2.8 days. Mean graft take was 99.5 ± 1.5%. Average time to complete re-epithelialization was 12 days. One patient suffered temporary disability. No patients suffered from compartment syndrome. Ring-associated burns are an uncommon source of injury in the burn population. Despite small burn TBSA, these patients are more likely to require split-thickness skin grafts and suffer dysfunction compared with similarly-sized burns in other body regions. Expedient treatment and coordination with occupational therapy should be undertaken to achieve optimal outcomes.

Increased in vitro differentiation of fibrocytes from keloid patients is inhibited by serum amyloid P.

Keloid scarring is a form of fibroproliferative dermal wound healing characterized by growth beyond the confines of the original wound. Fibrocytes, derived from peripheral blood mononuclear cells and inhibited by serum amyloid P (SAP), have been linked to other fibroproliferative diseases. We hypothesized that peripheral blood mononuclear cells of keloid formers have a higher propensity to differentiate into fibrocytes and are more resistant to the effects of SAP. To test this hypothesis, plasma was isolated from peripheral blood samples of keloid (n = 10) and age/sex/race-matched control (n = 10) subjects, and SAP levels were measured by enzyme-linked immunosorbent assay. Equal numbers of peripheral blood mononuclear cells were also isolated from these samples and fibrocytes cultured in serum-free media with increasing concentrations of SAP. No difference in plasma SAP levels was found between keloid and control subjects. In the absence of SAP, keloid patients (n = 7) had almost 20 times more fibrocytes than controls (n = 7) in culture (median: 1,087 cells vs. 60 cells; p < 0.01). SAP inhibited the differentiation of keloid fibrocytes in vitro, although a higher concentration of SAP was needed when compared with controls (20 µg/mL keloid vs. 5 µg/mL control). Fibrocytes may contribute to the pathogenesis of keloids, and SAP has potential as a therapeutic agent in the prevention of these lesions.

Wound healing characteristics of ICAM-1 null mice devoid of all isoforms of ICAM-1.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) permits leukocyte-endothelial adhesion and transmigration during inflammation. Membrane-bound ICAM-1 knockout mice have been used to understand this molecule's role in wound-healing, but expressed spliced isoforms of ICAM-1 that may have impacted results. We aimed to characterize wound-healing in an ICAM-1 null model devoid of all ICAM-1 isoforms. METHODS: Full-thickness 8-mm wounds were created on C57/BL6 wild-type (n = 24) and ICAM-1 null (n = 24) mice. Wound area was calculated using daily photographs. Histologic samples were harvested on postoperative Days 1, 3, 7, and 14. Wound margins were evaluated for mRNA expression of 13 inflammatory cytokines. A separate group of wild-type and ICAM-1 null mice (n = 24) received full-thickness incisions with tensiometry measured at Day 14. Separately, complete blood counts were measured in unwounded wild-type (n = 4) and ICAM-1 null mice (n = 4). RESULTS: Wound-closure was significantly delayed in ICAM-1 null mice through Day 7 by gross and histologic measurement. mRNA expression of VEGF-A was increased in ICAM-1 null mice on Day 3, although no increase in VEGF-A was observed in the wound bed by immunohistochemistry. ICAM-1 null wounds demonstrated higher stiffness by tensiometry on Day 14 compared to the wild-type (1880 ± 926 kPa versus 478 ± 117 kPa; P < 0.01), and had higher counts of white blood cells (10,009 versus 5720 cells/µL, P < 0.05), neutrophils (2130 versus 630 cells/µL, P < 0.01), and lymphocytes (7130 versus 4,740 cells/µL, P < 0.05). CONCLUSIONS: ICAM-1 null mice demonstrate delayed wound-healing and decreased wound elasticity compared to wild-type controls. This lag, however, was less than observed in earlier membrane-bound ICAM-1 knockouts, suggesting that other ICAM-1 isoforms may promote delayed wound-healing.

Near-infrared spectroscopy measurement of abdominal tissue oxygenation is a useful indicator of intestinal blood flow and necrotizing enterocolitis in premature piglets.

PURPOSE: A major objective of necrotizing enterocolitis (NEC) research is to devise a noninvasive method of early detection. We hypothesized that abdominal near-infrared spectroscopy (A-NIRS) readings will identify impending NEC in a large animal model. METHODS: Piglets were prematurely delivered and received parenteral nutrition followed by enteral feedings. Serial A-NIRS readings were obtained for 5 days, and animals were monitored for NEC. Separately, A-NIRS readings were obtained in healthy piglets to validate the correlation of A-NIRS with splanchnic oxygen delivery. RESULTS: Of 29 piglets, 3 developed NEC. Eleven piglets without NEC died prematurely. Fifteen piglets remained healthy, had normal histologic assessment of their intestines, and served as controls. Abdominal near-infrared spectroscopy readings within 12 hours of birth were significantly lower in animals that developed NEC compared with healthy littermates (4% vs 33%, P = .02). For all time-points measured, A-NIRS readings were significantly lower in the NEC group compared with controls (21% vs 55%, P < .001). Abdominal near-infrared spectroscopy readings correlated with both decreased pulse oximetry readings during apneic episodes (r = 0.96) and increased superior mesenteric artery flow in response to glucagon-like peptide 2 (r = 0.67). CONCLUSION: Abdominal near-infrared spectroscopy is capable of detecting alterations in intestinal oxygenation and perfusion in neonatal piglets and may allow early detection of neonates at risk for NEC.

Tumor volume to fetal weight ratio as an early prognostic classification for fetal sacrococcygeal teratoma.

PURPOSE: This study was designed to develop a prognostic factor for fetuses with sacrococcygeal teratoma (SCT) that may be useful to predict outcome and guide counseling early in pregnancy. We hypothesize that, in fetuses with SCT, the ratio of tumor size to estimated fetal weight in the second trimester predicts outcome. METHODS: We retrospectively reviewed charts of all patients evaluated at our Fetal Center for SCT between 2004 and 2009. Estimated fetal weight and tumor volume were calculated based on prenatal ultrasound or fetal magnetic resonance imaging. Patients were stratified based on tumor volume to fetal weight ratio (TFR), and their outcomes were analyzed by Fisher's Exact test. RESULTS: Tumor volume to fetal weight ratio before 24 weeks' gestation was predictive of outcome. Those with a TFR less than or equal to 0.12 (n = 5) had a significantly better outcome than patients with a TFR greater than 0.12 (n = 5, P < .05). All patients with poor outcomes had a TFR greater than 0.12 by 24 weeks' gestation. A TFR greater than 0.12 predicted poor outcome with 100% sensitivity and 83% specificity. All 4 patients who developed hydrops had a TFR greater than 0.12. CONCLUSION: In our series of fetuses with SCT, TFR before 24 weeks' gestation correlates with outcome. This novel, prenatal diagnostic tool may be useful in prenatal counseling and for early identification of high-risk fetuses.

Managing the relationship between quality and cost-effective burn care.

In the modern era of fiscal prudence, managing the relationship between quality health care and cost reduction is a complex and challenging task for policy makers and health care providers. Health economics is an applied field that aids in assessing the feasibility of incorporating new interventions in a certain field. Applying these tools when allocating funds for burn care is even more complicated due to the lack of clinical data regarding the cost effectiveness of different aspects in burn care. Herein we review the existing literature and summarize different approaches for achieving cost effective health care in general and in burn care specifically. Special considerations to funds allocation in burn care are also discussed.

Silicone-based scar therapy: a review of the literature.

Hypertrophic and keloid scars still are among the banes of plastic surgery. In the treatment arsenal at the disposal of the plastic surgeon, topical silicone therapy usually is considered the first line of treatment or as an adjuvant to other treatment methods. Yet, knowledge concerning its mechanisms of action, clinical efficacy, and possible adverse effects is rather obscure and sometimes conflicting. This review briefly summarizes the existing literature regarding the silicone elastomer's mechanism of action on scars, the clinical trials regarding its efficacy, a description of some controversial points and contradicting evidence, and possible adverse effects of this treatment method. Topical silicone therapy probably will continue to be the preferred first-line treatment for hypertrophic scars due to its availability, price, ease of application, lack of serious adverse effects, and relative efficacy. Hopefully, future randomized clinical trials will help to clarify its exact clinical efficacy and appropriate treatment protocols to optimize treatment results.

Simvastatin promotes angiogenesis and prevents microvascular remodeling in chronic renal ischemia.

We tested the hypothesis that statins would decrease renal injury in renal artery stenosis (RAS) by restoring angiogenesis and attenuating intrarenal microvascular (IMV) remodeling. Single-kidney hemodynamics and function were quantified using electron-beam-computed tomography (CT) in normocholesterolemic pigs after 12 wk of experimental RAS, RAS supplemented with simvastatin (RAS+simvastatin), and normal controls. Renal circulation was also studied in vivo using angiography and ex vivo using a unique 3D micro-CT imaging technique. Angiogenic and remodeling pathways were subsequently explored in renal tissue. Blood pressure and the degree of stenosis were similarly increased in RAS groups. Simvastatin in RAS enhanced both intrarenal angiogenesis and peri-stenosis arteriogenesis and increased the expression of angiogenic growth factors and hypoxia-inducible factor-1alpha. Furthermore, simvastatin decreased tissue-transglutaminase expression and IMV inward remodeling, restored IMV endothelial function, decreased fibrogenic activity, and improved renal function. Chronic simvastatin supplementation promoted angiogenesis in vivo, decreased ischemia-induced IMV remodeling, and improved IMV function in the stenotic kidney, independent of lipid lowering. These novel renoprotective effects suggest a role for simvastatin in preserving the ischemic kidney in chronic RAS.

Pathways of renal fibrosis and modulation of matrix turnover in experimental hypercholesterolemia.

Dyslipidemia often accompanies and accelerates renal disease, partly by promoting fibrosis. However, the mechanisms mediating this effect are unclear. We hypothesized that hypercholesterolemia modulates several interlinked pathways that promote deposition and blunt degradation of extracellular matrix, and that these could be manipulated by reversal of hypercholesterolemia. Fourteen pigs were fed a 16-week 2% high-cholesterol diet (HC-HC; n=7) or normal diet (n=7), whereas in 7 others, a 10-week HC was followed by a 6-week normal diet (HC-N). Renal endothelial function was assessed in vivo with electron-beam computed tomography, and renal tissue was then studied ex vivo using Western blot, real-time quantitative polymerase chain reaction, gelatin zymography, and immunostaining. HC-HC kidneys showed endothelial dysfunction, accompanied by increased intrarenal oxidative stress, inflammation, activation of the endothelin and transforming-growth factor-beta systems, and decreased matrix metalloproteinase expression and activity. Accordingly, HC-HC kidneys showed increased collagen IV expression and fibrosis. A lipid-lowering dietary intervention reversed most of these changes. In conclusion, this study indicates that renal fibrosis in early atherosclerosis is a result of a simultaneous increase in extracellular matrix deposition and blunted matrix metalloproteinase-mediated degradation, overall promoting perivascular and tubulointerstitial fibrosis. Notably, many of these pathways may be reversible in hypercholesterolemia, and crucial targets could potentially be identified for early interventions to preserve the kidney.