Paul Wurzer

Onset and duration of effect of incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA in the treatment of glabellar frown lines: a randomized, double-blind study

Background Three botulinum neurotoxin type A preparations (incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA) are widely approved in Europe and in the US for the treatment of glabellar frown lines. The purpose of this study was to determine and compare the time to onset and duration of treatment effect of incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA for the treatment of glabellar frown lines. Subjects and methods Subjects aged 20–60 years with moderate to severe glabellar frown lines received one treatment of either 21 units (U) incobotulinumtoxinA, 21 U onabotulinumtoxinA, or 63 U abobotulinumtoxinA. Assessments were made over a period of 180 days. Onset of treatment effect was defined as the day that the observer noted a decrease in glabellar muscle activity compared with baseline photographs and videos. Duration of treatment effect was defined as the time until glabellar muscle action returned to the baseline level. Analyses were performed using a Weibull log(T) regression model. Results The study enrolled 180 subjects; 60 per group. For all three products, onset of treatment effect occurred earlier in female subjects compared to male subjects. For both sexes, a significantly earlier time to onset of treatment effect was seen for incobotulinumtoxinA compared to onabotulinumtoxinA and abobotulinumtoxinA; in female subjects these times were 3.02 days, 5.29 days, and 5.32 days, respectively. The duration of treatment effect was longer for incobotulinumtoxinA compared to onabotulinumtoxinA and abobotulinumtoxinA; for all products, treatment effect duration was longer in females than in males. Time to onset was not a predictor of treatment duration. Conclusion IncobotulinumtoxinA demonstrated a more rapid onset and a longer duration of treatment effect than onabotulinumtoxinA (1:1 dose ratio) and abobotulinumtoxinA (1:3 dose ratio). Onset of effect was faster and duration of effect was longer in female subjects compared to male subjects.

Reversal of Growth Arrest with the Combined Administration of Oxandrolone and Propranolol in Severely Burned Children

Background: The hypercatabolic response in severely burned pediatric patients is associated with increased production of catecholamines and corticosteroids, decreased formation of testosterone, and reduced strength alongside growth arrest for up to 2 years after injury. We have previously shown that, in the pediatric burned population, the administration of the testosterone analog oxandrolone improves lean body mass accretion and bone mineral content and that the administration of the &bgr;1-, &bgr;2-adrenoceptor antagonist propranolol decreases cardiac work and resting energy expenditure while increasing peripheral lean mass. Here, we determined whether the combined administration of oxandrolone and propranolol has added benefit. Methods: In this prospective, randomized study of 612 burned children [52% ± 1% of total body surface area burned, ages 0.5–14 years (boys); ages 0.5–12 years (girls)], we compared controls to the individual administration of these drugs, and the combined administration of oxandrolone and propranolol at the same doses, for 1 year after burn. Data were recorded at discharge, 6 months, and 1 and 2 years after injury. Results: Combined use of oxandrolone and propranolol shortened the period of growth arrest by 84 days (P = 0.0125 vs control) and increased growth rate by 1.7 cm/yr (P = 0.0024 vs control). Conclusions: Combined administration of oxandrolone and propranolol attenuates burn-induced growth arrest in pediatric burn patients. The present study is registered at clinicaltrials.gov: NCT00675714 and NCT00239668.

Human herpes viruses in burn patients: A systematic review

OBJECTIVE The contribution of human herpes viruses, including herpes simplex virus (HSV), cytomegalovirus (CMV), and varicella zoster virus (VZV) to morbidity and mortality after burns remains controversial. This systematic review was undertaken to assess evidence of herpes virus-related morbidity and mortality in burns. MATERIALS AND METHODS PubMed, Ovid, and Web of Science were searched to identify studies of HSV, CMV, or VZV infections in burn patients. Exclusion criteria included: A level of evidence (LoE) of IV or V; nonhuman in vivo studies; and non-English articles. There was no limitation by publication date. RESULTS Fifty articles were subjected to full-text analysis. Of these, 18 had LoE between I-III and were included in the final review (2 LoE I, 16 LoE II-III). Eight had a prospective study design, 9 had a retrospective study design, and 1 included both. CONCLUSIONS No direct evidence linked CMV and HSV infection with increased morbidity and mortality in burns. Following burn, CMV reactivation was more common than a primary CMV infection. Active HSV infection impaired wound healing but was not directly correlated to mortality. Infections with VZV are rare after burns but when they occur, VZV infections were associated with severe complications including mortality. The therapeutic effect of antiviral agents administered after burns warrants investigation via prospective randomized controlled trials.

Comparison of Matrigel and Matriderm as a carrier for human amnion-derived mesenchymal stem cells in wound healing

Amnion-derived mesenchymal stem cells (AMSC) are a promising tool in regenerative medicine. Here we evaluated the utility of Matrigel and Matriderm as carrier for the topical application of AMSC to mice skin wounds. In both application forms, AMSC promoted neovascularization of the wound area. Matrigel proved as excellent matrix for AMSC and immigrating mouse cells, but the solid Matriderm enabled a more adequate positioning of AMSC into the wound. Although AMSC did not attach to Matriderm, they reliably induced wound reduction. Thus, a combined administration of AMSC/Matriderm could be beneficial to potentiate the encouraging effects on wound healing.

BurnCase 3D software validation study: Burn size measurement accuracy and inter-rater reliability

OBJECTIVE The aim of this study was to compare the accuracy of burn size estimation using the computer-assisted software BurnCase 3D (RISC Software GmbH, Hagenberg, Austria) with that using a 2D scan, considered to be the actual burn size. METHODS Thirty artificial burn areas were pre planned and prepared on three mannequins (one child, one female, and one male). Five trained physicians (raters) were asked to assess the size of all wound areas using BurnCase 3D software. The results were then compared with the real wound areas, as determined by 2D planimetry imaging. To examine inter-rater reliability, we performed an intraclass correlation analysis with a 95% confidence interval. RESULTS The mean wound area estimations of the five raters using BurnCase 3D were in total 20.7±0.9% for the child, 27.2±1.5% for the female and 16.5±0.1% for the male mannequin. Our analysis showed relative overestimations of 0.4%, 2.8% and 1.5% for the child, female and male mannequins respectively, compared to the 2D scan. The intraclass correlation between the single raters for mean percentage of the artificial burn areas was 98.6%. There was also a high intraclass correlation between the single raters and the 2D Scan visible. CONCLUSION BurnCase 3D is a valid and reliable tool for the determination of total body surface area burned in standard models. Further clinical studies including different pediatric and overweight adult mannequins are warranted.

Evidence of invasive and non-invasive treatment modalities for hypertrophic scars: A systematic review

Currently, there are various therapeutic approaches to reduce hypertrophic scarring; however, there is no standard evidence‐based treatment protocol. Hence, a systematic review was performed to obtain a summary of the latest clinical trials to evaluate evidence for the treatment of hypertrophic scars. The review protocol was registered and approved by PROSPERO (CRD42015027040). PubMed and Web of Science were searched using predefined MeSH‐Terms to identify studies published within the last 10 years regarding treatment for hypertrophic scars. Exclusion criteria included a level of evidence (LoE) lower than I, nonhuman in vivo studies, in vitro studies, studies on keloids, literature reviews, and non‐English articles. The literature search identified 1,029 unique articles, whereas 6 articles were prospective, randomized, blinded, controlled clinical trials with a LoE I, and were thus included in the systematic analysis. Three clinical trials evaluated silicone products and pressure garments, and the other three studies investigated the efficacy of intralesional injections of triamcinolone (TAC), 5‐Fluorouracil (5‐FU) combined with TAC as well as the additional irradiation with a 585 nm pulsed‐dye laser (PDL). Intralesional injections revealed significant improvements of the scar quality in terms of height, thickness, erythema, and pigmentation. Pressure garments showed favorable results but there was no evidence that silicone products were able to improve the scar quality. The systematic review demonstrated that there are just a few clinical trials with a LoE of I. Consequently, evidence is still lacking especially for noninvasive treatment regimens for hypertrophic scars. Intralesional injections of 5‐FU mixed with a low dose of TAC can be seen as most appropriate treatment modality. Prospective clinical trials to determine the efficiency of silicone products are warranted.

Transpulmonary Thermodilution Versus Transthoracic Echocardiography for Cardiac Output Measurements in Severely Burned Children

Introduction: Severe burns trigger a hyperdynamic state, necessitating accurate measurement of cardiac output (CO) for cardiovascular observation and guiding fluid resuscitation. However, it is unknown whether, in burned children, the increasingly popular transthoracic echocardiography (TTE) method of CO measurement is as accurate as the widely used transpulmonary thermodilution (TPTD) method. Patients and Methods: We retrospectively compared near-simultaneously performed CO measurements in severely burned children using TPTD with the Pulse index Continuous Cardiac Output (PiCCO) system or TTE. Outcomes were compared using t tests, multiple linear regression, and a Bland-Altman plot. Results: Fifty-four children (9 ± 5 years) with 68 ± 18% total body surface area burns were studied. An analysis of 105 data pairs revealed that PiCCO yielded higher CO measurements than TTE (190 ± 39% vs. 150 ± 50% predicted values; P < 0.01). PiCCO- and TTE-derived CO measurements correlated moderately well (R2 = 0.54, P < 0.01). A Bland-Altman plot showed a mean bias of 1.53 L/min with a 95% prediction interval of 4.31 L/min. Conclusions: TTE-derived estimates of CO may underestimate severity of the hyperdynamic state in severely burned children. We propose using the PiCCO system for objective cardiovascular monitoring and to guide goal-directed fluid resuscitation in this population.

Standardizing the complication rate after breast reduction using the Clavien-Dindo classification

Background. Published complication rates for breast reduction surgery, also known as reduction mammaplasty, vary between 4% and 54%. This wide range of complication rates could be attributable to the lack of a standardized classification of complications in plastic surgery. The aim of this study was to analyze our single‐center complication rates after reduction mammaplasty using the Clavien‐Dindo classification. Methods. We performed a retrospective chart review studying 804 patients between the ages of 18 and 81 years old who underwent breast reduction between 2005 and 2015 at our institution. Patients with a history of breast cancer, a previous breast operation, who did not undergo bilateral reduction mammaplasty, or who required systemic immunodeficiency/immunosuppressive drugs were excluded from our analysis. Complications were classified according to the Clavien‐Dindo classification from Grades I to V. Results. A total of 486 patients met the inclusion criteria for the analysis. Patients had an age (mean ± standard deviation) of 39 ± 13 years and a body mass index of 26 ± 4 kg/m2. Median follow‐up was 274 days (interquartile range: 90.5–378). The overall rate of complications of reduction mammaplasty was 63%, with the majority of those being Grades I (48%) and II (9%), comprising 92% of all the complications. Operative revisions were required in 6% (1% Grade IIIA and 5% Grade IIIB). There were no complications graded in categories IV and V. Conclusion. Although complications occurred in more than half of the cases, the majority did not require operative reintervention. The Clavien‐Dindo classification can classify the severity of complications and serve as a benchmark to compare complication rates between different practices. We believe that grading of complications should distinguish between those that do and do not require operative reinterventions.

Effects of different duration exercise programs in children with severe burns

INTRODUCTION Burns lead to persistent and detrimental muscle breakdown and weakness. Standard treatment at our institution includes a voluntary 12-week rehabilitative exercise program to limit and reverse the effects of increased muscle catabolism. In the present work, we investigated if different durations of exercise, 6 or 12 weeks, produce comparable improvements in muscle strength, body composition, and cardiopulmonary fitness. METHODS We prospectively enrolled and randomized patients with ≥30% total body surface area (TBSA) burned to receive 6 or 12 weeks of exercise rehabilitation. Patients were evaluated for muscle strength, oxygen consumption capacity, and lean body mass at discharge (n=42) and after exercise. After 6 weeks (n=18) or 12 weeks (n=24) of exercise training, leg muscle strength was assessed as peak torque per body weight using a Biodex isokinetic dynamometer. Oxygen consumption capacity, measured as peak VO2, was studied using a standard treadmill-based test, and lean body mass was determined using dual-energy X-ray absorptiometry. RESULTS Significant improvements in muscle strength, peak VO2, and lean body mass were seen after 6 weeks of exercise training (p<0.001), with only significant improvements in peak VO2 being seen after 6 weeks more of training. CONCLUSION These data suggest that a 6-week rehabilitative exercise program is sufficient for improving muscle strength, body composition, and cardiopulmonary fitness in pediatric burn patients. However, continuation of at- or near-home cardiopulmonary training following the 6 weeks of at-hospital rehabilitation may be useful.

Propranolol Reduces Cardiac Index But does not Adversely Affect Peripheral Perfusion in Severely Burned Children.

Purpose: The aim of this study was to quantify the effect of propranolol on hemodynamic parameters assessed using the PiCCO system in burned children. Methods: We analyzed hemodynamic data from patients who were randomized to receive either propranolol (4 mg/kg/day) or placebo (control), which was initiated as a prospective randomized controlled trial. Endpoints were cardiac index (CI), percent predicted heart rate (%HR), mean arterial pressure (MAP), percent predicted stroke volume (%SV), rate pressure product (RPP), cardiac work (CW), systemic vascular resistance index (SVRI), extravascular lung water index (EVLWI), arterial blood gases, events of lactic acidosis, and mortality. Mixed multiple linear regressions were applied, and a 95% level of confidence was assumed. Results: One hundred twenty-one burned children (control: n = 62, propranolol: n = 59) were analyzed. Groups were comparable in demographics, EVLWI, SVRI, %SV, arterial blood gases, Denver 2 postinjury organ failure score, incidence of lactic acidosis, or mortality. Percent predicted HR, MAP, CI, CW, and RPP were significantly reduced in the propranolol-treated group (P <0.01). Conclusions: Propranolol significantly reduces cardiogenic stress by reducing CI and MAP in children with severe burn injury. However, peripheral oxygen delivery was not reduced and events of lactic acidosis as well as organ dysfunction was not higher in propranolol treated patients.