David de Souza Gomez

Collagen and Elastic Content of Abdominal Skin After Surgical Weight Loss

BackgroundCollapsed skin folds after bariatric weight loss are often managed by plastic procedures, but changes in dermal composition and architecture have rarely been documented. Given the potential consequences on surgical outcome, a prospective histochemical study was designed. The hypothesis was that a deranged dermal fiber pattern would accompany major changes in adipose tissue.MethodsFemale surgical candidates undergoing postbariatric abdominoplasty (n = 40) and never obese women submitted to control procedures (n = 40) were submitted to double abdominal biopsy, respectively in the epigastrium and hypogastrium. Histomorphometric assessment of collagen and elastic fibers was executed by the Image Analyzer System (Kontron Electronic 300, Zeiss, Germany).ResultsDepletion of collagen, but not of elastic fibers, in cases with massive weight loss was confirmed. Changes were somewhat more severe in epigastrium (P = 0.001) than hypogastrium (P = 0.007). Correlation with age did not occur.Conclusions(1) Patients displayed lax, soft skin lacking sufficient collagen fiber network. (2) Elastic fiber content was not damaged, and was even moderately increased in epigastrium; (3) Preoperative obesity negatively correlated with hypogastric collagen concentration; (4) Future studies should pinpoint the roles of obesity, and especially of massive weight loss, on dermal architecture and response to surgery.

Fluconazole plasma concentration measurement by liquid chromatography for drug monitoring of burn patients

Fluconazole (2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)-2-propanol) is a triazole antifungal agent that has been available since 1990. Fluconazole is a broad-spectrum triazole antifungal agent that has emerged as a suitable alternative to amphotericin B in the treatment of a wide variety of superficial and systemic fungal infections.1 Triazole drugs act by inhibiting the enzyme 14-α-demethylase, which belongs to the microsomal CYP system; triazoles also act by blocking the biosynthesis of ergosterol, resulting in the accumulation of 14-α-methyl sterols and producing a fungistatic action. In general, fluconazole is well tolerated, with side effects including nausea, headache, skin rash, vomiting, abdominal pain, and diarrhea occurring during long-term therapy.2 Excellent bioavailability has been reported after oral dosing, and a linear pharmacokinetics has been demonstrated at a dose of 200–800 mg daily. The elimination half-life of fluconazole ranges from 27 to 37 hours, the apparent volume of distribution ranges from 0.5 to 0.7 L/kg, and approximately 80% of unchanged drug is excreted in the urine.3–6 Fluconazole is now used prophylactically in the management of various immune-compromised patient subsets1. High morbidity and mortality in patients with severe thermal injury were associated with fungal sepsis; thus, a study of the efficacy of this drug to prevent fungal sepsis in burn patients is necessary. It is well-known that patients with thermal injuries show many changes in the pharmacokinetics of several drugs, but data on the clinical efficacy of fluconazole related to its kinetics are very limited.7,8 Since changes in the pharmacokinetics of fluconazole are still unknown, it is imperative to investigate burn patients’ drug levels with a controlled clinical protocol. Analytical methods using microbiological, spectrophotometric, and chromatographic techniques have all been shown to determine fluconazole in biological samples. High-performance liquid chromatography (HPLC) is preferred due to its selectivity and the specificity of the assay. Methods for the determination of fluconazole in biological samples by HPLC-UV have been described previously.9–16 The objective of the present study was to develop a simple analytical method to determine fluconazole for plasma drug monitoring in patients with extensive thermal injury. An additional focus is its application to future pharmacokinetic studies. The method was validated as per FDA guidelines.17

Contraction and myofibroblasts in restored skin.

Myofibroblasts and the contraction of split skin-graft donor sites were studied in 18 patients. For each patient five samples were studied, taken on days 0, 14, 21, 28, and 35. On each occasion the extensions and densities of myofibroblasts were calculated. After the initial measurement, the subsequent extensions were expressed in percentages of the first, resulting in mean measurements of 100, 95, 97, 99, and 99%, respectively. The myofibroblasts in 10 dermic fields were counted under light microscopy at a magnification of 1000 marked with anti-alpha-smooth muscle actin antibodies using immunoperoxidase, resulting in the means of 0.2, 3.8, 1.3, 1.3, and 0.4, respectively. The contraction and the increase in density of myofibroblasts were transitory and significant in the samples measured on day 14, but in sample 35 neither of the variables was significantly different from the initial sample. These variables evolved concurrently, corroborating the hypothesis that myofibroblasts are responsible for the contraction.

Individualised vancomycin doses for paediatric burn patients to achieve PK/PD targets.

BACKGROUND The objective of the study was to investigate vancomycin dose adjustment in pediatric burn patients by evaluating trough drug concentrations and the pharmacokinetic and pharmacodynamic (PK/PD) correlation. METHODS Study subjects included 13 patients who were 6.0 years old, 25 kg (median). with normal renal function. These had at least a 30% total burn surface area and inhalation injury were present in 7/13 patients. The patients were investigated prospectively. Plasma monitoring and PK assessments were performed by serial blood sample collections (30 sets). Only 0.2 mL of each plasma sample was required for our plasma measurements, which were made by high performance liquid chromatography. The vancomycin PK/PD target was set at AUC0-24(ss)/MIC>400. RESULTS Trough values less than 10 μg/mL were obtained in 16/30 sets (53%) as a consequence of increased plasma clearance and the apparent volume of distribution. The daily dose was subsequently increased from 43.4 ± 9.0mg/kg (mean ± SD) to 98.0 ± 17.9 mg/kg, p<0.05. The PK/PD target was reached for pathogens with 0.5mg/L, 1mg/L, 2mg/L and 4 mg/L MIC in 93.3% (28/30), 66.7% (20/30), 33.3% (10/30) and 3.3% (1/30) of the sets, respectively. CONCLUSIONS To more rapidly achieve the PK/PD targets in pediatric burn patients with normal renal function, an initial dose of approximately 90-100mg/kg/day is recommended; however, this higher dosage regimen should be further evaluated in this population in terms of efficacy and toxicity as well as in terms of achieving pharmacodynamic goals.

Characterization of critically ill adult burn patients admitted to a Brazilian intensive care unit

INTRODUCTION To characterize the evolution of clinical and physiological variables in severe adult burn patients admitted to a Brazilian burn ICU, we hypothesized that characteristics of survivors are different from non-survivors after ICU admission. METHODS A five-year observational study was carried out. The clinical characteristics, physiological variables, and outcomes were collected during this period. RESULTS A total of 163 patients required ICU support and were analyzed. Median age was 34 [25,47] years. Total burn surface area (TBSA) was 29 [18,43]%, and hospital mortality rate was 42%. Lethal burn area at which fifty percent of patients died (LA50%) was 36.5%. Median SAPS3 was 41 [34,54]. Factors associated with hospital mortality were analyzed in three steps, the first incorporated ICU admission data, the second incorporated first day ICU data, and the third incorporated data from the first week of an ICU stay. We found a significant association between hospital mortality and SAPS3 [OR(95%CI)=1.114(1.062-1.168)], TBSA [OR(95%CI)=1.043(1.010-1.076)], suicide attempts [OR(95%CI)=8.126(2.284-28.907)], and cumulative fluid balance per liter within the first week [OR(95%CI)=1.090(1.030-1.154)]. Inhalation injury was present in 45% of patients, and it was not significantly associated with hospital mortality. CONCLUSIONS In this study of an ICU in a developing country, the mortality rate of critically ill burn patients was high and the TBSA was an independent risk factor for death. SAPS3 at admission and cumulative fluid balance in the first seven days, were also associated with unfavorable outcomes. The implementation of judicious fluid management after an acute resuscitation phase may help to improve outcomes in this scenario.

Estudo epidemiológico de queimaduras em crianças atendidas em hospital terciário na cidade de São Paulo

BACKGROUND: This study describes the experience with the care of burned children in the Burn Treatment Unit, Division of Plastic Surgery, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (Hospital of the Faculty of Medicine, University of Sao Paulo - HCFMUSP) over 15 consecutive months. METHODS: The data of 98 patients up to 13 years of age treated in the Burn Treatment Unit of HCFMUSP from October 2009 to December 2010 were analyzed. RESULTS: The average age of the children was 5.2 years; 67 (68.4%) were boys. Accidents were responsible for burns in 93 (94.9%) cases, whereas 1 (1%) case of burns was caused by aggression. There was a higher incidence of burns in children under 2 years of age. The main agent causing burns was hot liquids (48%), followed by fire (17%) and hot solids (17%). The mean body surface area affected by second- and third-degree burns was 10%. Six (6.1%) patients had burns over more than 20% of their body surface area - 5 (83.3%) of them had burns due to burning alcohol and 1 (16.7%) due to scalding water. All cases in which more than 30% of the body surface was affected by second- and third-degree burns were due to alcohol burns. CONCLUSIONS: This survey demonstrates the importance of burn injuries in pediatric patients. The dataset suggests prevention efforts should focus on the domestic environment, particularly against scalding in children less than 5 years of age. In children older than 5 years, prevention programs should focus on both domestic and extradomestic environments.

Pharmacokinetic-pharmacodynamic correlation of imipenem in pediatric burn patients using a bioanalytical liquid chromatographic method

Desenvolveu-se e aplicou-se metodo bioanalitico para quantificar concentracoes de imipenem livre para estudos de farmacocinetica (PK) e de correlacao PK/PD dos ajustes de dose requeridos para manter a efetividade antimicrobiana em pacientes pediatricos queimados. Utilizou-se coluna Supelcosil LC18 (250 x 4,6 mm 5 micra), fase movel binaria, consistindo de tampao fosfato 0,01M pH 7,0 e acetonitrila (99:1, v/v) e fluxo de 0,8 mL/min. O metodo mostrou boa recuperacao absoluta (acima de 90%), boa linearidade (0,25-100,0 µg/mL, r2=0.999), boa sensibilidade (LLOQ: 0,25 µg/mL; LLOD: 0,12 µg/mL) e estabilidade aceitavel. Os valores de precisao inter/intradia foram 7,3/5,9% e a exatidao media foi de 92,9%. O metodo bioanalitico foi aplicado para quantificar concentracoes de farmaco livre em criancas com queimaduras, Seis pacientes pediatricos queimados (idade media de 7,0 anos, 27,5 kg), com funcao renal normal e 33% da superficie total queimada foram investigados prospectivamente. Lesoes por inalacao estavam presentes em 4/6 (67%) dos pacientes. O monitoramento plasmatico e a as avaliacoes de PK foram efetuadas utilizando colecao de amostras seriais de sangue para cada serie, totalizando 10 conjuntos. O alvo PK/PD alcancado (40%T>MIC) para cada concentracao inibitoria minima (MIC: 0,5, 1,0, 2,0, 4,0 mg/L) ocorreu em porcentagem maior do que 80% dos conjuntos investigados e 100% apos o ajuste de dose. Em conclusao, a purificacao das amostras do plasma usando tecnica de ultrafiltracao seguida de quantificacao das medidas do imipenem no plasma usando metodo de cromatografia liquida e bastante simples, util e necessita de pequenos volumes para as amostras de sangue. Alem disso, pequena quantidade de plasma (0,25 mL) e necessario para garantir a efetividade do farmaco nos pacientes pediatricos queimados. Ha, ainda, baixo risco de neurotoxicidade, o que e importante, visto que as farmacocineticas sao imprevisiveis nesses pacientes criticos, com grave infeccao hospitalar. Finalmente, o alvo PK/PD foi alcancado para o imipenem no controle da sepse em pacientes pediatricos com queimaduras.

A new method for scoring active sweat glands

Division of Burns and Plastic Surgery, Hospital das Clinicas, Sao PauloUniversity Medical School – Sao Paulo/SP, Brazil.Heart Institute (InCor),Hospital das Clinicas, Sao Paulo University MedicalSchool – Sao Paulo/SP, Brazil.Plastic Surgery Division, Hospital das Clinicas, Sao Paulo University MedicalSchool – Sao Paulo/SP, Brazil.Email: davgomez@usp.br

Clinical Outcome and Antimicrobial Therapeutic Drug Monitoring for the Treatment of Infections in Acute Burn Patients

PURPOSE In critical burn patients, the pharmacokinetic parameters (absorption, distribution, metabolism, and excretion) of many classes of drugs, including antibiotics, are altered. The aim of this study was to compare 2 groups of burn patients undergoing treatment for health care-associated infections with and without therapeutic drug monitoring. METHODS A retrospective analysis of a clinical intervention (ie, a before/after study) was conducted with patients with health care-associated pneumonia, burn infection, bloodstream infection, and urinary tract infection in the burn intensive care unit of a tertiary care hospital. The patients were divided into 2 groups: (1) those admitted from May 2005 to October 2008 who received conventional antimicrobial dose regimens; and (2) those admitted from November 2008 to June 2011 who received antibiotics (imipenem, meropenem, piperacillin, and vancomycin) with doses adjusted according to plasma monitoring and pharmacokinetic modeling. General characteristics of the groups were analyzed, as were clinical outcomes and 14-day and in-hospital mortality. FINDINGS Sixty-three patients formed the conventional treatment group, and 77 comprised the monitored treatment group. The groups were homogeneous, median age was 31 years (range: 1-90) and 66% were male. Improvement occurred in 60% of the patients under monitored treatment (vs 52% with conventional treatment); 14-day mortality was 16% vs 14%; and the in-hospital mortality was similar between groups (39% vs 36%). In the final multivariate models, variables significantly associated with in-hospital mortality were total burn surface area ≥30%, older age, and male sex. Treatment group did not affect the prognosis. IMPLICATIONS Therapeutic drug monitoring of antimicrobial treatment did not alter the prognosis of these burn patients. More trials are needed to support the use of therapeutic drug monitoring to optimize treatment in burn patients.

Establishment of a protocol for storage of refrigerated autologous skin

Introduction: Autologous skin grafts are used for treatment of burn patients. These grafts can be stored and preserved, as long as the storage process is performed with strict quality control to reduce the risk of infection. Methods: A retrospective cohort study was conducted in the Burn Unit of the Hospital das Clínicas de São Paulo from February 2015 to July 2016. During this period, a protocol was established to store refrigerated skin, with control of collection, preservation, and packaging, and recording of all processes. To ensure quality, graft biopsies were collected for preand poststorage microbiology testing and a cross-sectional study for contamination was performed. Results: Critical deficiencies included inadequate packaging, lack of processing records, lack of biopsies for microbiology testing, and failure to discard specimens. Most of the samples were contaminated before and after storage (84.2%). Only two samples were sterile before storage but became contaminated after storage, with growth of Gram-positive skin bacteria. Conclusion: A promising method for the storage of refrigerated skin was established, but requires minor adjustments in quality control. ■ ABSTRACT