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BACKGROUND: The high prevalence of benign male breast tissue enlargement (gynecomastia) has resulted in a marked increase of gynecomastia cases. While about one third of male adults experience some form of gynecomastia, gynecomastia surgery (GS) outcome research is limited to small study populations and single-center/-surgeon databases. In this study, we aimed to access the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to identify preoperative risk factors for complications and investigate postoperative outcomes of GS. METHODS: In this retrospective study, we queried the ACS-NSQIP database from 2008 to 2021 to identify male adult patients who underwent GS. Postoperative outcomes involved the occurrence of any, surgical and medical complications, as well as reoperation, readmission, and mortality within a 30-day postoperative time period. Univariable and multivariable assessment were performed to identify risk factors for complications while adjusting for possible confounders. RESULTS: The study included 4,996 GS patients with a mean age of 33.7 ± 15 years and BMI of 28.2 ± 5.1 kg/m2. White patients constituted 54% (n = 2713) of the cohort, and 27% (n = 1346) were obese. Except for 2020, there was a steady increase in GS cases over the study period. Outpatient surgeries were most common at 95% (n = 4730), while general surgeons performed the majority of GS (n = 3580; 72%). Postoperatively, 91% (n = 4538) of patients were discharged home; 4.4% (n = 222) experienced any complications. Multivariable analysis identified inpatient setting (p < 0.001), BMI (p = 0.023), prior sepsis (p = 0.018), and bleeding disorders (p = 0.047) as independent risk factors for complications. CONCLUSION: In this study, we analyzed 4996 male adult GS patients from the ACS-NSQIP database, revealing an increased caseload and significant general surgeon involvement. Risk factors like bleeding disorders, inpatient status, and prior sepsis were linked to postoperative complications, while BMI was crucial for predicting adverse events. Overall, our findings may aid in enhancing patient care through advanced preoperative screening and closer perioperative management. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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BACKGROUND: The TMG flap is a popular choice for breast reconstruction. However, it remains unclear whether the side of flap harvest, subsequent flap shaping and inset impacts breast appearance and volume dispersion. This study compares the aesthetic outcome of the reconstructed breast following TMG flap harvest from the ipsilateral or contralateral thigh. PATIENT AND METHODS: A retrospective matched-pair multi-center study was conducted. Patients were grouped according to the side of flap harvest (ipsilateral vs. contralateral) and matched for age, BMI and mastectomy type. Between 01/2013 and 03/2020, 384 TMG breast reconstructions were performed, of which 86 were included (43 ipsilateral vs. 43 contralateral). Standardized pre- and postoperative photographs were evaluated using a modified assessment scale comprising of a symmetry score (SymS, max. 20 points), a volume discrepancy score (VDS, max. 8 points) and an aesthetic appearance score (AS, max. 10 points). Autologous fat grafting (AFG) procedures for breast refinement were compared. RESULTS: Pleasing breast symmetry (SymS Ipsi: 14.5/20; Contra: 14.9/20), volume (VDS Ipsi: 3.3/8; Contra: 2.4/8) and aesthetic appearance (AS Ipsi: 6.7/10; Contra: 6.7/10) were achieved with both surgical methods. No significant changes were present regarding the VDS (F(1.82) = 2.848, p = 0.095) or the SymS (F(1.82) = 1.031, p = 0.313) pre- to postoperatively. Significantly more autologous fat grafting was done in the contralateral group (p < 0.001). CONCLUSION: The side of the TMG flap harvest, different shaping and inset techniques do not impact the aesthetic breast outcome. Both surgical methods result in pleasing breast symmetry and volume. Secondary procedures are common and should be entailed in the reconstructive strategy.
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Neoplasias de la Mama , Mamoplastia , Colgajo Miocutáneo , Humanos , Femenino , Mastectomía/efectos adversos , Mastectomía/métodos , Estudios Retrospectivos , Neoplasias de la Mama/cirugía , Mamoplastia/métodos , Colgajo Miocutáneo/trasplante , EstéticaRESUMEN
BACKGROUND: Complex scalp defects are regularly reconstructed using microvascular tissue transfer. The latissimus dorsi free flap is one of the workhorse flaps used in scalp reconstruction. These cases necessitate, particularly in the elderly, a close cooperation between plastic surgeons and neurosurgeons. The purpose of this study was to evaluate the suitability of the latissimus dorsi free flap for complex scalp reconstructions and to analyze potential risk factors. METHODS: A retrospective study identified 43 patients undergoing complex scalp reconstruction using a latissimus dorsi free flap at our department between 2010 and 2022. RESULTS: The mean patient age was 61 ± 18 years. Defects were mostly caused by oncologic tumor resections (n = 23; 55%), exposure to a cranioplasty (n = 10; 23%) or infection (n = 4; 9%). The most frequent recipient vessels were the superficial temporal artery (n = 28; 65%), external carotid artery (n = 12; 28%) and the venae comitantes (n = 28; 65%), external jugular vein (n = 6; 14%). The reconstructive success rate was 97.7%. There was one total flap loss (2%). Partial flap loss occurred in five cases (12%). Follow-up was 8 ± 12 months. Major complications were seen in 13 cases, resulting in a revision rate of 26%. Multivariate logistic regression identified active tobacco use as the only risk factor for major complications (odds ratio 8.9; p = 0.04). CONCLUSION: Reconstruction of complex scalp defects using the latissimus dorsi free flap yielded high success rates. Among the potential risk factors, active tobacco use seems to affect the outcome of complex scalp reconstructions.
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The treatment of geriatric burn patients represents a major challenge in burn care. The objective of this study was to evaluate the efficacy of enzymatic debridement (ED) in geriatric burn patients. Adult patients who received ED for treatment of mixed pattern and full thickness burns (August 2017-October 2022) were included in this study and grouped in the younger (18-65 years) and geriatric (≥65 years) groups. Primary outcome was a necessity of surgery subsequent to ED. Both groups (patient characteristics, surgical and non-surgical treatment) were compared. Multiple logistic and linear regression models were used to identify the effect of age on the outcomes. A total of 169 patients were included (younger group: 135 patients, geriatric group: 34 patients). The burn size as indicated by %TBSA (24.2 ± 20.4% vs. 26.8 ± 17.1%, p = 0.499) was similar in both groups. The ASA (2.5 ± 1.1 vs. 3.4 ± 1.1, p < 0.001) and ABSI scores (6.1 ± 2.8 vs. 8.6 ± 2.3, p < 0.001) were significantly higher in the geriatric group. The %TBSA treated with ED (5.4 ± 5.0% vs. 4.4 ± 4.3%, p = 0.245) were similar in both groups. The necessity of additional surgical interventions (63.0 % vs. 58.8 %, p = 0.763) and the wound size debrided and grafted (2.9 ± 3.5% vs. 2.2 ± 2.1%; p = 0.301) were similar in both groups. Regression models yielded that age did not have an effect on efficacy of ED. We showed that ED is reliable and safe to use in geriatric patients. Age did not have a significant influence on the surgical outcomes of ED. In both groups, the size of the grafted area was reduced and, in many patients, surgery was avoided completely.
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BACKGROUND: Hybrid breast reconstruction (HBR) combines silicone implants with fat grafting to improve implant coverage, treating local tissue deficiencies and leading to a more natural breast appearance. Recent data also indicated less capsular contracture after HBR. The authors developed a novel technique and animal model of cell-assisted (CA) HBR to illuminate its effects on capsular contracture. METHODS: Animals received silicone implants in a dorsal submuscular pocket. Although animals of the HBR group received fat grafting around the implant without stem cell enrichment, rats of the CA-HBR1 and the CA-HBR2 groups received stem cell-enriched fat grafting with 2 × 10 6 and 4 × 10 6 adipose-derived stem cells immediately after implant insertion. On day 60, animals underwent sonography and elastography imaging and were euthanized, and outcome analysis was performed by means of histology, immunohistochemistry, chemical collagen quantification, and gene expression analysis. RESULTS: With this novel technique, long-term survival of adipose-derived stem cells within the implant pocket was demonstrated after 60 days after implant insertion. CA-HBR led to significantly reduced thickness and collagen density of capsular contractures. In addition, CA-HBR resulted in reduced fibrotic responses with less occurrence of collagen type I and transforming growth factor-ß in capsule tissue. Moreover, the addition of stem cells suppressed fibrotic and inflammatory responses on a genetic level with significant underexpression of collagen type I and transforming growth factor-ß1. CONCLUSIONS: With this new technique and animal model, the authors observed a preventive effect on capsular contracture substantiating the basis of clinical outcomes of HBR. The authors propose that the addition of stem cells to HBR might booster its beneficial results. CLINICAL RELEVANCE STATEMENT: Stem cell-enriched fat grafting around silicone implants may reduce the risk for capsular contracture after silicone breast implantation. While fat grafting alone already shows beneficial effects, the addition of stem cells to the fat graft can potentiate this effect.
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Implantación de Mama , Implantes de Mama , Contractura , Mamoplastia , Ratas , Animales , Implantes de Mama/efectos adversos , Colágeno Tipo I , Contractura Capsular en Implantes/etiología , Contractura Capsular en Implantes/prevención & control , Implantación de Mama/efectos adversos , Siliconas/uso terapéutico , Colágeno/uso terapéutico , Contractura/etiología , Contractura/prevención & control , Geles de Silicona/uso terapéuticoRESUMEN
Lipofilling is a frequently used and safe procedure for breast reconstruction. One of the most feared complications is soft tissue infection following lipofilling. Because of this, some surgeons propose the practice of rinsing fat grafts with antibiotics. This study investigates the effect of antibiotic rinses on fat grafts in an in vitro model. Adipocytes and stem cells were isolated from fat tissue harvested during 24 lipofilling procedures and incubated with different doses of clindamycin or cefazolin. Cell viability, metabolism, proliferation, and differentiation capacities were analyzed by gross morphology, fluorescence staining, -(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid (MTT-), and Glyceraldehyde 3 Phosphate Dehydrogenase (G3PD)-assay as well as reactive oxygen species (ROS)-assay. Cefazolin and clindamycin led to significant reduction of cell viability of adipocytes. High doses of both antibiotics led to a rupture of adipocytes with visible free lipid droplets. Cell metabolism was significantly decreased after incubation with both antibiotics. There was a significant increase in ROS production. Exposure to clindamycin and cefazolin led to morphological changes in stem cells in a dose- and time-dependent manner. Furthermore, differentiation potential was significantly reduced. Antibiotic susceptibility testing, however, showed that low concentrations of antibiotics effectively inhibited bacterial growth in contaminated fat grafts. This study confirms that rinsing fat grafts with clindamycin or cefazolin not only overly prevents infection but also has cytotoxic and metabolic effects on adipocytes. Therefore, based on these results, the routine clinical application in high doses cannot be recommended.
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Antibacterianos , Cefazolina , Antibacterianos/farmacología , Cefazolina/farmacología , Clindamicina/farmacología , Especies Reactivas de Oxígeno , Tejido AdiposoRESUMEN
BACKGROUND: Free adipocutaneous anterolateral thigh (ALT) flaps have evolved as workhorse flaps to reconstruct complex, multicompound defects. While coverage is safely achieved, flaps may remain bulky. As a standard of care, flaps are refined with liposuction, partial excision, or combination of both. Cryolipolysis is widely used for fat reduction in esthetic medicine. This pilot comparative study analyses whether cryolipolysis may serve as a safe alternative method to effectively reduce volume in fasciocutaneous flaps. Moreover, patients' satisfaction with the procedure is evaluated. METHODS: In this single-center, retrospective, interventional comparative cohort study, 10 patients with free subfascial ALT flaps for distal extremity reconstruction underwent cryolipolysis (60 minutes, -9°C). Circumference of the extremities and subcutaneous fat thickness were determined before (T1) and 12 weeks (T2) after cryolipolysis. Patient satisfaction was evaluated with a questionnaire of Likert's scale questions. Duration of hospital stay, intervention time, costs, and possible complications were analyzed and compared with surgical flap contouring (n = 12). RESULTS: All patients undergoing cryolipolysis were male, with a median age of 52 years without arterial disease-like state or deep vein thrombosis (DVT). At T2, a significant reduction of circumference of 1.8 ± 0.9 cm (p < 0.001) and subcutaneous fat layer of 7.7 ± 3.0 mm (p < 0.0001) was recorded. Overall, 90% of the patients were satisfied with the result. Cryolipolysis was well tolerated. One patient developed a second-degree frostbite which healed without further intervention. Cryolipolysis proofed to be as safe as surgical flap contouring. Hospital stay was significantly shorter (p < 0.01) and personal resources were spared when flap contouring was performed with cryolipolysis. CONCLUSION: This is a novel application of evolving body-contouring cryolipolysis from esthetic medicine into optimizing outcomes in reconstructive surgery. Cryolipolysis has been shown to be relatively safe and effective to reduce ALT's volume with high patients' satisfaction. This successful pilot study encourages further investigation with a prospective randomized control trial.
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Colgajos Tisulares Libres , Muslo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios de Cohortes , Estética , Estudios de Factibilidad , Colgajos Tisulares Libres/irrigación sanguínea , Extremidad Inferior , Proyectos Piloto , Estudios Prospectivos , Estudios Retrospectivos , Muslo/cirugía , Muslo/irrigación sanguínea , Resultado del TratamientoRESUMEN
BACKGROUND: The collagenase of the bacterium Clostridium histolyticum (CCH) is already an established treatment for fibroproliferative diseases like M. Dupuytren and M. Peyronie Although results are comparable to surgical intervention, skin laceration is a severe and relevant side effect. Doxycycline (DOX) recently rose interest as an inhibitor of matrix-metalloproteinases alongside its capabilities of skin accumulation. It therefore might be a potential skin protective agent in the use of CCH. METHODS: For simulation of a fibroproliferative disease adjacent to the skin, we utilized a rodent model of capsular fibrosis involving silicone implants and subsequent fibrotic capsule formation. For in-vitro studies, fibrotic capsules were excised and incubated with 0.9 mg/ml CCH and four different doses of DOX. For in-vivo experiments, animals received 0.0, 0.3 or 0.9 mg/ml CCH injections into the fibrotic capsules with or without prior oral DOX administration. Outcome analysis included histology, immunohistochemistry, gene expression analysis, chemical collagen and DOX concentration measurements as well as µCT imaging. RESULTS: In-vitro, DOX showed a dose-dependent inhibition of CCH activity associated with increasing capsule thickness and collagen density and content. In-vivo, oral DOX administration did neither interfere with capsule formation nor in effectiveness of CCH dissolving fibrotic capsule tissue. However, skin thickness and especially collagen density was significantly higher compared to control groups. This led to a reduced rate of clinical skin lacerations after DOX administration. CONCLUSION: DOX inhibits CCH and accumulates in the skin. Thereby, DOX can effectively reduce skin laceration after CCH treatment.
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Implantes de Mama , Contractura , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Laceraciones , Animales , Implantes de Mama/efectos adversos , Cápsulas , Colágeno , Colagenasas/efectos adversos , Doxiciclina/farmacología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Fibrosis , Laceraciones/etiología , Colagenasa Microbiana/farmacología , Roedores , Siliconas/efectos adversos , Resultado del TratamientoRESUMEN
We retrospectively compared 64 scaphoid reconstructions in cases that had not undergone previous surgery with 31 cases in which previous surgery had been performed. The characteristics of the groups were similar except that there were more smokers in the group without previous surgery and a more frequent use of vascularized bone grafts in the group with previous surgery. At final follow-up, 66 and 65 months, respectively, after reconstruction, union incidence was 89% and 90%. In patients with previous surgery, grip strength was higher but not when expressed in percent of the contralateral hand. There were no differences in pinch strength, active wrist motion, functional scores, carpal height or scapholunate angle. We conclude that repeat surgery to the scaphoid did not seem to be a major risk factor for the overall outcomes, keeping in mind that a vascularized bone graft was more frequently used for secondary reconstructions.Level of evidence: III.
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Fracturas no Consolidadas , Enfermedades Musculoesqueléticas , Hueso Escafoides , Trasplante Óseo , Fracturas no Consolidadas/cirugía , Humanos , Estudios Retrospectivos , Hueso Escafoides/cirugía , Articulación de la Muñeca/cirugíaRESUMEN
INTRODUCTION: Closed incision negative-pressure therapy (CINPT) has been shown to shorten the time to heal in post-bariatric abdominoplasty and to lower seroma rates in cosmetic abdominoplasty. The objective of this study was to assess the effect of CINPT on donor-site morbidity following abdominal-based free-flap breast reconstruction. PATIENTS AND METHODS: We reviewed medical records from 225 women who had undergone 300 microsurgical free-flap breast reconstructions from the abdomen from November 1, 2007 to March 31, 2019. Patients were grouped according to wound therapy, including 127 patients in the standard of care group and 98 patients in the CINPT group. Primary outcomes were minor (non-operative) and major (operative) surgical site complications. Secondary outcomes were time to drain removal, in-hospital length, and scar quality. RESULTS: Analysis of patient demographics showed an equal distribution with regard to the age, smoking status, prevalence of diabetes mellitus, preoperative chemotherapy, and previous abdominal surgery in both groups. Significantly more patients with obesity (29.6 vs. 15.8%; p = .01) and bilateral breast reconstruction (40.8 vs. 27.6%; p = .04) were included in the CINPT group. Compared to standard of care, the CINPT group had a lower incidence of major surgical site complications (26.0 vs. 11.2%; p = .001). There was no difference in minor surgical site complications and secondary outcomes between groups. CONCLUSION: The CINPT represents a reliable tool to reduce surgical site complications on the abdominal donor-site in abdominal-based free-flap breast reconstruction.
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Mamoplastia , Terapia de Presión Negativa para Heridas , Herida Quirúrgica , Abdomen , Femenino , Humanos , Incidencia , Mamoplastia/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Estudios RetrospectivosRESUMEN
PURPOSE: The transverse musculocutaneous gracilis (TMG) flap is as a valuable alternative in autologous breast reconstruction. The purpose of this study was to evaluate the donor site morbidity and secondary refinement procedures after TMG flap breast reconstruction. METHODS: A retrospective study was conducted, including all patients who received TMG flap breast reconstructions, from January 2012 to August 2019. Primary outcomes were surgical site complications of the donor site and secondary refinement procedures carried out for aesthetic or reconstructive purposes for the medial thigh. Secondary outcomes of interest were lipofilling procedures for optimization of the reconstructed breasts. RESULTS: Ninety-nine patients received 159 TMG flaps for breast reconstruction. Patients' mean BMI was 23.5 (15.6-32.5) kg/m2. Bilateral breast reconstructions were performed in 60.6%. The mean flap volume was 330 (231-440) g. Surgical site complications occurred in 14.5% of the TMG donor sites and wound dehiscence was the most common complication (9.4%). Lymphedema occurred in 1.8% of the donor thighs. Aesthetic refinement procedures were performed in 25.2% on the donor thigh or contralateral thigh. Secondary lipofilling was performed in 54.1% of the reconstructed breasts and fat was harvested in only 11.9% from the legs. CONCLUSION: The TMG flap breast reconstruction combines low donor site morbidity with adequate volume for appealing breast results, particularly in slim-to-normal weight patients. However, patients should be informed about the likelihood of secondary refinement procedures on the donor site and the need of lipofilling to optimize the breast shape and volume.
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Mamoplastia/métodos , Colgajos Quirúrgicos/trasplante , Trasplante Autólogo/métodos , Adulto , Anciano , Neoplasias de la Mama/cirugía , Femenino , Humanos , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Colgajos Quirúrgicos/patología , Muslo/cirugía , Trasplante Autólogo/efectos adversosRESUMEN
INTRODUCTION: Since its introduction in 2013 Bromelain-based Enzymatic Debridement (ED) is increasingly used in burn centers. Published evidence shows its efficiency in eschar removal as well as a superiority in blood loss and necessity of further surgical procedures compared to standard-of-care. While the procedure is safe and shows reliable results in experienced hands, some practical and logistical issues must be challenged that are not described sufficiently in available literature. METHOD: A multi-professional panel, consisting of experienced users of ED from German-speaking burn units has been invited to an expert workshop. Topics concerning indication, definition of treatment pathways, practical issues, post-treatment and handling of complications have been coordinated in advance to allow discussion during the workshop. RESULTS: To each topic practical recommendations were developed and consented. Summarizing key messages have been additionally highlighted. They aim on helping to achieve optimal results after establishing the technique by new users as well as optimizing results by experienced users. Amongst others, the resulting recommendations deal with indications for ED beyond the classic domain, different treatment pathways depending on burn depth and primary result after ED with adapted post-treatment, management of treatment failure and implementation of infrastructural conditions. DISCUSSION: While efficiency of ED as well as superiority in some aspects of treatment of burn wounds could be shown in available literature, user-oriented recommendations for practical implementation are scarce. Although the recommendations and experts opinions published here are only partly evidenced based, they are still based on the pooled experienced of the panelists that easily outnumbers the cases published in literature so far and allow valuable support for a successful implementation of the technique.
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Unidades de Quemados , Cicatrización de Heridas , Desbridamiento , HumanosRESUMEN
Enzymatic debridement (ED) has become a reliable tool for eschar removal. Although ED application is simple, wound bed evaluation and therapy decision post-intervention are prone to subjectivity and failure. Experience in ED might be the key, but this has not been proven yet. The aim of this study was to assess interrater reliability (IR) in post-intervention wound bed evaluation and therapy decision as well as the impact of experience. In addition, the authors introduce video assessment as a valuable tool for post-ED decision-making and education. A video-based survey was conducted among physicians with various experiences in ED. The survey involved multiple-choice and 5-point Likert scale questions about professional status, experience in ED, confidence in post-ED wound bed evaluation, and therapy decision. Subsequently, videos of 15 mixed pattern to full-thickness burns immediately after removal of the enzyme complex were demonstrated. Participants were asked for evaluation of each burn wound, including bleeding pattern and consequent therapy decision. IR ≥ 80% was considered as a consensus. Responses were stratified according to participants' experience in applying ED (<10, 10-19, 20-49, and ≥50 applications). IR was assessed by chi-square test (raw agreement [RA]; ≥80% was considered as a consensus) and by calculation of Krippendorff's alpha. In addition, expert consensus for therapy decision was compared with the actual clinical course of each shown patient. Last, participants were asked for their opinion on video as an assessment tool for post-ED wound bed evaluation, decision-making, and training. Thirty-one physicians from 11 burn centers participated in the survey. The overall consensus (raw agreement [RA] ≥ 80%) in post-ED wound bed evaluation and therapy decision was achieved in 20 and 40%, respectively. Krippendorff's alpha is given by 0.32 (95% confidence interval: 0.15, 0.49) and 0.31 (95% confidence interval: 0.16, 0.47), respectively. Subgroup analysis revealed that physicians with high experience in ED achieved significantly more consensus in post-intervention wound bed evaluation and therapy decision compared with physicians with moderate experience (60 vs 13.3%; P = .02 and 86.7 vs 33.3%; P = .04, respectively). Video analysis was considered a feasible (90.3%) and beneficial (93.5%) tool for post-intervention wound bed evaluation and therapy decision as well as useful for training purposes (100%). Reliability of wound bed evaluation and therapy decision after ED depends on the experience of the rating physician. Video analysis is deemed to be a valuable tool for ED evaluation, decision-making, and user training.
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Actitud del Personal de Salud , Quemaduras/terapia , Colagenasas/uso terapéutico , Consenso , Desbridamiento/métodos , Colagenasa Microbiana/uso terapéutico , Apósitos Biológicos , Competencia Clínica , Humanos , Relaciones Médico-Paciente , Cicatrización de HeridasRESUMEN
Activity of the transcription factor NFE2 is elevated in the majority of patients with myeloproliferative neoplasms (MPNs), either by overexpression of the wild-type alleles or by the presence of an activating mutation. In murine models, enhanced NFE2 activity causes an MPN phenotype with spontaneous transformation to acute leukemia. However, little is known about the downstream target genes activated by augmented NFE2 levels. Here, we describe that NFE2 regulates expression of the hematopoietic master regulators GATA2 and SCL/TAL1, which are in turn overexpressed in primary MPN cells, suggesting that concomitant aberrant activation of several transcription factors coordinately contributes to the cellular expansion characteristic of these disorders.