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Differentiation of fibroblasts to myofibroblasts is governed by the transforming growth factor beta (TGF-ß) through a mechanism involving redox signaling and generation of reactive oxygen species (ROS). Myofibroblasts synthesize proteins of the extracellular matrix (ECM) and display a contractile phenotype. Myofibroblasts are predominant contributors of wound healing and several pathological states, including fibrotic diseases and cancer. Inhibition of the ROS-generating enzyme NADPH oxidase 4 (NOX4) has been proposed to mitigate fibroblast to myofibroblast differentiation and to offer a therapeutic option for the treatment of fibrotic diseases. In this study, we addressed the role of NOX4 in physiological wound healing and in TGF-ß-induced myofibroblast differentiation. We explored the phenotypic changes induced by TGF-ß in primary skin fibroblasts isolated from Nox4-deficient mice by immunofluorescence, Western blotting and RNA sequencing. Mice deficient for Cyba, the gene coding for p22phox, a key subunit of NOX4 were used for confirmatory experiments as well as human primary skin fibroblasts. In vivo, the wound healing was similar in wild-type and Nox4-deficient mice. In vitro, despite a strong upregulation following TGF-ß treatment, Nox4 did not influence skin myofibroblast differentiation although a putative NOX4 inhibitor GKT137831 and a flavoprotein inhibitor diphenylene iodonium mitigated this mechanism. Transcriptomic analysis revealed upregulation of the mitochondrial protein Ucp2 and the stress-response protein Hddc3 in Nox4-deficient fibroblasts, which had however no impact on fibroblast bioenergetics. Altogether, we provide extensive evidence that NOX4 is dispensable for wound healing and skin fibroblast to myofibroblast differentiation, and suggest that another H2O2-generating flavoprotein drives this mechanism.
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Peróxido de Hidrogênio , Miofibroblastos , Animais , Humanos , Camundongos , Diferenciação Celular , Fibroblastos/metabolismo , Fibrose , Peróxido de Hidrogênio/metabolismo , Miofibroblastos/metabolismo , NADPH Oxidase 4/genética , NADPH Oxidase 4/metabolismo , NADPH Oxidases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1 , CicatrizaçãoRESUMO
Reconstruction of large chest wall defects is challenging. Here we discuss the process of decision-making in planning chest wall reconstruction, considering the requirements of tumor removal, stabilization of the chest wall, and soft tissue coverage, illustrated by a case of a hemi-chest wall defect in a child. Ewing sarcoma measuring 10 × 9 × 13 cm was resected in a 9-year-old boy, followed by stabilization using a Gore-Tex patch. Due to extension of the oncologic resection far into the superomedial quadrant of the chest, tension-free coverage with a classical latissimus-dorsi flap could not be achieved. Integrating the serratus-anterior muscle into the flap creating a chimeric latissimus-dorsi/serratus-anterior flap allowed for excellent soft tissue coverage of the foreign body. As the skin could be preserved, careful incision planning was necessary to allow for best possible exposure during oncologic resection and flap harvest, while ensuring skin vascularization impaired by underlying tumor resection. Two vertical skin incisions were chosen, one presternal and a second in the mid-axillary fold delineating a large bipedicled skin flap. Postoperative recovery was excellent. Solid skin vascularization and adequate soft tissue coverage of the alloplastic material allowed for the patient to receive two cycles of postoperative radiotherapy without developing wound dehiscence. Careful interdisciplinary planning of skin incisions allowed for good exposure for tumor resection and flap harvest while preserving skin vascularization. Choosing a chimeric latissimus-dorsi/serratus-anterior flap provided larger coverage than a classical latissimus-dorsi flap with minimal additional donor site morbidity. Taken together, we here present a pragmatic solution to a complex problem.
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Background: An increasing number of breast cancer patients undergo immediate or secondary breast reconstruction, but the ideal method in terms of patient satisfaction remains ambiguous. We compared the 3 most common breast reconstruction techniques to determine patient satisfaction and objective outcomes. Methods: Retrospective study of 184 patients with breast cancer who underwent a reconstructive procedure between 1993 and 2011 at our institution. Procedures evaluated were implant-based reconstruction (IBR) alone, latissimus dorsi (LD) flap reconstruction with/without implant, and deep inferior epigastric perforator (DIEP) free flap reconstruction. A retrospective patient satisfaction questionnaire was sent to all women. Twenty patients from each subgroup were matched to conduct a standardized objective assessment of the sensitivity of their reconstructed breast. A blinded photographic evaluation was also performed by 3 independent observers to assess the esthetic aspect and symmetry. Results: DIEP obtained significantly higher average scores regarding the esthetic outcome, immediate reconstruction impact, and overall score in the questionnaire evaluation. The IBR had the best results in the somatosensory evaluation, with DIEP scoring better than LD. DIEP received higher scores on average than LD for the criteria of size and symmetry in the esthetic evaluation. No statistically significant differences were observed between IBR and DIEP. Conclusions: Good results were reported overall for all breast reconstruction procedures, with more reserved scores for LD. The DIEP reconstruction appeared to be the most satisfactory and best experienced reconstruction method for patients, despite the complexity of the intervention. Clinicians should be encouraged to consider DIEP as the principal choice for breast reconstruction.
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BACKGROUND: Free flap reconstruction is the gold standard in complex head and neck reconstruction. The branches of the external carotid vessels (ECVs) are considered the most suitable recipients, but they may be unavailable in patients presenting "frozen necks" or "vessel-depleted necks" due to previous treatments. We report our experience using the transverse cervical vessels (TCV) in these situations. METHODS: Retrospective chart review of microsurgical head and neck reconstructions from 2005 to 2017. We focused our analysis on secondary procedures and compared the complication rate according to whether the TCV or the ECVs were used. RESULTS: A total of 97 free flaps were performed for secondary procedures in 89 patients, mainly due to oncological recurrence and fistulae. TCV were used in 14 procedures when external carotid vessel branches were unavailable. The overall complication rate (all grade III Dindo-Clavien) was of 21% versus 35%, respectively, in the TCV and ECVs group. Grade IIIb Dindo-Clavien complications, i.e., microsurgical complications (10%) and flap loss (1%), were only recorded in the ECVs group. Other complications recorded were seroma (7% versus 1%) and hematoma (17% versus 6%) in the TCV and ECVs groups, respectively, and corresponded to grade IIIa Dindo-Claviens. CONCLUSIONS: The use of TCV is a safe second-line recipient site for microsurgical head and neck reconstruction in vessel-depleted necks. Major advantages are their anatomical position outside the previous surgical and radiation zone, lower affinity for atherosclerotic damage, and similar diameter to the pedicles of the most used flaps.
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There is increasing interest in the use of adipose-derived mesenchymal stromal cells (ASCs) for wound repair. As the fate of administered cells is still poorly defined, we aimed to establish the location, survival, and effect of ASCs when administered either systemically or locally during wound repair under physiological conditions. To determine the behavior of ASCs, a rat model with wounds on the dorsal aspect of the hind paws was used and two treatment modes were assessed: ASCs administered systemically into the tail vein or locally around the wound. ASCs were transduced to express both firefly luciferase (Fluc) and green fluorescent protein to enable tracking by bioluminescence imaging and immunohistological analysis. Systemically administered ASCs were detected in the lungs 3 hours after injection with a decrease in luminescent signal at 48 hours and signal disappearance from 72 hours. No ASCs were detected in the wound. Locally administered ASCs remained strongly detectable for 7 days at the injection site and became distributed within the wound bed as early as 24 hours post injection with a significant increase observed at 72 hours. Systemically administered ASCs were filtered out in the lungs, whereas ASCs administered locally remained and survived not only at the injection site but were also detected within the wound bed. Both treatments led to enhanced wound closure. It appears that systemically administered ASCs have the potential to enhance wound repair distally from their site of entrapment in the lungs whereas locally administered ASCs enhanced wound repair as they became redistributed within the wound bed.
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Tecido Adiposo/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Cicatrização/efeitos dos fármacos , Tecido Adiposo/citologia , Animais , Modelos Animais de Doenças , Humanos , RatosRESUMO
Background: Keloids are debilitating fibrous skin proliferations with a high recurrence rate after surgical treatment. Postoperative radiotherapy (PORT) is a well-tolerated adjuvant treatment to reduce the risk of recurrence, but the optimal regimen for this combined treatment remains unknown. The aim of this study is to evaluate the efficacy of combining surgical excision and immediate PORT. Methods: We retrospectively reviewed the records of patients with keloid lesions treated with adjuvant PORT in the period 2005-2014 at Geneva University Hospitals. Main outcomes were the rates of complications and recurrence in patients with a minimal follow-up of 1 year, including the Patient and Observer Scar Assessment Scale satisfaction scores. Results: 10 patients with 16 keloids were eligible (mean follow-up, 37 months). Only one recurrence was reported (6%). In 12.5% of cases, mild erythema appeared in the early postoperative period. No major complications were observed. The overall patient and observer satisfaction rate was excellent. Conclusion: Surgical excision combined with immediate PORT is an effective and easy treatment with good esthetic results and an acceptable recurrence rate. It should be considered for patients with persistent keloid formation after failure of other treatments and those at high risk of relapse.
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BACKGROUND: The submental flap is a pedicled island flap with excellent color match for facial reconstruction. The flap can be raised with muscle, submandibular gland, or bone and can be transposed to reach defects up to two-thirds of the face. The authors report the primary author's (D.M.) experience of 25 years using the submental flap from its original description to most recent technical evolutions in both Europe and Africa. METHODS: This is a retrospective study including all patients with facial defects who underwent reconstruction using a submental flap between 1991 and 2016. This study included the use of all four variations of the submental flap: platysmal, digastric, extended, and superextended. The authors report technical adaptations and complications encountered. RESULTS: The authors performed 311 facial reconstructions using submental flaps: 32 platysmal, 133 digastric, 91 extended, and 45 superextended variations. In conjunction with these reconstructions, the authors performed 10 osteocutaneous submental flaps and two free flaps. The authors report two cases of total flap necrosis (0.6 percent) and 28 minor complications, including 23 cases of distal skin necrosis (7 percent), one reversible mandibular facial nerve palsy (0.3 percent), and three hematomas (1 percent). CONCLUSIONS: The submental flap has proven to be a reliable flap for head and neck reconstruction. The four technical modifications described use varying amounts of soft tissue to replace tissue lost and can include vascularized bone from the mandibular margin. This flap exemplifies Gillies' principle of "replacing like with like" and should be discussed as an alternative to free tissue transfer in facial reconstruction, especially in settings where resources are limited. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
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Face/cirurgia , Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica/métodos , Transplante de Pele/métodos , Adulto , África , Criança , Queixo , Europa (Continente) , Neoplasias Faciais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noma/cirurgia , Procedimentos de Cirurgia Plástica/tendências , Estudos Retrospectivos , Transplante de Pele/tendências , Coleta de Tecidos e Órgãos/métodos , Coleta de Tecidos e Órgãos/tendências , Técnicas de Fechamento de Ferimentos/tendênciasRESUMO
BACKGROUND: The adjunction of autologous platelet-rich plasma (PRP) is emerging as a promising approach to enhance the long-term survival of fat grafting, but there are still insufficient data on its efficacy. The aim of this in vivo study was to assess the effect of the addition of non-activated PRP on fat graft outcome. METHODS: Human adipose tissue mixed with 20% of non-activated PRP was injected under the scalp skin of nude Balb/cAnNRj mice and compared to grafted fat mixed with 20% of saline. The fat graft volume was analyzed by a computed tomography scan until day 90 and immunohistochemistry was then performed to assess adipocyte viability and graft revascularization. RESULTS: At day 90, the volume of fat graft was not enhanced by PRP compared to the saline control group. However, immunohistochemistry showed that PRP significantly increased the fat graft area occupied by intact adipocytes compared to the saline group (72.66% vs. 60.78%, respectively; p < 0.05). Vascularity was also significantly higher in the PRP group compared to the control group (6695 vs. 4244 CD31+ cells/µm2, respectively; p < 0.05). CONCLUSION: The adjunction of non-activated-PRP to fat grafts significantly increased adipocyte viability and tissue vascularity. However, in contrast to other studies adding activated-PRP, non-activated-PRP did not increase residual fat graft volume until day 90. Further studies are therefore needed to understand whether PRP has a positive effect on fat graft volume. As 3D computed tomography scan is a reproducible and precise technique, it should be used to analyze fat graft volume changes over time.
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Sobrevivência de Enxerto/efeitos dos fármacos , Plasma Rico em Plaquetas/metabolismo , Gordura Subcutânea Abdominal/transplante , Animais , Feminino , Humanos , Imageamento Tridimensional , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Gordura Subcutânea Abdominal/diagnóstico por imagem , Gordura Subcutânea Abdominal/efeitos dos fármacos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Median and paramedian craniofacial clefts are associated with hypertelorism, anterior encephalocele, positional abnormalities of the maxilla, and nasal deformity. Cleft lip and palate, eyelid coloboma, and widow's peak are frequently present. METHODS: The authors collected data from 30 patients (mean age, 5.8 years; range, 4 months to 18 years) operated between 1986 and 2017 with median or paramedian craniofacial clefts of differing degrees of severity. Malformations of the different anatomic units and their surgical treatment were assessed, as well as complication rates. RESULTS: All patients presented nasal malformations and either telecanthus (nâ¯=â¯16) or hypertelorism (nâ¯=â¯14). Most patients (nâ¯=â¯23) had anterior encephalocele. All patients underwent nasal corrections, and most of them had medial canthopexy (nâ¯=â¯24). Excision of encephalocele was associated with fronto-orbital remodeling. Medialization of the orbits was performed in 11 patients, mainly by box shift (nâ¯=â¯9). Patients from outside Switzerland (nâ¯=â¯23) were operated at an older age than those in the native patient group. Because of staged reconstruction, 13 patients had more than one operation. Surgical complications included three infections and one expander exposition. One patient had bone resorption of a frontal bone flap. Nasal correction needed more than one procedure in 5 patients, and medial canthopexy had to be repeated in 7 patients. Esthetic results were satisfactory, permitting social integration. CONCLUSION: Median and paramedian craniofacial clefts need adapted and carefully planned corrections respecting the growth of anatomic units. The quality of the medial canthal and nasal reconstruction is to a large extent responsible for the overall result.
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Anormalidades Craniofaciais/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Adolescente , Criança , Pré-Escolar , Encefalocele/cirurgia , Feminino , Humanos , Lactente , Masculino , Nariz/anormalidadesRESUMO
BACKGROUND: Eradication of chronic tibial osteomyelitis necessitates aggressive debridement is often followed by soft tissue reconstruction. Muscular flaps are said to be more effective than non-muscular flaps for infection treatment, while fasciocutaneous and perforator flaps are considered to be less invasive and offering a better aesthetic result. METHODS: In this study, we reviewed 24 consecutive cases of chronic tibial osteomyelitis treated according to a specific protocol in a tertiary hospital. Soft tissue coverage was done with either muscular or non-muscular free flaps. Infection recurrence and complications were compared between different flap types. Additionally, we assessed the long-term functional and aesthetic results and patient's satisfaction. RESULTS: Muscular flap was used in 13 patients (13 latissimus dorsi and 1 serratus anterior) and 11 patients underwent fasciocutaneous/perforator flaps [1 anterolateral thigh flap, 4 lateral arm flaps, 5 thoracodorsal artery perforator (TAP) flaps and 1 radial forearm flap]. Infection was resolved for 84.6% of patients in the muscular flaps group and 90.9% in the non-muscular flaps group. None of the patients with muscular flaps were satisfied with the aesthetic appearance of their reconstructed leg when compared to 83.3% of patients with non-muscular flaps. Also, a slight regain of touch sensitivity was acknowledged in the non-muscular flap group compared to the muscular. CONCLUSION: In this study of adult chronic tibial osteomyelitis cases, we demonstrated that fasciocutaneous and perforator free flaps offer a comparable efficacy to the muscle flaps for infection treatment, with a significantly higher patient satisfaction and aesthetic result.
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Long-segment tracheal reconstruction remains a challenge. The ideal tracheal substitute should be an epithelialized tube to prevent stenosis and sufficiently rigid to maintain airflow patency. An autologous technique using a radial forearm free flap reinforced by rib cartilage has been recently described for tracheal reconstruction. We report here two cases of complex tracheal reconstruction with a modification of this technique, which consists of the creation of two independent skin paddles to allow the reconstruction of the trachea and a second adjacent defect (eg, cervical skin, esophagus). Airway patency was achieved with no stenosis, prolonged stenting, fistula, or necrosis after 26 and 44 months, respectively. We suggest that the satisfactory outcome obtained with this modified technique is a valuable option for tracheal and adjacent defect reconstruction without the need for a second flap.
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Cartilagem Costal/transplante , Antebraço/irrigação sanguínea , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos/transplante , Neoplasias da Traqueia/cirurgia , Adulto , Idoso , Evolução Fatal , Humanos , Masculino , Planejamento de Assistência ao Paciente , Retalhos Cirúrgicos/irrigação sanguínea , Transplante AutólogoRESUMO
We report two rare cases of inflammatory reactions with multiple subcutaneous facial painful collections after Hyaluronic acid injections, expose their management and discuss aetiologic hypothesis. Due to unfavourable evolution despite antibiotic treatment, surgical drainage was performed. Immune-mediated delayed hypersensitivity reactions were the most probable cause.
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INTRODUCTION: Some surgeons consider a high body mass index (BMI) or important abdominal fat excess as contraindications for breast reconstruction with free deep inferior epigastric perforator (DIEP) flap. This study aimed to identify factors associated with post-operative complications by using this type of flap, with an emphasis on BMI and abdominal subcutaneous fat thickness. METHODS: A retrospective chart review of 105 consecutive patients who underwent DIEP flap breast reconstruction at our institution was performed to assess post-operative complications. Among other risk factors, we specifically studied the influence of BMI and abdominal wall thickness on complication occurrence. Abdominal wall thickness was measured at 10 different points on the angio-computed tomography scan performed pre-operatively. RESULTS: Median age was 49.8 years (range, 27-69); average BMI was 25.57 kg/m2 (range, 18.07-41.91). Immediate breast reconstruction was performed for 35% of patients, and five patients (4.7%) underwent bilateral reconstruction. Twenty-six patients (24.8%) presented 29 post-operative complications; 12 concerned abdominal complications (delayed wound healing [n = 6] and seroma [n = 6]) and 17 were related to complications of the reconstructed breast (six minimal necrosis treated conservatively, eight minor necrosis requiring surgical debridement and three total flap loss). The complication rate was not correlated with increased BMI or abdominal wall thickness. The only factor that significantly predicts DIEP flap complications was pre-operative radiotherapy (odds ratio = 4.05; p = 0.03). CONCLUSIONS: No significant correlation was observed between BMI of 25-35 kg/m2 or abdominal wall thickness and post-operative complications of the donor site or DIEP flap. Therefore, these factors should not be considered as contraindication criteria.
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Mama/patologia , Mamoplastia/efeitos adversos , Retalho Perfurante/efeitos adversos , Retalho Perfurante/patologia , Complicações Pós-Operatórias/etiologia , Gordura Subcutânea Abdominal/anatomia & histologia , Adulto , Idoso , Índice de Massa Corporal , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Pessoa de Meia-Idade , Necrose , Complicações Pós-Operatórias/cirurgia , Radioterapia/efeitos adversos , Reoperação , Estudos Retrospectivos , Fatores de Risco , Gordura Subcutânea Abdominal/diagnóstico por imagemRESUMO
The interdisciplinary management of patients with multiple organ injuries after lightning strike is of paramount importance. Cutaneous burns can be associated to other organ injuries requiring emergency and life-support treatment. We report the case of a lightning strike victim who presented with burns as well as cardiologic and neurologic complications.
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INTRODUCTION: Reconstruction of facial bone defects in children is challenging. The use of well-vascularized bone is mandatory to obtain stable lasting results. This study reports our experience of facial bone reconstruction using prefabricated vascularized calvarium flaps. METHODS: Retrospective case series of 50 patients who underwent 52 maxillary, malar, and mandibular reconstructions between 1988 and 2014 using prefabricated vascularized calvarium flaps. Forty-nine patients suffered from noma sequels; one patient had craniofacial cleft Tessier 3-11. Surgery consisted of a two-step procedure beginning with flap delay and prelamination with skin grafting on the galea. Flap harvest followed at least 2 weeks later (range, 2-16 weeks), including a full-thickness calvarium fragment, which was set into the facial defect. RESULTS: Early complications concerned wound healing and infections requiring surgical revision in six patients at the recipient and six at the donor site. There was one flap loss. Clinical long-term assessment at 15-year median follow-up (range, 1-27 years) showed good results, assuring facial height and contour. Radiological long-term results demonstrated excellent integration of the flap to the adjacent facial skeleton of the growing child. CONCLUSIONS: Prefabricated vascularized calvarium flaps are an effective, safe and lasting method for reconstruction of facial bone defects in children.
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Ossos Faciais/cirurgia , Reconstrução Mandibular/métodos , Crânio/cirurgia , Retalhos Cirúrgicos/cirurgia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos , Crânio/irrigação sanguínea , Retalhos Cirúrgicos/irrigação sanguínea , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Most post-bariatric patients seek body contouring procedures to correct skin excess after massive weight loss. Among these procedures, some surgeons are still wary of circular abdominoplasty, mainly because it is considered a major intervention associated with a high complication rate. The aim of this study was to assess the complication rate of circular abdominoplasty performed on patients presenting with massive weight loss, with a particular emphasis on patient selection and surgical technique. METHODS: Fifty-six consecutive patients who underwent circular abdominoplasty following massive weight loss between January 2001 and March 2015 were included in the study. The indications for the procedure were abdominal skin excess extending to the flanks and the posterior region of the lower trunk. Data were collected retrospectively through medical charts and photographs. RESULTS: Forty-nine patients were female. The mean age was 39.8 years, with a mean preoperative body mass index of 25.7 kg/m2. The mean time between bariatric surgery and circular abdominoplasty was 3.3 years. The overall complication rate was 23.2%, mostly minor, with only one (1.7%) early surgical revision under local anesthesia for delayed wound healing. Blood transfusion was required for 8.9% of patients. CONCLUSION: Patient selection (e.g., body mass index < 30 kg/m2), precise preoperative planning and markings, and simple and careful surgical technique with minimal liposuction and undermining are crucial. Ensuring these key factors renders circular abdominoplasty a reliable and safe procedure, with low complication rates.
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Abdominoplastia , Satisfação do Paciente , Seleção de Pacientes , Parede Abdominal/cirurgia , Abdominoplastia/efeitos adversos , Abdominoplastia/métodos , Adulto , Cirurgia Bariátrica/métodos , Feminino , Humanos , Lipectomia/métodos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Redução de PesoRESUMO
NADPH oxidases (NOX) mediate redox signaling by generating superoxide and/or hydrogen peroxide, which are involved in biosynthetic pathways, e.g. thyroid hormone generation, dityrosine crosslinking, as well as bacterial killing. Data investigating the role of NOX enzymes in cutaneous wound repair is limited and specifically their function in skin myofibroblast expression is unknown. The isoform NOX4 was recently shown to be a pre-requisite for the differentiation of cardiac and pulmonary myofibroblasts. In this study we investigate the role of NOX4 in wound repair using a wound model in NOX4 knockout mice (n=16) and wildtype mice (n=16). Wounds were photographed daily until complete wound closure. Mice were sacrificed at day 3, 7, 14; wound tissue was harvested. NOX4-deficient mice healed significantly slower (22 days, SD=1.9) than wild-type mice (17 days, SD=1.4, p<0.005). However, there was no difference in myofibroblast expression. Strong dityrosine formation was observed, but was significantly weaker in NOX4-/- mice (p<0.05). NOX2, HIF1α and CD31 expression was significantly weaker in NOX4-/- mice (p<0.05). In this study we show for the first time that NOX4 plays a role in cutaneous wound repair. Our data suggests that NOX4 mediates HIF1α expression and neoangiogenesis during wound repair. NOX4 deletion led to a decreased expression of NOX2, implying a role of NOX4 in phagocytic cell recruitment. NOX4 was required for effective wound contraction but not myofibroblast expression. We suggest that myofibroblast contraction in NOX4-deficient mice is less effective in contracting the wound because of insufficient dityrosine-crosslinking of the ECM, providing the first indication for a physiological function of dityrosine crosslinking in higher animals.
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Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , NADPH Oxidase 2/genética , NADPH Oxidase 4/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Cicatrização/genética , Animais , Vias Biossintéticas/genética , Fibroblastos , Regulação da Expressão Gênica , Peróxido de Hidrogênio/metabolismo , Camundongos , Camundongos Knockout , Miofibroblastos/metabolismo , Miofibroblastos/patologia , NADPH Oxidase 4/deficiência , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMO
OBJECTIVE: In this study, we assess interdisciplinary surgical and medical parameters associated to recurrences of infected pressure ulcers. BACKGROUND: There is a little in the published literature regarding factors associated with the outcome of treatment of infected pressure ulcers. METHODS: We undertook a single-center review of spinal injured adults hospitalized for an infected pressure ulcer or implant-free osteomyelitis and reviewed the literature on this topic from 1990-2015. RESULTS: We found 70 lesions in 31 patients (52 with osteomyelitis) who had a median follow-up of 2.7 years (range, 4 months to 19 years). The median duration of antibiotic therapy was 6 weeks, of which 1 week was parenteral. Clinical recurrence after treatment was noted in 44 infected ulcers (63%), after a median interval of 1 year. In 86% of these recurrences, cultures yielded a different organism than the preceding episode. By multivariate analyses, the following factors were not significantly related to recurrence: number of surgical interventions (hazard ratio 0.9, 95% confidence interval 0.5-1.5); osteomyelitis (hazard ratio 1.5; 0.7-3.1); immune suppression; prior sacral infections, and duration of total (or just parenteral) antibiotic sue. Patients with antibiotic treatment for <6 weeks had the same failure rate as those with as >12 weeks (χ test; Pâ=â0.90). CONCLUSIONS: In patients with infected pressure ulcers, clinical recurrence occurs in almost two-thirds of lesions, but in only 14% with the same pathogen(s). The number of surgical debridements, flap use, or duration of antibiotic therapy was not associated with recurrence, suggesting recurrences are caused by reinfections caused by other extrahospital factors.
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Úlcera por Pressão/microbiologia , Úlcera por Pressão/terapia , Dermatopatias Infecciosas/microbiologia , Dermatopatias Infecciosas/terapia , Adulto , Antibacterianos/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Falha de TratamentoRESUMO
BACKGROUND: Hyperglycemia is known to adversely affect the outcome of ischemic insults, but its interaction with ischemia has not been investigated in wound repair yet. In this study, we develop a new animal model allowing to investigate the interaction between hyperglycemia and ischemia during the wound repair process. We focus on myofibroblast differentiation, a key element of wound repair. METHODS: Ischemia was inflicted in Wistar rats by resection of the femoral to popliteal arteries on the left side, whereas arteries were dissected without resection on the right side. Full-thickness skin wounds (1 cm(2)) were created on both feet. Hyperglycemia was induced by injection of streptozotocin. Normoglycemic animals served as control (n = 23/group). Blood flow, wound closure, and myofibroblast expression were measured. RESULTS: Wound closure was significantly delayed in ischemic compared with nonischemic wounds in all rats. This delay was almost 5-fold exacerbated in hyperglycemic rats compared with normoglycemic rats, while hyperglycemia alone showed only a slight effect on wound repair. Delayed wound repair was associated with impaired wound contraction and myofibroblast differentiation. CONCLUSIONS: Our model allows to specifically quantify the effect of hyperglycemia and ischemia alone or in combination on wound repair. We show that hyperglycemia amplifies the inhibitory effect of ischemia on wound repair and myofibroblast expression. Our data reveal for the first time the synergic aspect of this interaction and therefore stress the importance of a strict glycemic control in the management of ischemic wounds.
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Introduction. Medical tourism for aesthetic surgery is popular. Nontuberculous mycobacteria (NTM) occasionally cause surgical-site infections. As NTM grow in biofilms, implantations of foreign bodies are at risk. Due to late manifestation, infections occur when patients are back home, where they must be managed properly. Case Report. A 39-year-old healthy female was referred for acute infection of the right gluteal area. Five months before, she had breast implants replacement, abdominal liposuction, and gluteal lipofilling in Mexico. Three months postoperatively, implants were removed for NTM-infection in Switzerland. Adequate antibiotic treatment was stopped after seven days for drug-related hepatitis. At entrance, gluteal puncture for bacterial analysis was performed. MRI showed large subcutaneous collection. Debridement under general anaesthesia was followed by open wound management. Total antibiotic treatment was 20 weeks. Methods. Bacterial analysis of periprosthetic and gluteal liquids included Gram-stain plus acid-fast stain, and aerobic, anaerobic and mycobacterial cultures. Results. In periprosthetic fluid, Mycobacterium abscessus, Propionibacterium, and Staphylococcus epidermidis were identified. The same M. abscessus strain was found gluteally. The gluteal wound healed within six weeks. At ten months' follow-up, gluteal asymmetry persists for deep scarring. Conclusion. This case presents major complications of multisite aesthetic surgery. Surgical-site infections in context of medical tourism need appropriate bacteriological investigations, considering potential NTM-infections.