Occipito-Cervico-Dorsal Flap for Neck Reconstruction After Postburn Contractures: A Case Report and Literature Review.

Because the head and neck are one of the most frequent locations of burns, it is of paramount importance that plastic surgeons and plastic surgical nurses understand the most effective surgical methods for treating neck contractures and the reconstructive technique required for each case. We introduce the case of a 42-year-old woman who presented with a severe postburn neck contracture that was reconstructed with a pedicled occipito-cervico-dorsal flap. We closed the donor-site wound primarily and completely covered the defect with good results. In addition to conventional skin grafts, dermal matrices, and microsurgical techniques, using an occipito-cervico-dorsal flap should be considered for reconstructing postburn neck contractures as it offers good aesthetic and functional outcomes, provides enough tissue and pliable skin, and results in minimal donor-site morbidity.

Bromelain-based enzymatic burn debridement: Spanish multidisciplinary consensus.

Background: Bromelain-based enzymatic debridement is gaining increased interest from burn specialists in the last few years. The objective of this manuscript is to update the previous, first Spanish consensus document from 2017 (Martínez-Méndez et al. 43:193-202, 2017), on the use of enzymatic debridement with NexoBrid® in burn injuries, adding the clinical experience of a larger panel of experts, integrating plastic surgeons, intensivists, and anesthesiologists. Methods: A consensus guideline was established by following a modified Delphi methodology of a 38-topic survey in two rounds of participation. Items were grouped in six domains: general indication, indication in critical patients, pain management, conditions for NexoBrid® application, NexoBrid® application technique, and post-debridement wound care. Results: In the first round, experts established consensus (strongly agree or agree) on 13 of the 38 statements. After the second round, a consensus was reached on 24 of the 25 remaining statements (97.2%). Conclusions: The present updated consensus document provides recommendations on the use of bromelain-based enzymatic debridement NexoBrid®, integrating the extensive clinical experience of plastic surgeons, intensivists, and anesthesiologists in Spain. Further clinical trials and studies are required to corroborate, modify, or fine tune the current statements.

Topical Administration of a Marine Oil Rich in Pro-Resolving Lipid Mediators Accelerates Wound Healing in Diabetic db/db Mice through Angiogenesis and Macrophage Polarization.

Impaired wound healing in patients with type 2 diabetes (DM2) is characterized by chronic inflammation, which delays wound closure. Specialized pro-resolving lipid mediators (SPMs) are bioactive molecules produced from essential polyunsaturated fatty acids (PUFAs), principally omega-3 docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). SPMs are potent regulators of inflammation and have been used to suppress chronic inflammation in peripheral artery disease, non-alcoholic fatty liver disease, and central nervous system syndromes. LIPINOVA® is a commercially available safe-grade nutritional supplement made from a fractionated marine lipid concentrate derived from anchovy and sardine oil that is rich in SPMs and EPA, as well as DHA precursors. Here, we assessed the effect of LIPINOVA® in wound dressing applications. LIPINOVA® showed biocompatibility with keratinocytes and fibroblasts, reduced the abundance of pro-inflammatory macrophages (Mφ1), and promoted in vitro wound closure. Daily application of the marine oil to open wounds made by punch biopsy in db/db mice promoted wound closure by accelerating the resolution of inflammation, inducing neoangiogenesis and Mφ1/Mφ2 macrophage polarization. In conclusion, LIPINOVA® displays pro-resolutive properties and could be exploited as a therapeutic agent for the treatment of diabetic ulcers.

Microvesicles from Human Adipose Tissue-Derived Mesenchymal Stem Cells as a New Protective Strategy in Osteoarthritic Chondrocytes.

BACKGROUND/AIMS: Chronic inflammation contributes to cartilage degeneration during the progression of osteoarthritis (OA). Adipose tissue-derived mesenchymal stem cells (AD-MSC) show great potential to treat inflammatory and degradative processes in OA and have demonstrated paracrine effects in chondrocytes. In the present work, we have isolated and characterized the extracellular vesicles from human AD-MSC to investigate their role in the chondroprotective actions of these cells. METHODS: AD-MSC were isolated by collagenase treatment from adipose tissue from healthy individuals subjected to abdominal lipectomy surgery. Microvesicles and exosomes were obtained from conditioned medium by filtration and differential centrifugation. Chondrocytes from OA patients were used in primary culture and stimulated with 10 ng/ml interleukin(IL)-1ß in the presence or absence of AD-MSC microvesicles, exosomes or conditioned medium. Protein expression was investigated by ELISA and immunofluorescence, transcription factor-DNA binding by ELISA, gene expression by real-time PCR, prostaglandin E2 (PGE2) by radioimmunoassay, and matrix metalloproteinase (MMP) activity and nitric oxide (NO) production by fluorometry. RESULTS: In OA chondrocytes stimulated with IL-1ß, microvesicles and exosomes reduced the production of inflammatory mediators tumor necrosis factor-α, IL-6, PGE2 and NO. The downregulation of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 would lead to the decreased PGE2 production while the effect on NO could depend on the reduction of inducible nitric oxide synthase expression. Treatment of OA chondrocytes with extracellular vesicles also decreased the release of MMP activity and MMP-13 expression whereas the production of the anti-inflammatory cytokine IL-10 and the expression of collagen II were significantly enhanced. The reduction of inflammatory and catabolic mediators could be the consequence of a lower activation of nuclear factor-κB and activator protein-1. The upregulation of annexin A1 specially in MV may contribute to the anti-inflammatory and chondroprotective effects of AD-MSC. CONCLUSIONS: Our data support the interest of AD-MSC extracellular vesicles to develop new therapeutic approaches in joint conditions.

Extracellular Vesicles from Adipose-Derived Mesenchymal Stem Cells Downregulate Senescence Features in Osteoarthritic Osteoblasts.

Osteoarthritis (OA) affects all articular tissues leading to pain and disability. The dysregulation of bone metabolism may contribute to the progression of this condition. Adipose-derived mesenchymal stem cells (ASC) are attractive candidates in the search of novel strategies for OA treatment and exert anti-inflammatory and cytoprotective effects on cartilage. Chronic inflammation in OA is a relevant factor in the development of cellular senescence and joint degradation. In this study, we extend our previous observations of ASC paracrine effects to study the influence of conditioned medium and extracellular vesicles from ASC on senescence induced by inflammatory stress in OA osteoblasts. Our results in cells stimulated with interleukin- (IL-) 1ß indicate that conditioned medium, microvesicles, and exosomes from ASC downregulate senescence-associated ß-galactosidase activity and the accumulation of γH2AX foci. In addition, they reduced the production of inflammatory mediators, with the highest effect on IL-6 and prostaglandin E2. The control of mitochondrial membrane alterations and oxidative stress may provide a mechanism for the protective effects of ASC in OA osteoblasts. We have also shown that microvesicles and exosomes mediate the paracrine effects of ASC. Our study suggests that correction of abnormal osteoblast metabolism by ASC products may contribute to their protective effects.

Tratamiento quirúrgico del paciente gran quemado: casuística de siete años en el Hospital Universitario y Politécnico la Fe de Valencia, España / Tratamento cirúrgico do paciente grande queimado: casuística de sete anos do Hospital Universitario y Politécnico la Fe de Valência, Espanha / Surgical treatment of the major burn: seven years experience in the University and Polytechnic La Fe Hospital of Valencia, Spain

Objetivo: Caracterizar los casos atendidos en el Hospital Universitario y Politécnico la Fe de Valencia, España, en el transcurso de 7 años de uso de un protocolo quirúrgico para pacientes con quemaduras de más del 50% de superfície corporal quemada (SCQ). Métodos: Se ha realizado un análisis descriptivo de los pacientes con quemaduras mayores al 50% de SCQ, tratados entre enero de 2011 y enero de 2017, en la Unidad de Quemados del Hospital La Fe (Valencia, España). Todos los pacientes fueron tratados de acuerdo al protocolo quirúrgico establecido en nuestra unidad para el paciente gran quemado. Resultados: Se trataron 35 pacientes, 25 varones y 10 mujeres, con edad media de 51,3±16,2 años. La llama fue el agente lesional más frecuente. La SC media afecta por quemadura fue 66,9±13,5%. La tasa de mortalidad (TM) neta fue del 55%, siendo el shock por quemadura la causa de muerte predominante en las primeras 48h y la sepsis tras las 48h. Conclusiones: El paciente gran quemado supone un reto terapéutico donde un enfoque multidisciplinar es determinante para su adecuada evolución. En nuestra serie, la estandarización del tratamiento quirúrgico mediante un protocolo ha permitido un adecuado manejo de los pacientes con una TM inferior a la estimada y comparable a la informada en la literatura.

Objetivo: Caracterizar os casos atendidos no Hospital Universitário y Politécnico la Fe de Valencia, Espanha, no transcurso de sete anos de uso de um protocolo cirúrgico para pacientes com queimaduras de superfície corporal queimada (SCQ) superior a 50%. Método: foi realizada análises descritiva dos casos de pacientes com SCQ superior a 50%, tratados entre janeiro de e janeiro de 2017, na Unidade de Queimados do Hospital La Fe (Valência, Espanha). Todos os pacientes foram tratados de acordo com o protocolo cirúrgico estabelecido na unidade para o paciente grande queimado. Resultados: Foram tratados 35 pacientes, 25 homens e 10 mulheres, com idade média de 51,3±16,2 anos. A chama foi o agente causador mais frequente. A SCQ media foi de 66,9±13,5%. A taxa de mortalidade (TM) foi de 55%, sendo o choque por queimadura a causa de morte predominante nas primeiras 48h e a sepses após 48h. Conclusões: O paciente grande queimado representa um desafio terapêutico no qual o foco multidisciplinar é determinante para sua adequada evolução. Nos casos estudados, a padronização do tratamento cirúrgico por meio de um protocolo permitiu um adequado manejo dos pacientes com una TM inferior à estimada e comparável à informada na literatura.

Objective: To characterize the cases treated at the University and Polytechnic la Fe Hospital in Valencia, Spain, over the course of 7 years with the use of a surgical protocol for patients with burns greater than 50% of total body surface area (TBSA). Methods: From January 2011 to January 2017, 35 patients with burns greater than 50% TBSA were treated in our Burn Unit. All patients were treated according to our major burn surgical protocol. Results: A total of 35 patients were treated, 25 men and 10 women, with a mean age of 51.3±16.2 years. Flame burn was the most common etiology. The mean TBSA affected was 66.9±13.5%. The mortality rate was 55%, with burn shock being the main cause of death in the first 48 hours. Conclusion: Patients with burns greater than 50% TBSA suppose a therapeutic challenge where a multidisciplinary approach is essential for its adequate evolution. In our series, the treatment standardization with a protocol has allowed an adequate management of the patients with a mortality rate similar to the literature report and lower than our estimated rate.

Recomendaciones de rehabilitación en el paciente quemado: revisión de literatura / Recomendações de reabilitação para paciente queimado: revisão da literatura / Rehabilitation recommendations in the burn patient: literature review

OBJETIVO: Realizar una revisión bibliográfica acerca de la rehabilitación en el paciente quemado, sintetizando las recomendaciones expuestas por los documentos de consenso internacionales y la bibliografía reciente. Además, exponemos la manera en que estas recomendaciones se han aplicado en la Unidad de Grandes Quemados del Hospital La Fe, en forma de un protocolo multidisciplinar de rehabilitación intensiva. MÉTODO: Se realizó una búsqueda bibliográfica de la literatura existente y los consensos internacionales centrados en el ámbito de la rehabilitación en el paciente quemado. Seguidamente, se relata la forma en que estas recomendaciones fueron implementadas en la Unidad de Grandes Quemados del Hospital La Fe de Valencia; en forma de un protocolo de rehabilitación intensivo y multidisciplinar. RESULTADOS: La bibliografía revisada refuerza los argumentos en favor del desarrollo y aplicación de protocolos de rehabilitación intensiva en las unidades de quemados para la mejora de los resultados funcionales de los pacientes. La experiencia en nuestra unidad en la cual se aplica un protocolo de este tipo coincide con los buenos resultados reportados. CONCLUSIONES: La aplicación precoz de una terapia rehabilitadora intensiva resulta clave a la hora de prevenir y tratar las posibles complicaciones funcionales y secuelas producidas por las quemaduras. Este tratamiento rehabilitador interdisciplinar se ha de centrar en la prevención de problemas a largo plazo, como las contracturas, la cicatrización anómala, deformidades, atrofia muscular, limitación de movilidad y otros problemas que merman la función física. Su utilización en cualquier unidad de quemados, permitirá optimizar los resultados funcionales de nuestros pacientes.(AU)

Objetivo: Realizar uma revisão da literatura científica sobre a reabilitação do paciente queimado, resumindo as recomendações estabelecidas por documentos de consenso internacional e na literatura recente. Além disso, apresentamos como essas recomendações foram implementadas na Unidade de Grandes Queimados do Hospital La Fe, na forma de um protocolo de reabilitação intensivo multidisciplinar. Método: Pesquisa bibliográfica da literatura e do consenso internacional existente centrado no campo da reabilitação no paciente queimado. Foi relatado como as recomendações internacionais foram implementadas para a prática dentro da unidade para atendimento ao grande queimado, no Hospital La Fe, no formato de um protocolo de reabilitação intensivo multidisciplinar. Resultados: A literatura existente reforça o desenvolvimento e implementação de protocolos de reabilitação intensiva em unidades de queimados para melhorar os resultados funcionais dos pacientes. A experiência em nossa unidade, em que esse tipo de protocolo é aplicado, corresponde aos bons resultados descritos na literatura. Conclusões: A aplicação antecipada de terapia de reabilitação intensiva é fundamental para a prevenção e tratamento de complicações e possíveis consequências funcionais causadas por queimaduras. Este tratamento interdisciplinar de reabilitação tem de se concentrar na prevenção de problemas de longo prazo, tais como contraturas, cicatrizes anormais, deformidades, atrofia muscular, dificuldade de locomoção e outros problemas que prejudicam a função física. Seu uso em qualquer unidade de queimados irá otimizar os resultados funcionais dos nossos pacientes.(AU)

ABSTRACT: OBJECTIVE: To perform a bibliographic review about rehabilitation of the burn patient, summarizing recommendations provided by international consensus documents and the most recent evidence. Moreover, we present the method in which this recommendations have been applied to the Great Burns Unit of the Hospital La Fe, in the format of a interdisciplinary intensive rehabilitation protocol. METHOD: A bibliographic search was performed among existent literature and international consensus documents focused on the field of burn patient rehabilitation. Following, the way in which this recommendations were applied at the Great Burns Unit of the Hospital La Fe of Valencia are presented in the shape of an intensive and multidisciplinar rehabilitation protocol. RESULTS: Reviewed bibliography supports the development and application of intensive rehabilitation protocols in burn units for the improvement of the functional results of their patients. The experience in our unit in which this sort of protocol is applied, matches the good results described in literature. CONCLUSIONS: Early intensive rehabilitation therapy is a key stone when it comes to prevention and treatment of functional complications. This interdisciplinary approach must focus in prevention of long term complications, such as contractures, abnormal scarring, deformities, muscular atrophy, mobility limitations and other issues which can decrease physical function. Its utilization in a Burn Unit, will help optimize functional results of their patients.(AU)

Paracrine effects of human adipose-derived mesenchymal stem cells in inflammatory stress-induced senescence features of osteoarthritic chondrocytes.

Aging and exposure to stress would determine the chondrocyte phenotype in osteoarthritis (OA). In particular, chronic inflammation may contribute to stress-induced senescence of chondrocytes and cartilage degeneration during OA progression. Recent studies have shown that adipose-derived mesenchymal stem cells exert paracrine effects protecting against degenerative changes in chondrocytes. We have investigated whether the conditioned medium (CM) from adipose-derived mesenchymal stem cells may regulate senescence features induced by inflammatory stress in OA chondrocytes. Our results indicate that CM down-regulated senescence markers induced by interleukin-1ß including senescence-associated ß-galactosidase activity, accumulation of γH2AX foci and morphological changes with enhanced formation of actin stress fibers. Treatment of chondrocytes with CM also decreased the production of oxidative stress, the activation of mitogen-activated protein kinases, and the expression of caveolin-1 and p21. The effects of CM were related to the reduction in p53 acetylation which would be dependent on the enhancement of Sirtuin 1 expression. Therefore, CM may exert protective effects in degenerative joint conditions by countering the premature senescence of OA chondrocytes induced by inflammatory stress.