The Mandible Ameliorates Facial Allograft Rejection and Is Associated with the Development of Regulatory T Cells and Mixed Chimerism.

Vascularized composite allografts contain various tissue components and possess relative antigenicity, eliciting different degrees of alloimmune responses. To investigate the strategies for achieving facial allograft tolerance, we established a mouse hemiface transplant model, including the skin, muscle, mandible, mucosa, and vessels. However, the immunomodulatory effects of the mandible on facial allografts remain unclear. To understand the effects of the mandible on facial allograft survival, we compared the diversities of different facial allograft-elicited alloimmunity between a facial osteomyocutaneous allograft (OMC), including skin, muscle, oral mucosa, and vessels, and especially the mandible, and a myocutaneous allograft (MC) including the skin, muscle, oral mucosa, and vessels, but not the mandible. The different facial allografts of a BALB/c donor were transplanted into a heterotopic neck defect on fully major histocompatibility complex-mismatched C57BL/6 mice. The allogeneic OMC (Allo-OMC) group exhibited significant prolongation of facial allograft survival compared to the allogeneic MC group, both in the presence and absence of FK506 immunosuppressive drugs. With the use of FK506 monotherapy (2 mg/kg) for 21 days, the allo-OMC group, including the mandible, showed prolongation of facial allograft survival of up to 65 days, whereas the myocutaneous allograft, without the mandible, only survived for 34 days. The Allo-OMC group also displayed decreased lymphocyte infiltration into the facial allograft. Both groups showed similar percentages of B cells, T cells, natural killer cells, macrophages, and dendritic cells in the blood, spleen, and lymph nodes. However, a decrease in pro-inflammatory T helper 1 cells and an increase in anti-inflammatory regulatory T cells were observed in the blood and lymph nodes of the Allo-OMC group. Significantly increased percentages of donor immune cells were also observed in three lymphoid organs of the Allo-OMC group, suggesting mixed chimerism induction. These results indicated that the mandible has the potential to induce anti-inflammatory effects and mixed chimerism for prolonging facial allograft survival. The immunomodulatory understanding of the mandible could contribute to reducing the use of immunosuppressive regimens in clinical face allotransplantation including the mandible.

A New Face Subunit Transplant Model in Mice, Containing Skin, Mandible, and Oral Mucosa for Future Face Vascularized Composite Allotransplantation Studies.

BACKGROUND: In immunologic research, mice have advantages over other animals, such as low costs, easy handling, suitable life cycle, and adequate laboratory resources. However, vascularized composite allotransplantation surgery using mice is not popular, partly because of technical difficulties and high mortality rates. The authors' goal was to demonstrate a face transplantation model in mice that includes skin, mandible, and oral mucosa. METHODS: The authors developed a new syngeneic face transplantation model composed of skin, mandible, teeth, and oral mucosa in C57BL/6 mice. The following assessment included measuring the length of the right incisor on the transplanted mandibles, computed tomographic scan in one mouse for mandibular structure evaluation, and histologic examination of different tissue samples in another mouse for viability evaluation. RESULTS: The authors performed five consecutive transplantations. The donor vessels were the common carotid artery (approximately equal to 0.4 mm) and the anterior facial vein (approximately equal to 0.2 mm), and the recipients were the common carotid artery and the posterior facial vein (approximately equal to 0.4 mm). The mean operative time was 80 minutes for the donor and 123 minutes for the recipient. There were neither flap failures nor animal deaths. The follow-up was 6 months. The right incisor of the transplant grew at different rates in all cases. Histologic samples showed viability in all tissues, including mandibular bone marrow. Computed tomography demonstrated normal structure of the transplanted bone. CONCLUSION: The authors' syngeneic partial face transplantation model in mice, which included skin, oral mucosa, and mandible with teeth, should be useful for future face allotransplantation research, as the myriad of tissues it provides, of different immunomodulatory functions, is similar to that in the clinical scenario.

Colgajos en hélice de las arterias perforantes para la reconstrucción de los defectos de cubrimiento en la extremidad inferior: experiencia de la IPS Universitaria, Medellín, Colombia / Propeller flap of perforating arteries in reconstruction of resection defects in the lower extremity: experience at the University IPS, Medellín, Colombia

Introducción. Los colgajos en hélice de las arterias perforantes son una opción reconstructiva regional y versátil para los defectos del miembro inferior. Materiales y métodos. Se trata de un estudio retrospectivo de cohorte, de 37 colgajos en 31 pacientes, hechos de agosto del 2012 a julio del 2015. Se recolectó la información demográfica, y de los factores perioperatorios, las complicaciones y los resultados. Resultados. La mediana de la edad de los pacientes fue de 44,3 años (rango: 18 a 82). La causa más común de los defectos fue el trauma (32 %), aunque las úlceras por presión y la osteomielitis también se presentaron con frecuencia. En cuanto a las comorbilidades, el 29 % de los pacientes presentaba hipertensión arterial sistémica, el 19 %, diabetes mellitus, y el 6 %, enfermedad arterial oclusiva crónica. Se presentaron dos casos de necrosis total (5 %) y 9 casos de necrosis parcial (24 %). La tasa de necrosis fue mayor en los pacientes con hipertensión arterial sistémica, con enfermedad arterial oclusiva crónica o con un puntaje de 3 en el sistema de clasificación de la American Society of Anesthesiologists (ASA), con una relación estadísticamente significativa. En conclusión, los colgajos en hélice de las arterias perforantes son un método de cubrimiento de gran versatilidad y confiable para tratar defectos de tejidos blandos del miembro inferior, con tasas de complicaciones similares a las de otros métodos tradicionales de cobertura

Introduction: Pedicled propeller perforator flaps are a versatile local reconstructive option for defects of the lower leg, ankle and foot. Material and methods: A retrospective review of 37 cases undergoing this procedure in the period 2012 to 2015 was performed. The analysis includes demographic and perioperative factors, complications and outcomes. Thirty-seven flaps were performed on a single perforator from any of the major vascular axes of the lower extremity Results: The mean age was 44.3 years (range 18 -82 years). Etiology of soft tissue defects was trauma in 32% of the cases, but osteomyelitis, pressure sores and vascular ulcers were also present. Pedicle rotation arch ranged between 90 to 180 degrees. There was 5% percent complete necrosis and 24% partial flap failure rate, both associated with arteriopathy and ASA 3 score. Conclusion: Propeller perforator flaps provide reliable coverage for lower limb defects, with a comparable rate of complications to traditional regional flaps

Episomal Induced Pluripotent Stem Cells Promote Functional Recovery of Transected Murine Peripheral Nerve.

Traumatic peripheral nerve neurotmesis occurs frequently and functional recovery is often slow and impaired. Induced pluripotent stem cells (iPSCs) have shown much promise in recent years due to its regenerative properties similar to that of embryonic stem cells. However, the potential of iPSCs in promoting the functional recovery of a transected peripheral nerve is largely unknown. This study is the first to investigate in vivo effects of episomal iPSCs (EiPSCs) on peripheral nerve regeneration in a murine sciatic nerve transection model. Episomal iPSCs refer to iPSCs that are generated via Oct3/4-Klf4-Sox2 plasmid reprogramming instead of the conventional viral insertion techniques. It represents a relatively safer form of iPSC production without permanent transgene integration which may raise questions regarding risks of genomic mutation. A minimal number of EiPSCs were added directly to the transected nerve. Functional recovery of the EiPSC group was significantly improved compared to the negative control group when assessed via serial five-toe spread measurement and gait analysis of ankle angles. EiPSC promotion of nerve regeneration was also evident on stereographic analysis of axon density, myelin thickness, and axonal cross-sectional surface area. Most importantly, the results observed in EiPSCs are similar to that of the embryonic stem cell group. A roughly ten-fold increase in neurotrophin-3 levels was seen in EiPSCs which could have contributed to peripheral nerve regeneration and recovery. No abnormal masses or adverse effects were noted with EiPSC administration after one year of follow-up. We have hence shown that functional recovery of the transected peripheral nerve can be improved with the use of EiPSC therapy, which holds promise for the future of nerve regeneration.

PATRONES SIMPLES DE ABLACIÓN PARA LA TERMINACIÓN DE ROTORES EN FIBRILACIÓN AURICULAR CRÓNICA. ESTUDIO DE SIMULACIÓN / SIMPLE ABLATION PATTERNS FOR TERMINATING ROTORS IN CHRONIC ATRIAL FIBRILLATION. A SIMULATION STUDY / PADRÕES SIMPLES ABLAÇÃO DE RESCISÃO DE ROTORES COM FIBRILAÇÃO ATRIAL CRÔNICA. ESTUDO DE SIMULAÇÃO

La fibrilación auricular (FA) es la arritmia más común en la práctica clínica y por la que más se consulta en los servicios médicos. Recientemente, se ha propuesto un mecanismo de mantenimiento de la FA, el cual consiste en la existencia de uno o varios rotores que activan el tejido a alta frecuencia. La ablación es uno de los tratamientos para la FA, en FA crónica son necesarios patrones de ablación complejos, por lo que actualmente se busca el patrón ideal con un mínimo número de líneas de ablación. En este trabajo se simula la actividad de un rotor en un modelo 2D de tejido auricular humano, bajo condiciones de FA crónica y se localiza su centro de giro (tip). Se proponen y evalúan seis diferentes patrones simples de ablación compuestos por un número reducido de líneas. El estudio demostró que aquellos patrones que atraviesan o encierran el tip del rotor y que adicionalmente se prolongan hasta una frontera de conducción son eficaces en la terminación del rotor.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and the most consulted in medical services. Recently it has been proposed a mechanism for maintaining the AF, which consists in one or more rotors activating the tissue at high frequency. Ablation is one of the treatments for AF, for chronic AF is needed complex ablation patterns, so currently it has been looking for an ideal pattern with a minimum number of ablation lines. In this work activity of a rotor was simulated in a 2D model of human atrial tissue, under chronic AF conditions, and the center of rotation (tip) was located. Six different simple ablation patterns composed of a limited number of lines were proposed and evaluated. The study showed that those patterns that passed through or encloses the tip of the rotor and additionally were extended to a conduction boundary are effective in the termination of the rotor.

A fibrilação atrial (FA) é a arritmia mais comum na prática clínica e na consulta que a maioria dos serviços médicos. Recentemente, é proposto um mecanismo para a manutenção da FA, que é a existência de um ou mais rotores que activam o tecido com elevada frequência. A ablação é um tratamento para fibrilação atrial em padrões crônicos de ablação de FA necessárias são complexas, por isso eles estão atualmente buscando o padrão ideal, com um número mínimo de linhas de ablação. Neste documento, a actividade de um rotor é simulada em um modelo em 2D do tecido atrial humano, sob condições de AF crónica e o seu centro de rotação (ponta) está localizado. São propostos e avaliados seis diferentes padrões de ablação individuais compostos de um pequeno número de linhas. O estudo mostrou que as que passam através de padrões ou encerram a ponta do rotor e se estendem para além de um limite de condução são eficazes na cessação do rotor.

Síndrome de brugada en un paciente con síncope: presentación de un caso y revisión de la literatura / Brugada syndrome in a patient with syncope: a case report and literature review

El síndrome de Brugada es una enfermedad autosómica dominante esporádica que afecta los canales de sodio de los miocardiocitos. Clínicamente se caracteriza por síncopes recurrentes y/o muerte súbita, que en el electrocardiograma simula un bloqueo de rama derecha, acompañado de elevación peculiar del segmento ST en las derivaciones precordiales derechas (V1, V2 y V3) sin alteración cardiaca estructural. Afecta principalmente a hombres en la cuarta década de la vida y tiene mayor prevalencia en el suroeste asiático. El caso que se describe corresponde a un paciente con antecedentes personales de síncopes, a quien se le encuentra un patrón electrocardiográfico tipo-2 de Brugada y quien además tiene un hermano con historia de síncopes. Con una prueba de mesa basculantes positivo para síncope mediado neuralmente se deja este diagnóstico, pero no se descarta la sospecha inicial de síndrome de Brugada.

Brugada syndrome is a sporadic autosomal dominant genetic disease that affects cardiac sodium channels. It is clinically characterized by recurrent syncope and/or sudden death with electrocardiographic manifestations that simulate a right bundle branch block accompanied by ST-segment elevation in the right precordial leads (V1, V2 and V3) without structural cardiac changes. It mainly affects men in their fourth decade and is most prevalent in southwestern Asia. We present the case of a patient with history of syncope, type-2 Brugada electrocardiographic pattern and who has a brother also with history of syncope. The patient had a positive tilt test for neurocardiogenic syncope. He was diagnosed as neurocardiogenic syndrome, without discarding the initial suspicion of Brugada syndrome.