RESUMO
BACKGROUND: Free vascularized fibula flap represents the gold standard vascularized bone graft for the management of segmental long bone defects after traumatic injury. The current study represents the largest retrospective multicenter data collection on the use of free fibula flap (FFF) for extremities' orthoplastic reconstruction after trauma aiming to highlight current surgical practice and to set the basis for updating current surgical indications. METHODS: The study is designed as a retrospective analysis of prospectively collected data between 2009 and 2021 from six European University hospitals. Patients who underwent fibula flap reconstruction after acute traumatic injury (AF) or as a late reconstruction (LF) after post-traumatic non-union of upper or lower limb were included. Only extra-articular, diaphyseal fracture were included in the study. Surgical data were collected. Time to bone healing and complications were reported as clinical outcomes. RESULTS: Sixty-two patients were included in the study (27 in the AF group and 35 in the LF group). The average patients' age at the time of the traumatic event was 45.3 ± 2.9 years in the AF group and 41.1 ± 2.1 years in the LF group. Mean bone defect size was 7.7 ± 0.6 cm for upper limb and 11.2 ± 1.1 cm (p = .32) for lower limb. Bone healing was uneventful in 69% of treated patients, reaching 92% after complementary procedures. Bone healing time was 7.6 ± 1.2 months in the acute group and 9.6 ± 1.5 months in the late group. An overall complication rate of 30.6% was observed, with a higher percentage of late bone complications in the LF group (34%), mostly non-union cases. CONCLUSIONS: FFF reconstruction represents a reliable and definitive solution for long bone defects with bone healing reached in 92% cases with a 8.4 months of average bone healing time.
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Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica , Humanos , Fíbula/transplante , Estudos Retrospectivos , Transplante Ósseo/métodos , Resultado do TratamentoRESUMO
BACKGROUND: The medial sural artery perforator (MSAP) flap shows advantages for reconstruction in the foot and ankle, where bulk is a liability. We evaluated the versatility of this flap and provide further evidence on its use for covering small-to-moderate size defects by comparing the outcome depending on the region of reconstruction. METHODS: Twenty-two patients with variable defects of 4 × 4 to 18 × 7 cm underwent MSAP flap reconstruction. Final outcomes of all patients were evaluated 12-months postoperatively using the AOFAS ankle-hindfoot, midfoot and hallux scale for clinical-functional evaluation, and the SF-36 health survey for quality-of-life measurement. The scores were compared in three groups according to the anatomic region of MSAP flap reconstruction. RESULTS: The flap size ranged between 6 × 4 and 21 × 9 cm. One venous congestion was salvaged by venous thrombectomy and reanastomosis, and one marginal flap necrosis healed by secondary intention. All flaps survived, and all patients returned to ambulation. Patients with reconstruction of the ankle-hindfoot or hallux showed significantly lower AOFAS ankle-hindfoot (P = 0.021) or hallux scores (P = 0.034), whereas reconstruction of the midfoot led to equal AOFAS midfoot scores (P = 0.265) as compared with patients without reconstruction in the respective region. Comparison of SF-36 physical (P = 0.936) and mental (P = 0.855) scores of all three regions remained insignificant. CONCLUSION: The MSAP flap provides thin soft tissue coverage, enabling good functional recovery after defect reconstruction all around the foot and ankle, with evident advantages in the midfoot. However, the functional outcomes after reconstruction of the ankle-hindfoot or hallux region depend on the preexistent functional impairment.
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Traumatismos do Tornozelo/cirurgia , Traumatismos do Pé/cirurgia , Retalhos de Tecido Biológico/transplante , Procedimentos de Cirurgia Plástica/métodos , Adulto , Idoso , Artérias/transplante , Feminino , Seguimentos , Retalhos de Tecido Biológico/irrigação sanguínea , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The composite anterolateral thigh flap with vascularized fascia lata (ALT-FL flap) for covering complex soft tissue defects involving the Achilles tendon has shown promising results. The age and body mass index (BMI) are important predictors of clinical outcome after surgical treatment of Achilles tendon ruptures. In this study, we investigate whether these also influence the outcome of patients after Achilles tendon reconstruction using the ALT-FL flap. METHODS: Twenty patients (mean age: 55.9 ± 8.7 years) with complex tissue defects involving the Achilles tendon underwent reconstruction with the ALT-FL flap. Both the Achilles tendon Total Rupture Score (ATRS) and the American Orthopaedic Foot and Ankle Society (AOFAS) score were assessed preoperatively and 12 months postoperatively. In addition, postoperative magnetic resonance imaging (MRI) studies and measurements of the ankle range of motion were performed and results compared with existing literature. RESULTS: All flaps survived and MRI studies confirmed complete anatomical integration of the fascia lata as "neotendon" at the recipient site. In our patient cohort, the age did not correlate with the outcome measurements, whereas the BMI showed significant negative correlation with the postoperative ATRS (p < 0.001) and AOFAS scores (p < 0.05). The ATRS and AOFAS scores of all patients improved significantly (p < 0.001). However, obese patients with a BMI of more than 30 kg/m2 achieved significant lower ATRS (p < 0.001) and AOFAS scores (p < 0.01), as well as patients with peripheral artery disease (PAD) (p < 0.05). The mean ankle range of motion after ALT-FL flap reconstruction remained statistical insignificant compared with previous avascular or vascularized tendon repairs of the Achilles tendon. CONCLUSION: The ALT-FL flap enables reconstruction of complex tissue defects involving the Achilles tendon with good functional results. However, the presence of an increased BMI or PAD, but not necessarily the age, proves to be a predictor of poor clinical outcome and therefore should be subject to scrutiny during patient selection.
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Tendão do Calcâneo/lesões , Fascia Lata/transplante , Retalhos de Tecido Biológico/irrigação sanguínea , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles/cirurgia , Tendão do Calcâneo/fisiopatologia , Tendão do Calcâneo/cirurgia , Fatores Etários , Idoso , Índice de Massa Corporal , Fascia Lata/irrigação sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Recuperação de Função Fisiológica , Estudos Retrospectivos , Lesões dos Tecidos Moles/fisiopatologia , Coxa da Perna , Resultado do TratamentoRESUMO
BACKGROUND: Advanced microsurgical techniques have emerged as a promising approach for the treatment of lymphedema, but achieving international standards is limited by a scarcity of adequate training models. The purpose of this report is to describe our in vivo porcine training model for microsurgery. STUDY DESIGN: Five female common-breed pigs (Sus scrofa domesticus) weighing 20 to 28 kg were placed under general anesthesia, and blue patent violet dye was injected to highlight lymphatic structures and prepare the pigs for anatomical exploration and microsurgery. The number and type of patent anastomoses achieved and lymph node flaps created and any anatomical differences between porcine and human vessels were noted, in light of evaluating the use of pigs as a training model for microsurgery in living tissue. RESULTS: Multiple lymphatic-venous anastomoses were created at the site of a single incision made at the subinguinal region, running medial and parallel to the saphenous vessels. Ten multiple lymphatic-venous anastomoses were created in total, and all were demonstrated to be patent. Four lymph node flaps were prepared for lymph node transfer. The superficial lymphatic collector system in the caudal limb of the pig was identified and described with particular reference to the superficial, medial (dominant), and lateral branches along the saphenous vein and its accessory. CONCLUSIONS: The authors present a safe and adaptable in vivo experimental microsurgical porcine model that provides the opportunity to practice several advanced lymphatic microsurgical techniques in the same animal. The ideal lymph node transfer training model can be developed from this anatomical detail, giving the opportunity to use it for artery-to-artery anastomoses, vein-to-vein anastomoses, and lymphatic-to-lymphatic anastomoses.
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Anastomose Cirúrgica/métodos , Linfonodos/cirurgia , Vasos Linfáticos/cirurgia , Microcirurgia/métodos , Animais , Humanos , Modelos Animais , Corantes de Rosanilina/administração & dosagem , SuínosRESUMO
BACKGROUND: Accumulating evidence shows the potential of bone marrow-derived endothelial colony-forming cells (bmECFCs) as promising tools for vascular repair. However, knowledge about their in vitro expansion, characterization, and functional behavior is still controversial. We demonstrate the in vitro generation of rat bmECFCs and analyze their ability to promote tissue reperfusion in a chronic hind-limb ischemia model. METHODS: Either in vitro-generated and characterized autologous bmECFCs or placebo was injected into ischemic hind limbs of Sprague-Dawley rats. Tissue perfusion was quantified by laser Doppler, in perfusion units (PU), at days 0, 15, and 30. RESULTS: Rat bmECFCs acquire a typical phenotype (CD34(+)VEGFR2(+)CD133(+)CXCR4(+)CD45(-)), culture, and functional behavior (Dil-ac-LDL+) in vitro. Injection of autologous bmECFCs improves tissue perfusion in ischemic hind limbs (183.5 ± 3.29 PU(bmECFCs/day 30)versus 131 ± 3.9 PU(controls/day 30), P < 0.001). CONCLUSIONS: We conclude that rat bmECFCs promote ischemic tissue reperfusion and their proangiogenic properties are a potential mechanism for this effect.
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Transplante de Medula Óssea/métodos , Células Endoteliais/transplante , Extremidades/irrigação sanguínea , Isquemia/cirurgia , Neovascularização Fisiológica , Fluxo Sanguíneo Regional , Animais , Células Cultivadas , Modelos Animais de Doenças , Extremidades/diagnóstico por imagem , Citometria de Fluxo , Isquemia/diagnóstico por imagem , Masculino , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento , Ultrassonografia DopplerRESUMO
INTRODUCTION: Although the effect of chronic compression and surgical decompression of the diabetic rat sciatic nerve has been evaluated by walking track analysis, the measurement of sensory function by response to thermal nociceptive stimulation has not been investigated. METHODS: Fifteen male Wistar rats with streptozotocin-induced diabetes underwent sciatic nerve compression through a 10-mm silicone band. Five rats had histology done 60 days after confirming chronic nerve compression. Pain threshold was measured using hindlimb withdrawal times (HLWT) from a heat stimulus. After 60 days of compression, the silicone tube was removed. Five nondiabetic, nonbanded rats were used as controls. RESULTS: Control mean HLWT was 9.7 ± 1.5 sec. In the diabetes group (60 days of compression), mean HLWT was 23.6 ± 2.4 sec. (p < 0.001). Thirty days after removal of the silicone, mean HLWT to painful stimuli was 14.9 ± 1.5 sec. (p < 0.001). CONCLUSION: Chronic compression of the diabetic rat sciatic nerve increases (worsens) the threshold to heat (pain) perception. Decompression reverses this effect (improves nociception).
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Descompressão Cirúrgica , Diabetes Mellitus Experimental/fisiopatologia , Membro Posterior/fisiopatologia , Temperatura Alta , Dor/fisiopatologia , Nervo Isquiático/fisiopatologia , Animais , Diabetes Mellitus Experimental/cirurgia , Membro Posterior/inervação , Membro Posterior/cirurgia , Masculino , Dor/etiologia , Medição da Dor , Limiar da Dor , Ratos , Ratos Wistar , Nervo Isquiático/lesões , Nervo Isquiático/cirurgiaRESUMO
Extrinsic chronic nerve compression induced by nonendothelium derived vascular tumors is a rare occurrence at the forearm level. We present a case of severe chronic compression of the radial sensory nerve (RSN) caused by an undiagnosed venous glomangioma. The tumor was excised with complete symptoms relief. In the presence of severe nerve compression syndromes in young age, without predisposing comorbidities, atypical extrinsic compression due to vascular tumors should be considered.
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Tumor Glômico/diagnóstico , Síndromes de Compressão Nervosa/etiologia , Neuropatia Radial/etiologia , Adulto , Doença Crônica , Antebraço/irrigação sanguínea , Antebraço/inervação , Tumor Glômico/complicações , Tumor Glômico/cirurgia , Humanos , MasculinoRESUMO
BACKGROUND: Perforator flaps account for a fraction of reconstructive procedures despite their growing popularity. Specific microsurgical skills are required for successful harvesting of perforator flaps, which are difficult to attain through direct operating room training. Cadaver and small animal dissection cannot simulate human perforator dissection, lacking either bleeding and vessel feedback or providing too small calibers. Thus, we have developed and refined over the last ten years five perforator flaps models in living pig, described their harvesting technique and provided evidence for their effectiveness as perforator flap training models. METHOD: CT angiography data from ten living pigs was used for detailed examination of the integument's vascular anatomy. Microsurgical techniques were used to standardize and harvest the perforator flaps in acute models. The same operator-assistant team, with no prior perforator flap harvesting experience, raised all flaps in a sequential manner, one animal per day, during a 7 weeks timespan. Porcine flaps were compared to human counterparts in terms of vessel caliber, dissection times. Immediate flap survival was measured as duration of perforator pulsation after completion of flap harvesting, measured every 10 minutes for up to two hours. RESULTS: Five perforator flaps were standardized, based on the deep cranial epigastric, thoracodorsal, lateral intercostal, cranial gluteal and dorsal cervical arteries and the operative technique was described in detail. Mean pig perforator size was 1.24±0.36 mm and mean pedicle diameter was 2.78±0.8 mm, which matched closely the human calibers for each flap. Total harvesting time increased 22.4% between the first two experiments due to a more cautious approach following the lack of perforator pulsation in all flaps in the first experimental animal. A total decrease of 44.4% harvesting time between second and last experiment was observed, as expected with all repetitive surgical procedures. Post-operative perforator pulsation time revealed a steep learning curve, with no or short-term pulsatile perforators in the first five pigs, followed by a 275% increase in total perforator pulsation time between 5th and 6th experimental animal. Based on these findings we provide a description of the most common mistakes, their consequences and gestures which can be trained using the pig perforator flaps, in order to overcome these mistakes. CONCLUSION: These five pig perforator flap models provide a fast and efficient learning tool to develop perforator flap harvesting skills safely. Surgical training using these five experimental models offers a similar hands-on perforator flap dissection experience as with human tissue, based on the similar sized calibers of both perforators and pedicles with their human counterparts.
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Retalho Perfurante , Procedimentos de Cirurgia Plástica , Animais , Artérias , Dissecação , Humanos , Microcirurgia/métodos , Retalho Perfurante/irrigação sanguínea , Procedimentos de Cirurgia Plástica/métodos , SuínosRESUMO
BACKGROUND: Microsurgical transplantation of vascularized lymph nodes (VLNT) or lymphatic vessels (VLVT) alongside derivative lymphaticovenous procedures are promising approaches for treatment of lymphedema. However, clinically relevant training models for mastering these techniques are still lacking. Here we describe a new training model in human cadaver and validate its use as training tool for microsurgical lymphatic reconstruction. METHODS: 10 surgeons with previous exposure to microsurgery were trained in a controlled environment. Lymphatic vessel mapping and dissection in 4 relevant body regions, harvesting of five different VLNTs and one VLVT were performed in 5 fresh-frozen cadavers. The number of lymphatic vessels and lymph nodes for each VLNT were recorded. Finally, the efficacy of this model as training tool was validated using the Dundee Ready Education Environment Measure (DREEM). RESULTS: The average cumulative DREEM score over each category was 30,75 (max = 40) while individual scoring for each relevant category revealed highly positive ratings from the perspective of teaching (39,3), training 40,5 (max = 48) and self perception of the training 30,5 (max = 32) from all participants. The groin revealed the highest number of lymphatic vessels (3.2 ± 0.29) as all other regions on the upper extremity, while the gastroepiploic VLNT had the highest number of lymph nodes (4.2 ± 0.37). CONCLUSIONS: This human cadaver model represents a new, reproducible "all-in-one" tool for effective training in lymphatic microsurgery. Its unique diligence in accurately reproducing human lymphatic anatomy, should make this model worth considering for each microsurgeon willing to approach lymphatic reconstruction.
Assuntos
Vasos Linfáticos , Linfedema , Anastomose Cirúrgica/métodos , Cadáver , Humanos , Linfonodos/cirurgia , Vasos Linfáticos/patologia , Vasos Linfáticos/cirurgia , Linfedema/patologia , Linfedema/cirurgia , Microcirurgia/métodosRESUMO
In this study, we evaluate the feasibility of propeller flaps, for soft tissue reconstruction in patients with peripheral arterial obstructive disease (PAOD). Five patients (average age, 72 years old), presenting with necrosis of several foot units, were diagnosed with stage IV PAOD and diabetes mellitus. All underwent revascularization, followed by soft tissue reconstruction using propeller flaps. A total of 6 flaps were performed, with dimensions ranging from 4 x 7 cm to 8 x 31 cm. Perforator origin was the peroneal (5 flaps) or the tibial posterior artery (1 flap). Average operative time was 190 minutes. Overall patency was 83.3%; 1 case was complicated with total flap loss followed by below-knee amputation; 1 case developed partial necrosis necessitating skin grafting. All flaps developed mild postoperative edema, which resolved spontaneously. Propeller flaps prove to be useful tools for soft tissue reconstruction in patients with PAOD because of low operative morbidity, easy technique with fast learning curve, and low complications rate.
Assuntos
Angiopatias Diabéticas/cirurgia , Perna (Membro)/cirurgia , Doenças Vasculares Periféricas/cirurgia , Retalhos Cirúrgicos , Idoso , Idoso de 80 Anos ou mais , Índice Tornozelo-Braço , Estudos de Viabilidade , Feminino , Gangrena/cirurgia , Humanos , Perna (Membro)/irrigação sanguínea , Masculino , Microcirurgia , Procedimentos de Cirurgia Plástica/métodosRESUMO
BACKGROUND: The lateral circumflex femoral artery one of the most favoured donor-site for a wide array of free flaps including either cutaneous, fascial and muscle components or a combination thereof. Here, we provide evidence on the safe use of the free vastus lateralis muscle flap and its feasibility for optimal soft tissue coverage of the weight-bearing foot. METHODS: Eighteen consecutive patients with soft tissue defects of the heel (n = 3, 16.6%) and plantar aspect of the mid- and forefoot (n = 15, 83.3%) of either post traumatic (n = 10), diabetic (n = 6) or ischemic (n = 2) etiology, received nineteen free vastus lateralis muscle free flaps covered with split-thickness skin grafts. The postoperative results in terms of wound healing, weight-bearing function, patient satisfaction were evaluated. In patients with chronic conditions (n = 8) the AOFAS (American Orthopaedic Foot and Ankle Society) scoring system was used preoperatively and 6 months postoperatively for evaluation of reconstruction outcomes. RESULTS: All flaps survived. Their complete anatomical integration allowed regaining normal walking in all patients. In five patients, partial loss of the skin graft which either healed spontaneously or necessitated a redo skin grafting was noted. One patient developed a late flap-skin interface ulcer, which was solved by primary excision and direct closure. Compared with the preoperative values, the mean AOFAS score in the evaluated patients (n = 8) improved significantly (34.13 vs. 77.63, p < 0.001). CONCLUSION: The skin-grafted free vastus lateralis muscle flap can safely be used as a "smart" tool for coverage of weight-bearing foot providing optimal cushioning and functional results without fearing donor-side morbidity.
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Traumatismos do Pé , Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Traumatismos do Pé/cirurgia , Humanos , Músculo Quadríceps/cirurgia , Transplante de Pele , Lesões dos Tecidos Moles/cirurgia , Suporte de CargaRESUMO
Propeller perforator flaps (PPFs) have long been proven as valid reconstructive tools for a wide range of soft tissue defects in different body regions. During the last decade, despite their numerous advantages, many authors have thoroughly analyzed outcomes of these flaps, sometimes discouraging their use mainly because of a high failure rate. Accurate patient selection, adequate preoperative planning, and an appropriate dissection technique seem to potentially improve outcomes. Our study provides a review of the relevant literature related to PPF complications and of our experience, describing reasons for failure, measures for preventing them, and approaches for a prompt evaluation and management of complications.
RESUMO
INTRODUCTION: The training to learn how to perform perforator flaps requires practice on a living model to optimize dissection and to evaluate outcome. The purpose of this study was to describe a training model that optimizes the use of animals in order to perform the maximum number of exercises per animal. MATERIAL AND METHODS: The sequence has been planned and practiced by the first and last author, recorded perfected and implemented in a two-day surgical course. The sequence was then evaluated by the trainers and the trainees by means of a questionnaire. RESULTS: All students were able to complete the sequence of exercises before the end of the second day except two (8/10) who could not complete one exercise each. The students considered the Deep Superior Epigastric Artery Perforator flap the most difficult to perform, being the most technically demanding. The sequence of exercises was judged either easily reproducible or reproducible by all the students. Two students suggested to postpone the DSEAP flap to the second day, after some training, to optimize the experience with the most challenging and rewarding flap. CONCLUSIONS: The training sequence proposed offers a wide range of exercises and allows four trainees, divided in two teams, to work and learn on the same animal. They can perform a wide range of flaps and also harvest the internal mammary vessels. The living model allows for evaluation of the quality of the surgical performance, judged by the difficulties and complications encountered during dissection, and finally through the feedback of flap perfusion.
Assuntos
Mamoplastia , Retalho Perfurante , Animais , Dissecação , Artérias Epigástricas , Humanos , Curva de AprendizadoRESUMO
Endoscopic internal mammary artery (IMA) approach represents a well-established procedure in coronary bypass surgery. However, such techniques require highly trained skills that need to be mastered in experimental models before taken into the clinic. To attain such skills, our aim was to develop a training model of thoracoscopic approach for harvesting of the IMA in pig. Ten pigs of either sex, weighing 20-28 kg, were used. The thoracic cavity was accessed with the animal in a lateral decubit position, through two ports of 10 mm and 1 of 5 mm, inserted on the anterior and posterior axillary lines immediately below the infrascapular angle into the pleural cavity, and a 30 degrees Hopkins II telescope. The internal mammary artery (IMA) was identified and dissected from its origin in the subclavian artery until its distal part where it becomes the deep superior epigastric artery. Afterward, the arterial segment was clipped and harvested. The mean operative time was 73 min. Postoperative survival at 72 hours was 100% and 90% at 4 weeks. A mean length of 3.2 cm of IMA graft was obtained (2.8-4 cm). The pig IMA has no intercostal branches; thus, the mobilization of the vessel being greatly facilitated. The procedure has two critical steps: the proper trocar insertion and the dissection of the middle one-third of the IMA. Endoscopic-assisted IMA, harvesting in pigs, represents a useful tool for training in minimally invasive heart surgery and supports further development toward other clinical applications.
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Ponte de Artéria Coronária/educação , Ponte de Artéria Coronária/métodos , Dissecação/métodos , Artéria Torácica Interna/cirurgia , Modelos Animais , Toracoscopia/métodos , Animais , Ponte de Artéria Coronária/efeitos adversos , Período Intraoperatório , Masculino , Modelos Educacionais , Complicações Pós-Operatórias , Suínos , Toracoscopia/efeitos adversosRESUMO
We showed previously that dendritic cells (DCs) treated with mitomycin C (MMC) tolerize allogeneic T cells in vitro and this might be mediated by downregulation of CD80, CD86, and ICAM-1. Here we analyze the suppression of the T-cell response induced by MMC-DCs in vivo. Rats injected with allogeneic DCs developed a strong lymph node reaction, whereas MMC-DCs induced no reaction. The same effect was obtained when CD80, CD86, and ICAM-1 expressed by DCs were blocked with antibodies. One injection of donor MMC-DCs strongly prolonged heart allograft survival in a donor-specific manner. Suppression of rejection was also achieved when donor DCs were pretreated with a combination of anti-CD80, anti-CD86, and anti-ICAM-1 antibodies, showing that downregulation of these molecules confers the DCs inhibitory properties. We conclude that allogeneic MMC-DCs specifically inhibit the T-cell response in vivo and that downregulation of CD80, CD86, and ICAM-1 is a potential mechanism of this effect.
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Células Dendríticas/efeitos dos fármacos , Rejeição de Enxerto/prevenção & controle , Transplante de Coração , Terapia de Imunossupressão/métodos , Mitomicina/farmacologia , Linfócitos T/imunologia , Animais , Anticorpos/farmacologia , Antígeno B7-1/metabolismo , Antígeno B7-2/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/transplante , Regulação para Baixo , Molécula 1 de Adesão Intercelular/metabolismo , Ativação Linfocitária , Ratos , Ratos Endogâmicos , Linfócitos T/efeitos dos fármacos , Doadores de TecidosRESUMO
BACKGROUND: Deliberately generated tolerogenic dendritic cells (DC) might be a useful tool for induction of donor-specific tolerance in transplantation. In this article, the authors study the effect of mitomycin C (MMC)-treated DC on rat T cells and delineate the mechanism of their conversion into tolerogenic cells. METHODS: The influence of MMC treatment on the capacity of DC to activate allogeneic T cells was tested in vitro, and the expression of cell surface molecules was studied by flow cytometry. RESULTS: MMC-treated DC lose their allostimulatory capacity, and this cannot be attributed to cell death or release of MMC. Interestingly, suppressed T cells cannot be restimulated, indicating that MMC-treated DC induce tolerance. MMC treatment selectively decreases adhesion (intercellular adhesion molecule [ICAM]-1) and co-stimulatory (CD80, CD86) molecules. Functional blocking of these molecules with specific antibodies confers to DC the same T-cell-suppressive properties as treatment with MMC. CONCLUSIONS: MMC treatment converts rat DC into tolerogenic cells. This mechanism is mediated by decrease of ICAM-1, CD80, and CD86.
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Alquilantes/farmacologia , Antígenos CD/metabolismo , Células Dendríticas/imunologia , Tolerância Imunológica , Mitomicina/farmacologia , Inibidores da Síntese de Ácido Nucleico/farmacologia , Linfócitos T/imunologia , Animais , Antígeno B7-1/metabolismo , Antígeno B7-2 , Células Dendríticas/efeitos dos fármacos , Regulação para Baixo , Molécula 1 de Adesão Intercelular/metabolismo , Glicoproteínas de Membrana/metabolismo , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos LewRESUMO
Transplantation faces an unprecedented shortage of organs available for transplantation, resulting in longer waiting times and transplant candidates on the waiting list dying before getting a transplant. This dramatic situation triggered the search for new approaches and innovations to increase the donor pool, such as extending the acceptance criteria concerning donor age or organ transplantation across blood group barriers. Herein, leading experts detailed the immunological and molecular concepts behind the successful clinical translation of these strategies. Organ rejection remains a constant challenge and transplantation tolerance is still elusive as the current paradigm aims for immunosuppression rather than immune modulation. Two contributions in this issue review two different molecular paradigms in harnessing the immunologic response after transplantation. The interplay between the intestinal innate and adaptive immunity is particularly intricate and the intestine remains the organ with the highest rate of acute rejection after transplantation. Experts in the field summarized both time-honored and recent knowledge in intestinal preservation and tolerance in intestinal transplantation with potential for further basic and translational research.
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Rejeição de Enxerto/imunologia , Tolerância Imunológica/imunologia , Transplante de Órgãos/métodos , Imunologia de Transplantes/imunologia , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto/imunologia , Humanos , Transplante de Órgãos/efeitos adversosRESUMO
The authors present their experience with the use of sural fasciocutaneous flaps for the treatment of various soft tissue defects in the lower limb. This paper is a review of these flaps carried out between 2003 and 2008. The series consists of 16 patients, 11 men and 5 women with an average age of 41 years (17-81) and with a follow-up period between 2 and 7 years. The etiology was major velocity accident in six cases, diabetes mellitus with osteomyelitis after ORIF for fractures (2), work accident in five, and another two cases with complications of lower limb injuries. The defect areas were located on calcaneus, malleolar area, tarsal area and lower tibia. Associated risk factors in the patients for the flap performance were diabetes (five patients) and cigarette smoking (ten patients).The technique is based on the use of a reverse-flow island sural flap combined with other flaps in three cases (cross-leg, peroneal, gastrocnemius). The anatomical structures which constituted the pedicle were the superficial and deep fascia, the sural nerve, the lesser saphenous vein and skin.The flap was viable in all 15 patients. On 8 cases was achieved direct closure, on three cases occurred a superficial necrosis and was skin grafted, on one case was observed partial necrosis which was treated with a second flap (posterior tibial perforator flap) and another one occurred delayed skin healing.The sural fasciocutaneous flap is useful for the treatment of severe and complex injuries and their complications in diabetic and non diabetic lower limbs. Its technical advantages are easy dissection, preservation of more important vascular structures in the limb and complete coverage of the soft tissue defects in just one operation without the need of microsurgical anastomosis. Thus this flap offers excellent donor sites for repairing soft tissue defects in foot and ankle.
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The aim of this study was to apply the hypothesis of ischemic preconditioning (IP) on free skeletal muscle (rat thigh flap). Five groups of Sprague-Dawley rats (n = 6) were used. In group A (control group), standard free autologous flap transfers were performed. Flaps in groups B and C underwent 4 and 6 h, respectively, of ischemia before transfer. In groups D and E, muscle flaps were preconditioned (3 x 10 min ischemia interrupted by 10 min of reperfusion, clip applied on the dissected artery of the flap) and subjected to 4 and 6 h, respectively, of ischemia before transfer. After 48 h of reperfusion, the muscle flaps were evaluated macroscopically as well as by histological and immunohystochemical staining. In group A, the viability was 100%, whereas in groups D and E the viability was 83.3% and 100%, respectively. Groups B and C had undergone macroscopically parceled to total necrosis, further confirmed by histological findings (fragmentation and disappearance of muscle striations, combined with tissue necrosis and intravascular thrombosis). The beneficial effect of IP demonstrated in the heart, liver, and small bowel extends to skeletal muscle, which can be used in free-flap transfers, if the transfer includes a long period of predictable ischemia.