Outcomes of Vascularized Bone Allotransplantation with Surgically Induced Autogenous Angiogenesis in a Large Animal Model: Bone Healing, Remodeling, and Material Properties.

BACKGROUND: Bone vascularized composite allotransplantation (VCA) is a possible alternative for the treatment of large bone defects. Clinical application of VCAs is limited by the need for life-long immunosuppression (IS). We report an alternative method to maintain bone allotransplant viability in a large animal model without the need for life-long IS by using autogenous vessel implantation. METHODS: Fourteen bone only VCAs were transplanted in a porcine tibia defect model with short-term IS. Two groups were used to evaluate the effect of the implantation of an autogenous arteriovenous (AV)-bundle, therefore the only difference between the groups was the patency of the AV-bundle. We radiographically evaluated bone healing and allogenic pedicle patency. AV-bundle patency and union were evaluated with micro-CT. Bone remodeling was assessed with histomorphometry and material properties were evaluated with axial compression testing and cyclic reference point indentation. RESULTS: Two subjects did not reach the final time point. Twelve tibiae healed proximally, and nine at the distal transplant-bone interface. Bone allotransplants showed their viability in the first 4 to 6 weeks by significant periosteal bridging arising from the transplant and maintained pedicle patency. Bone material properties were not affected by the implantation of an AV-bundle when compared with ligated AV-bundle controls, but diminished compared with normal bone. Significantly higher bone formation rates resulted from the implantation of a patent AV-bundle. CONCLUSION: New periosteal bone formation and subsequent bone healing result from blood flow through the microsurgically repaired nutrient blood supply, demonstrated by maintained allogenic pedicle patency. The implantation of a patent autogenous AV-bundle has no adverse effect on material properties, but a positive effect on bone remodeling of endosteal surfaces despite thrombosis of the allogenic pedicle. Bone material properties change after transplantation compared with normal bone, although 20-weeks survival time is relatively short for the final evaluation of bone material properties.

Bone vascularized composite allotransplantation model in swine tibial defect: Evaluation of surgical angiogenesis and transplant viability.

INTRODUCTION: In prior small animal studies, we maintained vascularized bone allotransplant viability without long-term immunotherapy. Instead, an autogenous neoangiogenic circulation is created from implanted vessels, sufficient to maintain bone viability with only 2 weeks immunosupression. Blood flow is maintained despite rejection of the allogeneic vascular pedicle thereafter. We have previously described a large animal (swine) pre-clinical model, reconstructing tibial defects with vascularized tibial allotransplants. In this manuscript, autologous angiogenesis is evaluated in this model and correlated with bone viability. MATERIALS AND METHODS: Allogeneic tibial segments were transplanted across a major swine leukocyte antigen mismatch. Microvascular repair of the bone VCA pedicle was combined with intraosseous implantation of an autogenous arteriovenous (AV) bundle. The bundle was ligated in group 1 (n = 4), and allowed to perfuse in group 2 (n = 4). Three-drug immunotherapy was given for 2 weeks. At 16 weeks micro-CT angiography quantified neoangiogenic vessel volume. Bone viability, rejection grade, and bone healing were analyzed. RESULTS: A substantial neoangiogenic circulation developed from the implanted AV-bundle in group 2, with vessel density superior to ligated AV-bundle controls (0.11 ± 0.05 vs. 0.01 ± 0.01, P = .029). Bone allotransplant viability was also significantly enhanced by neoangiogenesis (78.7 ± 4.4% vs. 27.7 ± 5.8%, P = .028) with higher bone healing scores (21.4 ± 2.9 vs. 12.5 ± 3.7, P = .029). Ligated control tibias demonstrated disorganized bone morphology and higher local inflammation (P = .143). CONCLUSION: Implantation of autogenous AV bundles into vascularized bone allotransplants resulted in the rapid formation of a neoangiogenic autogenous blood supply in a swine tibia model that maintained bone viability, improved bone healing, and minimized rejection.

Software-based video analysis of functional outcomes of face transplantation.

INTRODUCTION: Assessment of outcomes after face transplantation (FT) is necessary to provide sound evidence on the benefits of this life-giving surgery. Current methods for outcomes assessment, however, are imprecise or prone to subjectivity. Software-based video analysis may allow fast, objective and retrospective assessment of restoration of facial movements and functions after FT. PATIENTS AND METHODS: We recorded videos of 7 subjects before as well as every 3-6 months after facial transplantation. Patients performed the same sequence of facial movements in every video: smile, open mouth, purse lips, wrinkle nose, frown, close eyes, and lift eyebrows. The videos were retrospectively analyzed using EMOTIENT software, which is capable of automatic tracking and detailed measurements of facial movements and expressions. These measurements were subsequently compared to the same patient at different time points, as well as to the normal population. RESULTS: Open mouth, wrinkle nose and smile functions significantly improved in all patients when compared to pre-transplant functions; this improvement was significant at 3, 6, and 12 months after transplant, respectively. Lip purse, eye closure and frown functions improved by 6, 9, and 18 months after transplantation, respectively; however, improvement in these particular functions was not significantly with respect to pre-transplant. Face transplantation did not improve any of the patients' ability to lift their eyebrows. Most remarkably, mouth opening and smiling functions both reached values comparable to the normal population at 3 and 12 months after transplantation, respectively. CONCLUSION: Software-based video analysis provides a valuable assessment tool capable of objective, precise and reproducible analysis of facial movements and functions after FT.

The Collagenase of the Bacterium Clostridium histolyticum in the Treatment of Irradiation-Induced Capsular Contracture.

BACKGROUND: Irradiation therapy is an important pillar in the treatment of breast cancer. However, it can trigger capsular fibrosis, the most significant complication of implant-based breast reconstruction. As collagen is the main component of fibrotic capsules, the collagenase of the bacterium Clostridium histolyticum poses a potential treatment option for this pathological condition. METHODS: Thirty-six rats received miniature silicone implants on their backs. On day 1, the implant sites of two groups were irradiated with 10 Gy. On day 120, one irradiated group received collagenase injections into the implant pockets (n = 12). Non-irradiated (n = 12) and irradiated capsules (n = 12) were injected with plain solvent solution serving as controls. Data were analyzed by means of in vivo imaging, histology, immunohistochemistry and gene expression analysis. RESULTS: Compared with both controls, the injection of collagenase led to significantly thinner capsules. This was verified by in vivo imaging and histology. Although irradiation provoked alterations in capsule collagen structure and vessel wall thickness, the application of collagenase resulted in a significant reduction of collagen density. This was accompanied by an up-regulation of VEGF-A gene expression. Of note, hematoma formation inside the implant pocket occurred in two cases after collagenase injection. CONCLUSIONS: The collagenase of the bacterium Clostridium histolyticum is effective in degrading irradiation-induced capsular fibrosis around silicone implants. Hematoma formation occurred most likely because of irradiation-induced alterations in vessel wall architecture and capsule vascularization. Further studies need to be performed to address the clinical safety of this novel treatment option.

Evaluation of 389 patients following free-flap lower extremity reconstruction with respect to secondary refinement procedures.

INTRODUCTION: Primary functional and aesthetic results after free-flap salvage of lower extremities are occasionally suboptimal. The objective of this study was to identify predictors for secondary refinement procedures such as liposuction, dermolipectomy, or direct excision. In addition, patient-reported long-term satisfaction with the final reconstructive result was analyzed. PATIENTS AND METHODS: All patients undergoing free-flap lower extremity salvage between January 2011 and July 2015 were included in a comparative study. The patients of cohort 1 had no secondary refinement procedures, while those of cohort 2 had one or more procedures. The patient data, intraoperative characteristics, and postoperative course were reviewed. To assess the level of satisfaction, the patients were surveyed. RESULTS: Of the 389 patients included, 54 (13.9%) were identified with 1-3 secondary refinement procedures with an uneventful postoperative course. The most common procedure was surgical debulking (56.8%). The comparison of both cohorts revealed a statistical significance for patient's age (P < .01), gender (P = .02), ASA-score (P < .01), and localization (P < .01). Predictors for secondary refinement procedures were young age (<50 years), female gender, absence of comorbidities, and defects located at the feet or ankle. Overall patient satisfaction was negatively correlated with the number of secondary procedures performed. Patient-reported satisfaction with the overall (P < .01) and cosmetic (P = .02) result increased significantly with age. CONCLUSION: Secondary refinement procedures after successful free-flap lower extremity reconstruction are safe and not uncommon. Detailed information about the likelihood of secondary operations and the various techniques available should be part of the patient education to increase patient satisfaction and form realistic expectations.

The conjoined parascapular and latissimus dorsi free flap for reconstruction of extensive knee defects.

BACKGROUND: Extensive soft-tissue defects affecting the knee region pose a significant reconstructive challenge and may require separate or multiple flaps for coverage. We evaluated the conjoined parascapular and latissimus dorsi free flap as an alternative reconstructive option. METHODS: From January 2013 to December 15, 2016 patients (7 female and 8 male) with a mean age of 47.5 years underwent reconstruction of such defects. Causes were trauma (12 cases) and infection (3 cases). The mean defect size was 40.9 × 20.8 cm (range, 21.4×7.3 to 60.1×40.5 cm). The mean defect surface area was 820.0 cm2 (range, 273.2-2,400.4 cm2 ). The conjoined free flap was anastomosed to the femoral vessels in the adductor canal with (3 cases) or without an arterio-venous loop (8 cases), posterior tibial vessels (3 cases), or anterior tibial vessels (1 case). RESULTS: Postoperatively, 10 patients experienced a total of 14 complications, of which 9 (7 patients) were considered major (requiring additional surgery) and 5 (4 patients) minor (conservative treatment). There was no total flap loss. Partial flap loss occurred in 5 patients. Major donor-site complications occurred in 6 patients with impaired wound healing (4 cases), seroma (1 case), and hematoma (1 case). Reconstruction was successful in 14 out of 15 patients during a mean follow-up time of 28.6 months (range, 6.0-52.5 months). Twelve patients were able to walk at the last follow-up visit. CONCLUSIONS: The conjoined parascapular and latissimus dorsi free flap is a large and reliable flap. It allows for simultaneous 1-stage reconstruction of complex and unusually large soft-tissue defects of the knee region.

Evaluation of perfusion by near-infrared fluorescence imaging in late pedicle obstruction of a parascapular flap to the lower extremity: A case report.

Late free flap failures due to pedicle obstruction are rare adverse events. The purpose of this report is to present a case in which the near-infrared indocyanine green video angiography (ICG-NIR-VA) was used to evaluate the perfusion in a compromised fasciocutaneous flap in the late postoperative period. A 55-year-old male patient, who initially suffered from an open tibial fracture, developed concurrent osteomyelitis with fistulae of the proximal tibia requiring excision. Reconstruction was achieved using a parascapular flap of 25 × 8 cm, anastomosed to an arterio-venous (AV) Loop in the adductor canal. On the 2nd postoperative day the patient developed a thrombosis of the AV-Loop. After thrombectomy, the postoperative course was uneventful. Seven weeks postoperatively the patient presented with a mottled, partially bluish and cold flap. Anticoagulation prophylaxis was stopped 2 days earlier. Angiography confirmed a thrombus in the arterial pedicle leading to flap ischemia. Near infrared guided fluorescence imaging revealed a delayed recapillarization of the proximal part of the flap closest to the vascular pedicle, albeit flap overall perfusion remained intact. Thus, no surgical intervention was undertaken. However, anticoagulation and prostaglandin therapy was initiated and the flap was salvaged. Genetic analysis uncovered a polymorphism in the prothrombin genes. The flap remained viable and without further complications until the last follow-up visit at 36 weeks after microsurgical reconstruction. The patient was fully mobilized with complete return to function. Near-infrared guided fluorescence imaging may be a viable tool for the assessment of late fasciocutaneous free flap complications and guide the decision-making process.

A new porcine vascularized tibial bone allotransplantation model. Anatomy and surgical technique.

INTRODUCTION: Vascularized bone allotransplantation may provide new options for reconstruction of segmental defects if problems of long-term immune modulation can be solved. The current literature lacks an orthotopic large animal model, limited to bone and without the confounding effects of other tissue types, permitting a multifaceted evaluation before new methods are used clinically. The purpose of this study was to develop a large animal model for vascularized bone allotransplantation. MATERIALS AND METHODS: Eight porcine hind limbs were dissected. Length, diameter, and location of all hindlimb vessels were measured and a single nutrient vessel supplying the tibial diaphysis identified enabling its use as a vascularized bone allotransplant. Four Yucatan minipigs were divided into two pairs with a major swine leukocyte antigen mismatch. A 3.5 cm tibial segment including its nutrient pedicle was raised simultaneously from each pig and transplanted into the matched defect of the other animal. Microarterial anastomosis of the pedicle and 3-drug immunosuppression maintained VCA viability. Bone healing and limb function were followed for 16 weeks. RESULTS: A consistent tibia diaphyseal nutrient artery arose from the caudal tibial artery to enter bone a mean 2.8 mm distal to the tibial tubercle with a pedicle length of 6.6 ± 3.3 mm and diameter of 1.6 ± 0.2 mm. Using this pedicle, we reconstructed a 3.5 cm tibial defect with a vascularized bone allotransplant in four animals. Immediate weightbearing as well as progressive bone healing was demonstrated. CONCLUSION: We have developed a vascularized tibial bone allotranplantation large-animal model suitable for future bone-only allotranplantation research in mini-pigs.

Comparable functional motor outcomes after repair of peripheral nerve injury with an elastase-processed allograft in a rat sciatic nerve model.

BACKGROUND: A bridging nerve autograft is the gold standard for the repair of segmental nerve injury that cannot be repaired directly. However, limited availability and donor site morbidity remain major disadvantages of autografts. Here, a nerve allograft decellularized with elastase was compared with an autograft regarding functional motor outcome in a rat sciatic segmental nerve defect model. Furthermore, the effect of storage on this allograft was studied. METHODS: Sixty-six Lewis rats (250-300 g) underwent a 10-mm sciatic nerve reconstruction using either a cold- (n = 22) or frozen-stored (n = 22) decellularized nerve allograft or an autograft (n = 22). Sprague-Dawley rats (300-350 g) served as full major histocompatibility complex-mismatched donors. Functional motor outcome was evaluated after 12 and 16 weeks. Ankle angle, compound muscle action potential (CMAP), isometric tetanic force, wet muscle weight, and histomorphometry were tested bilaterally. RESULTS: For CMAP and isometric tetanic force, no significant differences were observed between groups. In contrast, for ankle angle, histomorphometry and muscle weight, the cold-stored allograft performed comparable to the autograft, while the frozen-stored allograft performed significantly inferior to the autograft. At week 16, ankle angle was 88.0 ± 3.1% in the cold-stored group, 77.4 ± 3.6% in the frozen-stored group, and 74.1 ± 3.1% in the autograft group (P < .001); At week 16, the muscle weight showed a recovery up to 71.1 ± 4.8% in the autograft group, 67.0 ± 6.6% in the cold-stored group, and 64.7 ± 3.7% in the frozen-stored group (P < .05). CONCLUSIONS: A nerve allograft decellularized with elastase, if stored under the right conditions, results in comparable functional motor outcomes as the gold standard, the autograft.

Optimizing decellularization techniques to create a new nerve allograft: an in vitro study using rodent nerve segments.

OBJECTIVE Commercially available processed nerve allografts have been shown to be inferior to autografts in previous animal studies. The authors hypothesized that combining different processing and storage techniques will result in improved nerve ultrastructure preservation, lower immunogenicity, and minimized cellular debris. Different processing protocols were evaluated using chemical detergents, enzymes, and irradiation, with the addition the of enzyme elastase, were used. Additionally, the difference between cold and frozen storage was investigated. The goal of this study was to create an optimized nerve allograft. METHODS Fifty rat nerves were decellularized with modifications of previous protocols and the addition of elastase. Subsequently, the nerve segments were stored at either 4°C or -80°C. Both processed and fresh control nerves were analyzed with confocal microscopy using immunohistochemical staining on the basal lamina (laminin γ-1), Schwann cells (S100 protein), and immunogenicity using major histocompatibility complex-I (MHCI) staining. Morphology of the ultrastructure and amount of cellular debris were analyzed on cross-sections of the nerves stained with toluidine blue and H & E, and by using electron microscopy. RESULTS Nerve ultrastructure was preserved with all decellularization protocols. Storage at -80°C severely altered nerve ultrastructure after any decellularization method. Elastase was found to significantly reduce the immunogenicity and amount of Schwann cells, while maintaining good structural properties. CONCLUSIONS Reduced immunogenicity, diminished cellular debris, and the elimination of Schwann cells was observed when elastase was added to the nerve processing while maintaining ultrastructure. Storage at -80°C after the decellularization process heavily damaged the nerve ultrastructure as compared with cold storage. Further in vivo studies are needed to prove the nerve regenerative capacity of these optimized allografts.

Safety and Suitability of Finger Replantations as a Residency Training Procedure: A Retrospective Cohort Study With Analysis of the Initial Postoperative Outcomes.

Finger replantations demand technical excellence in microsurgery and hand trauma care. The objective of this study was to determine whether finger replantations constitute an appropriate and safe procedure for residency training. Additionally, the prognostic risk factors for the need to take a replanted finger back to the operation room and replant failure were analyzed.All patients who underwent finger replantation after complete amputation between 2007 and 2015 were included in a retrospective comparative study. These patients were either treated by an attending plastic surgeon (cohort 1) or by a postgraduate year 5 or 6 resident under supervision (cohort 2). Logistic regression analysis was used to identify the prognostic risk factors for emergent take backs and replant failures.A total of 109 completely amputated fingers were replanted in 89 patients. Fifty-seven digits were replanted in cohort 1, and 52 digits were replanted in cohort 2. Patient demographic data revealed an equal distribution between the two cohorts with an overall finger-replantation success rate of 67.0%. The prognostic risk factors related to increased take back and replant failure rates were fewer than two venous anastomoses (take back odds ratio [AOR], 0.27; confidence interval (CI), 0.12-0.63; and replant failure AOR, 0.21; 95% CI, 0.08-0.55) and intraoperative noticeable problems regarding the vascular anastomoses (take back AOR, 2.26; 95% CI, 0.96-5.33 and replant failure AOR, 2.45; 95% CI, 1.00-6.00). The type of surgeon did not exhibit an influence on the risk of take back (OR, 1.14; 95% CI, 0.53-2.41) or replant failure (OR, 1.03; 95% CI, 0.46-2.30). Similarly, after adjusting for all risk factors, the risks for take backs (AOR, 1.04; 95% CI, 0.46-2.36) and replant failures (AOR, 0.91; 95% CI, 0.38-2.19) did not differ between the 2 cohorts.Finger replantations can be applied as a safe procedure in residency training under standardized conditions and do not negatively affect quality of care. Technical proficiency in microsurgery and elective and trauma hand care as well as supervision by an experienced plastic or hand surgeon are mandatory. Regardless of the surgeons' experience, fewer than 2 venous anastomoses and the presence of intraoperative vascular anomalies represent significant prognostic risk factors for postoperative complications.

A novel device for resistance-free biomechanical testing of the metaphysis of long bones.

BACKGROUND: Biomechanical testing is an essential component of bone research. In order to test the metaphyseal region of long bones, a typical location for the nowadays increasing field of osteoporotic bone changes, three-point bending and breaking test devices are suitable and widely used. The aim of our study was to increase the effectiveness of this method by using a newly developed ball-mounted platform design. This new design eliminates the negative effects of friction, present in previous studies, caused by the lengthening of the distal tibia along its diaphyseal axis while sliding over the surface of a fixed aluminum block. METHODS: 70 tibiae of 35 twelve week old, female Sprague Dawley rats were separated into two groups for a metaphyseal bending/breaking test. Group 1 was made up of the rat's right tibiae, Group 2 of the left tibiae. Group 1 was tested on a solid metal block according to previously established testing devices whereas Group 2 was tested on the newly designed device: the resistance-free gliding, ball-mounted platform. Stiffness (N/mm), yield Load (N), and failure Load (N) were registered. In the evaluation of both testing procedures, the results of the right and left tibiae were compared according to the rat they originated from. RESULTS: Stiffness (S) showed highly significant differences (p = 0.002) with 202.25 ± 27.010 N/mm SD (Group 1) and 184.66 ± 35.875 N/mm SD (Group 2). Yield Load (yL) showed highly significant differences (p < 0.001) with 55.31 ± 13.074 N SD (Group1) and 37.17 ± 12.464 N SD (Group2). The mean failure Load (fL) did not differ significantly (p < 0.231) between Group 1: 81.34 ± 11.972 N SD and Group 2: 79.63 ± 10.345 N SD. CONCLUSIONS: We therefore conclude that, used in the three-point bending/breaking test, the mobile, ball-mounted platform device is able to efficiently eliminate the influence of friction in terms of stiffness and yield load. Failure Load was not affected. We suggest that the new ball-mounted platform device, when compared to other existing techniques, generates more accurate test results when used in the three-point bending/breaking test of the metaphysis of long bones.

Neo-Angiogenesis, Transplant Viability, and Molecular Analyses of Vascularized Bone Allotransplantation Surgery in a Large Animal Model.

Vascularized composite allotransplantation of bone is a possible alternative treatment for large osseous defects but requires life-long immunosuppression. Surgical induction of autogenous neo-angiogenic circulation maintains transplant viability without this requirement, providing encouraging results in small animal models [1-3]. A preliminary feasibility study in a swine tibia model demonstrated similar findings [4, 5]. This study in swine tibial allotransplantation tests its applicability in a pre-clinical large animal model. Previously, we have demonstrated bone vascularized composite allotransplantation (VCA) survival was not the result of induction of tolerance nor an incompetent immune system [1]. Fourteen tibia vascularized bone allotransplants were microsurgically transplanted orthotopically to reconstruct size-matched tibial defects in Yucatan miniature swine. Two weeks of immunosuppression was used to maintain allotransplant pedicle patency during angiogenesis from a simultaneously implanted autogenous arteriovenous bundle. The implanted arteriovenous bundle was patent in group 1 and ligated in group 2 (a neo-angiogenesis control). At twenty weeks, we quantified the neo-angiogenesis and correlated it with transplant viability, bone remodeling, and gene expression. All patent arteriovenous bundles maintained patency throughout the survival period. Micro-angiographic, osteocyte cell count and bone remodeling parameters were significantly higher than controls due to the formation of a neo-angiogenic autogenous circulation. Analysis of gene expression found maintained osteoblastic and osteoclastic activity as well as a significant increase in expression of endothelial growth factor-like 6 (EGFL-6) in the patent arteriovenous bundle group. Vascularized composite allotransplants of swine tibia maintained viability and actively remodeled over 20 weeks when short-term immunosuppression is combined with simultaneous autogenous neo-angiogenesis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:288-296, 2020.

Effects of Surgical Angiogenesis on Segmental Bone Reconstruction With Cryopreserved Massive-Structural Allografts in a Porcine Tibia Model.

Cryopreserved bone allografts (CBA) used to reconstruct segmental bone defects provide immediate structural stability, but are vulnerable to infection, non-union and late stress fracture as the majority of the allograft remains largely avascular. We sought to improve the bone vascularity and bone formation of CBAs by surgical angiogenesis with an implanted arteriovenous (AV) bundle, using a porcine tibial defect model. Cryopreserved tibial bone allografts were transplanted in swine leukocyte antigen (SLA) mismatched Yucatan minipigs to reconstruct a 3.5 cm segmental tibial defect. A cranial tibial AV-bundle was placed within its intramedullary canal to induce angiogenesis. The AV bundle was patent in eight pigs and ligated in a control group of eight pigs. At 20 weeks neo-angiogenesis was evaluated by micro-angiography. Bone formation was measured by quantitative histomorphometry and micro-computed tomography. Seven of eight AV-bundles in the revascularized group were patent. One had thrombosed due to allograft displacement. Total vascular volume was higher in the revascularized allografts compared to the ligated group (p = 0.015). Revascularized allografts had increased levels of bone formation on the allograft endosteal surface compared to the ligated control group (p = 0.05). Surgical angiogenesis of porcine tibial CBAs by intramedullary implantation of an AV-bundle creates an enhanced autogenous neoangiogenic circulation and accelerates active bone formation on allograft endosteal surfaces. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1698-1708, 2019.

Feasibility and safety of enzymatic debridement for the prevention of operative escharotomy in circumferential deep burns of the distal upper extremity.

BACKGROUND: Burn-induced compartment syndrome is a severe sequela after circumferential burns of the extremities and is avoidable by immediate release of the underlying pressure under the eschar. Although the current gold standard is operative escharotomy, this procedure carries considerable morbidity. Our study evaluates the safety and effectiveness of immediate enzymatic debridement to prevent the need for operative escharotomy because of burn-induced compartment syndrome in selected patients. PATIENTS AND METHODS: From 2015 to 2017, all patients suffering from deep circumferential burns of the upper extremities requiring operative escharotomy were potential candidates for the treatment algorithm evaluated by this study. Exclusion criteria involved burn trauma > 12 hours, clinically established burn-induced compartment syndrome, intolerance to the enzymatic debriding agent, dry burns requiring presoaking, as well as blast and electrical injuries requiring fasciotomy or carpal tunnel release. All patients with the inclusion criteria received enzymatic debridement with Nexobrid immediately after admission to our burn center. Enzymatic debridement was applied according to the manufacturer's recommendations. After enzymatic debridement, extremities were revisited every 2 hours for 24 hours to determine the need for conversion to conventional operative escharotomy. The indication for and time to skin grafting was reviewed, and functional outcomes assessed during follow-up examination. RESULTS: Included in this sturdy were 13 patients with 20 burned upper extremities. Enzymatic debridement provided a sufficient eschar removal in all patients. Conversion to conventional operative escharotomy was thus not necessary in any patient. Secondary skin grafting was required in 9 patients. Functional outcomes were favorable 11.9 months after burn trauma. CONCLUSION: If the specific contraindications are respected, enzymatic debridement is safe and effective for the prevention of burn-induced compartment syndrome after deep circumferential burns at the upper extremity, and thus making operative escharotomy unnecessary.

[The interdisciplinary Microsurgeon - Results of the Consensus Workshop of the German Speaking Society for Microsurgery of Peripheral Nerves and Vessels]. / Der interdisziplinäre Mikrochirurg ­ Ergebnisse des Konsensus-Workshops der Deutschsprachigen Arbeitsgemeinschaft für Mikrochirurgie der peripheren Nerven und Gefäße am Beispiel unterschiedlicher Board-Formate.

Plastic and reconstructive surgery is characterized by a high degree of interdisciplinarity. Although Plastic surgery offers a wide range of reliable surgical treatment options independent departments for plastic and reconstructive surgery are not present in every university clinic or leading hospital in Germany. However, the ongoing improvements especially in the field of reconstructive microsurgery enabled and enhanced the treatment of complex defects in order to restore function as well as cosmetic outcome. Knowing the fact that patients are usually referred from other medical disciplines that are familiar with the development and treatment of the primary disease, creation of an interdisciplinary reconstructive treatment plan is crucial to guarantee best patient care. Thus, one of the future major challenges in plastic surgery will be the establishment of multidisciplinary boards in order to strengthen the role of plastic surgery within the medical system with the overall aim to solve complex reconstructive cases. During the 39th annual meeting of the German Speaking Society for Microsurgery of Peripheral Nerves and Vessels a workshop titled "The interdisciplinary microsurgeon" addressed this topic. In the present article we will highlight the consented results of the workshop and provide pitfalls and pearls concerning the implementation process of different multidisciplinary boards based on representative examples.

T lymphocytes in acute bacterial infection: increased prevalence of CD11b(+) cells in the peripheral blood and recruitment to the infected site.

T-cell activation, particularly of CD8(+) cells, is invariably associated with viral infections. We now provide evidence for the activation of T cells in patients with localized bacterial soft tissue infections. During acute disease we detected in the peripheral blood of these patients, small though conspicuous populations of CD4(+) CD28(+) CD11b(+) and CD8(+) CD28(+) CD11b(+) cells, indicative of an expansion of effector T cells. Moreover, we identified CD4(+) and CD8(+) cells at the infected site, in addition to highly activated polymorphonuclear neutrophils (PMN). In keeping with their role as first-line defence, PMN were preponderant, but T cells amounted to 20% of the infiltrated cells. The majority of the infiltrated T cells expressed CXCR6, a homing receptor for non-lymphoid tissue. The infiltrated T cells produced interferon-gamma (IFN-gamma), while the peripheral blood cells obtained at the same time did not. In conclusion, in response to localized bacterial infections, T cells are activated and recruited to the infected site. We propose that these T cells, e.g. by producing IFN-gamma, enhance the efficiency of the infiltrated phagocytic cells, particularly of the PMN, thereby supporting the local host defence.

Surgical Angiogenesis in Porcine Tibial Allotransplantation: A New Large Animal Bone Vascularized Composite Allotransplantation Model.

Segmental bone loss resulting from trauma, infection malignancy and congenital anomaly remains a major reconstructive challenge. Current therapeutic options have significant risk of failure and substantial morbidity. Use of bone vascularized composite allotransplantation (VCA) would offer both a close match of resected bone size and shape and the healing and remodeling potential of living bone. At present, life-long drug immunosuppression (IS) is required. Organ toxicity, opportunistic infection and neoplasm risks are of concern to treat such non-lethal indications. We have previously demonstrated that bone and joint VCA viability may be maintained in rats and rabbits without the need of long-term-immunosuppression by implantation of recipient derived vessels within the VCA. It generates an autogenous, neoangiogenic circulation with measurable flow and active bone remodeling, requiring only 2 weeks of IS. As small animals differ from man substantially in anatomy, bone physiology and immunology, we have developed a porcine bone VCA model to evaluate this technique before clinical application is undertaken. Miniature swine are currently widely used for allotransplantation research, given their immunologic, anatomic, physiologic and size similarities to man. Here, we describe a new porcine orthotopic tibial bone VCA model to test the role of autogenous surgical angiogenesis to maintain VCA viability. The model reconstructs segmental tibial bone defects using size- and shape-matched allogeneic tibial bone segments, transplanted across a major swine leukocyte antigen (SLA) mismatch in Yucatan miniature swine. Nutrient vessel repair and implantation of recipient derived autogenous vessels into the medullary canal of allogeneic tibial bone segments is performed in combination with simultaneous short-term IS. This permits a neoangiogenic autogenous circulation to develop from the implanted tissue, maintaining flow through the allogeneic nutrient vessels for a short time. Once established, the new autogenous circulation maintains bone viability following cessation of drug therapy and subsequent nutrient vessel thrombosis.

Recipient-derived angiogenesis with short term immunosuppression increases bone remodeling in bone vascularized composite allotransplantation: A pilot study in a swine tibial defect model.

Current vascularized composite allotransplantation (VCA) transplantation protocols rely upon life-long immune modulation to maintain tissue perfusion. Alternatively, bone-only VCA viability may be maintained in small animal models using surgical angiogenesis from implanted autogenous vessels to develop a neoangiogenic bone circulation that will not be rejected. This study tests the method's efficacy in a large animal model as a bridge to clinical practice, quantifying the remodeling and mechanical properties of porcine tibial VCAs. A segmental tibial defect was reconstructed in Yucatan miniature swine by transplantation of a matched tibia segment from an immunologically mismatched donor. Microsurgical repair of nutrient vessels was performed in all pigs, with simultaneous intramedullary placement of an autogenous arteriovenous (AV) bundle in Group 2. Group 1 served as a no-angiogenesis control. All received 2 weeks of immunosuppression. After 16 weeks, micro-CT and histomorphometric analyses were used to evaluate healing and remodeling. Axial compression and nanoindentation studies evaluated bone mechanical properties. Micro-CT analysis demonstrated significantly more new bone formation and bone remodeling at the distal allotransplant/recipient junction and on the endosteal surfaces of Group 2 tibias (p = 0.03). Elastic modulus and hardness were not adversely affected by angiogenesis. The combination of 2 weeks of immunosuppression and autogenous AV-bundle implantation within a microsurgically transplanted tibial allotransplant permitted long-term allotransplant survival over the study period of 16 weeks in this large animal model. Angiogenesis increased bone formation and remodeling without adverse mechanical effects. The method may allow future composite-tissue allotransplantation of bone without the risks associated with long-term immunosuppression. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1242-1249, 2017.

Low-energy extracorporeal shockwave therapy (ESWT) improves metaphyseal fracture healing in an osteoporotic rat model.

PURPOSE: As result of the current demographic changes, osteoporosis and osteoporotic fractures are becoming an increasing social and economic burden. In this experimental study, extracorporeal shock wave therapy (ESWT), was evaluated as a treatment option for the improvement of osteoporotic fracture healing. METHODS: A well-established fracture model in the metaphyseal tibia in the osteoporotic rat was used. 132 animals were divided into 11 groups, with 12 animals each, consisting of one sham-operated group and 10 ovariectomized (osteoporotic) groups, of which 9 received ESWT treatment. Different energy flux intensities (0.15 mJ/mm2, 0.35 mJ/mm2, or 0.55 mJ/mm2) as well as different numbers of ESWT applications (once, three times, or five times throughout the 35-day healing period) were applied to the osteoporotic fractures. Fracture healing was investigated quantitatively and qualitatively using micro-CT imaging, quantitative real-time polymerase chain reaction (qRT-PCR) analysis, histomorphometric analysis and biomechanical analysis. RESULTS: The results of this study show a qualitative and quantitative improvement in the osteoporotic fracture healing under low-energy (energy flux intensity: 0,15 mJ/mm2) ESWT and with fewer treatment applications per healing period. CONCLUSION: In conclusion, low-energy ESWT seems to exhibit a beneficial effect on the healing of osteoporotic fractures, leading to improved biomechanical properties, enhanced callus-quantity and -quality, and an increase in the expression of bone specific transcription factors. The results suggest that low-energy ESWT, as main treatment or as adjunctive treatment in addition to a surgical intervention, may prove to be an effective, simple to use, and cost-efficient option for the qualitative and quantitative improvement of osteoporotic fracture healing.