Faculty Bibliography

BACKGROUND:The goal of our study was to evaluate risk factors for wound complications in patients with diabetes mellitus undergoing transmetatarsal amputations (TMAs), given the paucity of research on this subject. MATERIALS AND METHODS/METHODS:We used the American College of Surgeons National Surgical Quality Improvement Program database. In this retrospective analysis, all surgical cases with a primary Current Procedural Terminology code for TMA from 2009 to 2015 were reviewed. RESULTS:A total of 2316 patients with diabetes mellitus who underwent TMA were identified. Overall wound complications occurred in 276 (11.9%) of patients. Univariate analysis showed that the operative time was significantly longer in patients who developed complications than those who did not (58.3 ± 39.5 versus 50.6 ± 39.4; P = 0.003). Furthermore, the rate of obesity was significantly higher among patients who developed wound complications than those who did not (47.1% versus 41.5%; P = 0.04). Multivariate analysis demonstrated that a longer operative time (odds ratio = 1.02; 95% confidence interval: 1.01-1.04; P = 0.01) and obesity (odds ratio = 1.60; 95% confidence interval: 1.06-2.40; P = 0.03) were independent risk factors for wound complications in our cohort. CONCLUSIONS:These findings emphasize the importance of having heightened clinical vigilance in obese patients with diabetes mellitus undergoing this procedure, close postoperative follow-up, and limiting operative time when possible.

Facial transplantation is emerging as a therapeutic option for self-inflicted gunshot wounds. The self-inflicted nature of this injury raises questions about the appropriate role of self-harm in determining patient eligibility. Potential candidates for facial transplantation undergo extensive psychosocial screening. The presence of a self-inflicted gunshot wound warrants special attention to ensure that a patient is prepared to undergo a demanding procedure that poses significant risk, as well as stringent lifelong management. Herein, we explore the ethics of considering mechanism of injury in the patient selection process, referring to the precedent set forth in solid organ transplantation. We also consider the available evidence regarding outcomes of individuals transplanted for self-inflicted mechanisms of injury in both solid organ and facial transplantation. We conclude that while the presence of a self-inflicted gunshot wound is significant in the overall evaluation of the candidate, it does not on its own warrant exclusion from consideration for a facial transplantation.

Proteases sustain hyperexcitability and pain by cleaving protease-activated receptor-2 (PAR₂) on nociceptors through distinct mechanisms. Whereas trypsin induces PAR₂ coupling to Gα_q, Gα_s, and β-arrestins, cathepsin-S (CS) and neutrophil elastase (NE) cleave PAR₂ at distinct sites and activate it by biased mechanisms that induce coupling to Gα_s, but not to Gα_q or β-arrestins. Because proteases activate PAR₂ by irreversible cleavage, and activated PAR₂ is degraded in lysosomes, sustained extracellular protease-mediated signaling requires mobilization of intact PAR₂ from the Golgi apparatus or de novo synthesis of new receptors by incompletely understood mechanisms. We found here that trypsin, CS, and NE stimulate PAR₂-dependent activation of protein kinase D (PKD) in the Golgi of HEK293 cells, in which PKD regulates protein trafficking. The proteases stimulated translocation of the PKD activator Gβγ to the Golgi, coinciding with PAR₂ mobilization from the Golgi. Proteases also induced translocation of a photoconverted PAR₂-Kaede fusion protein from the Golgi to the plasma membrane of KNRK cells. After incubation of HEK293 cells and dorsal root ganglia neurons with CS, NE, or trypsin, PAR₂ responsiveness initially declined, consistent with PAR₂ cleavage and desensitization, and then gradually recovered. Inhibitors of PKD, Gβγ, and protein translation inhibited recovery of PAR₂ responsiveness. PKD and Gβγ inhibitors also attenuated protease-evoked mechanical allodynia in mice. We conclude that proteases that activate PAR₂ by canonical and biased mechanisms stimulate PKD in the Golgi; PAR₂ mobilization and de novo synthesis repopulate the cell surface with intact receptors and sustain nociceptive signaling by extracellular proteases.

This study's objective was to mechanically characterize and validate the synthesis method of a polycrystalline composite comprised of 80% alumina reinforced with 20% translucent zirconia (zirconia-toughened alumina, ZTA) and compare to an experimental translucent zirconia. Experimental ZTA (ZTA ZPEX 80/20) and translucent Y-TZP (ZPEX) green-state disc-shaped specimens were obtained via uniaxial/isostatic ceramic powder pressing technique. The discs were sintered using a predefined protocol after both sides of the discs were polished. The specimens were subjected to nanoindentation testing to acquire their elastic modulus (E) and hardness (H) before and after a simulated low temperature degradation (LTD) challenge. Subsequently, the fabricated discs had their 3D surface topographical (Sa/Sq) parameters assessed via interferometry before and after exposure to a simulated LTD aging protocol. The specimens were evaluated using X-ray diffraction (XRD) to assess the tetragonal-monoclinic phase transformation and via scanning electron microscopy (SEM) to evaluate the homogeneity of the surfaces and distribution of the grains. The apparent density was measured using Archimedes"™ principle. All of the data were statistically evaluated through repeated measures ANOVA following post-hoc comparisons using the Tukey test (p < 0.05). The XRD patterns indicated a higher increase in the monoclinic peak for ZPEX compared to ZTA ZPEX 80/20 aged. LTD aging did not have an effect on the surface roughness (Sa/Sq) for both groups (p > 0.05). A significant decrease in the E values after the aging protocol was observed for both groups (p < 0.01). While ZTA ZPEX 80/20 did not show statistically significant differences in the hardness values after the aging protocol (p = 0.36), ZPEX demonstrated a significant decrease in the H values (p = 0.03). For ZTA ZPEX 80/20, simulated LTD aging did not affect the tested properties, except for the E values. Although artificial aging did not affect the surface roughness of ZPEX, the E and H values significantly decreased after aging.

BACKGROUND:Alveolar clefts are traditionally treated with secondary bone grafting, but this is associated with morbidity and graft resorption. Although recombinant human bone morphogenetic protein-2 (rhBMP-2) is under investigation for alveolar cleft repair, safety concerns remain. Dipyridamole is an adenosine receptor indirect agonist with known osteogenic potential. This study compared dipyridamole to rhBMP-2 at alveolar cleft defects delivered using bioceramic scaffolds. METHODS:Skeletally immature New Zealand White rabbits underwent unilateral, 3.5 × 3.5-mm alveolar resection adjacent to the growing suture. Five served as negative controls. The remaining defects were reconstructed with three-dimensionally printed bioceramic scaffolds coated with 1000 μm of dipyridamole (n = 6), 10,000 μm of dipyridamole (n = 7), or 0.2 mg/ml of rhBMP-2 (n = 5). At 8 weeks, new bone was quantified. Nondecalcified histologic evaluation was performed, and new bone was evaluated mechanically. Statistical analysis was performed using a generalized linear mixed model and the Wilcoxon rank sum test. RESULTS:Negative controls did not heal, whereas new bone formation bridged all three-dimensionally printed bioceramic treatment groups. The 1000-μm dipyridamole scaffolds regenerated 28.03 ± 7.38 percent, 10,000-μm dipyridamole scaffolds regenerated 36.18 ± 6.83 percent (1000 μm versus 10,000 μm dipyridamole; p = 0.104), and rhBMP-2-coated scaffolds regenerated 37.17 ± 16.69 percent bone (p = 0.124 versus 1000 μm dipyridamole, and p = 0.938 versus 10,000 μm dipyridamole). On histology/electron microscopy, no changes in suture biology were evident for dipyridamole, whereas rhBMP-2 demonstrated early signs of suture fusion. Healing was highly cellular and vascularized across all groups. No statistical differences in mechanical properties were observed between either dipyridamole or rhBMP-2 compared with native bone. CONCLUSION/CONCLUSIONS:Dipyridamole generates new bone without osteolysis and early suture fusion associated with rhBMP-2 in skeletally immature bone defects.

BACKGROUND:Facial transplantation introduced a paradigm shift in the reconstruction of extensive facial defects. Although the feasibility of the procedure is well established, new challenges face the field in its second decade. METHODS:The authors' team has successfully treated patients with extensive thermal and ballistic facial injuries with allotransplantation. The authors further validate facial transplantation as a reconstructive solution for irreparable facial injuries. Following informed consent and institutional review board approval, a partial face and double jaw transplantation was performed in a 25-year-old man who sustained ballistic facial trauma. Extensive team preparations, thorough patient evaluation, preoperative diagnostic imaging, three-dimensional printing technology, intraoperative surgical navigation, and the use of dual induction immunosuppression contributed to the success of the procedure. RESULTS:The procedure was performed on January 5 and 6, 2018, and lasted nearly 25 hours. The patient underwent hyoid and genioglossus advancement for floor-of-mouth dehiscence, and palate wound dehiscence repair on postoperative day 11. Open reduction and internal fixation of left mandibular nonunion were performed on postoperative day 108. Nearly 1 year postoperatively, the patient demonstrates excellent aesthetic outcomes, intelligible speech, and is tolerating an oral diet. He remains free from acute rejection. CONCLUSIONS:The authors validate facial transplantation as the modern answer to the classic reconstructive challenge imposed by extensive facial defects resulting from ballistic injury. Relying on a multidisciplinary collaborative approach, coupled with innovative emerging technologies and immunosuppression protocols, can overcome significant challenges in facial transplantation and reinforce its position as the highest rung on the reconstructive ladder. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Therapeutic, V.

There are over 2 million long bone defects treated in the USA annually, of which ~5% will not heal without significant surgical intervention. While autogenous grafting is standard of care in simple defects, a customized scaffold for large defects in unlimited quantities is not available. Recently, a three-dimensionally (3D) printed bioactive ceramic (3DPBC) scaffold has been successfully utilized in the of repair critical sized long bone defects in vivo. In this study, 3DPBC scaffolds were augmented with Dipyridamole, an adenosine A2A receptor (A_2A R) indirect agonist, because of its known effect to enhance bone formation. Critical-sized full thickness segmental defects (~11mm x full thickness) defects were created in the radial diaphysis in New Zealand White rabbits (n=24). A customized 3DPBC scaffold composed of β-tricalcium phosphate was placed into the defect site. Groups included scaffolds that were collagen-coated (COLL), or immersed in 10μM, 100μM, or 1000μM Dipyridamole solution. Animals were euthanized 8 weeks post-operatively and the radii/ulna-scaffold complex retrieved, en bloc, for micro-CT, histological and mechanical analysis. Bone growth was assessed exclusively within scaffold pores and evaluated by microCT and advanced reconstruction software. Biomechanical properties were evaluated utilizing nanoindentation to assess the newly regenerated bone for elastic modulus (E) and hardness (H). MicroCT reconstructions illustrated bone in-growth throughout the scaffold, with an increase in bone volume dependent on the Dipyridamole dosage. Histological evaluation did not indicate any adverse immune response while revealing progressive remodeling of bone. These customized biologic 3DPBC scaffolds have the potential of repairing and regenerating bone. This article is protected by copyright. All rights reserved.

Background/UNASSIGNED:Mastectomy flap and nipple-areola complex (NAC) ischemia can be devastating complications after nipple-sparing mastectomy (NSM). Predictors of reconstructive failure with major skin envelope ischemia and implications for decision-making remain to be fully elucidated. Methods/UNASSIGNED:All cases of implant-based reconstruction after NSM from 2006 to June 2018 with mastectomy flap necrosis or NAC necrosis requiring debridement were reviewed. Data on patient demographics, operative characteristics, additional complications, and the nature and management of ischemic complications were collected and analyzed. Results/UNASSIGNED:= 0.0494). Conclusions/UNASSIGNED:NSM cases with major ischemia requiring explantation had a lower body mass index and significantly higher rate of preoperative radiation, immediate implant placement, use of acellular dermal matrix/mesh, and concomitant major infection. These variables should be taken into account when discussing risks with patients preoperatively and assessing the quality of mastectomy flaps and subsequent reconstructive choices intraoperatively.