Faculty Bibliography

PURPOSE: To investigate whether complex midface fractures have a greater association with death and intracranial injury than simple midface fractures. MATERIALS AND METHODS: A retrospective chart review was performed for patients with blunt-mechanism midface fractures who had presented to an urban trauma center from 1998 to 2010. The survival and intracranial injury status was evaluated for patients with simple and complex midface fractures, including Le Fort, naso-orbitoethmoid, and/or zygomaticomaxillary fractures. Intracranial injury included hemorrhage and brainstem injury. Patients with upper face fractures were excluded to minimize confounding. Adjusted relative risk estimates were obtained using multivariate regression analysis. RESULTS: Of 3,291 patients with midface fractures, 213 (6.3%) died and 693 (21.3%) had an intracranial injury. The cumulative mortality reached 11.6% in patients with complex midface fractures and 5.1% in those with simple midface fractures (P < .001). Patients with complex midface fractures were 57% more likely to die (relative risk = 1.57; P < .005). Specifically, Le Fort II fractures independently conferred a 94% increased risk of death (relative risk = 1.94; P < .01), but Le Fort I and III fractures were not significantly associated with death. Among patients presenting without neurologic impairment, those with Le Fort II and III fractures remained 2.88-fold (P < .01) and 2.54-fold (P < .001) more likely to have an underlying intracranial injury, respectively. CONCLUSIONS: Le Fort II fractures are associated with increased mortality. Furthermore, Le Fort II and III fractures are associated with serious intracranial injury, even in the absence of alterations in consciousness. These patients should be monitored with heightened vigilance and followed up closely during hospitalization, regardless of the presenting clinical findings.

BACKGROUND: T regulatory cells (Tregs) have been associated with prolonged allograft survival and tolerance across a wide variety of species and organ types. We used our nonhuman primate model of facial vascularized composite allotransplantation (VCA) to study the association of Tregs with graft outcomes. METHODS: We quantified Tregs in peripheral blood and allograft biopsies from nonhuman primates after heterotopic partial facial segment allotransplantation from major histocompatibility complex class I-mismatched donors using flow cytometry and immunohistochemistry. Immunosuppression consisted of tacrolimus and mycophenolate mofetil without induction or depletional therapies. Circulating and graft skin Treg values were compared with graft outcomes and with histologic grade from concurrent biopsies. RESULTS: Treg proportion in peripheral blood ranged from 0.156% to 9.00% with a mean of 3.34%+/-0.22%. FoxP3 staining was observed in 3 of 29 graft biopsies. Median circulating Treg value did not predict time to Banff grade II rejection (hazard ratio, 0.9; confidence interval, 0.4-2.2) or graft loss (hazard ratio, 0.5; confidence interval, 0.01-5.3). Animals that experienced rejection did not have significantly different peripheral blood or graft skin Treg values from those that did not. Biopsy specimens with grade I or II rejection were more likely to contain Tregs (25% vs. 0%; P=0.044) despite no difference in concurrent circulating Tregs (3.56% vs. 3.36%; P=0.704). CONCLUSIONS: These findings in a clinically relevant model suggest that Tregs may have limited prognostic value with standard immunosuppressive protocols used in VCA. Further studies are necessary to determine the specific role of Tregs in VCA and any role of Treg monitoring in clinical practice.

BACKGROUND:Obesity is associated with a higher risk of developing cancer and co-morbidities that are part of the metabolic syndrome. Adipose tissue is recognized as an endocrine organ, as it affects a number of physiological functions, and contains adipose tissue-derived stem cells (ASCs). ASCs can differentiate into cells of multiple lineages, and as such are applicable to tissue engineering and regenerative medicine. Yet the question of whether ASC functionality is affected by the donor's body mass index (BMI) still exists. RESULTS:ASCs were isolated from patients having different BMIs (BMI-ASCs), within the ranges of 18.5-32.8. It was hypothesized that overweight BMI-ASCs would be more compromised in early adipogenic and osteogenic potential, and ability to form colonies in vitro. BMI was inversely correlated with ASC proliferation and colony forming potential as assessed by CyQUANT proliferation assay (fluorescence- based measurement of cellular DNA content), and colony forming assays. BMI was positively correlated with early time point (day 7) but not later time point (day 15) intracytoplasmic lipid accumulation as assessed by Oil-Red-O staining. Alizarin red staining and RT-PCR for alkaline phosphatase demonstrated that elevated BMI resulted in compromised ASC mineralization of extracellular matrix and decreased alkaline phosphatase mRNA expression. CONCLUSIONS:These data demonstrate that elevated BMI resulted in reduced ASC proliferation, and potentially compromised osteogenic capacity in vitro; thus BMI is an important criterion to consider in selecting ASC donors for clinical applications.

The ESET (also called SETDB1) protein contains an N-terminal tudor domain that mediates protein-protein interactions and a C-terminal SET domain that catalyzes methylation of histone H3 at lysine 9. We report here that ESET protein is transiently upregulated in prehypertrophic chondrocytes in newborn mice. To investigate the in vivo effects of ESET on chondrocyte differentiation, we generated conditional knockout mice to specifically eliminate the catalytic SET domain of ESET protein only in mesenchymal cells. Such deletion of the ESET gene caused acceleration of chondrocyte hypertrophy in both embryos and young animals, depleting chondrocytes that are otherwise available to form epiphyseal plates for endochondral bone growth. ESET-deficient mice are thus characterized by defective long bone growth and trabecular bone formation. To understand the underlying mechanism for ESET regulation of chondrocytes, we carried out co-expression experiments and found that ESET associates with histone deacetylase 4 to bind and inhibit the activity of Runx2, a hypertrophy-promoting transcription factor. Repression of Runx2-mediated gene transactivation by ESET is dependent on its H3-K9 methyltransferase activity as well as its associated histone deacetylase activity. In addition, knockout of ESET is associated with repression of Indian hedgehog gene in pre- and early hypertrophic chondrocytes. Together, these results provide clear evidence that ESET controls hypertrophic differentiation of growth plate chondrocytes and endochondral ossification during embryogenesis and postnatal development.

PURPOSE:: Slow-resorbing deproteinized bovine bone grafts have presented high success rates when used for sinus augmentation. However, histologic evaluation shows that this material is eventually excreted as a result of a foreign body reaction. The purpose of this study was to compare and to evaluate the performance of a recently introduced particulate porous graft material, consisting of pure titanium granule (PTG) to the deproteinized bovine bone grafts, when used as a sinus augmentation material. MATERIALS AND METHODS:: To understand the histological aspects of PTG, deproteinized bovine particulates (Bio-Oss) and PTG were placed contralaterally as sinus grafting materials in 2 patients. After 9 months, biopsies were performed for histologic and 3-dimensional analysis. RESULTS:: Both materials were in contact with newly formed bone. The Bio-Oss showed signs of foreign body reaction. In contrast, bone filled the space between the single PTG particulates, and no foreign body reaction was observed. CONCLUSIONS:: From a bone formation perspective, PTG grafts were comparable with the commonly used Bio-Oss grafts and may be regarded as a possible alternative for permanent grafting in sinus augmentation.

Congenital lower lip pits are cardinal findings of van der Woude syndrome [OMIM 119300]. The nosologic context of how lower lip pits are catalogued is easily lost because of insufficient clinical history, subtle findings misidentified as artifacts, lack of awareness by the pathologist, the perception that these are identify/confirm descriptive-diagnosis only, not necessarily an element of an actionable report, and/or the rarity with which these specimens are accessioned (in the authors' experience, less than 1 case per year). We present the salient findings on 19 lower lip pits specimens from the files of a single institution collected over the last 25 years.

BACKGROUND: The present study demonstrates our experience with a novel use of the Platysma in facial reanimation, as a balancing procedure by counteracting an overactive free muscle transfer, and improving oral continence by re-establishing the oral sphincter mechanism. MATERIAL AND METHODS: Twelve patients, nine female (75%) and three male (25%), with a mean age of thirty-eight years (range: 2-66) are presented. Of these, in seven patients (58%) who had excessive excursion of the free muscle, the contralateral pedicled platysma was transferred to counteract the excessive pull. Four patients (33%) underwent bilateral platysma transfer for oral sphincter restoration, while one (8%) had ipsilateral platysma transfer. Evaluation of aesthetic and functional results was performed by a panel of three independent observers, and the long term efficacy of the procedure was assessed through a patient questionnaire. RESULTS: All patients demonstrated significant upgrading of their oral competence associated with eating, drinking and smiling, as it was confirmed by the behavioural analysis (p < 0.01). Six of the ten patients that were available, responded to the Quality of Life Questionnaire. Five out of six were satisfied with their mouth appearance when they smile and five patients have a regular diet and without drooling. CONCLUSION: A novel use of Platysma transposition is described that can substitute for a paralysed orbicularis oris muscle in restoring oral sphincter function or to counter balance an excessively active free muscle that was previously transferred for smile restoration. This novel Platysma transfer technique is intended to be used as an adjunct to other reanimation procedures.

BACKGROUND:Free silicone injection for breast augmentation, which became widespread in the 1960s and continues illicitly to this day, has well-known adverse effects. In this retrospective chart review of 14 patients treated for silicone mastitis from 1990 to 2002, we present our experience with the surgical management of patients with silicone mastitis. METHODS:All the patients were women, ranging in age from 49 to 76 years old (mean age = 58.8). Patients presented to us a mean of 29.9 years after their free silicone breast injection. Treatment modalities were analyzed, and, specifically, methods of breast reconstruction involving autologous tissue transfers, implants, or a combination were evaluated. RESULTS:The majority of patients (12 of 14) required mastectomies for extensive silicone-infiltrated tissues. The remaining two patients had focal areas of disease and were successfully treated with excision and local breast parenchyma flaps. Autologous reconstruction was performed with a total of 20 flaps, including 12 free transverse rectus abdominis myocutaneous flaps, 4 free superior gluteal artery perforator (SGAP) flaps, and 4 pedicled latissimus dorsi (LD) flaps. Two patients had bilateral implant-based breast reconstruction. CONCLUSION/CONCLUSIONS:A variety of reconstructive options are available for patients presenting with silicone mastitis. Once an appropriate breast cancer workup has been performed, the surgical goal is to excise as much of the silicone-infiltrated tissues as possible before reconstruction. To our knowledge, this is the first reported series that incorporates the use of SGAP and LD flaps as a means of autologous tissue reconstruction for silicone-infiltrated breasts. LEVEL OF EVIDENCE IV/METHODS:This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .