Faculty Bibliography

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: This evaluation aimed to (1) validate micro-computed tomography (microCT) findings using scanning electron microscopy (SEM) imaging, and (2) quantify the volume of voids and the bonded surface area resulting from fiber-reinforced composite (FRC) dowel cementation technique using microCT scanning technology/3D reconstructing software. MATERIALS AND METHODS: A fiberglass dowel was cemented in a condemned maxillary lateral incisor prior to its extraction. A microCT scan was performed of the extracted tooth creating a large volume of data in DICOM format. This set of images was imported to image-processing software to inspect the internal architecture of structures. RESULTS: The outer surface and the spatial relationship of dentin, FRC dowel, cement layer, and voids were reconstructed. Three-dimensional spatial architecture of structures and volumetric analysis revealed that 9.89% of the resin cement was composed of voids and that the bonded area between root dentin and cement was 60.63% larger than that between cement and FRC dowel. CONCLUSIONS: SEM imaging demonstrated the presence of voids similarly observed using microCT technology (aim 1). MicroCT technology was able to nondestructively measure the volume of voids within the cement layer and the bonded surface area at the root/cement/FRC interfaces (aim 2). CLINICAL SIGNIFICANCE: The interfaces at the root dentin/cement/dowel represent a timely and relevant topic where several efforts have been conducted in the past few years to understand their inherent features. MicroCT technology combined with 3D reconstruction allows for not only inspecting the internal arrangement rendered by fiberglass adhesively bonded to root dentin, but also estimating the volume of voids and contacted bond area between the dentin and cement layer.

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 .

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: Infection requiring explantation remains the most devastating complication associated with implant-based breast reconstruction. There are many treatment algorithms to prevent reconstructive failure in face of infection using both oral and intravenous antibiotics. In the absence of patient-specific culture data, antibiotic selection is generally directed toward broad-spectrum coverage based on historical data. We hypothesize that reviewing our institution's microbiology data obtained from explanted implant-based breast reconstructions would provide a rational basis for antibiotic selection in the future. METHODS: A retrospective review of 902 consecutive immediate implant-based breast reconstructions at a single institution from November 2007 to May 2011 was conducted. Implant reconstructions requiring explantation or drainage by interventional radiology were identified. Patient demographics, implant characteristics, presence of skin necrosis, microbiological data, and outcomes were reviewed. RESULTS: Forty-three (4.76%) implant reconstructions requiring explantation or drainage by interventional radiology met the inclusion criteria for this study. Five patients (11.6%) had round, smooth silicone implants, and 36 (88.4%) had textured tissue expanders. Twenty-six implants were explanted because of infection; 3, because of exposure from skin necrosis; and 11, because of the combination of flap necrosis and infection; and 1, secondarily because of cancer invasion into the skin. Reconstruction was salvaged in 21 breasts (51.2%): 12 (57.1%) by implant reconstruction, 5 (23.8%) by pedicled latissimus dorsi flaps, and 4 (19.1%) with a microvascular free flap. Thirty explants had microbiology data available. The most common organism isolated was Staphylococcus epidermidis (10), followed by methicillin-sensitive Staphylococcus aureus (5), Serratia marcescens (5), Pseudomonas aeruginosa (4), enterococcus (3), Escherichia coli (2), Enterobacter (2), group B streptococcus (1), and Morganella morganii (1). Forty percent of the organisms were resistant to cefazolin; however, 86% were sensitive to gentamicin, 80% were sensitive to Levaquin, and 63% were sensitive to ciprofloxacin. CONCLUSIONS: Infection associated with implant-based breast reconstructions continues to threaten explantation and reconstructive failure. Based on our microbiological data, initial cellulitis amenable to oral antibiotics should be treated with oral fluoroquinolones as a first-line treatment. If this regimen fails, intravenous imipenem or gentamicin and vancomycin should be initiated. Obviously, clinical judgment regarding specific patient risk factors and compliance should play a role in decision making, but these data provide an evidence-based rationale for first-line oral antibiotic selection.

PURPOSE: Within the surgical community, it is commonly accepted that the length and cost of a surgical case increase when a resident physician participates. Many accountable care organizations, however, believe the opposite, that is, resident assistance enhances efficiency and diminishes operative time. The purpose of this study is to determine the opportunity cost to the attending surgeon for intraoperative teaching during index plastic surgery cases. METHODS: A single senior surgeon's experience over a 7-year period was evaluated retrospectively for Current Procedural Terminology codes 40700 (repair of primary, unilateral cleft lip) and 42200 (palatoplasty). Variables collected include operative time, the presence or absence of a physician learner, and postgraduate year level. Statistical analysis was performed with the Kruskal-Wallis test using the S+ programming language. A cost analysis was performed to quantify the effect of longer operative times in terms of relative value units (RVUs) lost. RESULTS: During the study period, a total of 45 patients had primary, unilateral cleft lip repair; 70 patients had cleft palate repair. Of those cases, 39 (87%) cleft lip repairs and 60 (86%) cleft palate repairs were performed with a resident or fellow present. There was a statistically significant difference in the amount of time required to perform either surgery with a physician learner than without, with operative times being 60% (p = 0.020) longer for cleft lip repair and 65% (p = 0.0016) longer for cleft palate repair. The results were further stratified based on level of training, with craniofacial fellows and plastic surgery residents (independent and integrated) compared separately. Cases where a craniofacial fellow was present required the longest operative times: 103% (p = 0.0012) longer for cleft lip repairs and 104% (p < 0.0001) longer for cleft palate repairs when compared with the senior surgeon operating alone. Using the 2011 physician work RVUs for these surgeries and the 2011 Medicare conversion factor for RVUs to dollars, the opportunity cost is over $275 per case per trainee for any physician learner. When craniofacial fellows are analyzed separately, over $440 is invested in intraoperative teaching per case per fellow. CONCLUSIONS: Resident involvement in the operating room is crucial to the education of independent surgeons. This involvement, however, comes at a significant opportunity cost to the attending surgeon. As an incentive to retain academic surgeons and uphold a quality academic environment in the OR, compensation should be offered for intraoperative teaching.

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.