Faculty Bibliography

BACKGROUND:Controversy exists regarding the optimal surgical approach for non-syndromic sagittal synostosis. This study provides the first comparative analysis of the long-term behavioral, psychological, and executive function outcomes for patients who underwent either cranial vault remodeling (CVR) or spring-assisted strip craniectomy (SAS). METHODS:Thirty-six CVR patients and 39 SAS patients were evaluated. Parents and caregivers completed the Behavior Rating Inventory of Executive Function (BRIEF) and the Behavior Assessment System for Children, Second Edition (BASC-2) to evaluate behavioral, emotional, social, adaptive, and executive functioning skills. RESULTS:There were no statistically significant differences between the CVR and the SAS groups (P > 0.05) in any of the BRIEF areas of function. Furthermore, the BASC-2 battery illustrated no significant differences in all areas analyzed except one. Among the 2 groups, the CVR group was rated as having fewer social withdrawal symptoms on the BASC-2 (47.00 ± 10.27) compared to the SAS cohort (54.64 ± 10.96), F = 6.79, P = 0.012, Cohen d = 0.688. However, both means were still within the normal range. CONCLUSIONS:Children undergoing SAS and CVR procedures for isolated sagittal synostosis were not rated as having clinically significant behavioral, emotional, social, adaptive, or executive functioning problems on parental forms.

BACKGROUND: The anterolateral thigh (ALT) flap is a useful flap with minimal donor site morbidity. Preoperative computed tomographic angiography (CTA) for lower extremity reconstruction can determine vessel integrity and plan for recipient vascular targets. This study reviews lower extremity CTAs to further characterize ALT vascular anatomy and associated clinical implications thereof. PATIENTS AND METHODS/METHODS: Lower extremity CTA studies were retrospectively reviewed, and information on ALT cutaneous perforator location, origin, and course was collected. RESULTS:. The majority of patients were females (23, 74.2%). The LCFA most commonly originated from the profunda femoris artery (87.3%), followed by the distal common femoral artery (9.1%). On average, there were 1.66 ± 0.69 cm perforators per extremity, with an average of 5.38 cm between adjacent perforators. Perforators originated from the descending branch of the LCFA in 89.6% of studies. Perforator caliber was <1 mm (29, 30.2%), 1 to 2 mm (55, 57.3%), or >2 mm (12, 12.5%). Mean distance from the most proximal perforator to the anterior superior iliac spine was 20.4 ± 4.82 cm. Perforators were musculocutaneous (46.9%), septocutaneous (34.4%), or septomyocutaneous (18.8%). In 58.1% of patients, only one thigh had easily dissectable septocutaneous and/or septomyocutaneous perforators, in which case preoperative CTA aided in donor thigh selection. CONCLUSION/CONCLUSIONS: ALT flap cutaneous perforator anatomy varies considerably. Using CTA, we report on rates of septocutaneous, myocutaneous, and septomyocutaneous perforators and underscore its utility in perforator selection.

Cancer cells secrete pro-nociceptive mediators that sensitize adjacent sensory neurons and cause pain. Identification and characterization of these mediators could pinpoint novel targets for cancer pain treatment. In the present study we identified candidate genes in cancer cell lines that encode for secreted or cell surface proteins that may drive nociception. To undertake this work, we utilized an acute cancer pain mouse model, transcriptomic analysis of publicly available human tumor-derived cell line data, and a literature review. Cancer cell line supernatants were assigned a phenotype based on evoked nociceptive behavior in an acute cancer pain mouse model. We compared gene expression data from nociceptive and non-nociceptive cell lines. Our analyses revealed differentially expressed genes (DEGs) and pathways; many of the identified genes were not previously associated with cancer pain signaling. Epidermal growth factor receptor (EGFR) and disintegrin metalloprotease domain 17 (ADAM17) were identified as potential targets among the DEGs. We found that the nociceptive cell lines contained significantly more ADAM17 protein in the cell culture supernatant compared to non-nociceptive cell lines. Cytoplasmic EGFR was present in almost all (>90%) tongue primary afferent neurons in mice. Monoclonal antibody against EGFR, cetuximab, inhibited cell line supernatant-induced nociceptive behavior in an acute oral cancer pain mouse model. We infer from these data that ADAM17-EGFR signaling is involved in cancer mediator-induced nociception. The differentially expressed genes and their secreted protein products may serve as candidate therapeutic targets for oral cancer pain and warrant further evaluation.

BACKGROUND:Authors have speculated that vascularized composite allotransplantation (VCA) recipients may require greater maintenance immunosuppression than solid organ transplant (SOT) recipients due to the higher antigenicity of skin. However, detailed comparisons of VCA and SOT immunosuppression regimens have been limited. METHODS:Hand and face VCA recipient immunosuppression data were collected through a systematic literature review. Kidney recipient data were obtained through a retrospective chart review of the authors' institution. Prednisone and mycophenolate mofetil (MMF) doses were compared between VCA and kidney recipients at predefined follow-up intervals (<1, 1-5, and >5 y). Tacrolimus target trough levels (TTTL) were compared at follow-up intervals of 1-5 and >5 y, and stratified into our institution's kidney transplant risk-based target ranges (4-6 ng/mL, 6-8 ng/mL) or higher (>8 ng/mL). RESULTS:Immunosuppression data were available for 57 VCA and 98 kidney recipients. There were no significant differences in prednisone doses between groups at all follow-up intervals. VCA recipient mean MMF dose was significantly greater at <1-y (1.71 ± 0.58 versus 1.16 ± 0.55 gm/d; P = 0.01). For VCA recipients, there was a significant difference (P = 0.02) in TTTL distribution over the three predefined therapeutic ranges (4-6 ng/mL, 6-8 ng/mL, and >8 ng/mL) between 1 and 5 y (24.0%, 20.0%, 56.0%, respectively) and >5 y (28.6%, 42.9%, 28.6%). CONCLUSIONS:At longer follow-up, VCA and kidney recipients receive comparable MMF/prednisone doses, and most VCA recipients are treated with TTTL similar to kidney recipients. Further research may improve our understanding of VCA's complex risk/benefit ratio, and enhance informed consent.

BACKGROUND:We examine the prognostic implications of mid-course nodal response in oropharyngeal cancer (OPX) to radiation therapy. METHODS:In 44 patients with node-positive OPX undergoing concurrent chemoradiation, nodal volumes were measured on cone beam CTs from days 1, 10, 20, and 35. Nodal decrease (ND) was based on percent shrinkage from day 1. RESULTS:At a median follow-up of 17 months, the 2-year disease-free survival (DFS), locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) were 87%, 92%, 89%, and 92%, respectively. Patients with ND ≥43% at D20 had improved LRC (100% vs 78.4%, P = .03) compared to D20 ND <43%. On multivariate analysis, D20 ≥43% was independently prognostic for LRC (HR 1.17, P = .05). CONCLUSION/CONCLUSIONS:Patients with low-risk oropharynx cancer with ND of ≥43% by treatment day 20 had significantly improved LRC. The prognostic benefit of ND may assist in identifying candidates for treatment de-escalation.

INTRODUCTION/UNASSIGNED:Clefts of the lip and palate are leading congenital facial anomalies. Underserved patients with these facial differences lack access to medical care, surgical expertise, prenatal care, or psychological support. Moreover, the disease results in significant economic strains on patients and their families. While surgical outreach programs have attempted to fill this void, significant challenges facing international comprehensive cleft care persist. OBJECTIVE/UNASSIGNED:Propose a path toward international sustainable cleft care based on the Global Smile Foundation experience. RESULTS/UNASSIGNED:International sustainable comprehensive cleft care can be achieved by regulating surgical outreach programs. Regulation of these missions would ensure standardized care and encourage stakeholders to cooperate and adequately allocate funding and resources. Capacity building can be achieved through "diagonal" cleft care delivery models, multidisciplinary workshops, fellowship programs, research and quality assurance, as well as leveraging emerging technologies such as Augmented Reality. CONCLUSION/UNASSIGNED:International comprehensive cleft care requires continuous collaborative efforts between visiting and local teams as well as international and national organizations. Standardizing and regulating current practices as well as promoting capacity building initiatives can contribute to sustainable cleft care.

WE43 Mg alloy proved to be an ideal candidate for production of resorbable implants in both clinical and trial settings. In previous studies we tested biocompatibility and degradation properties of WE43 (as-cast) and artificially aged (WE43-T5) Mg alloys in a sheep model. Both alloys showed excellent biocompatibility with the as-cast, WE43, form showing increased degradability compared to the artificially aged, WE43-T5. In the present study, our group assessed the biological behavior and degradation pattern of the same alloys when implanted as endosteal implants in a sheep model. Twelve screws (3x15 mm) were evaluated, one screw per each composition was placed bi-cortically in the mandible of each animal with a titanium (2x12 mm) screw serving as an internal positive control. At 6 and 24 weeks histomorphological analysis was performed, at 6 weeks as cast, WE43, yielded a higher degradation rate, increased bone remodeling and osteolysis compared to the WE43-T5 alloy; however, at 24 weeks WE43-T5 showed higher degradation rate and increased bone remodeling than as-cast. In vitro assay of cell growth, adhesion and differentiation was also conducted to investigate possible mechanisms underlying the behavior expressed from the alloys in vivo. In conclusion WE43-T5 indicated bone/implant interaction properties that makes it more suitable for fabrication of endosteal bone screws.