Faculty Bibliography

BACKGROUND:Nipple-sparing mastectomy (NSM) has become widely available for breast cancer prophylaxis. There are limited data on its long-term oncologic safety. The objective of this study was to determine the incidence of breast cancer in patients who underwent prophylactic NSM. METHODS:All patients undergoing prophylactic NSM at a single institution from 2006 through 2019 were retrospectively reviewed. Patient demographic factors, genetic predispositions, mastectomy specimen pathology, and oncologic occurrences at follow-up were recorded. Descriptive statistics were performed where necessary to classify demographic factors and oncologic characteristics. RESULTS:A total of 871 prophylactic NSMs were performed on 641 patients, with median follow-up of 82.0 months (standard error 1.24). A total of 94.4% of patients ( n = 605) underwent bilateral NSMs, although only the prophylactic mastectomy was considered. The majority of mastectomy specimens (69.6%) had no identifiable pathology. A total of 38 specimens (4.4%) had cancer identified in mastectomy specimens, with ductal carcinoma in situ being the most common (92.1%; n = 35). Multifocal or multicentric disease was observed in seven cases (18.4%) and lymphovascular invasion was identified in two (5.3%). One patient (0.16%), who was a BRCA2 variant carrier, was found to have breast cancer 6.5 years after prophylactic mastectomy. CONCLUSIONS:Overall primary oncologic occurrence rates are very low in high-risk patients undergoing prophylactic NSM. In addition to reducing the risk of oncologic occurrence, prophylactic surgery itself may be therapeutic in a small proportion of patients. Continued surveillance for these patients remains important to assess at longer follow-up intervals. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Risk, IV.

Pronator syndrome is a median nerve entrapment neuropathy that can be difficult to diagnose due to its variable presentation and objective findings. Neurolymphomatosis is an uncommon disease in which malignant lymphocytes infiltrate central or peripheral nerve endoneurium and is often missed for prolonged periods prior to diagnosis. We present a rare case of pronator syndrome and anterior interosseous nerve palsy due to neurolymphomatosis that was occult on initial MRI in spite of the presence of a median nerve mass discovered intra-operatively during neurolysis. This case demonstrates the value of ultrasound for the examination of peripheral nerve pathology and illustrates its utility as an adjunct to MRI, in part due to the ability to screen a large region.

INTRODUCTION/BACKGROUND:Facial masculinization surgery (FMS) is increasingly popular among cisgender and transgender men. The benefits of FMS are focused on facial identity and have been proven to decrease gender dysphoria in this population. Previous research showed increasing interest in gender affirmation surgery and facial feminization surgery, but the prevalence of FMS has not been explored. It is difficult to find these data based on surgical records alone because institutions do not have standardized methods of reporting and lack publications in the field. Our study aimed to analyze public interest in FMS by using worldwide Google Trends to quantify these trends. METHODS:A worldwide Google Trends search was completed from January 1, 2008, to December 31, 2022, for terms focused on FMS. Then, search terms were analyzed for nonfacial masculinization procedures and were aggregated. Lastly, a PubMed search was conducted for the terms "transgender" and "facial masculinization" from January 1, 2008, to December 31 st , 2022, to compare publication rates. RESULTS:Our data showed an increasing interest in FMS through Google search trends since the year 2008. A similar trend was demonstrated for non-FMS gender-affirming terms. PubMed analysis showed "transgender" medicine publishing rates were approximately 39.65 times greater than "facial masculinization" publishing rates, although "facial masculinization" medicine did produce a positive trend over the study period of approximately 4 publications per year. The medical literature on transgender surgeries rapidly outpaces publications specifically focusing on FMS. CONCLUSION/CONCLUSIONS:Our study showed increasing interest in gender affirmation surgery over time, particularly FMS. These increasing trends should encourage greater scientific exploration of FMS and research to properly quantify and assess surgical outcomes in this special population. Additional educational interventions for both the general public and medical providers, to increase awareness of unique challenges that impact this community and highlight changes in health care coverage over time, should be created to keep pace with increasing patient demand and address the physical, systemic, and psychosocial issues faced by people who identify as transgender.

OBJECTIVE(S)/OBJECTIVE:Previous literature has established a high prevalence of upper airway obstruction in children with craniofacial abnormalities. This study aims to perform quantitative airway volume measurements in patients with craniofacial abnormalities and compare them to age and sex-matched controls. METHODS:We performed a retrospective review of the records of all children with craniofacial abnormalities who underwent head-and-neck computed tomography (CT) imaging at a single tertiary-care center between 1/1/13 and 12/31/20 using the ICD-10 codes Q75.1, Q75.4, and Q87.0. These patients were then matched by age and sex to patients with isolated craniosynostosis (Q75.0). CT scans were imported into Dolphin Imaging software, and airway volumes were measured for the nasal cavity, nasopharynx, oropharynx, and hypopharynx. The primary outcome was the total airway volume, defined as the sum of these measurements. RESULTS:Thirty subjects with craniofacial syndromes were matched to 30 patients with isolated craniosynostosis (controls). In both groups, 18 subjects (60%) were male (p = 0.99). The average ages for syndromic patients and controls were 12.1 and 12.9 months, respectively (p = 0.84). On average, the total airway volumes of syndromic patients were 25% lower than those of controls (p = 0.02). Syndromic patients had 39% smaller nasal cavity volumes (p < 0.001) and 32% smaller nasopharyngeal volumes (p < 0.01). Significant volume differences were not observed for the oropharynx or hypopharynx. CONCLUSION/CONCLUSIONS:We present a unique technique to measure airway volumes in patients with craniofacial abnormalities. These findings will help practitioners to further understand the anatomy and pathophysiology of disturbed breathing in children with craniofacial syndromes. LEVEL OF EVIDENCE/METHODS:III Laryngoscope, 2023.

BACKGROUND:Hierarchical micro-nano structured topography along with surface chemistry modifications of dental implants have been suggested to positively contribute to the osseointegration process. However, the effect of such surface modifications on the molecular response as well as bone formation rate and quality are still unclear, especially in the early healing period. This study aimed to evaluate the effect of coating a double acid etched (DAE) implant surface with nano-sized (20 nm) hydroxyapatite (Nano) with respect to gene expression, histologic parameters, and nanomechanical properties when compared to DAE control at 1 and 2 weeks after implant placement in a rodent femur model. MATERIAL AND METHODS/METHODS:Expression of bone-related genes was determined by qRT-PCR (Col-I, Runx-2, Osx, Opn, Ocn, Alp). Histomorphometric evaluation of bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) within implant threads was performed using photomicrographs after histologic processing. Mechanical properties, reduced elastic modulus and hardness, were determined through nanoindentation. RESULTS:At 1 week, the Nano group demonstrated significantly higher expression of Col-I and Ocn compared to the DAE group, indicating upregulation of osteoprogenitor and osteoblast differentiation genes. At 2 weeks, Nano surface further exhibited enhanced gene expression of Col-I and Osx in comparison to the DAE surface, suggesting an increased mineralization of the newly formed bone. Nanoindentation analysis revealed that the Nano group presented no significant difference on the ranks of reduced elastic modulus and hardness compared to DAE for both timepoints. Histomorphometric analysis yielded no significant difference in the percentage of BIC and BAFO between the Nano and DAE surfaces at 1 and 2 weeks. However, Nano implants did present a higher mean value, ~50%, of BIC compared to DAE, ~30%, after 2 weeks in vivo. CONCLUSIONS:While no significant differences were observed in the amount and mechanical properties of newly formed bone, Nano surface positively and significantly increased the expression osteogenic genes compared to DAE surface at early healing periods.

BACKGROUND:To evaluate bone regenerative capacity of cryoprotected corticocancellous allogeneic bone graft performed in type II and III post-extraction sockets for ridge preservation after twelve weeks in-vivo. MATERIAL AND METHODS/METHODS:Twenty-seven type II or III bony-walled extraction sockets (mandible and maxilla) were selected for this study. Following atraumatic tooth-extraction a cryoprotected corticocancellous allogeneic bone graft material and a resorbable porcine-derived collagen membrane were used for ridge preservation. During re-entry surgery at approximately 12 weeks, bone core biopsies were obtained using a 3.2 mm trephine drill and samples were histologically processed and subjected to qualitative and quantitative histomorphometric analysis. Quantitative data was analyzed using a general linear mixed model with results presented as mean values with the corresponding 95% confidence interval values. RESULTS:Healing without incident and ridge preservation allowed for the placement of dental implants after 12 weeks in 25 out of the 27 treated socket sites. Analyses yielded an average of ~21.0±7% of old/native bone, ~17±5.5% of newly regenerated bone (total of ~38±12.8% for all bone), 0.23±0.14% of new bone presenting with nucleating sites within the matrix, ~52±5.12% of soft tissue, and 3.6±2.09% of damaged bone. The average regenerated bone was statistically analogous to that of old/native bone (p=0.355). Furthermore, an atypical histological pattern of bone regeneration was observed, with newly formed bone exhibiting "infiltration-like" behavior and with new bone nucleating sites observed within the demineralized bone matrix. CONCLUSIONS:Cryoprotected corticocancellous allogeneic bone-graft demonstrated osteoconductive, osteoinductive, and osteogenic properties, yielding unique healing patterns which does warrant further investigation.

Computer-aided design/computer-aided manufacturing and 3-dimensional (3D) printing techniques have revolutionized the approach to bone tissue engineering for the repair of craniomaxillofacial skeletal defects. Ample research has been performed to gain a fundamental understanding of the optimal 3D-printed scaffold design and composition to facilitate appropriate bone formation and healing. Benchtop and preclinical, small animal model testing of 3D-printed bioactive ceramic scaffolds augmented with pharmacological/biological agents have yielded promising results given their potential combined osteogenic and osteoinductive capacity. However, other factors must be evaluated before newly developed constructs may be considered analogous alternatives to the "gold standard" autologous graft for defect repair. More specifically, the 3D-printed bioactive ceramic scaffold's long-term safety profile, biocompatibility, and resorption kinetics must be studied. The ultimate goal is to successfully regenerate bone that is comparable in volume, density, histologic composition, and mechanical strength to that of native bone. In vivo studies of these newly developed bone tissue engineering in translational animal models continue to make strides toward addressing regulatory and clinically relevant topics. These include the use of skeletally immature animal models to address the challenges posed by craniomaxillofacial defect repair in pediatric patients. This manuscript reviews the most recent preclinical animal studies seeking to assess 3D-printed ceramic scaffolds for improved repair of critical-sized craniofacial bony defects.

OBJECTIVES/OBJECTIVE:For transwomen undergoing voice feminization interventions, fundamental frequency (F 0 ; vocal pitch) is a commonly reported functional outcome measure in the literature. However, F 0 may not correlate well with improvement in quality of life (QoL). Several validated voice-related QoL instruments have been used to assess QoL improvement in these patients, yet there is no consensus on the most appropriate instrument. This systematic review and meta-analysis aimed to assess the relationship between change in F 0 and QoL improvement following voice feminization, and to compare validated QoL instruments commonly used in this population. DATA SOURCES/METHODS:PubMed, Cochrane, and Embase. REVIEW METHODS/METHODS:A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Primary studies of transwomen undergoing voice feminization, reporting validated QoL outcomes were included. Meta-analyses for associations between mean change in QoL score and mean change in F 0 , as well as variations in mean change in QoL score by QoL instrument, were performed using a multilevel mixed effects model. RESULTS:No statistically significant correlation was found between change in F 0 and QoL score improvement post-intervention. Different validated instruments showed statistically significant variation in QoL score change, with the Trans Women Voice Questionnaire (TWVQ) capturing a greater improvement in QoL score relative to other instruments. CONCLUSIONS:Lack of correlation between changes in F 0 and QoL improvement further supports that F 0 alone is insufficient to assess the efficacy of voice feminizing interventions. Validated QoL measures are useful adjuncts. Of these, the TWVQ appears to be the most sensitive for measurement of QoL improvement following voice feminization.