Faculty Bibliography

Treatment of cleft lip and palate ordinarily requires multiple interventions spanning the time of birth to adulthood. Restriction of facial growth, a common occurrence in affected children, is due to multiple factors. There are multiple surgical and therapeutic options, which may have influence on facial growth in these patients. As restriction to facial development can have significant implications to form, function, and psychological well-being, practitioners should have an appreciation for the effects of the different cleft therapies to facial growth. We have outlined and thoroughly reviewed in chronological order all of the interventions from birth to adulthood necessary in the comprehensive care of the patient with cleft lip and palate, along with the effects they may or may not have on facial growth.

Surgical site infections represent one of the most common postoperative complications in patients undergoing aesthetic surgery. As with other postoperative complications, the incidence of these infections may be influenced by many factors, and varies depending on the specific operation performed. Understanding of the risk factors for the development of these infections is critical since careful patient selection and appropriate perioperative counselling will set the right expectations, and can ultimately improve patient outcomes and satisfaction. Various perioperative prevention measures may also be employed to minimize the incidence of these infections. Once the infection occurs, prompt diagnosis will allow management of the infection and any associated complications in a timely manner to ensure patient safety, optimize the postoperative course and avoid long-term sequelae.

Nipple-sparing mastectomy (NSM) places greater stress on the breast-skin envelope compared with traditional mastectomy techniques. Precise mastectomy flap dissection is critical to optimize breast skin flap thickness and minimize complication risk. This study evaluated patient-specific factors associated with mastectomy flap quality to improve technical success in NSM. Ideal NSM flap thickness was determined for all NSMs from 2006 to 2016 with available preoperative breast magnetic resonance imaging (MRIs). Demographic, operative variables, and flap thickness were compared for NSMs as stratified by body mass index (BMI) and mastectomy weight. Of the 1,037 NSMs, 420 cases (40.5%; 243 patients) had MRI data available, which included 379 (36.5%) preoperative breast MRIs. Average BMI was 24.08 kg/m², whereas average mastectomy weight was 442.28 g. NSMs were classified according to BMI <25 kg/m², 25-30 kg/m², and >30 kg/m². Average ideal overall NSM flap thicknesses in these groups were 10.43, 12.54, and 14.91 mm, respectively. Each incremental increase in average overall NSM flap thickness per BMI category was statistically significant (P < 0.0001; P < 0.0001; P = 0.0002). NSMs were also classified into mastectomy weight categories: <400 g, 400-799 g, and ≥800 g. Average overall NSM flap thicknesses in these groups were 9.97, 12.21, and 14.50 mm, respectively. Each incremental increase in average overall NSM flap thickness per mastectomy weight category was similarly statistically significant (P < 0.0001; P < 0.0001; P < 0.0001). NSM flap thickness and quality is related to BMI and breast size. Characterizing these anatomic variations preoperatively will help surgeons optimize mastectomy flap dissections and minimize ischemic complications in breast reconstruction after NSM.

Touch sensation is initiated by mechanosensory neurons that innervate distinct skin structures; however, little is known about how these neurons are patterned during mammalian skin development. We explored the cellular basis of touch-receptor patterning in mouse touch domes, which contain mechanosensory Merkel cell-neurite complexes and abut primary hair follicles. At embryonic stage 16.5 (E16.5), touch domes emerge as patches of Merkel cells and keratinocytes clustered with a previously unsuspected population of Bmp4-expressing dermal cells. Epidermal Noggin overexpression at E14.5 disrupted touch-dome formation but not hair-follicle specification, demonstrating a temporally distinct requirement for BMP signaling in placode-derived structures. Surprisingly, two neuronal populations preferentially targeted touch domes during development but only one persisted in mature touch domes. Finally, Keratin-17-expressing keratinocytes but not Merkel cells were necessary to establish innervation patterns during development. These findings identify key cell types and signaling pathways required for targeting Merkel-cell afferents to discrete mechanosensory compartments.

Implant-based breast reconstruction has evolved through advances in mastectomy and reconstruction techniques to offer excellent outcomes with both prepectoral and subpectoral implant placement. Proper patient selection and surgical technique are key for optimizing outcomes and minimizing complications regardless of implant location. Therefore, familiarity with the benefits and limitations of each technique is vital. Several patient characteristics, such as history of significant comorbidities, radiation or active smoking, portend higher risk of complications with prepectoral reconstruction, in which case subpectoral implant placement may be a safer option. Oncologic consideration such as location and size of tumors also play an important role in determining the appropriate technique. The most critical factor in the success of prepectoral reconstruction is the quality of mastectomy flaps. Thorough intraoperative evaluation of mastectomy flap perfusion and viability will determine whether immediate prepectoral reconstruction is possible or other alternatives such as subpectoral or delayed prepectoral techniques should be considered. Discussing these factors with patients preemptively as well as developing a coordinated plan with the patient and oncologic surgeon will maximize success in both subpectoral and prepectoral implant-based reconstruction.

Dog bites have been well described and characterized in the pediatric population. Comparatively, dog-bite injuries in adults and the settings in which surgeons become involved are less studied. An electronic hospital database identified all patients 18 years or older who were treated for dog bites from 2010 to 2014. Demographics, injury information, intervention type, and payer source were collected. Socioeconomic analysis was performed using Geographic Information Systems mapping. A total of 189 adults presented to the emergency department with dog-bite-related injuries. The most common injury location was the hand (n = 62, 32.8%), followed by the head and neck (n = 36, 19.1%). Of the 189 patients, 33 adults (17.5%) were forwarded to a surgical subspecialist for repair. A head and neck injury was significantly more likely to be repaired by a surgical specialist (P = 0.011). The most common breed of dog identified was pit bull (n = 29, 47.5%). The majority of pit bull attacks involved the extremities (65.5%) compared to other breeds of dogs. Pit bull victims were noted to have a lower average annual income compared to other breed victims ($64,708 versus $75,004; P = 0.16). Annual income between intervention group and no intervention group was not significantly different (P = 0.26). This study is the 1st to perform a socioeconomic analysis in the adult dog-bite population and encourages the use of a surgical specialist in the setting of a head and neck bite.

BACKGROUND:Posterior vault distraction (PVD) can rapidly expand calvarial volume in infancy. Limited data exist regarding its perioperative and postoperative safety profile. This study sought to investigate the patient profile, outcomes, and safety of PVD using a national pediatric database. METHODS:Posterior vault distraction patients between 2012 and 2016 were isolated from the National Surgical Quality Improvement Program Pediatric database. Patient background, perioperative outcomes, and risk factors were analyzed using chi-squared, t test analysis, and multivariate regression. RESULTS:Ninety-four patients who underwent PVD were isolated with 67 ultimately meeting inclusion criteria for the study. The majority of patients undergoing PVD had limited other documented comorbidities. No patients required reoperation or 30-day readmission. There were no incidences of stroke, surgical site infection, or death. Subdividing outcomes by specialty, plastic surgeons performed PVD on significantly older patients than neurosurgeons (188 days vs 138 days, P = 0.008). Increasing age was associated with increasing operative time (P < 0.001). Furthermore, increasing age is associated with greater absolute transfusion requirements (P = 0.018) and higher, but not significant, risk of requiring any volume of blood transfusion (P = 0.105). CONCLUSIONS:Posterior vault distraction is a safe procedure to rapidly expand calvarial volume in the setting of craniosynostosis. Increasing patient age is the strongest predictor for prolonged operative time and higher blood transfusion volumes.

BACKGROUND:mAb114 is a single monoclonal antibody that targets the receptor-binding domain of Ebola virus glycoprotein, which prevents mortality in rhesus macaques treated after lethal challenge with Zaire ebolavirus. Here we present expedited data from VRC 608, a phase 1 study to evaluate mAb114 safety, tolerability, pharmacokinetics, and immunogenicity. METHODS:In this phase 1, dose-escalation study (VRC 608), conducted at the US National Institutes of Health (NIH) Clinical Center (Bethesda, MD, USA), healthy adults aged 18-60 years were sequentially enrolled into three mAb114 dose groups of 5 mg/kg, 25 mg/kg, and 50 mg/kg. The drug was given to participants intravenously over 30 min, and participants were followed for 24 weeks. Participants were only enrolled into increased dosing groups after interim safety assessments. Our primary endpoints were safety and tolerability, with pharmacokinetic and anti-drug antibody assessments as secondary endpoints. We assessed safety and tolerability in all participants who received study drug by monitoring clinical laboratory data and self-report and direct clinician assessment of prespecified infusion-site symptoms 3 days after infusion and systemic symptoms 7 days after infusion. Unsolicited adverse events were recorded for 28 days. Pharmacokinetic and anti-drug antibody assessments were completed in participants with at least 56 days of data. This trial is registered with ClinicalTrials.gov, number NCT03478891, and is active but no longer recruiting. FINDINGS/RESULTS:Between May 16, and Sept 27, 2018, 19 eligible individuals were enrolled. One (5%) participant was not infused because intravenous access was not adequate. Of 18 (95%) remaining participants, three (17%) were assigned to the 5 mg/kg group, five (28%) to the 25 mg/kg group, and ten (55%) to the 50 mg/kg group, each of whom received a single infusion of mAb114 at their assigned dose. All infusions were well tolerated and completed over 30-37 min with no infusion reactions or rate adjustments. All participants who received the study drug completed the safety assessment of local and systemic reactogenicity. No participants reported infusion-site symptoms. Systemic symptoms were all mild and present only in four (22%) of 18 participants across all dosing groups. No unsolicited adverse events occurred related to mAb114 and one serious adverse event occurred that was unrelated to mAb114. mAb114 has linear pharmacokinetics and a half-life of 24·2 days (standard error of measurement 0·2) with no evidence of anti-drug antibody development. INTERPRETATION/CONCLUSIONS:mAb114 was well tolerated, showed linear pharmacokinetics, and was easily and rapidly infused, making it an attractive and deployable option for treatment in outbreak settings. FUNDING/BACKGROUND:Vaccine Research Center, US National Institute of Allergy and Infectious Diseases, and NIH.

Traumatic optic neuropathy (TON) is rare. The heterogeneity of injury patterns and patient condition on presentation makes diagnosis difficult. Fracture patterns associated with TON have never been evaluated. Retrospective review of 42 patients diagnosed with TON at the R. Adams Cowley Shock Trauma Center from May 1998 to August 2010 was performed. Thirty-three patients met criteria for study inclusion of fracture patterns. Additional variables measured included patient demographics and mechanism. Cluster analysis was used to form homogenous groups of patients based on different fracture patterns. Fracture frequency was analyzed by group and study population. Visual depiction of fracture patterns was created for each group. Cluster analysis of fracture patterns yielded five common "groups" or fracture patterns among the study population. Group 1 ( n  = 3, 9%) revealed contralateral lateral orbital wall (100%), zygoma (67%), and nasal bone (67%) fractures. Group 2 ( n  = 7, 21%) demonstrated fractures of the frontal bone (86%), nasal bones (71%), and ipsilateral orbital roof (57%). Group 3 ( n  = 14, 43%) involved fractures of the ipsilateral zygoma (100%), lateral orbital wall (29%), as well as frontal and nasal bones (21% each). Group 4 ( n  = 5, 15%) consisted of mid- and upper-face fractures; 100% fractured the ipsilateral orbital floor, medial and lateral walls, maxilla, and zygoma; 80% fractured the orbital roof and bilateral zygoma. Group 5 ( n  = 4, 12%) was characterized by fractures of the ipsilateral orbital floor, medial and lateral orbital walls (75% each), and orbital roof (50%). A notably high 15 of 33 patients (45%) sustained penetrating trauma. Our study demonstrates five fracture pattern groups associated with TON. Zygomatic, frontal, nasal, and orbital fractures were the most common. Fractures with a combination of frontal, nasal, and orbital fractures are particularly concerning and warrant close attention to the eye.