Faculty Bibliography

Craniofacial microsomia (CFM) is the second most common congenital facial anomaly, yet its genetic etiology remains unknown. We perform whole-exome or genome sequencing of 146 kindreds with sporadic (n = 138) or familial (n = 8) CFM, identifying a highly significant burden of loss of function variants in SF3B2 (P = 3.8 × 10^-10), a component of the U2 small nuclear ribonucleoprotein complex, in probands. We describe twenty individuals from seven kindreds harboring de novo or transmitted haploinsufficient variants in SF3B2. Probands display mandibular hypoplasia, microtia, facial and preauricular tags, epibulbar dermoids, lateral oral clefts in addition to skeletal and cardiac abnormalities. Targeted morpholino knockdown of SF3B2 in Xenopus results in disruption of cranial neural crest precursor formation and subsequent craniofacial cartilage defects, supporting a link between spliceosome mutations and impaired neural crest development in congenital craniofacial disease. The results establish haploinsufficient variants in SF3B2 as the most prevalent genetic cause of CFM, explaining ~3% of sporadic and ~25% of familial cases.

BACKGROUND:The effect of body mass index (BMI) on complication rates in prepectoral implant-based breast reconstruction is not well established. The purpose of this study was to compare complication rates between different BMI groups in subpectoral and prepectoral reconstruction. METHODS:A single-surgeon, 4-year, retrospective review was performed of consecutive prosthetic breast reconstructions. During this time, the senior author's practice shifted from a subpectoral to prepectoral technique. Patients were stratified into BMI subgroups (<25, 25-35, and >35 kg/m2) and complication rates were analyzed. A survey was administered to blinded medical personnel and patients comparing esthetic results. RESULTS:Implant-based reconstructions were performed in 195 patients (103 subpectoral and 92 prepectoral). No significant difference in major complication rate was observed between techniques. Among patients with BMI greater than 35 kg/m2, implant exposure occurred at a significantly higher rate in the prepectoral group (P = 0.04). In patients with BMI greater than 25 kg/m2, minor asymmetry was more prevalent with prepectoral reconstruction (12.3% vs 0%; P = 0.02). Regardless of technique, the odds of reoperation increased by 7% per point increase in BMI, although this did not reach statistical significance (P = 0.07; odds ratio, 1.07; 95% confidence interval, 0.99-1.15).A total of 66 survey responses were received. Physicians rated esthetic results more positively than patients did. Patients with a BMI of less than 25 kg/m2 were rated better than other BMI groups in nearly all categories. The position of submuscular reconstruction was rated significantly better than prepectoral. CONCLUSIONS:There is a trend toward higher complication rates in prepectoral versus subpectoral breast reconstruction with increasing BMI. Nonetheless, the technique appears to be safe, with comparable clinical and cosmetic results.

INTRODUCTION:We analyzed the perceptions of participants and faculty members in simulation-based comprehensive cleft care workshops regarding comprehensive cleft care delivery in developing countries. METHODS:Data were collected from participants and faculty members in 2 simulation-based comprehensive cleft care workshops organized by Global Smile Foundation. We collected demographic data and surveyed what they believed was the most significant barrier to comprehensive cleft care delivery and the most important intervention to deliver comprehensive cleft care in developing countries. We also compared participant and faculty responses. RESULTS:The total number of participants and faculty members was 313 from 44 countries. The response rate was 57.8%. The majority reported that the most significant barrier facing the delivery of comprehensive cleft care in developing countries was financial (35.0%), followed by the absence of multidisciplinary cleft teams (30.8%). The majority reported that the most important intervention to deliver comprehensive cleft care was creating multidisciplinary cleft teams (32.2%), followed by providing cleft training (22.6%). We found no significant differences in what participants and faculty perceived as the greatest barrier to comprehensive cleft care delivery (P = 0.46), or most important intervention to deliver comprehensive cleft care in developing countries (P = 0.38). CONCLUSIONS:Our study provides an appraisal of barriers facing comprehensive cleft care delivery and interventions required to overcome these barriers in developing countries. Future studies will be critical to validate or refute our findings, as well as determine country-specific roadmaps for delivering comprehensive cleft care to those who need it the most.

BACKGROUND:Given the current national conundrum of decreasing microsurgery case volume performed by hand surgery fellows despite interest, program directors were surveyed to evaluate opinions of exposure gaps in training and to determine the current state of microsurgery training in 2020. METHODS:Anonymous national surveys were distributed to hand surgery fellowship program directors by the American Society for Surgery of the Hand. Subgroups were compared by training location and size of the fellowship program. Accreditation Council for Graduate Medical Education public national data on graduate case log procedures by hand surgery fellows were reviewed. RESULTS:Eighty-eight surveys were distributed by the American Society for Surgery of the Hand to hand surgery fellowship program directors with a 44% (n = 39) response rate. Hand surgery fellowship programs from 19 US states participated. Most program's fellows had previous orthopedic surgery residency training with 41.03% of programs surveyed having 100% orthopedic surgery-trained fellows. The average number of weekly vascular microsurgical cases ranged from 25% of fellowships having no microsurgery cases per week, 46.2% having 1 per week, and only 7.7% having 5 or more cases per week. However, 60.5% of program directors prioritized a microvascular surgery case as the most valuable educational opportunity for fellows. Most program directors agreed (79.5%) that a 1-year hand surgery fellowship is sufficient to train a competent hand surgeon, who is proficient in microsurgery. In contrast, the majority disagreed (53.8%) that hand surgery microsurgery skills after a 1-year hand surgery fellowship are equivalent among graduates, regardless of a prior plastic surgery or orthopedic surgery residency training. There was a statistically significant difference in program directors' responses by geographic location regarding prior residency background impacting microsurgical skills (Kendall Ï„, -0.439; P = 0.001). Graduate case log data revealed an increasing trend in the number of microsurgery procedures performed by orthopedic hand surgery fellows until 2014, with a decline in cases per year and stagnating trend at 7% thereafter. CONCLUSIONS:In 2020, most hand surgery fellowship program directors highly value and prioritize microsurgery exposure for their hand surgery fellows' education despite the decrease in case volume for hand surgery fellows.

ABSTRACT/UNASSIGNED:Migraine affects ∼15% of the world's population greatly diminishing their quality of life. Current preventative treatments are effective in only a subset of migraine patients, and while cannabinoids appear beneficial in alleviating migraine symptoms, central nervous system (CNS) side effects limit their widespread use. We developed peripherally-restricted cannabinoids (PRCBs) that relieve chronic pain symptoms of cancer and neuropathies, without appreciable CNS side effects or tolerance development. Here we determined PRCB effectiveness in alleviating hypersensitivity symptoms in mouse models of migraine and medication overuse headache (MOH). Chronic glyceryl trinitrate (GTN, 10 mg/kg) administration led to increased sensitivity to mechanical stimuli, and increased expression of phosphorylated protein kinase A (p-PKA), neuronal nitric oxide synthase (nNOS), and transient receptor potential ankyrin 1 (TRPA1) proteins in trigeminal ganglia. PRCB pretreatment, but not posttreatment, prevented behavioral and biochemical correlates of GTN-induced sensitization. Low pH- and allyl isothiocyanate-activated currents in acutely isolated trigeminal neurons were reversibly attenuated by PRCB application. Chronic GTN treatment significantly enhanced these currents. Chronic sumatriptan treatment also led to development of allodynia to mechanical and cold stimuli which was slowly reversible after sumatriptan discontinuation. Subsequent challenge with a previously ineffective low-dose GTN (0.1-0.3 mg/kg) revealed latent behavioral sensitization and increased expression of p-PKA, nNOS, and TRPA1 proteins in trigeminal ganglia. PRCB pretreatment prevented all behavioral and biochemical correlates of allodynia and latent sensitization. Importantly, chronic PRCB treatment alone did not produce any behavioral or biochemical signs of sensitization. These data validate peripheral cannabinoid receptors as potential therapeutic targets in migraine and MOH.

SUMMARY/CONCLUSIONS:This video reviews the technique of a vascularized fibula flap for pediatric tibia reconstruction. A 4-year-old boy with a history of a left tibial infected nonunion status after multiple debridements presented with segmental bone loss and difficulty with ambulation. An ipsilateral vascularized fibula flap was used for reconstruction. The patient proceeded to union and was independently ambulatory with bracing.