Faculty Bibliography

Background  Length of immobilization after operative fixation of unstable distal radius fractures and management in elderly patients is an area of debate. Purpose  The purpose of this study is to delineate common practices of fellowship-trained hand surgeons and how they compare with current evidence-based protocols. Methods  Surveys were distributed to American Society for Surgery of the Hand members on preferred methods of fixation, postoperative immobilization, and variations in treatment of elderly patients with unstable distal radius fractures. Responses were analyzed in comparison to a literature review. Subgroups were compared with regard to training, practice type, and years in practice. Results  Four-hundred eighty-five surveys were analyzed. Volar fixed-angle plating was the most common choice of fixation (84.7%). Patients are most often immobilized for 1 to 2 weeks (40.0%) with range of motion (ROM) therapy begun most commonly between 1 and 4 weeks (47.2%). The majority of surgeons do not treat fractures differently in patients more than 65 years old. Physicians with more than 20 years of experience were significantly more likely to begin wrist ROM sooner with volar plating versus other fixation techniques compared with physicians with less than 20 years of experience (40.7% vs. 34.2%, respectively). Also, physicians in academic-only practices were more likely to immobilize patients for a shorter time after volar plating compared with those in privademics. Conclusion  Volar fixed-angle plating is the dominant fixation method for unstable distal radius fractures among fellowship-trained hand surgeons. Elderly patients are not treated more conservatively and rigid immobilization after operative fixation remains the treatment of choice despite current evidence-based protocols.

Craniosynostosis (CS) is a frequent congenital anomaly featuring the premature fusion of 1 or more sutures of the cranial vault. Syndromic cases, featuring additional congenital anomalies, make up 15% of CS. While many genes underlying syndromic CS have been identified, the cause of many syndromic cases remains unknown. We performed exome sequencing of 12 syndromic CS cases and their parents, in whom previous genetic evaluations were unrevealing. Damaging de novo or transmitted loss of function (LOF) mutations were found in 8 genes that are highly intolerant to LOF mutation (P = 4.0 × 10^-8); additionally, a rare damaging mutation in SOX11, which has a lower level of intolerance, was identified. Four probands had rare damaging mutations (2 de novo) in TFAP2B, a transcription factor that orchestrates neural crest cell migration and differentiation; this mutation burden is highly significant (P = 8.2 × 10^-12). Three probands had rare damaging mutations in GLI2, SOX11, or GPC4, which function in the Hedgehog, BMP, and Wnt signaling pathways; other genes in these pathways have previously been implicated in syndromic CS. Similarly, damaging de novo mutations were identified in genes encoding the chromatin modifier KAT6A, and CTNNA1, encoding catenin α-1. These findings establish TFAP2B as a CS gene, have implications for assessing risk to subsequent children in these families, and provide evidence implicating other genes in syndromic CS. This high yield indicates the value of performing exome sequencing of syndromic CS patients when sequencing of known disease loci is unrevealing.

Objective: The purpose of this study was to assess the association between extent of brachial plexus injury and shoulder abduction/external rotation outcomes after spinal accessory nerve (SAN) to suprascapular nerve (SSN) transfer. Methods: A systematic review of the literature was conducted according to PRISMA guidelines. Inclusion criteria were studies reporting outcomes on patients undergoing SAN to SSN nerve transfer. Patients were excluded for the following reasons: age under 18, nerve transfer for reanimation of the shoulder other than SAN to SSN, and less than 12 months of follow-up postoperatively. Pooled analysis was performed, and primary outcomes were Medical Research Council (MRC) score and range of motion (ROM) for shoulder abduction and external rotation. Univariate logistic regression analysis was used to assess the association between extent of brachial plexus injury and shoulder abduction/external rotation outcomes after SAN to SSN transfer. A multivariate logistic regression analysis model including age, injury to surgery interval, and extent of injury as factors was also created. Results: Univariate logistic regression analysis showed greater extent of injury to be a predictor of poorer shoulder abduction outcomes (OR: 0.502; 95% CI: 0.260-0.971, p = 0.040). Multivariate logistic regression analysis confirmed this association (OR: 0.55; 95% CI: 0.236-0.877, p = 0.019). Extent of injury was not significantly associated with external rotation outcomes on univariate analysis (OR: 0.435; 95% CI: 0.095-1.995, p = 0.284) or multivariate analysis (OR: 0.445; 95% CI: 0.097-2.046, p = 0.298). Age and injury to surgery interval were not significantly associated with postoperative outcomes. Conclusions: More extensive brachial plexus injuries are associated with inferior outcomes after SAN to SSN transfer. A potential explanation for this finding includes lost contribution of muscles from the shoulder girdle that receive innervation from outside of the upper brachial plexus. The relationship between extent of injury and postoperative outcomes is important to recognize when determining and discussing operative intervention with patients.

INTRODUCTION/BACKGROUND:Cleft palate is among the most common birth abnormalities. The success of primary surgery in the early months of life is crucial for successful feeding, speech, hearing, dental development and facial growth. Over recent decades, age at palatal surgery in infancy has reduced. This has led to palatal closure in one-stage procedures being carried out around the age of 12 months, but in some cases as early as 6 months. The primary objective of the Timing Of Primary Surgery for Cleft Palate (TOPS)trial is to determine whether surgery for cleft palate performed at 6 or 12 months of age is most beneficial for speech outcomes. METHODS AND ANALYSIS/UNASSIGNED:Infants with a diagnosis of non-syndromic isolated cleft palate will be randomised to receive standardised primary surgery (Sommerlad technique) for closure of the cleft at either 6 months or 12 months, corrected for gestational age. The primary outcome will be perceived insufficient velopharyngeal function at 5 years of age. Secondary outcomes measured across 12 months, 3 years and 5 years will include growth, safety of the procedure, dentofacial development, speech, hearing level and middle ear function. Video and audio recordings of speech will be collected in a standardised age-appropriate manner and analysed independently by multiple speech and language therapists. The trial aims to recruit and follow-up 300 participants per arm. Data will be analysed according to the intention-to-treat principle using a 5% significance level. All analyses will be prespecified within a full and detailed statistical analysis plan. ETHICS AND DISSEMINATION/UNASSIGNED:Ethical approval has been sought in each participating country according to country-specific procedures. Trial results will be presented at conferences, published in peer-reviewed journals and disseminated through relevant patient support groups. TRIAL REGISTRATION NUMBER/BACKGROUND:NCT00993551; Pre-results.

Proteases sustain hyperexcitability and pain by cleaving protease-activated receptor-2 (PAR₂) on nociceptors through distinct mechanisms. Whereas trypsin induces PAR₂ coupling to Gα_q, Gα_s, and β-arrestins, cathepsin-S (CS) and neutrophil elastase (NE) cleave PAR₂ at distinct sites and activate it by biased mechanisms that induce coupling to Gα_s, but not to Gα_q or β-arrestins. Because proteases activate PAR₂ by irreversible cleavage, and activated PAR₂ is degraded in lysosomes, sustained extracellular protease-mediated signaling requires mobilization of intact PAR₂ from the Golgi apparatus or de novo synthesis of new receptors by incompletely understood mechanisms. We found here that trypsin, CS, and NE stimulate PAR₂-dependent activation of protein kinase D (PKD) in the Golgi of HEK293 cells, in which PKD regulates protein trafficking. The proteases stimulated translocation of the PKD activator Gβγ to the Golgi, coinciding with PAR₂ mobilization from the Golgi. Proteases also induced translocation of a photoconverted PAR₂-Kaede fusion protein from the Golgi to the plasma membrane of KNRK cells. After incubation of HEK293 cells and dorsal root ganglia neurons with CS, NE, or trypsin, PAR₂ responsiveness initially declined, consistent with PAR₂ cleavage and desensitization, and then gradually recovered. Inhibitors of PKD, Gβγ, and protein translation inhibited recovery of PAR₂ responsiveness. PKD and Gβγ inhibitors also attenuated protease-evoked mechanical allodynia in mice. We conclude that proteases that activate PAR₂ by canonical and biased mechanisms stimulate PKD in the Golgi; PAR₂ mobilization and de novo synthesis repopulate the cell surface with intact receptors and sustain nociceptive signaling by extracellular proteases.

INTRODUCTION/BACKGROUND:Ongoing combat operations in Iraq, Afghanistan, and other theaters have led to an increase in high energy craniomaxillofacial (CMF) wounds. These challenging injuries are typically associated with complex tissue deficiencies, evolving areas of necrosis, and bony comminution with bone and ballistic fragment sequestrum. Restoring form and function in these combat-sustained CMF injuries is challenging, and frequently requires local and distant tissue transfers. War injuries are different than the isolated trauma seen in the civilian sector. Donor sites are limited on patients with blast injuries and they may have preferences or functional reasons for the decisions to choose flaps from the available donor sites. METHODS:A case series of patients who sustained severe combat-related CMF injury and were treated at Walter Reed National Military Medical Center (WRNMMC) is presented. Our study was exempt from Institutional Review Board review, and appropriate written consent was obtained from all patients included in the study for the use of representative clinical images. RESULTS:Four patients treated by the CMF team at Walter Reed National Military Medical Center are presented. In this study, we highlight their surgical management by the CMF team at WRNMMC, detail their postoperative course, and illustrate the outcomes achieved using representative patient clinical images. We also supplement this case series demonstrating military approaches to complex CMF injuries with CMF reconstructive algorithms utilized by the senior author (EDR) in the management of civilian complex avulsive injuries of the upper, mid, and lower face are thoroughly reviewed. CONCLUSION/CONCLUSIONS:While the epidemiology and characteristics of military CMF injuries have been well described, their management remains poorly defined and creates an opportunity for reconstructive principles proven in the civilian sector to be applied in the care of severely wounded service members. The War on Terror marks the first time that microsurgery has been used extensively to reconstruct combat sustained wounds of the CMF region. Our manuscript reviews various options to reconstruct these devastating CMF injuries and emphasizes the need for steady communication between the civilian and military surgical communities to establish the best care for these complex patients.

INTRODUCTION/BACKGROUND:Cleft palate repair has rare, but potentially life-threatening risks. Understanding the risk factors for adverse events following cleft palate repair can guide surgeons in risk stratification and parental counseling. METHODS:Patients under 2 years of age in National Surgical Quality Improvement Project Pediatric Database (NSQIP-P) from 2012 to 2016 who underwent primary cleft palate repair were identified. Risk factors for adverse events after cleft palate repair were identified. RESULTS:Outcomes for 4989 patients were reviewed. Mean age was 1.0 ± 0.3 years and 53.5% were males. Adverse events occurred in 6.4% (320) of patients. The wound dehiscence rate was 3.1%, and the reoperation rate was 0.9%.On multivariate analysis, perioperative blood transfusion (adjusted odds ratio [aOR] 30.2), bronchopulmonary dysplasia/chronic lung disease (aOR 2.2), and prolonged length of stay (LOS) (aOR 1.1) were significantly associated with an adverse event.When subdivided by type of adverse event, reoperation was associated with perioperative blood transfusion (aOR 286.5), cerebral palsy (aOR 11.3), and prolonged LOS (aOR 1.1). Thirty-day readmission was associated with American Society of Anesthesiologists Physical Status Classification class III (aOR 2.0) and IV (aOR 4.8), bronchopulmonary dysplasia/chronic lung disease (aOR 2.5), cerebral palsy (aOR 5.7), and prolonged LOS (aOR 1.1). Finally, wound dehiscence was significantly associated with perioperative blood transfusion only (aOR 8.2). CONCLUSIONS:Although adverse events following cleft palate surgery are rare, systemic disease remains the greatest predictor for readmission and reoperation. Neurologic and pulmonary diseases are the greatest systemic risk factors. Intraoperative adverse events requiring blood transfusion are the greatest surgical risk factor for post-surgical complications.

BACKGROUND: Delayed immediate (DI) autologous breast reconstruction consists of immediate postmastectomy tissue expander placement, radiation therapy, and subsequent autologous reconstruction. The decision between timing of reconstructive methods is challenging and remains to be elucidated. We aim to compare patient reported outcomes and quality of life between delayed and DI reconstruction. METHODS: A retrospective review of all patients, who underwent autologous breast reconstruction at Montefiore Medical Center from January 2009 to December 2016, was conducted. Patients who underwent postmastectomy radiotherapy were divided into two cohorts: delayed and DI autologous breast reconstruction. Patients were mailed a BREAST-Q survey and their responses, demographic information, complications, and need for revisionary procedures were analyzed. RESULTS: = 30) in the DI group. Responses showed similar satisfaction with their breasts, well-being, and overall outcome. CONCLUSIONS: Delayed and DI autologous breast reconstruction yield similar patient-reported satisfaction; however, patients undergoing DI reconstruction have higher rates of major mastectomy necrosis. Furthermore, patients in the DI group risk premature tissue expander removal.