Carolyn Chuang

Two locus inheritance of non-syndromic midline craniosynostosis via rare SMAD6 and common BMP2 alleles

Premature fusion of the cranial sutures (craniosynostosis), affecting 1 in 2000 newborns, is treated surgically in infancy to prevent adverse neurologic outcomes. To identify mutations contributing to common non-syndromic midline (sagittal and metopic) craniosynostosis, we performed exome sequencing of 132 parent-offspring trios and 59 additional probands. Thirteen probands (7%) had damaging de novo or rare transmitted mutations in SMAD6, an inhibitor of BMP – induced osteoblast differentiation (p<10−20). SMAD6 mutations nonetheless showed striking incomplete penetrance (<60%). Genotypes of a common variant near BMP2 that is strongly associated with midline craniosynostosis explained nearly all the phenotypic variation in these kindreds, with highly significant evidence of genetic interaction between these loci via both association and analysis of linkage. This epistatic interaction of rare and common variants defines the most frequent cause of midline craniosynostosis and has implications for the genetic basis of other diseases. DOI: http://dx.doi.org/10.7554/eLife.20125.001

The Hand Surgeon Consultation Improves Patient Knowledge in a Hand Surgery Mission to Honduras

BACKGROUND The purpose of this study was to assess impact of the surgeon consultation and informed consent process on patient education in an international hand surgery mission compared with a US academic hand surgery practice. These two groups were selected to evaluate communication difficulties in a surgical mission setting compared with standard of care in a high-income country. METHODS A multi-part survey was administered to patients presenting to a hand surgery mission during March 2012 and new patients of a university hand center in a 3-month period during 2011. Surveys were administered prior to and following surgeon consultation with one fellowship-trained hand surgeon. The survey assessed knowledge of basic hand anatomy, physiology, disease, individual diagnosis, and surgical risks. RESULTS 71 patients participated in the study (university n=36, mission n=35). Pre-consultation quiz score averaged 58% in the university group versus 27% in the mission group. Post-consultation quiz scores averaged 62% in the university group versus 40% in the mission group. Only the mission groups quiz score increase was statistically significant. 93% of the university group reported learning about their condition and diagnosis, but only 40% demonstrated correct insight into their diagnosis. In the mission group, 73% reported learning about their condition and diagnosis while 53% demonstrated correct insight into their diagnosis. Although all consultations involved discussion of surgical risks, only 62% of the university group and 52% of the mission group recalled discussing surgical risks. CONCLUSIONS The hand surgeon consultation was more effective in improving hand knowledge in the surgery mission group compared to in a university hand practice. This suggests that the surgeon consultation should be pursued despite communication barriers in surgical missions. However, the discrepancy between patient perception of knowledge gains and correct insight into diagnosis, and the deficit of patient retention of surgical risks need to be improved.

The Etiology of Neuronal Development in Craniosynostosis: A Working Hypothesis

Craniosynostosis is one of the most common craniofacial conditions treated by neurologic and plastic surgeons. In addition to disfigurement, children with craniosynostosis experience significant cognitive dysfunction later in life. Surgery is performed in infancy to correct skull deformity; however, the field is at a crossroads regarding the best approach for correction. Since the cause of brain dysfunction in these patients has remained uncertain, the role and type of surgery might have in attenuating the later-observed cognitive deficits through impact on the brain has been unclear. Recently, however, advances in imaging such as event-related potentials, diffusion tensor imaging, and functional MRI, in conjunction with more robust clinical studies, are providing important insight into the potential etiologies of brain dysfunction in syndromic and nonsyndromic craniosynostosis patients. This review aims to outline the cause(s) of such brain dysfunction including the role extrinsic vault constriction might have on brain development and the current evidence for an intrinsic modular developmental error in brain development. Illuminating the cause of brain dysfunction will identify the role of surgery can play in improving observed functional deficits and thus direct optimal primary and adjuvant treatment.

Abstract 64: Deterioration of Sensory Perception or Friction & Shear in Low Risk Braden Scores is Associated with Accelerated Development of Hospital Acquired Pressure Ulcers

PURPOSE: The Braden Scale is a risk stratification tool currently used by nurses to identify patients at risk of developing hospital acquired pressure ulcers (HAPUs). The tool operates on a 23-point system comprised of 6 components (Sensory Perception, Moisture, Activity, Mobility, Nutrition, Friction & Shear) where a threshold value of 18 distinguishes those with “low risk” (19–23 points) from those considered “high risk” (≤18 points). A Braden score is calculated on day of admission and updated throughout the hospital stay. Only patients deemed “high risk” are placed under special nursing protocols aimed at preventing pressure ulcer formation. Using linear regressions analysis, this study sought to better understand factors affecting the timing of HAPU development between high and low risk patients.

Abstract: Direct Brain Recordings in Craniosynostosis Can Predict Future Language Development

BACKGROUND: The mid-tibia region is a challenging reconstructive region given the paucity of soft tissue options and local muscle flaps available for reconstruction. A free-tissue transfer may not be an option in all cases due to patient comorbid conditions, personal preferences or operative resources availability. An extended medial gastrocnemius rotational flap may provide a safe, versatile and effective treatment option in the mid tibia region.

Functional and Quality of Life Outcomes of a Hand Surgery Mission to Honduras

Background: The objective of this study was to assess functional, quality of life, and satisfaction outcomes of a hand surgery short-term surgical mission (STSM) to Honduras, and determine whether patient demographics and surgery characteristics during a surgical mission correlate with outcome. Methods: A total of 63 patients who received upper extremity surgery at a week-long hand surgery STSM to Honduras in March 2013 participated in the study. A before-after study design was used. Before receiving surgery, participants completed the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire and the Short Form 12 Health Survey version 2 (SF12v2). Four months postoperatively, participants completed the QuickDASH, SF12v2, and Satisfaction Survey. Results: The mean QuickDASH score significantly improved preoperatively to postoperatively. Demographics measures of age, sex, education, and income did not correlate with QuickDASH scores. Preoperative QuickDASH statistically significantly correlated with surgery type: Carpal tunnel patients had the highest scores (worst functioning). Postoperatively, mass excision and scar contracture/skin graft patients were correlated with the lowest scores. Carpal tunnel and tendon surgery patients showed greatest correlation with QuickDASH improvement. SF-12 scores revealed improvements in mental domains and declines in physical domains. Conclusions: Hand surgery performed during STSMs can result in significant functional improvement, regardless of socioeconomic status. Patients benefited from both simpler and more complex operations. Four months after surgery, general health-related quality of life measures showed improved mental indices. Measured physical indices declined despite improved QuickDASH scores. This may be due to the early general postoperative state. Further outcome research in STSMs in additional countries and specialties is required to expand our conclusions to other STSM contexts and guide best practices in STSMs.

Abstract: Altered Brain Functional Connectivity Varies By Form of Craniosynostosis

Suday, O cber 8, 2017 INTRODUCTION: Explantation after prosthetic breast reconstruction may be performed due to various reasons including postoperative complications and patient request. The goals of this study were (1) to characterize a cohort of patients with device explantation after prosthetic breast reconstruction, (2) to perform a time based analysis of explantation, (3) to identify reasons for premature explantation, and (4) to review the bacteriology associated with explanted devices.

Abstract 121: Whole-Brain Intrinsic Connectivity in Nonsyndromic Craniosynostosis

PURPOSE: Nonsyndromic craniosynostosis (NSC) has been associated with a greater risk of neurocognitive aberrations such as learning disorders, memory and attention deficits, and visuospatial abilities. Previously, our group has performed resting-state functional MRI (fMRI) studies in patients with sagittal NSC (SSO), and has found altered functional connectivity that may underlie some of the neurocognitive deficits in these patients. This study seeks to determine if different forms of NSC, including metopic synostosis (MSO) and unilateral coronal synostosis (UCS), result in different aberrations of functional brain connectivity.

Abstract 24: Two Locus Inheritance of Non-Syndromic Midline Craniosynostosis Via Rare SMAD6 and Common BMP2 Alleles

PURPOSE: More than 30,000 people receive organ transplants every year in the US. Vascularized composite allotransplantation (VCA) is the newest realm of solid organ transplantation. The skin component of VCA is highly antigenic and mandates high doses of systemic immunosuppressive drugs. Oral dosing of immunosuppressive drugs such as tacrolimus (TAC), rapamycin (Rapa), and mycophenolic acid (MPA) leads to fluctuating, erratic, or unpredictable blood levels risking toxicity or lack of efficacy. We propose a drug delivery platform that can not only provide sustained drug release but also on-cue triggered drug release upon ultrasound stimulation (USS) in graft tissues with stable, low blood levels, minimizing overall drug exposure and facilitating long-term VCA survival with no systemic complications.