γ-Secretase Modulator BPN15606 Reduced Aß42 and Aß40 and Countered Alzheimer-Related Pathologies in a Mouse Model of Down Syndrome.

OBJECTIVES: Due to increased gene dose for the amyloid precursor protein (APP), elderly adults with Down syndrome (DS) are at a markedly increased risk of Alzheimer's disease (AD), known as DS-AD. How the increased APP gene dose acts and which APP products are responsible for DS-AD is not well understood, thus limiting strategies to target pathogenesis. As one approach to address this question, we used a novel class of γ-secretase modulators that promote γ-site cleavages by the γ-secretase complex, resulting in lower levels of the Aß42 and Aß40 peptides. METHODS: Ts65Dn mice, which serve as a model of DS, were treated via oral gavage with 10 mg/kg/weekday of BPN15606 (a potent and novel pyridazine-containing γ-secretase modulators). Treatment started at 3 months-of-age and lasted for 4 months. RESULTS: Demonstrating successful target engagement, treatment with BPN15606 significantly decreased levels of Aß40 and Aß42 in the cortex and hippocampus; it had no effect on full-length APP or its C-terminal fragments in either 2 N or Ts65Dn mice. Importantly, the levels of total amyloid-ß were not impacted, pointing to BPN15606-mediated enhancement of processivity of γ-secretase. Additionally, BPN15606 rescued hyperactivation of Rab5, a protein responsible for regulating endosome function, and normalized neurotrophin signaling deficits. BPN15606 treatment also normalized the levels of synaptic proteins and tau phosphorylation, while reducing astrocytosis and microgliosis, and countering cognitive deficits. INTERPRETATION: Our findings point to the involvement of increased levels of Aß42 and/or Aß40 in contributing to several molecular and cognitive traits associated with DS-AD. They speak to increased dosage of the APP gene acting through heightened levels of Aß42 and/or Aß40 as supporting pathogenesis. These findings further the interest in the potential use of γ-secretase modulators for treating and possibly preventing AD in individuals with DS. ANN NEUROL 2024;96:390-404.

Correlation of Orthognathic Surgical Movements to Perception of Facial Appearance in Patients With Cleft Lip and Palate.

STUDY DESIGN: Cephalometric scans were compared before and after surgery to assess the degree of correction. Correlations between skeletal movements and survey outcomes were determined using multivariate regression analysis. OBJECTIVE: This study aims to identify relationships between subjective observer-reported improvements in esthetics and emotional appearance with specific surgical movements. METHODS: Ten patients at a single tertiary institution (average age: 18.1 ± 0.8), 9 males and 1 female, underwent orthognathic repair and had comprehensive cephalometric records. Standardized anterior posterior and lateral pre and postoperative photographs of patients were included in a survey to clinicians to assess noncognitive domains on a Likert Scale (1-10). CLEFT-Q was administered to gauge patient satisfaction in categories of appearance, speech, and quality of life. RESULTS: Per clinicians, multiple domains increased including facial attractiveness (4.1 ± 0.7 versus 7.3 ± 0.7, P < 0.001), friendliness (4.5 ± 0.4 versus 7.3 ± 0.5, P < 0.001), confidence (4.1 ± 0.4 versus 7.1 ± 0.4, P < 0.001), and recommendation for surgery decreased (8.9 ± 0.1 versus 3.6 ± 0.5, P < 0.001). Speech distress decreased with increased SNA and convexity, whereas Psychological and Social scores decreased with an increased ANB. Functional eating and drinking scores increased with maxillary depth. CONCLUSIONS: Orthognathic surgery improves many noncognitive domains in patients with cleft lip and palate as assessed by both patients and clinicians on all aspects of facial attractiveness and perception. These findings demonstrate objective bases of skeletal adjustments for perceived improvements in facial appearance and emotion.

Use it or Lose it: Predictors of Compliance and Satisfaction With Postoperative Nasal Stent Therapy After Primary Cleft Lip Repair.

OBJECTIVE: Postoperative nasal stents (NSs) are used to improve esthetic outcomes after primary or secondary cleft lip repair (CLR). Prior studies have utilized anthropometric measurements or physician assessment to determine the efficacy of NS, but data on caregiver-reported outcomes is limited. This study aims to assess caregiver compliance and satisfaction with postoperative NS. METHODS: The authors designed a survey to collect parent-reported postoperative NS usage outcomes. Parents of infants with cleft lip (CL) who used postoperative NS after primary CLR were approached through social media to complete the survey. Data were analyzed to determine factors impacting compliance, satisfaction, and parent-reported outcomes. RESULTS: Eighty-five parents completed the questionnaire, and 60% reported noncompliance with NS. Parents with male children (odds ratio: 5.08, P = 0.019) and patients with incomplete CL (odds ratio: 5.72, P = 0.006) were more likely to be non-compliant with NS for over a week. Complete CL and use of presurgical molding therapy were each associated with better overall experience with postoperative NS ( P = 0.002 and P = 0.037), higher appearance ratings ( P = 0.005 and P = 0.0008), and greater satisfaction with nostril shape after surgery ( P = 0.016 and P = 0.001). CONCLUSIONS: Despite limited literature related to caregiver-reported outcomes after postoperative NS for primary CLR, the authors' results align with what has been published regarding this topic. These results can help guide surgeons in counseling patients preoperatively. Larger, multi-institutional studies are needed to better delineate and address factors associated with compliance and satisfaction after NS therapy.

Implementation of Mandibular Distraction Osteogenesis for Patients With Pierre Robin Sequence in a Developing Country Through International Collaboration: A Paradigm for Success.

OBJECTIVE: Though it has made significant strides, Vietnam remains a resource-constrained country of 98 million people. Vietnam National Children's Hospital (VNCH) provides tertiary care to a catchment of 40 million people and is the sole national children's hospital. As such, it is one of the few referral centers in the country equipped to take care of patients diagnosed with Pierre Robin sequence (PRS) as this requires pulmonary, critical care, otolaryngology, and plastic surgery expertise. Before 2015, the only surgical options were tongue lip adhesion or tracheostomy. Only 20% of patients successfully avoided tracheostomy, mechanical ventilation, or death. From 2015 to 2019, mandibular distraction osteogenesis (MDO) was introduced by visiting international surgeons on a short-term basis. Since 2020, local surgeons at VNCH have refined their technique and widely use MDO independently. This report seeks to capitulate their experience and identify factors leading to success. METHODS: A retrospective review was conducted of patients diagnosed with PRS at VNCH from 2015 to 2022. Paper records were digitized, translated, and reviewed for inclusion criteria, including demographics, indications, hospital course, and postoperative outcomes. RESULTS: Complete records satisfying inclusion criteria were available for 53 patients with a diagnosis of PRS who underwent MDO from 2020 to 2022. From 2015 to 2019, there were 19 cases of MDO, though records were incomplete. The median age at the time of MDO was 50 ± 43 days. Forty patients (75.5%) had isolated PRS and 13 (24.5%) were syndromic. Forty-four patients (83%) had a cleft palate. Fifty-one (96.2%) of patients required preoperative supplemental oxygen or mechanical ventilation. The active distraction and consolidation phase was 4.8 ± 1.3 months. The median days to discharge after surgery was 19.0 ± 8.3 days. Median weight at birth, at the time of surgery, and at the time of device removal were 6.8 ± 1.2, 7.7 ± 1.9, and 14.8 ± 2.8 pounds, respectively. Fifty-two patients (98.1%) had obstructive sleep apnea preoperatively with an average Apnea Hypopnea Index of 25.0 ± 10.6. Post-MDO, only 4 (7.5%) had obstructive sleep apnea and the average Apnea Hypopnea Index was 5.2 ± 0.6. No patients (0) required a tracheostomy for a 100% success rate. CONCLUSIONS: The tremendous success of the implementation of MDO by local surgeons in Vietnam after its introduction by visiting international surgeons illustrates a paradigm for capacity-enhancing global surgical endeavors. Mandibular distraction osteogenesis has replaced tongue lip adhesion as the surgical treatment of choice for PRS patients at VNCH. Surgical techniques can be transferred to operating environments with basic infrastructure through collaboration and resource optimization. These results demonstrate that global surgical engagement may be scalable and repeatable with direct benefits for patients in lower-middle-income countries.

Artificial Intelligence Methods for the Argenta Classification of Deformational Plagiocephaly to Predict Severity and Treatment Recommendation.

INTRODUCTION: Deformational plagiocephaly (DP) can be classified into 5 severity types using the Argenta scale (AS). Patients with type III or higher require referral to craniofacial surgery for management. Primary care pediatricians (PCPs) are often the first to encounter patients with DP, but current screening methods are subjective, increasing the risk of bias, especially for clinicians with little exposure to this population. The authors propose the use of artificial intelligence (AI) to classify patients with DP using the AS and to make recommendations for referral to craniofacial surgery. METHODS: Vertex photographs were obtained for patients diagnosed with unilateral DP from 2019 to 2020. Using the photographs, an AI program was created to characterize the head contour of these infants into 3 groups based on the AS. The program was trained using photographs from patients whose DP severity was confirmed clinically by craniofacial surgeons. To assess the accuracy of the software, the AS predicted by the program was compared with the clinical diagnosis. RESULTS: Nineteen patients were assessed by the AI software. All 3 patients with type I DP were correctly classified by the program (100%). In addition, 4 patients with type II were correctly identified (67%), and 7 were correctly classified as type III or greater (70%). CONCLUSIONS: Using vertex photographs and AI, the authors were able to objectively classify patients with DP based on the AS. If converted into a smartphone application, the program could be helpful to PCPs in remote or low-resource settings, allowing them to objectively determine which patients require referral to craniofacial surgery.

Postoperative Radiologic Imaging in Secondary Alveolar Bone Grafting for Cleft Lip and Palate: A Systematic Review and Meta-Analysis.

INTRODUCTION: Radiographs (XRs), computed tomography (CT) scans, and cone-beam CT (CBCT) scans are utilized for assessment of secondary alveolar bone graft (SABG) in patients with cleft lip and palate (CLP). However, the optimal choice for imaging modality remains unclear. This study compares the image fidelity and safety profile for XR, CT, and CBCT in the assessment of patients with CLP who have undergone SABG. METHODS: Articles from MEDLINE and Elsevier Embase were screened. The primary outcome was graft success rate. Secondary outcomes were percent-by-volume of graft maintained and patient safety, defined by radiation exposure. A random effects model was used to calculate the pooled outcomes for each imaging modality. Chi-squared analysis was used to compare pooled outcomes between different imaging modalities. RESULTS: Of the 149 articles identified initially, 14 were included. Computed tomography exhibited a significantly higher image fidelity demonstrated by a lower graft success rate (62.0%) compared with both XR (72.6%, P<0.01) and CBCT (69.8%, P<0.01). Cone-beam CT had the lowest reported percent-by-volume of graft maintained (32.1%). Computed tomography had a higher mean radiation dosage (39.7 milligray) than what has been reported for both XR and CBCT. CONCLUSION: Computed tomography demonstrated lower graft success rates than both XR and CBCT, possibly indicating a higher image fidelity. However, compared with CBCT, CT may have a higher radiation exposure. Randomized trials and longitudinal studies are necessary to perform a direct comparison between CT and CBCT and to correlate the image fidelity of these modalities with clinical outcomes.

The Limit Is Zero: A Prospective Evaluation of Ketorolac in Patients Undergoing Primary Palatoplasty to Reduce Narcotic Utilization.

BACKGROUND: Patients undergoing primary palatoplasty rely on narcotics for pain control, but narcotics can lead to sedation and respiratory depression. Recent research into Enhanced Recovery After Surgery (ERAS) pathways utilizing multimodal pain therapy has yielded promising results for patients undergoing palatoplasty in terms of decreased hospital length of stay (LOS), increased oral intake, and decreased narcotic usage. Despite the potential benefit of ketorolac after palatoplasty, there is a paucity of data regarding its use. METHODS: A single-center cohort study of patients undergoing primary palatoplasty was performed using 2 cohorts: a retrospective cohort treated with our institution's prior ERAS protocol from 2016 to 2018 and a prospective group of patients who also received ketorolac (ERAS+K) postoperatively from 2020 to 2022. RESULTS: A total of 85 patients (57 ERAS and 28 ERAS+K) were included. Compared with the ERAS group, the ERAS+K cohort had significantly decreased LOS (31.8 versus 55 h, P =0.02), decreased morphine milligram equivalents administered at 24 hours (1.5 versus 2.5, P =0.003), 48 hours (0 versus 1.5, P <0.001), and total inpatient morphine milligram equivalents (1.9 versus 3.8, P =0.001). The ERAS+K group also had a significant decrease in the prescribed narcotic rate (32.1% versus 61.4%, P =0.006). No bleeding issues, blood transfusions, or reoperations were noted in either cohort. CONCLUSIONS: This study illustrates many potential benefits of using ketorolac as a pain management adjunct in combination with a multimodal pain regimen. Our results demonstrated favorable outcomes, including decreased narcotic usage and LOS as well as increased hourly oral intake, without increasing bleeding complications.

Can Craniosynostosis be Diagnosed on Physical Examination? A Retrospective Review.

Craniosynostosis is a developmental craniofacial defect in which one or more sutures of the skull fuse together prematurely. Uncorrected craniosynostosis may have serious complications including elevated intracranial pressure, developmental delay, and blindness. Proper diagnosis of craniosynostosis requires a physical examination of the head with assessment for symmetry and palpation of sutures for prominence. Often, if craniosynostosis is suspected, computed tomography (CT) imaging will be obtained. Recent literature has posited that this is unnecessary. This study aims to address whether physical examination alone is sufficient for the diagnosis and treatment planning of single suture craniosynostosis. Between 2015 and 2022, the Divisions of Pediatric Neurosurgery and Pediatric Plastic Surgery at UTHealth Houston evaluated 140 children under 36 months of age with suspected craniosynostosis by physical examination and subsequently ordered CT imaging for preoperative planning. Twenty-three patients received a clinical diagnosis of multi-sutural or syndromic craniosynostosis that was confirmed by CT. One hundred seventeen patients were diagnosed with single suture craniosynostosis on clinical examination and follow-up CT confirmed suture fusion in 109 (93.2%) patients and identified intracranial anomalies in 7 (6.0%) patients. These patients underwent surgical correction. Eight (6.8%) patients showed no evidence of craniosynostosis on CT imaging. Treatment for patients without fused sutures included molding helmets and observation alone. This evidence suggests that physical examination alone may be inadequate to accurately diagnose single suture synostosis, and surgery without preoperative CT evaluation could lead to unindicated procedures.

It's Hip to Go Home: An Evaluation of Outpatient Alveolar Bone Grafting in Patients With Cleft Palate.

INTRODUCTION: Secondary alveolar bone grafting (ABG) is a common procedure performed at cleft care centers used to fill the alveolar cleft. The advent of techniques such as minimally invasive trephine drill harvest and placement of continuous-infusion pain pumps at the donor site has made outpatient ABG an increasingly feasible and cost-effective procedure. However, enhanced recovery after surgery protocols to maximize pain control and recovery times for this patient population have not been well established. METHODS: A retrospective single-institution review was conducted of pediatric patients with cleft palate who underwent iliac crest bone graft ABG at a large urban academic children's hospital from 2017 to 2022. Patient age, alveolar cleft repair laterality, pain scores, surgery duration, hospital LOS, readmissions, and re-operations within 30 days were examined. RESULTS: Fifty-four patients met our inclusion criteria. Fifty patients (92.6%) received a pain pump during the operation. The median duration of surgery and LOS in the post-anesthesia care unit were 1.28 and 1.75 hours, respectively. Fifty-two patients (96.3%) were discharged on the same day as their surgery whereas 2 patients (3.7%) stayed in the hospital overnight. The median pain score at the time of discharge was 0 (interquartile range 0, 0). There were 6 (11.1%) minor complications including 5 pain pump malfunctions and 1 recipient site wound breakdown. There was 1 readmission (1.9%) for development of a surgical site infection at the hip and no re-operations within 30 days of surgery. CONCLUSION: The described outpatient ABG protocol demonstrates effective postoperative pain control, short hospital LOS, and few complications requiring hospital readmission or reoperation.

Characterization of Regional Morphological Changes in Sagittal Craniosynostosis Following Endoscopic Strip Craniectomy With Post-operative Helmeting: Predictors for Success.

BACKGROUND: Sagittal craniosynostosis (SC) restricts craniofacial growth perpendicular to the sagittal plane resulting in scaphocephaly. The cranium grows in the anterior-posterior dimension causing disproportionate changes, which can be corrected with either cranial vault reconstruction (CVR) or endoscopic strip craniectomy (ESC) combined with post-operative helmet therapy. ESC is performed at an earlier age, and studies demonstrate benefits in risk profile and morbidity compared to CVR, with comparable results if the post-operative banding protocol is strictly upheld. We aim to identify predictors of successful outcome and, using three-dimensional (3D) imaging, assess cranial changes following ESC with post-banding therapy. MATERIALS AND METHODS: A single institution retrospective review was performed from 2015-19 for patients with SC who underwent ESC. Patients received immediate post-operative 3D photogrammetry for helmet therapy planning and implementation as well as post-therapy 3D imaging. Using these 3D images, the cephalic index (CI) for study patients was calculated before and after helmet therapy. In addition, Deformetrica™ was used to measure volume and shape changes of pre-defined anatomic skull regions (frontal, parietal, temporal, & occipital) based on the pre- and post-therapy 3D imaging results. Fourteen institutional raters evaluated the pre- and post-therapy 3D imaging in order to determine the success of the helmeting therapy. RESULTS: Twenty-one SC patients met our inclusion criteria. Using 3D photogrammetry, 14 raters at our institution rated 16 of the 21 patients to have had successful helmet therapy. There was a significant difference in CI following helmet therapy with both groups, but there was no significant difference in CI between the "successful" and "unsuccessful" groups. Furthermore, the comparative analysis demonstrated that the parietal region had a significantly higher change in mean RMS distance when compared to the frontal or occipital regions. CONCLUSION: For patients with SC, 3D photogrammetry may be able to objectively recognize nuanced findings not readily detectable when using CI alone. The greatest changes in volume were observed in the parietal region, which falls in line with treatment goals for SC. Patients deemed to have unsuccessful outcomes were found to be older at time of surgery and initiation of helmet therapy. This suggests that early diagnosis and management for SC may increase the likelihood of success.

Evaluation of Helmeting Therapy Duration After Endoscopic Strip Craniectomy for Metopic and Sagittal Craniosynostosis.

INTRODUCTION: Endoscopic strip craniectomy (ESC) is a minimally invasive option for early surgical treatment of metopic (MC) and sagittal craniosynostosis (SC). For ESC, however, the postoperative duration and compliance of helmet therapy are crucial to correct MC and SC asymmetry. The purpose of this study is to assess the period of postoperative band therapy and determine differences, if any, between MC and SC. METHODS: A single-institution retrospective review was performed for patients with MC and SC who underwent ESC from November 2015 to 2019. Patients received preoperative, postoperative, and post-band 3-dimensional imaging. Factors recorded included patient sex, insurance type, number of helmets needed, age at surgery, time of first helmet, and at time of completion of helmet therapy, cephalic index, interfrontal angle, and cranial vault asymmetry index. RESULTS: Patients with SC and MC had ESC surgery at 3.3 and 3.4 months of age, respectively.Patients with SC were found to have completed banding therapy at a younger age (7.88 versus 10.0 mo), with shorter duration (4.17 versus 6.00 mo), and less number of bands (1.54 versus 2.21) than patients with MC. After regression analysis, suture type was found to be a significant predictor of total time in band therapy (P=0.039) with MC requiring a longer duration of banding therapy when compared with SC. CONCLUSIONS: Suture type directly correlates with duration of helmeting therapy for patients, with patients with MC requiring longer periods of postop helmeting and increased number of bands as compared with SC.

Repeat Buccal Flaps Successfully Reduce Hypernasality in a Patient with Cleft Palate.

Surgical intervention can contribute to the development of velopharyngeal insufficiency (VPI) leading to hypernasality and regurgitation. In this case, a patient with a history of bilateral buccal flaps used for her primary CP repair presented to clinic with hypernasality and VPI as assessed by speech exam and imaging. She underwent repeat bilateral buccal flap palatal lengthening with division of the pedicles 3 months later. Three months after her division, her hypernasality score improved from moderate to mild and her posterior gap decreased. This study concluded buccal flaps can be used a second time for patients needing palatal revisions for VPI.

Is the Message Clear? Evaluation of Readability Levels for Cleft Lip, Cleft Palate, and Craniofacial Websites.

Web-based health information is the leading source of medical knowledge for patients and families. The American Medical Association (AMA) and US Department of Health and Human Services recommend reading material be at or below a sixth-grade reading level. This study aimed to evaluate and compare the readability of the most popularly searched cleft lip and/or palate (CL/P) and other craniofacial syndrome (CFS) websites.Google searches for "cleft lip," "cleft palate," and "craniofacial syndromes" were performed to identify the top 40 websites in an incognito window with the location set to the United States. Flesch Reading Ease Score (FRES) was used to determine ease of reading from 0 (most difficult) to 100 (greatest ease of reading) and Flesch-Kincaid Reading Grade (FKGL) for website content and compared between websites using an FRES of 80 to 90 and FKGL of 6.0 to 6.9 for a sixth-grade reading level.Readability was low for all sites with 6 CL/P websites and no CFS websites at or below a sixth-grade reading level. CL/P websites had FRES readability scores of 58.5 ± 12.3 and were at a 9.4 ± 2.3 grade level. CFS websites had readability scores on the FRES of 39.8 ± 13.1 and were at a 10.8 ± 1.8 grade level.Web-based information related to CL/P and CFS is on average several grade levels above the recommended sixth-grade reading level. Online information for CL/P and CFS may need to be revised to improve understanding for the public and families.

Binding interface and impact on protease cleavage for an RNA aptamer to HIV-1 reverse transcriptase.

RNA aptamers that bind HIV-1 reverse transcriptase (RT) inhibit RT in enzymatic and viral replication assays. Some aptamers inhibit RT from only a few viral clades, while others show broad-spectrum inhibition. Biophysical determinants of recognition specificity are poorly understood. We investigated the interface between HIV-1 RT and a broad-spectrum UCAA-family aptamer. SAR and hydroxyl radical probing identified aptamer structural elements critical for inhibition and established the role of signature UCAA bulge motif in RT-aptamer interaction. HDX footprinting on RT ± aptamer shows strong contacts with both subunits, especially near the C-terminus of p51. Alanine scanning revealed decreased inhibition by the aptamer for mutants P420A, L422A and K424A. 2D proton nuclear magnetic resonance and SAXS data provided constraints on the solution structure of the aptamer and enable computational modeling of the docked complex with RT. Surprisingly, the aptamer enhanced proteolytic cleavage of precursor p66/p66 by HIV-1 protease, suggesting that it stabilizes the productive conformation to allow maturation. These results illuminate features at the RT-aptamer interface that govern recognition specificity by a broad-spectrum antiviral aptamer, and they open new possibilities for accelerating RT maturation and interfering with viral replication.

Dual-Innervated Free Gracilis Muscle Transfer for Facial Reanimation in Children.

BACKGROUND: Facial palsy may have deleterious effects for pediatric patients. The most common reconstruction is 2-stage free gracilis muscle transfer (FGMT) after cross-face nerve graft (CFNG). This requires a prolonged period from time of surgery to smile. New techniques using both a CFNG and motor nerve to masseter (MNM) as dual power sources in a single-stage surgery have been described in adults. Here, we examine our experience with this technique in children. METHODS: A retrospective study was performed examining patients who underwent dual-innervated single-stage FGMT at 2 pediatric hospitals from 2016 to 2019. Demographics, etiology, perioperative characteristics, time to mandibular and emotional smile, and Sunnybrook scores were recorded. RESULTS: Five patients met inclusion criteria with a mean age of 11.8 (range, 8-20). Two patients had congenital facial palsy while 3 had acquired facial palsy. Four patients (80%) received dual end-to-end neural coaptations of the CFNG and MNM to the obturator nerve. One (20%) had end-to-side coaptation of the CFNG to the obturator nerve and end-to-end of the MNM to the obturator nerve. The average time to mandibular smile was 103 ± 15.4 days. The average time to emotional smile was 245 ± 48.1 days. The preoperative Sunnybrook scale was 32 ± 7.5 and improved to 55.3 ± 20.6 at 8 months postoperatively. CONCLUSIONS: Dual-innervated FGMT is effective for facial reanimation in children with unilateral facial palsy. Patients can harness a stronger motor source (MNM) and the component of an emotional stimulus (CFNG). This approach may be the new criterion standard pediatric facial reanimation.

Back to the Beginning: An Algorithmic Approach to Neonatal Myelomeningocele Repair.

INTRODUCTION: Myelomeningoceles are formed by prenatal failure of neural tube closure and can cause hydrocephalus, motor abnormalities, and developmental delay. Although small defects are amenable to primary closure, larger defects often require complex reconstruction. Our goal was to identify factors associated with postoperative soft tissue complications and develop a systematic approach for myelomeningocele closure. METHODS: A retrospective review was performed at the Children's Memorial Hermann Hospital from January 2013 to January 2019. Patients were identified using International Classification of Diseases, Ninth Revision/Tenth Revision , codes for myelomeningocele. Cohorts were stratified by reconstruction type and defect location. Primary outcomes were incidence of complications including cerebrospinal fluid leak, superficial and deep infection, and wound dehiscence. In addition, we developed an algorithm to standardize closure approach for patients with myelomeningoceles. RESULTS: A total of 172 patients with myelomeningocele were identified with 73 patients undergoing postnatal repair. Overall, 72% of defects were >5 cm. Defects were in the lumbar (9%), sacral (8%), and junctional (83%) regions. Overall, 30.1% patients underwent lumbar myofascial repair with 39.7% requiring fasciocutaneous flaps. Larger defects (>5 cm) were more likely to be closed with complex fasciocutaneous flaps (82.8% vs 66.0%, P = 0.11). No significant differences were observed in complication rates. CONCLUSIONS: In this series, patients with larger myelomeningoceles appear to benefit from complex flap closure. We propose a 5-layer closure for patients with myelomeningocele including the routine use of a myofascial layer. Cutaneous closure technique should be tailored based on specific defect characteristics as outlined in our algorithm. This approach streamlines myelomeningocele repair while optimizing outcomes and decreasing downstream complications.

Socioeconomic Factors Impact the Timing of Surgical Repair for Craniosynostosis - A Regional and National Assessment.

INTRODUCTION: Timing of repair for patients with craniosynostosis are usually categorized into early "minimally invasive" surgeries such as strip craniotomy (SC), whereas those presenting later undergoing traditional cranial vault remolding (CVR). The impact that sociodemographic and socioeconomic disparities have on time to presentation for craniosynostosis and treatment is unknown. Herein, we examined sociodemographic and socioeconomic factors among a heterogenous patient population at a single institution who underwent craniosynostosis repair and compared this cohort to a national database. METHODS: A retrospective review of patients at UTHealth who underwent craniosynostosis repair from 2016 to 2020 was performed. The patients were divided into cohorts based on type of operation: SC or cranial vault remolding. The Kid inpatient Database (KiD) database was used to assess sociodemographic factors in relation to craniosynostosis. Univariate and multivariate logistic regression were used to determine significant predictors and differences. RESULTS: Single Institution (Regional): Compared with nonHispanic white (NHW) patients, Hispanic (OR 0.11), and NonHispanic Black (NHB) (OR 0.14) had lower odds of undergoing SC. Compared to those on private insurance, patients on Medicaid (OR 0.36) had lower odds of undergoing SC. Using zip code median income levels, patients with a higher median income level had slightly higher odds of undergoing SC compared to patients with a lower median income (OR 1.000025). KIDS NATIONAL: Compared with non-Hispanic white patients, NHB (OR 0.32) and Asian (OR 0.47) patients had lower odds of undergoing repair before the age of 1. Compared to patients with private insurance, those with Medicaid (OR 0.67) and self-pay (OR 0.58) had lower odds of undergoing repair before the age of 1. Patients in the lowest income quartile (OR 0.68) and second lowest income quartile (OR 0.71) had lower odds of undergoing repair before the age of 1 compared to the highest quartile. CONCLUSIONS: Our findings indicate that sociodemographic and socioeconomic factors may play a role in diagnosis of craniosynostosis and access to care. Patients of NHB and Hispanic race, lower income quartiles by zip code, and those that use public insurance are less likely to undergo early repair, both nationally and at our institution. Further research is needed to delineate the casualty of this disparity in presentation and timing of surgery.

Where Are We Headed? Diagnosing Abnormal Head Shapes Through Virtual Care Visits.

PURPOSE: Since the beginning of the coronavirus disease 2019 pandemic in early March, there has been a push to expand virtual patient care visits instead of in-person clinic visits. Studies have found that telemedicine can provide efficient triaging, reduction in emergency room visits, and conservation of health care resources and personnel. Although virtual patient care has been implicated in providing similar outcomes to traditional face-to-face care in patients affected with coronavirus disease 2019, there are a lack of studies on the effectiveness of virtual care visits (VCVs) for patients with craniosynostosis or deformational plagiocephaly. This study aims to develop an understanding of whether physicians can accurately diagnose pediatric patients with craniosynostosis or deformational plagiocephaly via VCVs, and whether they can determine if affected patients will benefit from helmet correction or if surgical treatment is required. METHODS: An Institutional Review Board-approved retrospective chart analysis over a 4-month period (March 1, 2020 to June 30, 2020) was performed analyzing all pediatric patients (<18 years old) who underwent virtual care calls for diagnosis and treatment of abnormal head shape. Patients were referred to UT Physicians Pediatric Surgery clinic for evaluation by a member of the Texas Cleft-Craniofacial Team (2 surgeons or 1 physician's assistant). Variables such as patient demographics, diagnosis, and need for confirmation were pulled and recorded from Allscripts Electronic Medical Records software. RESULTS: Thirty-five patients were identified who fit our search criteria. Out of these patients, eleven (31.43%) cases were diagnosed with craniosynostosis, twenty-two (62.86%) cases were diagnosed with deformational plagiocephaly, and 2 (5.71%) cases were diagnosed as being normocephalic. Median age at virtual care evaluation was 14.10 months (Interquartile Range [IQR] 5.729, 27.542) for patients diagnosed with craniosynostosis and 6.51 months (IQR 4.669, 7.068) for patients diagnosed with deformational plagiocephaly. All eleven (100%) patients diagnosed with craniosynostosis were referred for a confirmatory computed tomography scan before undergoing surgical intervention and saw an alleviation in head shape postoperatively. Eighteen (81.82%) of patients diagnosed with deformational plagiocephaly were recommended to undergo conservative treatment and the remaining 4 (18.18%) were recommended for helmet therapy. Two cases were unable to be diagnosed virtually. These patients needed a follow-up visit in person to establish a diagnosis and plan of treatment. CONCLUSIONS: Virtual care visits are increasing in frequency and this includes consultations for abnormal head shapes. Our experience demonstrates that the majority of patients can be evaluated safely in this modality, with only 5.71% requiring additional imaging or in-person visits to confirm the diagnosis. Our study underscores the feasibility of virtually diagnosing and recommending a plan for treatment in pediatric patients with abnormal head shapes. This information can be implemented to further our knowledge on the accuracy of diagnosis and treatment options for patients with craniosynostosis and deformational plagiocephaly. Further analyses are needed to quantify the financial and patient-reported outcomes of VCVs for these patients.

Predictive Factors for Velopharyngeal Insufficiency Following Primary Cleft Palate Repair.

OBJECTIVE: Velopharyngeal insufficiency (VPI) remains a known complication of primary palatoplasty. We sought to identify factors associated with the incidence of VPI and create a predictive model for VPI development in our population. DESIGN: A single-institution, retrospective review. SETTING: Multidisciplinary clinic in a tertiary academic institution. PATIENTS: A total of 453 consecutive patients undergoing primary palatoplasty from 1999 to 2016 were reviewed. Inclusion required follow-up past age 5. Patients who were non-verbal, and thus unable to undergo speech evaluation, were excluded. MAIN OUTCOME MEASURES: Primary outcome was VPI, defined as revision palatoplasty or recommendation by speech-language pathology. RESULTS: Of 318 patients included, 179 (56%) were male. Median age at primary repair was 1.0 years (0.9-1.1) with a median age of 8.8 years at last follow-up. One hundred nineteen (37%) patients developed VPI at a median age of 5.0 years (3.8-6.5). Higher rates were seen with posterior fistula (65% vs 14%, P <.01) and straight-line repair (41% vs 9%, P <.01), with lower rates in patients with Veau I clefts (22% vs 39%, P <.05). Patients with VPI were older at last follow-up. Following multivariate regression, factors remaining significant were posterior fistula (odds ratio [OR]: 11.3, 95% CI: 6.1-22.0), primary Furlow repair (OR: 0.18, 95% CI: 0.03-0.68), genetic diagnoses (OR: 2.92, 95% CI: 1.1-7.9), and age at last follow-up (OR: 1.11, 95% CI: 1.01-1.2). CONCLUSIONS: Length of follow-up, posterior fistulae, and genetic diagnoses are associated with VPI formation. Furlow repair may protect against formation of VPI. Use of allograft, Veau class, birth type, birth weight, and race are not independently associated with VPI formation.

Epidemiology of Craniofacial Pathology in Northern Vietnam Using Digital Platforms: Utilization of Electronic Medical Records and an SMS-Based Reporting System in a Low-Middle Income Country.

INTRODUCTION: Current disease surveillance in Vietnam relies on underdeveloped electronic medical record (EMR) systems, which are insufficient for timely standardized data collection about craniofacial and cleft pathologies. Concurrently, the World Bank reports Vietnamese mobile cellular subscription rates (per 100 people) of 128, some of the highest in the world. Herein, we discuss the development of a short messaging service (SMS)-based surveillance system based in Hanoi, Vietnam, and its utility in contrast to an EMR-based approach to craniofacial epidemiology study. METHODS: Vietnam National Children's Hospital (VNCH) is a pediatric tertiary care center serving approximately 12 million children. Four plastic surgeons were trained in SMS data entry. The SMS database was designed using FrontlineSMS, a 2-way mobile gateway software application with automated messaging capabilities. The VNCH EMR database was queried for individual demographic data for patients seen by the department from 2010 to 2019. RESULTS: A corrected prevalence for cleft lip and palate of 0.098% (1 in 1020 live births) was calculated based on EMR data. Six rural provinces greater than 150 km from Hanoi were found to be significantly (P < 0.01) underserved surgically by the VNCH. A significantly (P < 0.01) higher rate of Pierre Robin in Lang Son province and facial clefts in Ha Tinh province were identified. The prospective data collection system received 7 patient data sets over 4 months, resulting in a capture rate of 2.9%. CONCLUSIONS: This feasibility study offers valuable insight into the true cleft and craniofacial prevalence in Vietnam and alternative methods to study in low- and middle-income countries.