Impact of Neighborhood Deprivation and Social Vulnerability on Outcomes and Interventions in Patients with Cleft Palate.

OBJECTIVE: To examine whether neighborhood disadvantage impacts length of follow-up, interventions, and outcomes for patients with cleft palate. DESIGN: Retrospective cohort. SETTING: Cleft Palate Craniofacial Institute Database at St. Louis Children's Hospital. PATIENTS/PARTICIPANTS: Patients with cleft palate following in St. Louis Children's Hospital Cleft Palate Multidisciplinary Team Clinic. INTERVENTIONS: Primary palatoplasty between 2012-2017. Patients were divided into quartiles across area deprivation index (ADI) and social vulnerability index (SVI), two validated, composite metrics of neighborhood disadvantage, to examine whether living in neighborhoods from different deprivation quartiles impacts outcomes of interest. MAIN OUTCOME MEASURE: Follow-up through age 5, surgeries and surgical complications, speech, developmental, and behavioral outcomes. RESULTS: 205 patients were included. 39% of patients belonged to the most deprived ADI quartile, while 15% belonged to the most vulnerable SVI quartile. There were no differences between ADI or SVI quartiles in number of operations received (p ≥ 0.40). Patients in the most deprived ADI quartile were significantly more likely to have speech/language concerns (OR 2.32, 95% CI [1.20-4.89], p = 0.01). Being in a more vulnerable SVI quartile was associated with developmental delay (OR 2.29, 95% CI [1.04-5.15], p = 0.04). ADI and SVI quartile did not impact risk of loss to follow-up in the isolated and combined cleft lip and palate subgroups (p ≥ 0.21). CONCLUSIONS: Neighborhood disadvantage impacts speech and developmental outcomes in patients with cleft palate despite comparable length of follow-up in multidisciplinary team clinic.

Impact of a Palatal Fistula After Cleft Palate Repair on Velopharyngeal Closure.

PURPOSE: A palatal fistula is an adverse outcome of cleft palate repair. It is unknown if a palatal fistula will influence velopharyngeal closure, even after repair of the fistula. This study determines the effect of a soft palate fistula on the risk of developing velopharyngeal insufficiency. METHODS: A retrospective chart review was conducted on patients who underwent primary cleft palate repair between 2000 and 2015, with complete records at 4 years of age. Fistulae involving the secondary palate following primary palatoplasty were classified as the soft or hard palate. A forced-entry multivariate logistic regression model was built to detect predictors of velopharyngeal dysfunction. RESULTS: Records of 329 patients were analyzed with a mean follow-up of 8.7 years. A palatal fistula was identified in 89/329 patients (27%) and 29/329 patients (9%) underwent an independent fistula repair. Of the patients with fistula, 44% were located in the hard palate only and 56% had soft palate involvement. Compared to patients without a fistula, rates of velopharyngeal dysfunction were significantly higher in patients with a fistula involving the soft palate (OR 3.875, CI: 1.964-7.648, P < .001) but not in patients with a hard palate fistula (OR 1.140, CI: 0.497-2.613, P = .757). Veau class, age at primary repair, and syndromic status were not significant predictors of VPI (0.128≤P ≤ .975). CONCLUSIONS: A palatal fistula involving the soft palate is a significant predictor for development of velopharyngeal dysfunction after primary palatoplasty. Surgical intervention, at the time of fistula repair, to add vascularized tissue may be indicated to prophylactically decrease the risk of velopharyngeal dysfunction.

Electrical stimulation or tacrolimus (FK506) alone enhances nerve regeneration and recovery after nerve surgery, while dual use reduces variance and combines strengths of each in promoting enhanced outcomes.

INTRODUCTION/AIMS: Repaired nerve injuries can fail to achieve functional recovery. Therapeutic options beyond surgery, such as systemic tacrolimus (FK506) and electrical stimulation (E-stim), can improve recovery. We tested whether dual administration of FK506 and E-stim enhances regeneration and recovery more than either therapeutic alone. METHODS: Rats were randomized to four groups: E-stim, FK506, FK506 + E-stim, and repair alone. All groups underwent tibial nerve transection and repair. Two sets of animals were created to measure outcomes of early nerve regeneration using nerve histology (n = 36) and functional recovery (n = 42) (21- and 42-day endpoints, respectively). Functional recovery was measured by behavioral analyses (walking track and grid walk) and, at the endpoint, muscle mass and force. RESULTS: Dual E-stim and FK506 administration produced histomorphometric measurements of nerve regeneration no different than either therapeutic alone. All treatments were superior to repair alone (FK506, P < .0001; E-stim, P < .05; FK506 + E-stim, P < .05). The E-stim and FK506 + E-stim groups had improved behavioral recovery compared with repair alone (at 6 weeks: E-stim, P < .05; FK506 + E-stim, P < .01). The FK506 group had improved recovery based on walking-track analysis (at 6 weeks: P < .001) and muscle force and mass (P < .05). The concurrent use of both therapies ensured earlier functional recovery and decreased variability in functional outcomes compared with either therapy alone, suggesting a moderate benefit. DISCUSSION: Dual administration of FK506 and E-stim showed minimal additive effects to further improve regeneration or recovery compared with either therapy alone. The data suggest the combination of FK506 and E-stim appears to combine the relative strengths of each therapeutic.

A feasibility study transplanting macrophages to a segmental nerve injury.

INTRODUCTION/AIMS: Promoting regeneration after segmental nerve injury repair is a challenge, but improving angiogenesis could be beneficial. Macrophages facilitate regeneration after injury by promoting angiogenesis. Our aim in this study was to evaluate the feasibility and effects of transplanting exogenous macrophages to a segmental nerve injury. METHODS: Bone marrow-derived cells were harvested from donor mice and differentiated to macrophages (BMDM), then suspended within fibrin hydrogels to facilitate BMDM transplantation. BMDM survival was characterized in vitro. The effect of this BMDM fibrin hydrogel construct at a nerve injury site was assessed using a mouse sciatic nerve gap injury. Mice were equally distributed to "fibrin+Mφ" (fibrin hydrogels containing culture medium and BMDM) or "fibrin" hydrogel control (fibrin hydrogels containing culture medium alone) groups. Flow cytometry (n = 3/group/endpoint) and immunohistochemical analysis (n = 5/group/endpoint) of the nerve gap region were performed at days 3, 5, and 7 after repair. RESULTS: Incorporating macrophage colony-stimulating factor (M-CSF) improved BMDM survival and expansion. Transplanted BMDM survived for at least 7 days in a nerve gap (~40% retained at day 3 and ~15% retained at day 7). From transplantation, macrophage quantities within the nerve gap were elevated when comparing fibrin+Mφ with fibrin control (~25% vs. 3% at day 3 and ~14% vs. 6% at day 7). Endothelial cells increased by about fivefold within the nerve gap, and axonal extension into the nerve gap increased almost twofold for fibrin+Mφ compared with fibrin control. DISCUSSION: BMDM suspended within fibrin hydrogels at a nerve gap do not impair regeneration.

Improving the Care of Our Patients: Twenty-Three Years of the James Barrett Brown Resident Research Day.

BACKGROUND: James Barrett Brown was one of the founders of Plastic and Reconstructive Surgery as a specialty in the United States. Susan Mackinnon started the James Barrett Brown Resident Research Day in 1997 in his honor to serve as an annual opportunity for trainees to present their research to the Division and a visiting contemporary leader in plastic surgery. We sought to determine the proportion of Resident Research Day projects that have progressed to publication. METHODS: Available internal records from 1998 to 2019 were used to identify presenters and projects. Academic productivity of presenters was estimated with the h-index from the Scopus database. RESULTS: One hundred forty-five students, residents, and fellows presented 276 projects at Resident Research Day from 1998 to 2019. These presentations were associated with 144 unique peer-reviewed publications, representing 52% of the presented projects. They were published an average of 1.8 years after presentation, and the presenter was the first or last author on 67% of them. The current average h-index of trainees who published at least 1 project (8.3) is significantly higher than the h-index of those who did not (5.0, P < 0.001). CONCLUSIONS: The James Barrett Brown Resident Research Day not only honors the legacy of Brown but also enhances scholarly activity of trainees. The opportunity to present and publish research teaches project planning, implementation, and data analysis, followed by manuscript preparation and the publication process. This important skill set can provide the foundation for the academic careers of future leaders in plastic surgery.

Variability and Excess in Opioid Prescribing Patterns After Cleft and Craniosynostosis Repairs.

OBJECTIVE: To critically analyze pediatric opioid prescription patterns after cleft and craniosynostosis repairs. DESIGN: Observational study 1) retrospectively reviewing pediatric opioid prescriptions from July 2018 to June 2019 and 2) prospectively surveying patients about actual opioid use from August 2019 to February 2020. SETTING: Academic tertiary care pediatric hospital. PATIENTS: 133 pediatric patients undergoing cleft lip and/or palate or craniosynostosis repairs. Prospective surveys were offered at postoperative visits; 45 of 69 eligible patients were enrolled. INTERVENTION: None. MAIN OUTCOME MEASURES: Opioid doses prescribed at discharge and actual home opioid use. RESULTS: 90 patients with cleft lip and/or palate and 43 patients with craniosynostosis were included. Median prescribed opioid doses were 10.3 for cleft lip and/or palate procedures (range 0-75), and 14.3 for craniosynostosis repairs (range 0-50). In patients with cleft lip and/or palate, there was a negative correlation between age at surgery and prescribed opioid doses (rs = -0.228, p = 0.031). 45 patients completed surveys of home opioid use. No patients used more than 10 doses. Forty percent used no opioids at home, 33% used 1 to 2 doses, 18% used 3 to 5 doses, and 9% used 6 to 10 doses. CONCLUSIONS: Opioid prescriptions vary widely after common craniofacial procedures. Younger patients with cleft lip and/or palate may be more likely to be prescribed more doses. Actual home opioid use is less than prescribed amounts, with most patients using five or fewer doses. A prescribing guideline is proposed.

Multidisciplinary Optimal Outcomes Reporting and Team Clinic Retention in Isolated Nonsyndromic Cleft Palate.

OBJECTIVE: Optimal Outcomes Reporting was recently introduced to categorize outcomes after cleft palate repair. We seek to propose an expanded version of Optimal Outcomes Reporting and to determine if correlation exists between the expanded outcomes and persistence with team care follow-up through age 9. DESIGN: Retrospective cohort study. SETTING: Cleft team at large pediatric hospital. PATIENTS: Patients with isolated nonsyndromic cleft palate (n = 83) born from 2001-2012. MAIN OUTCOME MEASURES: Patients who continued to present at age 5 or greater were assessed for optimal outcomes. Optimal outcomes were: surgery - no fistula or velopharyngeal insufficiency; otolaryngology - no obstructive sleep apnea or signs of chronic middle ear disease; audiology - no hearing loss; speech-language pathology - no assessed need for speech therapy. RESULTS: Of the 83 patients identified, 41 were assessed for optimal outcomes. Optimal outcome in any discipline was not associated with follow-up through age 9 (0.112 ≤ p ≤ 0.999). For all disciplines, the group with suboptimal outcomes had a higher proportion of patients from geographic areas in the most disadvantaged quartile of social vulnerability index, with the strongest association in the group with suboptimal speech outcome (OR 6.75, 95% CI 0.841-81.1). CONCLUSIONS: Optimal outcomes and retention in team clinic were not statistically significantly associated, but clinically relevant associations were found between patients in the most disadvantaged quartile of social vulnerability and their outcomes. A patient-centered approach, including caregiver education about long-term care for patients with cleft palate, would allow for enhanced resource utilization to improve retention for patients of concern.

Macrophage roles in peripheral nervous system injury and pathology: Allies in neuromuscular junction recovery.

Peripheral nerve injuries remain challenging to treat despite extensive research on reparative processes at the injury site. Recent studies have emphasized the importance of immune cells, particularly macrophages, in recovery from nerve injury. Macrophage plasticity enables numerous functions at the injury site. At early time points, macrophages perform inflammatory functions, but at later time points, they adopt pro-regenerative phenotypes to support nerve regeneration. Research has largely been limited, however, to the injury site. The neuromuscular junction (NMJ), the synapse between the nerve terminal and end target muscle, has received comparatively less attention, despite the importance of NMJ reinnervation for motor recovery. Macrophages are present at the NMJ following nerve injury. Moreover, in denervating diseases, such as amyotrophic lateral sclerosis (ALS), macrophages may also play beneficial roles at the NMJ. Evidence of positive macrophages roles at the injury site after peripheral nerve injury and at the NMJ in denervating pathologies suggest that macrophages may promote NMJ reinnervation. In this review, we discuss the intersection of nerve injury and immunity, with a focus on macrophages.

Long-Term Effects of Nasoalveolar Molding in Patients With Unilateral Cleft Lip and Palate: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis was to investigate long-term treatment effects of nasoalveolar molding (NAM) in patients with unilateral cleft lip and palate (UCLP). DESIGN: Included manuscripts met the following criteria: (1) involved patients with UCLP who received NAM; (2) included comparison group(s) who either received non-NAM passive presurgical infant orthopedic appliances (PSIO) or who did not receive any PSIO; (3) reported at least one objective or validated measure of nasolabial, craniofacial, or palatal form; and (4) had patient follow-up beyond 4 years of age. RESULTS: A total of 12 studies were included in this review. Meta-analyses were possible for Asher-McDade parameters and cephalometric measurements. Compared to patients who did not receive any PSIO, those who underwent NAM therapy were more likely to have good to excellent frontal nasal form (Risk ratio: 2.4, 95% CI: 1.24-3.68) and vermillion border (Risk ratio: 1.8, 95% CI: 1.19-2.71). However, there were no statistically significant differences in cephalometric measurements between these groups. Additionally, there were no statistically significant differences between patients receiving NAM versus non-NAM PSIO. There was insufficient evidence to determine the impact of NAM on dental arch development. CONCLUSIONS: The preponderance of evidence in this review suggests that NAM produces benefits in nasolabial aesthetic form when compared with no appliance-based presurgical treatment. However, there is insufficient evidence to conclude whether NAM produces such benefits when compared with other passive PSIOs.

Mind the Gap: Alveolar Bone Graft Revision in the Era of Computed Tomography.

OBJECTIVE: To determine the rate of revision alveolar bone grafting (ABG) in patients with cleft lip and palate (CLP) before and after the introduction of postoperative computed tomography (CT). DESIGN: Retrospective case-control study analyzing the incidence of revision ABG in patients with and without postoperative CT scans for graft success evaluation. SETTING: Academic tertiary care pediatric hospital. PATIENTS: Eighty-seven patients with CLP or cleft lip and alveolus treated with autologous iliac crest bone grafting for alveolar clefts over a 10-year period (January 2009 to March 2019) with minimum 6-month follow-up. Fifty patients had postoperative CT evaluation; 37 did not. INTERVENTIONS: Postoperative CT to determine ABG success, versus standard clinical examination and 2-dimensional radiographs. MAIN OUTCOME MEASURES: Requirement for revision ABG, defined as failure of the original graft by clinical or radiographic examination. RESULTS: Fifty-eight percent of patients underwent a postoperative CT scan at median interval of 10 months after surgery. Patients with postoperative CT evaluation had a 44% rate of revision ABG (22/50) for inadequate graft take, compared to 5% (2/37) in patients without postoperative CT (P < .001; 95% CT, 31%-58% in the CT group, 1%-16% in the non-CT group). CONCLUSIONS: Computed tomography evaluation after ABG is associated with a significantly increased revision rate for inadequate graft take. The presence of a secondary palatal fistula at the time of original ABG is not associated with revision requirement. Lack of standardized dental and orthodontic records complicates the study of ABG outcomes and presents an area for systems-based improvement.

Effect of Veau Class on Levator Veli Palatini Muscle Composition.

OBJECTIVE: To examine levator veli palatini muscle composition in patients with nonsyndromic cleft palate and investigate the impact of Veau class. DESIGN: Prospective cohort study. SETTING: Tertiary care academic hospital. PATIENTS/PARTICIPANTS: Thirteen patients with nonsyndromic cleft palate were recruited. INTERVENTIONS: During primary palatoplasty, a sample of levator veli palatini muscle was excised and prepared for histological analysis. MAIN OUTCOME MEASURES: Fat and collagen content were determined utilizing Oil Red and Sirius red stains, respectively, while muscle fiber cross-sectional areas were calculated from H&E-stained samples, with analysis using histomorphometric methods. Immunofluorescent staining of myosin heavy chain isoforms was performed. RESULTS: Patients underwent repair at 10.8 months of age (interquartile range [IQR] 10.2-12.9). Fat content of the levator veli palatini muscle was low in both groups, ranging from 0% to 5.2%. Collagen content ranged from 8.5% to 39.8%; neither fat nor collagen content showed an association with Veau classes. Mean muscle fiber cross-sectional area decreased with increasing Veau class, from 808 µm2 (range 692-995 µm2) in Veau II to 651 µm2 (range 232-750 µm2) in Veau III (P = .02). There was also a nonsignificant decrease in proportion of type I muscle fibers with increasing Veau class (44.3% [range 31.4%-84.4%] in Veau II vs 35.3% [range 17.4%-61.3%] in Veau III). CONCLUSIONS: Muscle fiber area in levator veli palatini muscles decreases in Veau III clefts in comparison to Veau II. The impact of these differences in velopharyngeal dysfunction requires further analysis of a larger cohort.

Factors contributing to delay or absence of alveolar bone grafting.

INTRODUCTION: Alveolar bone grafting (ABG) delay can lead to suboptimal outcomes. This study seeks to categorize reasons patients with cleft lip and palate have no record of ABG or who underwent later than typical ABG (≥13 years). METHODS: At a single tertiary care center, a retrospective review was performed of all patients with unilateral, complete cleft lip and palate, born 1998-2005. Database query identified which patients had timely, late, or no record of ABG. The retrospective cohort study was performed to categorize ABG delay or absence of recorded ABG. RESULTS: Of 135 participants, 82 (61%) had timely, 8 (6%) had late, and 45 (33%) had no record of ABG. The primary factor for late ABG was noncompliance or refusal (n = 5 of 8, 63%), comorbidity or medical complexity (n = 1 of 8, 13%), orthodontic unpreparedness (n = 1 of 8, 13%), or inaccurate prior assessment of alveolar sufficiency (n = 1 of 8, 13%). The primary factor for ABG record absence was loss to follow-up (n = 40 of 45, 89%), noncompliance or refusal (n = 3 of 45, 7%), comorbidity or medical complexity (n = 1 of 45, 2%), or orthodontic unpreparedness (n = 1 of 45, 2%). Racial majority (White, Asian) patients received preferred care (timely ABG or medically appropriate absence or delay) at a significantly higher rate (67%) than underrepresented minorities (African American, Hispanic, Native American, other) (35%, P = 0.016). Families with private insurance and those who were self-pay received preferred care at a significantly higher rate (77%) than families with Medicaid (42%) (P <0.001). CONCLUSIONS: The high number of patients lost to follow-up highlights the impact of poor retention on ABG completion. Possible health disparities based on race and insurance status warrant clinical focus.

Macrophage-Derived Vascular Endothelial Growth Factor-A Is Integral to Neuromuscular Junction Reinnervation after Nerve Injury.

Functional recovery in the end target muscle is a determinant of outcome after peripheral nerve injury. The neuromuscular junction (NMJ) provides the interface between nerve and muscle and includes non-myelinating terminal Schwann cells (tSCs). After nerve injury, tSCs extend cytoplasmic processes between NMJs to guide axon growth and NMJ reinnervation. The mechanisms related to NMJ reinnervation are not known. We used multiple mouse models to investigate the mechanisms of NMJ reinnervation in both sexes, specifically whether macrophage-derived vascular endothelial growth factor-A (Vegf-A) is crucial to establishing NMJ reinnervation at the end target muscle. Both macrophage number and Vegf-A expression increased in end target muscles after nerve injury and repair. In mice with impaired recruitment of macrophages and monocytes (Ccr2-/- mice), the absence of CD68+ cells (macrophages) in the muscle resulted in diminished muscle function. Using a Vegf-receptor 2 (VegfR2) inhibitor (cabozantinib; CBZ) via oral gavage in wild-type (WT) mice resulted in reduced tSC cytoplasmic process extension and decreased NMJ reinnervation compared with saline controls. Mice with Vegf-A conditionally knocked out in macrophages (Vegf-Afl/fl; LysMCre mice) demonstrated a more prolonged detrimental effect on NMJ reinnervation and worse functional muscle recovery. Together, these results show that contributions of the immune system are integral for NMJ reinnervation and functional muscle recovery after nerve injury.SIGNIFICANCE STATEMENT This work demonstrates beneficial contributions of a macrophage-mediated response for neuromuscular junction (NMJ) reinnervation following nerve injury and repair. Macrophage recruitment occurred at the NMJ, distant from the nerve injury site, to support functional recovery at the muscle. We have shown hindered terminal Schwann cell (tSC) injury response and NMJ recovery with inhibition of: (1) macrophage recruitment after injury; (2) vascular endothelial growth factor receptor 2 (VegfR2) signaling; and (3) Vegf secretion from macrophages. We conclude that macrophage-derived Vegf is a key component of NMJ recovery after injury. Determining the mechanisms active at the end target muscle after motor nerve injury reveals new therapeutic targets that may translate to improve motor recovery following nerve injury.

T-box transcription factor 21 is expressed in terminal Schwann cells at the neuromuscular junction.

INTRODUCTION/AIMS: Terminal Schwann cells (tSCs) are nonmyelinating Schwann cells present at the neuromuscular junction (NMJ) with multiple integral roles throughout their lifespan. There is no known gene differentiating tSCs from myelinating Schwann cells, making their isolation and investigation challenging. In this work we investigated genes expressed within tSCs. METHODS: A novel dissection technique was utilized to isolate the tSC-containing NMJ band from the sternomastoid muscles of S100-GFP mice. RNA was isolated from samples containing: (a) NMJ bands (tSCs with nerve and muscle), (b) nerve, and (c) muscle, and microarray genetic expression analysis was conducted. Data were validated by quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescent staining. To identify genes specific to tSCs compared with other NMJ components, analysis of variance and rank-order analysis were performed using the Partek Genomic Suite. RESULTS: Microarray analysis of the tSC-enriched NMJ band revealed upregulation (by 4- to 12-fold) of several genes unique to the NMJ compared with muscle or nerve parts alone (P < .05). Among these genes, Tbx21 (or T-bet) was identified, which showed a 12-fold higher expression at the NMJ compared with sciatic nerve (P < .002). qRT-PCR analysis showed Tbx21 mRNA expression was over ninefold higher (P < .05) in the NMJ relative to muscle and nerve. Tbx21 protein colocalized with tSCs and was not noted in myelinating SCs from sciatic nerve. DISCUSSION: We found TBX21 to be expressed in tSCs. Additional studies will be performed to determine the functional significance of TBX21 in tSCs. These studies may enhance the investigative tools available to modulate tSCs to improve motor recovery after nerve injury.

Using an Intake Form and Clinic Dashboard to Tailor and Improve the Cleft Team Clinic Visit for Families.

BACKGROUND: Multidisciplinary cleft care protocols commonly do not incorporate family needs, concerns, and preferences. SOLUTION: A family-centered model would incorporate family needs, concerns, and preferences with a view toward lessening burden of care while achieving outcomes important to families. WHAT WE DO: Our Intake Form helps us adapt visits to better meet families' needs, and our Dashboard enables Team Coordinators to direct efficient patient flows, lessening wait times and care burden.

Evaluation of Discipline-Specific Outcomes Through a Multidisciplinary Team Clinic for Patients With Isolated Cleft Palate.

OBJECTIVE: To describe the incidence and timing of provider-specific interventions for children with isolated cleft palate. DESIGN: This was a retrospective cohort study involving review of medical records. SETTING: Multidisciplinary team care clinic at a tertiary academic children's hospital between January 2000 and July 2019. PATIENTS: Patients with isolated nonsyndromic cleft palate seen by an American Cleft Palate-Craniofacial Association-approved team; 138 children were included. MAIN OUTCOME MEASURES: Study outcomes included incidence of secondary velopharyngeal management, tympanostomy tube insertion, speech therapy, hearing loss, dental/orthodontic treatment, and psychology interventions. Provider-specific outcomes were calculated for patients at ages 0 to 3, 3 to 5, and >5 years. RESULTS: Median follow-up time was 7.0 years (interquartile range: 3.3-11.8 years). At their last team assessment, 42% of patients still had conductive hearing loss. The rate of tympanostomy tube insertions not done alongside a palatoplasty was highest for ages 3 to 5 and dropped after new American Academy of Otolaryngology-Head and Neck Surgery Foundation guidelines in 2013 (P = .015); 54% of patients received speech-language therapy during follow-up. Palatoplasty, psychology, and dental/orthodontic treatment were all less common than speech or ENT treatment (P < .01). Secondary palatoplasty was performed in 31 patients (22%). Patients who received speech, dental/orthodontic, or psychology intervention followed up longer than those who did not (9.8 vs 2.1 years, P < .001). CONCLUSION: Half of the patients terminated team follow-up by age 7, suggesting that burden of care outweighed perceived benefits of continued follow-up for many families. These results can be used to adjust protocols for children with isolated cleft palate.

Gpr126/Adgrg6 contributes to the terminal Schwann cell response at the neuromuscular junction following peripheral nerve injury.

Gpr126/Adgrg6 is an adhesion G protein-coupled receptor essential for Schwann cell (SC) myelination with important contributions to repair after nerve crush injury. Despite critical functions in myelinating SCs, the role of Gpr126 within nonmyelinating terminal Schwann cells (tSCs) at the neuromuscular junction (NMJ), is not known. tSCs have important functions in synaptic maintenance and reinnervation, and after injury tSCs extend cytoplasmic processes to guide regenerating axons to the denervated NMJ. In this study, we show that Gpr126 is expressed in tSCs, and that absence of Gpr126 in SCs (SC-specific Gpr126 knockout, cGpr126) results in a NMJ maintenance defect in the hindlimbs of aged mice, but not in young adult mice. After nerve transection and repair, cGpr126 mice display delayed NMJ reinnervation, altered tSC morphology with decreased S100ß expression, and reduced tSC cytoplasmic process extensions. The immune response promoting reinnervation at the NMJ following nerve injury is also altered with decreased macrophage infiltration, Tnfα, and anomalous cytokine expression compared to NMJs of control mice. In addition, Vegfa expression is decreased in muscle, suggesting that cGpr126 non-cell autonomously modulates angiogenesis after nerve injury. In sum, cGpr126 mice demonstrated delayed NMJ reinnervation and decreased muscle mass following nerve transection and repair compared to control littermates. The integral function of Gpr126 in tSCs at the NMJ provides the framework for new therapeutic targets for neuromuscular disease.

Video-based Learning in Surgery: Establishing Surgeon Engagement and Utilization of Variable-duration Videos.

OBJECTIVE: To measure surgeon engagement and preferred video duration in a video-based learning program for nerve surgery. BACKGROUND: Educational videos can improve, standardize, and democratize best practices in surgery. To improve care internationally, educators must optimize their videos for learning. However, surgeon engagement and optimal video duration remain undefined. METHODS: A YouTube channel and a video-based learning website, PASSIO Education (passioeducation.com), were examined from 2011 to 2017. We assessed views, geographic location, audience engagement (average percent of video watched), audience retention (percent of viewers at each timepoint), and usage of short (median 7.4, range 4.1-20.3 min) and long (median 17.2, range 6.1-47.7 min) video formats for the same procedures. A survey of PASSIO Education membership examined preferred video duration. RESULTS: Our 117 nerve surgery videos attained over 3 million views with 69% originating outside of the United States. While YouTube achieved more international exposure, PASSIO Education attained a greater mean engagement of 48.4% (14.3% absolute increase, P < 0.0001). Surveyed surgeons (n = 304) preferred longer videos when preparing for infrequent or difficult cases compared with routine cases (P < 0.0001). Engagement declined with video duration, but audience retention between short and long video formats was correlated (τB = 0.52, P < 0.0001). CONCLUSIONS: For effective spread of best practices, we propose the joint use of YouTube for audience outreach and a surgeon-focused platform to maximize educational value. Optimal video duration is surgeon- and case-dependent and can be addressed through offering multiple video durations and interactive viewing options.

Inpatient Versus Outpatient Management of Negative Pressure Wound Therapy in Pediatric Patients.

BACKGROUND: Negative pressure wound therapy (NPWT) is commonly used to manage complex wounds in the pediatric population. With recently developed portable NPWT devices, providers have the opportunity to transition NPWT to the outpatient setting. However, there are no studies describing outpatient NPWT in pediatric patients. Therefore, the purpose of our study was to leverage a population-level analysis to advance our current knowledge about outpatient NPWT use in pediatric patients. MATERIALS AND METHODS: We analyzed the Truven Health Analytics MarketScan Commercial Claims Database from 2006 to 2014 to identify children treated with NPWT. We compared patient characteristics, indications, complications before and after NPWT, health care utilization within 30 d of NPWT initiation, and health care cost profile of patients treated with NPWT primarily as outpatients versus inpatients. Outpatient NPWT was defined as patients with ≤50% of NPWT coded during an inpatient hospitalization, whereas inpatient NPWT was defined as patients with >50% of NPWT. RESULTS: We identified 3184 patients (1621 inpatients and 1563 outpatients) aged 0-17 y, who were treated with NPWT from 2006 to 2014. Outpatient NPWT was implemented across multiple ages, comorbidities, and indications, with a low complication rate (2.4%). After controlling for hematologic comorbidity and indications, outpatient NPWT was associated with lower risk of complications (odds ratio: 0.57, 95% confidence interval 0.38-0.86) and lower median total costs ($5602.03) compared with inpatient ($15,233.21) therapy. CONCLUSIONS: Outpatient NPWT management in pediatric patients was associated with low complication rates. Additional studies are necessary to determine the most overall cost-effective treatment setting for NPWT in the pediatric population.

Proposed Federal Bill to Mandate Insurance Coverage for Children With Congenital Anomalies.

The Ensuring Lasting Smiles Act was reintroduced in United States Congress in March 2019. If enacted, the bill will substantially limit private insurers' ability to deny coverage for the medically necessary treatment of congenital anomalies, including cleft palate and craniofacial anomalies. Coverage denials are currently a barrier to care for these individuals, especially for patients residing in states lacking coverage mandates. The purpose of this article is to describe the issues underlying the proposed federal legislation and provide a policy discussion to better inform cleft and craniofacial providers about pending legislation relevant to their practice.