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.

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.

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.

Buccal Myomucosal Flap Repair for Velopharyngeal Dysfunction.

BACKGROUND: Velopharyngeal dysfunction (VPD) is the incomplete separation of the nasal and oral cavities during speech sound production that can persist following primary palatoplasty. Surgical technique used in management of VPD (palatal re-repair versus pharyngeal flap or sphincter pharyngoplasty) is often dictated by the preoperative velar closing ratio and closure pattern. Recently, buccal flaps have increased in popularity in management of VPD. Here, the authors investigate the effectiveness of buccal myomucosal flaps in the treatment of VPD. METHODS: A retrospective review was performed of all patients undergoing secondary palatoplasty with buccal flaps at a single center between 2016 and 2021. Preoperative and postoperative speech outcomes were compared. Speech assessments included perceptual examinations, graded on a four-point scale of hypernasality, and speech videofluoroscopy, from which the velar closing ratio was obtained. RESULTS: A total of 25 patients underwent buccal myomucosal flap procedures for VPD at a median of 7.1 years after primary palatoplasty. Patients had significantly increased velar closing postoperatively (95% versus 50%; P < 0.001) and improved speech scores ( P < 0.001). Three patients (12%) had continued hypernasality postoperatively. There were no occurrences of obstructive sleep apnea. CONCLUSIONS: Treatment of VPD with buccal myomucosal flaps leads to improved speech outcomes without the risk of obstructive sleep apnea. Traditionally, palatal re-repair techniques have been used for smaller preoperative velopharyngeal gaps; however, the addition of buccal flaps allows for anatomical velar muscle correction for patients with a larger preoperative velopharyngeal gap. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

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.

What do patients want to know about gender-affirming surgery? Analysis of common patient concerns and online health materials.

PURPOSE: Patients considering gender-affirming surgery often utilize online health materials to obtain information about procedures. However, the distribution of patient concerns and content of online resources for gender-affirming surgery have not been examined. We aimed to quantify and comprehensively analyze the most searched questions of patients seeking gender-affirming surgery and to examine the quality and readability of associated websites providing the answers. METHODS: Questions were extracted from Google using the search phrases "gender-affirming surgery," "transgender surgery," "top surgery," and "bottom surgery." Questions were categorized by topic and average search volume per month was determined. Websites linked to questions were categorized by type, and quality of the health information was evaluated utilizing the DISCERN instrument (16-80). Readability was assessed with the Flesch Reading Ease Score and Flesch-Kincaid Grade Level. RESULTS: Ninety questions and associated websites were analyzed. Common questions were most frequently answered by academic websites (30%). Topics included cost (27%), technical details of surgery (23%), and preoperative considerations (11%). Median (interquartile range) DISCERN score across all website categories was 42 (18). The mean readability was of a 12th-grade level, well above the grade six reading level recommended by the American Medical Association. CONCLUSIONS: Online gender-affirming surgery materials are difficult to comprehend and of poor quality. To enhance patient knowledge, informed consent, and shared decision-making, there is a substantial need to create understandable and high-quality online health information for those seeking gender-affirming surgery.

Terminal Schwann Cells Are Essential for Neuromuscular Junction Function and Recovery after Nerve Injury.

BACKGROUND: Terminal Schwann cells (tSCs), nonmyelinating glial cells at the neuromuscular junction (NMJ), are integral to NMJ development, function, remodeling, and response to injury. It is essential to understand their requirement for NMJ function. In this study, the authors assessed consequences of immune-mediated tSC ablation in adult S100 -GFP mice of both sexes in homeostasis and after nerve injury. METHODS: The authors examined NMJ morphology and function in the extensor digitorum longus muscle during homeostasis at post-tSC ablation days 3, 14, and 42 and after peroneal nerve transection and immediate repair at 3 and 6 weeks after nerve injury and tSC ablation (postinjury and ablation). RESULTS: tSC ablation resulted in significant decreases ( P < 0.05) in tSC numbers per NMJ and end plate fragmentation. NMJ innervation and EDL tetanic force were significantly decreased at post-tSC ablation day 14 ( P < 0.05) and tSCs reestablished their NMJ coverage at post-tSC ablation day 42. After nerve injury, motor end plate fragmentation increased ( P < 0.01) with tSC ablation compared with injured control mice. NMJ reinnervation and extensor digitorum longus tetanic force were significantly reduced ( P < 0.001), even at 6 weeks postinjury and ablation, compared with control mice. CONCLUSION: These results add to the understanding that tSCs, with their proregenerative potential, help maintain NMJ integrity in homeostasis and are necessary for NMJ reinnervation after peripheral nerve injury. CLINICAL RELEVANCE STATEMENT: Terminal Schwann cells are integral for efficient NMJ recovery after nerve injury. This cell population may provide a novel therapeutic target to improve outcomes for patients with nerve injuries; additional investigation is warranted.

Loss of Gata1 decreased eosinophils, macrophages, and type 2 cytokines in regenerating nerve and delayed axon regeneration after a segmental nerve injury.

The immune system has garnered attention for its role in peripheral nerve regeneration, particularly as it pertains to regeneration across segmental injuries. Previous work demonstrated that eosinophils are recruited to regenerating nerve and express interleukin-4, amongst potential cytokines. These results suggest a direct role for eosinophils in promoting nerve regeneration. Therefore, we further considered eosinophils roles in nerve regeneration using a segmental nerve injury and Gata1 knockout (KO) mice, which are severely eosinophil deficient, compared to wild-type BALB/c mice (WT). Mice receiving a sciatic nerve gap injury demonstrated distinct cytokine expression and leukocytes within regenerating nerve. Compared to controls, Gata1 KO regenerated nerves contained decreased expression of type 2 cytokines, including Il-5 and Il-13, and decreased recruitment of eosinophils and macrophages. At this early time point during ongoing regeneration, the macrophages within Gata1 KO nerves also demonstrated significantly less M2 polarization compared to controls. Subsequently, motor and sensory axon regeneration across the gap injury was decreased in Gata1 KO compared to WT during ongoing nerve regeneration. Over longer observation to allow for more complete nerve regeneration, behavioral recovery measured by grid-walk assessment was not different comparing groups but modestly delayed in Gata1 KO compared to WT. The extent of final axon regeneration was not different amongst groups. Our data provide additional evidence suggesting eosinophils contribute to nerve regeneration across a nerve gap injury, but are not essential to regeneration in this context. Our evidence also suggests eosinophils may regulate cytokines that promote distinct macrophage phenotypes and axon regeneration.

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.

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.

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.

Incidence and Management of Facial Paralysis After Skull Base Trauma, an Administrative Database Study.

OBJECTIVE: Report the incidence of and treatment patterns for facial nerve palsy after skull base fracture. STUDY DESIGN: Retrospective cohort study. SETTING: IBM MarketScan Commercial Database (2006-2019). PATIENTS: Human subjects with skull base fracture, per International Classification of Diseases-9th and 10th Revisions-Clinical Modification diagnosis codes. MAIN OUTCOME MEASURES: The primary outcomes were the incidence and median time to facial nerve palsy diagnosis within 30 days of skull base fracture. Secondary outcomes were treatments (corticosteroids, antivirals, facial nerve decompression, botulinum toxin, and facial reanimation), demographics, and rates of hearing loss, vertigo, tympanic membrane rupture, cerebrospinal fluid leak, comorbidities, and loss of consciousness. RESULTS: The 30-day incidence of facial nerve palsy after skull base trauma was 1.0% (738 of 72,273 patients). The median (95% confidence interval [CI]) time to diagnosis was 6 (6-7) days, and only 22.9% were diagnosed within 1 day. There were significantly higher rates (risk difference, 95% CI) of hearing loss (26%, 22-29%), tympanic membrane rupture (6.3%, 4.5-8.1%), cerebrospinal fluid leak (6.4%, 4.5-8.3%), comorbidity (14%, 10.4-17.6%), and loss of consciousness (24.3%, 20.7-27.9%). Loss of consciousness was associated with longer median (95% CI) time to facial nerve palsy diagnosis: 10 (9-10) days. Corticosteroids were the most common treatment but only reported for less than one-third of patients. Only eight patients underwent facial nerve decompression. CONCLUSIONS: Facial nerve palsy after skull base fracture is associated with higher comorbidity, and the diagnosis is often delayed. Few patients were treated with surgery, and there are inconsistencies in the types and timing of treatments.

Dispose with dish soap: A simple and convenient method to increase proper opioid disposal in postoperative pediatric patients.

BACKGROUND: The opioid abuse crisis is rampant in the United States. Children and adolescents are unique risk groups in this crisis; age-specific concerns include accidental ingestion and association with high-risk behaviors. Studies aimed at disposal are limited in pediatric patients. Our study aimed to determine whether an educational brochure detailing a simple opioid disposal method using dish soap could enhance disposal in postoperative pediatric patients. METHODS: A prospective survey study of pediatric plastic surgery patients at the St. Louis Children's Hospital was performed from January to December 2020. Patients were assigned into two groups: those who received the educational brochure at the time of surgery and those who did not. In clinic, patient caretakers completed anonymous preoperative and/or postoperative surveys regarding opioid use and disposal. RESULTS: Surveys of 326 patients were analyzed (188 preoperative, 120 pre/postoperative, and 18 postoperative). Prescribed opioids were all consumed in 19% of patients. Receiving the educational brochure significantly increased the opioid disposal of leftover medications: 78% versus 35% (OR 6.52, 95% CI [2.03, 21.37], p < 0.001). Although not statistically significant owing to small sample size (p = 0.09), 71.4% of families with excess opioids in the home preoperatively retained unused postoperative opioids versus 31.6% without preoperative opioids. CONCLUSIONS: Postoperative opioids are overprescribed for most pediatric plastic surgery patients. A simple brochure significantly increases proper postoperative opioid disposal, representing a cost-effective, convenient, risk-free method to decrease opioid misuse and accumulation in our communities.

Short-Duration, Pulsatile, Electrical Stimulation Therapy Accelerates Axon Regeneration and Recovery following Tibial Nerve Injury and Repair in Rats.

BACKGROUND: Repair of nerve injuries can fail to achieve adequate functional recovery. Electrical stimulation applied at the time of nerve repair can accelerate axon regeneration, which may improve the likelihood of recovery. However, widespread use of electrical stimulation may be limited by treatment protocols that increase operative time and complexity. This study evaluated whether a short-duration electrical stimulation protocol (10 minutes) was efficacious to enhance regeneration following nerve repair using rat models. METHODS: Lewis and Thy1-green fluorescent protein rats were randomized to three groups: 0 minutes of electrical stimulation (no electrical stimulation; control), 10 minutes of electrical stimulation, and 60 minutes of electrical stimulation. All groups underwent tibial nerve transection and repair. In the intervention groups, electrical stimulation was delivered after nerve repair. Outcomes were assessed using immunohistochemistry, histology, and serial walking track analysis. RESULTS: Two weeks after nerve repair, Thy1-green fluorescent protein rats demonstrated increased green fluorescent protein-positive axon outgrowth from the repair site with electrical stimulation compared to no electrical stimulation. Serial measurement of walking tracks after nerve repair revealed recovery was achieved more rapidly in both electrical stimulation groups as compared to no electrical stimulation. Histologic analysis of nerve distal to the repair at 8 weeks revealed robust axon regeneration in all groups. CONCLUSIONS: As little as 10 minutes of intraoperative electrical stimulation therapy increased early axon regeneration and facilitated functional recovery following nerve transection with repair. Also, as early axon outgrowth increased following electrical stimulation with nerve repair, these findings suggest electrical stimulation facilitated recovery because of earlier axon growth across the suture-repaired site into the distal nerve to reach end-organ targets. CLINICAL RELEVANCE STATEMENT: Brief (10-minute) electrical stimulation therapy can provide similar benefits to the 60-minute protocol in an acute sciatic nerve transection/repair rat model and merit further studies, as they represent a translational advantage.

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.

Incidence of Nerve Injury After Extremity Trauma in the United States.

BACKGROUND: Traumatic peripheral nerve injuries cause chronic pain, disability, and long-term reductions in quality of life. However, their incidence after extremity trauma remains poorly understood. METHODS: The IBM® MarketScan® Commercial Database from 2010 to 2015 was used to identify patients aged 18 to 64 who presented to emergency departments for upper and/or lower extremity traumas. Cumulative incidences were calculated for nerve injuries diagnosed within 2 years of trauma. Cox regression models were developed to evaluate the associations between upper extremity nerve injury and chronic pain, disability, and use of physical therapy or occupational therapy. RESULTS: The final cohort consisted of 1 230 362 patients with employer-sponsored health plans. Nerve injuries were diagnosed in 2.6% of upper extremity trauma patients and 1.2% of lower extremity trauma patients. Only 9% and 38% of nerve injuries were diagnosed by the time of emergency department and hospital discharge, respectively. Patients with nerve injuries were more likely to be diagnosed with chronic pain (hazard ratio [HR]: 5.9, 95% confidence interval [CI], 4.3-8.2), use physical therapy services (HR: 10.7, 95% CI, 8.8-13.1), and use occupational therapy services (HR: 19.2, 95% CI, 15.4-24.0) more than 90 days after injury. CONCLUSIONS: The incidence of nerve injury in this national cohort was higher than previously reported. A minority of injuries were diagnosed by emergency department or hospital discharge. These findings may improve practitioner awareness and inform public health interventions for injury prevention.

The Effects of Intraoperative Electrical Stimulation on Regeneration and Recovery After Nerve Isograft Repair in a Rat Model.

Background: Therapeutic electrical stimulation (ES) applied to repaired nerve is a promising treatment option to improve regeneration. However, few studies address the impact of ES following nerve graft reconstruction. The purpose of this study was to determine if ES applied to a nerve repair using nerve isograft in a rodent model could improve nerve regeneration and functional recovery. Methods: Adult rats were randomized to 2 groups: "ES" and "Control." Rats received a tibial nerve transection that was repaired using a tibial nerve isograft (1.0 cm length), where ES was applied immediately after repair in the applicable group. Nerve was harvested 2 weeks postrepair for immunohistochemical analysis of axon growth and macrophage accumulation. Independently, rats were assessed using walking track and grid-walk analysis for up to 21 weeks. Results: At 2 weeks, more robust axon regeneration and greater macrophage accumulation was observed within the isografts for the ES compared to Control groups. Both walking track and grid-walk analysis revealed that return of functional recovery was accelerated by ES. The ES group demonstrated improved functional recovery over time, as well as improved recovery compared to the Control group at 21 weeks. Conclusions: ES improved early axon regeneration into a nerve isograft and was associated with increased macrophage and beneficial M2 macrophage accumulation within the isograft. ES ultimately improved functional recovery compared to isograft repair alone. This study supports the clinical potential of ES to improve the management of nerve injuries requiring a nerve graft repair.

IL-4 expressing cells are recruited to nerve after injury and promote regeneration.

Interleukin-4 (IL-4) has garnered interest as a cytokine that mediates regeneration across multiple tissues including peripheral nerve. Within nerve, we previously showed endogenous IL-4 was critical to regeneration across nerve gaps. Here, we determined a generalizable role of IL-4 in nerve injury and regeneration. In wild-type (WT) mice receiving a sciatic nerve crush, IL-4 expressing cells preferentially accumulated within the injured nerve compared to affected sites proximal, such as dorsal root ganglia (DRGs), or distal muscle. Immunohistochemistry and flow cytometry confirmed that eosinophils (CD45+, CD11b+, CD64-, Siglec-F+) were sources of IL-4 expression. Examination of targets for IL-4 within nerve revealed macrophages, as well as subsets of neurons expressed IL-4R, while Schwann cells expressed limited IL-4R. Dorsal root ganglia cultures were exposed to IL-4 and demonstrated an increased proportion of neurons that extended axons compared to cultures without IL-4 (control), as well as longer myelinated axons compared to cultures without IL-4. The role of endogenous IL-4 during nerve injury and regeneration in vivo was assessed following a sciatic nerve crush using IL-4 knockout (KO) mice. Loss of IL-4 affected macrophage accumulation within injured nerve compared to WT mice, as well as shifted macrophage phenotype towards a CD206- phenotype with altered gene expression. Furthermore, this loss of IL-4 delayed initial axon regeneration from the injury crush site and subsequently delayed functional recovery and re-innervation of neuromuscular junctions compared to wild-type mice. Given the role of endogenous IL-4 in nerve regeneration, exogenous IL-4 was administered daily to WT mice following a nerve crush to examine regeneration. Daily IL-4 administration increased early axonal extension and CD206+ macrophage accumulation but did not alter functional recovery compared to untreated mice. Our data demonstrate IL-4 promotes nerve regeneration and recovery after injury.