Transforming the Degradation Rate of ß-tricalcium Phosphate Bone Replacement Using 3-Dimensional Printing.

BACKGROUND: ß-Tricalcium phosphate (ß-TCP) is one of the most common synthetic bone grafting materials utilized in craniofacial reconstruction; however, it is limited by a slow degradation rate. The aim of this study was to leverage 3-dimensional (3D) printing in an effort to accelerate the degradation kinetics of ß-TCP. METHODS: Twenty-two 1-month-old New Zealand white rabbits underwent creation of calvarial and alveolar defects, repaired with 3D-printed ß-TCP scaffolds coated with 1000 µM of osteogenic agent dipyridamole. Rabbits were euthanized after 2, 6, and 18 months after surgical intervention. Bone regeneration, scaffold degradation, and bone mechanical properties were quantified. RESULTS: Histological analysis confirmed the generation of vascularized and organized bone. Microcomputed tomography analysis from 2 to 18 months demonstrated decreased scaffold volume within calvarial (23.6% ± 2.5%, 5.1% ± 2.2%; P < 0.001) and alveolar (21.5% ± 2.2%, 0.2% ± 1.9%; P < 0.001) defects, with degradation rates of 54.6%/year and 90.5%/year, respectively. Scaffold-inducted bone generation within the defect was volumetrically similar to native bone in the calvarium (55.7% ± 6.9% vs 46.7% ± 6.8%; P = 0.064) and alveolus (31.4% ± 7.1% vs 33.8% ± 3.7%; P = 0.337). Mechanical properties between regenerated and native bone were similar. CONCLUSIONS: Our study demonstrates an improved degradation profile and replacement of absorbed ß-TCP with vascularized, organized bone through 3D printing and addition of an osteogenic agent. This novel additive manufacturing and tissue engineering protocol has implications to the future of craniofacial skeletal reconstruction as a safe and efficacious bone tissue engineering method.

The Surgical Treatment of Robin Sequence: Neonatal Mandibular Distraction Osteogenesis in the Unfavorable Patient.

INTRODUCTION: Neonates with severe Pierre Robin sequence (PRS) can be treated by mandibular distraction osteogenesis (MDO), tongue-lip adhesion, or tracheostomy; however, there is an active debate regarding the indications of MDO in this patient population. Published algorithms identify tracheomalacia, bronchomalacia, laryngomalacia, hypotonic syndromes, and central sleep apnea as contraindications for MDO and indications for tracheostomy, but these comorbidities may exist along a spectrum of severity. The authors propose that appropriately selected neonates with PRS who concurrently express 1 or more of these traditional contraindications may be successfully treated with MDO. METHODS: The authors performed a 5-year retrospective chart review of all neonates who underwent MDO for treatment of severe PRS. All patients expressed a comorbidity previously identified as an indication for tracheostomy. Pre- and postoperative characteristics were recorded. Apnea/hypopnea index (AHI) before and after MDO were compared using 2-tailed repeated measures t-test. RESULTS: The authors identified 12 patients with severe PRS and conditions associated with contraindications to MDO: 9 (75.0%) patients had laryngomalacia, 6 (50.0%) patients had tracheomalacia, 2 (16.6%) patients had bronchomalacia, 1 (8.3%) patient had central sleep apnea, and 3 (25.0%) patients had hypotonia. Five (41.7%) patients underwent concurrent gastrostomy tube placement due to feeding insufficiency. Average birthweight was 3.0 kg. Average pre-op AHI was 34.8. Average post-op AHI was 7.3. All patients successfully underwent MDO with avoidance of tracheostomy. CONCLUSIONS: By employing an interdisciplinary evaluation of patient candidacy, MDO can safely and effectively treat upper airway obstruction and avoid tracheostomy in higher-risk neonatal patients with traditional indications for tracheostomy.

A reappraisal of the presence of small or large fiber neuropathy in patients with erythromelalgia.

OBJECTIVE: To assess the contribution of large and small nerve fiber alteration in erythromelalgia (EM). METHODS: Thirty-three EM patients were included and underwent clinical evaluation based on EM severity score, DN4, and Utah Early Neuropathy Scale (UENS) score. Neurophysiological evaluation consisted in nerve conduction studies (NCS) for large nerve fibers and specific tests for small nerve fibers: electrochemical skin conductance, cold and warm detection thresholds, and laser evoked potentials. Finally, the evaluation of vascular changes was based on the presence of clinical feature of microvascular disorders and the measurement of the Toe Pressure Index (TPI). RESULTS: While 28 patients (85%) had vascular alteration on TPI or clinical features, 23 patients (70%) had small-fiber neuropathy on neurophysiological tests, and only 10 patients (30%) had large fiber neuropathy on NCS. Regarding clinical scores, there was no difference between groups (presence or absence of large- or small-fiber neuropathy or microvascular disorder) except for a higher UENS score in patients with large fiber neuropathy. CONCLUSION: Peripheral neuropathy, mostly involving small nerve fibers, is almost as common as microvascular changes in EM, but remains inconstant and not related to a specific neuropathic pattern or higher clinical severity. SIGNIFICANCE: The association of neuropathic and vascular factors is not systematic in EM, this syndrome being characterized by different pathophysiological mechanisms leading to a common clinical phenotype.

What Is the Burden of Care of Nasoalveolar Molding?

OBJECTIVE: This systematic review aims to evaluate nasoalveolar molding (NAM) in the context of burden of care defined as physical, psychosocial, or financial burden on caregivers. SEARCH METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 5 databases were searched from inception through December 24, 2019, for keywords and subject headings pertaining to cleft lip and/or palate and NAM. ELIGIBILITY CRITERIA: Clinical studies on NAM with reference to physical (access to care, number of visits, distance traveled), psychosocial (caregiver perceptions, family interactions, breast milk feeding), and financial (direct and indirect costs) burden were included. DATA COLLECTION AND ANALYSIS: Study selection was performed by 2 independent reviewers. RESULTS: The search identified 1107 articles and 114 articles remained for qualitative synthesis. Burden of care domains were discussed but not measured in 43% of articles and only 25% assessed burden of care through a primary outcome. Of these, 20 articles reported on physical, 8 articles on psychosocial, and 12 articles on financial burden. Quality of evidence is limited by study design and risk of bias. CONCLUSION: Nasoalveolar molding has been indiscriminately associated with burden of care in the literature. Although NAM may not be the ideal treatment option for all patients and families, the physical considerations are limited when accounting for the observed psychosocial advantages. Financial burden appears to be offset, but further research is required. Teams should directly assess the impact of this early intervention on the well-being of caregivers and advance strategies that improve access to care.

Sleep-Disordered Breathing and Airway Assessment Using Polysomnography in Pediatric Patients With Craniofacial Disorders.

Children with cleft and craniofacial conditions commonly present with concurrent airway anomalies, which often manifest as sleep disordered breathing. Craniofacial surgeons and members of the multidisciplinary team involved in the care of these patients should appreciate and understand the scope of airway pathology as well as the proper means of airway assessment. This review article details the prevalence and assessment of sleep disordered breathing in patients with craniofacial anomalies, with emphasis on indications, limitations, and interpretation of polysomnography.

Dipyridamole-loaded 3D-printed bioceramic scaffolds stimulate pediatric bone regeneration in vivo without disruption of craniofacial growth through facial maturity.

This study investigates a comprehensive model of bone regeneration capacity of dypiridamole-loaded 3D-printed bioceramic (DIPY-3DPBC) scaffolds composed of 100% beta-tricalcium phosphate (ß -TCP) in an immature rabbit model through the time of facial maturity. The efficacy of this construct was compared to autologous bone graft, the clinical standard of care in pediatric craniofacial reconstruction, with attention paid to volume of regenerated bone by 3D reconstruction, histologic and mechanical properties of regenerated bone, and long-term safety regarding potential craniofacial growth restriction. Additionally, long-term degradation of scaffold constructs was evaluated. At 24 weeks in vivo, DIPY-3DPBC scaffolds demonstrated volumetrically significant osteogenic regeneration of calvarial and alveolar defects comparable to autogenous bone graft with favorable biodegradation of the bioactive ceramic component in vivo. Characterization of regenerated bone reveals osteogenesis of organized, vascularized bone with histologic and mechanical characteristics comparable to native bone. Radiographic and histologic analyses were consistent with patent craniofacial sutures. Lastly, through application of 3D morphometric facial surface analysis, our results support that DIPY-3DPBC scaffolds do not cause premature closure of sutures and preserve normal craniofacial growth. Based on this novel evaluation model, this DIPY-3DPBC scaffold strategy is a promising candidate as a safe, efficacious pediatric bone tissue engineering strategy.

Unilateral Cleft Lip Repair: A Quantitative Scale Assessment of Postoperative Lip and Nose Scars Across 2 Operative Techniques.

BACKGROUND: There is no quantitative evidence supporting one unilateral cleft lip (UCL) repair technique over the other with regard to scarring. We sought to evaluate the difference between the extended Mohler and Millard techniques, using 3 scar assessment scales. METHODS: Postoperative frontal and basal photographs of patients undergoing UCL repair were reviewed. Three validated scar assessment scales were used: the Manchester Scar Scale (MSS), modified scar-rating scale (MSRS), and Stony Brook Scar Evaluation Scale. Lip and nose scars were rated by 5 independent raters using each of the scales. Interrater reliability was assessed using the intraclass correlation coefficient (ICC). RESULTS: Assessment of 116 images for 58 consecutive patients undergoing UCL repair (36 extended Mohler, 22 Millard) was performed. Interrater reliability was excellent for lip scars (ICCs, 0.903 [0.857-0.938] for MSS, 0.913 [0.872-0.944] for MSRS, and 0.850 [0.775-0.902] for SBES) and moderate for nose scar assessment (ICCs, 0.714 [0.579-0.816] for MSS, 0.693 [0.548-0.802] for MSRS, and 0.565 [0.359-0.720] for SBES). No statistically significant difference was found between the extended Mohler and Millard repairs in mean lip scar scores (MSS, 6.983 ± 1.469 vs 6.772 ± 1.175, P = 0.571; MSRS, 5.433 ± 1.530 vs 5.481 ± 1.290, P = 0.902; SBES, 3.633 ± 0.977 vs 3.446 ± 0.995, P = 0.483) or nose scar scores (MSS, 5.644 ± 1.131 vs 5.491 ± 0.689, P = 0.523; MSRS, 4.233 ± 0.987 vs 3.991 ± 0.705, P = 0.320; SBES, 3.933 ± 0.750 vs 4.018 ± 0.486, P = 0.603). CONCLUSIONS: Using 3 validated scar assessment scales, no significant difference was found between the extended Mohler and Millard techniques in terms of lip or nose scars.

Safety and Efficacy of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) in Craniofacial Surgery.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is one of the most commonly used osteogenic agents in the craniofacial skeleton. This study reviews the safety and efficacy of rhBMP-2 as applied to craniofacial reconstruction and assesses the level of scientific evidence currently available. METHODS: An extensive literature search was conducted. Randomized controlled trials (RCTs), case series and reports in the English language as well as Food and Drug Administration reports were reviewed. Studies were graded using the Oxford Center for Evidence-Based Medicine Levels of Evidence Scale. Data heterogeneity precluded quantitative analysis. RESULTS: Seventeen RCTs (Levels of evidence: Ib-IIb) were identified evaluating the use of rhBMP-2 in maxillary sinus, alveolar ridge, alveolar cleft, or cranial defect reconstruction (sample size: 7-160; age: 8-75 years). Study designs varied in rigor, with follow-up ranging 3-36 months, and outcome assessment relying on clinical exam, radiology, and/or histology. There was wide variation in rhBMP-2 concentrations, carriers, and controls. Most studies evaluating rhBMP-2 for cranial defect closure, mandibular reconstruction, or distraction osteogenesis consisted of retrospective cohorts and case reports. The evidence fails to support RhBMP-2 use in maxillary sinus wall augmentation, calvarial reconstruction, mandibular reconstruction, or distraction osteogenesis. RhBMP-2 may be effective in alveolar reconstruction in adults, but is associated with increased postoperative edema. CONCLUSIONS: A risk-benefit ratio favoring rhBMP-2 over alternative substitutes remains to be demonstrated for most applications in plastic and reconstructive surgery. Long-term data on craniofacial growth is lacking, and using rhBMP-2 in patients younger than 18 years remains off-label.

Qualitative Assessment of Columella Scar Quality After Extended Mohler Unilateral Cleft Lip Repair.

BACKGROUND: The Extended Mohler cleft lip repair restores upper lip form using a columellar flap to fill the defect created by the downward rotation of Cupid's bow. The resulting columella incision is mentioned as a potential drawback. This study seeks to evaluate the morbidity of the resulting scar. MATERIALS AND METHODS: This retrospective study enrolled 50 unilateral cleft lip patients treated using the Extended Mohler repair. 5 reviewers examined post-operative images. Three validated scar assessment scales were utilized: Manchester Scar Scale (MSS), Modified Scar-Rating Scale (MSRS), and Stony Brook Scar Evaluation Scale (SBSES). A scar score for the lip and columellar portion of each patient was determined. RESULTS: Three different scar scales demonstrated significantly better scar quality for the columellar portion of the scar compared to the lip portion. The average score for the lip and columella using the MSS was 7.0 ±â€Š1.4 and 5.7 ±â€Š1.1 (P <0.001). The average score for the lip and columella using the MSRS was 5.5 ±â€Š1.4 and 4.3 ±â€Š0.9 (P <0.001). The average score for the lip and columella using the SBSES was 3.5 ±â€Š1.1 and 3.9 ±â€Š0.7 (P = 0.014). The intraclass correlation coefficient for lip scar assessments was 0.901 (MSS), 0.91 (MSRS), and 0.873 (Stony Brook Evaluation Scale [SBES]). The intraclass correlation coefficient for columellar scar assessment was 0.786 (MSS), 0.761 (MSRS), and 0.726 (SBES). CONCLUSION: The Extended Mohler unilateral cleft lip columellar scar is of superior quality compared to the lip portion. This analysis ameliorates one of the major concerns regarding the Extended Mohler cleft lip repair.

Assessment of American Cleft Palate-Craniofacial Association-Approved Teams' Websites for Patient-Oriented Content and Readability.

OBJECTIVE: Informed decision-making relies on available information, including online resources. We evaluated the content and readability of websites published by American Cleft Palate-Craniofacial Association (ACPA)-approved cleft lip and/or palate (CLP) teams in the United States. DESIGN: Team websites were reviewed, and teams with no accessible website or <30 sentences of content were excluded. Website content was scored by presence/absence of 20 variables derived from ACPA approval standards. Readability was evaluated with 8 scales. Readability was then compared to American Medical Association (AMA) recommendations. The relationship between website content and readability was assessed. MAIN OUTCOME MEASURE(S): Content and readability of team websites. RESULTS: From 167 reviewed teams, 47 (28.1%) had nonfunctional links, 17 (10.2%) had no accessible website, and 39 (23.4%) had <30 sentences. The average content score for all 111 team websites included was 14.5 (2.6) of 20. The combined average reading level across all scales (10.7 [1.9]) exceeded the AMA-recommended sixth-grade reading level; this finding held true for each individual website. Children's Hospital-affiliated teams (n = 86) had a significantly higher content score (14.8 vs 13.5; P = .03) and better readability as evidenced by lower reading grade level (10.5 vs 11.4; P = .04). On linear regression, a higher content score significantly predicted better readability (ß = -0.226; P < .001). CONCLUSIONS: Websites published by ACPA-approved CLP teams vary in accessibility and content and exceed the recommended reading level. These findings could inform future efforts to improve patient-oriented resources.

Nasolabial Aesthetics Following Cleft Repair: An Objective Evaluation of Subjective Assessment.

OBJECTIVE: Assess the weight and contribution of each of the parameters of the Asher-McDade Scale to overall subjective assessment of nasolabial aesthetics following cleft lip repair. DESIGN: Retrospective cohort evaluation. SETTING: Cleft and craniofacial center. PARTICIPANTS: Forty-one patients who underwent unilateral cleft lip repair. INTERVENTIONS: Unilateral cleft lip repair. MAIN OUTCOME MEASURES: Nasolabial rating using the Asher-McDade scale and overall subjective assessment of nasolabial aesthetics using a rank score following unilateral cleft lip repair. RESULTS: Strong interrater reliability was observed between the 3 raters. Significant association was determined on bivariate analysis between nasal form score (ß = 27.06; P < .001), nasal symmetry score (ß = 26.41; P < .001), nasal profile score (ß = 28.75; P < .001), vermilion border score (ß = 13.40; P = .012), and the ranking score. Adjusted ß coefficients obtained from multivariate regression analysis were used to develop a modified nasolabial appearance score (over 5), that is, weighted for each of the 4 parameters: nasal form (over 8, adjusted ß = 14.33), nasal symmetry (over 5, adjusted ß = 7.96), nasal profile (over 5, adjusted ß = 9.44), and vermilion (over 2, adjusted ß = 3.31). Regression analysis between our modified nasolabial appearance score and patient ranking score demonstrated superior goodness of fit when compared to the Asher-McDade overall nasolabial appearance score (R2 = .80; P < .001 vs R2 = .69; P < .001). CONCLUSION: The parameters evaluated in the Asher-McDade scale have different weights and contribute differently to overall subjective assessment of nasolabial aesthetic outcomes following cleft lip repair. Adjusting for their weights results in a modified score that demonstrates superior correlation with overall subjective assessment of nasolabial aesthetic outcomes.

Breast Reconstruction in an Underserved Population: A Retrospective Study.

BACKGROUND: Breast reconstruction can help restore the shape and appearance of breasts after surgery. Studies have shown that minority and uninsured patients are less likely to receive breast reconstruction after mastectomy. OBJECTIVE: We sought to determine if post-mastectomy reconstruction varied by patient ethnicity and insurance status in a medically underserved population. METHODS: This was a retrospective study of mastectomy patients seen at Bellevue Hospital Center, a safety-net hospital in New York City, between January 2010 and December 2015. The Chi square test was used to compare patient characteristics versus type of reconstruction chosen and likelihood of reconstruction. Logistic regression was used to examine likelihood of reconstruction, controlling for patient insurance status, race, age, stage at presentation, and contralateral prophylactic mastectomy. RESULTS: Of the 750 patients included in the database, 220 underwent mastectomy. Overall, 73.6% of our patient population received breast reconstruction. Patients with Medicare insurance were less likely to get reconstruction compared with patients with other types of insurance (37.5%, p = 0.04). Hispanic patients were most likely to receive reconstruction (89.1%), followed by Black patients (80%) and Asian patients (66.7%) [p = 0.03]. There were no significant associations between patient race or stage at presentation and type of reconstruction. In a multivariate logistic regression, advancing age was associated with a decreased likelihood of reconstruction (adjusted odds ratio 0.91, p < 0.001). CONCLUSIONS: In our underserved patient population, patients received breast reconstruction at rates higher than the national average. Institutional availability of patient navigators and preoperative counseling may contribute to more equal access to breast reconstruction.

Extended wakefulness: compromised metabolics in and degeneration of locus ceruleus neurons.

Modern society enables a shortening of sleep times, yet long-term consequences of extended wakefulness on the brain are largely unknown. Essential for optimal alertness, locus ceruleus neurons (LCns) are metabolically active neurons that fire at increased rates across sustained wakefulness. We hypothesized that wakefulness is a metabolic stressor to LCns and that, with extended wakefulness, adaptive mitochondrial metabolic responses fail and injury ensues. The nicotinamide adenine dinucleotide-dependent deacetylase sirtuin type 3 (SirT3) coordinates mitochondrial energy production and redox homeostasis. We find that brief wakefulness upregulates SirT3 and antioxidants in LCns, protecting metabolic homeostasis. Strikingly, mice lacking SirT3 lose the adaptive antioxidant response and incur oxidative injury in LCns across brief wakefulness. When wakefulness is extended for longer durations in wild-type mice, SirT3 protein declines in LCns, while oxidative stress and acetylation of mitochondrial proteins, including electron transport chain complex I proteins, increase. In parallel with metabolic dyshomeostasis, apoptosis is activated and LCns are lost. This work identifies mitochondrial stress in LCns upon wakefulness, highlights an essential role for SirT3 activation in maintaining metabolic homeostasis in LCns across wakefulness, and demonstrates that extended wakefulness results in reduced SirT3 activity and, ultimately, degeneration of LCns.