Longitudinal Assessment of Neurodevelopment in Patients With Nonsyndromic Single-Suture Craniosynostosis: A Retrospective Review of 66 Patients.

The neurodevelopmental consequences of nonsyndromic single-suture (NSS) craniosynostosis are the subject of continued debate. Although the predictive validity of the Bayley Scales of Infant and Toddler Development (Third Edition) (BSID-III) have been questioned, this neurodevelopmental testing battery continues to be widely utilized among multidisciplinary craniofacial teams. The purpose of this study is to evaluate the neurodevelopmental functioning of patients with NSS craniosynostosis before and after surgical correction and the impact of surgical correction on neurodevelopmental trajectory based on BSID-III testing. All patients with NSS craniosynostosis who underwent cranial vault remodeling between 2009 and 2020 were considered for inclusion. Patients who failed to complete BSID-III testing within 2 months of surgery preoperatively and 2 years of surgery postoperatively were excluded. A total of 66 patients met criteria for the study. On language testing, both the preoperative mean score ( P =0.007) and postoperative mean score ( P =0.003) were significantly lower than the population norm. Furthermore, on motor testing, both the preoperative mean score ( P =0.005) and postoperative mean score ( P =0.001) were significantly lower than the population norm. Bayley Scales of Infant and Toddler Development (Third Edition) testing revealed no significant change between preoperative and postoperative neurodevelopmental functioning. Overall, this study suggests that patients with NSS craniosynostosis experience modest delays in language and motor development, which are present before and after cranial vault remodeling. In addition, this study provides evidence that cranial vault remodeling does not significantly impact the neurodevelopmental trajectory. Multicenter st udies and refined neurodevelopmental testing methods are necessary to definitively establish the neurodevelopmental implications of NSS craniosynostosis.

Assessing the Key Predictors of an Academic Career after Craniofacial Surgery Fellowship.

BACKGROUND: As craniofacial fellowship positions outnumber the availability of academic craniofacial jobs, it is important to understand the factors associated with securing an academic position after fellowship. The purpose of this study was to evaluate the impact of bibliometric indices and trainee demographics on the ability to obtain a full-time academic plastic surgery position on completion of a craniofacial fellowship. METHODS: Craniofacial fellowship graduates between 2009 and 2018 (n = 182) were identified. Initial job placement and demographic data were collected; bibliometric indices at fellowship completion were calculated. Chi-square and Fisher's exact tests and multivariable logistic regression were used to assess the association of select factors with job placement. RESULTS: Of the 48.9 percent of fellows that secured academic positions, 39.3 percent trained at five fellowship institutions. The majority of those completing residency at top institutions for academic surgery and research entered academic positions at fellowship completion. Geography influenced academic placement, as 72.7 percent of trainees in the Northeast secured academic positions. Only 20.3 percent of fellows completed dedicated postgraduate research time, but among these, 70.3 percent entered academic jobs. The h-index (OR, 1.14; p = 0.01) and total manuscripts (OR, 1.04; p = 0.02) were significantly associated with academic practice while adjusting for other covariates. CONCLUSIONS: Although residency training institution, geographic location, and postgraduate research may influence academic placement, the h-index and total manuscripts represent the best predictors of academic careers after craniofacial fellowship. This information is valuable for applicants who aspire to be academic craniofacial surgeons, and for programs and educators who can use these data to identify applicants with a propensity for academics.

Variation in the Utilization of Postoperative Computed Tomography for Patients With Nonsyndromic Craniosynostosis: A National Claims Analysis.

OBJECTIVE: Routine postoperative computed tomography (CT) imaging in nonsyndromic craniosynostosis remains controversial due to the hazards of radiation exposure. The extent to which postoperative head CTs are performed remains unknown. Therefore, we sought to measure the use of postoperative CTs in this population. DESIGN: The authors reviewed insurance claims from OptumInsight, using Current Procedural Terminology codes to identify procedures and postoperative imaging. Multilevel logistic regression was used to describe the odds of undergoing postoperative CTs, adjusting for patient and provider covariates. PARTICIPANTS: Craniosynostosis patients who underwent reconstruction between 2001 and 2017 were reviewed. Patients older than 5 years at surgery, postoperative lengths of stay >15 days, syndromic diagnoses, operative complications within 30 days of surgery, and cranial bone grafting merited exclusion. MAIN OUTCOME MEASURE: Odds of postoperative head CTs after cranial vault reconstruction. RESULTS: In this cohort (n = 1150), 326 (28.4%) patients underwent postoperative head CTs. The number of CTs ranged from 0 to 14. Older age at surgery (odds ratio [OR]: 1.32, P = .002), increasing years of follow-up (OR: 1.12, P < .001), and increasing comorbidities (OR: 1.21, P = .017) were associated with postoperative CTs. After adjusting for patient factors, provider factors accounted for 31.3% of variation in imaging. CONCLUSIONS: Over a quarter of patients underwent head CTs following reconstruction, and provider factors accounted for a large percentage of the variation. Given the risks of radiation, neurosurgeons and craniofacial surgeons face a critical need to establish postoperative imaging protocols to reduce unnecessary imaging in these vulnerable patients.

The Feasibility and Validity of PROMIS: A Novel Measure of Quality of Life among Children with Cleft Lip and Palate.

BACKGROUND: Health-related quality of life is inconsistently captured among children with cleft lip and palate. The Patient-Reported Outcomes Measurement Information System (PROMIS) captures health-related quality of life, with the added benefit of comparability across clinical conditions. In this study, the authors define the validity and feasibility of PROMIS among children with clefts. METHODS: Children with cleft lip and palate who were at least 5 years old and able to complete instruments independently were eligible for inclusion (n = 93). Children completed PROMIS anxiety, depression, and peer relationship item banks as short forms or computerized adaptive tests. Participants also completed the Pediatric Quality of Life Inventory. Construct validity was measured by Spearman correlations between PROMIS and the Pediatric Quality of Life Inventory controlling for race, sex, age, and income. Feasibility was measured using instrument completion time, reading level, and floor/ceiling effects. RESULTS: PROMIS computerized adaptive tests (peer relationship, r = 0.49; depression, r = -0.56; and anxiety, r = -0.36) and short forms (peer relationship, r = 0.65; depression, r = -0.54; and anxiety, r = -0.56) demonstrated moderate correlation with the Pediatric Quality of Life Inventory. Computerized adaptive tests had fewer floor (0 percent versus 0 percent) and ceiling (8.6 to 19.3 percent versus 21.8 to 41.9 percent) effects than short forms, and demonstrated better readability. Computerized adaptive tests required more time than short forms (peer relationship, 0.84 ± 0.67 versus 1.3 ± 0.92; depression, 0.52 ± 0.38 versus 1.1 ± 0.73; and anxiety, 0.53 ± 0.23 versus 1.1 ± 0.62; p = 0.001), as each computerized adaptive test included on average four more questions. CONCLUSIONS: PROMIS correlates well with the Pediatric Quality of Life Inventory and demonstrates similar accuracy, with better readability and efficiency. Use of PROMIS will improve our ability to compare children with cleft lip and palate to diverse populations and clinical conditions. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.

Morphomic measurement of the temporalis muscle and zygomatic bone as novel predictors of hospital-based clinical outcomes in patients with mandible fracture.

INTRODUCTION: Patients with mandibular fracture often have comorbidities and concomitant injuries making the decision for when and how to operate a challenge. Physicians describe "temporalis wasting" as a finding that indicates frailty; however, this is a subjective finding without quantitative values. In this study, we demonstrate that decreased morphomic values of the temporalis muscle and zygomatic bone are an objective measure of frailty associated with increased injury-induced morbidity as well as negative impact on overall hospital-based clinical outcomes in patients with mandible fracture. METHODS: Computed tomographic (CT) scans from all patients with a diagnosis of a mandible fracture in the University of Michigan trauma registry and with a hospital admission were collected from the years 2004 to 2011. Automated, high-throughput CT analysis was used to reconstruct the anatomy and quantify morphomic values (temporalis volume, area and thickness, and zygomatic thickness) in these patients using MATLAB v13.0 (MathWorks Inc, Natick, MA, USA). Subsequently, a subset of 16 individuals with a Glasgow Coma Scale of 14 or 15 was analyzed to control for brain injury. Clinical data were obtained, and the association between morphomic measurements and clinical outcomes was evaluated using Pearson correlation for unadjusted analysis and multiple regression for adjusted analysis. RESULTS: The mean age of patients in the study was 47.1 years. Unadjusted analysis using Pearson correlation revealed that decreases in zygomatic bone thickness correlated strongly with increases in hospital, intensive care unit, and ventilator days (P < 0.0001, P = 0.0003, and P = 0.0017, respectively). Furthermore, we found that decreases in temporalis mean thickness correlated with increases in hospital and ventilator days (P = 0.0264 and P = 0.0306, respectively). Similarly, decreases in temporalis local mean thickness are significantly correlated with increases in hospital and ventilator days (P = 0.0232 and P = 0.0472, respectively). CONCLUSIONS: Decreased thicknesses of the zygomatic bone and temporalis muscle are significantly correlated with higher hospital, ventilator, and intensive care unit days in patients with mandibular fracture receiving reconstructive operations. This morphomic methodology provides an accurate, quantitative means to evaluate craniofacial trauma patient frailty, injury, and outcomes using routinely obtained CT scans. In the future, we plan to apply this approach to determine preoperative risk stratification and assist in surgical planning.

Novel temporalis muscle and fat pad morphomic analyses aids preoperative risk evaluation and outcome assessment in nonsyndromic craniosynostosis.

INTRODUCTION: Analytical morphomics is the term we created to describe an innovative, highly automated, anatomically indexed processing of 3D medical imaging data captured during the course of a patients' preoperative CT scan. Our specific aim is to determine the efficacy of craniofacial morphomic indices (CMI) such as temporalis muscle and temporal fat pad morphometric values to predict blood transfusion requirement and hospital stay in a cohort of children with nonsyndromic craniosynostosis (NSC). METHODS: High-throughput, semi-automated image analysis was used to reconstruct the 3-dimensional anatomy of the temporalis muscle and temporal fat pad and to quantify CMIs. The prognostic effect of CMI on clinical outcomes were evaluated among all NSC patients and compared across various craniosynostosis subtypes using Wilcoxon nonparametric tests and Kendall's τ to determine significance. RESULTS: Using preoperative CT images, we evaluated 117 children with NSC from the University of Michigan Health System. Results demonstrate that increased temporal fat pad volume and local temporalis muscle volume are associated with better clinical outcomes in craniosynostosis patients. More specifically, temporal fat pad volume was shown to be a significant predictor of perioperative blood transfusion requirements (P = 0.0033) and increased temporal muscle volume correlated with decreased hospital stay (P = 0.016) when controlling for other covariates including age, sex, weight, and preoperative hematocrit. In addition, the same significant predictors were found when examining individual subtypes of craniosynostosis. CONCLUSION: Our findings demonstrate that maxillofacial CT scans provide a useful quantitative index reflecting general patient health, risk stratification, and probabilities of intervention in addition to their previously established ability to determine the specific pathology of the patient. We demonstrate that temporal morphomics predict the incidence of blood transfusion, hospital stay, and serve as a proxy for fitness in patients undergoing craniosynostosis surgery.

Dose-response effect of human equivalent radiation in the murine mandible: Part II. A biomechanical assessment.

BACKGROUND: Despite the widespread use of adjuvant irradiation for head and neck cancer, the extent of damage to the underlying bone is not well understood. However, patients can suffer serious clinical consequences, including pathologic fractures, nonunion, and osteoradionecrosis. The authors' specific aim was to objectively quantify the human equivalent radiation dose-response effect of radiation on the biomechanical properties of the murine mandible. METHODS: Twelve Sprague-Dawley rats were randomized into three radiation dosage groups--low (5.91 Gy), middle (7 Gy), and high (8.89 Gy)--delivered in five daily fractions. The fractionation regimen was used to approximate 75, 100, and 150 percent, respectively, of the bioequivalent dose humans receive in conventional head and neck cancer treatment. Fifty-six days after irradiation, hemimandibles were loaded to failure in a uniaxial tension at 0.5 mm/second. Load displacement curves were analyzed for yield and breaking load, and values were considered statistically significant at p<0.05. RESULTS: The authors' data demonstrated a statistically significant decrease in the yield and breaking load metrics. The authors' reported averages for low, middle, and high radiation dosages were 162, 136, and 69 N, respectively, for yield; and 215, 211, and 141 N, respectively, for breaking load. Both of these quantitative biomechanical properties were diminished in a dose-response pattern. CONCLUSIONS: In this article, the authors report a dose-response effect in the degradation of the biomechanical properties of the mandible after fractionated human equivalent radiation. The authors' findings and model can now be used to formulate therapies aimed at remediating those effects and augmenting bone regeneration and healing after adjuvant radiotherapy in head and neck cancer patients.

Dose-response effect of human equivalent radiation in the murine mandible: part I. A histomorphometric assessment.

BACKGROUND: The authors' laboratory previously demonstrated that radiation significantly alters new bone formation in the murine mandible, impeding the use of distraction osteogenesis as a viable reconstructive option after radiotherapy in head and neck cancer. The authors hypothesize that the deleterious effects of radiation on regenerate formation results from a dose-response depletion of essential osteogenic cells. The authors' specific aim was to use quantitative histomorphometry to objectively measure the human equivalent dose-response effects of radiation on the integrity of the mandible's cellular and tissue composition. METHODS: Twenty Sprague-Dawley rats were randomized into three radiation dosage groups: low (5.91 Gy), middle (7 Gy), and high (8.89 Gy), delivered in five daily fractions. These dosages approximated 75, 100, and 150 percent, respectively, of the biological equivalent dose the mandible experiences in the clinical regimen of head and neck cancer patients. Hemimandibles were harvested 56 days after radiation and stained with Gomori trichrome. Quantitative histomorphometry was performed using Bioquant software and analysis with a one-way analysis of variance Kruskal-Wallis test. RESULTS: The authors' data revealed a statistically significant diminution in the mean number of osteocytes. The authors also demonstrated a corresponding significant increase in the mean values of empty lacunae. Both of these quantitative histomorphometric changes demonstrated a dose-response relationship. CONCLUSIONS: The authors' study supports their hypothesis that radiation induces a dose-response depletion in osteocytes and an increase in empty lacunae. These reliable and reproducible metrics can now be used to determine the efficacy of therapies aimed at safeguarding the cells essential for optimal bone regeneration and potentially enhance the use of distraction osteogenesis in head and neck cancer patients.

Quantitative histomorphometric assessment of regenerate cellularity and bone quality in mandibular distraction osteogenesis after radiation therapy.

BACKGROUND: The use of mandibular distraction osteogenesis (MDO) for tissue replacement after oncologic resection in head and neck cancer could have immense therapeutic ramifications. We have previously demonstrated significantly decreased mechanical and microdensitomeric metrics of our MDO regenerate after 36-Gy radiation. Quantitative histomorphometry, a third metric, would permit objective investigation of the effects of radiation on tissue and cellular composition. Our hypothesis is that radiation-induced cellular depletion and diminution in function impair optimal bone regeneration. METHODS: Five rats received radiation to the left mandible; 5 received none. All animals underwent surgical placement of external fixators, creation of mandibular osteotomies, distraction to a 5.1-mm gap width, and consolidation. Point counting and color thresholding were performed. RESULTS: There was a significant increase in empty lacunae and a corresponding diminution in osteocytes after radiation. Whereas the volume fraction of mineralized, mature bone was not different, that of nonmineralized, immature osteoid was significantly increased in the radiated group compared with that in the nonradiated group. CONCLUSIONS: Our findings confirm our prior 2 metrics. Actually, all 3 diverse metrics--microdensitometry, biomechanical analysis, and histomorphometry--corroborate our hypothesis of cellular depletion and diminution of function as the potential mechanism of radiation-induced attenuation in the distracted regenerate. Furthermore, our findings of tissue and cellular changes in the irradiated regenerate elucidate the pathophysiology of decreased bone quality when amalgamated with our previous results. Therapeutic agents may now be introduced, and their effects on the irradiated regenerate critically measured, so that MDO may be used as a viable reconstructive option in patients with head and neck cancer.

Biomechanical assessment of regenerate integrity in irradiated mandibular distraction osteogenesis.

BACKGROUND: The role of mandibular distraction osteogenesis for reconstructing mandibular defects following radiation therapy depends on the quality of attenuated bone healing in the regenerate. This study investigated the regenerate properties after radiation therapy using yield and breaking load. The authors hypothesized that both would be significantly reduced in mandibular distraction osteogenesis following radiation therapy compared with mandibular distraction osteogenesis alone. METHODS: Male Sprague-Dawley rats underwent left mandibular fractionated 36-Gy preoperative external beam radiation therapy and then 2 weeks of recovery (n = 7) or no radiation therapy (n = 10) before surgery. External fixators were secured and unilateral osteotomies were created behind the third molar, followed by 4 days of latency and then mandibular distraction osteogenesis: 0.3 mm every 12 hours for 8 days (5.1 mm) and 4 weeks of consolidation. Unoperated controls received no radiation therapy (n = 13). Mandibles were tension tested at 0.5 mm/second to failure, and yield and breaking load were determined. RESULTS: There was a significantly lower breaking load for mandibular distraction osteogenesis following radiation therapy compared with mandibular distraction osteogenesis, alone, but there was no significant difference in yield between the groups. Both groups had significantly lower breaking load and yield when compared with unoperated controls. CONCLUSIONS: The lowered breaking load in mandibular distraction osteogenesis following radiation therapy reflects the reduced biomechanical quality of the regenerate, despite evidence of radiographic union. These data show that radiographic union is not an adequate outcome measure for regenerate healing and support the need to define quantitative bone-healing metrics in mandibular distraction osteogenesis following radiation therapy before implementation in head and neck reconstruction.