Introduction Traumatic facial injuries, leading to facial fractures represent a significant subset of traumatic events, with age emerging as a crucial determinant influencing both their etiology and outcomes. Understanding the age-related patterns of traumatic facial fractures is essential for developing targeted prevention and management strategies. In this context, the Appalachian tri-state area stands as an underexplored region concerning this issue, necessitating comprehensive research to elucidate the nuances of age-related traumatic facial fractures within this geographic context. Methods This retrospective study delves into the age-related patterns of traumatic facial fractures within the Appalachian tri-state area, drawing upon patient records from Cabell Huntington Hospital and Saint Mary\'s Medical Center spanning a five-year period. The study cohort encompasses 623 patients categorized into three age groups: individuals aged <22 years, those aged 22-65 years, and individuals over 65 years. Data analysis involves meticulous examination of mechanisms of injury, injury severity scores (ISSs), hospital length of stay, and the prevalence of surgical interventions across different age cohorts. Results Out of 623 patients, 104 (16.7%) were under 22 years old, 367 (58.9%) were between 22 and 65 years old, and 152 (24.4%) were over 65 years old. The majority were male (70%). Falls were the most common cause of facial fractures in patients over 65 (78%), while assaults were predominant in the 22-65 age group (24%), and motor vehicle collisions (MCVs) in those under 22 (34%). The median ISS and hospital stay durations were similar across age groups. 28% of patients underwent surgery, with significant variation among age groups (p<0.001): 38% for <22 years, 33% for 22-65 years, and 11% for >65 years. Mandibular fractures were more prevalent in younger patients, with rates of 12% for <22 years compared to 5.3% for >65 years. Logistic regression analysis revealed that patients aged 22-65 had 4.10 times higher odds (95% CI=2.38, 7.45, p<0.001) of undergoing surgery, while those under 22 had 5.14 times higher odds (95% CI=2.73, 10.0, p<0.001) compared to those over 65. Significant associations were found for mandibular and bilateral mandibular outcomes in patients aged 22-65 years. Discussion These findings underscore the imperative for tailored prevention strategies and age-specific treatment protocols to optimize patient outcomes. Fall prevention initiatives for the elderly and interventions addressing sports-related injuries for younger individuals are paramount. Moreover, the study highlights the necessity of specialized care protocols for elderly patients to minimize hospital stay durations and manage age-related comorbidities effectively. Moving forward, further research should address limitations, validate findings, and explore the efficacy of specific interventions, thereby paving the way for enhanced preventive measures and management strategies tailored to the diverse age cohorts affected by traumatic facial fractures in the Appalachian region.

UNASSIGNED: To determine the prevalence of maxillofacial fractures associated with persistent CSF leak, and to assess its bearing on clinical outcomes of consecutive patients managed at our centre.
UNASSIGNED: This was a retrospective cross-sectional study. The medical records of patients over 11-year period were analysed for age, gender, etiology of injuries, duration between injury and presentation to the hospital, types of facial fracture and their treatments, treatment done to control CSF leak, and complication(s). Descriptive and bivariate statistics were computed.
UNASSIGNED: Overall, 1473 patients were evaluated, 66 (4.5%) presented with craniofacial injuries associated with persistent CSF leak after 5 days of non-surgical treatment. Males (92.5%, P= 0.0000) and those in the 21 to 30 years age group (59.1 %, P=0.01) were predominant. The most common (68.2%) type of fracture combination was Le Fort I, II and III, NOE, zygomatic complex and mandible. The commonest clinical presentation of CSF leak was rhinorrhea only, in 66.7% of patients (P= 0.001).
UNASSIGNED: This study shows that the prevalence of maxillofacial fractures associated with persistent CSF leak was low, which was 4.5% of patients that presented with persistent CSF leak and 84.9% of the cases resolved after treatment of the various maxillofacial fractures.

UNASSIGNED: Vigilant monitoring for postoperative complications, including bleeding and dysrhythmia, is crucial in patients with craniosynostosis syndromes like Crouzon syndrome undergoing craniofacial surgery, with a thorough evaluation, including coagulation tests, assisting in diagnosing underlying conditions such as von Willebrand disease subtype 1 to inform appropriate management strategies.
UNASSIGNED: Crouzon syndrome is a rare genetic disorder affecting craniofacial structures. Its etiology is the premature fusion of cranial sutures. The LeFort III advancement surgery is a commonly used approach to correct malformations related to midface hypoplasia. Complications following surgical treatment of craniosynostosis and craniofacial syndromes can include both intracranial and extracranial problems. Reporting of this syndrome and the surgery complications, in addition to consideration of other differential diagnoses, can help improve the treatment plan and surgery outcomes. The aim of the article is to report a 14-year-old female with Crouzon syndrome who underwent the modified LeFort III osteotomy and developed unexpected massive bleeding during the surgery. Post-surgery, she experienced complications including dysrhythmia, hypothermia, and cyanosis. Treatment included fluid therapy, blood transfusions, and antibiotic therapy for suspected septic shock. Differential diagnosis was disseminated intravascular coagulation but was ruled out. Post-discharge, coagulation tests suggested von Willebrand disease subtype 1 as the diagnosis. Excessive bleeding during surgery for craniosynostosis syndromes is a significant and concerning issue in the surgical management of Crouzon syndrome. For patients with von Willebrand disease who are candidates for elective surgeries, von Willebrand factor concentrates or recombinant von Willebrand factor can be used.

Inflammatory myofibroblastic tumors (IMTs) represent rare neoplasms, particularly infrequent in the pediatric skull. We present a novel case of a newborn male with a 5 cm right temporal mass and discuss current diagnostic and treatment options for IMTs. A multidisciplinary effort to surgically remove the lesion was successful, and the patient\'s skull defect healed without neurological deficits. The etiology of IMTs remains elusive, with proposed associations with chromosomal mutations in the anaplastic lymphoma kinase (ALK) gene. Surgical excision remains the primary treatment for IMTs. Promising pharmacological treatments, like Crizotinib, warrant further research into understanding potential alternatives in IMT management.

OBJECTIVE: Hydrocephalic macrocephaly can result in poor psychosocial development, positioning difficulties, skin breakdown, and poor cosmesis. Although reduction cranioplasty can address these sequelae, the postoperative outcomes, complications, and mortality risk of reduction cranioplasty are not well understood given the rarity of hydrocephalic macrocephaly. Therefore, the primary objective of this systematic review was to evaluate the surgical outcomes of reduction cranioplasty for the treatment of hydrocephalic macrocephaly.
METHODS: A systematic review was performed using the PubMed, Scopus, and Web of Science databases while following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two independent reviewers screened 350 studies; 27 studies reporting surgical outcomes on reduction cranioplasty for hydrocephalic macrocephaly met inclusion criteria. Data on study design, patient demographics, operative details, and surgical outcomes were collected.
RESULTS: There were 65 reduction cranioplasties among the 27 included studies. Eighteen (66.7%) studies presented level V evidence, 7 (25.9%) presented level IV evidence, and 2 (7.4%) presented level III evidence. Following reduction cranioplasty, there was improvement in postoperative head positioning in 23 (85.2%) studies, improvement in postoperative cosmesis in 22 (81.5%) studies, and improvement in global postoperative neurological functioning in 20 (74.1%) studies. The median estimated blood loss was 633 mL (range 20-2600 mL). Shunt revisions were the most common complication, reported in 9 (47.4%) of the 19 studies assessing complications. Of the 65 patients, there was a mortality rate of 6.2% (n = 4).
CONCLUSIONS: The majority of the included studies reported improvement in head size, head positioning, cranial cosmesis, and global neurological functioning following reduction cranioplasty for hydrocephalic macrocephaly. However, the prevalence of lower-level evidence, risk of blood loss, complications, and mortality indicates the need for a serious discussion of surgical indication, an experienced team, and thorough perioperative planning to perform these complex surgeries.

OBJECTIVE: Occurring once in every 2000 live births, craniosynostosis (CS) is the most frequent cranial birth defect. Although the genetic etiologies of syndromic CS cases are well defined, the genetic cause of most nonsyndromic cases remains unknown.
METHODS: The authors analyzed exome or RNA sequencing data from 876 children with nonsyndromic CS, including 291 case-parent trios and 585 additional probands. The authors also utilized the GeneMatcher platform and the Gabriella Miller Kids First genome sequencing project to identify additional CS patients with AXIN1 mutations.
RESULTS: The authors describe 11 patients with nonsyndromic CS harboring rare, damaging mutations in AXIN1, an inhibitor of Wnt signaling. AXIN1 regulates signaling upstream of key mediators of osteoblast differentiation. Three of the 6 mutations identified in trios occurred de novo in the proband, while 3 were transmitted from unaffected parents. Patients with nonsyndromic CS were highly enriched for mutations in AXIN1 compared to both expectation (p = 0.0008) and exome sequencing data from > 76,000 healthy controls (p = 2.3 × 10-6), surpassing the thresholds for genome-wide significance.
CONCLUSIONS: These findings describe the first phenotype associated with mutations in AXIN1, with mutations identified in approximately 1% of nonsyndromic CS cases. The results strengthen the existing link between Wnt signaling and maintenance of cranial suture patency and have implications for genetic testing in families with CS.

Non-syndromic orofacial clefts (NSOFCs) are common birth defects with a complex etiology. While over 60 common risk loci have been identified, they explain only a small proportion of the heritability for NSOFCs. Rare variants have been implicated in the missing heritability. Thus, our study aimed to identify genes enriched with nonsynonymous rare coding variants associated with NSOFCs. Our sample included 814 non-syndromic cleft lip with or without palate (NSCL/P), 205 non-syndromic cleft palate only (NSCPO), and 2150 unrelated control children from Nigeria, Ghana, and Ethiopia. We conducted a gene-based analysis separately for each phenotype using three rare-variants collapsing models: (1) protein-altering (PA), (2) missense variants only (MO); and (3) loss of function variants only (LOFO). Subsequently, we utilized relevant transcriptomics data to evaluate associated gene expression and examined their mutation constraint using the gnomeAD database. In total, 13 genes showed suggestive associations (p = E-04). Among them, eight genes (ABCB1, ALKBH8, CENPF, CSAD, EXPH5, PDZD8, SLC16A9, and TTC28) were consistently expressed in relevant mouse and human craniofacial tissues during the formation of the face, and three genes (ABCB1, TTC28, and PDZD8) showed statistically significant mutation constraint. These findings underscore the role of rare variants in identifying candidate genes for NSOFCs.

OBJECTIVE: Previous work identified an association between genetics and neurodevelopmental delays in patients with nonsyndromic craniosynostosis. The authors investigated the role of genetic mutations on behavioral outcomes of patients with treated sagittal synostosis.
METHODS: Parents of children aged 6-18 years with surgically corrected sagittal synostosis were recruited to complete the Child Behavioral Checklist (overall behavioral problems), Conners 3rd Edition-Parent (attention-deficit/hyperactivity disorder), Social Responsiveness Scale 2nd Edition (autism spectrum disorder [ASD]), and Behavior Rating Inventory of Executive Function 2nd Edition (executive function). Genomic analysis was completed, and patients were identified if they had mutations in high probability of loss of function intolerant (pLI) genes (high pLI vs nonhigh pLI). Genetic burden was assessed relative to controls. Multivariate linear regression determined the association of mutations in high pLI genes with behavioral scores, while controlling for sociodemographic factors, age at surgery, surgery type, and IQ.
RESULTS: Sixteen of 45 patients were in the high pLI group. There were no differences between the groups in terms of sociodemographic factors. A greater proportion of children in the high pLI group scored at or above borderline clinical levels for aggression (18.8% vs 0.0%, p = 0.05) and externalizing problems (31.3% vs 3.7%, p = 0.02). Among children in the nonhigh pLI group, older age at surgery was associated with worse scores on the rule-breaking, aggression, and externalizing problems domains and four out of five ASD domains.
CONCLUSIONS: Children with treated nonsyndromic sagittal synostosis and mutations in high pLI genes had worse behavioral problems in externalizing behaviors and aggression, whereas older age at surgery was a significant predictor of worse behavioral outcomes in patients without mutations in high pLI genes.

Apical expansion of calvarial osteoblast progenitors from the cranial mesenchyme (CM) above the eye is integral to calvarial growth and enclosure of the brain. The cellular behaviors and signals underlying the morphogenetic process of calvarial expansion are unknown. Time-lapse light-sheet imaging of mouse embryos revealed calvarial progenitors intercalate in 3D in the CM above the eye, and exhibit protrusive and crawling activity more apically. CM cells express non-canonical Wnt/planar cell polarity (PCP) core components and calvarial osteoblasts are bidirectionally polarized. We found non-canonical ligand Wnt5a-/- mutants have less dynamic cell rearrangements and protrusive activity. Loss of CM-restricted Wntless (CM-Wls), a gene required for secretion of all Wnt ligands, led to diminished apical expansion of Osx+ calvarial osteoblasts in the frontal bone primordia in a non-cell autonomous manner without perturbing proliferation or survival. Calvarial osteoblast polarization, progressive cell elongation and enrichment for actin along the baso-apical axis were dependent on CM-Wnts. Thus, CM-Wnts regulate cellular behaviors during calvarial morphogenesis for efficient apical expansion of calvarial osteoblasts. These findings also offer potential insights into the etiologies of calvarial dysplasias.

OBJECTIVE: As many as 5% of normocephalic children may have a prematurely fused sagittal suture, yet the clinical significance and best course of management of this finding remain unclear. Providers in the Synostosis Research Group were surveyed to create a multicenter consensus on an optimal treatment and monitoring algorithm for this condition.
METHODS: A four-round modified Delphi method was utilized. The first two rounds consisted of anonymous surveys distributed to 10 neurosurgeons and 9 plastic surgeons with expertise in craniosynostosis across 9 institutions, and presented 3 patients (aged 3 years, 2 years, and 2 months) with incidentally discovered fused sagittal sutures, normal cephalic indices, and no parietal dysmorphology. Surgeons were queried about their preferred term for this entity and how best to manage these patients. Results were synthesized to create a treatment algorithm. The third and fourth feedback rounds consisted of open discussion of the algorithm until no further concerns arose.
RESULTS: Most surgeons preferred the term \"premature fusion of the sagittal suture\" (93%). At the conclusion of the final round, all surgeons agreed to not operate on the 3- and 2-year-old patients unless symptoms of intracranial hypertension or papilledema were present. In contrast, 50% preferred to operate on the 2-month-old. However, all agreed to utilize shared decision-making, taking into account any concerns about future head shape and neurodevelopment. Panelists agreed that patients over 18 months of age without signs or symptoms suggesting elevated intracranial pressure (ICP) should not undergo surgical treatment.
CONCLUSIONS: Through the Delphi method, a consensus regarding management of premature fusion of the sagittal suture was obtained from a panel of North American craniofacial surgeons. Without signs or symptoms of ICP elevation, surgery is not recommended in patients over 18 months of age. However, for children younger than 18 months, surgery should be discussed with caregivers using a shared decision-making process.