Concurrent impact of de novo mutations on cranial and cortical development in nonsyndromic craniosynostosis.

OBJECTIVE: Nonsyndromic craniosynostosis (nsCS), characterized by premature cranial suture fusion, is considered a primary skull disorder in which impact on neurodevelopment, if present, results from the mechanical hindrance of brain growth. Despite surgical repair of the cranial defect, neurocognitive deficits persist in nearly half of affected children. Therefore, the authors performed a functional genomics analysis of nsCS to determine when, where, and in what cell types nsCS-associated genes converge during development. METHODS: The authors integrated whole-exome sequencing data from 291 nsCS proband-parent trios with 29,803 single-cell transcriptomes of the prenatal and postnatal neurocranial complex to inform when, where, and in what cell types nsCS-mutated genes might exert their pathophysiological effects. RESULTS: The authors found that nsCS-mutated genes converged in cranial osteoprogenitors and pial fibroblasts and their transcriptional networks that regulate both skull ossification and cerebral neurogenesis. Nonsyndromic CS-mutated genes also converged in inhibitory neurons and gene coexpression modules that overlapped with autism and other developmental disorders. Ligand-receptor cell-cell communication analysis uncovered crosstalk between suture osteoblasts and neurons via the nsCS-associated BMP, FGF, and noncanonical WNT signaling pathways. CONCLUSIONS: These data implicate a concurrent impact of nsCS-associated de novo mutations on cranial morphogenesis and cortical development via cell- and non-cell-autonomous mechanisms in a developmental nexus of fetal osteoblasts, pial fibroblasts, and neurons. These results suggest that neurodevelopmental outcomes in nsCS patients may be driven more by mutational status than surgical technique.

Risk of ADHD, Autism Spectrum Disorder, and Executive Function Impairment in Metopic Craniosynostosis.

INTRODUCTION: Favorable behavioral interactions are critical for academic and interpersonal success. An association between metopic synostosis and behavioral impairments has not been fully elucidated. Behavioral dysfunction in school age children with surgically corrected metopic synostosis was evaluated using targeted testing to detect the most common behavioral abnormalities in this population. METHODS: Parents of children 6-18 years old with metopic synostosis completed the Conners Short 3 rd edition (Conners-3: ADHD), Social Responsiveness Scale 2 nd edition (SRS-2: autism spectrum disorder), Behavior Rating Inventory of Executive Function 2 nd edition (BRIEF-2: executive functioning), and Child's Behavioral Checklist (CBCL: behavioral/emotional functioning). Children also completed neurocognitive testing. Multivariable regression was used to determine predictors of clinically significant behavioral impairments. RESULTS: 60 children were enrolled. Average age at surgery was 9.2 ± 7.9 months, with an average age at assessment of 10.3 ± 3.5 years. Nearly half of patients demonstrated symptoms associated with ADHD, demonstrated by reaching or exceeding borderline clinical levels for inattention and hyperactivity subscales of the Conners-3. Greater age at surgery was associated with worse executive function, measured by reaching or exceeding clinically significant levels of the executive function subscale of the Conners-3 (p=0.04) and subscales of the BRIEF-2 (behavioral regulator index [p=0.05], cognitive regulatory index [p=0.03], and global executive composite [p=0.04]). CONCLUSIONS: Nearly half of patients with surgically corrected metopic synostosis reached borderline clinical scores for inattention and hyperactivity. Greater age at surgery was associated with worse executive function. Prompt surgical correction of metopic synostosis may portend improved long-term emotional and behavioral function.

"Morphologic Severity and Age at Surgery Are Associated with School Age Neurocognitive Outcomes in Metopic Craniosynostosis".

BACKGROUND: Radiographic severity of metopic synostosis has been suggested as a predictor of long-term neurocognitive outcomes, and artificial intelligence (AI) has recently been used to quantify severity. Age at surgery is predictive of long-term neurocognition in sagittal synostosis but has not been adequately explored in metopic synostosis. METHODS: Children ages 6 to 18 years old with corrected metopic synostosis underwent testing of intelligence quotient (IQ), academic achievement, and visuomotor integration (VMI). Various manual measurements and AI-derived severity scores were determined. Scans were categorized as moderate or severe for head-to-head comparisons and multivariable linear regressions were used to assess the relationship of age at surgery and severity with neurocognitive outcomes. RESULTS: 41 patients with average age at testing of 10.8 ± 3.4 years were included. 18 patients were in the severe group while 23 patients were in the moderate group with average ages at surgery 6.6 ± 2.7 and 10.6 ± 8.4 months, respectively (p = 0.062). Greater AI-derived severity was significantly associated with lower reading comprehension (p = 0.040 and 0.018) and reading composite scores (p = 0.024 and p = 0.008). Older age at surgery was significantly associated with lower VMI scores (p-values ranging from 0.017 to 0.045) and reading composite scores (p = 0.047 and 0.019). CONCLUSIONS: This study suggests an association between greater AI-derived radiographic severity and lower reading ability in corrected metopic synostosis. Older age at surgery was independently associated with lower reading ability and visuomotor integration. Surgical correction may mitigate neurodevelopmental differences based on severity that have been observed pre-operatively.

Tranexamic Acid in Facial Feminization Surgery: Quantifying a High-risk Setting With Exogenous Estrogen Supplementation.

Tranexamic acid (TXA) has been increasingly utilized in orthognathic surgery, aesthetic surgery, and craniofacial surgery. However, the risk of increasing venous thromboembolic events (VTE) must be carefully considered as TXA is a prothrombotic agent. Our study aimed to investigate the safety of TXA in the setting of facial feminization surgery. These patients are at an elevated risk for VTE at baseline given their uniform history of exogenous estrogen supplementation. A retrospective review of all patients that underwent facial feminization surgery at our medical center between December 2015 and September of 2022 was performed. Demographic information, procedure type, Caprini scores, hematoma rate, VTE rate, estimated blood loss, and operative time were all studied. Unpaired t tests were used to compare patients that received TXA and those who did not. In total, there were 79 surgeries performed during our study period. There were 33 surgeries (41.77%) that used TXA intraoperatively. Ten patients (12.65%) received anticoagulation postoperatively, 5 of whom received TXA intraoperatively. Of the 33 patients who received TXA, 30 patients remained on estrogen therapy. There was no statistically significant difference in VTE rates in patients who received TXA (n=33, 41.77%) and those who did not (n=46, 58.23%). Bleeding events, Caprini scores, estimated blood loss, and operative time were also not found to be significantly different between the 2 cohorts. The authors found no significant increase in VTE in facial feminization patients undergoing estrogen supplementation when intraoperative TXA was utilized. This is the first known report investigating the safety of TXA in this higher risk patient population.

Long-term neurocognitive outcomes in 204 single-suture craniosynostosis patients.

PURPOSE: Craniosynostosis, which describes premature fusion of one or more cranial sutures, has been associated with a variety of neurocognitive deficits. We sought to explore the cognitive profiles of the various types of single-suture, non-syndromic craniosynostosis (NSC). METHODS: A retrospective review of children 6-18 years old with surgically corrected NSC who underwent neurocognitive testing (Weschler Abbreviated Scale of Intelligence, Beery-Buktenica Developmental Test of Visuomotor Integration) from the years 2014-2022 was conducted. RESULTS: 204 patients completed neurocognitive testing (139 sagittal, 39 metopic, 22 unicoronal, 4 lambdoid suture). 110 (54%) of the cohort was male, and 150 (74%) were White. Mean IQ was 106.10±14.01 and mean age at surgery and testing were 9.0±12.2 months and 10.9±4.0 years, respectively. Sagittal synostosis was associated with higher scores than metopic synostosis, with significant differences in verbal IQ (109.42±15.76 vs 101.37±10.41), full-scale IQ (108.32±14.44 vs 100.05±11.76), visuomotor integration (101.62±13.64 vs 92.44±12.07), visual perception (103.81±12.42 vs 95.87±11.23), and motor coordination (90.45±15.60 vs 84.21±15.44). Sagittal synostosis was associated with significantly higher scores for visuomotor integration (101.62±13.64 vs 94.95±10.24) and visual perception (103.81±12.42 vs 94.82±12.75) than unicoronal synostosis. CONCLUSIONS: Compared to patients with sagittal synostosis, patients with metopic synostosis exhibited lower scores in verbal IQ, full-scale IQ, visuomotor integration, visual perception, and motor control after surgical correction. Despite surgical correction for premature metopic suture fusion, the effect on the adjacent frontal lobe and white matter connections to other regions of the brain may have a lasting functional impact. Patients with unicoronal synostosis exhibited lower visuomotor integration and visual perception scores.

Role of State Insurance Policy in Orthotic Helmet Access for Deformational Plagiocephaly.

BACKGROUND: Helmet therapy for deformational plagiocephaly has an ideal window for treatment, and timely access to care is vital to achieving optimal benefit. The authors evaluated the hypothesis that patients insured through Medicaid experience decreased access to helmet therapy. METHODS: This was a retrospective analysis of referrals for helmet therapy to Cranial Technologies, Inc. between 2014 and 2020 across 21 states. Outcome measures were likelihood of receiving a helmet, receiving a second helmet, receiving delayed treatment, and having delayed presentation. RESULTS: From 2014 to 2020, a total of 219,869 patients were referred and 141,513 of these received a helmet. Patients with Medicaid were less likely to receive treatment (OR, 0.63; P < 0.001) and more likely to present late (OR, 1.55; P < 0.001) or receive delayed treatment (OR, 3.24; P < 0.001) compared with the commercially insured. Patients with Medicaid were less likely to receive helmet therapy in nine states, with the strongest association in Texas (OR, 0.32; P < 0.001), and more likely to receive helmet therapy in five states, with the strongest association in Colorado (OR, 1.89; P < 0.001). Medicaid was associated with late presentation and delayed treatment in all states. CONCLUSIONS: Patients with Medicaid presented later and were less likely to receive helmet therapy. Findings reflected state-specific Medicaid policies, with patients in some states more likely to receive a helmet with Medicaid than with commercial insurance. However, late presentation and delays in treatment with Medicaid were observed across all states. State-specific Medicaid restrictions are likely a driving factor in determining access to helmet therapy.

Live Virtual Surgery and Virtual Reality in Surgery: Potential Applications in Hand Surgery Education.

Accelerated in part by the coronavirus disease 2019 pandemic, medical education has increasingly moved into the virtual sphere in recent years. Virtual surgical education encompasses several domains, including live virtual surgery and virtual and augmented reality. These technologies range in complexity from streaming audio and video of surgeries in real-time to fully immersive virtual simulations of surgery. This article reviews the current use of virtual surgical education and its possible applications in hand surgery. Applications of virtual technologies for preoperative planning and intraoperative guidance, as well as care in underresourced settings, are discussed. The authors describe their experience creating a virtual surgery subinternship with live virtual surgeries. There are many roles virtual technology can have in surgery, and this review explores potential value these technologies may have in hand surgery.

Utilizing Computer-Assisted Design and Virtual Surgical Planning for Correction of Unilateral Lambdoid Synostosis.

Unilateral lambdoid synostosis is the rarest form of single-suture craniosynostosis. Although various surgical approaches have been described, cranial vault remodeling remains the predominant approach. To aid in surgical planning, preoperative virtual surgical modeling using a patient's presenting computed tomography scan can be used to increase reconstructive precision and to reduce operative time. Presented is a 7-month-old male with unilateral lambdoid synostosis who underwent medically modeled cranial vault reconstruction.

Gaps in Access to Reconstruction Compared with Audiologic Care among Children with Microtia.

Reconstruction for microtia decreased psychosocial morbidity; timely referral for surgery is crucial. We evaluated specialist referrals for microtia at a major academic medical center. Only one-half of patients were evaluated at any point by a reconstructive craniofacial surgeon. Patients followed early for audiologic concerns may not be receiving timely referred for reconstruction.

Orthotic Helmet Therapy for Deformational Plagiocephaly: Stratifying Outcomes by Insurance.

OBJECTIVE: Deformational Plagiocephaly (DP) is commonly treated with cranial orthosis, or helmet therapy. A large, national study on the impact of insurance status on helmet outcomes is lacking. We assessed treatment outcomes for helmet therapy based on insurance status. DESIGN: This was a retrospective data analysis of patients referred to Cranial Technologies, Inc for helmet therapy between 2014-2020 across 21 states. PATIENTS, PARTICIPANTS: There were a total of 211,417 patients referred for helmeting, of whom 141,513 received helmet therapy. MAIN OUTCOMES MEASURES: Multivariate regression was used to assess the relationship of insurance status with post-treatment residual flattening, measured by cephalic index (CI) and cranial vault asymmetry index (CVAI), and treating provider rating of success. RESULTS: Patients with Medicaid were more likely to complete treatment with residual flattening measured by CI and CVAI when compared to patients with private insurance (OR: 1.58, CI: 1.51-1.65, p < 0.001 and OR: 1.21, CI: 1.15-1.28, p < 0.001, respectively). Providers of patients with Medicaid were more likely to give a low rating of success following treatment (OR: 3.25, CI: 2.70-3.92, p < 0.001). CONCLUSIONS: Our study investigating the impact of insurance status on helmet therapy across 21 states found that patients with Medicaid were more likely to experience residual flattening and have lower provider-rated outcomes compared to those with commercial insurance. Given significant caregiver burden posed by helmet therapy, which requires frequent visits and consistent helmet use, caregivers of patients with Medicaid may require greater support to reduce outcome disparities observed here.

Assessment of Sex Diversity Among Craniofacial Academic Faculty.

Sex diversity among plastic surgery and its subspecialties faculties lags behind many medical specialties. Despite the significant evidence in favor of diversity in leadership, female presence in high-ranking positions in medicine is lacking across multiple specialties. In this study, we aim to evaluate sex disparity among faculty across craniofacial fellowship programs by comparing the disparities among total number of faculty, program directors, years in practice, and academic rank. Our sample included 354 individuals including 193 craniofacial surgery journal editorial board members, 130 craniofacial surgery academic faculty members, and 31 craniofacial surgery association board members. A significant difference (P-value <0.0001) was seen among male and female craniofacial surgery faculty with 84.6% males. Faculty members were further subdivided by academic rank. A significant difference was found between the number of male and female faculty members at all academic positions (P-value =0.043). Of 41 full professors, 2.4% were female. There were 42 associate professors queried with 14.3% female. Similarly, 43 assistant professors were identified with 32.0% female. Years in practice after completing terminal training were analyzed across the academic faculty. There was a significant difference in the number of male and female faculty members across all experience levels (P-value =0.0037). Among the faculty with <10 years since completion of terminal training, 32.4 % were female. For faculty with 10 to 20 years after post-terminal training, 19.6% were female. For those with 20 to 30 years of experience, 0% were female. Finally, for the faculty with over 30 years since graduation, 5.9% were female. Board membership in 2 craniofacial surgery organizations was analyzed: the American Cleft Palate-Craniofacial Association and the American Society of Maxillofacial Surgeons. Among the 17 board members of the American Cleft Palate-Craniofacial Association, 8 (47.1%) were female. For the American Society of Maxillofacial Surgeons, 5 (35.7%) were female. Data were collected for 193 editorial board members from 2 craniofacial surgery journals. There was a significant difference between the number of male and female members across both journals (χ2 value: 33.3570; P-value <0.0001). Among 56 editorial board members from Cleft Palate-Craniofacial Journal, 26 (46.4%) members were female. In comparison, Journal of Craniofacial Surgery has 24.8% female editorial board members. Sex diversity among faculty members is really important and should be brought into light to highlight and improve areas of particular importance and of tremendous potential impact. Given our results, surgical residencies and fellowship programs should begin to show concrete commitment and increase their efforts to recruit and retain a diverse faculty not only for the educational benefit but more importantly to achieve a higher level of care for all.

Flap to Mastectomy Mass: Are Higher Ratios Associated with Greater Breast Reconstruction Satisfaction?

BACKGROUND: Autologous breast reconstruction is associated with superior patient-reported outcomes compared with prosthetic techniques, but little is known about the relationship between autologous flap mass and patient satisfaction. We hypothesized that a higher differential mass (ratio of flap mass to mastectomy mass) would be associated with greater satisfaction with reconstruction. METHODS: In this retrospective study, patients who underwent autologous breast reconstruction between 2015 and 2020 with a deep inferior epigastric perforator (DIEP) flap completed the BREAST-Q survey. Multivariate linear regression models were used to examine the relationship between differential mass and patient satisfaction. Models controlled for body mass index (BMI), age at surgery, reconstruction size preference, number of surgeries, previous surgery failure, whether the patient underwent radiation therapy, and whether reconstruction was unilateral or bilateral. RESULTS: Overall, 45 patients (70 breasts) completed the BREAST-Q survey. Mean age at reconstruction was 52.2 years and mean time to survey completion following surgery was 21.1 months. Most patients (59.4%) desired a smaller breast after reconstruction. The mean differential mass was +26.3% (flap mass greater than mastectomy mass). Differential mass was positively associated with all satisfaction measures with results being significant for satisfaction with breasts scores (p=0.032). CONCLUSION: In this preliminary study, a higher ratio of autologous flap mass to mastectomy mass was associated with overall higher patient-reported satisfaction. A 1:1 flap to mastectomy mass ratio may not adequately reapproximate desired breast size or shape. Larger autologous flap mass may be favorable for long-term patient satisfaction, and future studies should investigate the relationship between differential mass and breast esthetics.

Predictive Factors of Outcomes in Helmet Therapy for Deformational Plagiocephaly and Brachycephaly.

Deformational plagiocephaly and brachycephaly, or abnormal flattening of the infant skull due to external forces, are often managed with orthotic helmet therapy. Although helmet therapy is widely used, the factors that predict poor outcomes are not well characterized. In this study of over 140,000 patients who received helmet therapy, older age and greater severity at presentation, and noncompliance with treatment were each independently associated with worse craniometric and provider-reported outcomes. Each additional point of cranial vault asymmetry index or cephalic index at a presentation is associated with an increased likelihood of residual brachycephaly at completion [odds ratio (OR): 1.067; 95% Cl: 1.058-1.075; P <0.0001 and OR: 2.043; 95% CI: 2.021-2.065; P <0.0001, respectively], whereas each additional point of cranial vault asymmetry index at a presentation associated with increased likelihood of residual asymmetry at completion (OR: 2.148; 95% Cl: 2.118-2.179; P <0.0001). Patients were more likely to have residual brachycephaly or asymmetry with increasing age at treatment initiation (OR: 1.562; 95% CI: 1.524-1.600; P <0.0001 and OR: 1.673; 95% Cl: 1.634-1.713; P <0.0001, respectively, for each additional month of age at initiation). These results highlight a need for prompt referral for helmeting, especially in cases with severe features or when patients present late to care. Potentially modifiable factors are age at helmeting and compliance with treatment protocols, and consideration of these factors may be important for achieving success in some cases.

Racial and geographic disparities in reconstructive procedures following melanoma resection.

INTRODUCTION: Melanoma occurs most commonly in non-Hispanic White patients; however, Black and Hispanic patients experience greater morbidity and mortality. This study assesses how race and socioeconomic factors influence rates of reconstructive procedures and hospital-based outcomes in melanoma patients. METHODS: Data were extracted from the National Inpatient Sample database from the years 2010-2015. Patients with melanoma who underwent a reconstructive procedure were identified. Univariate and multivariate logistic regression analysis was used to identify the relationship between dependent variables and various patient/hospital components for patients undergoing reconstructive procedures. RESULTS: Black and Hispanic patients had a greater length of stay (LOS) than non-Hispanic White patients (OR: 2.252, p = 0.0307, and OR: 2.592, p = 0.0014), and Hispanic patients were less likely to receive more complex reconstructive procedures (OR: 0.449, p = 0.0487). Patients living in rural areas were less likely to receive complex reconstructive procedures than those in both urban teaching and non-teaching hospitals (OR: 3.313, p = 0.0135, and OR: 3.505, p = 0.0074). Pedicled or rotational flaps were less likely to be performed at medium- or large-sized hospitals (OR: 0.610, p = 0.0296, and OR: 0.496, p = 0.0002). CONCLUSION: Race and socioeconomic factors are important predictors of access to complex reconstructive procedures and hospital-based outcomes following extirpation in melanoma patients.

Limited Access to Facial Feminization Geographically Despite Nationwide Expansion of Other Gender-Affirming Surgeries.

Facial feminization surgery (FFS) is an integral aspect of gender-affirming surgery (GAS) for individuals seeking to align secondary sex characteristics and gender identity. Despite the importance of FFS in treating gender dysphoria, current trends and prevalence remain unknown. We sought to examine trends in GAS and FFS and investigate the payer status of facial feminization procedures in the United States. Methods: Data was extracted from the National Inpatient Sample from 2008 to 2017 by using International Classification of Diseases Ninth or Tenth diagnosis codes for gender identity disorder and procedure codes for FFS. Results: From 2008 to 2017, 3015 patients underwent GAS. The yearly number of cases increased as did the average cost of GAS, which rose from $13,657 in 2008 to $50,789 in 2017. From 2015 to 2017, when FFS data was available, 110 of 1215 (9.1%) GAS patients had FFS. Most were non-Hispanic White (66.7%) or Black (23.8%). Fifty percent of FFS cases occurred in the West, followed by the Northeast (31.8%), South (13.6%), and Midwest (4.8%) (P = 0.015). By payer the cases were, 36.4% self-pay, 31.8% Medicaid, and 27.3% private insurance (P < 0.0001). Approximately, 18% of patients undergoing male-to-female transition received FFS. Conclusions: From 2008 to 2017, GAS cases increased nationwide while the average cost of surgery rose steeply. FFS cases were primarily in the Western and Northeast United States. Despite high cost, roughly 18% of transgender women in our sample received FFS, highlighting the importance of FFS in gender transition.

Facial Trauma Call Reimbursement Patterns Among American Society of Maxillofacial Surgery Members.

Facial trauma accounts for over 3 million emergency room encounters each year in the United States and places significant financial burden on the health care system and surgeons. However, data on facial trauma call practices among plastic surgeons are lacking. We surveyed members of the American Society of Maxillofacial Surgeons (ASMS) regarding their experience with facial trauma call. A 27-question online survey was distributed through e-mail to ASMS members. Forty-five ASMS members completed the survey, of whom 64% were required to take facial trauma call and 44% were compensated for call. Respondents in the North-East were less likely [odds ratio (OR): 0.234, confidence interval (CI), 0.054-1.015; P =0.052] to be compensated for taking call, whereas those who worked at level 1 trauma centers were more likely odds ratio: 5.42, CI, 0.892-32.89; P =0.066) to be compensated. Surgeons required to take facial trauma call were 4.646 (CI, 1.203-17.944; P =0.026) times more likely to take call ≥5 days per month. These results highlight a relatively low proportion of plastic surgeons receiving additional compensation for facial trauma call while work at a level 1 trauma center was associated with higher likelihood of compensation. Surgeons in the Northeast may be compensated less frequently than other regions. Plastic surgeons should be aware of these trends, as they decide how to incorporate facial trauma call into their practice.