Digital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma.

BACKGROUND: Desmoplastic melanoma (DM) is a rare melanoma subtype characterized by dense fibrous stroma, a propensity for local recurrence, and a high response rate to programmed cell death protein 1 (PD-1) blockade. Occult sentinel lymph node positivity is significantly lower in both pure and mixed DM than in conventional melanoma, underscoring the need for better prognostic biomarkers to inform therapeutic strategies. METHODS: We assembled a tissue microarray comprising various cores of tumor, stroma, and lymphoid aggregates from 45 patients with histologically confirmed DM diagnosed between 1989 and 2018. Using a panel of 62 validated immune-oncology markers, we performed digital spatial profiling using the NanoString GeoMx platform and quantified expression in three tissue compartments defined by fluorescence colocalization (tumor (S100+/PMEL+/SYTO+), leukocytes (CD45+/SYTO+), and non-immune stroma (S100-/PMEL-/CD45-/SYTO+)). RESULTS: We observed higher expression of immune checkpoints (lymphocyte-activation gene 3 [LAG-3] and cytotoxic T-lymphocyte associated protein-4 [CTLA-4]) and cancer-associated fibroblast (CAF) markers (smooth muscle actin (SMA)) in the tumor compartments of pure DMs than mixed DMs. When comparing lymphoid aggregates (LA) to non-LA tumor cores, LAs were more enriched with CD20+B cells, but non-LA intratumoral leukocytes were more enriched with macrophage/monocytic markers (CD163, CD68, CD14) and had higher LAG-3 and CTLA-4 expression levels. Higher intratumoral PD-1 and LA-based LAG-3 expression appear to be associated with worse survival. CONCLUSIONS: Our proteomic analysis reveals an intra-tumoral population of SMA+CAFs enriched in pure DM. Additionally, increased expressions of immune checkpoints (LAG-3 and PD-1) in LA and within tumor were associated with poorer prognosis. These findings might have therapeutic implications and help guide treatment selection in addition to informing potential prognostic significance.

Longitudinal Outpatient and School-Based Service Use among Children with Nonsyndromic Craniosynostosis.

BACKGROUND: Although nonsyndromic craniosynostosis has been associated with neurodevelopmental sequelae, a lesser amount of emphasis has been placed on the need for related supportive services. This study assessed the prevalence of such services among children surgically treated for nonsyndromic craniosynostosis and identified predictors of service use. METHODS: Parents of children with nonsyndromic craniosynostosis were recruited from an online craniosynostosis support network and surveyed regarding their child's use of various outpatient and school-based services. Multiple stepwise regression was performed to identify predictive variables for each type of intervention. RESULTS: A total of 100 surveys were completed. Of these, 45 percent of parents reported use of one or more outpatient support services for their children. The most commonly used services were speech therapy (26.0 percent) and physical therapy (22.0 percent), although the use of services such as psychology/psychiatry increased among older children (18.2 percent in children aged 6 to 10 years). Among school-age children ( n = 49), the majority of parents (65.3 percent) reported school-based assistance for their children, most commonly for academic (46.9 percent) or behavioral (42.9 percent) difficulties. Significant predictive variables ( p < 0.05 following stepwise regression) for increases in various outpatient and school-based services included male sex, African American race/ethnicity, higher parental income, the presence of siblings in the household, increased age at the time of surgery, and sagittal synostosis. CONCLUSIONS: Parents of children with nonsyndromic craniosynostosis reported frequent use of outpatient and school-based supportive services throughout childhood. These services may incur a significant burden of care on families. The multifactorial nature of predictive models highlights the importance of cross-disciplinary collaboration to address each child's longitudinal needs.

Adipose Tissue Uses in Peripheral Nerve Surgery.

Currently, many different techniques exist for the surgical repair of peripheral nerves. The degree of injury dictates the repair and, depending on the defect or injury of the peripheral nerve, plastic surgeons can perform nerve repairs, grafts, and transfers. All the previously listed techniques are routinely performed in human patients, but a novel addition to these peripheral nerve surgeries involves concomitant fat grafting to the repair site at the time of surgery. Fat grafting provides adipose-derived stem cells to the injury site. Though fat grafting is performed as an adjunct to some peripheral nerve surgeries, there is no clear evidence as to which procedures have improved outcomes resultant from concomitant fat grafting. This review explores the evidence presented in various animal studies regarding outcomes of fat grafting at the time of various types of peripheral nerve surgery.

Functional Network Development in Sagittal Craniosynostosis Treated With Whole Vault Cranioplasty.

INTRODUCTION: In this study, the authors seek to clarify the neurological changes before and after whole vault cranioplasty (WVC) in patients born with sagittal craniosynostosis. METHODS: A case control study design was performed that included thirty functional MRI scans, from 25 individual patients. Functional MRI and diffusion tension imaging data were analyzed with BioImageSuite (Yale University, USA). 9 functional brain networks were analyzed, with appropriate correlated functional regions of the brain and utilized for analysis. RESULTS: Comparing functional MRI the infants after WVC versus infants before WVC group, the after WVC group demonstrated an increased connectivity in the left frontoparietal, secondary (V2), and third (V3) visual networks (P < 0.001). The right frontoparietal (RFPN) had decreased connectivity (P < 0.001). There is also a decrease and increase in anisotropy in the cingulum and precuneus despite surgery, respectively (P < 0.05). Adolescents treated with WVC compared to controls, demonstrated an increased connectivity in the salience and decreased connectivity in the RFPN relative to adolescent controls. CONCLUSIONS: Patients born with sagittal craniosynostosis have different connections in infancy in most of the defined cerebral networks compared to controls. After surgery, there are specific connectivity changes that occur in the RFPN, left frontoparietal, V2, and V3 networks, which are areas associated with executive function and emotional control. Changes identified in white matter tract microstructure connections could be influential in changes in functional connectivity. Although, as a child with sagittal craniosynostosis develops, much of the abnormal network connections, seen in infancy preoperatively, corrects to some degree after surgery. However, some aberrancies in the salience and RFPN networks remain potentially affecting executive functioning.

Classification of Subtypes of Crouzon Syndrome Based on the Type of Vault Suture Synostosis.

BACKGROUND: Patients with Crouzon syndrome develop various types of anatomic deformities due to different forms of craniosynostosis, yet they have similar craniofacial characteristics. However, exact homology is not evident. Different pathology then may be best treated by different forms of surgical technique. Therefore, precise classification of Crouzon syndrome, based on individual patterns of cranial suture involvement is needed. METHODS: Ninety-five computed tomography (CT) scans (Crouzon, n = 33; control, n = 62) were included in this study. All the CT scans are divided into 4 types based on premature closure of sutures: class I = coronal and lambdoidal synostosis; class II = sagittal synostosis; class III = pansynostosis; and class IV = "Others." The CT scan anatomy was measured by Materialise software. RESULTS: The class III, pansynostosis, is the most prevalent (63.6%). The classes I, III, and IV of Crouzon have significantly shortened entire anteroposterior cranial base length, with the shortest base length in class III. The external cranial measurements in class I show primarily a decreased posterior facial skeleton, while the class III presented with holistic facial skeleton reduction. Class II has the least severe craniofacial malformations, while class III had the most severe. CONCLUSION: The morphology of patients with Crouzon syndrome is not identical in both cranial base and facial characteristics, especially when they associated with different subtypes of cranial suture synostosis. The classification of Crouzon syndrome proposed in this study, summarizes the differences among each subgroup of craniosynostosis suture involvement, which, theoretically, may ultimately influence both the timing and type of surgical intervention.

Significance of Friction and Shear in the Prevention of Contemporary Hospital-acquired Pressure Ulcers.

BACKGROUND: Hospital-acquired pressure ulcers (HAPUs) are largely preventable yet still common occurrences in hospitals. The purpose of the current study is to determine how data from the electronic medical record can be used to better understand and predict HAPU formation over the course of a hospital admission. METHODS: A case-control study on HAPUs was performed over an 8-month period at Yale New Haven Hospital. A Cox regression analysis model analyzed the impact of multiple factors on HAPU development including friction and shear, among other Braden score components. A receiver operating characteristic curve was calculated to determine the sensitivity and specificity of changes in these factors in predicting HAPU development. RESULTS: On a sample of 8,790 admissions, HAPU incidence was 4.2% over the study period (6.3% per annum). The average hospital day for HAPU development was day 15.6 (± 19.3). The Cox regression analysis demonstrated that the volatility of the friction and shear component of Braden scores had a risk ratio of 28.6 (P < 0.01; CI, 14.5-56.4). Volatility in the friction and shear component was the most predictive factor with a high receiver operating characteristic curve area of 0.865 (CI, 0.847-0.882). CONCLUSIONS: Volatility of the friction and shear component of Braden scores appears to be the most significant factor preceding HAPU development at Yale New Haven Hospital. Efforts to place more focus on identifying and reducing volatility of this factor may help decrease HAPU risk for future patients.

Classification of Subtypes of Apert Syndrome, Based on the Type of Vault Suture Synostosis.

BACKGROUND: Apert syndrome patients are different in clinical pathology, including obstructive sleep apnea, cleft palate, and mental deficiency. These functional deficiencies may be due to anatomic deformities, which may be caused by different forms of associated suture fusion. Therefore, a classification system of Apert syndrome based on the type of craniosynostosis pattern might be helpful in determining treatment choices. METHODS: CT scans of 31 unoperated Apert syndrome and 51 controls were included and subgrouped as: class I. Bilateral coronal synostosis; class II. Pansynostosis; and class III. Perpendicular combination synostosis: a. unilateral coronal and metopic synostosis; b. sagittal with bilateral/unilateral lambdoid synostosis; and c. others. RESULTS: Class I is the most common (55%) subtype. The cranial base angulation of class I was normal; however, the cranial base angulation on the cranium side of the skull in class II increased 12.16 degrees (P = 0.006), whereas the facial side cranial base angle of class IIIa decreased 4.31 degrees (P = 0.035) over time. The external cranial base linear measurements of class I showed more evident reduction in anterior craniofacial structures than posterior, whereas other subtypes developed more severe shortening in the posterior aspects. CONCLUSIONS: Bicoronal synostosis is the most common subtype of Apert syndrome with the normalized cranial base angulation. Combined pansynostosis patients have flatter cranial base, whereas the combined unilateral coronal synostosis have a kyphotic cranial base. Class I has more significant nasopharyngeal airway compromise in a vertical direction, whereas classes II and III have more limited oropharyngeal space.

Association of Regional Cranial Base Deformity and Ultimate Structure in Crouzon Syndrome.

BACKGROUND: Considerable craniofacial features of Crouzon syndrome are attributed to the dysmorphology of the cranial base. As cephalometric studies have focused mainly on the facial deformity, rather than the cranial base, the underlying cause of deformity is not as well understood. Therefore, the authors compared the cranial base development of Crouzon syndrome to controls to trace the timing of deformity in the cranial base and face, to analyze their temporal correlation. METHODS: Ninety computed tomographic scans were included (Crouzon, n = 36; controls, n = 54) and divided into five age subgroups. Craniofacial cephalometric measurements were analyzed by Materialise software. RESULTS: The overall cranial base length in Crouzon syndrome compared with controls decreased 8 percent (p = 0.014) on average. The posterior cranial fossa shortening accounted for most of this reduction. The cranial base displaced with the distances from basion, sella, and ethmosphenoid to posterior nasal spine shortened by 21%, 18%, and 16%, respectively (all p < 0.01) during life. Although the cranial base angle on intracranial surface remains normal, the angles on facial surface narrowed were reduced. CONCLUSIONS: The cranial base deformity of Crouzon syndrome consists of the whole skull base and particularly anterior skull base shortening early, leading to a compensatory widened anterior skull base. However, when this widening did not compensate fully for the rapid enlargement of the brain, the posterior skull base displaced inferiorly and became kyphotic. The cranial base deformity develops sequentially anterior to posterior in a probable cascade of influence pattern. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Mandibular Spatial Reorientation and Morphological Alteration of Crouzon and Apert Syndrome.

BACKGROUND: From infancy to adulthood, the mandible develops increased ramus height, prominence of the chin, and laterally widened gonial angles. In Crouzon and Apert syndromes, both relative retrognathia and prognathic jaws have been reported. Growth is influenced by a variety of factors, including the growth and relative position of the skull base, functional coordination, and the spatial influence of the laryngopharynx. Thus, this study aimed to explore in detail the evolution of the mandible in both syndromes and its relationship with the entire facial structure and skull base. METHODS: One hundred twenty-three preoperative computed tomographic scans (Crouzon, n = 36; Apert, n = 33; control, n = 54) were included and divided into 5 age subgroups. Computed tomographic scans were measured using Materialise software. Cephalometrics relating to the mandible, facial structures, and cranial base were collected. Statistical analyses were performed using t test and statistical power analysis. RESULTS: In Crouzon syndrome, the angle between the cranial base and gnathion was increased prior to 6 months of age by 10.29 degrees (P < 0.001) and by adulthood to 11.95 degrees (P = 0.003) compared with normal. After 6 months of age, the distance between bilateral mandibular condylions (COR-COL) was narrower by 15% (P < 0.001) in Crouzon syndrome compared with control subjects. Before 6 months of age, Apert COR-COL decreased 16% (P < 0.001) compared with control subjects and 13% (P = 0.006) narrower than Crouzon. During 2 to 6 years of age, Apert mandibular ramus height caught up to, and became longer than, Crouzon by 12% (P = 0.011). The nasion-sella-articulare angle of the Apert skull was 5.04 degrees (P < 0.001) less than Crouzon overall. CONCLUSIONS: In Crouzon syndrome, the changes of the spatial relationship of the mandible to the cranial base develop earlier than the mandibular shape deformity, whereas in Apert syndrome, the spatial and morphological changes are synchronous. The morphological changes of the mandible are disproportional in 3 directions, initially significant shortening of the mandibular width and length, and, subsequently, reduced height. Crouzon has more shortening in mandibular height compared with Apert, reflecting the more shortened posterior cranial base length. The narrowed angle between the mandible and the posterior cranial base in Apert skulls is consistent with the more limited nasopharyngeal and oropharyngeal airway space.

What Is the Skull Structure Influence of Squamosal Suture Synostosis in Nonsyndromic and Syndromic Crouzon Craniosynostosis?

BACKGROUND: The morphologic effect of squamosal synostosis has not been clarified, due to its low occurrence rate, and its inclination to be combined with premature closure of other major sutures, especially in syndromic synostosis. This study's goal is to explore the morphological influence of squamosal synostosis in both syndromic and nonsyndromic craniosynostosis patients. METHODS: Twenty-five computed tomography (CT) scans from nonsyndromic squamosal synostosis (NSS), Crouzon syndrome with squamosal synostosis (CSS), Crouzon syndrome without squamosal synostosis, and normal controls were included. Three-dimensional (3D) cephalometry, entire cranial volume and cranial fossa volume were measured using Materialise software. RESULTS: The entire cranial volume of all groups was similar. The NSS developed a gradual reduction in the severity of reduced segmental volume from the anterior cranial fossa, to the middle cranial fossa, and to the unaffected volume of posterior cranial fossa. The CSS developed the most severe volume reduction of middle cranial fossa (12608.30 ±â€Š2408.61 mm vs 26077.96 ±â€Š4465.74 mm, 52%), with proportionate volume reduction of the anterior (7312.21 ±â€Š2435.97 mm vs 10520.63 ±â€Š2400.43 mm, 30%) and posterior cranial fossa (33487.29 ±â€Š5598.93 mm vs 48325.04 ±â€Š14700.44 mm, 31%). The NSS developed a narrower anterior cranial fossa, a clockwise rotated Frankfort horizontal plane, and a retracted chin (pogonion). CONCLUSION: Squamosal synostosis may alter the development of cranial fossa volume, especially the volume of middle cranial fossa. However, the development of cranial base, and related facial features are determined largely by major vault sutures and associated syndromic conditions, rather than the squamosal suture alone. LEVEL OF EVIDENCE: II.

The Endocranial Bifrontal Angle: A Longitudinal Evaluation in Two Patients With Metopic Synostosis.

BACKGROUND: Metopic craniosynostosis is the early fusion of the skull bones in the frontal region of the metopic suture, which leads to trigonocephaly and neurological sequelae. Severe metopic craniosynostosis is defined by an endocranial bifrontal angle less than 124°, and this serves as a threshold for neurological deficit and significant skull deformity, typically warranting surgical treatment. METHODS: Two patients presented for evaluation for metopic craniosynostosis. Low-dose computed tomography imaging was performed in both patients due to concern for underlying metopic craniosynostosis. RESULTS: In both patients, imaging demonstrated an initial endocranial bifrontal angle greater than 124°. However, in subsequent evaluation, the children developed severe trigonocephaly, and an angle less than 124°. CONCLUSION: The authors present 2 patients with metopic craniosynostosis, which became severe over time. The authors hypothesize that this may be due to an initial smaller head circumference, which later experienced rapid growth, leading to narrower endocranial bifrontal angle. Therefore, younger children with suspected metopic craniosynostosis, with initially smaller head circumference (but not meeting the threshold of 124°) should be followed longitudinally, as the head circumference may demonstrate greater narrowing subsequently into a more severe form of trigonocephaly and possibly surgery.

What is the Functional Difference Between Sagittal With Metopic and Isolated Sagittal Craniosynotosis?

INTRODUCTION: The purpose of this study is to understand the neurological differences between patients born with combined sagittal and metopic craniosynostosis (SMc) and isolated sagittal craniosynostosis (ISc) by studying aberrations in functional brain connectivity and white matter microstructure, before surgery, utilizing functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). METHODS: The authors collected DTI and resting-state (ie, no sedation and asleep) functional connectivity MRI data in 10 infant patients preoperatively: 5 in the SMc group (4.3 ±â€Š1 months) and 5 in the ISc group (4.8 ±â€Š1.1 months). Resting state fMRI imaging and DTI data were acquired using a 3-T Siemens Trio MRI system (Erlangen, Germany) while the infant patients slept. fMRI data were corrected for movement using SPM, underwent cerebrospinal fluid and white matter signal regression and further analyzed with BioImageSuite. For the DTI data, 3 diffusion runs were averaged, processed utilizing FMRIB Software Library, and analyzed statistically using BioImageSuite. RESULTS: Comparing the SMc versus ISc groups, SMc demonstrated that there was increased connectivity, statistically significant differences, in neural networks between children with sagittal synostosis alone versus those with sagittal with metopic synostosis, in the right BA 31 and BA 23 (corresponding to the posterior cingulate cortex (PCC) (P < 0.001). Analysis of the DTI revealed increased fractional anisotropy (normal maturation of white tracts) in the SMc group in the cingulum compared to the ISc group (P < 0.05). Differences in the functional networks include increased connectivity right frontoparietal network (RFPN) in ISc and increased connectivity in the primary visual network (V1) in SMc (P < 0.001). CONCLUSION: The SMc had increased connectivity as measured by fMR in the PCC, an area associated with attention deficit hyperactivity disorder. The DTI analysis demonstrated an increase in fractional anisotropy of the cingulum in the SMc group, a white matter tract projecting from the cingulate cortex; connections of the limbic (emotional regulation) system are instrumental. In SMc, increase of connectivity in the PCC correlates with an increase in maturation of the cingulum compared to ISc. There is increased connectivity of the RFPN network in the ISc and increased connectivity of the V1 network in the SMc patients. The SMc group has increased connectivity in the PCC, the original seed of the DMN network, and decreased connectivity to the RFPN network. The pattern of increased connectivity in the area of the DMN and decreased connectivity in the RFPN network is similar to the trend when comparing ADHD patients to normal controls. SMc has more similar functional network connectivity to ADHD as compared to ISc.

Spatial and temporal changes of midface in Apert's syndrome.

The dysplastic maxilla and retracted zygoma characterize Apert's syndrome. The relationship between the cranial base and facial development is believed to be influential and substantial. The purpose of this study is to explore the temporal relationships of maldevelopment of these structures to identify potential influence patterns. Fifty-four CT scans (unoperated Apert's, n = 18; control, n = 36) were included and divided into three age subgroups (0-6 months, 6 months-2 years, and 2-6 years). All measurements were analyzed by Materialize software. Cephalometrics relating to midface and cranial base were collected. In anteroposterior direction, prior to 6 months, the zygoma was markedly retruded by 12% in Apert's, followed by persistent retrusive shape into adulthood, averaging 17% shorter compared to controls. The maxillary anteroposterior dimension was 22% shorter than normal before 6 months of age, thereafter, it maintained at least an 18% deficiency into adulthood. In the horizontal direction, the transverse width of the zygoma increased 39% between 6 months and 2 years of age, and it was 14% wider on average overall into adulthood. The maxilla had normal growth in transverse and vertical directions. The zygoma is the most severely deformed anatomic facial structure in early infancy, in both positional relation and geometric shape in Apert's syndrome. This may develop as a 'bridge', influencing the structure, transmitting malformation stresses, caused by premature fused coronal and peri-zygomatic sutures, into facial structures and the maxilla.

Effect of Fat Grafting on Postoperative Edema After Orthognathic Surgery.

BACKGROUND: Autologous fat grafting concurrent with orthognathic surgery is a powerful adjunctive aesthetic tool, and has been shown to have anti-inflammatory properties in prior studies. The purpose of this study is to evaluate the effect of fat grafting on postoperative edema following orthognathic surgery, and also consider the impact of age and BMI. METHODS: A retrospective cohort study was performed. Three-dimensional photos (Canfield, Fairfield, NJ) from a series of postprocedure time-points were analyzed using Geomagic Studio 2013 (3D Systems, Morrisville, NC). An unstructured covariance linear mixed model was created to analyze the effect and extent of the effect of age, BMI, and fat using SPSS Statistics 24.0 (IBM, Armonk, NY). RESULTS: One hundred thirty postoperative three-dimensional pictures were analyzed, from 31 patients. The linear mixed model demonstrates that the fat injected (P<0.001), age (P=0.001), and BMI (P<0.001) are significant factors in the postoperative volume. Age and BMI increase postoperative edema by 3.63 cm per year and 14.60 cm per kg/m, respectively. Fat injected reduces postoperative edema by 8.72 cm per 1 cc injected. CONCLUSION: Increasing age and BMI lead to greater postoperative edema (3.88 cm per year and 14.60 cm per kg/m, respectively). Fat grafting concurrent with orthognathic surgery reduces postoperative edema by 8.72 cm per 1 cc injected, and hastens return to steady state. This impact is more profound in patients with a greater age and BMI.

Understanding the Learning Disabilities Linked to Sagittal Craniosynostosis.

OBJECTIVE: The purpose of this study is to investigate further findings that corroborate similarities between corrected sagittal craniosynostosis and attention deficit hyperactivity disorder (ADHD). The aim is to further characterize the neurocognitive deficits seen in adolescents with corrected craniosynostosis by comparing it to established learning deficits such as ADHD. METHODS: A total of 30 functional magnetic resonance imaging (fMRI) of 10 sagittal nonsyndromic craniosynostosis (sNSC), 10 ADHD-combined, and 10 control adolescents were studied. The fMRI scans were analyzed utilizing Statistical Parametric Mapping (University College London, UK) and analyzed with BioImageSuite (Yale University, New Haven, CT). RESULTS: The ADHD has lower connectivity to Brodmann area (BA) 11 (Montreal Neurological Institution [MNI]: -12,26,-21), BA20 (MNI: 62,-24,-25), and BA21 (MNI: 62,-32,-23) compared to sNSC and controls (P < 0.001). The sNSC has a unique visuospatial defect, compared to ADHD, created by decreased connectivity to BA31 (MNI: -3,-68,37), BA7 (MNI: -4,-68,41), BA19 (MNI: 0,-83,31), visual association cortex (MNI: -4,-78,22), and primary visual cortex (MNI: 7,-74,21) (P < 0.001). CONCLUSION: Patients born with sNSC have different neural connections than children born with ADHD. Patients born with sNSC have decreased connections in areas of visual processing and increased connections in areas of attention and auditory processing than patients with ADHD. Therefore, children with sagittal craniosynsotosis may have learning difficulties that, similar, yet different from ADHD.

Temporal Evaluation of Craniofacial Relationships in Apert Syndrome.

Complicated craniofacial malformations interfacing with multiple intracellular regulatory mechanisms, lead to ambiguous growth patterns in Apert syndrome. This study aims to explore the chronology and pathogenesis of the development of craniofacial anatomic relationships and to verify the positional correlates between skull and facial structures in Apert syndrome. Fifty-four computed tomography scans (Apert, n = 18; control, n = 36) were included and divided into 3 age subgroups. Craniofacial 3-dimensional cephalometries were analyzed by Materialize software. The angle between sella-nasion plane and maxillary plane widens 7.74° (P = 0.003) prior to 6 months of age; thereafter, this widening increases by 10.36° (P < 0.001) in 6 months to 2 years of age, and remains increased by 8.9° (P = 0.046) throughout childhood. The angle between Frankfort horizontal plane and maxillary plane widens 5.17° (P = 0.022) before 6 months. Angles SNA, SNB, and ANB showed decreases, averaging 12.23° (P < 0.001), 5.19° (P = 0.004), and 6.72° (P = 0.001), respectively. The linear measurements showed synchronicity and continuing deformity into adulthood. Between 6 months to 2 years of age, the distance from sella to nasion (S-N), anterior nasal spine (S-ANS), and posterior nasal spine (S-PNS) decreased 8% (P = 0.006), 16% (P < 0.001), and 19% (P = 0.002), respectively, and remained shortened into adulthood. The angulation changes occur earlier in development than linear distance reduction in Apert syndrome patients compared with controls. Angular adjustments were not sufficient to maintain normal cranial base length. Facial deformity of Apert syndrome temporally begins with the midface, and affects orbit and mandible later in life.

Epidemiologic Assessment of Microtia in Over 23 Million Consecutive United States Births.

PURPOSE: Conflicting data exist regarding the incidence, demographics, and abnormalities associated with microtia. Using a large national cohort database, a comprehensive evaluation of microtia in the United States was performed. METHODS: The Kids' Inpatient Database was reviewed over a 15-year consecutive period. Information regarding patient demographics, comorbidities, postoperative complications, and hospital setting was collected. Statistical tests were analyzed using independent t tests and χ analysis. RESULTS: A total of 23,479,792 births over 15 consecutive years from 1997 to 2012 were included in the study. Microtia was identified in 1563 births. Incidence of microtia was higher in males (P<0.01) and patients of Asian or Hispanic race (P<0.01). Patients with microtia had significantly more congenital anomalies relative to the rest of the population (P<0.01). Specifically, cardiac and genitourinary anomalies were 51 and 19 times, respectively, more likely in microtia patients. Risk of associated congenital anomalies with microtia was highest in female and Black patients. 12.6% of all microtia patients had an associated craniofacial syndrome with a comparable postsurgical course to the nonsyndromic population. CONCLUSION: This study represents the largest national, longitudinal study of microtia allowing for demographic, socioeconomic, and comorbidity commentary. By quantifying relative risk of associated congenital anomalies, it can help inform the type and utility of screening modalities when evaluating microtia patients.

Facial Malformation in Crouzon's Syndrome Is Consistent with Cranial Base Development in Time and Space.

BACKGROUND: In Crouzon's syndrome, cranial base deformities begin sequentially in the anterior cranial fossa initially, and later to the posterior cranial base. Facial characteristics are likely related to cranial base development. The temporal correlation between cranial base development and facial features is in need of clarification in Crouzon's patients, to clarify initial sites of deformity, which may impact surgical decision making. METHODS: Thirty-six computed tomography scans of unoperated Crouzon's syndrome patients and 54 controls were included and divided into 5 age-subgroups. All the planes used for analysis were set as perpendicular to a defined "midplane" to offset the confounding factor caused by potential asymmetry. RESULTS: The angle between Sella-Nasion plane and Frankfort horizontal plane was significantly increased before 6 months of age (P = 0.014), with an average 70% (P < 0.001) increase ultimately into adulthood. The angle between SN and maxillary plane and the angle between Sella-Nasion and occlusal planes increased consistently through infancy to adulthood (124% and 42%, respectively, both P < 0.001). The relative angle of mandibular plane to Frankfort horizontal plane increased before 6 months (28%, P = 0.007) with a peak timeframe from 2 to 18 years. Facial lateral curvature related measurements indicate the whole face is inclined posteriorly and inferiorly direction in relation to the anterior cranial base. CONCLUSION: Crouzon's facial malformation development is synchronous and positionally correlational with cranial base deformity. It transmitted from orbit to mandible, with the most evident morphologic changes are in the orbit and midface.

Normal angulation of skull base in Apert syndrome.

Apert syndrome is characterized by the severe craniofacial deformities. The subsequent process of skeletal maldevelopment is likely to be influenced by multiple interactions at several levels, at a given time. In this study, we aimed to explore the evolution of cranial basal dysmorphology and the chronology of these deformities in Apert syndrome, by objectively analyzing three-dimensional measurements. Fifty-four CT scans from unoperated patients (Apert, n = 18; control, n = 36) were included in this study, with age range from 3 days to 24 years. Before 6 months of age, Apert's anterior cranial base was widened 60%. Between 6 months and 2 years of age, the whole cranial base length, anterior cranial base length and posterior cranial base length decreased 8%, 8% and 14%, respectively. The greater sphenoid wing angle was wider by 26.0°, and continued into adulthood. The cranial base angles did not produce significant changes throughout life. The extra cranial distances synchronously and almost proportionally shortened after later infancy. The anterior and posterior cranial base length shortened at an almost proportional rate. The malformations of the skull vault are additive effects with cranial base fusion on skull length restriction, but the angulation of the skull base is virtually normal.

Harnessing Social Media to Advance Research in Plastic Surgery.

BACKGROUND: Social media have transformed plastic surgery, intersecting patient education, provider marketing, and academic interactions across the globe. Despite this, social media are seldom used in research. The authors sought to understand the primary incentives and deterrents for patient participation in research efforts. METHODS: Facebook groups for craniosynostosis families were identified; the largest two had 11,000 and 7200 members. Facebook group administrators were asked to post an open invitation to enroll in the authors' study. Interested participants contacted study personnel directly. Materials and written/video instructions were provided for collecting genetic specimens. Participants completed a follow-up survey to assess satisfaction. The authors subsequently conducted virtual neurocognitive sessions for functional assessment. RESULTS: Three hundred thirty-one of 384 genetic study participants (86 percent) were recruited by means of social media. Three hundred forty-three of 472 mailed packages (73 percent) were returned. Novel mutations identified explained craniosynostosis in 10 percent of participants. One hundred ninety-five families completed the follow-up survey. One hundred percent and 95 percent reported that the written and video instructions were helpful, respectively. The most frequently cited obstacles barring participation in research studies was travel to the study site (63 percent), significantly more than indirect monetary costs (p = 0.007), information confidentiality (p < 0.001), time required to participate (p < 0.001), and invasive study procedures (p < 0.001). Ninety-nine percent preferred participating in a study from home rather than a research center. Follow-up neurocognitive studies are ongoing. CONCLUSIONS: With proper planning, participation in social media-based research is easy, cost-effective, and time conscious. Requiring travel to a research facility is the factor most likely to deter families from contributing to research. The results emphasize the unrealized potential of social media for advancing research in plastic surgery.