Association of cranial base suture/synchondrosis fusion with severity of increased intracranial pressure in Crouzon syndrome.

This study investigated how the fusion states of the cranial base is related to the degree of increased intracranial pressure (ICP) in patients with Crouzon syndrome. This retrospective cohort study enrolled patients who were diagnosed with Crouzon syndrome between May 2007 and April 2022. We categorized the patients into three groups: A, B, and C, according to the severity of increased ICP and the number of cranial vault remodeling procedures for corrective operation. The preoperative fusion states of the cranial base sutures/synchondroses were examined using facial bone computed tomography and compared between groups. Overall, 22 patients were included in Groups A, B, and C, including 8, 7, and 7 patients, respectively. The preoperative average grades of the total cranial base suture/synchondrosis fusion appeared to significantly increase with severity, except for the frontoethmoidal suture, which showed the opposite tendency. In the subgroup analysis, frontosphenoidal, sphenoparietal, sphenosquamosal, parietomastoid, and occipitomastoid suture and petro-occipital synchondrosis were associated with earlier fusion in the more severe group. Premature closure of the cranial base sutures/synchodroses seems to be associated with increased ICP severity in patients with Crouzon syndrome. Precise evaluation of minor sutures/synchondroses at the first visit might help build subsequent operative plans and predict disease prognosis.

Staged reconstruction of a chronically infected large skull defect using free tissue transfer and a patient-specific polyetheretherketone implant.

Reconstructions of extensive composite scalp and cranial defects are challenging due to high incidence of postoperative infection and reconstruction failure. In such cases, cranial reconstruction and vascularized soft tissue coverage are required. However, optimal reconstruction timing and material for cranioplasty are not yet determined. Herein, we present a large skull defect with a chronically infected wound that was not improved by repeated debridement and antibiotic treatment for 3 months. It was successfully treated with anterolateral thigh (ALT) free flap transfer for wound salvage and delayed cranioplasty with a patient-specific polyetheretherketone implant. To reduce infection risk, we performed the cranioplasty 1 year after the infection had resolved. In the meantime, depression of ALT flap at the skull defect site was observed, and the midline shift to the contralateral side was reported in a brain computed tomography (CT) scan, but no evidence of neurologic deterioration was found. After the surgery, sufficient cerebral expansion without noticeable dead-space was confirmed in a follow-up CT scan, and there was no complication over the 1-year follow-up period.

Applicative Factors of Helmet Molding Therapy in Late-diagnosed Positional Plagiocephaly.

BACKGROUND: Although the benefits of helmet therapy for positional plagiocephaly are strongly correlated with age, the effective period remains controversial. However, most physicians agree that effective results can be obtained in patients within the age of 6 months. Owing to the characteristics of positional plagiocephaly in Koreans, many Korean patients have delayed diagnosis, and because this results in delayed onset of the helmet therapy, the outcomes remain largely underevaluated. In the management of late-diagnosed positional plagiocephaly, we aimed to determine the factors affecting the effective application of helmet therapy. METHODS: We recruited 39 consecutive patients with positional plagiocephaly who received helmet therapy and completed the treatment between December 2008 and June 2016. The ages at initiation and completion of treatment, duration of daily use, initial and final absolute diagonal differences, cephalic index, and cranial vault asymmetry index (CVAI) were analysed using data retrospectively collected from the patients' medical records. RESULTS: We identified 12 patients with late-diagnosed positional plagiocephaly, of whom 83.33% were effectively treated. The effective change in CVAI (%) was affected by age at treatment initiation (P = 0.001), initial absolute diagonal distance differences (P < 0.001), and initial CVAI (P < 0.001). Up to 9 months, a gradual change of at least 1% CVAI was attained. Treatment initiation at ages < 5.5 months was beneficial. Even at a later age, patients with an initial absolute diagonal distance difference of > 13.50 mm and initial CVAI of > 11.03% could receive effective helmet therapy. CONCLUSION: The efficacy of helmet therapy in late-diagnosed patients can be predicted on the basis of not only age at treatment initiation, but also initial absolute diagonal distance differences and initial CVAI. We anticipate that even patients with late-diagnosed positional plagiocephaly can expect better helmet therapy outcomes.

Quantitative Correlation of Nanotopography with Cell Spreading via Focal Adhesions Using Adipose-Derived Stem Cells.

Nanotopography mimicking extracellular environments reportedly impact cell morphological changes; however, elucidating this relationship has been challenging. To control cellular responses using nanostructures, in this study, the quantitative relationship between nanotopography and cell spreading mediated by focal adhesions (FAs) is demonstrated using adipose-derived stem cells (ASCs). The spreading of ASCs and area of FAs are analyzed for the distribution of filamentous actin and vinculin, respectively, using fluorescent images. FAs require a specific area for adhesion (herein defined as effective contact area [ECA]) to maintain cell attachment on nanopillar arrays. An ECA is the area of FAs supported by nanopillars, multiplying the area fraction (AF) of their top surface. Regarding the spreading of cells, the mean area of ASCs linearly decreases as the mean area of FAs increases. Because the area of FAs is inversely correlated to the AF of the nanopillar arrays, the spreading of cells can be quantitatively correlated with nanotopography. The results provide a conceptual framework for controlling cell behaviors to design artificial substrates for tissue-engineering applications.

Molecular Diagnosis of Craniosynostosis Using Targeted Next-Generation Sequencing.

BACKGROUND: Genetic factors play an important role in the pathogenesis of craniosynostosis (CRS). However, the molecular diagnosis of CRS in clinical practice is limited because of its heterogeneous etiology. OBJECTIVE: To investigate the genomic landscape of CRS in a Korean cohort and also to establish a practical diagnostic workflow by applying targeted panel sequencing. METHODS: We designed a customized panel covering 34 CRS-related genes using in-solution hybrid capture method. We enrolled 110 unrelated Korean patients with CRS, including 40 syndromic and 70 nonsyndromic cases. A diagnostic pipeline was established by combining in-depth clinical reviews and multiple bioinformatics tools for analyzing single-nucleotide variants (SNV)s and copy number variants (CNV)s. RESULTS: The diagnostic yield of the targeted panel was 30.0% (33/110). Twenty-five patients (22.7%) had causal genetic variations resulting from SNVs or indels in 9 target genes (TWIST1, FGFR3, TCF12, ERF, FGFR2, ALPL, EFNB1, FBN1, and SKI, in order of frequency). CNV analysis identified 8 (7.3%) additional patients with chromosomal abnormalities involving 1p32.3p31.3, 7p21.1, 10q26, 15q21.3, 16p11.2, and 17p13.3 regions; these cases mostly presented with syndromic clinical features. CONCLUSION: The present study shows the wide genomic landscape of CRS, revealing various genetic factors for CRS pathogenesis. In addition, the results demonstrate that an efficient diagnostic workup using target panel sequencing provides great clinical utility in the molecular diagnosis of CRS.

Analysis of factors involved in brain-death donor processing for face transplantation in Korea: How much time is available from brain death to transplantation?

BACKGROUND: Face transplantation has naturally evolved from reconstructive procedures. However, few institutions perform face transplantations, because it is time-consuming and it is necessary to justify non-vital organ transplantation. We investigated the process of organ donation from brain-dead patients and the possibility of incorporating face transplantation into the donation process. METHODS: A retrospective review was performed of 1,074 brain-dead patients from January 2015 to December 2016 in Korea. We analyzed the time intervals from admission to brain death decisions (first, second, and final), the causes of brain death, and the state of the transplanted organs. RESULTS: The patient base (n=1,074) was composed of 747 males and 327 females. The average period between admission to the first brain death decision was 8.5 days (±15.3). The average time intervals between the first brain death decision and medical confirmation using electroencephalography and between the first brain death decision and the final determination of brain death were 16 hours 58 minutes (±14 hours 50 minutes) and 22 hours 57 minutes (±16 hours 16 minutes), respectively. The most common cause of brain death was cerebral hemorrhage/stroke (42.3%), followed by hypoxia (30.1%), and head trauma (25.2%). CONCLUSIONS: When face transplantation is performed, the transplantation team has 22 hours 57 minutes on average to prepare after the first brain death decision. The cause of brain death was head trauma in approximately one-fourth of cases. Although head trauma does not always imply facial trauma, surgeons should be aware that the facial tissue may be compromised in such cases.

Effect of Relaxin Expression from an Alginate Gel-Encapsulated Adenovirus on Scar Remodeling in a Pig Model.

PURPOSE: Relaxin (RLX) is a transforming growth factor-ß1 (TGF-ß1) antagonist that is believed to function as a potent collagen re-arranger and a major suppressor of extracellular matrix components. Adenoviruses (Ads) are accepted vectors for cancer gene therapy. However, repeated treatments of Ad are limited by short-term biological activity in vivo. The efficacy of sustained RLX expression to scar remodeling was assessed using an injectable alginate gel-matrix system. MATERIALS AND METHODS: Pig scar tissue was treated with relaxin-expressing Ad loaded in alginate gel (gel/Ad-RLX). Surface areas, color, and pliability of scars were compared, and various factors influencing scar formation and collagen arrangement were analyzed. RESULTS: Gel/Ad-RLX decreased scar size, color index, and pliability. Immunohistochemistry showed decreased levels of major extracellular matrix proteins in the gel/Ad-RLX-treated group. Furthermore, treatment with gel/Ad-RLX reduced expression of tissue inhibitor of metalloproteinase-1 and alpha-smooth muscle actin and markedly increased expression of matrix metalloproteinase-1 in pig scar tissues. Gel/Ad-RLX also significantly downregulated TGF-ß1 and upregulated TGF-ß3 mRNAs in pig scar tissues. CONCLUSION: These results support a prominent role for RLX in scar remodeling and suggest that gel/Ad-RLX may have therapeutic effects on scar formation.

Extended temporalis flap for skull base reconstruction.

Traditionally, a galeal flap has been used for skull base reconstruction. In addition to the galeal flap, several other flaps, such as the temporalis muscle flap or the free vascularized flap, can be options for skull base reconstruction, and each option has advantages and disadvantages. Certain cases, however, can be challengeable in the application of these flaps. We successfully managed to cover a skull base defect using an extended temporalis flap. Herein, we present the case and introduce this novel method.

Treatment of fibrous dysplasia of the zygomaticomaxillary complex with radical resection and three-dimensional reconstruction with autologous calvarial bone graft.

Fibrous dysplasia (FD) is a rare, benign bone disease with abnormal bone maturation and fibroblastic proliferation. Optimal treatment of zone 1 craniofacial FD is radical resection and reconstruction. To achieve of structural, aesthetic, and functional goals, we use three-dimensionally designed calvarial bone graft for reconstruction of zygomatic defect after radical resection of FD. The authors used a rapid-prototyping model for simulation surgery for radical resection and immediate reconstruction. Donor site was selected from parietal bone reflect shape, contour, and size of defect. Then radical resection of lesion and immediate reconstruction was performed as planned. Outcomes were assessed using clinical photographs and computed tomography scans. Successful reconstruction after radical resection was achieved by three-dimensional calvarial bone graft without complications. After a 12-month follow-up, sufficient bone thickness and symmetric soft tissue contour was well-maintained. By considering three-dimensional configuration of zygomaticomaxillary complex, the authors achieved satisfactory structural, aesthetic and functional outcomes without complications.

Effects of Tranexamic Acid Based on its Population Pharmacokinetics in Pediatric Patients Undergoing Distraction Osteogenesis for Craniosynostosis: Rotational Thromboelastometry (ROTEMTM) Analysis.

Background: Distraction osteogenesis for craniosynostosis is associated with significant hemorrhage. Additionally, patients usually require several transfusions. Tranexamic acid (TXA) is effective for reducing blood loss and the need for transfusions during surgeries. However, the significance of TXA infusion has not been thoroughly described yet. Methods: Forty-eight children undergoing distraction osteogenesis for craniosynostosis were administered intraoperative TXA infusion (loading dose of 10 mg/kg for 15 min, followed by continuous infusion at 5 mg/kg/h throughout surgery; n = 23) or normal saline (control, n = 25). Rotational thromboelastometry (ROTEMTM) was conducted to monitor changes in coagulation perioperatively. Results: Blood loss during surgery was significantly lower in the TXA-treated group than it was in the control group (81 vs. 116 mL/kg, P = 0.003). Furthermore, significantly fewer transfusions of red blood cells and fresh frozen plasma were required in the TXA group. In the control group, clotting time during the postoperative period was longer than it was during the preoperative period. Similarly, clot strength was weaker during the postoperative period. D-dimer levels dramatically increased in the control group compared with the TXA group after surgery. The duration of mechanical ventilation and the number of postoperative respiratory-related complications were significantly greater in the control group than they were in the TXA group. Conclusions: TXA infusion based on population pharmacokinetic analysis is effective in reducing blood loss and the need for transfusions during the surgical treatment of craniosynostosis. It can also prevent the increase in D-dimer levels without affecting systemic hemostasis.

Demographic characteristics of craniosynostosis patients in Asia.

PURPOSE: Craniosynostosis (CRS) is a congenital condition resulting premature fusion of one or more cranial sutures. CRS is classified according to the involved sutures into sagittal, metopic, unicoronal, unilambdoid, bicoronal, and multiple-suture CRS, with sagittal suture fusion known to be the most common type. Although multiple studies have presented demographic characteristics of CRS patients, to date, there is no study representing an Asian population. We sought to compare the demographic characteristics of Asian patients to those of Western patients, considering previous reports. MATERIALS AND METHODS: A total of 266 CRS patients treated in a single institution from 1996 to 2016 were retrospectively reviewed. Data from the patients was collected regardless of whether they underwent operation. Patients' age at the time of presentation, sex, and maternal and paternal age at birth were reviewed. Patients were routinely investigated for abnormal genes (FGFR2 and FGFR3). The Bayley Scales of Infant Development, Second Edition (BSID-II), was used to assess the patients' cognitive and psychomotor development. One-way analysis of variance or the Kruskal-Wallis test was used to compare continuous variables. A p value of <0.05 was considered statistically significant. RESULTS: Our study included 157 males (59.02%) and 109 females (40.98%), with an age ranging from 0.1 to 10.5 years. The mean age at the time of diagnosis was 2.01 ± 2.57 years, and the mean age at operation was 2.16 ± 2.61 years. Of the patients, 27 (10.15%) were bicoronal, 28 patients (10.53%) were metopic, 48 patients (18.04%) were unicoronal, 50 patients (18.80%) were unilamboid, and 67 patients (25.19%) were sagittal. Patients with multiple-suture CRS totaled 46 (17.29%). Investigation of abnormal genes revealed six patients (2.20%), including two patients with abnormal FGFR2 and four patients with abnormal FGFR3. Maternal and paternal ages at the patients' birth were 32.18 ± 4.56 years and 34.71 ± 4.72 years, respectively. The mean BSID-II scores were 84.96 ± 22.77 for the Mental Development Index and 84.19 ± 25.62 for the Psychomotor Development Index. To examine the trend of diagnosis of CRS type, we also evaluated the number of new patients diagnosed with nonsyndromic CRS per year at our institution. New diagnoses of CRS generally increased from the year 2009, although variations continued. CONCLUSION: The mean age of our patients is relatively high compared to previous, Western studies. Through this research, we recognized that cultural discrepancies regarding the expectations of Asian parents may lead to prolonged diagnosis of CRS patients, and yet even relatively older CRS infants can successfully be treated with surgical intervention. The prevalence of CRS types and BSID-II development scores varied compared to those in previous Western studies. Further investigations at the genetic level are required to compare the different populations. To diagnose CRS in an effective and timely manner, a physician must be aware of the general characteristics and understand the variations between Western and Eastern populations.

Scaffold Free Bone Regeneration Using Platelet-Rich Fibrin in Calvarial Defect Model.

Bone regeneration is a complex process influenced by various physiological factors. Platelet-rich plasma (PRP) contains many growth factors and has shown osteogenic effects. The PRP is usually activated before use. However, the authors showed that nonactivated PRP (nPRP) and activated PRP have comparable osteogenic effects in the previous study. Generally, a scaffold has been needed for the application of PRP in the cranial defect model. In this study, the authors aimed to compare the performance of scaffold free platelet-rich fibrin (PRF) to nPRP as an adjuvant for bone regeneration.Twenty-four New Zealand White rabbits were randomly allocated into 3 groups: control, nPRP, and PRF. A 15 × 15 mm defect was created on each rabbit's cranium. Acellular collagen sponges (Gelfoam) were placed on the defects of the control group, Gelfoam with nPRP was used for the nPRP group, and PRF membrane was directly applied for the PRF group. nPRP and PRF were obtained from each subject's peripheral blood. Sixteen weeks later, the volume of regenerated bone was measured using 3-dimensional computed tomography. The surface area was measured via autopsy, and the samples were then obtained for histological analysis.Bone regeneration in the experimental groups was significantly greater than that in the control group. There were no significant differences in the area of regeneration or histological characteristics between the nPRP and PRF groups.In the calvarial defect of the rabbits, the use of PRF and scaffolded PRP showed comparable bone regeneration effects, which suggested that PRF might be a therapeutic alternative for bone grafts.

Analysis of the correlation between deformational plagiocephaly and neurodevelopmental delay.

BACKGROUND: Deformational plagiocephaly (DP) refers to cranial asymmetry resulting from uneven external forces. A strong association exists between DP and developmental delay. We investigated the effect of DP severity on developmental delay. METHODS: Between 2010 and 2016, data from 155 patients with DP were reviewed retrospectively. Two indices were used to evaluate the deformation quantitatively: cranial index (CI) and cranial vault asymmetry index (CVAI). The Bayley Scales of Infant Development-II was used to evaluate the neurodevelopment of patients. RESULTS: According to the CI of the study population, 2 patients showed scaphocephaly, 12 showed mesocephaly, and 141 showed brachycephaly. For CVAI, 10 patients showed values of <3.5, 10 patients showed mild deformity (3.5-6.25), 27 patients showed moderate deformity (6.25-8.75), and 108 patients showed severe deformity. The means of the mental development index (MDI) and psychomotor development index (PDI) were 91.69 ± 16.8 and 92.28 ± 17.59, respectively; after the exclusion of patients with confounding factors, the values were 96.26 and 92.9, respectively. The Spearman correlation coefficients between MDI and CI and CVAI were -0.019662 and 0.118916, respectively, whereas for PDI, the values were -0.195428 and -0.012386, respectively. CONCLUSIONS: There was a statistically significant neurodevelopmental delay in patients with DP. However, accelerated neurodevelopment was also encountered in many patients. MDI was found to be more affected by multiple confounding factors than PDI, whereas PDI was only affected by congenital anomalies. There was no definitive relationship between the severity of DP and the degree of developmental delay in our study group.

Effect of Relaxin Expressing Adenovirus on Scar Remodeling: A Preliminary Study.

BACKGROUND: Relaxin is a transforming growth factor ß1 antagonist. To determine the effects of relaxin on scar reduction, we investigated the scar remodeling process by injecting relaxin-expressing adenoviruses using a pig scar model. METHODS: Scars with full thickness were generated on the backs of Yorkshire pigs. Scars were divided into two groups (relaxin [RLX] and Control). Adenoviruses were injected into the RLX (expressing relaxin) and Control (not expressing relaxin) groups. Changes in the surface areas, color index and pliability of scars were compared. RESULTS: Fifty days after treatment, the surface areas of scars decreased, the color of scars was normalized, and the pliability of scars increased in RLX group. CONCLUSION: Relaxin-expressing adenoviruses improved the surface area, color, and pliability of scars. The mechanism of therapeutic effects on scar formation should be further investigated.

The Unnecessity of Positron Emission Tomography Computed Tomography in the Etiologic Evaluation of Neurodevelopmental Delay in Craniosynostosis Patients.

BACKGROUND: In evaluation of craniosynostosis patients in terms of neurodevelopmental delay, positron emission tomography computed tomography (PET-CT) scan can be used to assess brain abnormalities through glucose metabolism. We aimed to determine the unnecessity of PET-CT in this study. METHODS: Thirty-eight patients diagnosed with craniosynostosis who underwent distraction osteogenesis from October, 2010 to November, 2013 were reviewed. Magnetic resonance imaging (MRI) and PET-CT scan were carried out for evaluation of the brain structure and function, whereas X-ray and CT scan were taken for evaluation of the skull. RESULTS: Nine patients reported abnormal MRI findings which were not significant, and five patients showed local problem on brain on PET-CT scan. No correlation was found among them. CONCLUSION: PET-CT evaluation of possible abnormal brain findings do not affect surgical planning or require additional therapy. Preoperative PET-CT scan is not the essential study to get any etiologic information of the disease consequences or to establish the treatment plan.

Adipose Tissue Formation Utilizing Fat Flap Distraction Technique.

Co-regulation between adipocytes and supporting vasculature is considered an important process in adipose tissue generation. The objective of this study was to evaluate the mechanical and biological effects of a distraction technique on adipose tissue formation and maintenance. Based on the hypothesis that fat flaps gradually receding from each other can develop an adipose tissue construct, perforated polycarbonate syringe-shaped chambers were implanted in a rabbit model. Latency (1 week) and distraction (3 weeks) periods were followed by a consolidation period in the experimental groups (4, 8, and 12 weeks). In the distraction group, the volume of fat pad gradually increased up to 16 weeks. A transition zone was observed at 8 weeks, indicating the initiation of tissue generation. Histomorphologic analysis showed adipose and collagen connective tissue at 8 weeks. At 16 weeks, the relative composition was altered significantly. Adipose components occupied most of the tissue, and connective tissue was reduced. Blood vessels with endothelial lining were noted adjacent to adipocyte clusters, as well as in inter-adipocyte areas. The vessels had increased in number and were evenly distributed by 16 weeks. Our distraction technique produced more balanced adipose tissue generation than a non-distraction method, with co-development of adipose and vascular tissues.

Virtual Reality and Augmented Reality in Plastic Surgery: A Review.

Recently, virtual reality (VR) and augmented reality (AR) have received increasing attention, with the development of VR/AR devices such as head-mounted displays, haptic devices, and AR glasses. Medicine is considered to be one of the most effective applications of VR/AR. In this article, we describe a systematic literature review conducted to investigate the state-of-the-art VR/AR technology relevant to plastic surgery. The 35 studies that were ultimately selected were categorized into 3 representative topics: VR/AR-based preoperative planning, navigation, and training. In addition, future trends of VR/AR technology associated with plastic surgery and related fields are discussed.

Altered cerebrospinal fluid dynamics in neurofibromatosis type l: severe arachnoid thickening in patients with neurofibromatosis type 1 may cause abnormal CSF dynamic.

INTRODUCTION: The object of this study is to understand abnormal dynamic of cerebrospinal fluid (CSF) in patients with neurofibromatosis type 1 (NF1), which may cause temporal lobe herniation and bulging of temporal fossa. METHODS: Four patients, three females and one male, with NF1 were studied retrospectively. They presented with a similar craniofacial deformity, which consisted of pulsatile exophthalmos, an enlarged bony orbit, dysplasia of the sphenoid wing with the presence of a herniation of the temporal lobe into the orbit, and a bulging temporal fossa. RESULTS AND DISCUSSION: Surgical exploration demonstrated abnormally thickened arachnoid membrane in one case. Protruding temporal lobe, which was one of the main symptoms in NF1 patients, could be stopped by control of intracranial pressure (ICP) via programmable ventriculoperitoneal shunt (VPS) or extra ventricle drainage implantation. The dense fibrosis of the arachnoid membrane and consequent altered hemispheric CSF dynamics may cause symptoms including pulsatile exophthalmos and consequent worsening of vision, prolapse of the temporal lobe, and enlargement of the temporal fossa. This finding may not present with general features of hydrocephalus, so that delays in diagnosis often result. CONCLUSION: For the NF1 patients with cranio-orbito-temporal deformities, prior to any surgical reconstruction, control of increased ICP (IICP) should be primarily considered.