Assessment of Ecotropic Viral Integration Site 2B (EVI2B) Gene in Juvenile Myelomonocytic Leukemia and Neurofibromatosis Type 1 NF1 Tumors.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disease that affects the development and growth of various tissues. NF1 is a major risk factor for the development of malignancies, particularly malignant peripheral nerve sheath tumors, optic gliomas, and leukemia. NF1 encodes a neurofibromin. Three genes, EVI2A, EVI2B, and OMGP, are embedded within intron 27b of NF1. However, the function of these genes remains unclear. EVI2A and EVI2B encode for putative transmembrane proteins. Mouse homologs are associated with viral insertions involved in leukemia in mice. Mouse Evi2b has been identified as a direct target gene of C/EBPα, a transcription factor critical for myeloid differentiation. Also possible is that these genes are related to the leukemia observed in patients with NF1. These genes might act as modifiers of NF1 phenotypic variations. Therefore, we investigated the EVI2B gene in leukemia and NF1 tumors. We analyzed DNA from 10, 20, and 3 patients with NF1, leukemia, and NF1-leukemia, respectively, and six NF1 tumor tissues. DNA sequencing analysis was used to identify the viral integration sequence, and the protein amounts and EVI2B gene expression were analyzed by flow cytometry and quantitative real-time PCR techniques. The EVI2B gene expression was increased in cutaneous neurofibroma compared with the control both at the level of protein and mRNA. However, its expression in plexiform neurofibroma was decreased significantly at protein level and increased at mRNA level compare to control. Moreover, integration of 455 bases near the 3' end of the exon was detected. When this integrated sequence was blasted into the NCBI retroviral genome database, an 87% match with the HIV-1 virus envelope gene was obtained. These preliminary results show that EVI2B might be important in NF1 tumorigenesis and leukemia.

Endovascular Treatment of Peripheral Arteriovenous Malformations (AVMs): Do Angiographic Outcomes Relate to the Quality of Life?

PURPOSE: Patients with arteriovenous malformations (AVMs) have a lower health-related quality of life (QoL) than the general population. QoL assessment of patients with peripheral AVMs after endovascular treatment is scarce in the literature. Radiologic and clinical outcomes are not always correlated in vascular malformation treatment. This study aimed to investigate the relationship between clinical outcomes, QoL, and angiographic outcomes. MATERIALS AND METHODS: Patients with peripheral AVM that underwent endovascular treatment between January 2009 and December 2021 in a single center were retrospectively evaluated. Patients' characteristics (age, sex), AVM characteristics (Schobinger classification, location, angiographic architecture), previous treatment, treatment characteristics (type of endovascular approach, embolizing agent and number of sessions), percentages of angiographic response, complications, and recurrence were evaluated. The angiographic architecture was evaluated according to the Yakes classification. The questionnaire was applied for evaluation of clinical response and QoL. Patients older than 12 years and those who can be contacted were included in clinical and QoL analysis. Clinical response was defined as improvement in the patient's most important pretreatment symptom. Treatment response was defined as clinical response plus >50% angiographic response. RESULTS: Eighty-six patients (41 males [47.7%], 45 females [52.3%]) were included in angiographic analysis. The mean age was 28.44±12.99 years (range=5-61). Forty-three patients (50%) had previous treatment. The median number of sessions was 2 (range 1-15, InterQuartile Range [IOR]=2). Sixty-one patients (30 males [49.2%], 31 females [50.8%]) were included in clinical analysis. The clinical response rate was 73.8%, 95% confidence interval (CI) [0.60, 0.84]. The treatment response rate was 45.9%, 95% CI [0.33, 0.59]. The complication rate was 8.2%. Before treatment, 48 patients (78.7%) reported a negative impact on their QoL. Thirty-three of 48 patients (68.8%) reported improvement on their QoL after treatment. Higher Schobinger stages were related to a negative impact on QoL before treatment (p<0.01). Yakes types were not related to QoL (p=0.065). Clinical response was related to improvement on QoL after treatment (p<0.01). Angiographic and treatment responses were not related to improved QoL after treatment (p=0.52 and p=0.055, respectively). CONCLUSION: Angiographic architecture and outcomes were not always reflected in QoL after endovascular treatment. CLINICAL IMPACT: This study's findings will help clinicians with what to focus on in AVM treatment and how to monitor patients with peripheral AVM after endovascular treatment. Rather than relying too much on the angiographic response, patients should be checked for symptoms and quality of life improvement. No clear data in the literature regarding the applicability of the Yakes Classification in patients with previous treatment. This study questioned the applicability of the Yakes Classification in patients with previous treatments. In this study, type 4 AVMs were more common in patients with previous treatment.

Autologous Adipose-Derived Tissue Stromal Vascular Fraction (AD-tSVF) for Knee Osteoarthritis.

Adipose tissue contains adult mesenchymal stem cells that may modulate the metabolism when applied to other tissues. Stromal vascular fraction (SVF) can be isolated from adipose tissue mechanically and/or enzymatically. SVF was recently used to decrease the pain and improve the function of knee osteoarthritis (OA) patients. Primary and/or secondary OA causes inflammation and degeneration in joints, and regenerative approaches that may modify the natural course of the disease are limited. SVF may modulate inflammation and initiate regeneration in joint tissues by initiating a paracrine effect. Chemokines released from SVF may slow down degeneration and stimulate regeneration in joints. In this review, we overviewed articular joint cartilage structures and functions, OA, and macro-, micro-, and nano-fat isolation techniques. Mechanic and enzymatic SVF processing techniques were summarized. Clinical outcomes of adipose tissue derived tissue SVF (AD-tSVF) were evaluated. Medical devices that can mechanically isolate AD-tSVF were listed, and publications referring to such devices were summarized. Recent review manuscripts were also systematically evaluated and included. Transferring adipose tissues and cells has its roots in plastic, reconstructive, and aesthetic surgery. Micro- and nano-fat is also transferred to other organs and tissues to stimulate regeneration as it contains regenerative cells. Minimal manipulation of the adipose tissue is recently preferred to isolate the regenerative cells without disrupting them from their natural environment. The number of patients in the follow-up studies are recently increasing. The duration of follow up is also increasing with favorable outcomes from the short- to mid-term. There are however variations for mean age and the severity of knee OA patients between studies. Positive outcomes are related to the higher number of cells in the AD-tSVF. Repetition of injections and concomitant treatments such as combining the AD-tSVF with platelet rich plasma or hyaluronan are not solidified. Good results were obtained when combined with arthroscopic debridement and micro- or nano-fracture techniques for small-sized cartilage defects. The optimum pressure applied to the tissues and cells during filtration and purification of the AD-tSVF is not specified yet. Quantitative monitoring of articular joint cartilage regeneration by ultrasound, MR, and synovial fluid analysis as well as with second-look arthroscopy could improve our current knowledge on AD-tSVF treatment in knee OA. AD-tSVF isolation techniques and technologies have the potential to improve knee OA treatment. The duration of centrifugation, filtration, washing, and purification should however be standardized. Using gravity-only for isolation and filtration could be a reasonable approach to avoid possible complications of other methodologies.

ALX-Related Frontonasal Dysplasias: Clinical Characteristics and Surgical Management.

AIM: The term frontonasal dysplasia (FND) represents a spectrum of anomalies and its genetics have not been well defined. Recently, the critical role of the aristaless-like homeobox (ALX) gene family on the craniofacial development has been discovered. In the present study, we aimed to propose a systematic surgical treatment plan for the ALX-related FNDs according to the genotypic classification as well as demonstrating their clinical characteristics to help surgeons diagnose the underlying pathology accurately. DESIGN: Single-institution retrospective. SETTING: Tertiary health care. PATIENTS AND METHODS: Eighty-nine FND cases were evaluated. Eight of them had ALX1-related FND3, 3 had ALX3-related FND1, and 2 had ALX4-related FND2. Phenotype characteristics of ALX-related FNDs were evaluated, and relevant surgical interventions were assessed. RESULTS: The ALX1-related FND3 phenotype is striking due to the involvement of the eyes in addition to the presence of hypertelorism, facial clefts, and nasal deformities. A widened philtrum and prominent philtral columns are remarkable features of the ALX3-related FND1, whereas the ALX4-related FND2 has more severe deformities: severe hypertelorism, brachycephaly, large parietal bone defects, broad nasal dorsum, and alopecia. Facial bipartition, box osteotomies, eyelid coloboma repair, cleft lip and palate repair, nasal reconstruction, and fronto-orbital advancement can be performed in ALX-related FNDs based on the characteristics of each subtype. CONCLUSIONS: This genetic classification system will help surgeon diagnose patients with FND with unique features and draw a roadmap for their treatment with a better surgical perspective.

Airflow Considerations and the Effect of Webster's Triangle in Reduction Rhinoplasty.

BACKGROUND: Reduction rhinoplasties, regardless of the methods used (structural or preservation), can cause a reduction in the internal nasal volume, which may lead to breathing problems. In 1977, Webster proposed preserving a little triangle in the beginning of the lower lateral osteotomy line to prevent breathing problem. However, its importance is still controversial. OBJECTIVES: and methods: This prospective randomized controlled study (level of evidence 1) included 46 patients without nasal breathing problem. High-to-low (Webster's triangle preservation) osteotomy (control group, n = 23) and low-to-low osteotomy (study group, n = 23) were performed. All operations were performed according to the proposed volumetric rhinoplasty steps (examination/measurement, prevention and treatment). Nasal obstruction symptom evaluation (NOSE) test, visual analog scale, acoustic rhinometry, rhinomanometry, peak nasal inspiratory flow (PNIF), and three-dimensional measurements were performed in all patients. Breathing tests were repeated before and 6 months after surgery with and without xylometazoline administration. RESULTS: No statistically significant difference in NOSE and visual analog scale scores was found between the two groups. Acoustic rhinometry, PNIF, and rhinomanometry findings showed no statistically significant breathing difference between the two groups. CONCLUSIONS: In reduction rhinoplasties, a decrease in the internal volume may be expected as directly proportional with the reduction amount. The decrease in the internal volume may create nasal breathing problems. To prevent it, nasal airflow should be adjusted according to new anatomy. In this study, we discussed "volumetric rhinoplasty" steps to prevent breathing problems in reduction rhinoplasty. Following these steps, not preserving Webster's triangle (low-to-low osteotomy) has no effect on the nasal airway. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Defining a Preauricular Safe Zone: A Cadaveric Study of the Frontotemporal Branch of the Facial Nerve.

BACKGROUND: In the preauricular region, the frontotemporal branch of the facial nerve is vulnerable to injury, which can result in facial palsy and poor cosmesis after surgical interventions. OBJECTIVES: The purpose of this study was to describe variations in the branching patterns of the frontotemporal branch of the facial nerve and the relation between this branch and the surrounding anatomic landmarks. Based on our findings, we propose a Danger Zone and Safe Zones for preauricular interventions to avoid frontal branch injury. METHODS: Twenty cadaveric half-heads, 10 freshly frozen and 10 embalmed, were dissected. The anatomy of the auriculotemporal nerve, facial nerve, and variations of its branching pattern in the preauricular region were investigated. RESULTS: The mean [standard deviation] number of frontotemporal branches crossing the zygomatic arch was 2.05 [0.6]. Beginning from the X point at the apex of the intertragal notch, frontal branches ran over the zygomatic arch at a distance extending from 10 to 31 mm anterior to the tragus, which can be defined as the Danger Zone for frontal branches. Safe Zones A and B are triangular regions located behind and in front of the Danger Zone, respectively. CONCLUSIONS: Mapping of these Safety and Danger Zones is a reliable and simple approach in preauricular interventions to avoid frontal branch injury because the facial nerve typically has multiple frontal branches. This approach provides practical information for surgeons rather than estimating the trajectory of a single frontal branch from Pitanuy's line.

Loss-of-Function Mutations in ELMO2 Cause Intraosseous Vascular Malformation by Impeding RAC1 Signaling.

Vascular malformations are non-neoplastic expansions of blood vessels that arise due to errors during angiogenesis. They are a heterogeneous group of sporadic or inherited vascular disorders characterized by localized lesions of arteriovenous, capillary, or lymphatic origin. Vascular malformations that occur inside bone tissue are rare. Herein, we report loss-of-function mutations in ELMO2 (which translates extracellular signals into cellular movements) that are causative for autosomal-recessive intraosseous vascular malformation (VMOS) in five different families. Individuals with VMOS suffer from life-threatening progressive expansion of the jaw, craniofacial, and other intramembranous bones caused by malformed blood vessels that lack a mature vascular smooth muscle layer. Analysis of primary fibroblasts from an affected individual showed that absence of ELMO2 correlated with a significant downregulation of binding partner DOCK1, resulting in deficient RAC1-dependent cell migration. Unexpectedly, elmo2-knockout zebrafish appeared phenotypically normal, suggesting that there might be human-specific ELMO2 requirements in bone vasculature homeostasis or genetic compensation by related genes. Comparative phylogenetic analysis indicated that elmo2 originated upon the appearance of intramembranous bones and the jaw in ancestral vertebrates, implying that elmo2 might have been involved in the evolution of these novel traits. The present findings highlight the necessity of ELMO2 for maintaining vascular integrity, specifically in intramembranous bones.

Clinical and Molecular Study of ELMO-2-Related Massive Intraosseous Vascular Malformations: Lessons Learned From 25 Years of Follow-up.

Massive intraosseous vascular malformations, a relatively rare entity in the vascular malformation spectrum, deserves attention as involving the membranous bones of the craniofacial skeleton and may lead to severe life-threatening hemorrhages and even death. The main aim of this study was to summarize the 25 years of clinical experience with these vascular malformation osseous patients, focus on the molecular and genetic aspect of the clinical entity, and to emphasize the certain challenging conditions in the treatment of these patients. All the patients appeared to be unaffected at birth, whereas initial symptoms occasionally began with painless swelling in the mandible in early childhood. The disease was progressive in behavior especially in the pubertal ages and was specifically involving the maxilla and mandible of the craniofacial skeleton in all the patients. Calvarium and cranial base were the second most common involved regions among these patients (62.5%). Clavicular (50%), costal (25%), and vertebral (25%) involvements were also a significant manifestation of the disease. Tissue samples obtained from the affected individuals and the blood samples from their families were matched, revealing a loss of function mutation in the ELMO-2 gene of chromosome 20 leading to developmental abnormality of the vascular structures via RAC1 signaling and leading to abnormally enlarged vessels in the intraosseus portion of the membranous bone. Immunohistochemical staining revealed positive CD31 and smooth muscle actin staining but negative proliferation and maturity markers such as Ki-67, desmin, h-caldesmon, and myofibroblast-like desmin. The follow-up of 3 of 5 patients ended up with mortality (60%). vascular malformation osseous is intraosseous vascular malformation with aggressive biological behavior associated with ELMO-2 gene mutation. Further studies for obtaining prenatal diagnosis and achievement of gene therapy should take place. As the disease rapidly progresses as the affected individual grows, surgical interventions should be taken into consideration before the initiation of complications.

Heightened CXCR4 and CXCL12 expression in NF1-associated neurofibromas.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a common autosomal dominantly inherited disorder that affects both the skin and the nervous system. NF1 occurs due to the mutations in the NF1 gene. Neurofibromas are the most common Schwann cell-based tumors in NF1 patients, which are mainly categorized into dermal and plexiform neurofibromas. Studies on different tumor types demonstrate that CXCR4 expression increases in tumor tissues and is linked to metastasis and cancer progression. PURPOSE: In the present study, we aimed to analyze the gene expression of CXCR4, and its ligand CXCL12, in human neurofibromas. METHODS: Eight NF1 patients aged between 5 and 37 (2 males, 6 females) were selected. The patient group comprised 1 plexiform neurofibroma, 1 pheochromocytoma, and 6 dermal neurofibromas. Following pathological examination and diagnosis, tumors were co-stained with antibodies against Schwann cell marker S100 and target molecule CXCR4. CXCR4 expression in Schwann cell-based tumors was detected at the protein level. RNA isolated from the same tumors was used for RT-PCR-based studies to measure the quantitative expression of CXCR4 and CXCL12. RESULTS: CXCR4 gene expression increased 3- to 120-fold and CXCL12 gene expression increased 33- to 512-fold in all human Schwann cell-based tumors. CONCLUSION: In order to validate the role of CXCR4 and its relationship with CXCL12 in NF1, future studies should be performed with additional tumors and different tumor types.

Humanitarian Activities of Interplast Turkiye: 6 Years of Experience in Uzbekistan for Surgical Treatment of Cleft Patients and Related Secondary Deformities.

Cleft lip and palate (CL/P) is one of the leading congenital deformities among the world. Children born with CL/P experience problems with feeding, speech, hearing, and dentition. In developed countries, CL/P patients are receiving optimal health care involving multidisciplinary team approach and staged surgical operations, whereas in developing countries, there is severe shortage of both medical and financial sources. To overcome these limitations, humanitarian surgical missions are essential. The aim of this article is to share our experience of humanitarian surgical mission in Uzbekistan consisting of 6 consecutive visits between 2009 and 2014. The series of these humanitarian activities consisting of 6 consecutive visits was organized by the cooperation of Interplast Turkiye and governmental Turkish Coordination and Cooperation Agency. After initial evaluation, triage at the initial setting and prompt anesthesia evaluation among many more of them, 529 patients mostly with cleft, craniofacial, or congenital deformities were operated. The success of this type of mission is not solely based on the expertise of the team members, but also meticulous planning, patient selection, good coordination with the local colleagues and communication. At this point, caregivers attending from a culturally close and similar language-spoken countries will certainly have more advantages in achieving a mission. Volunteer surgical missions for congenital deformities can be an important relief for this burden in developing countries. Nevertheless, training the native surgeons and supporting the plastic surgery foundations in these countries are as important as providing the necessary health care by such humanitarian missions.

Correction of Brachymetatarsia and Medial Angulation of the Great Toe of Apert Foot By Distraction Osteogenesis: A Review of 7 Years of Experience.

BACKGROUND: Apert foot anomalies may cause severe problems such as pain and development of callus formation related to weight redistribution, problems with footwear, and gait disturbances that may limit their daily activities. The main purpose of this study was to review our experience with distraction osteogenesis for the correction of brachymetatarsia and the great toe angulation of the patients with Apert syndrome. METHODS: This study retrospectively reviewed 7 patients (14 extremities) followed up for Apert syndrome who underwent distraction for the correction of bilateral congenital brachymetatarsia and angulation of the great toe between 2004 and 2008. Correction of the metatarsal inclination angle, the medial angulation of the great toe, the percentage of lengthening, and lengthening rates of distracted bones were evaluated. RESULTS: Patients ranged in age from 4 to 8 years at the distraction operation, with a mean age of 5.4±1.3 years, and the average length of follow-up was 86.6±21.0 months. The length of the first metatarsal bone increased significantly from the average length of 32.6±5.7 mm to an average of 46.7±6.5 mm (P<0.001). The mean lengthening rate and lengthening percentages of distracted bones were 0.4%±0.1%/month and 30.2%±6.4%/month, respectively. Preoperative and postoperative metatarsal inclination angles were at a mean of 43.8±5.12 and 32.6±3.8, respectively, and the correction of metatarsal inclination was considered as statistically significant (P<0.001). The mean angulation of the great toe reduced significantly from 49.8±11.76 to 13.2±8.5 degrees after distraction (P<0.001). Minor complications such as pin loosening, pin-tract infection, and early union that required reoperation were observed in 5 extremities (35.7%). CONCLUSIONS: Anatomic features of Apert foot may lead to complaints that may limit patients' daily activities and require as much attention as associated hand and craniofacial anomalies. Distraction appears to be an effective and safe approach for the simultaneous correction of the shortness of the first ray and medial angulation of the great toe. LEVEL OF EVIDENCE: Level IV.

Poly(L-Lactide)/Poly(ε-Caprolactone) and Collagen/ß-Tricalcium Phosphate Scaffolds for the Treatment of Critical-Sized Rat Alveolar Defects: A Microtomographic, Molecular-Biological, and Histological Study.

OBJECTIVE: To determine the efficacy of a newly developed scaffold (col/ß-TCP) in a preclinical rat model as compared with the gold standard treatment (autograft) and control scaffolds (PLLA/PCL). DESIGN: Fifty-six Sprague-Dawley rats were randomized into four experimental groups, and critical-sized alveolar defects (7 × 4 × 3 mm) were created in each animal. Group A was the blank defect group, group B received autograft, group C received col/ß-TCP scaffolds, and group D received PLLA/PCL blend scaffolds to fill the bone defects. New bone formation was assessed radiomorphometrically, histomorphometrically, and molecular-biologically at 1 and 4 months following surgery. RESULTS: Radiomorphometrically, the best new bone volume rate at 1 month (43.7%) and 4 months (45.4%) was observed in the autograft group, and the difference was significantly higher than in the other three groups (P < .005, P < .001, P < .001 for 1 month and P = .004, P < .001, P < .001 for 4 months). Even though the new bone volume rate in the col/ß-TCP group (21.5%) was higher than that of the PLLA/PCL group (18.2%), the difference was not significant (P = .08). Molecular-genetic analysis revealed significantly higher BSP and ALP gene expression levels in the autograft and col/ß-TCP groups than in the blank defect group (P = .002 and P = .004). CONCLUSION: The engineered tissue scaffolds described herein have great potential as an alternative treatment option when cost, donor region morbidity, and duration of hospitalization are considered.

Application of C-Shaped Osteotomy and Distraction Osteogenesis for Correction of Radial Angulation Deformities of the Hand in Children With Apert Syndrome: Review of 10 Years of Experience.

Apert syndrome is characterized by short, radially deviated thumbs, leading to difficulties in daily life such as holding a fork or a spoon and buttoning up. The main goal of surgery is to achieve thumb to index finger pinch to overcome these difficulties. Seven patients (14 extremities) followed up with Apert syndrome underwent distraction after a C-shaped osteotomy to simultaneously correct the brachydactyly and the angulation deformity of the bilateral thumbs. The patients ranged in age from 4 to 7 years at the distraction operation, with a mean (SD) of 4.7 (1.7) years, and the mean (SD) length of follow-up was 100.6 (14.95) months. The mean (SD) length of the phalanges at the beginning of distraction was 19.1 (3.26) mm, and the mean (SD) length of the distracted phalanx at long-term follow-up visit was 26.2 (5.63) mm. The mean (SD) correction of radial angulation was calculated as 42.6 (9.95) degrees, and the difference was considered as being statistically significant (P < 0.001). Minor complications such as pin loosening were observed in 6 extremities of 4 patients, and 2 patients were treated for pin tract infection. Index-to-thumb pinching was acquired by all the patients after distraction and correction of angulation. The hand features of Apert syndrome are as noteworthy as the craniofacial features and thus may lead to functional impairment and limitations in daily life. Distraction with a C-shaped osteotomy seems to be a promising method to correct both the shortness and the radial angulation of the thumb to achieve functional results.

Intraarterial polidocanol injection for the treatment of peripheral arteriovenous malformations.

PURPOSE: The purpose of this study was to investigate the efficacy and safety of intraarterial transcatheter administration of polidocanol as an alternative treatment for peripheral arteriovenous malformations (AVMs). METHODS: The study comprised 10 patients (six males and four females) with a mean age of 28.8 years (range 8-52 years). All patients had trunk or extremity AVMs. Following the administration of general anesthesia or intravenous (IV) sedation, the patients underwent staged intraarterial polidocanol sclerotherapy with or without additional embolizations for their AVMs. The administration of polidocanol was executed by intraarterial infusion through a microcatheter or by direct percutaneous entry into the nidus under ultrasound guidance. RESULTS: A total of 19 sessions were accomplished in 10 patients. Polidocanol was used alone in six of the 19 sessions. In 13 sessions, polidocanol was used in combination with another agent (including n-butyl cyanoacrylate (NBCA), lipiodol, and ethanol) and/or coils. In two sessions, polidocanol was administered percutaneously under ultrasound guidance directly into the nidus documented by arteriography. No major complications occurred. CONCLUSION: Intraarterial transcatheter administration of polidocanol alone or in combination with other agents is a safe and effective alternative treatment for peripheral AVMs.

A Case of Nasal Glial Heterotopia That Can Be Misdiagnosed as Storiform Patterned Sclerotic Fibroma/Collagenoma.

OBJECTIVE: Nasal glioma, also known as nasal glial heterotopia, is a rare tumor-like lesion that often affects newborns or infants with no hereditary predisposition. CASE REPORT: A 4-year-old child with a growth on the nasal dorsum since birth was diagnosed with nasal glial heterotopia/nasal glioma. The lesion showed a sclerotic fibroma/collagenoma-like storiform pattern with entrapped glial tissue that was S100 and GFAP positive. CONCLUSION: When a biopsy of the nasal dorsum demonstrates sclerotic microscopic findings with a storiform pattern, nasal glioma should be considered before making a diagnosis in the collagen-rich tissue spectrum (collagenoma or Gardner's fibroma), and an immunohistochemical panel should be requested to demonstrate the presence of an unrecognized light microscopically visible glial component.

Disruption of ALX1 causes extreme microphthalmia and severe facial clefting: expanding the spectrum of autosomal-recessive ALX-related frontonasal dysplasia.

We present an autosomal-recessive frontonasal dysplasia (FND) characterized by bilateral extreme microphthalmia, bilateral oblique facial cleft, complete cleft palate, hypertelorism, wide nasal bridge with hypoplasia of the ala nasi, and low-set, posteriorly rotated ears in two distinct families. Using Affymetrix 250K SNP array genotyping and homozygosity mapping, we mapped this clinical entity to chromosome 12q21. In one of the families, three siblings were affected, and CNV analysis of the critical region showed a homozygous 3.7 Mb deletion containing the ALX1 (CART1) gene, which encodes the aristaless-like homeobox 1 transcription factor. In the second family we identified a homozygous donor-splice-site mutation (c.531+1G > A) in the ALX1 gene, providing evidence that complete loss of function of ALX1 protein causes severe disruption of early craniofacial development. Unlike loss of its murine ortholog, loss of human ALX1 does not result in neural-tube defects; however, it does severely affect the orchestrated fusion between frontonasal, nasomedial, nasolateral, and maxillary processes during early-stage embryogenesis. This study further expands the spectrum of the recently recognized autosomal-recessive ALX-related FND phenotype in humans.

Anesthetic risks associated with Antley-Bixler syndrome.

Antley-Bixler syndrome is an autosomal recessive disorder characterized by multiple bone and cartilaginous abnormalities. The main features of this syndrome include brachycephaly, midface hypoplasia, dysplasia of ears and nose, radiohumeral synostosis, choanal stenosis, or atresia. Distinctive features are based on craniofacial deformity and humeroradial synostosis. In this report, we describe the anesthesia management of a 20-year-old Antley-Bixler syndrome patient who underwent maxillary advancement via Le Fort I osteotomy. During surgical management of craniofacial syndrome patients, particularly Antley-Bixler syndrome, the whole surgical team should be aware of possible deformities involving the airway, which may be underestimated or nondetected prior to surgery. These deformities including choanal atresia/stenosis may lead to failure of nasotracheal intubation and mask ventilation, therefore jeopardizing the surgical procedure and/or patient safety. Accurate preoperative preparation and being aware of the components of this syndrome is vital to eliminate respiratory complications and enable uneventful anesthetic and surgical management.

Meridian pedicle-based breast shaping in reduction mammaplasty: a technical modification.

BACKGROUND: We present a technical modification of vertical reduction mammaplasty which provides a reliable pedicle that can be used in large and highly ptotic breasts with confidence when compared to vertical mammaplasty techniques without sacrificing conical breast shape and projection, in contrast to Wise pattern reduction techniques. METHODS: Thirty-two patients under general anesthesia were operated on using this modification between 2008 and 2012. The surgical technique is as follows: after general anesthesia induction and local anesthetic infiltration, skin incisions are made according to preoperative drawings. The breast meridian is prepared by superior and inferior plication of the vertical pedicle, including two dermal and one central attachment to the chest wall. Lateral and medial tissue resections are performed, thus preparing medial and lateral pillars after skin undermining. The pillars are sutured to the meridian to reconstruct a projectile conical breast shape. Inverted-T scar (87.5%, n=28) and vertical scar (12.5%, n=4) were used for closure. RESULTS: All patients were satisfied with the outcome regarding breast projection, shape, and size at 12 (n=30) and 24 months (n=15) after surgery except for 12 cases that needed reoperations: 2 cases for bottoming out and lower pole deformity, 2 cases needed more reduction by liposuction or re-excision, and 8 scar revisions. CONCLUSION: Early and late results (up to 2 years) regarding breast shape and projection were found to be satisfactory while providing a reliable pedicle with less postoperative drainage. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Surgical method for critical sized cranial defects in rat cranium.

Cranial tissue models are a widely used model to show the bone repair and the regeneration ability of candidate biomaterials for tissue engineering purposes. Until now, efficacy studies of different biomaterials for calvarial defect bone regeneration have been reported, generally in small animal models. This paper offers a versatile, reliable, and reproducible surgical method for creating a critical-sized cranial defect in rats including critical steps and tried-and-tested tips. The method proposed here,•Shows a general procedure for in vivo cranial models.•Provide an insight to restore bone tissue repair that may be used in combination with several tissue engineering strategies•Is a crucial technique that may guide in vivo bone tissue engineering.