Patient Blood Management in Craniosynostosis Surgery

Background: Craniosynostosis surgery is one of the most hemorrhagic interventions, where transfusion rates vary from 20% to 100% depending on the study. Objective: To describe intraoperative and postoperative outcomes in a secondary analysis of children who underwent craniosynostosis surgery included in the initial retrospective study with the aim of proposing intraoperative implementation optimization protocols for postoperative outcome improvement. Methods: Secondary analysis. The study was approved by the Ethics Committee. Results: There were 69 children with a median age of 10 [0 - 207] months. Eight (11.6%) patients had intraoperative and/or postoperative complications. One patient (1.5%) had intraoperative hemorrhagic shock, and two patients (2.9%) had intraoperative broncholaryngospasm. One patient (1.5%) had postoperative anaphylaxis. One patient (1.5%) had postoperative hemorrhagic shock. One patient (1.5%) had postoperative respiratory failure. Two patients (2.9%) had postoperative neurologic failure. One patient (1.5%) had neuro-meningeal sepsis. One patient (1.5%) had a re-operation. There was no in-hospital mortality. Fourty-eight patients (69.6%) had intraoperative transfusions. Conclusion: Transfusion protocols guided with point-of-care tests should be included in patient blood management programs in craniosynostosis surgery.

Bilateral squamosal suture synostosis: A rare form of isolated craniosynostosis in Crouzon syndrome

Craniosynostosis is a pathologic condition which is characterized by the premature fusion of cranial sutures.It may occur alone or in association with other anomalies making up various syndromes.Crouzon syndrome is the most common craniosynostosis syndrome.Bicoronal sutures fusion is most commonly involved in Crouzon syndrome.There have only been a handful of cases of squamosal suture synostosis described in the surgery literature with the few ones described in Crouzon syndrome associated with other types of craniosynostosis.To the best of our knowledge,we are presenting the first case of isolated bilateral squamosal suture synostosis in a patient with Crouzon syndrome in a radiology journal with emphasis on its radiological appearance.

Early Rehabilitation After Craniosynostosis Surgery

Craniosynostosis is a common congenital craniofacial deformity caused by premature ossification and closure of one or more cranial sutures.Craniosynostosis will not only affect the normal development of the skull,but also may cause a variety of complications,damage the nervous system,and cause long-term effects on the development of physical and mental health.Therefore,it is particularly important to provide new ideas for clinical treatment by studying the rehabilitation methods of craniosynostosis,and to improve the cure rate.To this end,this paper studies the early rehabilitation methods after craniosynostosis surgery and designs a comprehensive early rehabilitation process and corresponding comprehensive early rehabilitation measures after surgery.The comparative data also shows that after comprehensive early rehabilitation nursing measures,the duration of the postoperative swelling of sick children was reduced and the degree was significantly reduced,which alleviated the discomfort of sick children;and the time of sick children spent in ICU treatment and monitoring was reduced,and the separation time between sick children and their parents was shorten,is of great significance to the postoperative rehabilitation of craniosynostosis.In addition,the total cost of hospitalization was reduced accordingly,which greatly increased the satisfaction of patients.

Syndromic craniosynostosis associated with microdeletion of chromosome 19p13.12-19p13.2

Craniosynostosis,a condition in which the cranial sutures prematurely fuse,can lead to elevated intracranial pressure and craniofacial abnormalities in young children.Currently surgical intervention is the only therapeutic option for patients with this condition.Craniosynostosis has been associated with a variety of different gene mutations and chromosome anomalies.Here we describe three cases of partial deletion of chromosome 19p.Two of the cases present with syndromic craniosynostosis while one has metopic ridging.A review of the genes involved in the rearrangements between the three cases suggests several gene candidates for craniosynostosis.CALR and DAND5,BMP regulators involved in osteoblast differentiation,and MORG1,a mediator of osteoclast dysregulation may play a role in abnormal cranial vault development.Additionally,CACNA1A,a gene that when mutated is associated with epilepsy and CC2D1A,a gene associated with non-syndromic mental retardation may contribute to additional phenotypic features seen in the patients we describe.In addition,these findings further support the need for genetic testing in cases of syndromic craniosynostosis.

Maternal hyperthyroidism increases the synthesis activity and the osteogenic markers expression of calvarial osteoblasts from offspring in a murine model

To evaluate the characteristics and synthesis activity of osteoblasts extracted from the calvaria of offspring of rats exposed to maternal hyperthyroidism.Twelve adult Wistar rats were divided into two groups,one control and one treated with daily administration of L-thyroxine by an orogastric tube(50μg/animal/day)during pregnancy.Three days after delivery and confirmation of the mothers’hyperthyroidism,the offspring were euthanized for the extraction of osteoblasts from the calvaria.At 7,14,and 21 days,proliferation activity was assessed using MTT assay,while alkaline phosphatase(ALP)activity was assessed by the BCIP/NBT method.At 21 days,the total area of the mineralized matrix stained by von Kossa was evaluated by morphometry.The expression of gene transcripts for Runx2,Bmp2,Fgfr1,collagen type 1(Col1),osteocalcin(Oc),and osteopontin(Op)were evaluated by real-time RT-PCR.Means were compared using the Student’s t-test.FA activity was significantly higher at 14 and 21 days in cultures of osteoblasts extracted from offspring exposed to maternal hyperthyroidism,while MTT conversion was significantly lower at 21 days in this group.Osteoblast cultures of neonates exposed to maternal hyperthyroidism also showed a larger total area of mineralized matrix and greater expression of gene transcripts for Oc and Op.Maternal hyperthyroidism increases the activity of matrix synthesis,alkaline phosphatase activity,and expression of gene transcripts for osteocalcin and osteopontin in the osteoblasts,extracted from the calvaria of the offspring,which may be one of the mechanisms of premature fusion of cranial sutures.

Crouzon syndrome in a fraternal twin:A case report and review of the literature

BACKGROUND Crouzon syndrome(CS;OMIM 123500)is an autosomal dominant inherited craniofacial disorder caused by mutations in the fibroblast growth factor receptor 2(FGFR2)gene.CS is characterized by craniofacial dysostosis,exophthalmos,and facial anomalies with hypoplastic maxilla and relative mandibular prognathism.CASE SUMMARY Our report involves a 6-year-old fraternal twin boy with many caries in the oral cavity who presented with characteristic features of CS based on clinical and radiographic examinations along with Sanger sequencing.The fraternal girl did not show any abnormalities indicating CS.Carious teeth and poor oral hygiene were managed promptly through administering appropriate behavior guidance,orthodontic treatment was planned,and preventive procedures were described.CONCLUSION CS could occur in a fraternal twin caused by a de novo mutation of the FGFR2 gene.Oral hygiene instruction,preventive programs on oral hygiene,orthodontic treatment,and maxillary osteotomy were required for treatment.

Three dimensional finite element biomechanical analysis of unilateral coronal synostosis and reconstructive operation

Objective To establish finite element models of skull, fronto-orbital advancement and fronto-orbital distraction osteogenesis of craniosynostosis, to analyze the mechanical characteristics of skull base and fronto-orbital operation area, so as to guide the later app lication of distractors. Methods One 6-year-old male patient with unilateral coronal synostosis was enrolled in October 2015. Three-dimensional (3D) computed tomography (CT) scan of skull was performed. DICOM data was imported into Mimics 17.0 for contour extraction and cranial 3D reconstruction. The skull model was processed by Mimics, Geomagic Studio 12.0, Hypermesh 12.0 and other software to establish a three-dimensional finite element model. The unilateral and bilateral fronto-orbital anterior osteotomy models were simulated respectively. The mechanical analysis was performed at point A in forehead area and point B in temporal area. Three different groups of traction forces were loaded:(1) 50 Newton for point A, 50 Newton for point B;(2) 80 Newton for point A and 50 Newton for point B;(3) 100 Newton for point A and 50 Newton for point B, to obtain the optimized traction force.. Results Stress analysis was performed on established cranial finite element model, as well as unilateral and bilateral fronto-orbital advancement procedures. The stress distribution of the anterior and middle cranial fossae was found to be concentrated. After unilateral fronto-orbital advancement, the stress of anterior cranial fossa, especially the affected side, was decreased. The stress on both side in anterior cranial fossa was decreased after bilateral fronto-orbital advancement. After force was applied to point A and point B, the optimum deviation result at supraorbital notch point, midpoint of supraorbital margin, frontal temporal point and frontal zygomatic suture point in 3D (Deviation result of X value:-29.4%,-20.5%,-8.6%,-9.3%, Deviation result of Y value: 20.9%, 31.5%, 73.0%, 539.4%;Deviation result of Z value: 4.4%, 1.9%, 0.1%, 11.8) demonstrated the application of traction force can inwardly, downwardly and forwardly move the bone flap. The optimized traction was 80N at point A and 50N at point B by preliminary assessment. Conclusion The finite element analysis of the fronto-orbital advancement can be used for more accurate preoperative simulation, to clarify the influence of fronto-orbital advancement on craniofacial morphology and development, as well as skull base. It also facilitates surgical decision and predicts the postoperative distraction vectors.

Fibroblast growth factor(FGF)signaling in development and skeletal diseases

Fibroblast growth factors(FGF)and their receptors serve many functions in both the developing and adult organism.Humans contain 18 FGF ligands and four FGF receptors(FGFR).FGF ligands are polypeptide growth factors that regulate several developmental processes including cellular proliferation,differentiation,and migration,morphogenesis,and patterning.FGF-FGFR signaling is also critical to the developing axial and craniofacial skeleton.In particular,the signaling cascade has been implicated in intramembranous ossification of cranial bones as well as cranial suture homeostasis.In the adult,FGFs and FGFRs are crucial for tissue repair.FGF signaling generally follows one of three transduction pathways:RAS/MAP kinase,PI3/AKT,or PLCg.Each pathway likely regulates specific cellular behaviors.Inappropriate expression of FGF and improper activation of FGFRs are associated with various pathologic conditions,unregulated cell growth,and tumorigenesis.Additionally,aberrant signaling has been implicated in many skeletal abnormalities including achondroplasia and craniosynostosis.The biology and mechanisms of the FGF family have been the subject of significant research over the past 30 years.Recently,work has focused on the therapeutic targeting and potential of FGF ligands and their associated receptors.The majority of FGF-related therapy is aimed at age-related disorders.Increased understanding of FGF signaling and biology may reveal additional therapeutic roles,both in utero and postnatally.This review discusses the role of FGF signaling in general physiologic and pathologic embryogenesis and further explores it within the context of skeletal development.

Notch signaling:Its essential roles in bone and craniofacial development

Notch is a cellecell signaling pathway that is involved in a host of activities including development,oncogenesis,skeletal homeostasis,and much more.More specifically,recent research has demonstrated the importance of Notch signaling in osteogenic differentiation,bone healing,and in the development of the skeleton.The craniofacial skeleton is complex and understanding its development has remained an important focus in biology.In this review we briefly summarize what recent research has revealed about Notch signaling and the current understanding of how the skeleton,skull,and face develop.We then discuss the crucial role that Notch plays in both craniofacial development and the skeletal system,and what importance it may play in the future.

Signaling pathways in osteogenesis and osteoclastogenesis:Lessons from cranial sutures and applications to regenerative medicine

One of the simplest models for examining the interplay between bone formation and resorption is the junction between the cranial bones.Although only roughly a quarter of patients diagnosed with craniosynostosis have been linked to known genetic disturbances,the molecular mechanisms elucidated from these studies have provided basic knowledge of bone homeostasis.This work has translated to methods and advances in bone tissue engineering.In this review,we examine the current knowledge of cranial suture biology derived from human craniosynostosis syndromes and discuss its application to regenerative medicine.

Molecular basis of cranial suture biology and disease:Osteoblastic and osteoclastic perspectives

The normal growth and development of the skull is a tightly regulated process that occurs along the osteogenic interfaces of the cranial sutures.Here,the borders of the calvarial bones and neighboring tissues above and below,function as a complex.Through coordinated remodeling efforts of bone deposition and resorption,the cranial sutures maintain a state of patency from infancy through early adulthood as the skull continues to grow and accommodate the developing brain’s demands for expansion.However,when this delicate balance is disturbed,a number of pathologic conditions ensue;and if left uncorrected,may result in visual and neurocognitive impairments.A prime example includes craniosynostosis,or premature fusion of one or more cranial and/or facial suture(s).At the present time,the only therapeutic measure for craniosynostosis is surgical correction by cranial vault reconstruction.However,elegant studies performed over the past decade have identified several genes critical for the maintenance of suture patency and induction of suture fusion.Such deeper understandings of the pathogenesis and molecular mechanisms that regulate suture biology may provide necessary insights toward the development of non-surgical therapeutic alternatives for patients with cranial suture defects.In this review,we discuss the intricate cellular and molecular interplay that exists within the suture among its three major components:dura mater,osteoblastic related molecular pathways and osteoclastic related molecular pathways.

Apert’s syndrome:Study by whole exome sequencing

In the present study we attempted a parente-child trio,whole exome sequencing(WES)approach to study Apert’s syndrome.Clinical characteristics of the child were noted down and WES was carried out using Ion Torrent System that revealed the presence of previously reported P253R mutation in FGFR2 gene.Presence of two SNPs rs1047057 and rs554851880 in FGFR2 gene with an allelic frequency of 0.5113 and 0.001176 respectively and 161 complete damaging mutations were found.This study is the first reported case of exome sequencing approach on an Apert’s syndrome patient aimed at providing better genetic counselling in a non-consanguineous relationship.