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1.
J Craniofac Surg ; 33(1): 270-275, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34967523

RESUMO

ABSTRACT: Midface advancement at the monobloc level can be the seminal life event for patients with craniofacial dysostosis. Monobloc reconstruction, when planned appropriately, can simultaneously and definitively address multiple functional and aesthetic deficiencies in these patients. The application of distraction has reduced the morbidity experienced with traditional monobloc surgery. The purpose of this study is to report on the outcomes, stability, and growth in younger patients after monobloc advancement in syndromic craniosynostosis patients. The authors report a consecutive series of thirty patients with craniofacial dysostosis treated through monobloc differential distraction osteogenesis. Detailed history, photographic, and long-term radiographic data are reviewed, including a subset of patients who were skeletally immature at the time of their treatment. Differential distraction allows control of midface pitch, roll, and yaw, optimizing functional and aesthetic outcomes. There were no infectious complications requiring reoperation. The average surgical age for all patients was 12.5 years. For the 7 patients age <7 years, average age was 6 years. For all patients, the mean horizontal movement was 12 mm at nasion and 10 mm at A-point. At mean follow-up (4.8 years entire group and 6.2 years age <7 years group) a positive horizontal advancement of 1.1 mm at nasion and 0.8 mm at A-point was observed. More pronounced positive horizontal changes were seen in the age <7 years group. Monobloc differential distraction osteogenesis affords safe and precise repositioning of the midface. The advancement is skeletally stable and young patients show moderate continued growth.


Assuntos
Disostose Craniofacial , Craniossinostoses , Osteogênese por Distração , Criança , Disostose Craniofacial/cirurgia , Estética Dentária , Face , Humanos
3.
Water Res ; 204: 117594, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34474249

RESUMO

Hydraulic modeling of a foul sewer system (FSS) enables a better understanding of the behavior of the system and its effective management. However, there is generally a lack of sufficient field measurement data for FSS model development due to the low number of in-situ sensors for data collection. To this end, this study proposes a new method to develop FSS models based on geotagged information and water consumption data from smart water meters that are readily available. Within the proposed method, each sewer manhole is firstly associated with a particular population whose size is estimated from geotagged data. Subsequently, a two-stage optimization framework is developed to identify daily time-series inflows for each manhole based on physical connections between manholes and population as well as sewer sensor observations. Finally, a new uncertainty analysis method is developed by mapping the probability distributions of water consumption captured by smart meters to the stochastic variations of wastewater discharges. Two real-world FSSs are used to demonstrate the effectiveness of the proposed method. Results show that the proposed method can significantly outperform the traditional FSS model development approach in accurately simulating the values and uncertainty ranges of FSS hydraulic variables (manhole water depths and sewer flows). The proposed method is promising due to the easy availability of geotagged information as well as water consumption data from smart water meters in near future.


Assuntos
Disostose Craniofacial , Água , Humanos , Probabilidade , Esgotos , Incerteza , Águas Residuárias
4.
Arch Oral Biol ; 131: 105253, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34500259

RESUMO

OBJECTIVE: This retrospective radiographic controlled study investigates the dental phenotype in patients with Crouzon syndrome to determine if differences are observed as suggested by the FGFR2C342Y/+ Crouzon mouse models, and whether these models could be of interest to study the role of this mutation in tooth development. DESIGN: We assessed dental phenotype using dedicated linear measurements in 22 children with Crouzon syndrome and compared tooth morphology in both primary and permanent dentitions to an age-matched control group. Descriptive statistics were performed with "Sex" and "Age" as covariates for the permanent tooth models and "Sex" only for the primary tooth models, to take into account potential confounding factors. RESULTS: We showed that permanent but not primary tooth dimensions were globally reduced in Crouzon syndrome, without microdontia. In permanent dentition, crown height, mesiodistal and faciolingual cervical diameters were reduced by 6.3%, 5.7% and 5.5% respectively (p < 0.05). CONCLUSION: Our results underline the implication of Fibroblast Growth Factor Receptor 2 (FGFR2) in dental development of humans and contribute to support FGFR2C342Y/+ Crouzon mouse models as partial replicas of this condition, including in the oral region.


Assuntos
Disostose Craniofacial , Animais , Disostose Craniofacial/diagnóstico por imagem , Disostose Craniofacial/genética , Modelos Animais de Doenças , Humanos , Camundongos , Mutação , Fenótipo , Estudos Retrospectivos
5.
J Neurosurg Pediatr ; 28(4): 425-431, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34388723

RESUMO

OBJECTIVE: Crouzon syndrome with acanthosis nigricans (CAN) is a rare and clinically complex subtype of Crouzon syndrome. At three craniofacial centers, this multicenter study was undertaken to assess clinical signs in relation to the required interventions and treatment course in patients with CAN. METHODS: A retrospective cohort study of CAN was performed to obtain information about the clinical treatment course of these patients. Three centers participated: Erasmus Medical Centre, Rotterdam, the Netherlands; John Radcliffe Hospital, Oxford, United Kingdom; and Hôpital Necker-Enfants Malades, Paris, France. RESULTS: Nineteen patients (5 males, 14 females) were included in the study. All children were operated on, with a mean of 2.2 surgeries per patient (range 1-6). Overall, the following procedures were performed: 23 vault expansions, 10 monobloc corrections, 6 midface surgeries, 11 foramen magnum decompressions, 29 CSF-diverting surgeries, 23 shunt-related interventions, and 6 endoscopic third ventriculostomies, 3 of which subsequently required a shunt. CONCLUSIONS: This study demonstrates that patients with the mutation c.1172C>A (p.Ala391Glu) in the FGFR3 gene have a severe disease trajectory, requiring multiple surgical procedures. The timing and order of interventions have changed among patients and centers. It was not possible to differentiate the effect of a more severe clinical presentation from the effect of treatment order on outcome.


Assuntos
Acantose Nigricans/cirurgia , Disostose Craniofacial/cirurgia , Acantose Nigricans/complicações , Acantose Nigricans/genética , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Protocolos Clínicos , Estudos de Coortes , Anormalidades Craniofaciais/cirurgia , Disostose Craniofacial/complicações , Disostose Craniofacial/genética , Descompressão Cirúrgica , Feminino , Forame Magno/cirurgia , França , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Mutação/genética , Países Baixos , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Reino Unido , Ventriculostomia
6.
Br J Radiol ; 94(1124): 20200061, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34233472

RESUMO

For decades, CT has been the primary imaging modality for the diagnosis and surveillance of paediatric craniofacial disorders. However, the deleterious effects of ionising radiation in the paediatric population are well established and remain an ongoing concern. This is especially so in the head and neck region, which has relatively poor soft tissue shielding with many radiosensitive organs. The development of "black bone" imaging utilising low flip angles and short echo time (TE) has shown considerable promise in alleviating the use of ionising radiation in many cases of craniofacial disorders. In this review article, we share our experience of utilising "black bone" sequence in children with craniofacial pathologies, ranging from traumatic injuries to craniosynostosis and focal osseous/fibro-osseous lesions such as fibrous dysplasia and Langerhans cell histiocytosis (LCH). A detailed discussion on the technical aspects of "black bone" sequence, including its potential pitfalls and limitations, will also be included.


Assuntos
Doenças Ósseas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Crânio/diagnóstico por imagem , Criança , Disostose Craniofacial/diagnóstico por imagem , Displasia Fibrosa Craniofacial , Ossos Faciais/diagnóstico por imagem , Ossos Faciais/lesões , Humanos , Crânio/lesões
7.
Plast Reconstr Surg ; 148(1): 145-156, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34181610

RESUMO

BACKGROUND: Little is known about the detailed growth of the cranial fossae, even though they provide an important structural connection between the cranial vault and the facial skeleton. This study details the morphologic development of isolated cranial vault synostosis and associated syndromes on cranial fossa development. METHODS: A total of 125 computed tomographic scans were included (nonsyndromic bicoronal synostosis, n = 36; Apert syndrome associated with bicoronal synostosis, n = 24; Crouzon syndrome associated with bicoronal synostosis, n = 11; and controls, n = 54). Three-dimensional analyses were produced using Materialise software. RESULTS: The regional anterior and middle cranial fossae volumes of nonsyndromic bicoronal synostosis are characterized by significant increases of 43 percent (p < 0.001) and 60 percent (p < 0.001), respectively, and normal posterior cranial fossa volume. The cranial fossae depths of nonsyndromic bicoronal synostosis were increased, by 37, 42, and 21 percent (all p < 0.001) for anterior, middle, and posterior cranial fossae, respectively, accompanying the shortened cranial fossae lengths. The volume and morphology of all cranial fossae in Apert syndrome nearly paralleled nonsyndromic bicoronal synostosis. However, Crouzon syndrome had reduced depths of cranial fossae, and more restricted fossa volumes than both Apert syndrome and nonsyndromic bicoronal synostosis. CONCLUSIONS: Cranial vault suture synostosis is likely to be more influential on cranial fossae development than other associated influences (genetic, morphologic) in Apert and Crouzon syndromes. Isolated Apert syndrome pathogenesis is associated with an elongation of the anterior cranial fossa length in infants, whereas in Crouzon syndrome, there is a tendency to reduce cranial fossa depth, suggesting individual adaptability in cranial fossae development related to vault synostosis.


Assuntos
Acrocefalossindactilia/complicações , Disostose Craniofacial/complicações , Craniossinostoses/complicações , Base do Crânio/crescimento & desenvolvimento , Acrocefalossindactilia/diagnóstico , Adolescente , Criança , Pré-Escolar , Disostose Craniofacial/diagnóstico , Craniossinostoses/diagnóstico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Base do Crânio/diagnóstico por imagem , Tomografia Computadorizada por Raios X
8.
J Craniomaxillofac Surg ; 49(10): 905-913, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33965326

RESUMO

The aim of the study was to determine if the additional surgical complexity of Lefort II distraction with zygomatic repositioning (LF2ZR) results in increased complications compared to Lefort III distraction (LF3). A retrospective review was performed of all LF3 and LF2ZR advancements performed by the senior author over 15 years. Demographic, operative, postoperative, and cephalometric data were collected from initial procedure through greater than 1 year postoperatively. Univariate and multivariate analyses were performed to compare procedures. 19 LF2ZR and 39 LF3 in 53 patients met inclusion criteria. Diagnoses differed between procedures, with more Crouzon Syndrome in LF3 and more Apert Syndrome in LF2ZR. Complication rate was 7/19 for LF2ZR and 12/39 for LF3 with no severe morbidity or mortality, and no difference between procedures (p = 0.56). The types of complications encountered differed between procedures. LF2ZR had a significantly longer operative time (506 ± 18 vs. 358 ± 24 min, p<0.001). However, a greater number of LF2ZR patients underwent concomitant procedures (15/19 vs. 13/39, p<0.001). Multivariate analysis revealed that Apert Syndrome and reoperative midface advancement were the most significant predictors of increased blood loss. LF2ZR has an equivalent complication rate to LF3. Therefore, it is our treatment of choice for cases requiring differential sagittal and vertical distraction of the central midface.


Assuntos
Disostose Craniofacial , Osteogênese por Distração , Cefalometria , Disostose Craniofacial/cirurgia , Humanos , Osteogênese por Distração/efeitos adversos , Osteotomia de Le Fort , Estudos Retrospectivos , Resultado do Tratamento
9.
Clin Plast Surg ; 48(3): 497-506, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34051901

RESUMO

The introduction of distraction osteogenesis to frontofacial monobloc advancement has increased the safety of the procedure. One hundred forty-seven patients with syndromic craniosynostosis underwent frontofacial monobloc advancement using 4 internal distractors. Twenty-five were aged 18 months or less. Ten patients presented with a tracheostomy, 5 (50%) were decannulated after surgery, and 3 others (30%) required an additional intervention before decannulation. Six patients required the addition of a transfacial pin and external traction. Very early frontofacial monobloc with 4 internal distractors is a safe and effective treatment to protect the ophthalmic, neurologic, and respiratory functions in infants with severe syndromic craniosynostosis.


Assuntos
Disostose Craniofacial/cirurgia , Osteogênese por Distração/métodos , Disostose Craniofacial/complicações , Craniossinostoses/complicações , Craniossinostoses/cirurgia , Ossos Faciais/anormalidades , Ossos Faciais/cirurgia , Feminino , Humanos , Lactente , Masculino , Placas Oclusais , Osteogênese por Distração/instrumentação , Síndromes da Apneia do Sono/etiologia , Síndromes da Apneia do Sono/cirurgia , Traqueostomia
10.
Clin Plast Surg ; 48(3): 507-519, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34051902

RESUMO

Monobloc and bipartition advancement by external distraction plays a major role in the treatment of syndromic craniosynostosis. They can reverse the associated facial deformity and play a role in the management of ocular exposure, intracranial hypertension, and upper airway obstruction. Facial bipartition distraction corrects the intrinsic facial deformities of Apert syndrome. Both procedures are associated with relatively high complication rates principally related to ascending infection and persistent cerebrospinal fluid leaks. Modern perioperative management has resulted in a significant decline in complications. External distractors allow fine tuning of distraction vectors and improve outcome but are less well tolerated than internal distractors.


Assuntos
Acrocefalossindactilia/cirurgia , Disostose Craniofacial/cirurgia , Osteogênese por Distração/métodos , Ossos Faciais/anormalidades , Ossos Faciais/cirurgia , Feminino , Humanos , Masculino , Osteogênese por Distração/efeitos adversos , Osteogênese por Distração/instrumentação
11.
Clin Plast Surg ; 48(3): 521-529, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34051903

RESUMO

Monobloc and facial bipartition combined with distraction osteogenesis (MFBDO) has gained popularity over the past several years as a treatment of syndromic craniosynostosis, in part because this surgical technique effectively removes many stigmatic clinical features associated with the syndromic face. The objective of this study is to detail the surgical planning used to achieve medialization of the orbits and describe the authors' experience using MFBDO to destigmatize the syndromic face. By using MFBDO, hypertelorism, vertical orbital dystopia, and downslanting of the palpebral fissure were surgically corrected in all patients, thereby destigmatizing the syndromic face.


Assuntos
Acrocefalossindactilia/cirurgia , Disostose Craniofacial/cirurgia , Procedimentos Cirúrgicos Ortognáticos/métodos , Osteogênese por Distração/métodos , Adulto , Criança , Face/cirurgia , Feminino , Humanos , Masculino , Osteogênese por Distração/instrumentação
12.
Neurosurg Focus ; 50(4): E12, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33794489

RESUMO

The aim of this study was to report on a single center's experience with spring-assisted cranial vault expansion (SAE) in patients with Crouzon syndrome and sagittal suture synostosis. Strip craniotomy with SAE has resulted in successful outcomes with low complication and revision rates in patients with isolated scaphocephaly. However, recent experience suggests that outcomes in patients with Crouzon syndrome and sagittal synostosis (SS) who undergo SAE are less favorable compared with the outcomes of those who undergo frontobiparietal (FBP) expansion. The authors reviewed both operations performed at a single center and noticed an upward expansion of the skull, which may be related to ventriculomegaly, with concurrent intracranial hypertension and poor aesthetic outcome. All patients diagnosed with Crouzon syndrome and SS who were treated with SAE required a revision FBP operation. Based on this outcome, the authors consider Crouzon syndrome a contraindication for correcting SS with springs.


Assuntos
Disostose Craniofacial , Craniossinostoses , Hipertensão Intracraniana , Procedimentos Cirúrgicos Reconstrutivos , Disostose Craniofacial/diagnóstico por imagem , Disostose Craniofacial/cirurgia , Craniossinostoses/diagnóstico por imagem , Craniossinostoses/cirurgia , Craniotomia , Humanos , Lactente , Hipertensão Intracraniana/cirurgia , Crânio/diagnóstico por imagem , Crânio/cirurgia
13.
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 35(4): 371-374;379, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33794641

RESUMO

Children with microtia are often associated with maxillofacial dysostosis, such as Treacher Collins syndrome, Goldenhar syndrome, and Nager syndrome, and they are prone to suffer from obstructive sleep apnea(OSA). Obstruction widely occurred in the upper airway is the main mechanism of OSA in these children, and dysplasia of the pharynx and neurodevelopmental abnormalities may also participate. Early diagnosis requires symptom screening and polysomnography. Imaging techniques and endoscopy can be adopted to fully assess the upper airway status to guide further treatment. According to the child's condition and the main obstruction site, treatment methods include maxillofacial deformity correction, continuous positive pressure ventilation and tracheotomy. OSA in microtia children with maxillofacial dysostosis needs to be identified and treated in time to reduce the adverse effects on the growth and development of children.


Assuntos
Microtia Congênita , Disostose Craniofacial , Anormalidades Maxilofaciais , Apneia Obstrutiva do Sono , Criança , Anormalidades do Olho , Humanos , Distúrbios da Fala
14.
Neoreviews ; 22(4): e250-e257, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33795400

RESUMO

Craniosynostosis is the premature fusion of 1 or more sutures that normally separate the bony plates of an infant's skull and occurs in about 1 in 2,000 to 2,500 live births. Primary or congenital craniosynostoses represent the majority of cases and consist of single-suture and multisuture synostoses. Multisuture synostoses are typically associated with distinct craniofacial syndromes, including Muenke syndrome, Apert syndrome, Crouzon syndrome, and Pfeiffer syndrome, and are thus categorized under syndromic craniosynostoses. Secondary causes of craniosynostoses include metabolic or hematologic disorders that affect bone metabolism and typically present much later than primary synostoses. The severity of the deformity and the presence of increased intracranial pressure dictate the need for early surgical intervention, prompting the importance of early recognition and timely referral. Infants with craniosynostosis are also at increased risk for neurodevelopmental impairment and thus require close follow-up and monitoring. The early recognition and referral of craniosynostosis is imperative for the optimization of management and minimization of potential neurologic impairments that may develop.


Assuntos
Disostose Craniofacial , Craniossinostoses , Humanos , Recém-Nascido , Crânio , Síndrome
15.
Childs Nerv Syst ; 37(6): 2001-2009, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33866411

RESUMO

PURPOSE: The most commonly occurring syndromic craniosynostoses are Apert syndrome, Crouzon syndrome, Pfeiffer syndrome, and Saethre-Chotzen syndrome. There is insufficient data regarding postoperative syndrome-related outcomes following the posterior vault distraction osteogenesis (PVDO) procedure, as well as data addressing whether or not additional procedures will be subsequently necessary to comprehensively treat children who undergo PVDO. Thus, the objective of this study is to describe and compare syndrome-related potential complications and outcomes associated with the PVDO procedure. METHODS: An observational retrospective study was performed on consecutive patients (n=24) with Apert syndrome, Crouzon syndrome, Pfeiffer syndrome, or Saethre-Chotzen syndrome, respectively, who underwent PVDO between 2012 and 2019. Demographic data (patient gender and age when the PVDO procedure was performed), diagnosis, surgery-related data, and outcome data (perioperative and midterm complications and need for additional surgery) were verified. RESULTS: Total relative blood transfusion volumes per kilogram for the patients were as follows: 22.75 ± 9.30 ml for Apert syndrome, 10.73 ± 2.28 ml for Crouzon syndrome (Apert versus Crouzon, p<0.05), 18.53 ± 8.08 ml for Pfeiffer syndrome, and 19.74 ± 9.12 ml for Saethre-Chotzen syndrome. None of the patients required a secondary procedure to alleviate intracranial pressure except for a Saethre-Chotzen patient. CONCLUSION: PVDO is an effective technique to address elevated intracranial pressure in SC patients that alleviates the need for secondary procedures at midterm follow-up. Apert syndrome patients presented relatively higher total blood transfusion rates than Crouzon syndrome patients who were operated on at a later age and weighed more.


Assuntos
Acrocefalossindactilia , Disostose Craniofacial , Craniossinostoses , Osteogênese por Distração , Acrocefalossindactilia/cirurgia , Criança , Disostose Craniofacial/cirurgia , Humanos , Osteogênese por Distração/efeitos adversos , Estudos Retrospectivos
16.
Childs Nerv Syst ; 37(10): 3105-3111, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33904938

RESUMO

INTRODUCTION: With the increasing possibilities of surgical treatment addressing the complex spectrum of defects in Crouzon syndrome (CS), it is of utmost importance to obtain accurate assessment of the malformation. Evaluating the volume of the posterior fossa is of great importance since many authors, considering that its volume is always decreased, favor posterior fossa enlargement as a first step in the treatment of CS. MATERIAL AND METHODS: We studied CT scans of children with CS, which were vestibular-oriented (VO) in order to conform with physiological landmarks, and we measured intracranial volume by manual segmentation; these abnormal CT scans were superposed with VO 3D-CT scanners of age-matched controls. We studied the volume index of the posterior fossa for each CS patient defined as the ratio of its volume in CS patients with the normal for age calculated from normal controls. RESULTS: We studied the imaging of 41 children with CS and 70 control. Among CS patients, the volume of the posterior fossa was increased in 10, compared with control. We found closure of the sphenoidal synchondrosis was correlated with age and with the width of the posterior fossa, but not with its length nor with the posterior fossa volume index. CONCLUSION: Segmentation on VO-CT scanner and superposition with CT scanners of normal controls is a powerful tool for the study of the impact of CS or other synostoses on volume and shape. We found that CS is more heterogeneous than previously thought, and surgical strategies should be adapted accordingly.


Assuntos
Fossa Craniana Posterior , Disostose Craniofacial , Criança , Fossa Craniana Posterior/diagnóstico por imagem , Disostose Craniofacial/diagnóstico por imagem , Disostose Craniofacial/cirurgia , Humanos , Tomografia Computadorizada por Raios X
17.
Medicine (Baltimore) ; 100(10): e24991, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725872

RESUMO

RATIONALE: Crouzon syndrome is an autosomal dominant genetic disorder caused by mutations in fibroblast growth factor receptor 2 (FGFR2) and one of the most common types of craniosynostosis. Here we report the detection of FGFR2 mutation and its related clinical findings in 2 patients with Crouzon syndrome from a Chinese family. PATIENT CONCERNS: We report a case of a 28-year-old male patient presented with the chief complaint of gradually blurring of his eyes over the last 6 months before visiting our clinics. History revealed low visual acuity in his right eye since childhood. Physical examination showed that both the patient and his mother have the appearance of craniofacial dysostosis, mandibular prognathism, ocular proptosis, short superior lip, scoliosis, and thoracic deformity. DIAGNOSIS: Auxiliary examinations lead to the diagnosis of Crouzon syndrome with binocular optic atrophy, myelinated retina nerve fibers, and ametropia in both eyes, and amblyopia in the right eye of the male patient. The molecular genetic analysis confirmed the diagnosis by detecting a heterozygous pathogenic mutation c.1026C > G (C342W) in exon 10 of FGFR2 in both the patient and his mother, but not in any of the unaffected family members. INTERVENTIONS AND OUTCOMES: None. LESSONS: Our study confirms the presence of optic nerve atrophy in patients with Crouzon syndrome carrying FGFR2 C342W mutations and indicates that MRI and funduscopy should be performed to examine the optic nerve changes for patients with Crouzon syndrome.


Assuntos
Disostose Craniofacial/complicações , Atrofias Ópticas Hereditárias/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Adulto , China , Disostose Craniofacial/genética , Análise Mutacional de DNA , Éxons/genética , Feminino , Angiofluoresceinografia , Heterozigoto , Humanos , Imageamento por Ressonância Magnética , Masculino , Mutação de Sentido Incorreto , Atrofias Ópticas Hereditárias/diagnóstico , Nervo Óptico/diagnóstico por imagem , Linhagem , Tomografia Computadorizada por Raios X
18.
Biophys J ; 120(5): 844-854, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33524372

RESUMO

Freeman-Sheldon syndrome (FSS) is characterized by congenital contractures resulting from dominant point mutations in the embryonic isoform of muscle myosin. To investigate its disease mechanism, we used Drosophila models expressing FSS myosin mutations Y583S or T178I in their flight and jump muscles. We isolated these muscles from heterozygous mutant Drosophila and performed skinned fiber mechanics. The most striking mechanical alteration was an increase in active muscle stiffness. Y583S/+ and T178I/+ fibers' elastic moduli increased 70 and 77%, respectively. Increased stiffness contributed to decreased power generation, 49 and 66%, as a result of increased work absorbed during the lengthening portion of the contractile cycle. Slower muscle kinetics also contributed to the mutant phenotype, as shown by 17 and 32% decreases in optimal frequency for power generation, and 27 and 41% slower muscle apparent rate constant 2πb. Combined with previous measurements of slower in vitro actin motility, our results suggest a rate reduction of at least one strongly bound cross-bridge cycle transition that increases the time myosin spends strongly bound to actin, ton. Increased ton was further supported by decreased ATP affinity and a 16% slowing of jump muscle relaxation rate in T178I heterozygotes. Impaired muscle function caused diminished flight and jump ability of Y583S/+ and T178I/+ Drosophila. Based on our results, assuming that our model system mimics human skeletal muscle, we propose that one mechanism driving FSS is elevated muscle stiffness arising from prolonged ton in developing muscle fibers.


Assuntos
Disostose Craniofacial , Drosophila , Animais , Drosophila melanogaster , Humanos , Contração Muscular , Músculo Esquelético , Miosinas/genética
19.
Br J Surg ; 108(4): 373-379, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33611431

RESUMO

BACKGROUND: The combination of conventional transarterial chemoembolization (cTACE) and systemic therapy has the potential to treat chemotherapy-refractory unresectable colorectal liver metastases (CRLMs). This study aimed to compare survival after this combined treatment versus systemic chemotherapy alone. METHODS: This single-centre RCT included patients with unresectable CRLMs that progressed after first-line treatment. Patients were randomized on a 1 : 1 basis to either systemic chemotherapy with or without cTACE, without further stratification. The primary outcome was progression-free survival (PFS). Secondary outcomes were overall response rate, disease control rate, conversion rate to liver resection, overall survival, and adverse events. RESULTS: Of 180 patients recruited, 168 were randomized. Eighty-five patients in arm A received systemic chemotherapy plus cTACE and 83 in arm B received systemic chemotherapy alone. Median PFS was longer in arm A than B (6.7 versus 3.8 months; hazard ratio (HR) 0.67, 95 per cent c.i. 0.49 to 0.91; P = 0.009), but did not translate into prolonged median overall survival (18.4 versus 14.8 months; HR = 0.92, 0.62 to 1.36; P = 0.669). Overall response rates (20 versus 22 per cent; P = 0.788) and conversion rate to liver resection (18 versus 16 per cent; P = 0.730) were no different between arms A and B. The disease control rate was higher in arm A than arm B (67 versus 51 per cent; P = 0.030). No adverse event higher than grade 3 according to the Common Terminology Criteria for Adverse Events was observed during treatment. CONCLUSION: Systemic chemotherapy plus cTACE is a safe option as second-line treatment for unresectable colorectal liver metastases, with a modest effect on PFS. Registration number: NCT03783559 (http://www.clinicaltrials.gov).


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioembolização Terapêutica/métodos , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Disostose Craniofacial , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Humanos , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Deformidades Congênitas dos Membros , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/uso terapêutico , Intervalo Livre de Progressão , Análise de Sobrevida , Resultado do Tratamento
20.
Br J Oral Maxillofac Surg ; 59(5): 579-585, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33581885

RESUMO

The altered orbital morphology of patients with Crouzon syndrome could have an impact on the planning of treatment in diverse populations, in spite of the confounding influences of different cranial suture synostosis. This study attempted to explore the differences in orbital characteristics between Asian, Caucasian patients with Crouzon syndrome, associated pansynostosis. Eighty-six preoperative computed tomograms (CT) were included (Asian Crouzon syndrome: n=10; Asian controls: n=24; Caucasian Crouzon syndrome: n=19; Caucasian controls: n=33) and measured using Mimics software (Materialise). Unique cephalometric measurements related to orbital morphology and position were designed. Crouzon syndrome and race both have interactive effects on protrusion of the globe (p=0.009) and medial horizontal angle (p=0.012) in the assessment of orbital morphology. They also interact in the width of the ethmoid sinus (p=0.009) and influence bilateral orbital relations. The anteroposterior orbital roof in Caucasian patients with Crouzon syndrome was shortened by 4.09mm (p=0.002) compared with Caucasian controls. However, in Asian patients this dimension developed normally. The anteroposterior orbital floor was significantly reduced to a similar extent in both Asian and Caucasian Crouzon patients (both p<0.001). The visual axes in Caucasian patients with Crouzon showed more inferior rotation, by 4.38° (p=0.031) than they did in Caucasian controls, but did not achieve a statistically significant difference in other comparisons. The effect of Crouzon syndrome on orbital malformation and placement is influenced by race, especially structures related to the ethmoid sinus. Asian patients need greater infraorbital advancement for better correction of orbital proptosis and aesthetic benefits, but may require less fronto-orbital advancement than Caucasian patients.


Assuntos
Disostose Craniofacial , Craniossinostoses , Cefalometria , Disostose Craniofacial/diagnóstico por imagem , Estética Dentária , Humanos , Órbita/diagnóstico por imagem , Tomografia Computadorizada por Raios X
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