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1.
Brain Spine ; 4: 102671, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510632

RESUMO

Introduction: The incidence of intramedullary spinal cord tumors ranges from 2 to 4% of all central nervous system tumors. Only 6-8% are astrocytomas. The gold standard to diagnose a spinal cord tumor is the spinal cord MRI in toto. Specific radiological criteria orient the diagnosis of the intradural intramedullary lesion. Most of the authors studied adult populations of astrocytomas. However, pediatric astrocytomas present certain particularities. Research question: This work aims to determine if the usual radiological criteria of intramedullary astrocytomas (IMAs) are different depending on the patient's age. Material & methods: We evaluated the radiological features of IMAs in adult and pediatric groups through a retrospective study. Results: We collected 31 patients with IMAs (11 children and 20 adults). We observed some trends but we did not highlight any statistically significant difference between all the radiological criteria studied (sagittal and axial spinal cord localization, T1-and T2-weighted characteristics, contrast uptake, infiltrating character, presence of necrosis, heterogeneous lesion, necrotic, hemorrhagic, presence of edema) and the patient's age. Discussion & conclusion: Given the rarity of IMAs and the lack of large specific pediatric studies, it seems essential to routinely report all cases encountered and create multicentric pediatric databases to draw more robust conclusions.

2.
Cancers (Basel) ; 15(14)2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37509335

RESUMO

Ependymomas are the most common intramedullary tumors in adults. While gross total resection is the aim of surgery, tumor infiltration might limit resection. In cases of subtotal removal, the necessary adjuvant management remains unclear. The aim of our study was to assess the need for adjuvant radiotherapy after an incomplete resection of grade II intramedullary ependymomas (IME-II). We retrospectively reviewed all cases of IME-II operated upon at a single tertiary neurosurgical center from 2009 to 2018. Patients with anaplastic or myxopapillary ependymomas, and patients with a follow-up of less than three years, were excluded. We included 46 patients: 19 (41.3%) had a gross total resection; 21 (45.7%) had a subtotal resection; and 6 (13%) had a partial resection. None of the patients underwent adjuvant radiotherapy. Over a median follow-up of 79 months (range = 36-186), seven patients presented a radiological tumor progression with a mean delay of 50.9 months (range = 18-85), of which two were symptomatic (4.3%). Progression-free survival (PFS) was 90.1% at 5 years and 76.8% at 10 years. The extent of the resection was the only significant risk factor for secondary tumor progression (p = 0.012). Four of the seven patients with recurring IME-II were treated: three patients had a second surgery, leading to two GTR and one STR, followed by radiotherapy in one case, and one patient underwent radiotherapy alone. In this study, the rate of symptomatic progression and retreatment after incomplete resection of IME-II without adjuvant radiotherapy was low, suggesting a conservative approach in such cases.

3.
Acta Neuropathol Commun ; 11(1): 46, 2023 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-36934287

RESUMO

Central Nervous System (CNS) embryonal tumors represent a heterogeneous group of highly aggressive tumors occurring preferentially in children but also described in adolescents and adults. In 2021, the CNS World Health Organization (WHO) classification drastically changed the diagnosis of the other CNS embryonal tumors including new histo-molecular tumor types. Here, we report a pediatric case of a novel tumor type among the other CNS embryonal tumors classified within the methylation class "CNS Embryonal Tumor with BRD4-LEUTX Fusion". The patient was a 4-year girl with no previous history of disease. For a few weeks, she suffered from headaches, vomiting and mild fever associated with increasing asthenia and loss of weight leading to a global deterioration of health. MRI brain examination revealed a large, grossly well-circumscribed tumoral mass lesion located in the left parietal lobe, contralateral hydrocephalus and midline shift. Microscopic examination showed a highly cellular tumor with a polymorphic aspect. The majority of the tumor harbored neuroectodermal features composed of small cells with scant cytoplasm and hyperchromatic nuclei associated with small "medulloblastoma-like" cells characterized by syncytial arrangement and focally a streaming pattern. Tumor cells were diffusely positive for Synaptophysin, CD56, INI1 and SMARCA4 associated with negativity for GFAP, OLIG-2, EMA, BCOR, LIN28A and MIC-2. Additional IHC features included p53 protein expression in more than 10% of the tumor's cells and very interestingly, loss of H3K27me3 expression. The Heidelberg DNA-methylation classifier classified this case as "CNS Embryonal Tumor with BRD4:LEUTX Fusion". RNA-sequencing analyses confirmed the BRD4 (exon 13)-LEUTX (exon 2) fusion with no other molecular alterations found by DNA sequencing. Our case report confirmed that a new subgroup of CNS embryonal tumor with high aggressive potential, loss of H3K27me3 protein expression, BRDA4-LEUTX fusion, named "Embryonal CNS tumor with BRD4-LEUTX fusion", has to be considered into the new CNS WHO classification.


Assuntos
Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Neoplasias Cerebelares , Neoplasias Embrionárias de Células Germinativas , Tumores Neuroectodérmicos Primitivos , Feminino , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Neoplasias do Sistema Nervoso Central/genética , Neoplasias Cerebelares/genética , DNA/metabolismo , DNA Helicases/genética , Metilação de DNA , Histonas/genética , Tumores Neuroectodérmicos Primitivos/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Pré-Escolar
4.
ACS Nano ; 17(6): 5459-5471, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36912862

RESUMO

We use in situ synchrotron grazing incidence X-ray diffraction and X-ray reflectivity to investigate with high resolution the structure of a two-dimensional single layer of tantalum sulfide grown on a Au(111) surface and its evolution during intercalation by Cs atoms and deintercalation, which decouples and recouples the two materials, respectively. The grown single layer consists of a mixture of TaS2 and its S-depleted version, TaS, both aligned with gold, and forming moirés where 7 (respectively 13) lattice constants of the 2D layer almost perfectly match 8 (respectively 15) substrate lattice constants. Intercalation fully decouples the system by lifting the single layer by ∼370 pm and induces an increase of its lattice parameter by 1-2 picometers. The system gradually evolves, during cycles of intercalation/deintercalation assisted by an H2S atmosphere, toward a final coupled state consisting of the fully stoichiometric TaS2 dichalcogenide whose moiré is found very close to the 7/8 commensurability. The reactive H2S atmosphere appears necessary to achieve full deintercalation, presumably by preventing S depletion and the concomitant strong bonding with the intercalant. The structural quality of the layer improves during the cyclic treatment. In parallel, because they are decoupled from the substrate by the intercalation of cesium, some of the TaS2 flakes rotate by 30°. These produce two additional superlattices with characteristic diffraction patterns of different origins. The first is aligned with gold's high symmetry crystallographic directions and is a commensurate moiré ((6 × 6)-Au(111) coinciding with (3√3 × 3√3)R30°-TaS2). The second is incommensurate and corresponds to a near coincidence of (6 × 6) unit cells of 30°-rotated TaS2 with (4√3 × 4√3)Au(111) surface ones. This structure, which is less coupled to gold, might be related to the ∼(3× 3) charge density wave previously reported even at room temperature in TaS2 grown on noninteracting substrates. A (3 × 3) superstructure of 30°-rotated TaS2 islands is indeed revealed by complementary scanning tunneling microscopy.

5.
Phys Rev Lett ; 129(9): 096101, 2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36083654

RESUMO

Two-dimensional confinement of lattices produces a variety of order and disorder phenomena. When the confining walls have atomic granularity, unique structural phases are expected, of relevance in nanotribology, porous materials, or intercalation compounds where, e.g., electronic states can emerge accordingly. The interlayer's own order is frustrated by the competing interactions exerted by the two confining surfaces. We revisit the concept of orientational ordering, introduced by Novaco and McTague to describe the twist of incommensurate monolayers on crystalline surfaces. We predict a two-way twist of the monolayer as its density increases. We discover such a behavior in alkali atom monolayers (sodium, cesium) confined between graphene and an iridium surface, using scanning tunneling microscopy and electron diffraction.

6.
Neuropathol Appl Neurobiol ; 48(1): e12758, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34388852

RESUMO

AIMS: The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems-level analysis. METHODS: Imaging-based cortical structural maps from a large-scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell-type deconvolution, differential expression analysis and cell-type enrichment analyses were used to identify differences in cell-type distribution. These differences were followed up in post-mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell-type-specific depletion was used in a murine model of acquired epilepsy. RESULTS: We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post-mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non-spatial memory test seen in epileptic mice not depleted of microglia. CONCLUSIONS: These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.


Assuntos
Epilepsia , Microglia , Animais , Encéfalo , Células Endoteliais , Epilepsia/metabolismo , Camundongos , Microglia/metabolismo , Convulsões
7.
Acta Neurochir (Wien) ; 162(4): 957-959, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31960142

RESUMO

BACKGROUND: Hemangioblastomas (HBL) are benign tumors occurring sporadically or associated with Von Hippel-Lindau syndrome (VHL). METHOD: We present the pre-, per-, and postoperative course of a rare case with radicular HBL presenting with subarachnoid hemorrhage (SAH) in the frame of VHL. We describe the microsurgical approach. CONCLUSION: Complete microsurgical in bloc resection has been performed. Postoperative course was uneventful.


Assuntos
Hemangioblastoma/cirurgia , Microcirurgia/métodos , Procedimentos Neurocirúrgicos/métodos , Complicações Pós-Operatórias/prevenção & controle , Hemorragia Subaracnóidea/cirurgia , Doença de von Hippel-Lindau/cirurgia , Hemangioblastoma/complicações , Humanos , Microcirurgia/efeitos adversos , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Hemorragia Subaracnóidea/etiologia
8.
Chem Sci ; 12(6): 2257-2267, 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34163992

RESUMO

Catechols are ubiquitous substances often acting as antioxidants, thus of importance in a variety of biological processes. The Fenton and Haber-Weiss processes are thought to transform these molecules into aggressive reactive oxygen species (ROS), a source of oxidative stress and possibly inducing degenerative diseases. Here, using model conditions (ultrahigh vacuum and single crystals), we unveil another process capable of converting catechols into ROSs, namely an intramolecular redox reaction catalysed by a Cu surface. We focus on a tri-catechol, the hexahydroxytriphenylene molecule, and show that this antioxidant is thereby transformed into a semiquinone, as an intermediate product, and then into an even stronger oxidant, a quinone, as final product. We argue that the transformations occur via two intramolecular redox reactions: since the Cu surface cannot oxidise the molecules, the starting catechol and the semiquinone forms each are, at the same time, self-oxidised and self-reduced. Thanks to these reactions, the quinone and semiquinone are able to interact with the substrate by readily accepting electrons donated by the substrate. Our combined experimental surface science and ab initio analysis highlights the key role played by metal nanoparticles in the development of degenerative diseases.

9.
Acta Neurochir (Wien) ; 162(4): 831-837, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31873794

RESUMO

INTRODUCTION: Primary paragangliomas (PG) of the spine are extremely rare entities. The present study reviews our experience over a period of 30 years. METHODS: This is a retrospective, single center, observational study. Patients surgically treated for a spinal PG with confirmed anatomopathological diagnosis were included. The McCormick classification was used as a reference for clinical evaluation. Follow-up MRI and clinical assessment took place at 6 weeks, 3 months, 6 months, and 1 year after surgery and on yearly basis after. RESULTS: Six cases have been operated in our institution. The mean age was 37.8 (median 35.5, 30-53). The mean follow-up period was 9.6 years (median 9.5, 1-23). Preoperative duration of symptoms varied between a few hours to 4 years. Low back pain was most common sign. One presented with hemorrhage and acute onset of paraplegia. All patients underwent single surgery, with the exception of one case, which had two surgeries on the same anatomical site and a third surgery on another location of the same tumor type. Preoperatively, McCormick scale was I in four cases, and II and IV in one case, respectively. Postoperatively, all patients in McCormick I retained the same class; one patient in McCormick II passed to McCormick III; the case in McCormick IV recovered to McCormick II. Five of eight surgeries achieved total resection, while two surgeries accomplished a partial microsurgical excision and one a gross total resection. Three patients had spinal leptomeningeal dissemination. Two of them benefited from extended spine radiotherapy, while the other of a "wait-and-scan" policy. Spinal leptomeningeal dissemination was stable in all patients at last follow-up. CONCLUSION: We consider surgery as primary treatment in all PG. In our experience, preoperative diagnosis is difficult and caution must be taken to perioperative course in these cases. We do not routinely perform postoperative radiation if there is a residual tumor. We regularly perform clinical and radiological follow-up, so as to be able to document recurrent cases, which have been reported even up to 30 years after primary surgical excision.


Assuntos
Paraganglioma/cirurgia , Neoplasias da Medula Espinal/cirurgia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Paraganglioma/diagnóstico por imagem , Paraganglioma/patologia , Período Pós-Operatório , Radiografia , Estudos Retrospectivos , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/patologia , Resultado do Tratamento
10.
J Gynecol Obstet Hum Reprod ; 48(5): 315-317, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30794954

RESUMO

PURPOSE: Performing an antibiotic prophylaxis (ATBP) with a surgical abortion (SA) is recommended in numerous countries, including France where the CNGOF has issued guidelines. There is little data regarding the actual application of these guidelines in clinical practice. The aim of this study was to evaluate the practice of ATBP with SA and to assess the degree of compliance with the national guidelines. METHODS: This longitudinal, prospective, multicenter, non-interventional study was undertaken between December 2013 and July 2014 with the objective of assessing the modalities of prescription of ATBP under real-life conditions in the setting of SA, and to compare it with the national guidelines. RESULTS: A total of 542 pregnant patients agreed to participate and were included by 36 French hospitals. Of these 36 active centers, 18 (50%) systematically prescribed an ATBP, while 10 (27.8%) prescribed an ATBP depending on the risks for the patient. Of these 542 patients, 263 (48.5%) received an ATBP prescription, 274 (50.6%) did not receive such a prescription. The prescribed ATBP was metronidazole (88/263 (33.5%)), azythromycin (76/263 (28.9%)), or doxycycline (44/263 (16.7%)). In total, 208/263 (79.1%) of the patients received an ATBP. Finally, three factors were identified as independent contributors that influence the prescription of an ATBP: the prescribed cervix preparation, the type of center, and the number of surgical abortions per year in the center over 500/year. CONCLUSION: Only half of the patients who undergo an SA receive a prescription for ATBP. Of the prescribed antibiotics, 80% correspond with the recommended ones.


Assuntos
Aborto Induzido , Antibioticoprofilaxia , Prescrições de Medicamentos/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Adolescente , Adulto , Feminino , França/epidemiologia , Humanos , Estudos Longitudinais , Doença Inflamatória Pélvica/prevenção & controle , Padrões de Prática Médica/estatística & dados numéricos , Estudos Prospectivos , Adulto Jovem
11.
Nano Lett ; 18(8): 4812-4820, 2018 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-29975539

RESUMO

Chemical vapor deposition (CVD) on metals is so far the best suited method to produce high-quality, large-area graphene. We discovered an unprecedentedly large family of small size-selective carbon clusters that form together with graphene during CVD. Using scanning tunneling microscopy (STM) and density functional theory (DFT), we unambiguously determine their atomic structure. For that purpose, we use grids based on a graphene moiré and a dilute atomic lattice that unambiguously reveal the binding geometry of the clusters. We find that the observed clusters bind in metastable configurations on the substrate, while the thermodynamically stable configurations are not observed. We argue that the clusters are formed under kinetic control and establish that the evolution of the smallest clusters is blocked. They are hence products of surface reactions in competition with graphene growth, rather than intermediary species to the formation of extended graphene, as often assumed in the literature. We expect such obstacles to the synthesis of perfect graphene to be ubiquitous on a variety of metallic surfaces.

12.
J Phys Chem Lett ; 9(10): 2523-2531, 2018 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-29688019

RESUMO

In crystal growth, surfactants are additive molecules used in dilute amount or as dense, permeable layers to control surface morphologies. We investigate the properties of a strikingly different surfactant: a 2D and covalent layer with close atomic packing, graphene. Using in situ, real-time electron microscopy, scanning tunneling microscopy, kinetic Monte Carlo simulations, and continuum mechanics calculations, we reveal why metallic atomic layers can grow in a 2D manner below an impermeable graphene membrane. Upon metal growth, graphene dynamically opens nanochannels called wrinkles, facilitating mass transport while at the same time storing and releasing elastic energy via lattice distortions. Graphene thus behaves as a mechanically active, deformable surfactant. The wrinkle-driven mass transport of the metallic layer intercalated between graphene and the substrate is observed for two graphene-based systems, characterized by different physicochemical interactions, between graphene and the substrate and between the intercalated material and graphene. The deformable surfactant character of graphene that we unveil should then apply to a broad variety of species, opening new avenues for using graphene as a 2D surfactant forcing the growth of flat films, nanostructures, and unconventional crystalline phases.

13.
Brain ; 141(2): 391-408, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29365066

RESUMO

Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. We ranked brain structures in order of greatest differences between patients and controls, by meta-analysing effect sizes across 16 subcortical and 68 cortical brain regions. We also tested effects of duration of disease, age at onset, and age-by-diagnosis interactions on structural measures. We observed widespread patterns of altered subcortical volume and reduced cortical grey matter thickness. Compared to controls, all epilepsy groups showed lower volume in the right thalamus (Cohen's d = -0.24 to -0.73; P < 1.49 × 10-4), and lower thickness in the precentral gyri bilaterally (d = -0.34 to -0.52; P < 4.31 × 10-6). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = -1.73 to -1.91, P < 1.4 × 10-19), and lower thickness in extrahippocampal cortical regions, including the precentral and paracentral gyri, compared to controls (d = -0.36 to -0.52; P < 1.49 × 10-4). Thickness differences of the ipsilateral temporopolar, parahippocampal, entorhinal, and fusiform gyri, contralateral pars triangularis, and bilateral precuneus, superior frontal and caudal middle frontal gyri were observed in left, but not right, MTLE (d = -0.29 to -0.54; P < 1.49 × 10-4). Contrastingly, thickness differences of the ipsilateral pars opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = -0.27 to -0.51; P < 1.49 × 10-4). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < -0.0018; P < 1.49 × 10-4). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed.


Assuntos
Mapeamento Encefálico , Encéfalo/diagnóstico por imagem , Epilepsia/patologia , Adulto , Encéfalo/patologia , Correlação de Dados , Estudos Transversais , Epilepsia/diagnóstico por imagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Cooperação Internacional , Imageamento por Ressonância Magnética , Masculino , Metanálise como Assunto
14.
BMC Med Genet ; 18(1): 48, 2017 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-28464862

RESUMO

BACKGROUND: Autosomal recessive defects of either the B1, E1, M1 or S1 subunit of the Adaptor Protein complex-4 (AP4) are characterized by developmental delay, severe intellectual disability, spasticity, and occasionally mild to moderate microcephaly of essentially postnatal onset. CASE PRESENTATION: We report on a patient with severe microcephaly of prenatal onset, and progressive spasticity, developmental delay, and severe intellectual deficiency. Exome sequencing showed a homozygous mutation in AP4M1, causing the replacement of an arginine by a stop codon at position 338 of the protein (p.Arg338X). The premature stop codon truncates the Mu homology domain of AP4M1, with predicted loss of function. Exome analysis also showed heterozygous variants in three genes, ATR, MCPH1 and BLM, which are known causes of autosomal recessive primary microcephaly. CONCLUSIONS: Our findings expand the AP4M1 phenotype to severe microcephaly of prenatal onset, and more generally suggest that the AP4 defect might share mechanisms of prenatal neuronal depletion with other genetic defects of brain development causing congenital, primary microcephaly.


Assuntos
Complexo 4 de Proteínas Adaptadoras/genética , Microcefalia/genética , Mutação , Humanos , Recém-Nascido , Masculino
15.
J Surg Case Rep ; 2017(8): rjx162, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29308182

RESUMO

In this article, we report a male patient that developed psychotic symptoms after the excision of an arachnoid cyst from the posterior fossa detected by magnetic resonance and subsequent clinical improvement after anti-psychotic treatment.

16.
Oncotarget ; 7(51): 85306-85317, 2016 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-27852035

RESUMO

Von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary cancer syndrome that predisposes affected individuals to the development of multiple benign and malignant tumors. One of the main manifestations of VHL is renal cell carcinoma (RCC). RCC is increasingly being treated with targeted therapies, which offer an alternative treatment option for patients with VHL disease. This study investigated the effectiveness of sunitinib in VHL patients with advanced tumors or tumors unsuitable for surgery.This multicenter, phase II, open-label study from the PREDIR VHL network, treated patients with genetically-confirmed advanced VHL disease with oral sunitinib (50 mg/day for 28 days then a 2-week rest period) until progression. Lesions were performed using magnetic resonance imaging (MRI) and computed tomographic (CT) scan. The primary endpoint was objective response rate; secondary endpoints included tolerability and overall survival.All five patients showed stable disease as best response at 6 months. Two patients showed impressive transitory clinical improvement during early cycles. No patient died during sunitinib treatment. Reasons for discontinuing sunitinib therapy were disease progression (n=1), unacceptable toxicity (n=3) and lack of clinical improvement after 7 cycles (10.5 months) with unacceptable toxicity (n=1).In conclusion, sunitinib was of limited benefit in patients with advanced VHL disease, but had better efficacy against metastatic RCC than other VHL-related lesions. Treatment-related toxicity is an important limiting factor in this frail patient population. New agents with different mechanisms of action are required to treat this disease.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Indóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias/tratamento farmacológico , Pirróis/uso terapêutico , Doença de von Hippel-Lindau/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/etiologia , Carcinoma de Células Renais/mortalidade , Feminino , França , Humanos , Neoplasias Renais/etiologia , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias/etiologia , Neoplasias/mortalidade , Estudos Prospectivos , Sunitinibe , Análise de Sobrevida , Resultado do Tratamento , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/mortalidade
17.
Acta Neurochir (Wien) ; 158(7): 1333-41, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27185165

RESUMO

OBJECT: The purpose of this study was to analyze the surgical outcome and complications of a single-center series of medulla oblongata (MO) hemangioblastomas. METHODS: We retrospectively reviewed the medical charts of all medulla oblongata hemangioblastomas operated on at our institution between 1996 and 2015. All patients had a pre- and postoperative MRI and a minimum follow-up of 6 months. Patients were scored according to the Karnofsky Performance Scale (KPS) and McCormick Scale at the moment of admission, discharge and the last follow-up. RESULTS: Thirty-one surgical procedures were performed on 27 patients (16 females and 11 males). The mean age was 33 years, and 93 % of patients had von Hippel Lindau (VHL) disease. Three patients experienced very complicated postoperative courses, with one case ending in the death of the patient. Two patients required tracheostomy. According to McCormick's classification, 7 (23 %) of the 31 operations resulted in aggravation and 23 (74 %) in no change. Considering the seven patients with aggravation at discharge, four patients (60 %) returned to their preoperative status, one (14 %) improved but remained below his preoperative McCormick grade and two (29 %) did not improve. At last follow-up, KPS was ameliorated in 53 %, stable in 40 % and worsened in 7 % of cases. CONCLUSION: Surgery of medulla oblongata hemangioblastomas is a challenging procedure characterized by an acceptable morbidity. Transient morbidity is not negligible even if the long-term outcome is in most cases favorable. A compromised neurological condition seems to be the best predictor of unfavorable outcome.


Assuntos
Hemangioblastoma/cirurgia , Bulbo/cirurgia , Complicações Pós-Operatórias , Adolescente , Adulto , Feminino , Hemangioblastoma/diagnóstico por imagem , Hemangioblastoma/patologia , Humanos , Avaliação de Estado de Karnofsky , Imageamento por Ressonância Magnética , Masculino , Bulbo/diagnóstico por imagem , Bulbo/patologia , Pessoa de Meia-Idade , Resultado do Tratamento
18.
Brain Behav ; 6(2): e00422, 2016 02.
Artigo em Inglês | MEDLINE | ID: mdl-27110445

RESUMO

INTRODUCTION: There is emerging evidence that brain atrophy is a part of the pathophysiology of Multiple Sclerosis (MS) and correlates with several clinical outcomes of the disease, both physical and cognitive. Consequently, brain atrophy is becoming an important parameter in patients' follow-up. Since in clinical practice both 1.5Tesla (T) and 3T magnetic resonance imaging (MRI) systems are used for MS patients follow-up, questions arise regarding compatibility and a possible need for standardization. METHODS: Therefore, in this study 18 MS patients were scanned on the same day on a 1.5T and a 3T scanner. For each scanner, a 3D T1 and a 3D FLAIR were acquired. As no atrophy is expected within 1 day, these datasets can be used to evaluate the median percentage error of the brain volume measurement for gray matter (GM) volume and parenchymal volume (PV) between 1.5T and 3T scanners. The results are obtained with MSmetrix, which is developed especially for use in the MS clinical care path, and compared to Siena (FSL), a widely used software for research purposes. RESULTS: The MSmetrix median percentage error of the brain volume measurement between a 1.5T and a 3T scanner is 0.52% for GM and 0.35% for PV. For Siena this error equals 2.99%. When data of the same scanner are compared, the error is in the order of 0.06-0.08% for both MSmetrix and Siena. CONCLUSIONS: MSmetrix appears robust on both the 1.5T and 3T systems and the measurement error becomes an order of magnitude higher between scanners with different field strength.


Assuntos
Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/instrumentação , Esclerose Múltipla/diagnóstico por imagem , Adulto , Atrofia/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Interpretação de Imagem Assistida por Computador , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Prospectivos , Software , Adulto Jovem
19.
Eur J Obstet Gynecol Reprod Biol ; 194: 212-7, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26448133

RESUMO

OBJECTIVE: To compare the level of pain reported by women by dose of mifepristone, 200 or 600mg, and describe the main factors related to the pain level in the 5 days after a medical abortion. STUDY DESIGN: Observational study in 11 medical centers in France between October 2013 and September 2014. The protocols were 200 or 600mg orally mifepristone on day 1 of the medical abortion and 400, 600 or 800µg orally misoprostol on day 3. Women returned a questionnaire that they completed during 5 days following the abortion; pain was recorded on a visual analog scale (0-10) daily. RESULTS: 453 women were included; the mean age was 29 years (range 18-49 years). Pain was greater with 200 than 600mg mifepristone: 33% of women reported a pain level of ≥8 on day 3 with 200mg as compared with 16% with 600mg. This difference remained after controlling for age, gestational age, gravidity, usual painful menstruation and misoprostol dose. Percentages of symptoms as vomiting or diarrhea were also lower with 600mg mifépristone than 200mg. CONCLUSION: The mean pain severity experienced by women undergoing medical abortion is high; it is higher with a regimen of 200mg mifepristone. The findings emphasize the need to improve analgesic strategies and invite to opt for a protocol of 600mg instead of 200mg mifepristone.


Assuntos
Abortivos Esteroides/administração & dosagem , Aborto Induzido/efeitos adversos , Mifepristona/administração & dosagem , Dor Pós-Operatória/etiologia , Dor Abdominal/tratamento farmacológico , Dor Abdominal/etiologia , Abortivos não Esteroides/administração & dosagem , Adolescente , Adulto , Fatores Etários , Analgésicos/uso terapêutico , Feminino , França , Número de Gestações , Humanos , Pessoa de Meia-Idade , Misoprostol/administração & dosagem , Medição da Dor , Dor Pós-Operatória/tratamento farmacológico , Gravidez , Inquéritos e Questionários , Adulto Jovem
20.
J Neuroradiol ; 42(3): 162-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25454398

RESUMO

PURPOSE: To compare magnetic resonance angiography (MRA) at 3 Tesla (3T) and digital subtraction angiography (DSA) for the detection and characterization of unruptured intracranial aneurysms (UIA). MATERIALS AND METHODS: This study has been approved by our local ethical committee. From February to August 2010, 40 consecutive patients with UIA contemporarily underwent MRA at 3T including time-of-flight (TOF-MRA) and contrast enhanced (CE-MRA) techniques and DSA. MR images were independently reviewed by 3 radiologists and DSA images were reviewed by 2 radiologists together. Interobserver and intertechnique agreements were assessed for aneurysm detection and characterization including maximal diameter, neck width and the presence of a bleb or a branch arising from the sac. RESULTS: DS angiography revealed 56 aneurysms. Mean sensitivity and positive predictive value of MRA were 91.4% and 93.4% respectively. For UIA < 3 mm and those ≥ 3 mm, MRA had a mean sensitivity of 74.1% and 100% respectively. Intertechnique and interobserver agreements were substantial for the measurement of UIA maximal diameter (mean κ, 0.607 and 0.601 respectively) and were moderate and fair for neck width measurement respectively (mean κ, 0.456 and 0.285 respectively). For bleb detection, intertechnique and interobserver agreements were fair and slight respectively (mean κ, 0.312 and 0.116 respectively) whereas both were slight for detection of branches arising from the sac (mean κ, 0.151 and 0.070 respectively). CONCLUSION: MR angiography at 3T has a high sensitivity for the detection of UIA. However, it remains significantly inferior to DSA for morphological characterization of UIA.


Assuntos
Angiografia Digital/métodos , Aneurisma Intracraniano/diagnóstico , Angiografia por Ressonância Magnética/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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