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1.
Radiother Oncol ; 164: 66-72, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34537290

RESUMO

BACKGROUND AND PURPOSE: Radio(chemo)therapy is standard in the adjuvant treatment of glioblastoma. Inevitably, brain tissue surrounding the target volume is also irradiated, potentially causing acute and late side-effects. Diffusion imaging has been shown to be a sensitive method to detect early changes in the cerebral white matter (WM) after radiation. The aim of this work was to assess possible changes in the mean diffusivity (MD) of WM after radio(chemo)therapy using Diffusion-weighted imaging (DWI) and to compare these effects between patients treated with proton and photon irradiation. MATERIALS AND METHODS: 70 patients with glioblastoma underwent adjuvant radio(chemo)therapy with protons (n = 20) or photons (n = 50) at the University Hospital Dresden. MRI follow-ups were performed at three-monthly intervals and in this study were evaluated until 33 months after the end of therapy. Relative white matter MD changes between baseline and all follow-up visits were calculated in different dose regions. RESULTS: We observed a significant decrease of MD (p < 0.05) in WM regions receiving more than 20 Gy. MD reduction was progressive with dose and time after radio(chemo)therapy (maximum: -7.9 ± 1.2% after 24 months, ≥50 Gy). In patients treated with photons, significant reductions of MD in the entire WM (p < 0.05) were seen at all time points. Conversely, in proton patients, whole brain MD did not change significantly. CONCLUSIONS: Irradiation leads to measurable MD reduction in white matter, progressing with both increasing dose and time. Treatment with protons reduces this effect most likely due to a lower total dose in the surrounding white matter. Further investigations are needed to assess whether those MD changes correlate with known radiation induced side-effects.

2.
MAGMA ; 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33786695

RESUMO

OBJECTIVE: Brain atrophy has the potential to become a biomarker for severity of radiation-induced side-effects. Particularly brain tumour patients can show great MRI signal changes over time caused by e.g. oedema, tumour progress or necrosis. The goal of this study was to investigate if such changes affect the segmentation accuracy of normal appearing brain and thus influence longitudinal volumetric measurements. MATERIALS AND METHODS: T1-weighted MR images of 52 glioblastoma patients with unilateral tumours acquired before and three months after the end of radio(chemo)therapy were analysed. GM and WM volumes in the contralateral hemisphere were compared between segmenting the whole brain (full) and the contralateral hemisphere only (cl) with SPM and FSL. Relative GM and WM volumes were compared using paired t tests and correlated with the corresponding mean dose in GM and WM, respectively. RESULTS: Mean GM atrophy was significantly higher for full segmentation compared to cl segmentation when using SPM (mean ± std: ΔVGM,full = - 3.1% ± 3.7%, ΔVGM,cl = - 1.6% ± 2.7%; p < 0.001, d = 0.62). GM atrophy was significantly correlated with the mean GM dose with the SPM cl segmentation (r = - 0.4, p = 0.004), FSL full segmentation (r = - 0.4, p = 0.004) and FSL cl segmentation (r = -0.35, p = 0.012) but not with the SPM full segmentation (r = - 0.23, p = 0.1). CONCLUSIONS: For accurate normal tissue volume measurements in brain tumour patients using SPM, abnormal tissue needs to be masked prior to segmentation, however, this is not necessary when using FSL.

3.
Eur J Paediatr Neurol ; 29: 2-13, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33162302

RESUMO

Over the past few years, increasing interest in the role of autoantibodies against myelin oligodendrocyte glycoprotein (MOG-abs) as a new candidate biomarker in demyelinating central nervous system diseases has arisen. MOG-abs have now consistently been identified in a variety of demyelinating syndromes, with a predominance in paediatric patients. The clinical spectrum of these MOG-ab-associated disorders (MOGAD) is still expanding and differs between paediatric and adult patients. This first part of the Paediatric European Collaborative Consensus emphasises the diversity in clinical phenotypes associated with MOG-abs in paediatric patients and discusses these associated clinical phenotypes in detail. Typical MOGAD presentations consist of demyelinating syndromes, including acute disseminated encephalomyelitis (ADEM) in younger, and optic neuritis (ON) and/or transverse myelitis (TM) in older children. A proportion of patients experience a relapsing disease course, presenting as ADEM followed by one or multiple episode(s) of ON (ADEM-ON), multiphasic disseminated encephalomyelitis (MDEM), relapsing ON (RON) or relapsing neuromyelitis optica spectrum disorders (NMOSD)-like syndromes. More recently, the disease spectrum has been expanded with clinical and radiological phenotypes including encephalitis-like, leukodystrophy-like, and other non-classifiable presentations. This review concludes with recommendations following expert consensus on serologic testing for MOG-abs in paediatric patients, the presence of which has consequences for long-term monitoring, relapse risk, treatments, and for counselling of patient and families. Furthermore, we propose a clinical classification of paediatric MOGAD with clinical definitions and key features. These are operational and need to be tested, however essential for future paediatric MOGAD studies.


Assuntos
Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/classificação , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/diagnóstico , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/imunologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Adolescente , Autoanticorpos/imunologia , Autoantígenos/imunologia , Criança , Feminino , Humanos , Masculino , Fenótipo
4.
Eur J Paediatr Neurol ; 29: 32-40, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33183945

RESUMO

There is increasing knowledge on the role of antibodies against myelin oligodendrocyte glycoprotein (MOG-abs) in acquired demyelinating syndromes and autoimmune encephalitis in children. Better understanding and prediction of outcome is essential to guide treatment protocol decisions. Therefore, this part of the Paediatric European Collaborative Consensus provides an oversight of existing knowledge of clinical outcome assessment in paediatric MOG-ab-associated disorders (MOGAD). The large heterogeneity in disease phenotype, disease course, treatment and follow-up protocols is a major obstacle for reliable prediction of outcome. However, the clinical phenotype of MOGAD appears to be the main determinant of outcome. Patients with a transverse myelitis phenotype in particular are at high risk of accruing neurological disability (motor and autonomic), which is frequently severe. In contrast, having a single episode of optic neuritis any time during disease course is broadly associated with a lower risk of persistent disability. Furthermore, MOG-ab-associated optic neuritis often results in good functional visual recovery, although retinal axonal loss may be severe. The field of cognitive and behavioural outcome and epilepsy following demyelinating episodes has not been extensively explored, but in recent studies acute disseminated encephalomyelitis (-like) phenotype in the young children was associated with cognitive problems and epilepsy in long-term follow-up. In conclusion, main domains of importance in determining clinical outcome in paediatric MOGAD are visual, motor, autonomic and cognitive function. A standardised evaluation of these outcome domains in all children is of importance to allow adequate rehabilitation and follow-up.


Assuntos
Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/complicações , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/diagnóstico , Glicoproteína Mielina-Oligodendrócito/imunologia , Adolescente , Autoanticorpos/imunologia , Autoantígenos , Criança , Pré-Escolar , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/reabilitação , Progressão da Doença , Feminino , Humanos , Masculino , Fenótipo
5.
Mol Metab ; 41: 101046, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32599075

RESUMO

OBJECTIVE: Cancer cachexia and muscle loss are associated with increased morbidity and mortality. In preclinical animal models, blocking activin receptor (ACVR) ligands has improved survival and prevented muscle wasting in cancer cachexia without an effect on tumour growth. However, the underlying mechanisms are poorly understood. This study aimed to identify cancer cachexia and soluble ACVR (sACVR) administration-evoked changes in muscle proteome. METHODS: Healthy and C26 tumour-bearing (TB) mice were treated with recombinant sACVR. The sACVR or PBS control were administered either prior to the tumour formation or by continued administration before and after tumour formation. Muscles were analysed by quantitative proteomics with further examination of mitochondria and nicotinamide adenine dinucleotide (NAD+) metabolism. To complement the first prophylactic experiment, sACVR (or PBS) was injected as a treatment after tumour cell inoculation. RESULTS: Muscle proteomics in TB cachectic mice revealed downregulated signatures for mitochondrial oxidative phosphorylation (OXPHOS) and increased acute phase response (APR). These were accompanied by muscle NAD+ deficiency, alterations in NAD+ biosynthesis including downregulation of nicotinamide riboside kinase 2 (Nrk2), and decreased muscle protein synthesis. The disturbances in NAD+ metabolism and protein synthesis were rescued by treatment with sACVR. Across the whole proteome and APR, in particular, Serpina3n represented the most upregulated protein and the strongest predictor of cachexia. However, the increase in Serpina3n expression was associated with increased inflammation rather than decreased muscle mass and/or protein synthesis. CONCLUSIONS: We present evidence implicating disturbed muscle mitochondrial OXPHOS proteome and NAD+ homeostasis in experimental cancer cachexia. Treatment of TB mice with a blocker of activin receptor ligands restores depleted muscle NAD+ and Nrk2, as well as decreased muscle protein synthesis. These results indicate putative new treatment therapies for cachexia and that although acute phase protein Serpina3n may serve as a predictor of cachexia, it more likely reflects a condition of elevated inflammation.


Assuntos
Proteínas de Fase Aguda/metabolismo , Músculo Esquelético/metabolismo , NAD/metabolismo , Serpinas/metabolismo , Receptores de Ativinas/antagonistas & inibidores , Receptores de Ativinas/efeitos dos fármacos , Receptores de Ativinas/metabolismo , Ativinas/metabolismo , Ativinas/farmacologia , Proteínas de Fase Aguda/fisiologia , Animais , Caquexia/metabolismo , Caquexia/fisiopatologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Masculino , Camundongos , Mitocôndrias/metabolismo , Músculo Esquelético/fisiologia , Atrofia Muscular/metabolismo , Miostatina/metabolismo , Fosforilação Oxidativa , Serpinas/fisiologia
6.
Eur J Paediatr Neurol ; 26: 29-33, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32115367

RESUMO

PURPOSE: To analyze the association between pubertal stage, menstrual cycle and migraine attacks in girls with migraine. In addition, headache frequency, accompanying symptoms, duration and onset in relation to the specific phase of the cycle were investigated. METHODS: Girls between 7 and 18 years old, diagnosed with headaches that met "International Classification of Headache Disorders II" diagnostic criteria for migraine without aura, kept a daily headache and menstrual cycle diary over 8 weeks. Ovulatory cycles were identified by weekly progesterone saliva tests. RESULTS: 47 girls participated in the study and were divided into three groups according to Tanner stage and onset of regular menstruation: pre- (n = 16), peri- (n = 19) and post-pubertal (n = 12). A significant difference in migraine frequency was found between pre- and post-pubertal girls (p = 0.005). No significant differences with regard to headache characteristics were detected. Interestingly, a higher frequency of attacks in follicular phase occurred compared to luteal phase in peri- and post-pubertal girls (p = 0.030). CONCLUSION: During puberty, migraine patterns in girls change to a typical adult pattern of migraine in a stepwise manner not clearly related to menarche. The first sign of this transition phase could be the higher frequency of migraine attacks in post-pubertal girls.


Assuntos
Transtornos de Enxaqueca , Maturidade Sexual , Adolescente , Criança , Feminino , Humanos , Ciclo Menstrual/fisiologia , Menstruação/fisiologia , Transtornos de Enxaqueca/etiologia , Transtornos de Enxaqueca/fisiopatologia
7.
Patient Educ Couns ; 103(1): 5-14, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31447194

RESUMO

OBJECTIVES: Several concepts on collaboration between patients and healthcare systems have emerged in the literature but there is little consensus on their meanings and differences. In this study, "patient participation" and related concepts were studied by focusing on the dimensions that compose them. This review follows two objectives: (1) to produce a detailed and comprehensive overview of the "patient participation" dimensions; (2) to identify differences and similarities between the related concepts. METHODS: A scoping review was performed to synthesize knowledge into a conceptual framework. An electronic protocol driven search was conducted in two bibliographic databases and a thematic analysis was used to analyse the data. RESULTS: The search process returned 39 articles after exclusion for full data extraction and analysis. Through the thematic analysis, the dimensions, influencing factors and expected outcomes of "patient participation" were determined. Finally, differences between the included concepts were identified. CONCLUSION: This global vision of "patient participation" allows us to go beyond the distinctions between the existing concepts and reveals their common goal to include the patient in the healthcare system. PRACTICE IMPLICATIONS: This scoping review provides useful information to propose a conceptual model of "patient participation", which could impact clinical practice and medical training programs.


Assuntos
Participação do Paciente , Humanos
8.
Eur J Cancer ; 116: 67-76, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31173964

RESUMO

BACKGROUND: Tumour mutational burden (TMB) estimated from whole exome sequencing or comprehensive gene panels has previously been established as predictive factor of response to immune checkpoint inhibitors (ICIs). Its predictive value for the efficacy of concurrent chemoradiation (cCRTX), a potential combination partner of ICI, remains unknown. METHODS: The accuracy of TMB estimation by an in-house 327-gene panel was established in the Cancer Genome Atlas (TCGA) head and neck squamous cell carcinoma (HNSCC) data set. Interference of TMB with outcome after cCRTX was determined in a multicentre cohort of patients with locally advanced HNSCC uniformly treated with cCRTX. Targeted next-generation sequencing was successfully applied in 101 formalin-fixed, paraffin-embedded pretreatment tumour samples. In a subset of cases (n = 40), tumour RNA was used for immune-related gene expression profiling by the nanoString platform. TMB was correlated with TP53 genotype, human papilloma virus (HPV) status, immune expression signatures and survival parameters. Results were validated in the TCGA HNSCC cohort. RESULTS: A high accuracy of TMB estimation by the 327-gene panel was established. High TMB was significantly associated with an increased prevalence of TP53 mutations and immune gene expression patterns unrelated to T cell-inflamed gene expression profiles. Kaplan-Meier analysis revealed significantly reduced overall survival in the patient group with high TMB (hazard ratio for death: 1.79, 95% confidence interval: 1.02-3.14; P = 0.042) which remained significant after correcting for confounding factors in the multivariate model. The prognostic value of TMB was confirmed in the TCGA HNSCC cohort. CONCLUSION: High TMB identifies HNSCC patients with poor outcome after cCRTX who might preferentially benefit from CRTX-ICI combinations.


Assuntos
Quimiorradioterapia/métodos , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Feminino , Alemanha , Neoplasias de Cabeça e Pescoço/imunologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Mutação , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Transcriptoma , Resultado do Tratamento
9.
Clin Radiol ; 74(6): 489.e1-489.e7, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30954236

RESUMO

AIM: To test a new parameter to assess the position of the fetal cerebellar vermis in the posterior fossa (PF) using intrauterine magnetic resonance imaging (MRI). MATERIALS AND METHODS: The angle between the cerebellar vermis and the internal occipital crest (vermian-crest angle, VCA) was assessed retrospectively using MRI in fetuses with and without PF anomalies. Spearman's rank test was used to investigate correlation of the VCA with gestational age (GA). Groups were compared using Student's t-test and the one-way analysis of variance (ANOVA) with the Bonferroni adjustment. Box-and-whisker plots were also used. RESULTS: One hundred and two normal cases were identified. Mean±SD GA at MRI was 26.5±2.8 weeks (range: 22-32 weeks). The VCA was 64.49±11.5° independently of GA (r=0.19; p=0.12). In addition, 30 fetuses at 19-28 weeks were identified with Blake's pouch cyst (BPC; n=5), Dandy-Walker malformation (DWM; n=12), mega cisterna magna (MCM; n=10), and vermian hypoplasia (VH; n=3). The VCA was significantly different in the DWM (p<0.001) and BPC (p<0.001) subgroups, but was not significantly different in cases of VH (p=0.84) and MCM (p=0.95) in comparison with controls. CONCLUSIONS: A new method to assess vermian position within the PF using intrauterine MRI was assessed. In combination with the other existing parameters, it may be helpful for addressing the categorisation of upward rotation of the fetal cerebellar vermis; however, further studies are necessary to strengthen the present findings.


Assuntos
Vermis Cerebelar/diagnóstico por imagem , Vermis Cerebelar/embriologia , Imageamento por Ressonância Magnética/métodos , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Diagnóstico Pré-Natal/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Rotação , Adulto Jovem
11.
Transbound Emerg Dis ; 65(2): e231-e242, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29119682

RESUMO

Tick-borne diseases are considered a major hindrance to the health and productive performance of cattle in Bangladesh. To elucidate the epidemiology of tick-borne pathogens (TBPs) in local cattle, a cross-sectional study was performed in the 12 subdistricts (Upazilas) of Mymensingh district in Bangladesh. Blood samples and ticks were collected from 384 clinically healthy cattle kept by 135 farmers from 96 randomly selected villages. DNA extracted from the blood samples was subsequently screened by polymerase chain reaction (PCR) and a Reverse Line Blot (RLB) hybridization assay using an in-house prepared chemiluminescence solution for the presence of Anaplasma, Ehrlichia, Rickettsia, Babesia and Theileria spp. A total of 2,287 ticks were collected from 232 infested cattle (60.4%, 232/384) and identified morphologically as Rhipicephalus (Boophilus) microplus (n = 1,432, 62.6%) and Haemaphysalis bispinosa (n = 855; 37.4%). The RLB results demonstrated that the majority of the cattle (62.2%) were infected with at least one TBP. Theileria orientalis infections were most common (212/384, 55.2%) followed by infections with Anaplasma bovis (137/384, 35.67%), Anaplasma marginale (16/384, 4.17%), Babesia bigemina (4/384, 1.04%) and Babesia bovis (2/384, 0.52%). A previously uncharacterized Anaplasma sp. (Anaplasma sp. Mymensingh) and Babesia sp. (Babesia sp. Mymensingh), which are genetically closely related to Anaplasma platys and B. bigemina, were detected in 50 of 384 (13.0%) and 1 of 384 (0.3%) of the blood samples, respectively. Key risk factors for the occurrence of T. orientalis, A. marginale and Anaplasma sp. Mymensingh were identified. In conclusion, this study revealed that cattle in Mymensingh district are mainly infested with R. microplus and H. bispinosa ticks and may carry multiple TBPs. In addition, two previously uncharacterized pathogens were detected in the bovine blood samples. The pathogenicity of these species remains to be determined.


Assuntos
Anaplasma/isolamento & purificação , Babesia/isolamento & purificação , Doenças dos Bovinos/epidemiologia , Doenças Transmitidas por Carrapatos/veterinária , Carrapatos , Anaplasma/genética , Animais , Babesia/genética , Técnicas de Tipagem Bacteriana/veterinária , Bangladesh/epidemiologia , Bovinos , Doenças dos Bovinos/microbiologia , Doenças dos Bovinos/parasitologia , Estudos Transversais , Ehrlichia/genética , Ehrlichia/isolamento & purificação , Tipagem de Sequências Multilocus/veterinária , Filogenia , Reação em Cadeia da Polimerase/veterinária , Rickettsia/genética , Rickettsia/isolamento & purificação , Theileria/genética , Theileria/isolamento & purificação , Doenças Transmitidas por Carrapatos/epidemiologia , Doenças Transmitidas por Carrapatos/microbiologia , Doenças Transmitidas por Carrapatos/parasitologia , Carrapatos/microbiologia , Carrapatos/parasitologia
12.
Trials ; 18(1): 608, 2017 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-29262836

RESUMO

BACKGROUND: In early-stage non-small cell lung cancer (NSCLC) without affected lymph nodes detected at staging, surgical resection is still the mainstay of treatment. However, in patients with metastatic mediastinal lymph nodes (pN2) or non-radically resected primary tumors (R1/R2), postoperative radiotherapy (possibly combined with chemotherapy) is indicated. So far, investigations about time factors affecting postoperative radiotherapy have only examined the waiting time defined as interval between surgery and start of radiotherapy, but not the overall treatment time (OTT) itself. Conversely, results from trials on primary radio(chemo)therapy in NSCLC show that longer OTT correlates with significantly worse local tumor control and overall survival rates. This time factor of primary radio(chemo)therapy is thought to mainly be based on repopulation of surviving tumor cells between irradiation fractions. It remains to be elucidated if such an effect also occurs when patients with NSCLC are treated with postoperative radiotherapy after surgery (and chemotherapy). Our own retrospective data suggest an advantage of shorter OTT also for postoperative radiotherapy in this patient group. METHODS/DESIGN: This is a multicenter, prospective randomized trial investigating whether an accelerated course of postoperative radiotherapy with photons or protons (7 fractions per week, 2 Gy fractions) improves locoregional tumor control in NSCLC patients in comparison to conventional fractionation (5 fractions per week, 2 Gy fractions). Target volumes and total radiation doses will be stratified in both treatment arms based on individual risk factors. DISCUSSION: For the primary endpoint of the study we postulate an increase in local tumor control from 70% to 85% after 36 months. Secondary endpoints are overall survival of patients; local recurrence-free and distant metastases-free survival after 36 months; acute and late toxicity and quality of life for both treatment methods. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02189967 . Registered on 22 May 2014.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Fracionamento da Dose de Radiação , Neoplasias Pulmonares/reabilitação , Fótons/uso terapêutico , Terapia com Prótons/métodos , Carcinoma Pulmonar de Células não Pequenas/secundário , Protocolos Clínicos , Intervalo Livre de Doença , Alemanha , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Fótons/efeitos adversos , Pneumonectomia , Polônia , Estudos Prospectivos , Terapia com Prótons/efeitos adversos , Qualidade de Vida , Radioterapia Adjuvante , Projetos de Pesquisa , Fatores de Tempo , Resultado do Tratamento
13.
Arch Gynecol Obstet ; 296(6): 1117-1124, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28993867

RESUMO

PURPOSE: The purpose of our study was to evaluate the outcome of selective pelvic arterial embolisation (PAE) in women with severe postpartum hemorrhage (PPH). METHODS: We performed a retrospective, controlled, single-center cohort study. A total of 16 consecutive women with PPH who underwent therapeutic PAE were included. As historical control group, we included 22 women with similar severity of PPH who were managed without PAE. Outcome measures included necessity of surgical interventions such as postpartum hysterectomy and laparotomy after vaginal delivery, the amount of red blood cell transfusions, and hematologic findings after the procedure. RESULTS: PAE was successful in stopping PPH and preserving the uterus in all 16 women in the study group. No woman in the PAE group required a postpartum hysterectomy, whereas postpartum hysterectomy was unavoidable in two women in the control group. Laparotomy after vaginal delivery was necessary in two women of the group without embolisation. Hematologic parameters after the treatment were better in the PAE group than in the control group, although these differences were only in part statistically significant. There were no unwarranted effects of PAE identifiable in the study group. CONCLUSION: This is the first controlled study assessing the efficacy of PAE for the treatment of PPH. Our data suggest that PAE is effective for the treatment of severe PPH. In view of the lack of complications and unwarranted effects, clinical use of PAE in severe PPH seems justified, particularly in view of the life-threatening condition and the potential to preserve fertility in affected patients. Further evidence from well-designed prospective randomized-controlled trials would be nevertheless desirable in the future.


Assuntos
Embolização Terapêutica/métodos , Artéria Ilíaca , Pelve/irrigação sanguínea , Hemorragia Pós-Parto/terapia , Adulto , Parto Obstétrico , Feminino , Fertilidade , Humanos , Gravidez , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Artéria Uterina , Útero
14.
Ann Oncol ; 28(6): 1230-1242, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28184416

RESUMO

Chordomas are rare, malignant bone tumors of the skull-base and axial skeleton. Until recently, there was no consensus among experts regarding appropriate clinical management of chordoma, resulting in inconsistent care and suboptimal outcomes for many patients. To address this shortcoming, the European Society of Medical Oncology (ESMO) and the Chordoma Foundation, the global chordoma patient advocacy group, convened a multi-disciplinary group of chordoma specialists to define by consensus evidence-based best practices for the optimal approach to chordoma. In January 2015, the first recommendations of this group were published, covering the management of primary and metastatic chordomas. Additional evidence and further discussion were needed to develop recommendations about the management of local-regional failures. Thus, ESMO and CF convened a second consensus group meeting in November 2015 to address the treatment of locally relapsed chordoma. This meeting involved over 60 specialists from Europe, the United States and Japan with expertise in treatment of patients with chordoma. The consensus achieved during that meeting is the subject of the present publication and complements the recommendations of the first position paper.


Assuntos
Cordoma/terapia , Guias de Prática Clínica como Assunto , Humanos , Recidiva Local de Neoplasia
16.
Clin Genet ; 92(1): 86-90, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28075028

RESUMO

The semaphorins constitute a large family of secreted and membrane-associated proteins that regulate many developmental processes, including neural circuit assembly, bone formation and angiogenesis. Recently, bi-allelic loss-of-function variants in SEMA3A (semaphorin 3A) were identified in a single patient with a particular pattern of multiple congenital anomalies (MCA). Using homozygosity mapping combined with exome sequencing, we identified a homozygous SEMA3A variant causing a premature stop codon in an 8 year old boy with the same pattern of MCA. The phenotype of these patients is characterized by postnatal short stature, skeletal anomalies of the thorax, a minor congenital heart or vascular defect, camptodactyly, micropenis, and variable additional anomalies. Motor development is delayed in both patients, and intellectual development is delayed in one patient. Our observation of a second case supports the notion that bi-allelic mutations in SEMA3A cause an autosomal recessive type of syndromic short stature.


Assuntos
Anormalidades Múltiplas/genética , Artrogripose/genética , Nanismo/genética , Semaforina-3A/genética , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/fisiopatologia , Alelos , Artrogripose/complicações , Artrogripose/diagnóstico por imagem , Artrogripose/fisiopatologia , Criança , Pré-Escolar , Nanismo/complicações , Nanismo/diagnóstico por imagem , Nanismo/fisiopatologia , Homozigoto , Humanos , Masculino , Linhagem , Fenótipo
17.
Clin Exp Dermatol ; 42(1): 64-67, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27905128

RESUMO

In 2012, a new Ehlers-Danlos (ED) variant, characterized by severe progressive kyphoscoliosis, neonatal myopathy and hearing loss, with normal urinary lysylpyridinoline to hydroxylysylpyridinoline ratio and most often a recurrent homozygous mutation in the FKBP14 gene, was reported. Because one of the major affected tissues in ED syndrome is the skin, recognition of the cutaneous features of this newly recognized EDS variant is important. We describe the cutaneous phenotype of an adolescent girl harbouring the recurrent homozygous FKBP14 mutation. Distinctive features included molluscoid pseudotumours and multiple isolated comedones. Molluscoid pseudotumours are a characteristic finding in patients with the classic ED variant, but are rarely reported in other variants. We discuss the cutaneous phenotype of FKBP14-deficient EDS and compare it with other kyphoscoliotic variants.


Assuntos
DNA/genética , Síndrome de Ehlers-Danlos/genética , Mutação , Peptidilprolil Isomerase/genética , Pele/patologia , Adolescente , Biópsia , Análise Mutacional de DNA , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/metabolismo , Feminino , Homozigoto , Humanos , Peptidilprolil Isomerase/metabolismo , Fenótipo
18.
Eur J Dent Educ ; 21(1): 37-45, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26642844

RESUMO

INTRODUCTION: Assessment of practical skills in undergraduate dental education has difficulties, including a lack of transparency/objectivity in student evaluations. This prospective study investigated whether agreement between student- and faculty-based assessments increased when students were trained to use the assessment criteria. MATERIALS AND METHODS: Assessment criteria were available for 6 tasks in the Phantom course of Conservative Dentistry: Class II cavity preparation, composite restoration, gold and ceramic partial crown preparation, trepanation and access cavity preparation, and root canal filling. Forty-two students were allocated to three different assessment training groups. Students' self-assessments of practical tests were compared with instructors' assessments, depending on training intensity and task type (Pearson's rho, ANOVA, Tukey's post hoc test, Kruskal-Wallis test). Students/instructors were questioned regarding benefits/drawbacks of the criteria. RESULTS: Student self-assessments showed either consent (24.2%), overestimation (31%) or underestimation (44.8%). Gender differences were negligible. Regarding passing/failing grades, more intensive training yielded significantly increased agreement only for preparation of gold partial crowns (rho = +0.313, P = 0.044). Ratings exhibited significant differences amongst tasks (P = 0.002), for example, trepanation assessment had significantly lower differences than gold or ceramic preparation assessments. These discrepancies decreased with increased training. Students consistently reported benefitting most from learning the criteria for gold preparations, followed by composite and ceramic preparations. They also reported that learning the criteria was beneficial for knowledge transfer/feedback. Instructors rated the criteria as helpful for task evaluation and feedback efficiency. CONCLUSIONS: Pre-defined assessment criteria may increase consistency between student self-assessment and instructor assessment depending on the task, improving transparency and feedback in dental education.


Assuntos
Educação em Odontologia/normas , Avaliação Educacional/métodos , Competência Clínica , Currículo , Educação em Odontologia/métodos , Avaliação Educacional/normas , Docentes de Odontologia , Feminino , Humanos , Masculino , Estudos Prospectivos , Autoavaliação (Psicologia) , Estudantes de Odontologia
19.
Acta Neurol Scand ; 136(1): 59-63, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27726124

RESUMO

OBJECTIVES: Primary familial brain calcification (PFBC) is a rare neurological disease often inherited as a dominant trait. Mutations in four genes (SLC20A2, PDGFB, PDGFRB, and XPR1) have been reported in patients with PFBC. Of these, point mutations or small deletions in SLC20A2 are most common. Thus far, only one large deletion covering entire SLC20A2 and several smaller, exonic deletions of SLC20A2 have been reported. The aim of this study was to identify the causative gene defect in a Finnish PFBC family with three affected patients. MATERIALS AND METHODS: A Finnish family with three PFBC patients and five unaffected subjects was studied. Sanger sequencing was used to exclude mutations in the coding and splice site regions of SLC20A2, PDGFRB, and PDGFB. Whole-exome (WES) and whole-genome sequencing (WGS) were performed to identify the causative mutation. A SNP array was used in segregation analysis. RESULTS: Copy number analysis of the WGS data revealed a heterozygous deletion of ~578 kb on chromosome 8. The deletion removes the 5' UTR region, the noncoding exon 1 and the putative promoter region of SLC20A2 as well as the coding regions of six other genes. CONCLUSIONS: Our results support haploinsufficiency of SLC20A2 as a pathogenetic mechanism in PFBC. Analysis of copy number variations (CNVs) is emerging as a crucial step in the molecular genetic diagnostics of PFBC, and it should not be limited to coding regions, as causative variants may reside in the noncoding parts of known disease-associated genes.


Assuntos
Encefalopatias/genética , Calcinose/genética , Deleção de Genes , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/genética , Região 5'-Flanqueadora , Encefalopatias/diagnóstico , Calcinose/diagnóstico , Variações do Número de Cópias de DNA , Exoma , Feminino , Heterozigoto , Humanos , Masculino , Linhagem , Mutação Puntual
20.
Br J Pharmacol ; 173(17): 2657-68, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27391165

RESUMO

BACKGROUND AND PURPOSE: 4-Methyl-N-methylcathinone (mephedrone) is a synthetic stimulant that acts as a substrate-type releaser at transporters for dopamine (DAT), noradrenaline (NET) and 5-HT (SERT). Upon systemic administration, mephedrone is metabolized to several phase I compounds: the N-demethylated metabolite, 4-methylcathinone (nor-mephedrone); the ring-hydroxylated metabolite, 4-hydroxytolylmephedrone (4-OH-mephedrone); and the reduced keto-metabolite, dihydromephedrone. EXPERIMENTAL APPROACH: We used in vitro assays to compare the effects of mephedrone and synthetically prepared metabolites on transporter-mediated uptake and release in HEK293 cells expressing human monoamine transporters and in rat brain synaptosomes. In vivo microdialysis was employed to examine the effects of i.v. metabolite injection (1 and 3 mg·kg(-1) ) on extracellular dopamine and 5-HT levels in rat nucleus accumbens. KEY RESULTS: In cells expressing transporters, mephedrone and its metabolites inhibited uptake, although dihydromephedrone was weak overall. In cells and synaptosomes, nor-mephedrone and 4-OH-mephedrone served as transportable substrates, inducing release via monoamine transporters. When administered to rats, mephedrone and nor-mephedrone produced elevations in extracellular dopamine and 5-HT, whereas 4-OH-mephedrone did not. Mephedrone and nor-mephedrone, but not 4-OH-mephedrone, induced locomotor activity. CONCLUSIONS AND IMPLICATIONS: Our results demonstrate that phase I metabolites of mephedrone are transporter substrates (i.e. releasers) at DAT, NET and SERT, but dihydromephedrone is weak in this regard. When administered in vivo, nor-mephedrone increases extracellular dopamine and 5-HT in the brain whereas 4-OH-mephedrone does not, suggesting the latter metabolite does not penetrate the blood-brain barrier. Future studies should examine the pharmacokinetics of nor-mephedrone to determine its possible contribution to the in vivo effects produced by mephedrone.


Assuntos
Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Metanfetamina/análogos & derivados , Animais , Células Cultivadas , Células HEK293 , Humanos , Masculino , Metanfetamina/química , Metanfetamina/metabolismo , Ratos , Ratos Sprague-Dawley
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