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1.
Kinase alterations are increasingly recognised as oncogenic drivers in mesenchymal tumours. Infantile fibrosarcoma and the related renal tumour, congenital mesoblastic nephroma, were among the first solid tumours shown to harbour recurrent tyrosine kinase fusions, with the canonical ETV6::NTRK3 fusion identified more than 20 years ago. Although targeted testing has long been used in diagnosis, the advent of more robust sequencing techniques has driven the discovery of kinase alterations in an array of mesenchymal tumours. As our ability to identify these genetic alterations has improved, as has our recognition and understanding of the tumours that harbour these alterations. Specifically, this study will focus upon mesenchymal tumours harbouring NTRK or other kinase alterations, including tumours with an infantile fibrosarcoma-like appearance, spindle cell tumours resembling lipofibromatosis or peripheral nerve sheath tumours and those occurring in adults with a fibrosarcoma-like appearance. As publications describing the histology of these tumours increase so, too, do the variety kinase alterations reported, now including NTRK1/2/3, RET, MET, RAF1, BRAF, ALK, EGFR and ABL1 fusions or alterations. To date, these tumours appear locally aggressive and rarely metastatic, without a clear link between traditional features used in histological grading (e.g. mitotic activity, necrosis) and outcome. However, most of these tumours are amenable to new targeted therapies, making their recognition of both diagnostic and therapeutic import. The goal of this study is to review the clinicopathological features of tumours with NTRK and other tyrosine kinase alterations, discuss the most common differential diagnoses and provide recommendations for molecular confirmation with associated treatment implications. 相似文献
2.
Michels Guido Horn Rudolf Helfen Andreas Hagendorff Andreas Jung Christian Hoffmann Beatrice Jaspers Natalie Kinkel Horst Greim Clemens-Alexander Knebel Fabian Bauersachs Johann Busch Hans-Jörg Kiefl Daniel Spiel Alexander O. Marx Gernot Dietrich Christoph F. 《Der Anaesthesist》2022,71(4):307-310
Die Anaesthesiologie - 相似文献
3.
背景:原发性线粒体病具有高度的临床和遗传异质性,其中周围神经是线粒体病的常见受累器官之一。
目的:总结COX20基因变异相关周围神经病的临床表型及遗传学特征。
设计:病例系列报告。
方法:回顾性收集2018年5月至2020年5月复旦大学附属儿科医院诊治的COX20基因变异相关周围神经病患儿的临床资料,总结其临床表现、基因检测结果及治疗效果,并以“COX20”、“线粒体复合物Ⅳ缺乏症(Complex Ⅳ deficiency)”为关键词检索中英文数据库。检索时间均为从建库至2021年12月。总结已报道COX20基因变异与临床表型的关系。
主要结局指标:临床表型和COX20基因变异位点。
结果:4例患儿纳入分析,男、女各2例,其中3例自幼运动发育落后。4例均在儿童期起病,均以行走不稳为首发症状。肌电图均提示多发性周围神经损害改变,感觉神经轴索受累为主。4例患儿均携带COX20基因复合杂合变异,包括错义变异2个,无义变异和移码变异各1个,其中移码变异c.262delG(p.E88Kfs*35)尚未见报道。文献复习目前共报道COX基因变异18个家系22例患儿(包括本文病例),起病中位年龄为5(1.0~17)岁,22例均以行走困难或步态不稳起病,11例(50.0%)有精神运动发育迟滞,病程中14例(63.6%)出现构音障碍,14例(63.6%)出现肌力下降和/或足部畸形,8例(36.4%)出现共济失调,6例(27.3%)出现肌张力障碍,5例(22.7%)存在认知倒退等。21例患儿行神经传导及肌电图检查,19例(90.5%)提示多发性周围神经病变。头颅(18例)及脊髓(10例)MR检查提示,脊髓萎缩4例(40%),小脑萎缩4例(22.2%)。9例患儿已无法独立行走,丧失独立行走能力中位年龄为10(7~21)岁。目前共报道9个变异位点,4种变异类型,其中错义变异5个,剪切变异2个,无义变异和移码变异各1个。
结论:COX20基因变异患者多早期起病,以周围神经系统病变为主要表现,可合并构音障碍、共济失调、肌张力障碍、认知倒退等,病情逐渐进展,致残率高。COX20基因变异类型以错义变异最常见。 相似文献
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6.
Victoria L. Parker Matthew C. Winter John A. Tidy Barry W. Hancock Julia E. Palmer Naveed Sarwar Baljeet Kaur Katie McDonald Xianne Aguiar Kamaljit Singh Nick Unsworth Imran Jabbar Allan A. Pacey Robert F. Harrison Michael J. Seckl 《International journal of cancer. Journal international du cancer》2023,152(5):986-997
Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus. 相似文献
7.
Vilar-Compte Mireya Gaitán-Rossi Pablo Félix-Beltrán Lucía Bustamante Arturo V. 《Journal of immigrant and minority health / Center for Minority Public Health》2022,24(1):65-77
Journal of Immigrant and Minority Health - COVID-19 has disproportionally affected underrepresented minorities (URM) and low-income immigrants in the United States. The aim of the study is to... 相似文献
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A Coupled FEM-BEM Approach for the Solution of the Free-Boundary Axi-Symmetric Plasma Equilibrium Problem 下载免费PDF全文
M. Bonotto D. Abate P. Bettini & F. Villone 《Communications In Computational Physics》2022,31(1):27-59
In this paper we present a coupled Finite Element Method – Boundary Element Method (FEM-BEM) approach for the solution of the free-boundary axi-symmetric
plasma equilibrium problem. The proposed method, obtained from an improvement
of the Hagenow-Lackner coupling method, allows to efficiently model the equilibrium
problem in unbounded domains by discretizing only the plasma region; the external
conductors can be modelled either as 2D or 3D models, according to the problem of interest. The paper explores different iterative methods for the solution of the nonlinear
Grad-Shafranov equation, such as Picard, Newton-Raphson and Newton-Krylov, in order to provide a robust and reliable tool, able to handle large-scale problems (e.g. high
resolution equilibria). This method has been implemented in the FRIDA code (FRee-boundary Integro-Differential Axisimmetric – https://github.
om/matteobonotto/
FRIDA), together with a suitable Adaptive Integration Technique (AIT) for the computation of the source term. FRIDA has been successfully tested and validated against
experimental data from RFX-mod device, and numerical equilibria of an ITER-like device. 相似文献