Mesenchymal neoplasms with NTRK and other kinase gene alterations

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.     

Treatment of multiple adjacent RT 1 gingival recessions with the modified coronally advanced tunnel (MCAT) technique and a collagen matrix or palatal connective tissue graft: 9-year results of a split-mouth randomized clinical trial

Clinical Oral Investigations - To evaluate t he long-term outcomes following treatment of RT 1 multiple adjacent gingival recessions (MAGR) using the modified coronally advanced tunnel (MCAT) with...     

CD19 + CD21lo/neg cells are increased in systemic sclerosis-associated interstitial lung disease

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21^lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21^lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21^lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21^lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.

     

Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma

Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.     

基于CiteSpace可视化分析代谢组学在中医药领域的研究现状及趋势＊

目的 应用可视化方法分析代谢组学在中医药领域的现状及趋势。方法 检索中国知网数据库（CNKI）和Web of Science 核心合集数据库2021年3月15日之前收录的中医药领域代谢组学研究的相关文献，应用CiteSpace软件对纳入的文献进行关键词、作者、研究机构等内容进行可视化分析。结果 共纳入中文文献247篇，英文文献350篇。文献数量在波动中迅速上升。中、英文文献作者合作网络显示，张爱华是中医药领域代谢组学研究发文量最多的作者，并形成了核心研究团队。发文机构显示，中国医学科学院是该领域的重要研究机构，机构间合作紧密。中、英文文献关键词分析显示，研究内容主要集中在核磁共振、代谢标记物、冠心病、质谱技术、代谢通路等相关领域。结论 中医药领域代谢组学研究的热点主要为中医药治疗代谢性疾病的机制研究。研究趋势为卵泡代谢组学研究及中药有效成分的研究。     

北京市三级甲等医院结直肠癌患者就医流向规律分析

目的 分析不同特征的结直肠癌患者就医行为选择在中医院（含中西医结合医院）、西医院及肿瘤专科医院间的差异，为合理引导结直肠癌患者适宜就医及制订相关政策提供依据。方法 收集北京地区2018年1月-2019年12月17家三级甲等医院21894例首诊结直肠癌成年住院患者的病案首页数据，采用EmpowerStats 2.0对数据进行描述性分析。结果 21894例结直肠癌患者中就诊于中医院的有862例（3.93%），西医院的有8723例（39.85%），肿瘤专科医院的有12309例（56.22%）。对于不同医疗机构，男性占比均大于女性，58-68岁患者占比最大。且结直肠癌患者年龄、医疗付款方式及肿瘤分期在不同医疗机构间的分布存在差异（P<0.001）。西医院及肿瘤专科医院结直肠癌Ⅲ期患者占比最大，而就诊于中医院患者中结直肠癌Ⅳ期最多。从地域分布来看，异地就诊比例（57.32%）大于本地，且就诊于肿瘤专科医院的患者中73.66%来自外地。患者来源前三名分别是北京市、河北省及内蒙古自治区。而在北京市内，西医院患者主要来源于朝阳区、海淀区及西城区，中医院患者主要来源于海淀区、朝阳区及丰台区，肿瘤专科医院则主要来源于朝阳区、海淀区及丰台区。结论 应大力倡导年轻以及早期结直肠癌患者向中医院分流，充分施展中医药在结直肠癌患者中的治疗优势；发挥三级医院带动作用，建立对口帮扶医院，减少不必要的跨省流动及提倡结直肠癌的早筛早治，以降低结直肠癌死亡率。