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.     

Do social support and community engagement act as mechanisms in the association between neighbourhood income inequality and the mental health of mothers in Calgary,Canada? A mediation analysis

PurposeAccording to the social determinants of health framework, income inequality is a potential risk factor for adverse mental health. However, few studies have explored the mechanisms suspected to mediate this relationship. The current study addresses this gap through a mediation analysis to determine if social support and community engagement act as mediators linking neighbourhood income inequality to maternal anxiety and depressive symptoms within a cohort of new mothers living in the City of Calgary, Canada.MethodsData collected at three years postpartum from mothers belonging to the All Our Families (AOF) cohort were used in the current study. Maternal data were collected between 2012 and 2015 and linked to neighbourhood socioeconomic data from the 2006 Canadian Census. Income inequality was measured using Gini coefficients derived from 2006 after-tax census data. Generalized structural equation models were used to quantify the associations between income inequality and mental health symptoms, and to assess the potential direct and indirect mediating effects of maternal social support and community engagement.ResultsIncome inequality was not significantly associated with higher depressive symptoms (β = 0.32, 95%CI = −0.067, 0.70), anxiety symptoms (β = 0.11, 95%CI = −0.39, 0.60), or lower social support. Income inequality was not associated with community engagement. For the depression models, higher social support was significantly associated with lower depressive symptoms (β = −0.13, 95%CI = −0.15, −0.097), while community engagement was not significantly associated with depressive symptoms (β = 0.059, 95%CI = −0.15, 0.27). Similarly, for the anxiety models, lower anxiety symptoms were significantly associated with higher levels of social support (β = −0.17, 95%CI = −0.20, −0.13) but not with higher levels of community engagement (β = 0.14, 95%CI = −0.14, 0.41).ConclusionThe current study did not find clear evidence for social support or community engagement mediating the relationship between neighbourhood income inequality and maternal mental health. Future investigations should employ a broader longitudinal approach to capture changes in income inequality, potential mediators, and mental health symptomatology over time.     

Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy

1. Download : Download high-res image (268KB)
2. Download : Download full-size image

     

女性致密性骨炎血清骨转换生化标志物水平变化研究

背景 致密性骨炎（OCI）和其他疾病有时难以鉴别，探讨血清骨转换生化标志物可为OCI的鉴别诊断提供依据。 目的 探索女性OCI患者的血清骨转换生化标志物的水平变化及临床意义。 方法 回顾性选取2013年6月至2022年2月在北京积水潭医院门诊及住院诊断为OCI的61例女性患者作为观察组，年龄15~50岁，平均（33.8±6.6）岁，病程2周~15年。选择同期61例女性体检健康者作为对照组，年龄15~48岁，平均（35.6±7.6）岁。比较两组一般临床资料和血清骨转换生化标志物水平，并对血清骨转换生化标志物与病情相关指标进行相关性分析。 结果 观察组血清白蛋白（45.4±2.9）g/L低于对照组（46.5±2.8）g/L（t=2.190，P<0.05）。血清骨转换生化标志物比较结果显示，观察组血清1型胶原羧基末端肽β特殊序列（β-CTX）〔0.28（0.23，0.37）μg/L〕、N-端骨钙素（OC）〔13.1（11.2，16.2）μg/L〕、25-羟维生素D3〔25-（OH）VD3〕〔（14.1±5.1）μg/L〕低于对照组〔0.36（0.29，0.48）μg/L，15.6（13.7，17.3）μg/L，（17.5±6.6）μg/L〕（Z=-2.983、-3.255，t=3.081，P<0.05）。长病程亚组OC水平〔14.6（12.4，18.5）μg/L〕高于短病程亚组〔11.7（10.2，14.0）μg/L〕（Z=-2.407，P<0.05）。多孕亚组β-CTX〔0.25（0.22，0.32）μg/L〕、OC水平〔12.2（10.3，15.0）μg/L〕低于非多孕亚组〔0.33（0.26，0.44）μg/L、13.4（12.0，18.8）μg/L〕（Z=-2.486、-1.897，P<0.05）。相关性分析显示，观察组血清1型前胶原氨基端延长肽（tP1NP）与妊娠次数、生产次数均呈负相关（rs=-0.276、-0.298，P<0.05），OC与体质指数（BMI）、视觉模拟评分法（VAS）评分、妊娠次数均呈负相关（rs=-0.284、-0.374、-0.360，P<0.05），25-（OH）VD3水平与BMI呈正相关（rs=0.275，P<0.05）。 结论 女性OCI患者血清OC、β-CTX水平明显降低，可为鉴别其他疾病提供依据；血清OC水平可以反映OCI患者的严重程度，同时OC水平与患者妊娠次数相关；tP1NP与妊娠次数、生产次数相关。     

China special issue on gastrointestinal tumors-Radiological features of pathological complete response in mismatch repair deficient colorectal cancer after neoadjuvant PD-1 blockade: A post hoc analysis of the PICC phase II trial

Neoadjuvant programmed cell death protein 1 (PD-1) blockade exhibits promising efficacy in patients with mismatch repair deficient (dMMR) colorectal cancer (CRC). However, discrepancies between radiological and histological findings have been reported in the PICC phase II trial (NCT 03926338). Therefore, we strived to discern radiological features associated with pathological complete response (pCR) based on computed tomography (CT) images. Data were obtained from the PICC trial that included 36 tumors from 34 locally advanced dMMR CRC patients, who received neoadjuvant PD-1 blockade for 3 months. Among the 36 tumors, 28 (77.8%) tumors achieved pCR. There were no statistically significant differences in tumor longitudinal diameter, the percentage change in tumor longitudinal diameter from baseline, primary tumor sidedness, clinical stage, extramural venous invasion status, intratumoral calcification, peritumoral fat infiltration, intestinal fistula and tumor necrosis between the pCR and non-pCR tumors. Otherwise, tumors with pCR had smaller posttreatment tumor maximum thickness (median: 10 mm vs 13 mm, P = .004) and higher percentage decrease in tumor maximum thickness from baseline (52.9% vs 21.6%, P = .005) compared to non-pCR tumors. Additionally, a higher proportion of the absence of vascular sign (P = .003, odds ratio [OR] = 25.870 [95% CI, 1.357-493.110]), nodular sign (P < .001, OR = 189.000 [95% CI, 10.464-3413.803]) and extramural enhancement sign (P = .003, OR = 21.667 [2.848-164.830]) was observed in tumors with pCR. In conclusion, these CT-defined radiological features may have the potential to serve as valuable tools for clinicians in identifying patients who have achieved pCR after neoadjuvant PD-1 blockade, particularly in individuals who are willing to adopt a watch-and-wait strategy.     

Seroprevalence and trends of transfusion transmissible infections among retrospective blood donors in Western Azerbaijan Regional Blood Transfusion Center,Iran: A ten-years evaluation

Transfusion transmissible infections (TTIs) have been a public health challenge for the accessibility, quality and safety of blood transfusion. The present study aimed to consider the prevalence and the trends of hepatitis B virus (HBV), hepatitis C virus (HCV), Human T-cell leukemia virus type 1 (HTLV-1), human immunodeficiency virus (HIV) and syphilis across the ten years among retrospective blood donors. A retrospective investigation of blood donors’ data covering the period from 22 May 2009 to 22 May 2019 was done. Data was accumulated and analyzed from Blood Transfusion Center records, pertaining to all donors who were screened for various TTIs using respective immunological techniques. Out of the 682,171 screened donors in the 2009–2019 study period, 2470 (0.36 %) were infected with at least one infectious agent. The overall prevalence of HBV, HCV, HTLV-1, HIV and syphilis were 1700 (0.25 %), 184 (0.027 %), 335 (0.05 %), 4 (0.0.05 %) and 247 (0.036 %), respectively. The study showed male dominated donor pool (96.79 %) with higher prevalence (0.34 %) of TTIs compared to female donors (0.02 %) with 3.21 % population. Despite the low prevalence of TTIs in our study, HBV, HCV, syphilis and HIV have remained a big threat to safe blood transfusion in Iran. Strict adherence to selection criteria, algorithm of donor screening, use of highly sensitive and specific methods for detection of TTIs, regular consultation and health education programs, prevention and sanitization strategies to reduce the risk of TTIs are recommended to reduce the risk of TTIs and ensure the safety of blood transfusion for recipient.