Diffusion-weighted MRI and PET/CT reproducibility in epithelial ovarian cancers during neoadjuvant chemotherapy

PurposeTo investigate the reproducibility of diffusion-weighted (DW) MRI and ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG)-Positron emission tomography/CT (PET/CT) in monitoring response to neoadjuvant chemotherapy in epithelial ovarian cancer.Materials and methodsTen women (median age, 67 years; range: 41.8–77.3 years) with stage IIIC-IV epithelial ovarian cancers were included in this prospective trial (NCT02792959) between 2014 and 2016. All underwent initial laparoscopic staging, four cycles of carboplatine-paclitaxel-based chemotherapy and interval debulking surgery. PET/CT and DW-MRI were performed at baseline (C0), after one cycle (C1) and before surgery (C4). Two nuclear physicians and two radiologists assessed five anatomic sites for the presence of ≥ 1 lesion. Target lesions in each site were defined and their apparent diffusion coefficient (ADC), maximal standardized uptake value (SUV-max), SUV-mean, SUL-peak, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were monitored (i.e., 10 patients × 5 sites × 3 time-points). Their relative early and late changes were calculated. Intra/inter-observer reproducibilities of qualitative and quantitative analysis were estimated with Kappa and intra-class correlation coefficients (ICCs).ResultsFor both modalities, inter- and intra-observer agreement percentages were excellent for initial staging but declined later for DW-MRI, leading to lower Kappa values for inter- and intra-observer variability (0.949 and 1 at C0, vs. 0.633 and 0.643 at C4, respectively) while Kappa values remained > 0.8 for PET/CT. Inter- and intra-observer ICCs were > 0.75 for SUV-max, SUL-peak, SUV-mean and their change regardless the time-point. ADC showed lower ICCs (range: 0.013–0.811). ANOVA found significant influences of the evaluation time, the measurement used (ADC, SUV-max, SUV-mean, SUV-max, SUL-peak, MTV or TLG) and their interaction on ICC values (P = 0.0023, P< 0.0001 and P =0.0028, respectively).ConclusionWhile both modalities demonstrated high reproducibility at baseline, only SUV-max, SUL-peak, SUV-mean and their changes maintained high reproducibility during chemotherapy.     

NUDT15 is a key genetic factor for prediction of hematotoxicity in pediatric patients who received a standard low dosage regimen of 6-mercaptopurine

6-Mercaptopurine (6-MP) is commonly used for treatment of acute lymphoblastic leukemia (ALL). The incidence of hematotoxicity caused by this drug is quite high in Asians even using a standard low dosage regimen. The present study was aimed to elucidate the impact of thiopurine S-methyltransferase (TPMT), a nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15), inosine triphosphatase (ITPA) and ATP Binding Cassette Subfamily C Member 4 (ABCC4) polymorphisms on hematotoxicity in pediatric patients who received a standard low starting dose of 6-MP. One hundred and sixty-nine pediatric patients were enrolled and their genotypes were determined. Patients who carried NUDT15¹3 and NUDT15¹2 genotypes were at a 10–15 fold higher risk of severe neutropenia than those of the wild-type during the early months of the maintenance phase. Risk of neutropenia was not significantly increased in patients with other NUDT15 variants as well as in patients with TPMT, ITPA or ABCC4 variants. These results suggest that NUDT15 polymorphisms particularly, NUDT15¹3 and NUDT15¹2, play major roles in 6-MP-induced severe hematotoxicity even when using a standard low dosage of 6-MP and genotyping of these variants is necessary in order to obtain precise tolerance doses and avoid severe hematotoxicity in pediatric patients.     

Applications of geospatial analyses in health research among homeless people: A systematic scoping review of available evidence

BackgroundUnequal housing access resulted in more than 150 million homeless people worldwide, with millions more expected to be added every year due to the ongoing climate-related crises. Homeless population has a counterproductive effect on the social, psychological integration efforts by the community and exposure to other severe health-related issues. Geographic Information Systems (GIS) have long been applied in urban planning and policy, housing and homelessness, and health-related research.MethodsWe used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method to systematically review 24 articles collected from multiple databases (n = 10) that focused on health-related issues among homeless people and used geospatial analysis techniques in their research.ResultsOur findings indicated a geographic clustering of case study locations– 26 out of the 31 case study sites are from the USA and Canada. Studies used spatial analysis techniques to identify hotspots, clusters and patterns of patient location and population distribution. Studies also reported relationships among the location of homeless shelters and substance use, discarded needles, different infectious and non-infectious disease clusters.ConclusionMost studies were restricted in analyzing and visualizing the patterns and disease clusters; however, geospatial analyses techniques are useful and offer diverse techniques for a more sophisticated understanding of the spatial characteristics of the health issues among homeless people. Better integration of GIS in health research among the homeless would help formulate sensible policies to counter health inequities among this vulnerable population group.     

Lateral Lymph Nodes in Rectal Cancer: Do we all Think the Same? A Review of Multidisciplinary Obstacles and Treatment Recommendations

Lateral lymph nodes in low, locally advanced, rectal cancer have proven implications for local recurrence rates, which increase drastically in the presence of persistently enlarged lateral lymph nodes. These clinical implications warrant a thorough understanding of lateral nodal disease with awareness and knowledge from all three specialties involved – radiology, radiation oncology, and surgery – to ensure proper treatment. Relevant literature for each specialty, including all current guidelines and perspectives, were examined. Variations in definitions and treatment paradigms were evaluated. There is still no consensus for the standardized treatment of lateral nodal disease. Each discipline works according to their own available evidence, but relevant data are scarce. Current international guidelines and standard recommendations for the diagnostics and treatment of lateral lymph nodes are lacking. This results in differing perspectives and interpretations between the disciplines which can lead to challenging communication in an area where multidisciplinary collaboration is essential. This review addresses this by presenting the current evidence, perspectives and practices of each specialty and makes suggestions for each phase of the diagnostic and treatment process for patients with lateral nodal disease. By doing this, steps are taken toward achieving international consensus, and multidisciplinary collaboration.     

Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

应用磁共振波谱研究针刺合谷穴前额叶神经递质Glu与GABA相关性＊

目的 探讨手针针刺健康受试者右侧合谷穴，前额叶Glu⁺、Glx⁺及GABA⁺浓度变化差异及相关性，从兴奋和抑制性神经递质关系方面初步探讨针刺效应的脑机制。方法 录入健康志愿者76名，随机接受手针及纤毛针两种刺激，并采集刺激前和刺激时BOLD功能磁共振脑成像（fMRI）及磁共振波谱（MRS）数据，分析手针和纤毛针组刺激前与刺激时Glu⁺、Glx⁺、GABA⁺浓度差异及相关性，以及Glu⁺、Glx⁺与GABA⁺浓度的相关性。结果 手针及纤毛针组间和组内各亚组（依据不同BOLD信号）针刺前与针刺时Glu⁺、Glx⁺、GABA⁺浓度差异无统计学意义（P均>0.05）。但手针组整组的Glu⁺、Glx⁺、GABA⁺，零、负激活亚组的Glu⁺、Glx⁺和零激活GABA⁺针刺前与针刺时浓度呈正相关（P均<0.05）。针刺前手针组整组、零、负激活亚组的Glu⁺、Glx⁺均与GABA⁺呈正相关q（P均<0.05）；纤毛针组整组、正、负激活亚组Glu⁺、Glx⁺均与GABA⁺及零激活Glu⁺与GABA⁺均呈正相关（P均<0.05）；针刺时手针组整组、负激活亚组Glu⁺与GABA⁺呈正相关，零激活亚组Glx⁺与GABA⁺呈正相关（P均<0.05）。结论 针刺前与针刺时Glu⁺、Glx⁺与GABA⁺多呈正相关，可作为针刺脑机制研究的神经递质观察指标。     

结直肠癌肿瘤组织中TMPRSS4、c-Met、KIF18A表达水平与其病理特性和生存状态的关系

目的探讨结直肠癌肿瘤组织中跨膜丝氨酸蛋白酶4(TMPRSS4)、间质表皮转化因子(c-Met)、驱动蛋白家族成员18A(KIF18A)表达水平与其病理特性和生存状态的关系。方法选取该院于2015年3月至2017年6月确诊的102例结直肠癌患者作为研究对象,比较癌变组织和癌旁组织TMPRSS4、c-Met阳性率及KIF18A水平的差异,不同病理状态及生存状态患者的TMPRSS4、c-Met阳性率及KIF18A水平的差异,分析患者的病理状态及生存状态与TMPRSS4、c-Met阳性率和KIF18A水平的相关性。结果癌变组织TMPRSS4、c-Met阳性率及KIF18A水平明显高于癌旁组织(P<0.05);不同性别、年龄患者TMPRSS4、c-Met阳性率及KIF18A水平比较差异均无统计学意义(P>0.05),而不同病程、TNM分期、临床分型患者之间比较差异有统计学意义(P<0.05);通过对患者的随访,生存患者61例,死亡患者41例,生存组TMPRSS4、c-Met阳性率及KIF18A水平明显低于死亡组(P<0.05);患者的TNM分期、临床分型、病程及生存状态与TMPRSS4、c-Met阳性率及KIF18A的水平呈正相关(r=0.165~0.998,P<0.05)。结论结直肠癌肿瘤组织中TMPRSS4、c-Met阳性率及KIF18A水平与其病理特性和生存状态存在一定的相关性,可作为结直肠癌患者诊断辅助参考之一。