Risk stratification in breast cancer screening: Cost-effectiveness and harm-benefit ratios for low-risk and high-risk women

In mammography screening programmes, women are screened according to a one-size-fits-all principle. Tailored screening, based on risk levels, may lead to a better balance of benefits and harms. With microsimulation modelling, we determined optimal mammography screening strategies for women at lower (relative risk [RR] 0.75) and higher (RR 1.8) than average risk of breast cancer, eligible for screening, using the incremental cost-effectiveness ratio (ICER) of current uniform screening in the Netherlands (biennial [B] 50-74) as a threshold ICER. Strategies varied by interval (annual [A], biennial, triennial [T]) and age range. The number of life-years gained (LYG), breast cancer deaths averted, overdiagnosed cases, false-positive mammograms, ICERs and harm-benefit ratios were calculated. Optimal risk-based screening scenarios, below the threshold ICER of €8883/LYG, were T50-71 (€7840/LYG) for low-risk and B40-74 (€6062/LYG) for high-risk women. T50-71 screening in low-risk women resulted in a 33% reduction in false-positive findings, a similar reduction in costs and improved harm-benefit ratios compared to the current screening schedule. B40-74 in high-risk women led to an increase in screening benefit, compared to current B50-74 screening, but a relatively higher increase in false-positive findings. In conclusion, optimal screening consisted of a longer interval and lower stopping age than current uniform screening for low-risk women, and a lower starting age for high-risk women. Extending the interval for women at lower risk from biennial to triennial screening reduced harms and costs while maintaining most of the screening benefit.     

Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case–control sets from EPIC

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR_1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR_1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR_1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR_1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR_1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.     

A case of Klebsiella pneumoniae spondylitis and bacteremia potentially due to inflammation around a fecalith

We herein report a case of Klebsiella pneumoniae (K. pneumoniae) spondylitis and bacteremia in a 90-year-old man with diabetes mellitus who had undergone sigmoidectomy and had a fecalith. Two months prior to admission, he had received antimicrobial treatment for 2 weeks for K. pneumoniae bacteremia whose entry was unclear and he was readmitted to our hospital owing to fever and stomachache. K. pneumoniae was isolated from two sets of blood cultures, and computed tomography and magnetic resonance imaging revealed inflammation and destruction of the 8th and 9th thoracic vertebra. The diagnosis was spondylodiscitis secondary to K. pneumoniae bacteremia. Although the entry point for K. pneumoniae was unclear, we suggest that inflammation of the mucosa around the fecalith might have caused the Enterobacteriaceae bacteremia.     

A nutraceutical extract from Inula viscosa leaves: UHPLC-HR-MS/MS based polyphenol profile,and antioxidant and cytotoxic activities

Nowadays, advanced extraction techniques and highly sensitive metabolic profiling methods are effectively employed to get new information on plant chemical constituents. Among them wild medicinal plants or their parts, with large and ancient use in folk medicine, are investigated for their potential functional use and cultivation. In this context, Inula viscosa leaves engaged our attention. A simple experimental design, based on Soxhlet extraction and chromatographic fractionation, allowed us to obtain the investigated polyphenol fraction (IvE). UHPLC-HRMS analyses revealed shikimoyl depsides of caffeic acid and unusual dihydrobenzofuran lignans as main secondary metabolites. These compounds, together with cinchonain-type phenols, and hydroxycinnamoyl flavonol glycosides, are reported for the first time in inula. Overall, forty-three secondary metabolites were identified. The extract exerted a remarkable antiradical activity towards DPPH^? and ABTS^+?. Furthermore, it was able to inhibit cell viability and mitochondrial redox activity of neuroblastoma, hepatoblastoma and colon carcinoma cells, whereas it did not affect cell density of HaCaT cells immortalized human keratinocytes. As detected by the oxidant-sensing probe 2′,7′-dichlorodihydrofluorescein diacetate, the inhibitory responses seemed to be related to IvE-induced increase of intracellular reactive oxygen species (ROS). The obtained results highlighted that inula leaves, nowadays even undervalued and unexplored, could be considered a renewable source of nutraceutical compounds.     

乳腺癌21基因检测的研究进展

乳腺癌是一类具有异质性的肿瘤，不同患者的治疗方法和疗效都不相同。尽管目前仍在努力为激素受体（hormone receptor，HR）阳性（+）、人表皮生长因子受体2（human epidermal growth factor receptor 2,HER-2）阴性（-）、淋巴结（axillary lymph node，ALN）阴性（-）的早期乳腺癌患者寻找合适的治疗方法，但其术后是否需要化疗仍然是肿瘤科医生面临的一个难题。以往治疗主要依赖于经典的组织病理学和免疫组织化学技术，随着精准医疗时代的到来，我们需要更定量的诊断方法和合理的个体化治疗。虽然化疗可降低疾病复发风险并提高生存率，但它带来的不良反应事件会降低患者的生活质量，尤其低复发风险（recurrence risk,RS)有可能超过化疗益处。21基因检测不仅可以预测这类早期乳腺癌化疗疗效及评估预后，还可提供精准的个体化治疗方案指导用药，为患者增添信心。本文就乳腺癌21基因检测的研究进展进行综述。     

Addressing risk management difficulties in children with food allergies

Risk is a concept inherent in every medical procedure. It can be defined as the probability of an adverse event in a defined population over a specified period of time. In the frame of food allergy management, it might be related to a diagnostic procedure, a treatment, or the consumption of foods. The risk of an adverse event can also be augmented by individual factors. This rostrum article discusses various aspects faced by children with food allergies in the light of risk, and their practical implications. Identifying personal risks for severe reaction, such as unstable asthma, and correcting them whenever possible also contribute to a reduction of the risk inherent to food allergy. Among the facets discussed, oral food challenges (OFC) are the most common diagnostic procedures implying an inherent risk. The risk of OFCs can be minimized by correct indication and timing of the test, a safe setting, as well as by ensuring that the patient is otherwise well without potential stressor potentially increasing the risk of a more severe reaction. Oral immunotherapy (OIT) has been studied as a potential treatment for increasing the threshold dose for reaction, and thus reducing the risk of accidental reaction. Nevertheless, the procedure is not devoid of risk as the patients may and do often react during the course of the procedure. Ingestion of trace amounts in processed foods, mainly in community settings such as restaurants, schools, or day care, represents a potential risk of reactions, although for a minority of patients. Precautionary allergen labeling (PAL) is a widespread strategy to reduce the potential risk of reactions due to traces. However, PAL is currently inefficient due to inconsistent labeling, also not indicating a clear maximum amount possibly present in the manufactured food. Finally, cost-effectiveness needs to be considered in risk management, as many risk reduction procedures are clearly not cost-effective.     

Baseline immune activation as a risk factor for the onset of depression during interferon-alpha treatment.

BACKGROUND: Major depression has been associated cross-sectionally with increased cell-mediated immune activation but causality has been difficult to establish. This study prospectively investigated the hypothesis that baseline level of immune activation predicts the development of depression during interferon-alpha (IFN-alpha) treatment. METHODS: Sixteen hepatitis C patients without psychiatric disorder underwent IFN-alpha treatment. Proinflammatory and anti-inflammatory cytokines were determined before starting treatment. Presence of a major depressive disorder (MDD) was assessed at baseline and several times during treatment. RESULTS: Baseline soluble interleukin-2 receptor (sIL-2r), interleukin-6 (IL-6), and interleukin-10 (IL-10) concentrations were significantly increased in the five subjects that developed MDD during treatment compared with those that did not, with standardized effect sizes of 1.08, 1.16, and 1.25, respectively, controlling for marijuana use, cigarette smoking, and baseline level of depressive symptoms. CONCLUSIONS: Results suggest that increased immune activation, rather than an epiphenomenon, is a causal risk factor for the development of MDD.     

肝移植术后糖尿病危险因素分析

目的 探讨肝移植术后糖尿病（PTDM）的发生及发展的危险因素。方法 回顾性分析98例肝移植受者的临床资料。根据其肝移植术后是否发生糖尿病，分为糖尿病组（36例）和非糖尿病组（62例）。以术前和术后可能的9个危险因素作为分析指标，进行这些指标的单因素分析和χ^2检验。结果 在对两组患者的年龄、乙型肝炎病毒（HBV）感染情况、有无肝硬化及肝硬化的程度、术前糖耐量情况、免疫抑制剂的选择及其血药浓度、激素的使用时间的比较分析中发现：术前肝硬化患者PTDM的发生率明显高于无肝硬化者；肝硬化失代偿期患者PTDM的发生率高于代偿期。术前糖耐量异常的患者PTDM的发生率明显高于糖耐量正常者。激素半年内撤离的患者PTDM的发生率明显低于半年内未撤离者。而两组患者的年龄、HBV的感染情况、免疫抑制剂的选择及其血药浓度相比较，差异均无统计学差异。结论 肝硬化、尤其是肝硬化失代偿期，糖耐量异常，长期使用激素是PTDM发生的危险因素。     

hs-CRP、TAS联合血脂检测在早老性痴呆症诊断中的应用研究

[目的]研究超敏C反应蛋白（hs-CRP）、总抗氧化状态（TAS）联合血脂检测在早老性痴呆症诊断中的应用价值：[方法]选择浦东新区精神卫生中心早老性痴呆专科门诊患者54例，作超敏C反应蛋白、总抗氧化状态与血脂检测。[结果]与对照组比较，实验组hs-CRP、TAS差异非常显著，t1=4．55，t2=2．79，P1〈0．001，P2〈0．01；血脂中甘油三酯、低密度脂蛋白胆固醇、载脂蛋白B、Lp（a）差异显著；t1=3.01，P1〈0．01，t2=2．21，P2〈0．05，t3=2．64，P3〈0．01，t4=1．91，P4〈0．05。[结论]超敏C反应蛋白、总抗氧化状态联合血脂（甘油三酯、低密度脂蛋白胆固醇、载脂蛋白B、Lp（a））检测对实验室诊断早老性痴呆症具有较好敏感性和特异性，临床应用前景乐观。