滤泡辅助性T细胞和滤泡调节性T细胞在骨肉瘤患者中的数量变化及临床意义

目的探讨滤泡辅助性T细胞(TFH)和滤泡调节性T细胞(TFR)在骨肉瘤患者外周血中的数量变化及与预后的关系。方法收集2015年1月至2018年12月20例骨肉瘤患者和20例健康体检者的静脉血,采用流式细胞术检测骨肉瘤患者和健康体检者外周血循环TFH细胞和TFR细胞频率,分析骨肉瘤患者不同年龄段、不同性别以及不同分期上述指标及TFH/TFR细胞频率比值。将外周血循环TFH/TFR细胞频率比值按中位值对骨肉瘤患者进行分层,并根据随访数据分析总生存期(OS)。结果流式细胞术检测结果显示,20例骨肉瘤患者外周血TFH细胞频率[(6.916±1.778)%vs.(2.310±0.874)%,P=0.004)]和TFR细胞频率[(3.016±0.760)%vs.(0.472±0.174)%,P=0.002)]均显著高于健康体检者。骨肉瘤患者TFH/TFR细胞频率比值为2.679±1.246,低于健康体检者的5.830±2.464(P=0.005)。10~25岁患者的外周血TFH细胞和TFR细胞频率明显高于其他年龄段(P<0.05),Ⅲ期患者外周血TFH细胞和TFR细胞频率明显高于Ⅰ期和Ⅱ期患者(P<0.05)。男性和女性骨肉瘤患者外周血TFH细胞和TFR细胞频率的差异无统计学意义(P>0.05)。以20例骨肉瘤患者外周血循环TFH/TFR细胞频率比值的中位数2.362为界值,分为低比值组(≤2.362)和高比值组(>2.362)各10例。20例骨肉瘤患者的中位OS为27个月。其中低比值组中位OS为19个月,低于高比值组的32个月,差异有统计学意义(P=0.036)。结论在骨肉瘤致病过程中,TFH细胞和TFR细胞频率显著升高,与年龄和分期有关。     

Considerations for Treatment-free Remission in Patients With Chronic Myeloid Leukemia: A Joint Patient–Physician Perspective

Treatment-free remission (TFR) after discontinuation of tyrosine kinase inhibitor therapy is now an emerging treatment goal for patients with chronic myeloid leukemia, who have achieved a deep and stable response to treatment. Although guidance is now available, patients’ questions regarding this progressive concept have yet to be addressed. The overall aim of this European Steering Group is a patient-centered approach that educates patients on their treatment options, including TFR, facilitates better patient–physician relationships, and meets patients’ emotional and psychological needs. The present report outlines 5 key topic areas on discontinuing tyrosine kinase therapy and the implications of TFR for patient–physician consideration: what TFR is; when TFR is appropriate; which patients might and might not be eligible for TFR; and patients’ considerations for discontinuing therapy, such as tyrosine kinase withdrawal syndrome, potential psychological implications, molecular recurrence, and repeat treatment. This Steering Group advocates that patients with chronic myeloid leukemia should have access to high-quality, frequent molecular monitoring and be treated in a specialist center with appropriate medical and psychological support. As patient concerns with attempting TFR become forefront in patient–physician discussions, a greater number of eligible patients might be willing to discontinue therapy.     

The cost of relapse in patients with schizophrenia in the European SOHO (Schizophrenia Outpatient Health Outcomes) study

Background

Relapse in schizophrenia is one of the greatest burdens of the illness.

Aims

To estimate the costs associated with relapse in a pan-European naturalistic setting.

Method

The SOHO study is a 3-year, prospective, observational study of 10,972 outpatients with schizophrenia across 10 European countries. The cost of resource use (inpatient stay, day care, psychiatrist visits and medication) for those who ever relapsed in three years was compared to those who never relapsed. One-year costs for both groups were also compared for a more stringent comparison. The analyses were adjusted for patient characteristics and took account of non-normality of the cost data by using a log-link function. UK unit costs were applied to resource use. The analysis was repeated after multiple imputation for missing data.

Results

Costs incurred by patients who ever relapsed (£14,055) during three years were almost double to those incurred by patients who never relapsed (£7417). 61% of the cost difference was accounted for by hospital stay. The impact of relapse was even greater in the 1-year cost comparison. Results from the additional analysis with imputed missing data remained largely consistent.

Conclusions

Our findings confirm the significant economic burden of relapse, and show such costs were mainly due to hospital stay. Nevertheless, the use of UK unit costs requires caution when interpreting this costing in the context of a specific country, as resource use and their associated costs will differ by country.     

Disparate phenotypic expression of ALAS2 R452H (nt 1407 G --> A) in two brothers, one with severe sideroblastic anemia and iron overload, hepatic cirrhosis, and hepatocellular carcinoma

We report the case of a man with severe X-linked sideroblastic anemia, severe iron overload, and hepatic cirrhosis who died of hepatocellular carcinoma. Evaluation of family members using DNA sequencing revealed that he was hemizygous for the novel ALAS2 mutation R452H (exon 9; nt 1407 G --> A). The proband's brother, an ALAS2 R452H hemizygote, had mild anemia and mild iron overload. Four female relatives were ALAS2 R452H heterozygotes, but they had mild or no anemia and no iron overload. Sequencing of TFR2, HFE, FPN1 (SLC40A1), HAMP, HJV, and the erythrocyte pyruvate kinase genes of family members was also performed. We thus detected the novel TFR2 missense mutation I449V (exon 10; nt 1345 A --> G) in the proband's wife and daughter, neither of whom had anemia or iron overload. Possible explanations for the disparate red blood cell and iron phenotypes of the proband and his family members are discussed.     

Polymorphisms in Iron Homeostasis Genes and Urinary Cadmium Concentrations among Nonsmoking Women in Argentina and Bangladesh

Background: Cadmium (Cd) is a human toxicant and carcinogen. Genetic variation might affect long-term accumulation. Cd is absorbed via iron transporters.Objectives: We evaluated the impact of iron homeostasis genes [divalent metal transporter 1 (SLC11A2), transferrin (TF), transferrin receptors (TFR2 and TFRC), and ferroportin (SLC40A1)] on Cd accumulation.Methods: Subjects were nonsmoking women living in the Argentinean Andes [n = 172; median urinary Cd (U-Cd) = 0.24 µg/L] and Bangladesh (n = 359; U-Cd = 0.54 µg/L) with Cd exposure mainly from food. Concentrations of U-Cd and Cd in whole blood or in erythrocytes (Ery-Cd) were measured by inductively coupled plasma mass spectrometry. Fifty polymorphisms were genotyped by Sequenom. Gene expression was measured in whole blood (n = 72) with Illumina DirectHyb HumanHT-12 v4.0.Results: TFRC rs3804141 was consistently associated with U-Cd. In the Andean women, mean U-Cd concentrations were 22% (95% CI: –2, 51%), and they were 56% (95% CI: 10, 120%) higher in women with GA and AA genotypes, respectively, relative to women with the GG genotype. In the Bangladeshi women, mean U-Cd concentrations were 22% (95% CI: 1, 48%), and they were 58% (95% CI: –3, 157%) higher in women with GA and AA versus GG genotype, respectively [adjusted for age and plasma ferritin in both groups; p_trend = 0.006 (Andes) and 0.009 (Bangladesh)]. TFRC expression in blood was negatively correlated with plasma ferritin (r_S = –0.33, p = 0.006), and positively correlated with Ery-Cd (significant at ferritin concentrations of < 30 µg/L only, r_S = 0.40, p = 0.046). Rs3804141 did not modify these associations or predict TFRC expression. Cd was not consistently associated with any of the other polymorphisms evaluated.Conclusions: One TFRC polymorphism was associated with urine Cd concentration, a marker of Cd accumulation in the kidney, in two very different populations. The consistency of the findings supports the possibility of a causal association.     

转铁蛋白和转铁蛋白受体对慢性肾功能衰竭的临床意义

目的　探讨血清转铁蛋白受体对慢性肾功能衰竭 (CRF)的临床意义。方法　采用免疫比浊法测定 2 0例健康体检者和 82例慢性肾功能衰竭者血清中转铁蛋白、转铁蛋白受体和前白蛋白含量 ,并将治疗前后进行对比分析。结果　慢性肾功衰中透析组的TFR ,sTFR和PAB与对照组比较存在显著性差异 (P <0 0 1)与非透析组比较存在显著性差异 (P <0 0 5 )。结论　TFR、sTFR、PAB可以作为CRF诊断和判断治疗效果的有效辅助指标     

单克隆抗体与阿霉素偶联物介入治疗胃癌

目的:了解转铁蛋白受体单克隆抗体与阿霉素偶联,制成阿霉素单抗偶联物,分别通过胃镜下瘤体直接注射,动脉插管灌注和静脉输注三种方法治疗对胃癌的疗效 方法:采用30%氧化葡聚糖偶联法,将转铁蛋白受体单克隆抗体与阿霉素通过葡聚糖Dextran-10按一定程序偶联.将阿霉素单抗偶联物分别通过胃镜下注射、动脉插管灌注和静脉输注三种方法治疗胃癌共同46例 结果:胃镜下注射、动脉插管灌注和静脉输注三种方法的总缓解率分别为46.67%(7/15),56.25%(9/16)和33.33%(5/15)出现毒副反应的例数分别3例,5例和6例.统计学比较,胃镜下注射组疗效与动脉插管灌注组无明显差异(p>0 05),比静脉输注组效果好(p<0.05),而毒副作用方而则前组明显少于后两组(P<0.05)结论:胃镜下瘤体直接注射与动脉插管灌注单抗偶联化疗药物治疗胃癌效果好,毒副反应少     

癌性贫血患者 Hep、EPO、HJV、FPN 和 TFR2的表达特点及其意义

目的：研究癌性贫血患者中铁调素（Hepcidin）、促红细胞生成素（EPO）、铁调素调节蛋白（HJV）、膜转铁蛋白（FPN）和转铁蛋白受体2（TFR2）的表达特点及其意义。方法应用双抗夹心生物素-亲和素-酶联免疫吸附试验（ABC-ELISA）检测51例癌性贫血患者和51例癌无贫血患者的血清 Hep、EPO、HJV、FPN、TFR2及铁蛋白,并分析它们之间的相互关系。结果（1）贫血组 Hepcidin、TFR2、EPO 均高于无贫血组（均 P ＜0．05）,而贫血组的 HJV 及 FPN 明显低于无贫血组（均 P ＜0．05）。（2）贫血组铁蛋白与 Hepcidin 及 TFR2呈负相关（r＝-0．38及-0．22,均 P ＜0．05）。EPO、Hepcidin 及 TFR2与血红蛋白呈负相关（r ＝-0．328、-0．211及-0．295,均 P ＜0．05）。结论癌性贫血的发生是一个复杂的过程,在此过程中 EPO 的水平升高但相对不足,TFR2、HJV、Hepci-din、FPN 的表达异常导致的铁失利用是其中的关键因素。