Use of Patient and Disease Characteristics as Predictive Indicators of Rituximab Infusion-Related Reactions in Adult Malignant Hematology Patients at an Academic Medical Center

BackgroundIdentification of predictive indicators for rituximab infusion-related reactions (R-IRRs) may allow clinicians to modify treatment plans for patients at high risk of reaction to reduce incidence. Use of predictive indicators would significantly improve the patient experience, reduce hospital resource utilization, and decrease infusion chair time.Patients and MethodsThis retrospective, single-center, observational study evaluated 173 adult malignant hematology patients who received their first dose of rituximab inpatient between July 31, 2015 and July 31, 2018. Patients were excluded if they received prior rituximab, and/or induction chemotherapy, or were pregnant at the time of exposure. The primary outcome was the overall incidence of R-IRRs during the study period. The secondary outcomes were associations between specific patient and disease characteristics and R-IRRs.ResultsOf the 173 patients evaluated, 109 met inclusion criteria and 64 were excluded. The overall incidence of R-IRRs was 31 (28.4%) of 109. The following patient and disease characteristics were significantly associated with R-IRRs on univariate analysis: higher actual body weight (P = .04), diagnosis (P = .01), lower hemoglobin (P = .02), and bone marrow involvement (P = .001). In a confirmatory stepwise regression model, higher actual body weight (P = .01) and bone marrow involvement (P = .003) were positively associated with R-IRRs.ConclusionActual body weight and bone marrow involvement may be utilized as potential predictive indicators of R-IRRs. Further study is needed to validate these indicators and determine appropriate utilization in practice.     

A Positive Feedback Loop Between Th17 Cells and Dendritic Cells in Patients with Endplate Inflammation

Background: Endplate inflammation remains a difficult disease to treat, in part due to its unclear pathology. Previous experiments showed that patients with idiopathic inflammation presented a systemic upregulation of Th17 cells. Here, we investigated how this change might affect the inflammatory environment in endplate inflammation.

Methods: Peripheral blood was obtained from patients and healthy controls, and Th17 cells were examined.Results: Th17 cells significantly increased the differentiation of CD11c+ and DC-SIGN+ dendritic cells (DCs) from circulating monocytes in the absence of exogenous stimulation as well as in the presence of LPS stimulation. Th17 cells also increased CD80 and CD86 expression by DCs. Importantly, although Th17 cells from both healthy controls and patients with endplate inflammation could induce CD11c, DC-SIGN, CD80, and CD86 expression, Th17 cells from patients with endplate inflammation showed significantly more potent capacity. Both contact-dependent and IL-17-dependent mechanisms were employed by Th17 cells, since blocking cell-to-cell contact significantly inhibited Th17-mediated differentiation of CD11c+ DCs, and neutralization of IL-17 reduced the expression of CD80 and CD86. Strikingly, DCs following incubation with Th17 cells, but not the DCs derived directly from monocytes without Th17 cells, could significantly promote the expression of IL-17 from naive CD4+ T cells.

Conclusions: These results demonstrated that Th17 cells from patients with endplate inflammation could potently induce the differentiation and activation of DCs that preferentially promoted IL-17 response in a positive feedback loop.     

结核特异性抗原与CD4+T细胞计数比值对AIDS合并肺结核的辅助诊断价值

目的:评价结核特异性抗原(TBAg)与CD4⁺T淋巴细胞(简称“CD4”)计数的比值(TBAg/CD4)对AIDS合并活动性肺结核(PTB)的辅助诊断价值。方法:采用前瞻性研究的方法,参照入组标准纳入2018年1月至2020年12月苏州市第五人民医院收治的262例疑似活动性PTB的AIDS患者,并将患者分为AIDS+PTB组(152例)和AIDS组(110例)。采集患者入院次日清晨静脉血进行干扰素体外释放酶联免疫法(TB-IGRA)、血常规、CD4检测,比较两组间TBAg水平和TBAg/CD4比值的差异。以临床诊断为参考标准,评价TB-IGRA检测AIDS合并PTB的效能,并以受试者工作特征曲线(ROC曲线)下面积(AUC)确定诊断效能最佳的检测指标。结果:以临床诊断为参考标准,TB-IGRA检测AIDS合并活动性PTB的敏感度和特异度分别为53.95%(82/152)和75.45%(83/110)。TB-IGRA检测AIDS+PTB组的TBAg、TBAg/CD4水平[分别为92.51(-68.20,906.10)pg/ml和1.01(0.00,10.12)]均明显高于AIDS组[分别为85.20(-33.80,801.30)pg/ml和0.11(0.00,2.07)],对照培养管抗原浓度[529.50(12.50,1160.50)pg/ml]明显低于AIDS组[694.50(29.90,990.00)pg/ml],差异均有统计学意义(Z=-3.481、-9.557、3.289,P值均<0.001)。ROC曲线分析显示,对照培养管抗原浓度、TBAg、TBAg/CD4对诊断AIDS合并活动性PTB的AUC值分别为0.718、0.637和0.842;当TBAg/CD4的临界值为0.592时,约登指数最大,其敏感度为88.10%,特异度为77.10%。结论:相较于AIDS患者,AIDS合并PTB患者的TBAg和TBAg/CD4水平均明显升高,尤以TBAg/CD4诊断价值高,结合患者免疫状态的影响,认为TBAg/CD4对AIDS合并PTB患者具有一定辅助诊断价值。     

电离辐射对小鼠骨髓造血干/祖细胞中CD47表达的影响

探讨X射线全身照射后小鼠骨髓造血干/祖细胞（HSCs/HPCs）损伤和其中CD47表达水平的变化，初步阐明CD47在HSCs/HPCs电离辐射损伤中发挥的作用。     

膜辅助蛋白CD46 rs1970530遗传变异对肝癌发病风险的影响

背景与目的：膜辅助蛋白CD46可保护宿主细胞免受补体依赖的细胞毒性作用，研究表明，CD46可能作为肝细胞癌（hepatocellular carcinoma，HCC）患者的潜在生物标志物。探讨CD46基因表达及启动子区遗传变异与HCC发病风险的关系。方法：通过基因表达谱交互分析（gene expression profiling interactive analysis，GEPIA）在线网站分析HCC组织和正常肝组织CD46表达的差异；2011—2015年在华北理工大学附属唐山市工人医院和华北理工大学附属唐山市人民医院经病理学检查确诊且未经放化疗的240例HCC患者作为病例组，对照组为同时期入院体检的500名健康人群。采用聚合酶链反应-限制性片段长度多态性分析（polymerase chain reaction-restriction fragment length polymorphism，PCR-RFLP）法进行基因分型，检测两组基因型频率和等位基因频率，评估CD46 rs1970530遗传变异与HCC发病风险的关系。结果：CD46在HCC组织与正常组织中的表达差异有统计学意义（P<0.05）。经非条件logistic回归分析发现，CD46 rs1970530至少携带一个G等位基因型在病例组及对照组之间差异有统计学意义（OR=0.666，95% CI：0.448~0.990，P<0.05）；两组间等位基因G频率差异有统计学意义（OR=0.689，95% CI：0.478~0.994，P<0.05）。分层分析结果显示，至少携带一个G等位基因者可降低高年龄组（>60岁）（P=0.048）和男性（P=0.023）人群的HCC发病风险，在女性和低年龄组（≤60岁）中差异无统计学意义（P>0.05）。按吸烟状态进行分层分析，rs1970530变异与HCC易感性无明显关联（P>0.05）。结论：HCC中CD46基因高表达及CD46 rs1970530遗传变异影响HCC发病风险。     

Methodological advances in the design of peptide-based vaccines

The tremendous advances in genomics, recombinant DNA technology, bioengineering and nanotechnology, in conjunction with the development of high-end computations, have been instrumental in the process of rational design of peptide-based vaccines. The use of peptide vaccines was limited owing to their inherent instability when systemically administered; however, advanced formulation techniques have been developed for their systemic delivery, thereby overcoming their degradation, clearance, cellular uptake and off-target effects. With the rise of sophisticated immunological predictors and experimental techniques, several methodological advances have occurred in this field. This review examines contemporary methods to identify and optimize epitopes, engineer their immunogenic properties and develop their safe and efficient delivery into the host.     

Temporal changes in extra-axial brain hematoma's signal intensity in magnetic resonance images of trauma patients: A preliminary,technical study

IntroductionDating the exact or estimated time of trauma is an important issue facing forensic medicine. Several clinical and radiological methods were used to achieve this purpose. In the recent study, we aimed to track the changes in the signal intensity of the extra-axial brain hematoma using magnetic resonance imaging (MRI) conventional sequences as well as diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC).Materials and methodsConsidering inclusion and exclusion criteria, all patients with blunt head trauma were involved. After proper management., stabilization, and resuscitation, the participants were assessed using conventional sequences of MRI and DWI twenty-four hours, forty-eight hours, and three weeks after the injury. Temporal changes of signal intensity were compared by Wilcoxon ranged test.ResultsSixteen patients sustaining blunt head trauma were included in this study. The study showed that during the time, diffusion restriction could be seen in an extraaxial hematoma. At the first 24 hours, the signal of hematoma was void in 87.5% of DWI and 100% of ADC. On the second day, they were hypo-signal in 75% of DWI and 100% 0f ADCs, and after three weeks, 100% of cases were hyper-signal in DWI and hypo-signal ADCs.ConclusionThis preliminary study has shown that the DWI can be used to detect and track the extra-axial hematoma. The signal intensity was void during the first twentyfour hours, although it became hypo-signal after 48 hours. Of note, the diffusion restriction is noted after three weeks.