Differential sensitivity of von Willebrand factor (VWF) ‘activity’ assays to large and small VWF molecular weight forms: a cross‐laboratory study comparing ristocetin cofactor,collagen‐binding and mAb‐based assays

Summary. Background:  von Willebrand disease (VWD), the most common inherited bleeding disorder, is caused by deficiencies and/or defects in von Willebrand factor (VWF). An effective diagnostic and VWD typing strategy requires plasma testing for factor VIII, and VWF antigen plus one or more VWF ‘activity’ assays. VWF activity is classically assessed by using VWF ristocetin cofactor activity (VWF:RCo), although VWF collagen‐binding (VWF:CB) and VWF mAb‐based (VWF activity [VWF:Act]) assays are used by some laboratories. Objective:  To perform a cross‐laboratory study to specifically evaluate these three VWF activity assays for comparative sensitivity to loss of high molecular weight (HMW) VWF, representing the form of VWF that is most functionally active and that is absent in some types of VWD, namely 2A and 2B. Methods:  A set of eight samples, including six selectively representing stepwise reduction in HMW VWF, were tested by 51 different laboratories using a variety of assays. Results:  The combined data showed that the VWF:CB and VWF:RCo assays had higher sensitivity to the loss of HMW VWF than did the VWF:Act assay. Moreover, within‐method analysis identified better HMW VWF sensitivity of some VWF:CB assays than of others, with all VWF:CB assays still showing better sensitivity than the VWF:Act assay. Differences were also identified between VWF:RCo methodologies on the basis of either platelet aggregometry or as performed on automated analyzers. Conclusions:  We believe that these results have significant clinical implications for the diagnosis of VWD and monitoring of its therapy, as well as for the future diagnosis and therapy monitoring of thrombotic thrombocytopenic purpura.     

Non-Mass Breast Lesions on Ultrasound: Feature Exploration and Multimode Ultrasonic Diagnosis

The aim of this study was to analyze the features of non-mass breast lesions (NMLs) on B-mode ultrasound (US), color Doppler US, strain elastography (SE) and contrast-enhanced ultrasound (CEUS) and to develop a multimode ultrasonic method for NML differentiation. Seventy-one NMLs were included in this retrospective study. Binary logistic regression was used to identify the independent risk factors. Pathology results were used as the standard criterion. Microcalcification on US, high stiffness on SE and hyper-enhanced intensity on CEUS were identified as features correlated with malignancy. A multimode method to evaluate NMLs based on the logistic regression was developed. The sensitivity and specificity for US, US?+?Doppler, US?+?SE, US?+?CEUS and the multimode method were 100% and 29%, 92.5% and 41.9%, 97.5% and 58.1%, 90.0% and 58.1% and 95.0% and 77.4%, respectively. The accuracy of these methods was 69.0%, 70.4%, 80.2%, 76.1% and 87.3%, respectively. The multimode ultrasonic method is simple and exhibited high diagnostic performance, which might be helpful for predicting the potential malignancy of NMLs.     

Hepatocellular carcinoma: Where there is unmet need

Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor most commonly associated with underlying chronic liver disease, especially hepatitis. It is a growing problem in the United States and worldwide. There are two potential ways to prevent HCC. Primary prevention which is based on vaccination or secondary prevention involving agents that slow down carcinogenesis. Several pathways have been thought to play a role in the development of HCC; specifically, those involving vascular endothelial growth factor (VEGF)‐mediated angiogenesis, WNT, phosphatidylinositol 3‐kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR), AMP‐activated protein kinase (AMPK), and c‐MET. Currently, there are only a limited number of drugs which have been proven as effective treatment options for HCC and several clinical trials are testing drugs which target aberrations in the pathways mentioned above. In this review, we discuss currently approved therapies, monotherapies and combination therapy for the treatment of HCC.     

A comparison of two molecular methods for diagnosing leptospirosis from three different sample types in patients presenting with fever in Laos

ObjectivesTo compare two molecular assays (rrs quantitative PCR (qPCR) versus a combined 16SrRNA and LipL32 qPCR) on different sample types for diagnosing leptospirosis in febrile patients presenting to Mahosot Hospital, Vientiane, Laos.MethodsSerum, buffy coat and urine samples were collected on admission, and follow-up serum ∼10 days later. Leptospira spp. culture and microscopic agglutination tests (MAT) were performed as reference standards. Bayesian latent class modelling was performed to estimate sensitivity and specificity of each diagnostic test.ResultsIn all, 787 patients were included in the analysis: 4/787 (0.5%) were Leptospira culture positive, 30/787 (3.8%) were MAT positive, 76/787 (9.7%) were rrs qPCR positive and 20/787 (2.5%) were 16SrRNA/LipL32 qPCR positive for pathogenic Leptospira spp. in at least one sample. Estimated sensitivity and specificity (with 95% CI) of 16SrRNA/LipL32 qPCR on serum (53.9% (33.3%–81.8%); 99.6% (99.2%–100%)), buffy coat (58.8% (34.4%–90.9%); 99.9% (99.6%–100%)) and urine samples (45.0% (27.0%–66.7%); 99.6% (99.3%–100%)) were comparable with those of rrs qPCR, except specificity of 16SrRNA/LipL32 qPCR on urine samples was significantly higher (99.6% (99.3%–100%) vs. 92.5% (92.3%–92.8%), p <0.001). Sensitivities of MAT (16% (95% CI 6.3%–29.4%)) and culture (25% (95% CI 13.3%–44.4%)) were low. Mean positive Cq values showed that buffy coat samples were more frequently inhibitory to qPCR than either serum or urine (p <0.001).ConclusionsSerum and urine are better samples for qPCR than buffy coat, and 16SrRNA/LipL32 qPCR performs better than rrs qPCR on urine. Quantitative PCR on admission is a reliable rapid diagnostic tool, performing better than MAT or culture, with significant implications for clinical and epidemiological investigations of this global neglected disease.     

脂蛋白（a）和胱抑素C联合检测在2型糖尿病中的临床应用效果分析

目的：对胱抑素C和脂蛋白（ a）在2型糖尿病临床诊断治疗中的价值进行分析探讨。方法：对我院收治的2型糖尿病患者和体检中心选取的正常组进行胱抑素C和脂蛋白（ a）检验，采用免疫比浊法进行检测，并将2组检验结果进行比较，分析2组检验结果之间的差异，概括两者在2型糖尿病诊断治疗中的价值。结果：观察组的胱抑素C水平和脂蛋白（ a）水平与健康组之间存在明显差异，其胱抑素C和脂蛋白（a）水平均明显高于健康组，p＜0．05，且胱抑素C与脂蛋白（a）之间呈正相关关系。结论：糖尿病患者的胱抑素C和脂蛋白（ a）水平明显高于正常健康人群，是2型糖尿病临床诊断治疗的重要指标，对其进行联合检测能够有效监测糖尿病发展，预防和控制并发症发生。