A diagnostic ceiling for exome sequencing in cerebellar ataxia and related neurological disorders

Genetic ataxias are associated with mutations in hundreds of genes with high phenotypic overlap complicating the clinical diagnosis. Whole‐exome sequencing (WES) has increased the overall diagnostic rate considerably. However, the upper limit of this method remains ill‐defined, hindering efforts to address the remaining diagnostic gap. To further assess the role of rare coding variation in ataxic disorders, we reanalyzed our previously published exome cohort of 76 predominantly adult and sporadic‐onset patients, expanded the total number of cases to 260, and introduced analyses for copy number variation and repeat expansion in a representative subset. For new cases (n = 184), our resulting clinically relevant detection rate remained stable at 47% with 24% classified as pathogenic. Reanalysis of the previously sequenced 76 patients modestly improved the pathogenic rate by 7%. For the combined cohort (n = 260), the total observed clinical detection rate was 52% with 25% classified as pathogenic. Published studies of similar neurological phenotypes report comparable rates. This consistency across multiple cohorts suggests that, despite continued technical and analytical advancements, an approximately 50% diagnostic rate marks a relative ceiling for current WES‐based methods and a more comprehensive genome‐wide assessment is needed to identify the missing causative genetic etiologies for cerebellar ataxia and related neurodegenerative diseases.     

Invasive breast cancer: Current perspectives and emerging views

Invasive breast cancer constitutes a heterogeneous group of tumors. They comprise various histological types that differ in clinical presentation, imaging features, histopathological characteristics, biomarker profiles, prognostic and predictive parameters. The current classification of invasive breast cancer is based primarily on histopathological features. Invasive carcinoma of no special type accounts for the majority, with some rare entities also being described. With recent research and advances, there are emerging concepts, including new genetic insights of invasive breast cancer and the role of the stromal microenvironment. With greater understanding of the pathogenesis of invasive breast cancer, changes based on the correlation of histologic and genetic findings have been incorporated in the latest World Health Organization classification of breast tumors. Medullary carcinomas are subsumed as invasive carcinoma of no special type with basal‐like and medullary features, regarded as part of the spectrum of tumor infiltrating lymphocyte‐rich breast cancers. Tall cell carcinoma with reversed polarity is proposed as a distinct entity in recognition of unique IDH2 mutations. This article reviews conventional prognostic parameters, new histological entities, and updates on breast cancer classification, with inclusion of some genetic insights into breast cancer and the role of tumor infiltrating lymphocytes.     

Combining real-time elastography with fine-needle aspiration biopsy to identify malignant thyroid nodules

ObjectivesTo evaluate the diagnostic performance of real-time elastography (RTE) combined with fine-needle aspiration (FNA) biopsy in identifying malignant thyroid nodules.MethodsThis was a single-centre, retrospective study and involved patients who had underogone partial or total thyroidectomy from 01 January 2014 to 31 December 2018 at our centre. Eligible patients were at least18 years of age, had reliable grayscale ultrasound imaging results, a RTE evaluation and had undergone a FNA biopsy.ResultsData were available from 437 patients. A high RTE score was a significant independent risk factors for malignancy. RTE plus FNA biopsy increased diagnostic accuracy compared with either method alone and the sensitivity and specificity of the combined model were 86% and 78%, respectively.ConclusionsThe combination of RTE imaging with FNA biopsy improves the diagnostic performance in differentiating benign and malignant thyroid nodules.     

基于MEMS传感器的可穿戴式老年人跌倒监测系统的设计

为了缩短老年人跌倒后的救助时间和提高安全保障,我们设计了一种基于加速度和角速度传感器的跌倒监测装置。该装置结合机械微电子系统(microelectro mechanical system,MEMS)传感器、数字信号处理及无线传输技术应用于智能手机上。为区分人体跌倒事件和日常行为,结合人体三轴加速度和角速度联合对跌倒事件进行判断,通过大量实验选取合适阈值。针对老年人的生活特点,数据通过蓝牙装置发送至手机上进行处理,通过手机语音报警、手机GPS定位系统和短信通知医院和用户监护人,使得老年人跌倒后能够在第一时间获得救治,减小伤害。经过大量的实验测试结果统计,相比较于传统的三轴加速度判断跌倒事件,结合三轴加速度和加速度联合判断使该系统的准确率从84.29%提高至100%。结果表明:基于MEMS传感器的可穿戴式跌倒监测系统具有便捷、准确、功耗低的特点,能够准确监测出跌倒事件并进行报警。     

血清糖化白蛋白水平升高对糖尿病视网膜病变的诊断价值

目的:分析血清糖化白蛋白(GA)水平升高对2型糖尿病(T2DM)视网膜病变(DR)患者的诊断效能。方法:T2DM患者120例,依据是否合并DR将其分为DR组(50例)和非DR组,即T2DM组(70例)。液态酶法测定血清GA,液相色谱法测定全血HbA1c,比较两组GA和HbA1c水平差异及其对DR诊断的敏感度、特异度、阳性似然比和阴阳性预测值,分析GA和HbA1c与DR危险性的关系。结果:DR组GA、HbA1c水平(25.11±6.50%和9.38±1.77%)较T2DM组(21.21±4.50%和8.71±1.31%)明显升高(P0.05)。GA和HbA1cROC曲线下面积最大值分别为0.68和0.61,对应的诊断DR的cut off值分别为24.00%和9.35%,GA诊断DR灵敏度为62.00%,高于HbA1c的38.00%(P0.05),GA诊断DR的特异度、阴阳性预测值略优于HbA1c,但差异无统计学意义(P0.05)。GA诊断DR的阳性似然比为2.71,优于HbA1c的1.48。Logistic回归分析,GA回归系数的Waldχ2值为7.488(P0.05),其致DR的危险因子(OR)为1.16;HbA1c的Waldχ2为0.226(P0.05)。结论:DR患者GA水平明显高于非DR患者,是DR的危险因素;GA24.00%可作为DR的诊断指征。     

超声显像在脐尿管囊肿病灶中的特点及其诊断价值研究

目的：探讨超声显像在脐尿管囊肿病灶中的特点,研究其诊断价值。方法：分析观察24例脐尿管囊肿超声声像图表现,和手术结果做一对比。结果：24例患者经手术证实都为脐尿管囊肿,其中单纯囊肿16例,超声诊断符合率75％,单纯囊肿中单发单纯囊肿12例,超声诊断符合率最高,达到100％,其超声特点,在脐部至膀胱尖中间的腹壁内显示类圆形无回声,边界清晰,形态规则,壁薄且光滑,内部透声较好,没有血流信号,并且与膀胱不相通。脐尿管囊肿伴感染患者8例,超声诊断符合率50％。其中4例表现为无回声的囊壁比较厚且不光滑,囊内部呈细密点状低回声,透声性差。另外4例表现为下腹壁内形态不规则的低回声,位置在膀胱尖部与脐之间,界线不清楚,膀胱壁局部较厚。24例患者中,18例病变部位位于脐尿管的中下部,4例于膀胱尖,2例位于脐尿管上部。24例患者中,20例患者超声显示单一个病灶,有4例患者显示多个病灶。结论：通过超声显像,脐尿管囊肿疾病的诊断符合率高,对于合并感染的脐尿管囊肿通过临床观察分析可以提高诊断符合率,在临床诊断中有很高的价值。