多参数信息融合实现非脑电的睡眠结构分期

目前临床睡眠分析的主要手段是多导睡眠图（Polysomnograph,PSG）,用仪器记录被测者整晚的脑电、眼动电和颏肌电等生理参数,计算机进行自动睡眠分期,再由技术人员依据国际标准进行校正.几十年来PSG保持着睡眠分期金标准的地位.提出在不使用脑电的条件下,利用较易获得的心动周期、呼吸、体动等基本生理参数,提取其中与睡眠过程及其变化有关的规律和信息,建立知识规则库,采用不确定推理的证据理论进行多参数睡眠信息融合计算,实现睡眠结构分期.50余例与PSG对照试验结果表明：醒睡的平均符合率达90%以上,基本睡眠结构的平均符合率达75%以上,证明该技术达到了应用的要求.     

Limiting factors for cytopathological diagnosis of high-grade squamous intraepithelial lesions: a cytohistological correlation between findings in cervical smears and loop electrical excision procedure.

The present study sought possible factors leading to the cytological diagnosis of atypical squamous cells of uncertain significance (ASCUS) in cases of high-grade squamous intraepithelial lesions (HSIL). Based on retrospective histopathological analysis of loop electrical excision procedure (LEEP) products that diagnosed HSIL, two study groups were randomly selected. The first was consisted of cases with two consecutive Papanicolaou (Pap) smears with the diagnosis of ASCUS. The second (control) group was represented by cases diagnosed as HSIL by cytology. From the Pap smears diagnosed as ASCUS, the sampling limitations was different from control group (P < 0.05). The median size of the largest lesion in each case with ASCUS was 2.66 mm (+/- 1.71 mm). In the control group, the median size of the largest lesion was 5.15 mm (+/-2.58 mm) (P < 0.05). The size of the lesion and sample limitations led patients with cervical intraepithelial neoplasms to be diagnosed as ASCUS for two consecutive times, after a 6-mo period.     

14例恶性潜能未定的前列腺间质肿瘤病例分析

目的: 探讨恶性潜能未定的前列腺间质肿瘤(stromal tumor of uncertain malignant potential,STUMP)的临床及影像学表现、病理特点、治疗及预后情况。方法: 回顾性分析2008年10月至2020年4月北京大学第一医院泌尿外科诊治的14例STUMP患者的临床资料,年龄27~78岁(平均54岁), 病程1~180个月(平均46个月)。以排尿困难、尿路刺激症状为主要表现,直肠指诊可提示前列腺肿物,血清前列腺特异性抗原(prostate specific antigen, PSA)正常或轻度升高,经直肠超声及磁共振提示前列腺肿瘤或前列腺增生结节。结果: 3例仅行前列腺穿刺活检术,2例仅行经尿道前列腺切除术,9例经病理明确诊断后行根治性前列腺切除术或经尿道前列腺切除术。镜下观察前列腺间质细胞过度增生,呈梭形细胞,细胞异型性不明显,核分裂像少见。免疫组织化学检查,PSA均为阴性,波形蛋白均为阳性,CD34及孕激素受体多呈阳性,Ki67阳性指数为1%~20%(平均6%)。病理诊断为恶性潜能未定的前列腺间质肿瘤。随访时间10~96个月(平均65个月), 失访2例,死亡1例,9例术后未见复发,2例因局部复发而多次行经尿道前列腺切除术。结论: STUMP的影像学表现具有特征性,可通过前列腺穿刺活检获得病理学诊断;早期发现确诊,结合临床制定手术为主的综合治疗方案,有助于改善患者预后。     

Identification of Genetic Causes of Focal Segmental Glomerulosclerosis Increases With Proper Patient Selection

ObjectiveTo increase the likelihood of finding a causative genetic variant in patients with a focal segmental glomerulosclerosis (FSGS) lesion, clinical and histologic characteristics were analyzed.Patients and MethodsIndividuals 18 years and older with an FSGS lesion on kidney biopsy evaluated at Mayo Clinic from November 1, 1999, through October 31, 2019, were divided into 4 groups based on clinical and histologic characteristics: primary FSGS, secondary FSGS with known cause, secondary FSGS without known cause, and undetermined FSGS. A targeted gene panel and a customized gene panel retrieved from exome sequencing were performed.ResultsThe overall rate of detection of a monogenic cause was 42.9% (21/49). Individuals with undetermined FSGS had the highest rate of positivity (87.5%; 7/8) followed by secondary FSGS without an identifiable cause (61.5%; 8/13) and secondary FSGS with known cause (33.3%; 5/15). Four of 5 (80%) individuals in the latter group who had positive genetic testing results also had a family history of kidney disease. Univariate analysis showed that family history of kidney disease (odds ratio [OR], 13.8; 95% CI, 3.7 to 62.4; P<.001), absence of nephrotic syndrome (OR, 8.2; 95% CI, 1.9 to 58.1; P=.004), and female sex (OR, 5.1; 95% CI, 1.5 to 19.9; P=.01) were strong predictors of finding a causative genetic variant in the entire cohort. The most common variants were in the collagen genes (52.4%; 11/21), followed by the podocyte genes (38.1%; 8/21).ConclusionIn adults with FSGS lesions, proper selection of patients increases the rate of positive genetic testing significantly. The majority of individuals with undetermined FSGS in whom the clinical presentation and histologic parameters are discordant had a genetic diagnosis.     

A familial amyotrophic lateral sclerosis pedigree discordant for a novel p.Glu46Asp heterozygous OPTN variant and the p.Ala5Val heterozygous SOD1 missense mutation

About 10% of Amyotrophic Lateral Sclerosis (ALS) cases are familial (FALS), mainly related to mutations in C9ORF72, SOD1, TARDBP, and FUS genes. Recent data revealed the presence of multiple variants in ALS-associated genes in FALS in excess of what is to be expected by chance. FALS patients not carrying a pathogenic genetic mutation detected in their kindred have been reported. We report a FALS case, who did not carry the p.Ala5Val heterozygous SOD1 mutation that had been detected in other affected subjects of his kindred. He underwent Next-Generation Sequencing, revealing a novel p.Glu46Asp heterozygous OPTN variant of uncertain significance (VUS). Discordant genetic test results in FALS cases within the same family and the detection of variants of uncertain significance increase the complexities of genetic counselling.     

Monoclonal gammopathy of renal significance: Early diagnosis is key

Monoclonal gammopathy of renal significance is a clinical–pathological entity grouping renal disorders secondary to the secretion of a monoclonal immunoglobulin synthesized by a B-cell-derived clone and/or plasma cells in a patient with no diagnostic criteria for multiple myeloma. This term applies to a concept recently introduced owing to the need to differentiate this entity from monoclonal gammopathy of undetermined significance, given the negative prognostic impact of its high morbidity and mortality resulting from both renal and systemic involvement, occasionally even progressing to advanced chronic kidney disease. The renal damage occurs via both direct pathogenic mechanisms, with the deposition of the monoclonal protein in different renal structures, as well as indirect mechanisms, acting as an autoantibody provoking dysregulation of the alternative complement pathway. The detection of this monoclonal protein and an early hematologic study are essential, as is the need for a kidney biopsy to establish the associated nephropathological diagnosis. Consequently, this then leads to the start of specific hematologic treatment to detain the production of the monoclonal protein and minimize renal and systemic injury.     

Precision Medicine Approaches to Vascular Disease: JACC Focus Seminar 2/5

In this second of a 5-part Focus Seminar series, we focus on precision medicine in the context of vascular disease. The most common vascular disease worldwide is atherosclerosis, which is the primary cause of coronary artery disease, peripheral vascular disease, and a large proportion of strokes and other disorders. Atherosclerosis is a complex genetic disease that likely involves many hundreds to thousands of single nucleotide polymorphisms, each with a relatively modest effect for causing disease. Conversely, although less prevalent, there are many vascular disorders that typically involve only a single genetic change, but these changes can often have a profound effect that is sufficient to cause disease. These are termed “Mendelian vascular diseases,” which include Marfan and Loeys-Dietz syndromes. Given the very different genetic basis of atherosclerosis versus Mendelian vascular diseases, this article was divided into 2 parts to cover the most promising precision medicine approaches for these disease types.     

Clinical significance of HPV DNA cotesting in Korean women with ASCUS or ASC‐H

The purpose of this study was to evaluate the clinical significance of Human papillomavirus (HPV) DNA cotesting in Korean women with abnormal Papanicolaou (Pap) smear results based on colposcopic pathology. A total of 1012 women underwent liquid‐based Pap smears and hybrid capture II HPV DNA tests followed by colposcopy at the Korea University Hospital from January 2007 to May 2012. Of these women, 832 women were included in this retrospective study. The mean patient age was 45.4 ± 13.7 years (range:15–80). The distribution of Pap smear results was normal (4.7%), atypical squamous cells of uncertain significance (ASCUS) (42.1%), low‐grade squamous intraepithelial lesion (26.8%), ASC‐H (7.0%), and high‐grade squamous intraepithelial lesion (HSIL) (19.5%). In women with ASCUS, none of the 87 HPV‐negative had ≥cervical intraepithelial neoplasia (CIN2) (P < 0.001). In women with ASC‐H, only one out of 17 HPV‐negative vs. 14 out of 41 HPV‐positive had ≥CIN2 (P = 0.025). In patients with HSIL, 54.5% of HPV‐negative had ≥CIN2, as compared to 80.8% of HPV‐positive with ≥CIN2 (P = 0.039). Patients were further analyzed by age groups: <30 and ≥30 years. In HPV‐negative women, there was a significant difference in the ratio of ≥CIN2 (30.8% <30 vs. 4.5% ≥30, P = 0.005). When the HPV DNA test was negative in women ≥30, the risk of ≥CIN2 was significantly lower (P < 0.001). HPV DNA cotesting in women with ASCUS and ASC‐H furnish healthcare providers with informative data. There is a lower proportion of ≥CIN2 in HPV‐negative women and a higher proportion of ≥CIN2 in HPV‐positive. When HPV data were further evaluated by age group, the risk of ≥CIN2 was lower in HPV‐negative women, especially in women ≥30. Diagn. Cytopathol. 2014;42:1058–1062. © 2014 Wiley Periodicals, Inc.