慢性酒依赖患者的失匹配负波改变与其人格特征的关系

目的:探讨慢性酒依赖(CAD)患者失匹配负波(MMN)改变与其人格特征的关系。方法:采用改良的艾森克人格问卷(EPQ-R)对33例CAD患者(CAD组)和33名健康对照志愿者(对照组)进行评估,同时进行事件相关电位(ERP)检测,分析CAD患者MMN指标与其人格特征的关系。结果:CAD组EPQ-R中神经质(N)、精神质(P)和掩饰性(L)维度评分显著高于对照组(P<0.05或P<0.01);ERP各通道MMN潜伏期显著延长(P<0.05或P<0.01)。相关分析显示,CAD患者MMN指标与其人口学资料及人格特征无相关性。结论:CAD患者具有神经质、精神质的人格特征,其MMN潜伏期延长,但MMN改变与其人格特征无相关性。     

微卫星不稳定型子宫内膜癌的临床特点和治疗

子宫内膜癌（endometrial cancer,EC）近年发病率呈上升趋势,传统的病理组织分型不能精准地指导患者的个体化治疗及评估预后,基于分子生物学技术提出的EC分子分型应运而生,这种分子分型在EC患者术后放化疗、免疫治疗及靶向治疗中均具有重要的指导作用。其中,微卫星不稳定（microsatellite instability,MSI）型EC为癌症基因组图谱（The Cancer Genome Atlas,TCGA）分子分型中的一种,MSI型EC具有独特的临床特征和病理学特征,并且在治疗及预后方面也与其他分型的EC较为不同。分子分型现已整合到欧洲妇科肿瘤学会指南中,研究表明,MSI型EC患者化疗获益不高,但受益于免疫治疗,现已推荐使用免疫治疗联合抗血管生成药物治疗。目前关于MSI型EC患者的病理特点、预后和治疗方面仍存在一些争议,对MSI型EC患者的几项药物联合治疗仍在研究中,在EC患者中根据分子分型进行个体化治疗已成为研究的重点。     

One‐step and sequential SARSCOV‐2 polymerase chain reaction tests would not work every time

IntroductionRT‐PCR is widely used as a diagnostic test for the detection of SARS‐CoV‐2. In this study, we aim to describe the clinical utility of serial PCR testing in the final detection of COVID‐19.MethodWe collected multiple nasopharyngeal swab samples from patients who had negative RT‐PCR test on the first day after hospitalization. RT‐PCR tests were performed on the second day for all patients with initial negative result. For the patients with secondary negative results on day 2, tertiary RT‐PCR tests were performed on day 3 after hospitalization.ResultAmong 68 patients with initial negative test results, at the end of follow‐up, the mortality number was 20 (29.4%). About 33.8% of patients had subsequent positive PCR test results for the second time and 17.4% of the patients who performed third PCR test had positive result.ConclusionBased on this study, serial RT‐PCR testing is unlikely to yield additional information.     

Mid-term outcomes of rapid deployment aortic prostheses in patients with small aortic annulus

 Open in a separate windowOBJECTIVESThe Edwards Intuity valve is a rapid deployment aortic prosthesis that favours less invasive approaches. However, evidence about the clinical behaviour of their smaller sizes is scarce. Herein, we studied haemodynamic behaviours and clinical outcomes of small Intuity prostheses (19–21 mm) in comparison to larger Intuity prostheses (>21 mm).METHODSThis is an observational study including patients implanted with an Edwards Intuity rapid deployment aortic prosthesis. Patients with prosthesis sizes 19–21 and >21 mm were included. Baseline and perioperative variables, as well as adverse events during the follow-up were recorded and compared between groups.RESULTSA total of 122 patients (37% female, mean age 75 ± 4.5 years) were included, of whom 54 (45%) were implanted with a small prosthesis and 68 (55%) with a prosthesis >21 mm. There were no significant differences between patients with small Intuity prostheses and patients with larger prostheses regarding in-hospital mortality (2% vs 4%, P = 0.43) or mortality during the follow-up (3.41 vs 2.45 per 100 patients-years; P = 0.58). Survival in the small Intuity valve group was 95% at 1 year and 83% at 6 years, whereas in the larger Intuity valve group was 96% at 1 year and 78% at 6 years. The presence of a small prosthesis did not influence mid-term survival (log-rank P-value = 0.62).CONCLUSIONSThis study showed good clinical performance of Intuity aortic prostheses with appropriate mid-term survival in patients with the small aortic annulus. Thus, the Edwards Intuity rapid deployment aortic prosthesis may be considered as a potential option in patients with the small aortic annulus.     

Genetic syndromes predisposing to paediatric brain tumours: the chicken or the egg?

Cancer in childhood is a disorder of growth and development. Up to 10% of patients diagnosed with cancer during childhood have a known underlying genetic predisposition syndrome. Affected individuals usually have multisystem involvement from the underlying syndrome and certain syndromes are associated with development of characteristic tumours with sites of predilection within the neuraxis. For the healthcare professionals involved with paediatric patients it is important to have basic knowledge of the cancer susceptibility syndromes. A holistic multidisciplinary approach is required for the overall management of the syndrome itself with specific recommendations for imaging surveillance and genetic counselling based on the pattern of inheritance and the relative risk of developing a tumour. Appropriate knowledge of these syndromes will help paediatricians manage and refer patients at risk to specialist neuro-oncology centres. A typical brain tumour diagnosis can also indicate certain underlying genetic disorders and examples of such tumours include optic pathway glioma, choroid plexus carcinoma and subependymal giant cell astrocytoma. A detailed family history can be helpful in identifying at risk patients and families as the typical clinical signs associated with the genetic condition are often not fully apparent in young children. This article focuses on well-known genetic diagnoses associated with or predisposing to childhood brain tumours. In some instances, the brain tumour diagnosis subsequently leads to the diagnosis of an underlying genetic syndrome.     

Muir-Torre综合征的研究进展

Muir-Torre综合征是一种罕见的常染色体显性遗传病,是Lynch综合征（又称遗传性非息肉性大肠癌）的一个亚型,临床特征为皮脂腺肿瘤或角化棘皮瘤至少合并一种内脏恶性肿瘤,种系DNA错配修复基因突变是本病的遗传学特征。本文对近年来Muir-Torre综合征的流行病学、基因研究、临床特征和预防治疗等方面进展加以综述,以提高对Muir-Torre综合征的认识。     

Symmetric patterns with different luminance polarity (anti‐symmetry) generate an automatic response in extrastriate cortex

People can quickly detect bilateral reflection in an image. This is true when elements of the same luminance are matched on either side of the axis (symmetry) and when they have opposite luminance polarity (anti‐symmetry). Using electroencephalography, we measured the well‐established sustained posterior negativity (SPN) response to symmetry and anti‐symmetry. In one task, participants judged the presence or absence of regularity (Regularity Discrimination Task). In another, they judged the presence or absence of rare colored oddball trials (Colored Oddball Task). Previous work has concluded that anti‐symmetry is only detected indirectly, through serial visual search of element locations. This selective attention account predicts that the anti‐symmetry SPN should be abolished in the Colored Oddball Task because there is no need to search for anti‐symmetry. However, this prediction was not confirmed: The symmetry and anti‐symmetry SPN waves were not modulated by task. We conclude that at least some forms of anti‐symmetry can be extracted from the image automatically, in much the same way as symmetry. This is an important consideration for models of symmetry perception, which must be flexible enough to accommodate opposite luminance polarity, while also accounting for the fact anti‐symmetry is often perceptually weaker than symmetry.     

Relationship between MLH1, PMS2, MSH2 and MSH6 gene-specific alterations and tumor mutational burden in 1057 microsatellite instability-high solid tumors

Microsatellite instability-high (MSI-H) and tumor mutational burden (TMB) are predictive biomarkers for immune-checkpoint inhibitors (ICIs). Still, the relationship between the underlying cause(s) of MSI and TMB in tumors remains poorly defined. We investigated associations of TMB to mismatch repair (MMR) protein expression patterns by immunohistochemistry (IHC) and MMR mutations in a diverse sample of tumors. Hypothesized differences were identified by the protein/gene affected/mutated and the tumor histology/primary site. Overall, 1057 MSI-H tumors were identified from the 32 932 tested. MSI was examined by NGS using 7000+ target microsatellite loci. TMB was calculated using only nonsynonymous missense mutations sequenced with a 592-gene panel; a subset of MSI-H tumors also had MMR IHC performed. Analyses examined TMB by MMR protein heterodimer impacted (loss of MLH1/PMS2 vs. MSH2/MSH6 expression) and gene-specific mutations. The sample was 54.6% female; mean age was 63.5 years. Among IHC tested tumors, loss of co-expression of MLH1/PMS2 was more common (n = 544/705, 77.2%) than loss of MSH2/MSH6 (n = 81/705, 11.5%; P < .0001), and was associated with lower mean TMB (MLH1/PMS2: 25.03 mut/Mb vs MSH2/MSH6 46.83 mut/Mb; P < .0001). TMB also varied by tumor histology: colorectal cancers demonstrating MLH1/PMS2 loss had higher TMBs (33.14 mut/Mb) than endometrial cancers (20.60 mut/Mb) and other tumors (25.59 mut/Mb; P < .0001). MMR gene mutations were detected in 42.0% of tumors; among these, MSH6 mutations were most common (25.7%). MSH6 mutation patterns showed variability by tumor histology and TMB. TMB varies by underlying cause(s) of MSI and tumor histology; this heterogeneity may contribute to differences in response to ICI.     

Solid‐type poorly differentiated adenocarcinoma of the stomach: Deficiency of mismatch repair and SWI/SNF complex

ARID1A, one of the subunits in SWI/SNF chromatin remodeling complex, is frequently mutated in gastric cancers with microsatellite instability (MSI). The most frequent MSI in solid‐type poorly differentiated adenocarcinoma (PDA) has been reported, but the SWI/SNF complex status in solid‐type PDA is still largely unknown. We retrospectively analyzed 54 cases of solid‐type PDA for the expressions of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), SWI/SNF complex subunits (ARID1A, INI1, BRG1, BRM, BAF155, and BAF170) and EBER, and mutations in KRAS and BRAF. We analyzed 40 cases of another histological type of gastric cancer as a control group. The solid‐type PDAs showed coexisting glandular components (76%), MMR deficiency (39%), and complete/partial loss of ARID1A (31%/7%), INI1 (4%/4%), BRG1 (48%/30%), BRM (33%/33%), BAF155 (13%/41%), and BAF170 (6%/2%), EBER positivity (4%), KRAS mutation (2%), and BRAF mutation (2%). Compared to the control group, MMR deficiency and losses of ARID1A, BRG1, BRM, and BAF155 were significantly frequent in solid‐type PDAs. Mismatch repair deficiency was associated with the losses of ARID1A, BRG1, and BAF155 in solid‐type PDAs. In the MMR‐deficient group, solid components showed significantly more frequent losses of ARID1A, BRG1, BRM, and BAF155 compared to glandular components (P = .0268, P = .0181, P = .0224, and P = .0071, respectively). In the MMR‐proficient group, solid components showed significantly more frequent loss of BRG1 compared to glandular components (P = .012). In conclusion, solid‐type PDAs showed frequent losses of MMR proteins and the SWI/SNF complex. We suggest that loss of the SWI/SNF complex could induce a morphological shift from differentiated‐type adenocarcinoma to solid‐type PDA.