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NR3C2 microdeletions-an underrecognized cause of pseudohypoaldosteronism type 1A: a case report and literature review. NR3C2微缺失--假性醛固酮增多症1A型的一个未被充分认识的病因:病例报告和文献综述。
Pub Date : 2024-09-04 DOI: 10.1093/labmed/lmae005
Bobby L Boyanton, Yuri A Zarate, Brannon G Broadfoot, Thomas Kelly, Brendan D Crawford

Objectives: Pseudohypoaldosteronism type 1A (PHA1A) is caused by haploinsufficiency of the mineralocorticoid receptor (MR). Heterozygous small insertions/deletions, transitions, and/or transversions within NR3C2 comprise the majority (85%-90%) of pathogenic copy number variants. Structural chromosomal abnormalities, contiguous gene deletion syndromes, and microdeletions are infrequent. We describe a neonate with PHA1A due to a novel NR3C2 microdeletion involving exons 1-2.

Methods: Literature review identified 39 individuals with PHA1A due to NR3C2 microdeletions. Transmission modality, variant description(s), testing method(s), exon(s) deleted, and affected functional domain(s) were characterized.

Results: In total, 40 individuals with NR3C2 microdeletions were described: 19 involved contiguous exons encoding a single MR domain; 21 involved contiguous exons encoding multiple MR domains. Transmission modality frequency was familial (65%), de novo (20%), or unknown (15%). Sequencing (Sanger or short-read next-generation) failed to detect microdeletions in 100% of tested individuals (n = 38). All were detected using deletion/duplication testing modalities. In 2 individuals, only microarray-based testing was performed; microdeletions were detected in both cases.

Conclusion: Initial testing for PHA1A should rely on sequencing to detect the most common genetic alterations. Deletion/duplication analysis should be performed when initial testing is nondiagnostic. Most NR3C2 microdeletions are parentally transmitted, thus highlighting the importance of familial genetic testing and counseling.

目的:假性醛固酮增多症 1A 型(PHA1A)是由矿质皮质激素受体(MR)单倍体缺陷引起的。在致病拷贝数变异中,大多数(85%-90%)是 NR3C2 中的杂合子小插入/缺失、转换和/或反转。染色体结构异常、连续基因缺失综合征和微缺失并不常见。我们描述了一名因新型 NR3C2 微缺失(涉及 1-2 号外显子)而患有 PHA1A 的新生儿:方法:文献综述确定了 39 例因 NR3C2 微缺失而患有 PHA1A 的患者。对传播方式、变异描述、检测方法、删除的外显子和受影响的功能域进行了特征描述:结果:共描述了 40 例 NR3C2 微缺失患者:其中 19 例涉及编码单个 MR 功能域的连续外显子;21 例涉及编码多个 MR 功能域的连续外显子。传播方式的频率为家族性(65%)、新发现(20%)或未知(15%)。测序(桑格测序或短线程下一代测序)未能在100%的受测个体(n = 38)中检测到微缺失。所有患者都是通过缺失/重复检测方式检测到的。有 2 人仅进行了基于微阵列的检测;在这两个病例中都检测到了微缺失:结论:PHA1A 的初步检测应依靠测序来检测最常见的基因改变。结论:PHA1A 的初步检测应依靠测序来检测最常见的基因改变,如果初步检测无法确诊,则应进行缺失/重复分析。大多数 NR3C2 微缺失是由父母遗传的,因此强调了家族遗传检测和咨询的重要性。
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引用次数: 0
High-grade B-cell lymphoma with a quadruple-hit genetic profile including concurrent MYC, BCL2, BCL6, and CCND1 gene rearrangements. 高度B细胞淋巴瘤,具有四重基因突变,包括并发MYC、BCL2、BCL6和CCND1基因重排。
Pub Date : 2024-09-04 DOI: 10.1093/labmed/lmae017
Marie-France Gagnon, Reid G Meyer, Eric J Weaver, Adam J Wood, Dudley A Dupuy, Sudeep J Menachery, Min Shi, Linda B Baughn, Rhett P Ketterling, Jess F Peterson

Several reports of concurrent MYC, BCL2, BCL6, and CCND1 rearrangements in high-grade B-cell lymphoma (HGBL) have been recently described. Herein, we aimed to delineate the scope of this entity through a review of HGBL with a "quadruple-hit" genetic profile identified at our institution. We performed a retrospective review (2015-2023) at our institution of B-cell lymphoma (BCL) cases that were evaluated with concurrent MYC, BCL2, and BCL6 break-apart and IGH::MYC and IGH::CCND1 dual-color dual-fusion fluorescence in situ hybridization studies. Of 203 cases meeting inclusion criteria, 2 (1%) with a quadruple-hit genetic profile were identified. Case 1 represented a 59-year-old female with widespread lymphadenopathy and a diagnosis of HGBL who exhibited primary refractoriness to dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) chemotherapy. Case 2 represented a 58-year-old male with mediastinal and abdominal lymphadenopathy and a diagnosis of large BCL who died from disease after 1 cycle of DA-EPOCH-R chemotherapy. Similarly, a literature review of 7 previously reported cases of HGBL with a quadruple-hit profile also demonstrated aggressive disease behavior. Our study adds 2 new cases to the rarely encountered quadruple-hit HGBL, and a brief meta-analysis of the 9 available cases indicates aggressive disease behavior conferred by this constellation of genetic events.

最近有多篇关于高级别B细胞淋巴瘤(HGBL)中同时存在MYC、BCL2、BCL6和CCND1重排的报道。在此,我们旨在通过对本机构发现的具有 "四重打击 "基因图谱的HGBL进行回顾性研究,来界定这一实体的范围。我们对本机构的 B 细胞淋巴瘤 (BCL) 病例进行了回顾性研究(2015-2023 年),这些病例同时进行了 MYC、BCL2 和 BCL6 分裂以及 IGH::MYC 和 IGH::CCND1 双色双融合荧光原位杂交研究。在符合纳入标准的 203 个病例中,发现了 2 个(1%)具有四重基因突变的病例。病例 1 是一名 59 岁的女性,患有广泛淋巴结病并被诊断为 HGBL,对剂量调整后的依托泊苷、泼尼松、长春新碱、环磷酰胺、多柔比星和利妥昔单抗(DA-EPOCH-R)化疗表现出原发性难治性。病例2是一名58岁的男性,患有纵隔和腹腔淋巴结病,诊断为大BCL,在接受一个周期的DA-EPOCH-R化疗后因病死亡。同样,对之前报道的7例具有四重打击特征的HGBL病例的文献综述也显示了侵袭性疾病行为。我们的研究为罕见的四重基因突变的 HGBL 增加了 2 个新病例,对现有的 9 个病例进行的简要荟萃分析表明,这种基因事件的组合具有侵袭性疾病行为。
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引用次数: 0
Laboratory stewardship perceptions and testing patterns at a pediatric tertiary care center. 儿科三级医疗中心的实验室管理认知和检测模式。
Pub Date : 2024-09-04 DOI: 10.1093/labmed/lmae003
Tejas S Desai, Ken Tang, Viveak Kaul, Ivan M Blasutig, Melanie Buba

Background: Despite stewardship efforts, laboratory testing overuse persists across medicine.

Objectives: To understand laboratory stewardship perceptions and testing patterns at a tertiary care pediatric hospital so that we could identify potential improvement opportunities.

Methods: An electronic survey exploring laboratory stewardship was sent to all pediatric medicine resident and staff physicians. Laboratory testing data were also assessed for patterns of testing and overuse.

Results: The survey response rate was 54% (43/80). The results indicated good familiarity with stewardship but poor familiarity with testing specifics (eg, cost). A mobile reference application was the most preferred quality improvement intervention, and online modules were the least desired. Overuse was apparent, with as many as 53% of laboratory tests being repeated within 7 days and only half of repeated tests subsequently yielding abnormal results.

Conclusions: Altogether, the data we collated demonstrated poor understanding of laboratory stewardship and substantial repeat testing with few abnormal results. These study findings suggest that laboratory stewardship is lacking at our center, and that multiple improvement opportunities exist.

背景:尽管在管理方面做出了努力,但整个医学界仍存在实验室检测过度使用的现象:尽管在实验室管理方面做出了努力,但过度使用实验室检测的现象在整个医学界依然存在:目的:了解一家三级儿科医院对实验室管理的看法和检测模式,从而确定潜在的改进机会:方法:我们向所有儿科住院医师和工作人员发送了一份关于实验室管理的电子调查问卷。我们还对实验室检测数据进行了评估,以了解检测和过度使用的模式:结果:调查回复率为 54%(43/80)。结果表明,人们对管理工作的熟悉程度较高,但对检测的具体内容(如成本)的熟悉程度较低。移动参考应用程序是最受欢迎的质量改进干预措施,而在线模块则是最不受欢迎的。过度使用是显而易见的,多达 53% 的实验室检测项目在 7 天内重复进行,只有一半的重复检测项目随后出现异常结果:总之,我们整理的数据表明,人们对实验室管理的认识不足,重复化验次数多,但异常结果少。这些研究结果表明,我们的中心缺乏实验室管理,存在多种改进机会。
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引用次数: 0
The thiol/disulfide balance is shifted towards oxidation in psoriatic arthritis compared to controls and is associated with higher disease activity. 与对照组相比,银屑病关节炎患者体内的硫醇/二硫化物平衡偏向于氧化,这与疾病活动性增高有关。
Pub Date : 2024-09-04 DOI: 10.1093/labmed/lmae014
Ahmet Kor, Selçuk Akan, Esra Fırat Oğuz, Yüksel Maraş, Salim Neşelioğlu, Şükran Erten

Objective: This study was designed to compare thiol/disulfide and ischemia-modified albumin (IMA) levels between psoriatic arthritis (PsA) and healthy controls and evaluate the correlation between these molecules and the disease activity scores used in PsA.

Methods: A total of 63 PsA patients and 49 healthy volunteers were included in the study. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), modified disease activity score 28 (DAS28), and Bath Ankylosing Spondylitis Functional Index (BASFI) scores were used as disease activity indices for PsA patients. Calculations of native thiol (-SH), disulfide (-SS), and total thiol (-SH+-SS) molecules were made by the automatic spectrophotometric method, and the albumin cobalt binding test was used to measure IMA levels.

Results: In the PsA group, -SS/-SH and -SS/(-SH+-SS) levels were higher and -SH/(-SH+-SS) levels were lower than in controls. In the linear regression analysis, a significant correlation relationship was detected between DAS28-erythrocyte sedimentation rate (ESR) and -SS/(-SH+-SS) (β = 0.795, CI 95%, 0.196-1.395; P = .010), -SH/(-SH+-SS) (β = -0.475, CI 95%, 0.114-0.836; P = .010) and IMA (β = 3.932, CI 95%, 0.859-7.005; P = .013). Additionally, a significant correlation was detected between IMA and BASDAI and BASFI.

Conclusion: In PsA, thiol/disulfide homeostasis has shifted in favor of disulfide as an oxidative indicator. Serum thiol/disulfide levels are correlated with PsA disease activity indices.

研究目的本研究旨在比较银屑病关节炎(PsA)和健康对照组之间的硫醇/二硫化物和缺血修饰白蛋白(IMA)水平,并评估这些分子与 PsA 中使用的疾病活动度评分之间的相关性:研究共纳入了 63 名 PsA 患者和 49 名健康志愿者。巴斯强直性脊柱炎疾病活动指数(BASDAI)、改良疾病活动评分 28(DAS28)和巴斯强直性脊柱炎功能指数(BASFI)被用作 PsA 患者的疾病活动指数。采用自动分光光度法计算原生硫醇(-SH)、二硫化物(-SS)和总硫醇(-SH+-SS)分子,并使用白蛋白钴结合试验测量 IMA 水平:结果:与对照组相比,PsA组的-SS/-SH和-SS/(-SH+-SS)水平较高,-SH/(-SH+-SS)水平较低。在线性回归分析中,DAS28-红细胞沉降率(ESR)与-SS/(-SH+-SS)之间存在显著的相关关系(β = 0.795,CI 95%,0.196-1.395;P = .010)、-SH/(-SH+-SS)(β = -0.475,CI 95%,0.114-0.836;P = .010)和 IMA(β = 3.932,CI 95%,0.859-7.005;P = .013)。此外,还发现 IMA 与 BASDAI 和 BASFI 之间存在明显的相关性:结论:在 PsA 中,硫醇/二硫化物平衡已发生变化,二硫化物更倾向于作为氧化指标。血清硫醇/二硫化物水平与 PsA 疾病活动指数相关。
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引用次数: 0
The Arg/Arg genotype of leptin receptor gene Gln223Arg polymorphism may be an independent risk factor for nonalcoholic fatty liver disease. 瘦素受体基因 Gln223Arg 多态性的 Arg/Arg 基因型可能是非酒精性脂肪肝的独立风险因素。
Pub Date : 2024-09-04 DOI: 10.1093/labmed/lmae016
Mahsa Navari, Fatemeh Zarei, Shiva Sayedsalehi, Touraj Mahmoudi, Mitra Rostami, Aidin Mahban, Gholamreza Rezamand, Asadollah Asadi, Reza Dabiri, Hossein Nobakht, Hamid Farahani, Seidamir Pasha Tabaeian, Mohammad Reza Zali

Background: Given that obesity and insulin resistance play key roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the connection between leptin and these metabolic diseases, the association between NAFLD and a leptin receptor gene (LEPR) polymorphism was examined.

Methods: In this genetic case-control association study, 144 biopsy-proven NAFLD patients and 144 controls were genotyped for the LEPR gene Gln223Arg (rs1137101) polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method.

Results: The distributions of genotypes and alleles of Gln223Arg variant were in accordance with the Hardy-Weinberg equilibrium in the study groups (P > .05). Multivariate logistic regression analysis showed that the LEPR Gln223Arg Arg/Arg genotype was an independent risk factor for NAFLD; the Arg/Arg genotype, compared with the Gln/Gln genotype, was associated with a 2.09-fold increased risk for NAFLD (P = .036, odds ratio = 2.09 [95% CI = 1.31-5.95]).

Conclusions: We found that the LEPR Gln223Arg Arg/Arg genotype was independently associated with a more than 2-fold rise in biopsy-proven NAFLD risk. Our findings, however, need to be corroborated by further studies.

背景:鉴于肥胖和胰岛素抵抗在非酒精性脂肪肝(NAFLD)的发病机制中起着关键作用,以及瘦素与这些代谢性疾病之间的联系,我们研究了非酒精性脂肪肝与瘦素受体基因(LEPR)多态性之间的关联:在这项基因病例对照关联研究中,采用聚合酶链式反应-限制性片段长度多态性方法对 144 名经活检证实的非酒精性脂肪肝患者和 144 名对照者进行了 LEPR 基因 Gln223Arg(rs1137101)多态性的基因分型:Gln223Arg变异的基因型和等位基因在研究组中的分布符合Hardy-Weinberg平衡(P > .05)。多变量逻辑回归分析表明,LEPR Gln223Arg Arg/Arg基因型是非酒精性脂肪肝的独立风险因素;与Gln/Gln基因型相比,Arg/Arg基因型与非酒精性脂肪肝风险增加2.09倍相关(P = .036,几率比 = 2.09 [95% CI = 1.31-5.95]):我们发现,LEPR Gln223Arg Arg/Arg 基因型与活检证实的非酒精性脂肪肝风险增加 2 倍以上有独立关联。然而,我们的发现还需要进一步的研究来证实。
{"title":"The Arg/Arg genotype of leptin receptor gene Gln223Arg polymorphism may be an independent risk factor for nonalcoholic fatty liver disease.","authors":"Mahsa Navari, Fatemeh Zarei, Shiva Sayedsalehi, Touraj Mahmoudi, Mitra Rostami, Aidin Mahban, Gholamreza Rezamand, Asadollah Asadi, Reza Dabiri, Hossein Nobakht, Hamid Farahani, Seidamir Pasha Tabaeian, Mohammad Reza Zali","doi":"10.1093/labmed/lmae016","DOIUrl":"10.1093/labmed/lmae016","url":null,"abstract":"<p><strong>Background: </strong>Given that obesity and insulin resistance play key roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the connection between leptin and these metabolic diseases, the association between NAFLD and a leptin receptor gene (LEPR) polymorphism was examined.</p><p><strong>Methods: </strong>In this genetic case-control association study, 144 biopsy-proven NAFLD patients and 144 controls were genotyped for the LEPR gene Gln223Arg (rs1137101) polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method.</p><p><strong>Results: </strong>The distributions of genotypes and alleles of Gln223Arg variant were in accordance with the Hardy-Weinberg equilibrium in the study groups (P > .05). Multivariate logistic regression analysis showed that the LEPR Gln223Arg Arg/Arg genotype was an independent risk factor for NAFLD; the Arg/Arg genotype, compared with the Gln/Gln genotype, was associated with a 2.09-fold increased risk for NAFLD (P = .036, odds ratio = 2.09 [95% CI = 1.31-5.95]).</p><p><strong>Conclusions: </strong>We found that the LEPR Gln223Arg Arg/Arg genotype was independently associated with a more than 2-fold rise in biopsy-proven NAFLD risk. Our findings, however, need to be corroborated by further studies.</p>","PeriodicalId":94124,"journal":{"name":"Laboratory medicine","volume":" ","pages":"590-594"},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140208743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diagnostic and prognostic value of circulating exosomal glypican-1 in pancreatic cancer: a meta-analysis. 循环外泌体 glypican-1 在胰腺癌中的诊断和预后价值:一项荟萃分析。
Pub Date : 2024-09-04 DOI: 10.1093/labmed/lmae013
Zengyun Qiao, Enbo Wang, Boyang Bao, Xiaodong Tan, Hailong Chen, Dong Wang, Liu Yuan

Background: Pancreatic cancer (PC) is usually detected in the advanced stages. Liquid biopsy has become a revolutionary strategy for cancer diagnosis and prognosis prediction. This study aims to investigate the diagnostic and prognostic value of circulating exosomal glypican-1 (GPC-1) in PC.

Methods: We systematically searched relevant studies. For diagnostic accuracy, pooled sensitivity and specificity and the area under the summary receiver operating characteristic curve (AUC) were calculated. Regarding prognostic value, hazard ratios (HRs) and 95% CIs for overall survival (OS) were summarized by using a random-effects model.

Results: We found 8 studies that examined the diagnostic value of circulating exosomal GPC-1 in PC, and 3 studies that investigated its prognostic value. Pooled sensitivity and specificity were 0.88 (95% CI, 0.65-0.97) and 0.86 (95% CI, 0.72-0.94). The AUC was 0.93 (95% CI, 0.90-0.95). Prognostic analysis showed that higher levels of circulating exosomal GPC-1 were associated with poorer OS in PC patients, and the combined HR for OS was 4.59 (random-effects model, 95% CI = 1.17-18.03, P = .022). The results of both studies were robust and neither had publication bias.

Conclusion: Circulating exosomal GPC-1 may be used as a diagnostic and prognostic biomarker for PC. However, this result needs to be validated by further research using a larger sample size.

背景:胰腺癌(PC)通常在晚期才被发现。液体活检已成为癌症诊断和预后预测的革命性策略。本研究旨在探讨循环外泌体glypican-1(GPC-1)在PC中的诊断和预后价值:方法:我们系统检索了相关研究。方法:我们系统地检索了相关研究,计算了诊断准确性、汇总灵敏度和特异性以及汇总接收者操作特征曲线下面积(AUC)。关于预后价值,采用随机效应模型总结了总生存率(OS)的危险比(HRs)和 95% CIs:我们发现有 8 项研究探讨了循环外泌体 GPC-1 在 PC 中的诊断价值,有 3 项研究探讨了其预后价值。汇总的敏感性和特异性分别为 0.88(95% CI,0.65-0.97)和 0.86(95% CI,0.72-0.94)。AUC为0.93(95% CI,0.90-0.95)。预后分析表明,循环外泌体GPC-1水平越高,PC患者的OS越差,OS的综合HR为4.59(随机效应模型,95% CI = 1.17-18.03,P = .022)。这两项研究的结果都很可靠,而且都没有发表偏倚:结论:循环外泌体GPC-1可作为PC的诊断和预后生物标志物。然而,这一结果还需要通过更大样本量的进一步研究来验证。
{"title":"Diagnostic and prognostic value of circulating exosomal glypican-1 in pancreatic cancer: a meta-analysis.","authors":"Zengyun Qiao, Enbo Wang, Boyang Bao, Xiaodong Tan, Hailong Chen, Dong Wang, Liu Yuan","doi":"10.1093/labmed/lmae013","DOIUrl":"10.1093/labmed/lmae013","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer (PC) is usually detected in the advanced stages. Liquid biopsy has become a revolutionary strategy for cancer diagnosis and prognosis prediction. This study aims to investigate the diagnostic and prognostic value of circulating exosomal glypican-1 (GPC-1) in PC.</p><p><strong>Methods: </strong>We systematically searched relevant studies. For diagnostic accuracy, pooled sensitivity and specificity and the area under the summary receiver operating characteristic curve (AUC) were calculated. Regarding prognostic value, hazard ratios (HRs) and 95% CIs for overall survival (OS) were summarized by using a random-effects model.</p><p><strong>Results: </strong>We found 8 studies that examined the diagnostic value of circulating exosomal GPC-1 in PC, and 3 studies that investigated its prognostic value. Pooled sensitivity and specificity were 0.88 (95% CI, 0.65-0.97) and 0.86 (95% CI, 0.72-0.94). The AUC was 0.93 (95% CI, 0.90-0.95). Prognostic analysis showed that higher levels of circulating exosomal GPC-1 were associated with poorer OS in PC patients, and the combined HR for OS was 4.59 (random-effects model, 95% CI = 1.17-18.03, P = .022). The results of both studies were robust and neither had publication bias.</p><p><strong>Conclusion: </strong>Circulating exosomal GPC-1 may be used as a diagnostic and prognostic biomarker for PC. However, this result needs to be validated by further research using a larger sample size.</p>","PeriodicalId":94124,"journal":{"name":"Laboratory medicine","volume":" ","pages":"543-552"},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140103109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
DNA variants detected in primary and metastatic lung adenocarcinoma: a case report and review of the literature. 在原发性和转移性肺腺癌中检测到的 DNA 变异:病例报告和文献综述。
Pub Date : 2024-09-04 DOI: 10.1093/labmed/lmae019
Christina Kelly, Caitlin Raymond, Song Han, Youmin Lin, Linyijia Chen, Gengming Huang, Jianli Dong

Non-small cell lung cancer (NSCLC) has been found to have recurrent genetic abnormalities, and novel therapies targeting these aberrations have improved patient survival. In this study, specimens from benign tissue, primary tumors, and brain metastases were obtained at autopsy from a 55-year-old White female patient diagnosed with NSCLC and were examined using next-generation sequencing (NGS) and chromosomal microarray assay (CMA). No genetic aberrations were noted in the benign tissue; however, NGS identified a mutation in the KRAS proto-oncogene, GTPase (KRAS): KRAS exon 2 p.G12D in primary and metastatic tumor specimens. We observed 7 DNA copy number aberrations (CNAs) in primary and metastatic tumor specimens; an additional 7 CNAs were exclusively detected in the metastatic tumor specimens. These DNA alterations may be genetic drivers in the pathogenesis of the tumor specimen from our patient and may serve as biomarkers for the classification and prognosis of NSCLC.

研究发现,非小细胞肺癌(NSCLC)具有复发性遗传异常,针对这些畸变的新型疗法提高了患者的生存率。在这项研究中,研究人员从一名被诊断为 NSCLC 的 55 岁白种女性患者的尸检中获得了良性组织、原发肿瘤和脑转移灶的标本,并使用新一代测序(NGS)和染色体微阵列分析(CMA)对标本进行了检测。良性组织中未发现基因畸变,但 NGS 发现 KRAS 原癌基因 GTPase(KRAS)发生了突变:然而,NGS 在原发性和转移性肿瘤标本中发现了 KRAS 原癌基因 GTPase(KRAS)的突变:KRAS 外显子 2 p.G12D。我们在原发性和转移性肿瘤标本中观察到 7 个 DNA 拷贝数畸变(CNA);另外 7 个 CNA 只在转移性肿瘤标本中检测到。这些DNA畸变可能是患者肿瘤标本发病机制中的遗传驱动因素,可作为NSCLC分类和预后的生物标志物。
{"title":"DNA variants detected in primary and metastatic lung adenocarcinoma: a case report and review of the literature.","authors":"Christina Kelly, Caitlin Raymond, Song Han, Youmin Lin, Linyijia Chen, Gengming Huang, Jianli Dong","doi":"10.1093/labmed/lmae019","DOIUrl":"10.1093/labmed/lmae019","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) has been found to have recurrent genetic abnormalities, and novel therapies targeting these aberrations have improved patient survival. In this study, specimens from benign tissue, primary tumors, and brain metastases were obtained at autopsy from a 55-year-old White female patient diagnosed with NSCLC and were examined using next-generation sequencing (NGS) and chromosomal microarray assay (CMA). No genetic aberrations were noted in the benign tissue; however, NGS identified a mutation in the KRAS proto-oncogene, GTPase (KRAS): KRAS exon 2 p.G12D in primary and metastatic tumor specimens. We observed 7 DNA copy number aberrations (CNAs) in primary and metastatic tumor specimens; an additional 7 CNAs were exclusively detected in the metastatic tumor specimens. These DNA alterations may be genetic drivers in the pathogenesis of the tumor specimen from our patient and may serve as biomarkers for the classification and prognosis of NSCLC.</p>","PeriodicalId":94124,"journal":{"name":"Laboratory medicine","volume":" ","pages":"658-662"},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140290088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Noninvasive biomarkers for lupus nephritis. 狼疮肾炎的无创生物标志物。
Pub Date : 2024-09-04 DOI: 10.1093/labmed/lmae015
Ting Liu, Yun-Long Yang, Yan Zhou, Yong-Mei Jiang

Lupus nephritis (LN) is one of the most severe clinical manifestations of systemic lupus erythematosus (SLE). Notably, the clinical manifestations of LN are not always consistent with the histopathological findings. Therefore, the diagnosis and activity monitoring of this disease are challenging and largely depend on invasive renal biopsy. Renal biopsy has side effects and is associated with the risk of bleeding and infection. There is a growing interest in the development of novel noninvasive biomarkers for LN. In this review, we summarize most of the LN biomarkers discovered so far by correlating current knowledge with future perspectives. These biomarkers fundamentally reflect the biological processes of kidney damage and repair during disease. Furthermore, this review highlights the role of urinary cell phenotype detection in the diagnosis, monitoring, and treatment of LN and summarizes the limitations and countermeasures of this test.

狼疮性肾炎(LN)是系统性红斑狼疮(SLE)最严重的临床表现之一。值得注意的是,狼疮肾炎的临床表现并不总是与组织病理学结果一致。因此,这种疾病的诊断和活动监测具有挑战性,主要依赖于侵入性肾活检。肾活检有副作用,并伴有出血和感染的风险。人们对开发新型 LN 非侵入性生物标志物的兴趣与日俱增。在这篇综述中,我们总结了迄今为止发现的大多数 LN 生物标志物,并将现有知识与未来展望联系起来。这些生物标志物从根本上反映了疾病期间肾脏损伤和修复的生物学过程。此外,本综述还强调了尿液细胞表型检测在 LN 诊断、监测和治疗中的作用,并总结了这种检测方法的局限性和对策。
{"title":"Noninvasive biomarkers for lupus nephritis.","authors":"Ting Liu, Yun-Long Yang, Yan Zhou, Yong-Mei Jiang","doi":"10.1093/labmed/lmae015","DOIUrl":"10.1093/labmed/lmae015","url":null,"abstract":"<p><p>Lupus nephritis (LN) is one of the most severe clinical manifestations of systemic lupus erythematosus (SLE). Notably, the clinical manifestations of LN are not always consistent with the histopathological findings. Therefore, the diagnosis and activity monitoring of this disease are challenging and largely depend on invasive renal biopsy. Renal biopsy has side effects and is associated with the risk of bleeding and infection. There is a growing interest in the development of novel noninvasive biomarkers for LN. In this review, we summarize most of the LN biomarkers discovered so far by correlating current knowledge with future perspectives. These biomarkers fundamentally reflect the biological processes of kidney damage and repair during disease. Furthermore, this review highlights the role of urinary cell phenotype detection in the diagnosis, monitoring, and treatment of LN and summarizes the limitations and countermeasures of this test.</p>","PeriodicalId":94124,"journal":{"name":"Laboratory medicine","volume":" ","pages":"535-542"},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140141287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rainbow phlebotomy collection and urine aliquots for emergency department add-on testing in the era of pandemic-driven supply shortages. 在大流行病导致供应短缺的时代,彩虹抽血采集和尿液等分,用于急诊科附加检验。
Pub Date : 2024-09-04 DOI: 10.1093/labmed/lmae011
Scott Potter, Joseph W Rudolf, Lauren N Pearson

Background: Rainbow blood draws for add-on testing in the emergency department (ED) are a common practice at our institution. We sought to determine the prevalence of this practice among reference laboratory clients and characterize the impact of pandemic-driven supply shortages.

Methods: This cross-sectional study surveyed 354 client laboratories to understand specimen collection practices in specific clinical environments and how these practices may have been affected by supply chain shortages. Data analysis by descriptive statistics was performed in Qualtrics.

Results: A total of 138 laboratories took the survey (39% response rate) with 57% indicating that their ED performed rainbow draws. Of these, 16% have a formal policy regarding rainbow draws, and 76% of respondents indicated that their institution was required to modify practices due to pandemic-driven supply shortages. A total of 19% indicated they routinely collect multiple urine aliquots for add-on testing.

Conclusion: Rainbow draws and collection of urine aliquots in the ED for add-on testing are relatively common practices, with few institutions maintaining formal policies regarding the practice. Pandemic-driven supply chain shortages affected a majority of respondent laboratories and local cost-benefit analysis regarding extra specimen collection is recommended to limit waste of laboratory resources.

背景:在我院,急诊科(ED)抽取彩虹血进行附加检验是一种常见的做法。我们试图确定这种做法在参考实验室客户中的普遍程度,并描述大流行病导致的供应短缺的影响:这项横断面研究调查了 354 家客户实验室,以了解在特定临床环境中的标本采集实践,以及供应链短缺对这些实践的影响。数据分析在 Qualtrics 中通过描述性统计进行:共有 138 家实验室接受了调查(回复率为 39%),其中 57% 的实验室表示他们的 ED 进行过彩虹抽血。其中 16% 的受访者制定了有关彩虹抽血的正式政策,76% 的受访者表示,由于大流行导致供应短缺,他们所在的机构需要修改做法。共有 19% 的受访者表示,他们会例行收集多个尿液等分样品用于附加检测:结论:在急诊室进行彩虹抽血和收集尿液等分进行附加检验是相对常见的做法,但很少有机构对这种做法制定正式的政策。大流行导致的供应链短缺影响了大多数受访实验室,建议对额外标本采集进行本地成本效益分析,以限制实验室资源的浪费。
{"title":"Rainbow phlebotomy collection and urine aliquots for emergency department add-on testing in the era of pandemic-driven supply shortages.","authors":"Scott Potter, Joseph W Rudolf, Lauren N Pearson","doi":"10.1093/labmed/lmae011","DOIUrl":"10.1093/labmed/lmae011","url":null,"abstract":"<p><strong>Background: </strong>Rainbow blood draws for add-on testing in the emergency department (ED) are a common practice at our institution. We sought to determine the prevalence of this practice among reference laboratory clients and characterize the impact of pandemic-driven supply shortages.</p><p><strong>Methods: </strong>This cross-sectional study surveyed 354 client laboratories to understand specimen collection practices in specific clinical environments and how these practices may have been affected by supply chain shortages. Data analysis by descriptive statistics was performed in Qualtrics.</p><p><strong>Results: </strong>A total of 138 laboratories took the survey (39% response rate) with 57% indicating that their ED performed rainbow draws. Of these, 16% have a formal policy regarding rainbow draws, and 76% of respondents indicated that their institution was required to modify practices due to pandemic-driven supply shortages. A total of 19% indicated they routinely collect multiple urine aliquots for add-on testing.</p><p><strong>Conclusion: </strong>Rainbow draws and collection of urine aliquots in the ED for add-on testing are relatively common practices, with few institutions maintaining formal policies regarding the practice. Pandemic-driven supply chain shortages affected a majority of respondent laboratories and local cost-benefit analysis regarding extra specimen collection is recommended to limit waste of laboratory resources.</p>","PeriodicalId":94124,"journal":{"name":"Laboratory medicine","volume":" ","pages":"585-589"},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140023870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bone marrow reinvestigation leading to the diagnosis of VEXAS syndrome. 通过骨髓再探查诊断出 VEXAS 综合征。
Pub Date : 2024-09-04 DOI: 10.1093/labmed/lmae020
Bernhard Strasser, Wolfgang Kranewitter, Harald Hofer, Alexander Haushofer

A 46-year-old male patient presented with inflammatory diseases over more than 3 years. The patient suffered from recurrent pleuritis, polychondritis, orbital phlegmon, fever, and skin lesions. A bone marrow puncture added myelodysplastic syndrome to the patient's history. A focused cytomorphological reinvestigation of the archived bone marrow aspirate smears detected significant vacuolization of erythroid and myeloid precursor cells. Target sequencing revealed the UBA1 (p.Met41Thr) hotspot mutation that established the diagnosis of VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome.

一名 46 岁的男性患者出现炎症性疾病超过 3 年。患者反复出现胸膜炎、多软骨炎、眼眶痰、发热和皮肤损害。骨髓穿刺结果显示患者患有骨髓增生异常综合征。对存档的骨髓穿刺涂片进行了重点细胞形态学再调查,发现红细胞和骨髓前体细胞明显空泡化。靶向测序发现了 UBA1(p.Met41Thr)热点突变,从而确定了 VEXAS(空泡、E1 酶、X 连锁、自身炎症、体细胞)综合征的诊断。
{"title":"Bone marrow reinvestigation leading to the diagnosis of VEXAS syndrome.","authors":"Bernhard Strasser, Wolfgang Kranewitter, Harald Hofer, Alexander Haushofer","doi":"10.1093/labmed/lmae020","DOIUrl":"10.1093/labmed/lmae020","url":null,"abstract":"<p><p>A 46-year-old male patient presented with inflammatory diseases over more than 3 years. The patient suffered from recurrent pleuritis, polychondritis, orbital phlegmon, fever, and skin lesions. A bone marrow puncture added myelodysplastic syndrome to the patient's history. A focused cytomorphological reinvestigation of the archived bone marrow aspirate smears detected significant vacuolization of erythroid and myeloid precursor cells. Target sequencing revealed the UBA1 (p.Met41Thr) hotspot mutation that established the diagnosis of VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome.</p>","PeriodicalId":94124,"journal":{"name":"Laboratory medicine","volume":" ","pages":"655-657"},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Laboratory medicine
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