S. T. Tiel, L. Utomo, J. D. Swart, E. Blois, M. Jong, Y. Bastiaansen-Jenniskens, M. Bernsen
Background: Macrophages are crucial in the development and progression of various diseases. To monitor their role, various proteins expressed by macrophages may be used as imaging target. In this preclinical study we investigate the value of the somatostatin receptor subtype 2 (SSTR2) as a novel imaging marker for pro-inflammatory macrophages, using an experimental osteoarthritis (OA) mouse model. Methods: SSTR2 gene expression levels in pro-inflammatory macrophages and human synovium was determined by qPCR. Tracer binding was determined in macrophages and human osteoarthritic synovium after in vitro stimulation with IFN γ and TNF α . Presence of pro-inflammatory macrophages in OA mice was determined by anti-CD64 + staining. Accumulation of the tracer in OA knees was determined by μSPECT. Results: Human macrophages and synovial tissue stimulated with IFN γ +TNF α had significantly upregulated SSTR2 gene expression and showed increased uptake of SSTR2-targeting tracer. Shortly after OA induction an increase in the presence of pro-inflammatory macrophages was seen as assessed by immunohitochemsitry. Similar findings were obtained with SPECT, with peak uptake of the SSTR2-targeting tracer immediately after surgery followed by a gradual decrease during the course of the next 8 weeks. Conclusions : Pro-inflammatory macrophages have elevated SSTR2 expression which makes it possible to image an inflammatory process in the knee with a radiolabeled somatostatin analog for SPECT.
{"title":"Evaluation of a radiolabeled somatostatin analog for SPECT imaging of pro-inflammatory macrophages","authors":"S. T. Tiel, L. Utomo, J. D. Swart, E. Blois, M. Jong, Y. Bastiaansen-Jenniskens, M. Bernsen","doi":"10.15761/BRR.1000136","DOIUrl":"https://doi.org/10.15761/BRR.1000136","url":null,"abstract":"Background: Macrophages are crucial in the development and progression of various diseases. To monitor their role, various proteins expressed by macrophages may be used as imaging target. In this preclinical study we investigate the value of the somatostatin receptor subtype 2 (SSTR2) as a novel imaging marker for pro-inflammatory macrophages, using an experimental osteoarthritis (OA) mouse model. Methods: SSTR2 gene expression levels in pro-inflammatory macrophages and human synovium was determined by qPCR. Tracer binding was determined in macrophages and human osteoarthritic synovium after in vitro stimulation with IFN γ and TNF α . Presence of pro-inflammatory macrophages in OA mice was determined by anti-CD64 + staining. Accumulation of the tracer in OA knees was determined by μSPECT. Results: Human macrophages and synovial tissue stimulated with IFN γ +TNF α had significantly upregulated SSTR2 gene expression and showed increased uptake of SSTR2-targeting tracer. Shortly after OA induction an increase in the presence of pro-inflammatory macrophages was seen as assessed by immunohitochemsitry. Similar findings were obtained with SPECT, with peak uptake of the SSTR2-targeting tracer immediately after surgery followed by a gradual decrease during the course of the next 8 weeks. Conclusions : Pro-inflammatory macrophages have elevated SSTR2 expression which makes it possible to image an inflammatory process in the knee with a radiolabeled somatostatin analog for SPECT.","PeriodicalId":92337,"journal":{"name":"Biomedical research and reviews","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67432829","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}
Psychopathology researchers, like other scale developers, often fail to establish that underlying pathology scores are quantitative, concentrating instead on construction of numeric assignment procedures. By doing so, researchers risk that there may be no qualitative data relations that correspond to the quantitative structure inherent in the numerical assignment. Without representational data correspondence, numbers and their operations are devoid of meaning in a measurement context. As a basis for quantitative establishment, a logic of quantification is presented. Pathology as a medical condition is presumed to exist in amounts referred to as magnitudes. A theory of measurable magnitudes is offered founded on seven axioms of quantity. The central conclusion from a measurement perspective is that for any ratio of two magnitudes of the same pathology, a / b , there exists a corresponding rational measure-number. If magnitude b is a unit of measurement, then the measure-number is the number of measure units contained in magnitude a . Thus, measurement is definable as the act of determining the measure-number corresponding to a target magnitude a given a unit of measurement b . The utility of the definition, however, depends upon the extent to which observable data support the quantitative hypothesis. A test that pathology scores are quantitative is provided. If supported, pathology scores can be treated as numeric in subsequent analyses.
{"title":"On establishing that pathology scores are quantitative","authors":"D. W. Drewes","doi":"10.15761/brr.1000132","DOIUrl":"https://doi.org/10.15761/brr.1000132","url":null,"abstract":"Psychopathology researchers, like other scale developers, often fail to establish that underlying pathology scores are quantitative, concentrating instead on construction of numeric assignment procedures. By doing so, researchers risk that there may be no qualitative data relations that correspond to the quantitative structure inherent in the numerical assignment. Without representational data correspondence, numbers and their operations are devoid of meaning in a measurement context. As a basis for quantitative establishment, a logic of quantification is presented. Pathology as a medical condition is presumed to exist in amounts referred to as magnitudes. A theory of measurable magnitudes is offered founded on seven axioms of quantity. The central conclusion from a measurement perspective is that for any ratio of two magnitudes of the same pathology, a / b , there exists a corresponding rational measure-number. If magnitude b is a unit of measurement, then the measure-number is the number of measure units contained in magnitude a . Thus, measurement is definable as the act of determining the measure-number corresponding to a target magnitude a given a unit of measurement b . The utility of the definition, however, depends upon the extent to which observable data support the quantitative hypothesis. A test that pathology scores are quantitative is provided. If supported, pathology scores can be treated as numeric in subsequent analyses.","PeriodicalId":92337,"journal":{"name":"Biomedical research and reviews","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67432755","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}
Nihal Saraner, Ezgi Fikirdeşici, B. Guney, Onur Saglam
{"title":"Determination of bezafibrate in human plasma by using liquid chromatography-tandem mass spectrometry","authors":"Nihal Saraner, Ezgi Fikirdeşici, B. Guney, Onur Saglam","doi":"10.15761/brr.1000124","DOIUrl":"https://doi.org/10.15761/brr.1000124","url":null,"abstract":"","PeriodicalId":92337,"journal":{"name":"Biomedical research and reviews","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67431902","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}
{"title":"Hirudinea Lamarck 1818: Evolutionary origin and taxonomy of the six medicinal leeches (genus Hirudo) known today","authors":"U. Kutschera, D. Shain","doi":"10.15761/brr.1000126","DOIUrl":"https://doi.org/10.15761/brr.1000126","url":null,"abstract":"","PeriodicalId":92337,"journal":{"name":"Biomedical research and reviews","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67432607","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}
Alyson RB Monteiro, Gabriel CG Scarlato, Diego F Cavalini, Gilberto E Shiguemoto
Energy is frequently defined as the ability to perform work, and every work demands some sort of movement. The biggest part of these energetic transformations bioenergetic goes through the mitochondria with also develop an important role as integrators of a variety of intracellular signals. Besides that, this interesting organelle is considered an important local generator of systemic responses. New evidence has pointed the discovery of two peptides named Humanin and mitochondrial Open Reading Frames (ORF) of the twelve S c (MOTS-c), which are derivative from mtDNA and have an important systemic performance. Few works have accomplished studies regarding mitochondrial systemic responses practiced by mitochondrial peptides faced with controlled stress, such as physical stress. Therefore, the goal of this review is to describe the biological effects of these two mitochondrial peptides as well as possible benefic interactions between them and the physical exercise. Thus, we hope that the present review may raise the interest of new clinical studies that better investigate the responses of this new class of peptides faced intervention of the physical exercise, considering the correct manipulation of the components of the training load that modulate both Humanin’s response and MOTS-c’s response, with therapeutic potential in combating various diseases.
能量通常被定义为完成工作的能力，而每项工作都需要某种运动。这些能量转化的最大部分是生物能量通过线粒体，线粒体也作为各种细胞内信号的整合者发挥重要作用。除此之外，这种有趣的细胞器被认为是系统反应的重要局部发生器。新的证据指出，人类蛋白和线粒体开放阅读框架(ORF)的12 S c (MOTS-c)的两个肽的发现，它们是mtDNA的衍生物，具有重要的系统性能。很少有研究完成了线粒体肽面对可控应激(如物理应激)时的线粒体系统反应。因此，本综述的目的是描述这两种线粒体肽的生物学效应以及它们与体育锻炼之间可能的有益相互作用。因此，我们希望本综述可以引起新的临床研究的兴趣，更好地研究这类新肽面对体育锻炼干预的反应，考虑到调节Humanin反应和MOTS-c反应的训练负荷成分的正确操作，在对抗各种疾病方面具有治疗潜力。
{"title":"Humanin, MOTS-c and physical exercise: A new perspective","authors":"Alyson RB Monteiro, Gabriel CG Scarlato, Diego F Cavalini, Gilberto E Shiguemoto","doi":"10.15761/brr.1000129","DOIUrl":"https://doi.org/10.15761/brr.1000129","url":null,"abstract":"Energy is frequently defined as the ability to perform work, and every work demands some sort of movement. The biggest part of these energetic transformations bioenergetic goes through the mitochondria with also develop an important role as integrators of a variety of intracellular signals. Besides that, this interesting organelle is considered an important local generator of systemic responses. New evidence has pointed the discovery of two peptides named Humanin and mitochondrial Open Reading Frames (ORF) of the twelve S c (MOTS-c), which are derivative from mtDNA and have an important systemic performance. Few works have accomplished studies regarding mitochondrial systemic responses practiced by mitochondrial peptides faced with controlled stress, such as physical stress. Therefore, the goal of this review is to describe the biological effects of these two mitochondrial peptides as well as possible benefic interactions between them and the physical exercise. Thus, we hope that the present review may raise the interest of new clinical studies that better investigate the responses of this new class of peptides faced intervention of the physical exercise, considering the correct manipulation of the components of the training load that modulate both Humanin’s response and MOTS-c’s response, with therapeutic potential in combating various diseases.","PeriodicalId":92337,"journal":{"name":"Biomedical research and reviews","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67432679","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}
Yuchen Xiao, Yang Yang, Jianping Yong, Canzhong Lu
Areca catechu L. is a palm plant, widely distributed in the tropical and subtropical districts, such as southeast Asia and Hainan, Taiwan, Hunan and Fujian in China. Some studies on the chemical components (alkaloids, flavonoids, tannins, triterpenes, fatty acids, etc.) and biological activities (anti-bacterial, anti-viral and antitumor, anti-oxidation, anthelmintic action, effects on the nervous system and effects on the digestive system) have been reported. This review briefly describes the research progress of the chemical components and biological activities of Areca catechu L, to provide the reference to the researchers. *Correspondence to: Jianping Yong, Xiamen Institute of Rare-earth Materials, Haixi Institute, Chinese Academy of Sciences, China, Tel: +86-591-63173162, E-mail: jpyong@fjirsm.ac.cn
{"title":"Chemical Components and Biological Activities of Areca catechu L.","authors":"Yuchen Xiao, Yang Yang, Jianping Yong, Canzhong Lu","doi":"10.15761/brr.1000131","DOIUrl":"https://doi.org/10.15761/brr.1000131","url":null,"abstract":"Areca catechu L. is a palm plant, widely distributed in the tropical and subtropical districts, such as southeast Asia and Hainan, Taiwan, Hunan and Fujian in China. Some studies on the chemical components (alkaloids, flavonoids, tannins, triterpenes, fatty acids, etc.) and biological activities (anti-bacterial, anti-viral and antitumor, anti-oxidation, anthelmintic action, effects on the nervous system and effects on the digestive system) have been reported. This review briefly describes the research progress of the chemical components and biological activities of Areca catechu L, to provide the reference to the researchers. *Correspondence to: Jianping Yong, Xiamen Institute of Rare-earth Materials, Haixi Institute, Chinese Academy of Sciences, China, Tel: +86-591-63173162, E-mail: jpyong@fjirsm.ac.cn","PeriodicalId":92337,"journal":{"name":"Biomedical research and reviews","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67432737","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}
Gabriel Smester, J. Medina, C. Brown, A. Fish, V. Wells, M. Beggs, J. Medina
Pulmonologists frequently encounter indeterminate pulmonary nodules. Predicting the risk of developing lung cancer is a difficult task as evidenced by the high rate of overdiagnosis and overtreatment of indolent disease. There is an unmet clinical need for a non-invasive, easy to administer, diagnostic assay to help prevent the potentially serious consequences of overdiagnosis. Here we report on the clinical work-up of a high-risk patient with an indeterminate pulmonary nodule. This case suggests that applying a new blood test in a point of care setting in a community-based practice can accurately characterize scan identified, or incidentally found, lung nodules. The novel assay may potentially minimize aggressive interventions in patients with benign disease. *Correspondence to: Amanda L Fish, MagArray Inc, Milpitas CA, USA, E-mail: Amanda.Fish@magarray.com Received: March 10, 2019; Accepted: March 25, 2019; Published: March 28, 2019 Introduction With cigarette smoking as the acknowledged root cause, lung cancer remains a leading cause of cancer deaths worldwide, with high mortality largely attributed to its diagnosis late in the disease process when cure is not possible [1]. The National Lung Screening Trial (NLST) brought hope that screening high-risk patients with a yearly chest low-dose CT scan could lead to a 20% relative risk reduction in lung cancer deaths [2]. This decrease in mortality was paralleled by an increase in the diagnosis of stage I non-small cell lung cancer, implying that this screening paradigm leads to decreased mortality by shifting the stage at diagnosis to an earlier, curative stage. Coupled with the increase in chest CT scans performed for lung cancer screening, CT imaging is increasingly used for the diagnosis and evaluation of thoracic and extra-thoracic disease, all leading to increased identification of pulmonary nodules [3]. In the National Lung Screening Trial (NLST), 24% of screened patients were found to have a concerning pulmonary nodule with only 4% of those ultimately determined to be malignant, even in this high-risk population [2]. The current paradigm for management of pulmonary nodules > 8 mm diameter is centered on estimates of a pretest probability for malignancy. Those nodules with a high pretest probability (> 65%) are aggressively managed (typically surgical resection), whereas those at low risk (05%) are managed conservatively. Intermediate-risk nodules (5%-65%), which constitute almost one-half of the pulmonary nodules identified by chest CT scan, require further diagnostic evaluation, including other imaging, bronchoscopy, percutaneous biopsy, or surgical biopsy [4]. Even minimally invasive procedures carry significant risks and anxiety to patients, and the cost of diagnostic evaluation increases 28fold when biopsy is performed [5,6]. Patients with intermediate-risk nodules would therefore benefit from additional risk stratification tools to determine those truly in need of more aggressive evalua
肺科医生经常遇到不确定的肺结节。预测发生肺癌的风险是一项艰巨的任务，因为惰性疾病的过度诊断和过度治疗率很高。临床需要一种非侵入性、易于管理的诊断检测方法，以帮助预防过度诊断的潜在严重后果。在这里，我们报告一个高风险的不确定肺结节患者的临床检查。本病例提示，在社区实践的护理点应用新的血液检查可以准确地描述扫描发现或偶然发现的肺结节。这种新的检测方法可能潜在地减少对良性疾病患者的积极干预。*通讯:Amanda L Fish, MagArray Inc, Milpitas CA, USA, E-mail: Amanda.Fish@magarray.com收稿时间:2019年3月10日;录用日期:2019年3月25日;导言吸烟是公认的根本原因，肺癌仍然是全球癌症死亡的主要原因，其高死亡率在很大程度上归因于其在疾病晚期诊断而无法治愈。国家肺部筛查试验(NLST)带来了希望，即通过每年一次胸部低剂量CT扫描筛查高危患者，可以使肺癌死亡的相对风险降低20%。死亡率的下降与I期非小细胞肺癌诊断的增加相一致，这意味着这种筛查模式通过将诊断阶段转移到更早的治疗阶段而导致死亡率下降。再加上用于肺癌筛查的胸部CT扫描的增加，CT成像越来越多地用于胸部和胸外疾病的诊断和评估，所有这些都导致肺结节[3]的识别增加。在国家肺部筛查试验(NLST)中，24%的筛查患者被发现有一个相关的肺结节，只有4%的患者最终被确定为恶性，即使在这个高危人群中也是如此。目前治疗直径为8mm的肺结节的范例主要集中在预诊恶性概率的估计上。那些高预诊概率(> 65%)的结节采用积极治疗(典型的手术切除)，而低风险(05%)的结节采用保守治疗。中危性结节(5%-65%)几乎占胸部CT扫描发现的肺结节的一半，需要进一步的诊断评估，包括其他影像学检查、支气管镜检查、经皮活检或手术活检。即使是微创手术也会给患者带来巨大的风险和焦虑，并且当进行活检时，诊断评估的成本增加了28倍[5,6]。因此，中等风险结节患者将受益于额外的风险分层工具，以确定那些真正需要更积极的评估，以及那些需要低风险方法的患者。这些愿望引起了人们对鉴别基于血液的生物标志物的极大兴趣，这些标志物可以区分肺癌和良性疾病结节[7]。最近的一份出版物强调了一种新的、多路复用的血浆蛋白信号作为风险评估工具的临床验证和性能。作者通过VA临床因素模型[9]确定了该检测有助于正确识别肺结节的恶性风险，该结节属于肺癌不确定的中间风险。采用277个样本对该检测方法进行评估，这些样本均来自患有直径为4- 30mm的不确定肺结节的当前吸烟者，并据此定义了一种风险分类算法。然后在一个由97名受试者组成的独立验证队列中对该检测方法和算法进行评估。在97名验证研究对象中，68名被VA模型分为中度风险。基于生物标志物算法的测试正确地将44个(65%)中等风险样本识别为低风险(n = 16)或高风险(n = 28)。该试验显示，在癌症患病率为25%的预期使用人群中，敏感性为94%，阴性预测值(NPV)为94%。几乎所有受试者(98%)都有早期疾病，定义为肺癌I期或II期bbb。这种新颖的血液检测在准确识别低风险肺癌患者，从而排除危险的积极行动方面的有效性。因此，血浆蛋白检测有可能帮助临床医生更准确地表征当前吸烟者放射学不确定的肺结节。Smester G(2019)克服当前肺癌风险评估的陷阱:通过一种新的血浆蛋白生物标志物测试改进肺结节表征vol . 3: 2-4 Biomed Res Rev, 2019 doi: 10.15761/BRR。 肺科医生经常遇到不确定的肺结节。预测发生肺癌的风险是一项艰巨的任务，因为惰性疾病的过度诊断和过度治疗率很高。临床需要一种非侵入性、易于管理的诊断检测方法，以帮助预防过度诊断的潜在严重后果。在这里，我们报告一个高风险的不确定肺结节患者的临床检查。本病例提示，在社区实践的护理点应用新的血液检查可以准确地描述扫描发现或偶然发现的肺结节。这种新的检测方法可能潜在地减少对良性疾病患者的积极干预。*通讯:Amanda L Fish, MagArray Inc, Milpitas CA, USA, E-mail: Amanda.Fish@magarray.com收稿时间:2019年3月10日;录用日期:2019年3月25日;导言吸烟是公认的根本原因，肺癌仍然是全球癌症死亡的主要原因，其高死亡率在很大程度上归因于其在疾病晚期诊断而无法治愈。国家肺部筛查试验(NLST)带来了希望，即通过每年一次胸部低剂量CT扫描筛查高危患者，可以使肺癌死亡的相对风险降低20%。死亡率的下降与I期非小细胞肺癌诊断的增加相一致，这意味着这种筛查模式通过将诊断阶段转移到更早的治疗阶段而导致死亡率下降。再加上用于肺癌筛查的胸部CT扫描的增加，CT成像越来越多地用于胸部和胸外疾病的诊断和评估，所有这些都导致肺结节[3]的识别增加。在国家肺部筛查试验(NLST)中，24%的筛查患者被发现有一个相关的肺结节，只有4%的患者最终被确定为恶性，即使在这个高危人群中也是如此。目前治疗直径为8mm的肺结节的范例主要集中在预诊恶性概率的估计上。那些高预诊概率(> 65%)的结节采用积极治疗(典型的手术切除)，而低风险(05%)的结节采用保守治疗。中危性结节(5%-65%)几乎占胸部CT扫描发现的肺结节的一半，需要进一步的诊断评估，包括其他影像学检查、支气管镜检查、经皮活检或手术活检。即使是微创手术也会给患者带来巨大的风险和焦虑，并且当进行活检时，诊断评估的成本增加了28倍[5,6]。因此，中等风险结节患者将受益于额外的风险分层工具，以确定那些真正需要更积极的评估，以及那些需要低风险方法的患者。这些愿望引起了人们对鉴别基于血液的生物标志物的极大兴趣，这些标志物可以区分肺癌和良性疾病结节[7]。最近的一份出版物强调了一种新的、多路复用的血浆蛋白信号作为风险评估工具的临床验证和性能。作者通过VA临床因素模型[9]确定了该检测有助于正确识别肺结节的恶性风险，该结节属于肺癌不确定的中间风险。采用277个样本对该检测方法进行评估，这些样本均来自患有直径为4- 30mm的不确定肺结节的当前吸烟者，并据此定义了一种风险分类算法。然后在一个由97名受试者组成的独立验证队列中对该检测方法和算法进行评估。在97名验证研究对象中，68名被VA模型分为中度风险。基于生物标志物算法的测试正确地将44个(65%)中等风险样本识别为低风险(n = 16)或高风险(n = 28)。该试验显示，在癌症患病率为25%的预期使用人群中，敏感性为94%，阴性预测值(NPV)为94%。几乎所有受试者(98%)都有早期疾病，定义为肺癌I期或II期bbb。这种新颖的血液检测在准确识别低风险肺癌患者，从而排除危险的积极行动方面的有效性。因此，血浆蛋白检测有可能帮助临床医生更准确地表征当前吸烟者放射学不确定的肺结节。Smester G(2019)克服当前肺癌风险评估的陷阱:通过一种新的血浆蛋白生物标志物测试改进肺结节表征vol . 3: 2-4 Biomed Res Rev, 2019 doi: 10.15761/BRR。 1000125，并有助于提供额外的见解，以支持对
{"title":"Overcoming the pitfalls of current lung cancer risk assessment: Improved lung nodule characterization by a novel plasma protein biomarker test","authors":"Gabriel Smester, J. Medina, C. Brown, A. Fish, V. Wells, M. Beggs, J. Medina","doi":"10.15761/brr.1000125","DOIUrl":"https://doi.org/10.15761/brr.1000125","url":null,"abstract":"Pulmonologists frequently encounter indeterminate pulmonary nodules. Predicting the risk of developing lung cancer is a difficult task as evidenced by the high rate of overdiagnosis and overtreatment of indolent disease. There is an unmet clinical need for a non-invasive, easy to administer, diagnostic assay to help prevent the potentially serious consequences of overdiagnosis. Here we report on the clinical work-up of a high-risk patient with an indeterminate pulmonary nodule. This case suggests that applying a new blood test in a point of care setting in a community-based practice can accurately characterize scan identified, or incidentally found, lung nodules. The novel assay may potentially minimize aggressive interventions in patients with benign disease. *Correspondence to: Amanda L Fish, MagArray Inc, Milpitas CA, USA, E-mail: Amanda.Fish@magarray.com Received: March 10, 2019; Accepted: March 25, 2019; Published: March 28, 2019 Introduction With cigarette smoking as the acknowledged root cause, lung cancer remains a leading cause of cancer deaths worldwide, with high mortality largely attributed to its diagnosis late in the disease process when cure is not possible [1]. The National Lung Screening Trial (NLST) brought hope that screening high-risk patients with a yearly chest low-dose CT scan could lead to a 20% relative risk reduction in lung cancer deaths [2]. This decrease in mortality was paralleled by an increase in the diagnosis of stage I non-small cell lung cancer, implying that this screening paradigm leads to decreased mortality by shifting the stage at diagnosis to an earlier, curative stage. Coupled with the increase in chest CT scans performed for lung cancer screening, CT imaging is increasingly used for the diagnosis and evaluation of thoracic and extra-thoracic disease, all leading to increased identification of pulmonary nodules [3]. In the National Lung Screening Trial (NLST), 24% of screened patients were found to have a concerning pulmonary nodule with only 4% of those ultimately determined to be malignant, even in this high-risk population [2]. The current paradigm for management of pulmonary nodules > 8 mm diameter is centered on estimates of a pretest probability for malignancy. Those nodules with a high pretest probability (> 65%) are aggressively managed (typically surgical resection), whereas those at low risk (05%) are managed conservatively. Intermediate-risk nodules (5%-65%), which constitute almost one-half of the pulmonary nodules identified by chest CT scan, require further diagnostic evaluation, including other imaging, bronchoscopy, percutaneous biopsy, or surgical biopsy [4]. Even minimally invasive procedures carry significant risks and anxiety to patients, and the cost of diagnostic evaluation increases 28fold when biopsy is performed [5,6]. Patients with intermediate-risk nodules would therefore benefit from additional risk stratification tools to determine those truly in need of more aggressive evalua","PeriodicalId":92337,"journal":{"name":"Biomedical research and reviews","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67432546","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}
R. Arfoosh, K. Nguyen, Amanda L. Fish, V. Wells, Denise Rebeor, A. Seger, M. Beggs, Gregory G Allen, R. El-Bizri, Richard Torricelli, DeEtta DeBault, A. Vallejo, J. Medina, Rana Hasan, K. Melby, D. Miller, Bryce Cowgill, Thomas DeMarini
Background: To reduce overdiagnosis and overtreatment of non-cancerous pulmonary nodules found on chest imaging, an accurate non-invasive and easily administered test is needed to assist in the detection and diagnosis of cancers in a cost-effective manner at an early stage, when curative interventions are still possible. Objective: To assess the results of a novel, plasma-based multiplexed protein assay in a clinical experience program. Methods: Fifty-four consecutive plasma samples were evaluated in a CLIA-certified laboratory using the novel blood test. All samples were from patients who are current smokers, aged 25 years and older, and have an indeterminate pulmonary nodule 0.4 to 3 cm in diameter. Results: The mean patient age was 65.5 years and the mean nodule size was 1.0 cm. 26 patients were male (52% female). Of the 54 tests, the assay results for 23 individuals were determined to be in the lower risk of malignancy range (score ≤49). 42 patients had a pre-test probability in the intermediate risk range as calculated by the VA Clinical Model. Of those patients, the assay characterized 22 as having a lower risk of malignancy (52%). Conclusion: The risk stratification of individuals with an indeterminate pulmonary nodule appears to be enhanced by identifying benign nodules compared to current methods in clinical practice. We hypothesize patients with benign disease may benefit the most from this assay by avoiding unnecessary subsequent overtreatment such as lung biopsy or bronchoscopy, while improving patient quality of care and reducing associated risks and costs from these procedures. Providers and their patients in whom they suspect lung cancer may consider using this novel assay prior to proceeding with more aggressive interventions. *Correspondence to: Amanda L Fish, MagArray Inc, Milpitas CA, USA, E-mail: Amanda.Fish@magarray.com
背景:为了减少在胸部影像学上发现的非癌性肺结节的过度诊断和过度治疗，需要一种准确的、无创的、易于实施的检查，以经济有效的方式在早期阶段帮助发现和诊断癌症，当治疗干预仍然是可能的。目的:在临床经验项目中评估一种新型的、基于血浆的多重蛋白测定的结果。方法:在clia认证的实验室使用新型血液检测对54份连续血浆样本进行评估。所有样本均来自年龄在25岁及以上的吸烟者，并且有一个直径0.4至3cm的不确定肺结节。结果:患者平均年龄65.5岁，平均结节大小1.0 cm。男性26例(女性52%)。在54项检测中，23人的检测结果被确定为恶性肿瘤风险较低(评分≤49)。根据VA临床模型计算，42例患者的预测概率在中间风险范围内。在这些患者中，有22例具有较低的恶性肿瘤风险(52%)。结论:在临床实践中，与目前的方法相比，通过识别良性结节，不确定肺结节个体的风险分层似乎得到了加强。我们假设良性疾病的患者可能从该检测中获益最多，因为它避免了不必要的后续过度治疗，如肺活检或支气管镜检查，同时提高了患者的护理质量，降低了这些手术的相关风险和成本。提供者和他们怀疑肺癌的患者可以考虑在进行更积极的干预之前使用这种新的检测方法。*收件人:Amanda L Fish, MagArray Inc, Milpitas CA, USA, E-mail: Amanda.Fish@magarray.com
{"title":"Risk assessment of indeterminate lung nodule characterization by a novel plasma-protein multiplexed assay in current smokers: Results of a clinical experience program","authors":"R. Arfoosh, K. Nguyen, Amanda L. Fish, V. Wells, Denise Rebeor, A. Seger, M. Beggs, Gregory G Allen, R. El-Bizri, Richard Torricelli, DeEtta DeBault, A. Vallejo, J. Medina, Rana Hasan, K. Melby, D. Miller, Bryce Cowgill, Thomas DeMarini","doi":"10.15761/brr.1000128","DOIUrl":"https://doi.org/10.15761/brr.1000128","url":null,"abstract":"Background: To reduce overdiagnosis and overtreatment of non-cancerous pulmonary nodules found on chest imaging, an accurate non-invasive and easily administered test is needed to assist in the detection and diagnosis of cancers in a cost-effective manner at an early stage, when curative interventions are still possible. Objective: To assess the results of a novel, plasma-based multiplexed protein assay in a clinical experience program. Methods: Fifty-four consecutive plasma samples were evaluated in a CLIA-certified laboratory using the novel blood test. All samples were from patients who are current smokers, aged 25 years and older, and have an indeterminate pulmonary nodule 0.4 to 3 cm in diameter. Results: The mean patient age was 65.5 years and the mean nodule size was 1.0 cm. 26 patients were male (52% female). Of the 54 tests, the assay results for 23 individuals were determined to be in the lower risk of malignancy range (score ≤49). 42 patients had a pre-test probability in the intermediate risk range as calculated by the VA Clinical Model. Of those patients, the assay characterized 22 as having a lower risk of malignancy (52%). Conclusion: The risk stratification of individuals with an indeterminate pulmonary nodule appears to be enhanced by identifying benign nodules compared to current methods in clinical practice. We hypothesize patients with benign disease may benefit the most from this assay by avoiding unnecessary subsequent overtreatment such as lung biopsy or bronchoscopy, while improving patient quality of care and reducing associated risks and costs from these procedures. Providers and their patients in whom they suspect lung cancer may consider using this novel assay prior to proceeding with more aggressive interventions. *Correspondence to: Amanda L Fish, MagArray Inc, Milpitas CA, USA, E-mail: Amanda.Fish@magarray.com","PeriodicalId":92337,"journal":{"name":"Biomedical research and reviews","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67432621","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}
Pub Date : 2018-12-01Epub Date: 2018-11-23DOI: 10.15761/brr.1000123
Neil N Trivedi, James K Brown, Tess Rubenstein, Abigail D Rostykus, Amanda L Fish, Heng Yu, Luis Carbonell, Alice Juang, Sandy Kamer, Bhavin Patel, Manpreet Sidhu, Doris Vuong, Shan Wang, Mike Beggs, Alan Hb Wu, Mehrdad Arjomandi
Background: In the National Lung Screening Trial, 96.4% of nodules had benign etiology. To avoid unnecessary actions and exposure to harm, individuals with benign disease must be identified. We describe herein the analytical validation of a multi-analyte immunoassay for characterizing the risk that a lung nodule found on CT is malignant. Those at lower risk may be considered for serial surveillance to avoid unnecessary and potentially harmful procedures. While those nodules characterized at higher risk may be appropriate for more aggressive actions.
Objective: To validate the analytical performance of multiplexed plasma protein assays used in a novel test for lung nodule characterization.
Methods: A multiplexed immunoassay panel for the measurement of plasma proteins in current smokers who present with a lung nodule on CT scan was evaluated in a clinical testing laboratory. Assay analytical sensitivity, reproducibility, precision, and recovery of Epidermal Growth Factor Receptor (EGFR), Prosurfactant protein B (ProSB), and Tissue Inhibitor of Metalloproteinases 1 (TIMP1) from human EDTA plasma samples were evaluated across multiple runs, lots, and technicians. Interfering substances and sample pre-analytical storage conditions were evaluated for their effect on analyte recovery. The lung nodule risk score reproducibility was assessed across multiple lots.
Results: The assay sensitivities were 0.10 ng/mL EGFR, 0.02 ng/mL ProSB, and 0.29 ng/mL TIMP1 with over three orders of magnitude in the assay dynamic ranges. The assays and analytes are robust to pre-analytical sample handling and the plasma can be stored for up to 4 days at 4°C either when freshy collected or thawed after long-term storage at -80°C. Total imprecision after 20 days of testing remained under 9% for all three assays. Risk score variability remained within a ± 10% risk score range.
Conclusions: The three protein assays comprising the multi-analyte plasma test for lung nodule characterization performed quite acceptably in a clinical laboratory.
{"title":"Analytical validation of a novel multi-analyte plasma test for lung nodule characterization.","authors":"Neil N Trivedi, James K Brown, Tess Rubenstein, Abigail D Rostykus, Amanda L Fish, Heng Yu, Luis Carbonell, Alice Juang, Sandy Kamer, Bhavin Patel, Manpreet Sidhu, Doris Vuong, Shan Wang, Mike Beggs, Alan Hb Wu, Mehrdad Arjomandi","doi":"10.15761/brr.1000123","DOIUrl":"10.15761/brr.1000123","url":null,"abstract":"<p><strong>Background: </strong>In the National Lung Screening Trial, 96.4% of nodules had benign etiology. To avoid unnecessary actions and exposure to harm, individuals with benign disease must be identified. We describe herein the analytical validation of a multi-analyte immunoassay for characterizing the risk that a lung nodule found on CT is malignant. Those at lower risk may be considered for serial surveillance to avoid unnecessary and potentially harmful procedures. While those nodules characterized at higher risk may be appropriate for more aggressive actions.</p><p><strong>Objective: </strong>To validate the analytical performance of multiplexed plasma protein assays used in a novel test for lung nodule characterization.</p><p><strong>Methods: </strong>A multiplexed immunoassay panel for the measurement of plasma proteins in current smokers who present with a lung nodule on CT scan was evaluated in a clinical testing laboratory. Assay analytical sensitivity, reproducibility, precision, and recovery of Epidermal Growth Factor Receptor (EGFR), Prosurfactant protein B (ProSB), and Tissue Inhibitor of Metalloproteinases 1 (TIMP1) from human EDTA plasma samples were evaluated across multiple runs, lots, and technicians. Interfering substances and sample pre-analytical storage conditions were evaluated for their effect on analyte recovery. The lung nodule risk score reproducibility was assessed across multiple lots.</p><p><strong>Results: </strong>The assay sensitivities were 0.10 ng/mL EGFR, 0.02 ng/mL ProSB, and 0.29 ng/mL TIMP1 with over three orders of magnitude in the assay dynamic ranges. The assays and analytes are robust to pre-analytical sample handling and the plasma can be stored for up to 4 days at 4°C either when freshy collected or thawed after long-term storage at -80°C. Total imprecision after 20 days of testing remained under 9% for all three assays. Risk score variability remained within a ± 10% risk score range.</p><p><strong>Conclusions: </strong>The three protein assays comprising the multi-analyte plasma test for lung nodule characterization performed quite acceptably in a clinical laboratory.</p>","PeriodicalId":92337,"journal":{"name":"Biomedical research and reviews","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38374754","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}
Pub Date : 2018-01-01Epub Date: 2018-03-25DOI: 10.15761/BRR.1000110
Ryan C Turner, Brandon P Lucke-Wold, Sohyun Boo, Charles L Rosen, Cara L Sedney
Chiropractic cervical manipulation is a common practice utilized around the world. Most patients are never cleared medically for manipulation, which can be devastating for those few who are at increased risk for dissections. The high velocity thrust used in cervical manipulation can produce significant strain on carotid and vertebral vessels. Once a dissection has occurred, the risk of thrombus formation, ischemic stroke, paralysis, and even death is drastically increased. In this case report, we highlight a case of a 32-year-old woman who underwent chiropractic manipulation and had vertebral artery dissection with subsequent brainstem infarct. She quickly deteriorated and passed away shortly after arrival to the hospital. Although rare, one in 48 chiropractors have experienced such an event. We utilize this case to highlight the risk associated with cervical manipulation and urge open dialogue between chiropractors and physicians. Receiving medical clearance prior to cervical manipulation in potential at risk patients would drastically reduce morbidity and mortality.
{"title":"The potential dangers of neck manipulation & risk for dissection and devastating stroke: An illustrative case & review of the literature.","authors":"Ryan C Turner, Brandon P Lucke-Wold, Sohyun Boo, Charles L Rosen, Cara L Sedney","doi":"10.15761/BRR.1000110","DOIUrl":"10.15761/BRR.1000110","url":null,"abstract":"<p><p>Chiropractic cervical manipulation is a common practice utilized around the world. Most patients are never cleared medically for manipulation, which can be devastating for those few who are at increased risk for dissections. The high velocity thrust used in cervical manipulation can produce significant strain on carotid and vertebral vessels. Once a dissection has occurred, the risk of thrombus formation, ischemic stroke, paralysis, and even death is drastically increased. In this case report, we highlight a case of a 32-year-old woman who underwent chiropractic manipulation and had vertebral artery dissection with subsequent brainstem infarct. She quickly deteriorated and passed away shortly after arrival to the hospital. Although rare, one in 48 chiropractors have experienced such an event. We utilize this case to highlight the risk associated with cervical manipulation and urge open dialogue between chiropractors and physicians. Receiving medical clearance prior to cervical manipulation in potential at risk patients would drastically reduce morbidity and mortality.</p>","PeriodicalId":92337,"journal":{"name":"Biomedical research and reviews","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36265502","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}
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