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New markers in chronic obstructive pulmonary disease. 慢性阻塞性肺病的新指标。
Pub Date : 2024-01-01 Epub Date: 2024-07-03 DOI: 10.1016/bs.acc.2024.06.001
Yonca Senem Akdeniz, Seda Özkan

Chronic obstructive pulmonary disease (COPD), a global healthcare and socioeconomic burden, is a multifaceted respiratory disorder that results in substantial decline in health status and life quality. Acute exacerbations of the disease contribute significantly to increased morbidity and mortality. Consequently, the identification of reliable and effective biomarkers for rapid diagnosis, prediction, and prognosis of exacerbations is imperative. In addition, biomarkers play a crucial role in monitoring responses to therapeutic interventions and exploring innovative treatment strategies. Although established markers such as CRP, fibrinogen and neutrophil count are routinely used, a universal marker is lacking. Fortunately, an increasing number of studies based on next generation analytics have explored potential biomarkers in COPD. Here we review those advances and the need for standardized validation studies in the appropriate clinical setting.

慢性阻塞性肺疾病(COPD)是一种多发性呼吸系统疾病,会导致健康状况和生活质量大幅下降,是全球医疗保健和社会经济的负担。疾病的急性加重会大大增加发病率和死亡率。因此,为快速诊断、预测和预后病情加重而鉴定可靠有效的生物标志物势在必行。此外,生物标志物在监测治疗干预反应和探索创新治疗策略方面也发挥着至关重要的作用。虽然 CRP、纤维蛋白原和中性粒细胞计数等已确立的标志物已被常规使用,但仍缺乏通用的标志物。幸运的是,越来越多基于新一代分析技术的研究探索了慢性阻塞性肺病的潜在生物标志物。在此,我们回顾了这些进展以及在适当的临床环境中进行标准化验证研究的必要性。
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引用次数: 0
A spotlight on the aged pulmonary artery. 聚焦老年肺动脉。
Pub Date : 2024-01-01 Epub Date: 2024-06-20 DOI: 10.1016/bs.acc.2024.06.006
Dalma Horvat, Lucia Agoston-Coldea

The ever-increasing life expectancy of the global population introduces a critical perspective on the impact of aging as an immutable cardiovascular risk factor, particularly manifesting in the alterations observed in the pulmonary artery (PA). Mechanisms contributing to aging-induced changes in PA include endothelial dysfunction, chronic inflammation, and structural changes in the arterial wall over time. These alterations extend beyond mere elasticity, exerting profound effects on pulmonary hemodynamics. The propensity of PAs to develop atherosclerotic plaques underscores an intriguing facet of vascular aging, although the available literature is currently insufficient to comprehensively assess their true incidence. While recognizing the inherent risk of periprocedural complications, right heart catheterization (RHC) stands out as the gold standard for precise hemodynamic evaluation. Echocardiography, a widely employed method, proves valuable for screening pulmonary hypertension (PH), yet falls short of diagnostic capability. Technological advancements usher in a new era with non-invasive modalities such as cardiac magnetic resonance (CMR) imaging emerging as promising tools. These innovations demonstrate their prowess in providing accurate assessments of PA stiffness and hemodynamics, offering a glimpse into the future landscape of diagnostic methodologies. As we navigate the intersection of aging and pulmonary vascular health, this review aims to address mechanisms and techniques for assessing PA aging, highlighting the need for comprehensive assessments to guide clinical decision making in an increasingly aging population.

随着全球人口预期寿命的不断延长,老龄化作为一种不可改变的心血管风险因素,其影响尤其体现在肺动脉(PA)的变化上,这为我们提供了一个重要的视角。导致肺动脉老化引起变化的机制包括内皮功能障碍、慢性炎症和动脉壁结构的长期变化。这些变化不仅仅是弹性的变化,还会对肺血流动力学产生深远影响。肺动脉瓣有形成动脉粥样硬化斑块的倾向,这凸显了血管老化的一个耐人寻味的方面,尽管目前现有的文献还不足以全面评估其真实发生率。右心导管检查(RHC)固然存在围手术期并发症的固有风险,但却是精确评估血液动力学的黄金标准。超声心动图作为一种广泛使用的方法,被证明对肺动脉高压(PH)的筛查很有价值,但在诊断能力方面仍有不足。技术进步开创了一个新时代,心脏磁共振(CMR)成像等无创模式成为前景广阔的工具。这些创新技术在提供 PA 硬度和血流动力学的准确评估方面表现出了卓越的能力,让我们看到了诊断方法的未来前景。在我们探索老龄化与肺血管健康的交叉点时,本综述旨在探讨评估 PA 老化的机制和技术,强调在人口日益老龄化的情况下,需要进行全面评估以指导临床决策。
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引用次数: 0
Uric acid en route to gout. 尿酸导致痛风。
Pub Date : 2023-01-01 Epub Date: 2023-06-07 DOI: 10.1016/bs.acc.2023.05.003
Wei-Zheng Zhang

Gout and hyperuricemia (HU) have generated immense attention due to increased prevalence. Gout is a multifactorial metabolic and inflammatory disease that occurs when increased uric acid (UA) induce HU resulting in monosodium urate (MSU) crystal deposition in joints. However, gout pathogenesis does not always involve these events and HU does not always cause a gout flare. Treatment with UA-lowering therapeutics may not prevent or reduce the incidence of gout flare or gout-associated comorbidities. UA exhibits both pro- and anti-inflammation functions in gout pathogenesis. HU and gout share mechanistic and metabolic connections at a systematic level, as shown by studies on associated comorbidities. Recent studies on the interplay between UA, HU, MSU and gout as well as the development of HU and gout in association with metabolic syndromes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular, renal and cerebrovascular diseases are discussed. This review examines current and potential therapeutic regimens and illuminates the journey from disrupted UA to gout.

痛风和高尿酸血症(HU)由于患病率的增加而引起了极大的关注。痛风是一种多因素代谢和炎症性疾病,当尿酸(UA)升高诱导HU导致关节中单钠尿酸盐(MSU)晶体沉积时就会发生。然而,痛风的发病机制并不总是涉及这些事件,HU也不总是导致痛风发作。降低UA治疗可能无法预防或降低痛风发作或痛风相关合并症的发生率。UA在痛风发病机制中表现出促炎和抗炎功能。如相关合并症的研究所示,HU和痛风在系统水平上有着共同的机制和代谢联系。讨论了UA、HU、MSU与痛风之间的相互作用,以及HU和痛风与代谢综合征、非酒精性脂肪肝(NAFLD)以及心血管、肾脏和脑血管疾病的发展。这篇综述考察了目前和潜在的治疗方案,并阐明了从UA紊乱到痛风的过程。
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引用次数: 0
Advances in clinical chemistry patient-based real-time quality control (PBRTQC). 基于患者的临床化学实时质量控制(PBRTQC)研究进展
Pub Date : 2023-01-01 Epub Date: 2023-11-01 DOI: 10.1016/bs.acc.2023.08.003
Mark A Cervinski, Andreas Bietenbeck, Alex Katayev, Tze Ping Loh, Huub H van Rossum, Tony Badrick

Patient-Based Real-Time Quality Control involves monitoring an assay using patient samples rather than external material. If the patient population does not change, then a shift in the long-term assay population results represents the introduction of a change in the assay. The advantages of this approach are that the sample(s) are commutable, it is inexpensive, the rules are simple to interpret and there is virtually continuous monitoring of the assay. The disadvantages are that the laboratory needs to understand their patient population and how they may change during the day, week or year and the initial change of mindset required to adopt the system. The concept is not new, having been used since the 1960s and widely adopted on hematology analyzers in the mid-1970s. It was not widely used in clinical chemistry as there were other stable quality control materials available. However, the limitations of conventional quality control approaches have become more evident. There is a greater understanding of how to collect and use patient data in real time and a range of powerful algorithms which can identify changes in assays. There are more assays on more samples being run. There is also a greater interest in providing a theoretical basis for the validation and integration of these techniques into routine practice.

基于患者的实时质量控制包括使用患者样本而不是外部材料来监测检测。如果患者群体没有变化,那么长期测定人群结果的变化代表了测定方法的变化。这种方法的优点是样品是可交换的,价格低廉,规则易于解释,并且几乎可以连续监测分析。缺点是,实验室需要了解他们的患者群体,以及他们在一天、一周或一年中可能发生的变化,以及采用该系统所需的心态的初步变化。这个概念并不新鲜,自20世纪60年代以来一直在使用,并在20世纪70年代中期广泛应用于血液分析仪。由于没有其他稳定的质量控制材料,在临床化学中没有广泛应用。然而,传统的质量控制方法的局限性已经变得更加明显。人们对如何实时收集和使用患者数据有了更深入的了解,并有一系列强大的算法可以识别分析中的变化。对更多的样本进行更多的分析。还有一个更大的兴趣是为这些技术的验证和集成到日常实践中提供理论基础。
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引用次数: 0
Measurement uncertainty. 测量不确定度。
Pub Date : 2023-01-01 Epub Date: 2023-09-27 DOI: 10.1016/bs.acc.2023.06.001
Neda Milinković, Snežana Jovičić

Over time, the metrological concept of uncertainty in measurement has been very successfully integrated into laboratory sciences. For proper implementation, an understanding of specific metrology terminology and additional concepts such as metrology traceability and commutability is necessary. Although the original thinking about measurement uncertainty in laboratory medicine suggests the complexity of the concept, it basically refers to the result as the end product of the entire laboratory process. Although the data on measurement uncertainty can be expressed quantitatively, the basis of this concept is the continuous evaluation of all phases of the laboratory process. This means that laboratory experts should keep in mind that the extra-analytical phases (on which the uncertainty of the measurement results may depend the most) must be continuously monitored. The analytical phase can be "held in check" by established internal and external quality control processes. It is the internal/external quality control data that is used to calculate the numerical value of the measurement uncertainty of the measurement results. Although over time the awareness of laboratory experts regarding the concept of measurement uncertainty has increased, there are still many challenges that need to be followed, and the last one is how to achieve a balance between understanding, evaluation process and application of measurement uncertainty data of measurement results for complete and ultimate practical use.

随着时间的推移,测量不确定度的计量概念已经非常成功地融入了实验室科学。为了正确实施,有必要了解特定的计量术语和其他概念,如计量可追溯性和可交换性。尽管实验室医学中关于测量不确定性的最初想法表明了概念的复杂性,但它基本上是指作为整个实验室过程的最终产品的结果。尽管测量不确定度的数据可以定量表示,但这一概念的基础是对实验室过程所有阶段的连续评估。这意味着实验室专家应记住,必须持续监测额外的分析阶段(测量结果的不确定性可能最为依赖)。分析阶段可以通过已建立的内部和外部质量控制流程进行“检查”。用于计算测量结果的测量不确定度数值的是内部/外部质量控制数据。尽管随着时间的推移,实验室专家对测量不确定性概念的认识有所提高,但仍有许多挑战需要遵循,最后一个挑战是如何在理解、评估过程和应用测量结果的测量不确定性数据之间取得平衡,以供完整和最终的实际使用。
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引用次数: 0
Predictive risk markers in alcoholism. 酒精中毒的预测风险标志物。
Pub Date : 2023-01-01 Epub Date: 2023-06-14 DOI: 10.1016/bs.acc.2023.05.002
Onni Niemelä

The medical disorders of alcoholism rank among the leading public health problems worldwide and the need for predictive and prognostic risk markers for assessing alcohol use disorders (AUD) has been widely acknowledged. Early-phase detection of problem drinking and associated tissue toxicity are important prerequisites for timely initiations of appropriate treatments and improving patient's committing to the objective of reducing drinking. Recent advances in clinical chemistry have provided novel approaches for a specific detection of heavy drinking through assays of unique ethanol metabolites, phosphatidylethanol (PEth) or ethyl glucuronide (EtG). Carbohydrate-deficient transferrin (CDT) measurements can be used to indicate severe alcohol problems. Hazardous drinking frequently manifests as heavy episodic drinking or in combinations with other unfavorable lifestyle factors, such as smoking, physical inactivity, poor diet or adiposity, which aggravate the metabolic consequences of alcohol intake in a supra-additive manner. Such interactions are also reflected in multiple disease outcomes and distinct abnormalities in biomarkers of liver function, inflammation and oxidative stress. Use of predictive biomarkers either alone or as part of specifically designed biological algorithms helps to predict both hepatic and extrahepatic morbidity in individuals with such risk factors. Novel approaches for assessing progression of fibrosis, a major determinant of prognosis in AUD, have also been made available. Predictive algorithms based on the combined use of biomarkers and clinical observations may prove to have a major impact on clinical decisions to detect AUD in early pre-symptomatic stages, stratify patients according to their substantially different disease risks and predict individual responses to treatment.

酒精中毒的医学障碍是世界范围内主要的公共卫生问题之一,对评估酒精使用障碍(AUD)的预测和预后风险标志物的需求已得到广泛认可。早期发现问题饮酒和相关组织毒性是及时开始适当治疗和提高患者对减少饮酒目标的承诺的重要先决条件。临床化学的最新进展为通过检测独特的乙醇代谢产物磷脂酰乙醇(PEth)或乙基葡糖苷酸(EtG)来特异性检测重度饮酒提供了新的方法。碳水化合物缺乏转铁蛋白(CDT)测量可用于指示严重的酒精问题。危险饮酒通常表现为大量的偶发性饮酒,或与其他不利的生活方式因素相结合,如吸烟、身体不活动、不良饮食或肥胖,这些因素以超加性的方式加剧了酒精摄入的代谢后果。这种相互作用也反映在多种疾病的结果以及肝功能、炎症和氧化应激生物标志物的明显异常中。单独使用预测性生物标志物或将其作为专门设计的生物算法的一部分,有助于预测具有此类风险因素的个体的肝脏和肝外发病率。评估纤维化进展(AUD预后的主要决定因素)的新方法也已问世。基于生物标志物和临床观察的联合使用的预测算法可能会对临床决策产生重大影响,这些决策包括在症状前期早期检测AUD,根据患者明显不同的疾病风险对患者进行分层,并预测个体对治疗的反应。
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引用次数: 1
Advances in preeclampsia testing. 子痫前期检测的进展。
Pub Date : 2023-01-01 Epub Date: 2023-09-26 DOI: 10.1016/bs.acc.2023.08.004
Jessica J Miller, Victoria Higgins, Annie Ren, Samantha Logan, Paul M Yip, Lei Fu

Preeclampsia is a multisystem hypertensive disorder and one of the leading causes of maternal and fetal morbidity and mortality. The clinical hallmarks such as hypertension and proteinuria, and additional laboratory tests currently available including liver enzyme testing, are neither specific nor sufficiently sensitive. Therefore, biomarkers for timely and accurate identification of patients at risk of developing preeclampsia are extremely valuable to improve patient outcomes and safety. In this chapter, we will first discuss the clinical characteristics of preeclampsia and current evidence of the role of angiogenic factors, such as placental growth factor (PlGF) and soluble FMS like tyrosine kinase 1 (sFlt-1) in the pathogenesis of preeclampsia. Second, we will review the clinical practice guidelines for preeclampsia diagnostic criteria and their recommendations on laboratory testing. Third, we will review the currently available PlGF and sFlt-1 assays in terms of their methodologies, analytical performance, and clinical diagnostic values. Finally, we will discuss the future research needs from both an analytical and clinical perspective.

子痫前期是一种多系统高血压疾病,是孕产妇和胎儿发病和死亡的主要原因之一。高血压和蛋白尿等临床标志,以及目前可用的其他实验室检测,包括肝酶检测,既不具有特异性,也不够敏感。因此,及时准确地识别有子痫前期风险的患者的生物标志物对于改善患者的预后和安全性是非常有价值的。在本章中,我们将首先讨论子痫前期的临床特征和血管生成因子,如胎盘生长因子(PlGF)和可溶性FMS如酪氨酸激酶1 (sFlt-1)在子痫前期发病机制中的作用的最新证据。其次,我们将回顾临床实践指南子痫前期诊断标准和他们的实验室检测建议。第三,我们将回顾目前可用的PlGF和sFlt-1检测方法,分析性能和临床诊断价值。最后,我们将从分析和临床的角度讨论未来的研究需求。
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引用次数: 0
Immunohematological testing and transfusion management of the prenatal patient. 产前患者的免疫血液学检测与输血管理。
Pub Date : 2023-01-01 Epub Date: 2023-09-19 DOI: 10.1016/bs.acc.2023.08.002
NurJehan Quraishy, Suneeti Sapatnekar

The primary indication for immunohematological testing in the prenatal patient is to detect and identify maternal red cell antibodies. If there are antibodies that are expected to hemolyze the fetus' red cells, their strength of reactivity must be tested, and the fetus' antigen status determined. After delivery, testing is performed to assess the extent of fetomaternal hemorrhage, as a large hemorrhage may require other therapeutic interventions. Another major role for immunohematological testing is to select blood components appropriately when intrauterine transfusion is required for fetal anemia resulting from maternal alloimmunization or some other cause. Supplementation with molecular methods has transformed the practice of immunohematology, particularly as it applies to typing for the D antigen of the Rh blood group system. Notwithstanding the advances in testing, close coordination and communication between the transfusion service and the obstetrics service are the foundation for ensuring the finest care for prenatal patients, and for new mothers and their infants. This review describes testing and transfusion practices for prenatal patients, using case presentations to highlight the management of selected immunohematological findings. It also includes a discussion of key patient management topics that are currently unresolved.

产前患者免疫血液学检测的主要指征是检测和识别母体红细胞抗体。如果有抗体预期会溶血胎儿的红细胞,则必须检测其反应强度,并确定胎儿的抗原状态。分娩后,进行测试以评估胎母出血的程度,因为大出血可能需要其他治疗干预。免疫血液学检测的另一个主要作用是,当因母体同种异体免疫或其他原因引起的胎儿贫血需要宫内输血时,选择适当的血液成分。补充分子方法已经改变了免疫血液学的实践,特别是当它适用于Rh血型系统的D抗原分型时。尽管在检测方面取得了进展,但输血服务和产科服务之间的密切协调和沟通是确保对产前病人和新生儿及其婴儿提供最佳护理的基础。这篇综述描述了产前患者的检测和输血实践,使用病例介绍来强调选定的免疫血液学发现的管理。它还包括对目前尚未解决的关键患者管理主题的讨论。
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引用次数: 0
Biomarkers in psychiatric disorders. 精神疾病的生物标志物。
Pub Date : 2023-01-01 Epub Date: 2023-09-26 DOI: 10.1016/bs.acc.2023.05.005
Jemmyson Romário de Jesus, Tatianny de Araujo Andrade, Eduardo Costa de Figueiredo

Psychiatric disorders represent a significant socioeconomic and healthcare burden worldwide. Of these, schizophrenia, bipolar disorder, major depressive disorder and anxiety are among the most prevalent. Unfortunately, diagnosis remains problematic and largely complicated by the lack of disease specific biomarkers. Accordingly, much research has focused on elucidating these conditions to more fully understand underlying pathophysiology and potentially identify biomarkers, especially those of early stage disease. In this chapter, we review current status of this endeavor as well as the potential development of novel biomarkers for clinical applications and future research study.

精神疾病是世界范围内一个重大的社会经济和医疗负担。其中,精神分裂症、双相情感障碍、重度抑郁障碍和焦虑症最为普遍。不幸的是,诊断仍然存在问题,并且由于缺乏疾病特异性生物标志物而在很大程度上变得复杂。因此,许多研究都集中在阐明这些情况上,以更全面地了解潜在的病理生理学,并潜在地识别生物标志物,尤其是早期疾病的生物标志物。在本章中,我们回顾了这项工作的现状,以及用于临床应用和未来研究的新型生物标志物的潜在发展。
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引用次数: 0
Phosphorylated tau in Alzheimer's disease. 阿尔茨海默病中磷酸化的tau。
Pub Date : 2023-01-01 Epub Date: 2023-06-09 DOI: 10.1016/bs.acc.2023.05.001
Julia Telser, Kirsten Grossmann, Niklas Wohlwend, Lorenz Risch, Christoph H Saely, Philipp Werner

There is a need for blood biomarkers to detect individuals at different Alzheimer's disease (AD) stages because obtaining cerebrospinal fluid-based biomarkers is invasive and costly. Plasma phosphorylated tau proteins (p-tau) have shown potential as such biomarkers. This systematic review was conducted according to the PRISMA guidelines and aimed to determine whether quantification of plasma tau phosphorylated at threonine 181 (p-tau181), threonine 217 (p-tau217) and threonine 231 (p-tau231) is informative in the diagnosis of AD. All p-tau isoforms increase as a function of Aβ-accumulation and discriminate healthy individuals from those at preclinical AD stages with high accuracy. P-tau231 increases earliest, followed by p-tau181 and p-tau217. In advanced stages, all p-tau isoforms are associated with the clinical classification of AD and increase with disease severity, with the greatest increase seen for p-tau217. This is also reflected by a better correlation of p-tau217 with Aβ scans, whereas both, p-tau217 and p-tau181 correlated equally with tau scans. However, at the very advanced stages, p-tau181 begins to plateau, which may mirror the trajectory of the Aβ pathology and indicate an association with a more intermediate risk of AD. Across the AD continuum, the incremental increase in all biomarkers is associated with structural changes in widespread brain regions and underlying cognitive decline. Furthermore, all isoforms differentiate AD from non-AD neurodegenerative disorders, making them specific for AD. Incorporating p-tau181, p-tau217 and p-tau231 in clinical use requires further studies to examine ideal cut-points and harmonize assays.

需要血液生物标志物来检测不同阿尔茨海默病(AD)阶段的个体,因为获得基于脑脊液的生物标志物具有侵入性且成本高昂。血浆磷酸化tau蛋白(p-tau)已显示出作为此类生物标志物的潜力。这项系统综述是根据PRISMA指南进行的,旨在确定苏氨酸181(p-tau181)、苏氨酸217(p-tau217)和苏氨酸231(p-tau231)磷酸化的血浆tau的定量是否对AD的诊断有帮助。所有p-au亚型都作为aβ-积累的函数而增加,并以高精度将健康个体与临床前AD阶段的个体区分开来。P-tau231增加最早,其次是P-tau181和P-tau217。在晚期,所有p-tau亚型都与AD的临床分类有关,并随着疾病严重程度的增加而增加,其中p-tau217的增加最大。这也反映在p-tau217与aβ扫描的更好相关性上,而p-tau218和p-tau181与tau扫描的相关性相等。然而,在非常晚期,p-tau181开始趋于平稳,这可能反映了Aβ病理学的轨迹,并表明与AD的中等风险有关。在整个AD连续体中,所有生物标志物的增量增加与广泛的大脑区域的结构变化和潜在的认知能力下降有关。此外,所有亚型都将AD与非AD神经退行性疾病区分开来,使其对AD具有特异性。在临床应用中结合p-tau181、p-tau217和p-tau231需要进一步的研究来检查理想的分界点并协调测定。
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引用次数: 0
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Advances in clinical chemistry
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