Non-invasive diagnostics

非侵入性诊断
  • 文章类型: Letter
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  • 文章类型: Journal Article
    背景:代谢功能障碍相关的脂肪变性肝病(MASLD),以前被称为非酒精性脂肪性肝病,影响了全球30%的人口。该教育试点侧重于初级保健提供者在提供基于指南的代谢功能障碍相关脂肪性肝炎(MASH)护理中可能发挥的作用。
    目的:加快基于指南的MASH护理路径在临床工作流程中的应用。
    方法:2021年召集了由六名肝病学家组成的小组,以开发护理途径,随后的试点于2022年至2023年之间进行。试点是在三个美国卫生系统进行的:波士顿医疗中心(波士顿),卫理公会卫生系统(达拉斯),和威尔康奈尔医学(纽约)。对临床医生进行了有关护理途径的教育,并完成了基线/随访评估。19名初级保健临床医生参加了教育试点基线评估,九名初级保健临床医生完成了为期两个月的评估,15名初级保健临床医生完成了为期4个月的评估.主要终点是评估临床医生报告的对护理途径的依从性和满意度。该试点被西方共识集团机构审查委员会视为豁免。
    结果:在基线时,38.10%(n=8)的受访者认为他们已经接受了足够的培训,何时将怀疑代谢功能障碍相关肝病的患者转诊到肝病学。42.86%(n=9)的患者在1个月内没有将任何疑似代谢功能障碍相关肝病的患者转诊至肝病科.干预后四个月,79%(n=15)的受访者同意或强烈同意他们接受了足够的培训,何时将怀疑代谢功能障碍相关肝病的患者转诊到肝病学。自我报告对该机构转诊指南的依从性增加了25.7%。护理途径依从性的障碍包括手动计算纤维化-4评分的负担和难以订购非侵入性诊断。
    结论:预计今年将进入市场的疗法,卫生系统领导层必须考虑简化识别的机会,转介,与代谢功能障碍相关的脂肪性肝炎患者的管理。代谢功能障碍相关的脂肪性肝炎护理途径的电子整合可以解决实施挑战。
    BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly referred to as nonalcoholic fatty liver disease, impacts 30% of the global population. This educational pilot focused on the role primary care providers may play in the delivery of guidelines-based metabolic dysfunction-associated steatohepatitis (MASH) care.
    OBJECTIVE: Accelerate the application of guidelines-based MASH care pathways to clinical workflows.
    METHODS: A panel of six hepatologists was convened in 2021 to develop the care pathway and the subsequent pilot occurred between 2022 - 2023. The pilot was conducted across three U.S. health systems: Boston Medical Center (Boston), Methodist Health System (Dallas), and Weill Cornell Medicine (New York). Clinicians were educated on the care pathway and completed baseline/follow-up assessments. 19 primary care clinicians participated in the educational pilot baseline assessment, nine primary care clinicians completed the two-month assessment, and 15 primary care clinicians completed the four-month assessment. The primary endpoint was to assess clinician-reported adherence to and satisfaction with the care pathway. The pilot was deemed exempt by the Western Consensus Group Institutional Review Board.
    RESULTS: At baseline, 38.10% (n = 8) of respondents felt they had received sufficient training on when to refer a patient suspected of metabolic dysfunction-associated liver disease to hepatology, and 42.86% (n = 9) had not referred any patients suspected of metabolic dysfunction-associated liver disease to hepatology within a month. At four months post-intervention, 79% (n = 15) of respondents agreed or strongly agreed they received sufficient training on when to refer a patient suspected of metabolic dysfunction-associated liver disease to hepatology, and there was a 25.7% increase in self-reported adherence to the institution\'s referral guidelines. Barriers to care pathway adherence included burden of manually calculating fibrosis-4 scores and difficulty ordering non-invasive diagnostics.
    CONCLUSIONS: With therapeutics anticipated to enter the market this year, health systems leadership must consider opportunities to streamline the identification, referral, and management of patients with metabolic dysfunction-associated steatohepatitis. Electronic integration of metabolic dysfunction-associated steatohepatitis care pathways may address implementation challenges.
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  • 文章类型: Journal Article
    该研究的目的是使用激光散斑流图描述受颈动脉海绵窦瘘(CCF)影响的眼睛中的眼部血流变化。我们假设同时对视网膜小动脉和小静脉中的血流速度波形进行成像将揭示动静脉(AV)连接的特定特征。
    这项研究是一个观察性案例系列,回顾性病例对照分析。
    使用激光散斑血流图测量了5例CCF患者的眼部血流。回顾性比较了对照组的健康受试者(n=32)和眼内压升高或无AV瘘的静脉流出道受损的患者(n=40)之间的血流。结果来自小动脉和小静脉血流速度波形,包括A-V相延迟和流量脉动。
    活性CCF的存在与视网膜小静脉测得的峰值速度延迟增加有关(心动周期持续时间的10.7%±2.2%),与未受影响的同伴眼(1.8%±0.2%;p=0.05)或正常受试者的对照眼(2.7%±0.3%;p=0.02)相比。这种延迟在瘘血栓形成后消失,并且在视网膜中央静脉阻塞(CRVO)的眼中不存在,青光眼,非动脉炎性前部缺血性视神经病变(NAION),或者乳头水肿。收缩期静脉血流速度下降(在某些情况下暂时停止),在小动脉振幅归一化后,导致小静脉中的脉冲延迟,其振幅大于其他眼睛和正常对照组(1.71±0.3vs0.54±0.03vs0.59±0.02;p=8.0E-12)。这种特定的AV延迟也可以在扫描激光检眼镜(SLO;SPECTRALIS®)视频中识别。
    激光散斑流图显示受CCF影响的眼睛中动态的视网膜血管变化,在健康对照组或其他眼部疾病患者中不存在,随着治疗的逆转。
    UNASSIGNED: The purpose of the study was to describe ocular blood flow changes in eyes affected by a carotid-cavernous fistula (CCF) using laser speckle flowgraphy. We hypothesized that imaging blood flow velocity waveforms in the retinal arterioles and venules simultaneously would reveal specific characteristics of an arteriovenous (AV) connection.
    UNASSIGNED: The study was an observational case series, with a retrospective case-control analysis.
    UNASSIGNED: Five patients with a CCF underwent measurement of ocular blood flow using laser speckle flowgraphy. The blood flow was compared retrospectively between a control group of healthy subjects (n = 32) and patients with an elevated intraocular pressure or venous outflow impairment without an AV fistula (n = 40). The outcomes were derived from the arteriole and venule blood flow velocity waveforms, including an A-V phase delay and flow pulsatility.
    UNASSIGNED: The presence of an active CCF was associated with an increased delay in the peak velocity measured in the retinal venule (10.7% ± 2.2% of the cardiac cycle duration) compared with unaffected fellow eyes (1.8% ± 0.2%; p = 0.05) or control eyes of normal subjects (2.7% ± 0.3%; p = 0.02). This delay disappeared after fistula thrombosis and was not present in eyes with a central retinal vein occlusion (CRVO), glaucoma, non-arteritic anterior ischemic optic neuropathy (NAION), or papilledema. The venule blood flow velocity decreased during systole (and in some cases momentarily stopped), leading to a delayed pulse with a greater amplitude in the venules than in fellow eyes and normal controls after normalizing to the arteriole amplitude (1.71 ± 0.3 vs 0.54 ± 0.03 vs 0.59 ± 0.02; p = 8.0E-12). This specific AV delay could also be identified in a scanning laser ophthalmoscope (SLO; SPECTRALIS®) video.
    UNASSIGNED: Laser speckle flowgraphy reveals dynamic retinal vascular changes in eyes affected by a CCF, which are not present in healthy controls or patients with other eye conditions, and which reverses with treatment.
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  • 文章类型: Journal Article
    背景:用于诊断COVID-19的常见生物样本包括鼻咽,鼻部,或者口咽拭子,和唾液样本。在四项小型子研究中评估了吸“棒棒糖”拭子检测SARS-CoV-2病毒的性能特征。
    方法:在每个子研究中,将植绒拭子吸20s,并进行SARS-CoV-2病毒的PCR检测。
    结果:在所有研究中,69名(75.4%)COVID-19阳性参与者中有52名“棒棒糖”拭子呈阳性。17名“棒棒糖”拭子阴性的COVID-19阳性参与者中有12名从其鼻/鼻咽拭子中得知相应的周期阈值>37,取样时病毒载量低的迹象。在配对样本子研究中,“棒棒糖”拭子的敏感性和特异性分别为100%和98%。
    结论:“棒棒糖”拭子表现令人满意,尤其是在COVID-19急性感染患者中。“棒棒糖”拭子是检测SARS-CoV-2病毒的简单样品收集方法,需要额外考虑。
    BACKGROUND: Common biologic samples used to diagnose COVID-19 include nasopharyngeal, nasal, or oropharyngeal swabs, and salivary samples. The performance characteristics of a sucked \"lollipop\" swab to detect SARS-CoV-2 virus is assessed in four small sub-studies.
    METHODS: In each sub-study, a flocked swab was sucked for 20 s and submitted for PCR detection of SARS-CoV-2 virus.
    RESULTS: Across all studies, 52 of 69 (75.4%) COVID-19 positive participants had positive \"lollipop\" swabs. Twelve of the 17 COVID-19 positive participants with negative \"lollipop\" swabs had known corresponding cycle threshold values of >37 from their nasal/nasopharyngeal swabs, an indication of low viral load at time of sampling. In a paired samples sub-study, the sensitivity and specificity of the \"lollipop\" swabs were 100% and 98%.
    CONCLUSIONS: \"Lollipop\" swabs performed satisfactorily especially in individuals with acute infection of COVID-19. \"Lollipop\" swabs are a simple method of sample collection for detecting SARS-CoV-2 virus and warrants additional consideration.
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  • 文章类型: Journal Article
    晚发性败血症(LOS)的早期诊断和治疗对于生存至关重要。但具有挑战性。肠道微生物群和代谢组改变先于LOS的临床发作,早产肠道被认为是细菌病原体的重要来源。粪便挥发性有机化合物(VOCs),由早产肠道的生理和病理生理代谢过程形成,反映了人类宿主之间复杂的相互作用,环境,和微生物群。疾病相关的粪便VOC可以用一系列设备进行检测,这些设备具有开发用于临床前LOS检测的即时测试(POCT)的各种潜力。虽然已经描述了常见LOS病原体的特征性VOC,由于代谢途径的相似性,它们的VOC谱通常与其他病原体重叠,阻碍了特定物种配置文件的构建。临床研究表明,然而,使用对革兰氏阴性病原体具有最高预测价值的粪便VOC分析,成功区分了LOS患者与健康个体。这篇综述讨论了基于粪便VOC的非侵入性POCT用于早期诊断LOS的当前进展。这可能为早期干预和针对性治疗提供机会,并可能改善临床新生儿结局。识别影响VOC合成的混杂变量,选择最佳检测设备,标准化采样协议的开发将允许在不久的将来开发新的POCT。
    Early diagnosis and treatment of late-onset sepsis (LOS) is crucial for survival, but challenging. Intestinal microbiota and metabolome alterations precede the clinical onset of LOS, and the preterm gut is considered an important source of bacterial pathogens. Fecal volatile organic compounds (VOCs), formed by physiologic and pathophysiologic metabolic processes in the preterm gut, reflect a complex interplay between the human host, the environment, and microbiota. Disease-associated fecal VOCs can be detected with an array of devices with various potential for the development of a point-of-care test (POCT) for preclinical LOS detection. While characteristic VOCs for common LOS pathogens have been described, their VOC profiles often overlap with other pathogens due to similarities in metabolic pathways, hampering the construction of species-specific profiles. Clinical studies have, however, successfully discriminated LOS patients from healthy individuals using fecal VOC analysis with the highest predictive value for Gram-negative pathogens. This review discusses the current advancements in the development of a non-invasive fecal VOC-based POCT for early diagnosis of LOS, which may potentially provide opportunities for early intervention and targeted treatment and could improve clinical neonatal outcomes. Identification of confounding variables impacting VOC synthesis, selection of an optimal detection device, and development of standardized sampling protocols will allow for the development of a novel POCT in the near future.
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  • 文章类型: Journal Article
    尽管血液仍然是检测运动引起的氧化损伤水平升高的最常用介质,唾液诊断由于其非侵入性和运动员友好的收集过程而越来越受欢迎。鉴于月经周期的各个阶段对氧化损伤水平的贡献可能不同,这项研究的目的是评估女性游泳者在月经周期的卵泡(F)和黄体(L)阶段和运动后的唾液和血浆脂质过氧化产物水平之间的一致性。检查了12名训练有素的女游泳运动员,年龄为19.6±1.1岁。我们测量了二烯共轭物(DC),三烯共轭物(TC),和希夫碱(SB)在脂质中立即从唾液和血浆中提取。所有女游泳运动员都接受了两次研究,在一个月经周期的两个不同阶段,高强度间歇运动(IIIE)前后。DC的唾液和血浆水平,TC,与运动前相比,运动后的SB显着增加,在F和L阶段。DCs浓度之间呈高度正相关,TC,F和L期参与者的唾液和血浆中的SB,都在休息和跟随他。普通最小二乘回归分析表明,数据中没有比例和差分偏差。Bland-Altman方法还声明没有差分偏差,由于相等线在唾液和血浆DC水平之间的平均差的95%置信区间内,TC,和女性游泳运动员的SB,在F和L阶段,在他之前和之后。Bland-Altman地块也没有比例偏差。因此,这是第一项报告DC量化之间高度一致的研究,TC,F和L期女性游泳者的唾液和血浆中的SB,在休息和跟随他。
    Although blood still remains the most commonly utilized medium to detect increased levels of oxidative damage induced by exercise, saliva diagnostics have gained increasing popularity due to their non-invasive nature and athlete-friendly collection process. Given that the contribution of various phases of the menstrual cycle to the levels of oxidative damage may differ, the aim of this study was to evaluate an agreement between salivary and plasmatic levels of lipid peroxidation products in female swimmers in both the follicular (F) and luteal (L) phases of the menstrual cycle at rest and following exercise. Twelve well-trained female swimmers aged 19.6 ± 1.1 years old were examined. We measured diene conjugates (DCs), triene conjugates (TCs), and Schiff bases (SBs) in lipids immediately after their extraction from both saliva and blood plasma. All female swimmers were studied two times each, in the two different phases of one menstrual cycle, before and after high-intensity interval exercise (HIIE). Salivary and plasmatic levels of DCs, TCs, and SBs significantly increased post-exercise compared to pre-exercise, in both the F and L phases. A high positive correlation was observed between the concentrations of DCs, TCs, and SBs in the saliva and blood plasma of participants in the F and L phases, both at rest and following HIIE. Ordinary least products regression analysis indicates that there was no proportional and differential bias in the data. The Bland-Altman method also declares that there was no differential bias, since the line of equality was within the 95% confidence interval of the mean difference between salivary and plasmatic levels of DCs, TCs, and SBs in female swimmers, in both the F and L phases, before and after HIIE. There was also no proportional bias in the Bland-Altman plots. Thus, this is the first study to report a high agreement between the quantifications of DCs, TCs, and SBs in the saliva and blood plasma of female swimmers in both the F and L phases, at rest and following HIIE.
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  • 文章类型: Journal Article
    最近,泪液分析由于其非侵入性样本收集方法,在基于生物标志物的诊断领域已经引起了相当大的关注。眼泪涵盖不仅有助于诊断眼部疾病而且还有助于诊断系统性疾病的各种列表的生物标志物的储库。这凸显了在临床环境中使用泪液作为潜在的非侵入性诊断样本的灵敏和可靠的筛查方法的必要性。已经进行了大量研究以研究基于拉曼光谱的研究在各种诊断应用中用于泪液分析的潜力。拉曼光谱(RS)是一种高度灵敏且无标记的光谱技术,可通过评估分子键的振动频率来帮助研究样品的分子结构。由于不同样品的化学成分不同,可以获得样品特定的光谱指纹。拉曼光谱获得的独特光谱指纹使研究人员能够识别样品中存在的特定化合物或官能团,帮助不同的生物医学应用。它对分子结构或环境变化的敏感性为与各种疾病相关的微妙变化提供了宝贵的见解。因此,拉曼光谱具有辅助诊断和治疗以及预后评估的潜力。拉曼光谱具有若干优点,如样品的无损检测,对结构变化非常敏感,样品制备的最低先决条件,来自水的干扰可以忽略不计,以及泪液样本实时调查的适宜性。这篇综述的目的是强调拉曼光谱技术在通过非侵入性泪液分析促进各种眼科和全身性疾病的临床诊断方面的潜力。此外,该综述深入研究了拉曼光谱在纸基传感基材和泪液分析方法方面的进展。此外,本综述还探讨了在临床环境中实施拉曼光谱作为基于泪液分析的常规诊断工具的相关障碍和未来可能性.
    In recent times, tear fluid analysis has garnered considerable attention in the field of biomarker-based diagnostics due to its noninvasive sample collection method. Tears encompass a reservoir of biomarkers that assist in diagnosing not only ocular disorders but also a diverse list of systemic diseases. This highlights the necessity for sensitive and dependable screening methods to employ tear fluid as a potential noninvasive diagnostic specimen in clinical environments. Considerable research has been conducted to investigate the potential of Raman spectroscopy-based investigations for tear analysis in various diagnostic applications. Raman Spectroscopy (RS) is a highly sensitive and label free spectroscopic technique which aids in investigating the molecular structure of samples by evaluating the vibrational frequencies of molecular bonds. Due to the distinct chemical compositions of different samples, it is possible to obtain a sample-specific spectral fingerprint. The distinctive spectral fingerprints obtained from Raman spectroscopy enable researchers to identify specific compounds or functional groups present in a sample, aiding in diverse biomedical applications. Its sensitivity to changes in molecular structure or environment provides invaluable insights into subtle alterations associated with various diseases. Thus, Raman Spectroscopy has the potential to assist in diagnosis and treatment as well as prognostic evaluation. Raman spectroscopy possesses several advantages, such as the non-destructive examination of samples, remarkable sensitivity to structural variations, minimal prerequisites for sample preparation, negligible interference from water, and the aptness for real-time investigation of tear samples. The purpose of this review is to highlight the potential of Raman spectroscopic technique in facilitating the clinical diagnosis of various ophthalmic and systemic disorders through non-invasive tear analysis. Additionally, the review delves into the advancements made in Raman spectroscopy with regards to paper-based sensing substrates and tear analysis methods integrated into contact lenses. Furthermore, the review also addresses the obstacles and future possibilities associated with implementing Raman spectroscopy as a routine diagnostic tool based on tear analysis in clinical settings.
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  • 文章类型: Journal Article
    循环无细胞DNA(cfDNA)是指在血液等几种体液中程序性细胞死亡和坏死后释放的DNA分子的小片段,唾液,尿液,和脑脊液.cfDNA的发现彻底改变了肿瘤领域的非侵入性诊断领域,在产前检查中,和器官移植。尽管cfDNA的潜力和最近文献中发表的可靠结果,仍然存在一些挑战,以低丰度为代表,需要高度敏感的检测,和分析问题。在这次审查中,介绍和讨论了cfDNA分析的主要技术进步,全面审查每个领域目前可用的方法。考虑到cfDNA的潜在优势,这种生物标志物正在增加临床医生的共识,因为它允许我们以简单和非侵入性的方式监测患者的状况,提供更个性化的护理。然而,cfDNA分析仍被认为是需要进一步验证的诊断标记,很少有中心在常规诊断中实施其分析。由于技术改进提高了cfDNA分析的性能,它的应用将横向改善患者的生活质量。
    Circulating cell-free DNA (cfDNA) refers to small fragments of DNA molecules released after programmed cell death and necrosis in several body fluids such as blood, saliva, urine, and cerebrospinal fluid. The discovery of cfDNA has revolutionized the field of non-invasive diagnostics in the oncologic field, in prenatal testing, and in organ transplantation. Despite the potential of cfDNA and the solid results published in the recent literature, several challenges remain, represented by a low abundance, a need for highly sensitive assays, and analytical issues. In this review, the main technical advances in cfDNA analysis are presented and discussed, with a comprehensive examination of the current available methodologies applied in each field. Considering the potential advantages of cfDNA, this biomarker is increasing its consensus among clinicians, as it allows us to monitor patients\' conditions in an easy and non-invasive way, offering a more personalized care. Nevertheless, cfDNA analysis is still considered a diagnostic marker to be further validated, and very few centers are implementing its analysis in routine diagnostics. As technical improvements are enhancing the performances of cfDNA analysis, its application will transversally improve patients\' quality of life.
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  • 文章类型: Journal Article
    用于流体的非侵入性诊断的生物检测,尤其是尿液,由于目标浓度低,对科学家来说仍然是一个挑战。并且检测靶标的生物复合物可能含有也干扰任何测定的污染物。登革热非结构蛋白1(DengueNS1)是登革热出血热和登革热休克综合征的重要生物标志物。这里,我们开发了一个Au修饰的纳米线平台,并将其与夹心荧光团连接的免疫吸附孔板测定法(FLISA)一起用于检测尿液中的登革热NS1。对于平台来说,我们制造了氧化锌(ZnO)纳米线以提供高表面积,然后用金纳米颗粒(ZnO/Au纳米线)涂覆它们以简单地修饰登革热NS1抗体并增强荧光强度。我们的平台采用了具有高灵敏度的三明治FLISA,特异性检测登革热NS1,检测限(LOD)为1.35pg/mL。该LOD比用于登革热NS1酶联免疫吸附测定的市售试剂盒的LOD低4500倍。我们相信我们的ZnO/Au纳米线平台有可能彻底改变登革热的非侵入性诊断领域。
    Biodetection for non-invasive diagnostics of fluids, especially urine, remains a challenge to scientists due to low target concentrations. And biological complexes of the detection target may contain contaminants that also interfere with any assay. Dengue non-structural 1 protein (Dengue NS1) is an important biomarker for dengue hemorrhagic fever and dengue shock syndrome. Here, we developed an Au-decorated nanowire platform and applied it with a sandwich fluorophore-linked immunosorbent well plate assay (FLISA) to detect Dengue NS1 in urine. For the platform, we fabricated zinc oxide (ZnO) nanowires to provide a high surface area and then coated them with gold nanoparticles (ZnO/Au nanowires) to simply modify the Dengue NS1 antibody and enhance the fluorescence intensity. Our platform employs a sandwich FLISA that exhibits high sensitivity, specifically detecting Dengue NS1 with a limit of detection (LOD) of 1.35 pg/mL. This LOD was 4500-fold lower than the LOD of a commercially available kit for Dengue NS1 enzyme-linked immunosorbent assay. We believe that our ZnO/Au nanowire platform has the potential to revolutionize the field of non-invasive diagnostics for dengue.
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  • 文章类型: Journal Article
    UNASSIGNED: Onychomykose ist weit verbreitet und sollte von anderen Nagelerkrankungen unterschieden werden. Eine rasche und genaue Diagnostik ist für die optimale Behandlung des Patienten und ein bestmögliches Ergebnis erforderlich. Nichtinvasive Techniken haben ein wachsendes Potenzial bei der Diagnose von Nagelerkrankungen, einschließlich Onychomykose. In dieser Studie wurde die konfokale Line-Field optische Kohärenztomographie (LC-OCT) als schnelle nichtinvasive Methode zur Diagnose von Onychomykose im Vergleich zur konfokalen Laserscanmikroskopie (KLM), optischen Kohärenztomographie (OCT) und konventionellen Methoden bewertet.
    UNASSIGNED: In dieser prospektiven Studie wurden 86 Patienten mit klinischem Verdacht auf Onychomykose und 14 Kontrollen mittels LC-OCT, OCT und KLM untersucht. KOH-Präparation, Pilzkultur, PCR und Histopathologie wurden als vergleichende konventionelle Methoden eingesetzt.
    UNASSIGNED: LC-OCT hatte die höchste Sensitivität und den höchsten negativen Vorhersagewert aller verwendeten Methoden, dicht gefolgt von PCR und OCT. Die Spezifität und der positive Vorhersagewert der LC-OCT waren genauso hoch wie bei der KLM, während OCT deutlich schlechter abschnitt. Das Goldstandardverfahren Pilzkultur zeigte die geringste Sensitivität und den niedrigsten negativen Vorhersagewert. Nur PCR und Kultur ermöglichten eine Differenzierung der Pilzspezies.
    UNASSIGNED: LC-OCT ermöglicht eine schnelle und nichtinvasive Diagnostik von Onychomykose, mit Vorteilen gegenüber KLM und OCT und ähnlicher diagnostischer Genauigkeit wie die PCR, aber ohne Differenzierung der Pilzarten. Für eine genaue Nageluntersuchung erfordert die LC-OCT gut geschulte und erfahrene Anwender.
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