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BACKGROUND: 15-oxo-eicosatetraenoic acid (15-oxo-ETE), is a product of arachidonic acid (AA) metabolism in the 15-lipoxygenase-1 (15-LOX-1) pathway. 15-oxo-ETE was overproduced in the nasal polyps of patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). In this study we investigated the systemic biosynthesis of 15-oxo-ETE and leukotriene E4 (LTE4) and assessed their diagnostic value to identify patients with N-ERD. METHODS: The study included 64 patients with N-ERD, 59 asthmatics who tolerated aspirin well (ATA), and 51 healthy controls. A thorough clinical characteristics of asthmatics included computed tomography of paranasal sinuses. Plasma and urinary 15-oxo-ETE levels, and urinary LTE4 excretion were measured using high-performance liquid chromatography and tandem mass spectrometry. Repeatability and precision of the measurements were tested. RESULTS: Plasma 15-oxo-ETE levels were the highest in N-ERD (p < .001). A receiver operator characteristic (ROC) revealed that 15-oxo-ETE had certain sensitivity (64.06% in plasma, or 88.24% in urine) for N-ERD discrimination, while the specificity was rather limited. Modeling of variables allowed to construct the Aspirin Hypersensitivity Diagnostic Index (AHDI) based on urinary LTE4-to-15-oxo-ETE excretion corrected for sex and the Lund-Mackay score of chronic rhinosinusitis. AHDI outperformed single measurements in discrimination of N-ERD among asthmatics with an area under ROC curve of 0.889, sensitivity of 81.97%, specificity of 87.23%, and accuracy of 86.87%. CONCLUSIONS: We confirmed 15-oxo-ETE as a second to cysteinyl leukotrienes biomarker of N-ERD. An index based on these eicosanoids corrected for sex and Lund-Mackay score has a similar diagnostic value as gold standard oral aspirin challenge in the studied group of patients with asthma.
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With the aim to shorten the time for diagnosis and accelerate access to correct management, a non-invasive diagnostic test for endometriosis was developed and validated. The IVD test combines an ELISA test kit to quantify CA125 and BDNF concentrations in serum and a data treatment algorithm hosted in medical software processing results from the ELISA test and responses to six clinical variables. Serum samples and clinical variables extracted from psychometric questionnaires from 77 patients were collected from the Oxford Endometriosis CaRe Centre biobank (UK). Case/control classification was performed based on laparoscopy and histological verification of the excised lesions. Biomarkers serum concentrations and clinical variables were introduced to the software, which generates the qualitative diagnostic result ("positive" or "negative"). This test allowed the detection of 32% of cases with superficial endometriosis, which is an added value given the limited efficacy of existing imaging techniques. Even in the presence of various confounding medical conditions, the test maintained a specificity of 100%, supporting its suitability for use in patients with underlying medical conditions.
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Biomarcadores , Antígeno Ca-125 , Endometriosis , Humanos , Endometriosis/diagnóstico , Endometriosis/sangre , Endometriosis/patología , Femenino , Adulto , Antígeno Ca-125/sangre , Biomarcadores/sangre , Factor Neurotrófico Derivado del Encéfalo/sangre , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Persona de Mediana Edad , Proteínas de la Membrana/sangre , Algoritmos , Pruebas Diagnósticas de Rutina/métodos , Sensibilidad y EspecificidadRESUMEN
The emergence of variants of SARS-CoV-2 has created challenges for the testing infrastructure. Although large-scale genome sequencing of SARS-CoV-2 has facilitated hospital and public health responses, access to sequencing facilities globally is variable and turnaround times can be significant, so there is a requirement for rapid and cost-effective alternatives. Applying a polymerase chain reaction (PCR)-based single nucleotide polymorphism (SNP) approach enables rapid (<4 h) identification of SARS-CoV-2 lineages from nucleic acid extracts, through the presence or absence of a panel of defined of genomic polymorphisms. For example, the B.1.1.7 lineage ("UK", "Alpha", or "Kent" variant) is characterised by 23 mutations compared to the reference strain, and the most biologically significant of these are found in the S gene. We have developed a SARS-CoV-2 typing assay focused on five positions in the S gene (HV69/70, N501, K417, E484 and P681). This configuration can identify a range of variants, including all the "Variants of Concern" currently designated by national and international public health bodies. The panel has been evaluated using a range of clinical isolates and standardised control materials at four UK hospitals and shows excellent concordance with the known lineage information derived from full sequence analysis. The assay has a turnaround time of about three hours for a set of up to 24 samples and has been utilised to identify emerging variants in a clinical setting.
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Prueba de Ácido Nucleico para COVID-19/métodos , COVID-19/diagnóstico , Reacción en Cadena de la Polimerasa Multiplex/métodos , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Genoma Viral/genética , Humanos , Técnicas de Amplificación de Ácido Nucleico/métodos , Polimorfismo de Nucleótido Simple/genética , Sensibilidad y Especificidad , Glicoproteína de la Espiga del Coronavirus/genética , Secuenciación Completa del Genoma/métodosRESUMEN
Introduction: Traumatic spinal cord injury (TSCI) presents a diagnostic challenge as it may have dramatic consequences for the affected patient. Additional biomarkers are needed for improved care and personalized therapy. Objective: Serum selenium binding protein 1 (SELENBP1) has been detected in myocardial infarction, reflecting hypoxic tissue damage and recovery odds. As SELENBP1 is usually not detected in the serum of healthy subjects, we tested the hypothesis that it may become detectable in TSCI and indicate tissue damage and regeneration odds. Methods: In this prospective observational study, patients with comparable injuries were allocated to three groups; vertebral body fractures without neurological impairment (control "C"), TSCI without remission ("G0"), and TSCI with signs of remission ("G1"). Consecutive serum samples were available from different time points and analyzed for SELENBP1 by sandwich immunoassay, for trace elements by X-ray fluorescence and for cytokines by multiplex immunoassays. Results: Serum SELENBP1 was elevated at admission in relation to the degree of neurological impairment [graded as A, B, C, or D according to the American Spinal Injury Association (AISA) impairment scale (AIS)]. Patients with the most severe neurological impairment (classified as AIS A) exhibited the highest SELENBP1 concentrations (p = 0.011). During the first 3 days, SELENBP1 levels differed between G0 and G1 (p = 0.019), and dynamics of SELENBP1 correlated to monocyte chemoattractant protein 1, chemokine ligand 3 and zinc concentrations. Conclusion: Circulating SELENBP1 concentrations are related to the degree of neurological impairment in TSCI and provide remission odds information. The tight correlation of SELENBP1 with CCL2 levels provides a novel link between Se metabolism and immune cell activation, with potential relevance for neurological damage and regeneration processes, respectively.
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BACKGROUND: In most of the world, diagnostic surgery remains the most frequent approach for indeterminate thyroid cytology. Although several molecular tests are available for testing in centralized commercial laboratories in the United States, there are no available kits for local laboratory testing. The aim of this study was to develop a prototype in vitro diagnostic (IVD) gene classifier for the further characterization of nodules with an indeterminate thyroid cytology. METHODS: In a first stage, the expression of 18 genes was determined by quantitative polymerase chain reaction (qPCR) in a broad histopathological spectrum of 114 fresh-tissue biopsies. Expression data were used to train several classifiers by supervised machine learning approaches. Classifiers were tested in an independent set of 139 samples. In a second stage, the best classifier was chosen as a model to develop a multiplexed-qPCR IVD prototype assay, which was tested in a prospective multicenter cohort of fine-needle aspiration biopsies. RESULTS: In tissue biopsies, the best classifier, using only 10 genes, reached an optimal and consistent performance in the ninefold cross-validated testing set (sensitivity 93% and specificity 81%). In the multicenter cohort of fine-needle aspiration biopsy samples, the 10-gene signature, built into a multiplexed-qPCR IVD prototype, showed an area under the curve of 0.97, a positive predictive value of 78%, and a negative predictive value of 98%. By Bayes' theorem, the IVD prototype is expected to achieve a positive predictive value of 64-82% and a negative predictive value of 97-99% in patients with a cancer prevalence range of 20-40%. CONCLUSIONS: A new multiplexed-qPCR IVD prototype is reported that accurately classifies thyroid nodules and may provide a future solution suitable for local reference laboratory testing.
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Regulación Neoplásica de la Expresión Génica , Proteínas de Neoplasias/metabolismo , Glándula Tiroides/metabolismo , Neoplasias de la Tiroides/diagnóstico , Nódulo Tiroideo/diagnóstico , Biomarcadores de Tumor/metabolismo , Biopsia con Aguja Fina , Chile/epidemiología , Estudios de Cohortes , Biología Computacional , Diagnóstico Diferencial , Sistemas Especialistas , Estudios de Seguimiento , Humanos , Aprendizaje Automático , Proteínas de Neoplasias/genética , Estadificación de Neoplasias , Guías de Práctica Clínica como Asunto , Valor Predictivo de las Pruebas , Prevalencia , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Glándula Tiroides/patología , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/epidemiología , Nódulo Tiroideo/metabolismo , Nódulo Tiroideo/patologíaRESUMEN
In the 17(th) issue of News from the Biological Stain Commission (BSC) under the heading of Regulatory affairs, the Biological Stain Commission's International Affairs Committee presents information from the 20(th) meeting of ISO/TC 212 Clinical laboratory testing and in vitro diagnostic test systems held on October 15 - 17, 2014 in Toronto, Canada, and from the 29(th) meeting of CEN/TC 140 In vitro diagnostic medical devices held on February 3, 2015 in Berlin, Germany.
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Coloración y Etiquetado , Colorantes , Congresos como Asunto , Humanos , Coloración y Etiquetado/tendenciasRESUMEN
In the 16(th) issue of News from the Biological Stain Commission (BSC) under the heading of Regulatory affairs, the Biological Stain Commission's International Affairs Committee presents information from the 28(th) meeting of CEN/TC 140 In vitro diagnostic medical devices held on October 23, 2013 in Berlin, Germany. Information is also presented from the 19(th) meeting of ISO/TC 212 Clinical laboratory testing and in vitro diagnostic test systems held on October 19 - 21, 2013 in Singapore.