Biomarker Insights最新文献

{"title":"Caveat Medicus: It's Time to Re-Think Stratification, You May Not Be Helping.","authors":"Ognjen Arandjelović","doi":"10.1177/11772719231174746","DOIUrl":"https://doi.org/10.1177/11772719231174746","url":null,"abstract":"<p><strong>Background: </strong>The focus of the present Letter is on the large and seemingly fertile body of work captured under the umbrella of 'patient stratification'.</p><p><strong>Objectives: </strong>I identify and explain a fundamental methodological flaw underlying the manner in which the development of an increasingly large number of new stratification strategies is approached.</p><p><strong>Design: </strong>I show an inherent conflict between the assumptions made, and the very purpose of stratification and its application in practice.</p><p><strong>Methods: </strong>I analyse the methodological underpinnings of stratification as presently done and draw parallels with conceptually similarly flawed precedents which are now widely recognized.</p><p><strong>Results: </strong>The highlighted flaw is shown to undermine the overarching ultimate goal of improved patient outcomes by undue fixation on an ill-founded proxy.</p><p><strong>Conclusion: </strong>I issue a call for a re-think of the problem and the processes leading to the adoption of new stratification strategies in the clinic.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"18 ","pages":"11772719231174746"},"PeriodicalIF":3.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10186568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9495459","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}

{"title":"Validation of Prognostic Club Cell Secretory Protein (CC16) Cut-point in an Independent ALTA Cohort.","authors":"Sultan Almuntashiri,&nbsp;Aaron Chase,&nbsp;Andrea Sikora,&nbsp;Duo Zhang","doi":"10.1177/11772719231156308","DOIUrl":"https://doi.org/10.1177/11772719231156308","url":null,"abstract":"<p><strong>Background: </strong>Club cell secretory protein (CC16) has demonstrated utility as a lung-specific biomarker in predicting mortality in acute respiratory distress syndrome (ARDS). These findings have been observed in pre-clinical trials and a re-analysis of a large, randomized controlled trial of ARDS (Fluid and Catheter Treatment Trial (FACTT)).</p><p><strong>Objectives: </strong>The purpose of this study was to validate previous findings by evaluating CC16 level as a mortality predictor in patients from the albuterol to treat acute lung injury (ALTA) trial.</p><p><strong>Design and method: </strong>In this secondary biomarker analysis, plasma CC16 level was measured from 100 ALTA subjects using enzyme-linked immunosorbent assay (ELISA). The rate of mortality was assessed in patients with high (⩾45 ng/mL) versus low CC16 (<45 ng/mL) levels. This cut-off level was applied based on our previous analysis from FACTT trial. Significance was assessed using Kaplan-Meier curves and a log-rank test.</p><p><strong>Results: </strong>Subjects were an average of 50 years old and 46% of them were females. Patients with high CC16 levels had higher 90-day mortality compared to those with low CC16 levels, (37.73% vs 8.95%, <i>P</i> < .001). Other clinical outcomes including ICU-free days, ventilator-free days, and organ failure free days were significantly different between the groups (All <i>P</i> < .05).</p><p><strong>Conclusion: </strong>In this validation study, we demonstrated that ARDS patients with high plasma CC16 concentration had a higher mortality rate than those with low CC16 levels, confirming previous findings that CC16 levels are associated with ARDS mortality.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"18 ","pages":"11772719231156308"},"PeriodicalIF":3.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4b/71/10.1177_11772719231156308.PMC9940244.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9088963","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}

{"title":"What is the Diagnostic Accuracy of Novel Urine Biomarkers for Urinary Tract Infection?","authors":"George Edwards,&nbsp;Anna Seeley,&nbsp;Adam Carter,&nbsp;Maia Patrick Smith,&nbsp;Elizabeth LA Cross,&nbsp;Kathryn Hughes,&nbsp;Ann Van den Bruel,&nbsp;Martin J Llewelyn,&nbsp;Jan Y Verbakel,&nbsp;Gail Hayward","doi":"10.1177/11772719221144459","DOIUrl":"https://doi.org/10.1177/11772719221144459","url":null,"abstract":"<p><strong>Background: </strong>Urinary tract infection (UTI) affects half of women at least once in their lifetime. Current diagnosis involves urinary dipstick and urine culture, yet both methods have modest diagnostic accuracy, and cannot support decision-making in patient populations with high prevalence of asymptomatic bacteriuria, such as older adults. Detecting biomarkers of host response in the urine of hosts has the potential to improve diagnosis.</p><p><strong>Objectives: </strong>To synthesise the evidence of the diagnostic accuracy of novel biomarkers for UTI, and of their ability to differentiate UTI from asymptomatic bacteriuria.</p><p><strong>Design: </strong>A systematic review.</p><p><strong>Data sources and methods: </strong>We searched MEDLINE, EMBASE, CINAHL and Web of Science for studies of novel biomarkers for the diagnosis of UTI. We excluded studies assessing biomarkers included in urine dipsticks as these have been well described previously. We included studies of adult patients (≥16 years) with a suspected or confirmed urinary tract infection using microscopy and culture as the reference standard. We excluded studies using clinical signs and symptoms, or urine dipstick only as a reference standard. Quality appraisal was performed using QUADAS-2. We summarised our data using point estimates and data accuracy statistics.</p><p><strong>Results: </strong>We included 37 studies on 4009 adults measuring 66 biomarkers. Study quality was limited by case-control design and study size; only 4 included studies had a prospective cohort design. IL-6 and IL-8 were the most studied biomarkers. We found plausible evidence to suggest that IL-8, IL-6, GRO-a, sTNF-1, sTNF-2 and MCR may benefit from more rigorous evaluation of their potential diagnostic value for UTI.</p><p><strong>Conclusions: </strong>There is insufficient evidence to recommend the use of any novel biomarker for UTI diagnosis at present. Further evaluation of the more promising candidates, is needed before they can be recommended for clinical use.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"18 ","pages":"11772719221144459"},"PeriodicalIF":3.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9902898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10679738","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}

{"title":"Copeptin Reflect Left Ventricular Systolic Function at Early Stage of Acute Myocardial Infarction in a Pig Model.","authors":"Wenjia Li,&nbsp;Wenjian Sun,&nbsp;Liang Lyu,&nbsp;Gang Wang,&nbsp;Weixin Yang,&nbsp;Hongfei An,&nbsp;Liling Chen,&nbsp;Jianhui Fan,&nbsp;Yan Yue,&nbsp;Rongshun Zhang","doi":"10.1177/11772719231171764","DOIUrl":"https://doi.org/10.1177/11772719231171764","url":null,"abstract":"<p><strong>Introduction: </strong>Measurement of biomarkers early after acute myocardial infarction (AMI) might provide a cost-effective and widely available tool to assess infarct severity, myocardial dysfunction, and clinical outcomes. We aimed to induce AMI in miniature pigs, measure the levels of serum biomarkers and global LV function dynamically and explore the release kinetics and optimal sampling time points of copeptin and its correlation with global LV function.</p><p><strong>Methods: </strong>We induced AMI in the experimental group using a closed-chest model. Left ventricular (LV) function was detected by dual-source computed tomography (DSCT) and serum copeptin was determined by ELISA.</p><p><strong>Results: </strong>The serum copeptin levels were increased at 1 hour, peaked at 3 hours, gradually decreased after 6 hours, and returned to baseline 3 days after AMI. At 3 to 6 hours, the copeptin cutoff of 16.97 to 17.44 pmol/l had 100% sensitivity and 100% specificity (<i>P</i> ⩽ .001) for AMI. Serum copeptin levels at 3 hours and 3 days were negatively correlated with the 3-hours LVEF (<i>P</i> ⩽ .001), respectively.</p><p><strong>Conclusion: </strong>Serum copeptin levels change in time, and measurements at 3 to 6 hours after AMI had the highest predictive value.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"18 ","pages":"11772719231171764"},"PeriodicalIF":3.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/02/e7/10.1177_11772719231171764.PMC10155031.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10289659","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}

{"title":"Implementation of a Customized Tertiary Analysis Platform for the Reporting of Somatic Variants.","authors":"Kala F Schilter,&nbsp;Sarah Dubay,&nbsp;Matt Stachowiak,&nbsp;Alysia Kaplan,&nbsp;Abby Stauffenger,&nbsp;Honey V Reddi","doi":"10.1177/11772719231178618","DOIUrl":"https://doi.org/10.1177/11772719231178618","url":null,"abstract":"<p><p>Precision medicine for oncology requires the evaluation of variants identified in molecular profiling of solid tumors and hematologic malignancies. This includes evaluation of pre-analytical and postanalytical quality metrics, variant interpretation, classification, and tiering as outlined in established guidelines, association with clinical significance such as FDA approved drugs and clinical trials, and finally comprehensive reporting. This study documents our experience with the customization and implementation of a software platform that facilitates these requirements for effective reporting of somatic variants.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"18 ","pages":"11772719231178618"},"PeriodicalIF":3.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/63/ba/10.1177_11772719231178618.PMC10259170.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9686203","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}

{"title":"Identification of Potential Urinary Metabolite Biomarkers of Pseudomonas aeruginosa Ventilator-Associated Pneumonia","authors":"B. Jongers, A. Hotterbeekx, Kenny Bielen, P. Vervliet, J. Boddaert, C. Lammens, E. Fransen, G. Baggerman, A. Covaci, H. Goossens, S. Malhotra-Kumar, P. Jorens, S. Kumar-Singh","doi":"10.1177/11772719221099131","DOIUrl":"https://doi.org/10.1177/11772719221099131","url":null,"abstract":"Introduction: Ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa is a major cause of morbidity and mortality in hospital intensive care units (ICU). Rapid identification of P. aeruginosa-derived markers in easily accessible patients’ samples can enable an early detection of P. aeruginosa VAP (VAP-PA), thereby stewarding antibiotic use and improving clinical outcomes. Methods: Metabolites were analysed using liquid chromatography-mass spectrometry (LC-MS) in prospectively collected urine samples from mechanically ventilated patients admitted to the Antwerp University Hospital ICU. Patients were followed from the start of mechanical ventilation (n = 100 patients) till the time of clinical diagnosis of VAP (n = 13). Patients (n = 8) in whom diagnosis of VAP was further confirmed by culturing respiratory samples and urine samples were studied for semi-quantitative metabolomics. Results: We first show that multivariate analyses highly discriminated VAP-PA from VAP–non-PA as well as from the pre-infection groups (R2 = .97 and .98, respectively). A further univariate analysis identified 58 metabolites that were significantly elevated or uniquely present in VAP-PA compared to the VAP–non-PA and pre-infection groups (P < .05). These comprised both a known metabolite of histidine as well as a novel nicotine metabolite. Most interestingly, we identified 3 metabolites that were not only highly upregulated for, but were also highly specific to, VAP-PA, as these metabolites were completely absent in all pre-infection timepoints and in VAP–non-PA group. Conclusions: Considerable differences exist between urine metabolites in VAP-PA compared to VAP due to other bacterial aetiologies as well to non-VAP (pre-infection) timepoints. The unique urinary metabolic biomarkers we describe here, if further validated, could serve as highly specific diagnostic biomarkers of VAP-PA.","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46598480","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":"Advantages and Limitations of Monitoring Circulating Tumor DNA Levels to Predict the Prognosis of Patients Diagnosed With Gastric Cancer.","authors":"Wan He,&nbsp;Jingxin Yang,&nbsp;Xiao Sun,&nbsp;Shunda Jiang,&nbsp;Jinchan Jiang,&nbsp;Ming Liu,&nbsp;Tianhao Mu,&nbsp;Yingmei Li,&nbsp;Xiaoni Zhang,&nbsp;Jingxian Duan,&nbsp;Ruilian Xu","doi":"10.1177/11772719221141525","DOIUrl":"https://doi.org/10.1177/11772719221141525","url":null,"abstract":"<p><p>Next-generation sequencing-based genomic profiling facilitates biomarker detection by cell-free DNA (cfDNA) liquid biopsy. However, the efficiency of mutation calling and the prognostic value of cfDNA biomarkers are disputed. We investigated 24 patients with gastric cancer in this study, using a 605-gene sequencing panel to sequence their plasma cfDNA and tumor tissue DNA. The mutation concordance between plasma cfDNA and tumor tissue DNA was 70.6% in stage IV gastric cancer and 30.2% in stage III gastric cancer, indicating insufficient mutation detection rates in stage III and early-stage cancer. When compared with total cfDNA load and blood tumor mutation burden (bTMB), the variant allele frequencies (VAF) of commonly mutated genes are highly accurate in representing disease burden. Further, VAF are a better prognostic indicator compared with serum biomarkers including carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), cancer antigen 125 (CA125), and alpha-fetoprotein (AFP). The use of cfDNA in molecular profiling of patients allows prediction of patient survival and clinical response, as well as the development of personalized therapy regimens.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"17 ","pages":"11772719221141525"},"PeriodicalIF":3.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/33/80/10.1177_11772719221141525.PMC9751168.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10406501","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}

{"title":"Utilization of Prognostic Biomarker Soluble Urokinase Plasminogen Activator Receptor in the Emergency Department: A Tool for Safe and More Efficient Decision-making","authors":"Ria M Holstein, M. Mäkinen, M. Castrén, J. Kaartinen","doi":"10.1177/11772719221081789","DOIUrl":"https://doi.org/10.1177/11772719221081789","url":null,"abstract":"Introduction: Risk stratification in the emergency departments (EDs) is in critical need for new applications due to ED overcrowding and hospitalization of older people. We aimed to evaluate the expediency, efficiency and safety of a prognostic biomarker, soluble urokinase plasminogen activator receptor (suPAR), as a tool for the risk assessment of patients arriving at the ED. Methods: We performed a comparative cross-sectional study in 2 emergency departments (EDs), suPAR measurements being incorporated into routine blood sampling in the intervention ED. The primary outcome was the number of discharges from the ED. The importance of the outcomes was examined by appropriate multi- or bivariate analysis. Results: The absolute and relative number of discharges were similar between the intervention and control groups [121 (55.3%) vs 62 (55.9%)]. No significant differences between the groups were seen in the length of stays in the ED. Patients with low suPAR values were more likely discharged and patients with high suPAR values more likely admitted to hospital. Two admitted patients with low suPAR values could have been discharged safely. Conclusion: The utilization of suPAR did not increase the risk for neither positive nor negative outcomes. Low suPAR values could be potential in discharging more patients safely. Instead of unselected patient populations, the benefits of suPAR measurements in the ED could emerge in the assessment of a more precisely determined and selected group of patients.","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"17 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44637318","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":"Immune Checkpoint Inhibitors in Triple Negative Breast Cancer: The Search for the Optimal Biomarker","authors":"SA Qureshi, N. Chan, Mridula A. George, S. Ganesan, D. Toppmeyer, C. Omene","doi":"10.1177/11772719221078774","DOIUrl":"https://doi.org/10.1177/11772719221078774","url":null,"abstract":"Triple negative breast cancer (TNBC) is a high-risk and aggressive malignancy characterized by the absence of estrogen receptors (ER) and progesterone receptors (PR) on the surface of malignant cells, and by the lack of overexpression of human epidermal growth factor 2 (HER2). It has limited therapeutic options compared to other subtypes of breast cancer. There is now a growing body of evidence on the role of immunotherapy in TNBC, however much of the data from clinical trials is conflicting and thus, challenging for clinicians to integrate the data into clinical practice. Landmark phase III trials using immunotherapy in the early-stage neoadjuvant setting concluded that the addition of immunotherapy to chemotherapy improved the pathologic complete response (pCR) rate compared to chemotherapy with placebo while others found no significant improvement in pCR. Phase III trials have investigated the utility of immunotherapy in previously untreated metastatic TNBC, and these studies have similarly arrived at inconsistent conclusions. Some studies showed no benefit while others demonstrated a clinically significant improvement in overall survival in the PD-L1 positive population. It is not yet clear which biomarkers are most useful, and assays for these biomarkers have not been standardized. Given the often serious and severe side effects of immunotherapy, it is important and necessary to identify predictive biomarkers of response and resistance in order to enhance patient selection. In this review, we will discuss both the challenges of traditional biomarkers and the opportunities of emerging biomarkers for patient selection.","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47216587","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":"The Availability of Human Biospecimens to Support Biomarker Research","authors":"T. Tarling, J. Byrne, Peter H. Watson","doi":"10.1177/11772719221091750","DOIUrl":"https://doi.org/10.1177/11772719221091750","url":null,"abstract":"Preserved biospecimens held in biobank inventories and clinical archives are important resources for biomarker research. Recent advances in technologies have led to an increase in use of clinical archives in particular, in order to study retrospective cohorts and to generate data relevant to tissue biomarkers. This raises the question of whether the current sizes of biobank inventories are appropriate to meet the demands of biomarker research. This commentary discusses this question by considering data concerning overall biobank and biospecimen numbers to estimate current biospecimen supply and use. The data suggests that biospecimen supply exceeds current demand. Therefore, it may be important for individual biobanks to reassess the targets for their inventories, consider culling unused portions of these inventories, and shift resources towards providing prospective custom biobanking services.","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46273835","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}