W. Siljan, D. Sivakumaran, C. Ritz, S. Jenum, T. Ottenhoff, E. Ulvestad, J. Holter, L. Heggelund, H. Grewal
{"title":"Host Transcriptional Signatures Predict Etiology in Community-Acquired Pneumonia: Potential Antibiotic Stewardship Tools","authors":"W. Siljan, D. Sivakumaran, C. Ritz, S. Jenum, T. Ottenhoff, E. Ulvestad, J. Holter, L. Heggelund, H. Grewal","doi":"10.1177/11772719221099130","DOIUrl":"https://doi.org/10.1177/11772719221099130","url":null,"abstract":"Background: Current approaches for pathogen identification in community-acquired pneumonia (CAP) remain suboptimal, leaving most patients without a microbiological diagnosis. If better diagnostic tools were available for differentiating between viral and bacterial CAP, unnecessary antibacterial therapy could be avoided in viral CAP patients. Methods: In 156 adults hospitalized with CAP classified to have bacterial, viral, or mixed viral-bacterial infection based on microbiological testing or both microbiological testing and procalcitonin (PCT) levels, we aimed to identify discriminatory host transcriptional signatures in peripheral blood samples acquired at hospital admission, by applying Dual-color-Reverse-Transcriptase-Multiplex-Ligation-dependent-Probe-Amplification (dc-RT MLPA). Results: In patients classified by microbiological testing, a 9-transcript signature showed high accuracy for discriminating bacterial from viral CAP (AUC 0.91, 95% CI 0.85-0.96), while a 10-transcript signature similarly discriminated mixed viral-bacterial from viral CAP (AUC 0.91, 95% CI 0.86-0.96). In patients classified by both microbiological testing and PCT levels, a 13-transcript signature showed excellent accuracy for discriminating bacterial from viral CAP (AUC 1.00, 95% CI 1.00-1.00), while a 7-transcript signature similarly discriminated mixed viral-bacterial from viral CAP (AUC 0.93, 95% CI 0.87-0.98). Conclusion: Our findings support host transcriptional signatures in peripheral blood samples as a potential tool for guiding clinical decision-making and antibiotic stewardship in CAP.","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46684929","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}
Camille C Gunderson, Rangasudhagar Radhakrishnan, Rohini Gomathinayagam, Sanam Husain, Sheeja Aravindan, Kathleen M Moore, Danny N Dhanasekaran, Muralidharan Jayaraman
{"title":"Circulating Tumor Cell-Free DNA Genes as Prognostic Gene Signature for Platinum Resistant Ovarian Cancer Diagnosis.","authors":"Camille C Gunderson, Rangasudhagar Radhakrishnan, Rohini Gomathinayagam, Sanam Husain, Sheeja Aravindan, Kathleen M Moore, Danny N Dhanasekaran, Muralidharan Jayaraman","doi":"10.1177/11772719221088404","DOIUrl":"https://doi.org/10.1177/11772719221088404","url":null,"abstract":"<p><p>Clinical management of gynecological cancer begins by optimal debulking with first-line platinum-based chemotherapy. However, in ~80% patients, ovarian cancer will recur and is lethal. Prognostic gene signature panel identifying platinum-resistance enables better patient stratification for precision therapy. Retrospectively collected serum from 11 \"poor\" (<6 months progression free interval [PFI]) and 22 \"favorable\" (>24 months PFI) prognosis patients, were evaluated using circulating cell-free DNA (cfDNA). DNA from both groups showed 50 to 10 000 bp fragments. Pairwise analysis of sequenced cfDNA from patients showed that gene dosages were higher for 29 genes and lower for 64 genes in poor than favorable prognosis patients. Gene ontology analysis of higher dose genes predominantly grouped into cytoskeletal proteins, while lower dose genes, as hydrolases and receptors. Higher dosage genes searched for cancer-relatedness in Reactome database indicated 15 genes were referenced with cancer. Among them 3 genes, TGFBR2, ZMIZ2, and NRG2, were interacting with more than 4 cancer-associated genes. Protein expression analysis of tumor samples indicated that TGFBR2 was downregulated and ZMIZ2 was upregulated in poor prognosis patients. Our results indicate that the cfDNA gene dosage combined with protein expression in tumor samples can serve as gene signature panel for prognosis determination amongst ovarian cancer patients.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"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/82/30/10.1177_11772719221088404.PMC8966103.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10677071","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}
S. Shultz, Caroline J Taylor, Riemke Aggio-Bruce, W. T. O'Brien, Mujun Sun, Adrian V Cioanca, George A. Neocleous, Georgia F Symons, R. Brady, A. Hardikar, M. Joglekar, Daniel M Costello, T. O’Brien, R. Natoli, S. McDonald
{"title":"Decrease in Plasma miR-27a and miR-221 After Concussion in Australian Football Players","authors":"S. Shultz, Caroline J Taylor, Riemke Aggio-Bruce, W. T. O'Brien, Mujun Sun, Adrian V Cioanca, George A. Neocleous, Georgia F Symons, R. Brady, A. Hardikar, M. Joglekar, Daniel M Costello, T. O’Brien, R. Natoli, S. McDonald","doi":"10.1177/11772719221081318","DOIUrl":"https://doi.org/10.1177/11772719221081318","url":null,"abstract":"Introduction: Sports-related concussion (SRC) is a common form of brain injury that lacks reliable methods to guide clinical decisions. MicroRNAs (miRNAs) can influence biological processes involved in SRC, and measurement of miRNAs in biological fluids may provide objective diagnostic and return to play/recovery biomarkers. Therefore, this prospective study investigated the temporal profile of circulating miRNA levels in concussed male and female athletes. Methods: Pre-season baseline blood samples were collected from amateur Australian rules football players (82 males, 45 females). Of these, 20 males and 8 females sustained an SRC during the subsequent season and underwent blood sampling at 2-, 6- and 13-days post-injury. A miRNA discovery Open Array was conducted on plasma to assess the expression of 754 known/validated miRNAs. miRNA target identified were further investigated with quantitative real-time PCR (qRT-PCR) in a validation study. Data pertaining to SRC symptoms, demographics, sporting history, education history and concussion history were also collected. Results: Discovery analysis identified 18 candidate miRNA. The consequent validation study found that plasma miR-221-3p levels were decreased at 6d and 13d, and that miR-27a-3p levels were decreased at 6d, when compared to baseline. Moreover, miR-27a and miR-221-3p levels were inversely correlated with SRC symptom severity. Conclusion: Circulating levels of miR-27a-3p and miR-221-3p were decreased in the sub-acute stages after SRC, and were inversely correlated with SRC symptom severity. Although further studies are required, these analyses have identified miRNA biomarker candidates of SRC severity and recovery that may one day assist in its clinical management.","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46526443","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}
Biomarker InsightsPub Date : 2021-10-26eCollection Date: 2021-01-01DOI: 10.1177/11772719211053449
Ker Rui Wong, William T O'Brien, Mujun Sun, Glenn Yamakawa, Terence J O'Brien, Richelle Mychasiuk, Sandy R Shultz, Stuart J McDonald, Rhys D Brady
{"title":"Serum Neurofilament Light as a Biomarker of Traumatic Brain Injury in the Presence of Concomitant Peripheral Injury.","authors":"Ker Rui Wong, William T O'Brien, Mujun Sun, Glenn Yamakawa, Terence J O'Brien, Richelle Mychasiuk, Sandy R Shultz, Stuart J McDonald, Rhys D Brady","doi":"10.1177/11772719211053449","DOIUrl":"https://doi.org/10.1177/11772719211053449","url":null,"abstract":"<p><strong>Introduction: </strong>Serum neurofilament light (NfL) is an emerging biomarker of traumatic brain injury (TBI). However, the effect of peripheral injuries such as long bone fracture and skeletal muscle injury on serum NfL levels is unknown. Therefore, the aim of this study was to determine whether serum NfL levels can be used as a biomarker of TBI in the presence of concomitant peripheral injuries.</p><p><strong>Methods: </strong>Rats were randomly assigned to one of four injury groups: polytrauma (muscle crush + fracture + TBI; n = 11); peripheral injuries (muscle crush + fracture + sham-TBI; n = 12); TBI-only (sham-muscle crush + sham-fracture + TBI; n = 13); and triple-sham (n = 7). At 2-days post-injury, serum levels of NfL were quantified using a Simoa HD-X Analyzer.</p><p><strong>Results: </strong>Compared to triple-sham rats, serum NfL concentrations were higher in rats with peripheral injuries-only, TBI-only, and polytrauma. When compared to peripheral injury-only rats, serum NfL levels were higher in TBI-only and polytrauma rats. No differences were found between TBI-only and polytrauma rats.</p><p><strong>Conclusion: </strong>Serum NfL levels did not differ between TBI-only and polytrauma rats, indicating that significant peripheral injuries did not affect the sensitivity and specificity of serum NfL as a biomarker of moderate TBI. However, the finding of elevated serum NfL levels in rats with peripheral injuries in the absence of a TBI suggests that the presence of such injuries may limit the utility of NfL as a biomarker of less severe TBI (eg, concussion).</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2021-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8d/d9/10.1177_11772719211053449.PMC8554541.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39831627","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}
Biomarker InsightsPub Date : 2021-10-11eCollection Date: 2021-01-01DOI: 10.1177/11772719211047763
Vasiliki Valla, Saba Alzabin, Angeliki Koukoura, Amy Lewis, Anne Ahlmann Nielsen, Efstathios Vassiliadis
{"title":"Companion Diagnostics: State of the Art and New Regulations.","authors":"Vasiliki Valla, Saba Alzabin, Angeliki Koukoura, Amy Lewis, Anne Ahlmann Nielsen, Efstathios Vassiliadis","doi":"10.1177/11772719211047763","DOIUrl":"https://doi.org/10.1177/11772719211047763","url":null,"abstract":"<p><p>Companion diagnostics (CDx) hail promise of improving the drug development process and precision medicine. However, there are various challenges involved in the clinical development and regulation of CDx, which are considered high-risk in vitro diagnostic medical devices given the role they play in therapeutic decision-making and the complications they may introduce with respect to their sensitivity and specificity. The European Union (E.U.) is currently in the process of bringing into effect in vitro Diagnostic Medical Devices Regulation (IVDR). The new Regulation is introducing a wide range of stringent requirements for scientific validity, analytical and clinical performance, as well as on post-market surveillance activities throughout the lifetime of in vitro diagnostics (IVD). Compliance with General Safety and Performance Requirements (GSPRs) adopts a risk-based approach, which is also the case for the new classification system. This changing regulatory framework has an impact on all stakeholders involved in the IVD Industry, including Authorized Representatives, Distributors, Importers, Notified Bodies, and Reference Laboratories and is expected to have a significant effect on the development of new CDx.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2021-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6b/bb/10.1177_11772719211047763.PMC8512279.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39525134","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}
Biomarker InsightsPub Date : 2021-10-11eCollection Date: 2021-01-01DOI: 10.1177/11772719211049852
Steve E Kalloger, Joanna M Karasinska, Cassia Warren, Daniel J Renouf, David F Schaeffer
{"title":"Advancing the Care of Pancreatic Cancer Patients: Moving Beyond Just Tumour Tissue.","authors":"Steve E Kalloger, Joanna M Karasinska, Cassia Warren, Daniel J Renouf, David F Schaeffer","doi":"10.1177/11772719211049852","DOIUrl":"https://doi.org/10.1177/11772719211049852","url":null,"abstract":"<p><p>Biobanking efforts, to establish and grow the pool of available tissue from which evidence on aetiology, therapeutic susceptibility and prognosis of various diseases, have been underway for decades. This is illustrated nowhere better than in cancer. High incidence cancers such as breast, colorectal and lung have seen massive increases in their requisite formularies that have yielded improved prognoses. These discoveries, on a very fundamental level, were made by scientists who had access to tumour tissue and associated clinical data from patient donors. As the research space for higher incidence malignancies became increasingly crowded, attention has turned towards those malignancies with lower incidence. In the same time span, technology has continued to evolve, allowing the next generation of scientists and clinicians to ask more nuanced questions. Inquiries are no longer limited to the -omics of tumour tissue but also include biomarkers of blood and excretory products, concurrent disease status and composition of the gut microbiome. The impact of these new technologies and the questions now facing researchers in low-incidence cancers will be summarized and discussed. Our experience with pancreatic ductal adenocarcinoma will be used as a model for this review.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2021-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/37/55/10.1177_11772719211049852.PMC8512230.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39525136","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}
Biomarker InsightsPub Date : 2021-10-11eCollection Date: 2021-01-01DOI: 10.1177/11772719211049848
Nikhil V Kotha, Rohith S Voora, Alex S Qian, Abhishek Kumar, Edmund M Qiao, Tyler F Stewart, Brent S Rose, Ryan K Orosco
{"title":"Prognostic Utility of Pretreatment Neutrophil-Lymphocyte Ratio in Advanced Larynx Cancer.","authors":"Nikhil V Kotha, Rohith S Voora, Alex S Qian, Abhishek Kumar, Edmund M Qiao, Tyler F Stewart, Brent S Rose, Ryan K Orosco","doi":"10.1177/11772719211049848","DOIUrl":"https://doi.org/10.1177/11772719211049848","url":null,"abstract":"<p><strong>Purpose: </strong>Neutrophil-lymphocyte ratio has been explored as a prognosticator in several cancer types, but its association with larynx cancer outcomes is not well known. We aimed to identify an optimal NLR cutoff point and examine the prognostic utility of this biomarker in patients with locoregionally advanced larynx cancer treated with curative intent.</p><p><strong>Methods: </strong>In the Veterans Affairs' (VA) national database, we identified patients with locoregionally advanced (T3-4N0-3M0) laryngeal squamous cell carcinoma diagnosed between 2000 and 2017 and treated with curative intent. NLR cutoff points were calculated using Contal/O'Quigley's method. Outcomes of larynx cancer-specific survival (CSS), overall survival (OS), and non-larynx cancer survival (NCS) were evaluated in multivariable Cox and Fine-Gray models.</p><p><strong>Results: </strong>In 1047 patients, the optimal pretreatment NLR cutoff was identified as 4.17 - 722 patients with NLR ⩽ 4.17, 325 patients with NLR > 4.17. The elevated NLR cohort had a higher proportion of T4 disease (39.4% vs 28.4%), node positive disease (52.3% vs 43.1%), and surgical treatment (43.7% vs 35.2%). In multivariable analysis, NLR > 4.17 was independently associated with worse OS (HR 1.31, 95% CI 1.12-1.54, <i>P</i> = .001) and worse CSS (HR 1.46, 95% CI 1.17-1.83, <i>P</i> < .001), but not with NCS (HR 0.94, 95% CI 0.75-1.18, <i>P</i> = .58).</p><p><strong>Conclusion: </strong>In locoregionally advanced larynx cancer treated with curative intent, we identified elevated NLR to be associated with inferior OS and CSS. Further prospective studies are needed to investigate pretreatment NLR and our identified 4.17 cutoff as a potential larynx cancer-specific marker for this high risk population.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2021-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/90/02/10.1177_11772719211049848.PMC8512256.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39525135","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}
Biomarker InsightsPub Date : 2021-08-15eCollection Date: 2021-01-01DOI: 10.1177/11772719211034685
Izzet Altintas, Jesper Eugen-Olsen, Santeri Seppälä, Jens Tingleff, Marius Ahm Stauning, Nora Olsen El Caidi, Sanaá Elmajdoubi, Hejdi Gamst-Jensen, Mette B Lindstrøm, Line Jee Hartmann Rasmussen, Klaus Tjelle Kristiansen, Christian Rasmussen, Jan O Nehlin, Thomas Kallemose, Harri Hyppölä, Ove Andersen
{"title":"suPAR Cut-Offs for Risk Stratification in Patients With Symptoms of COVID-19.","authors":"Izzet Altintas, Jesper Eugen-Olsen, Santeri Seppälä, Jens Tingleff, Marius Ahm Stauning, Nora Olsen El Caidi, Sanaá Elmajdoubi, Hejdi Gamst-Jensen, Mette B Lindstrøm, Line Jee Hartmann Rasmussen, Klaus Tjelle Kristiansen, Christian Rasmussen, Jan O Nehlin, Thomas Kallemose, Harri Hyppölä, Ove Andersen","doi":"10.1177/11772719211034685","DOIUrl":"https://doi.org/10.1177/11772719211034685","url":null,"abstract":"<p><strong>Objectives: </strong>Elevated soluble urokinase Plasminogen Activator Receptor (suPAR) is a biomarker associated with adverse outcomes. We aimed to investigate the associations between plasma suPAR levels (testing the cut-offs ⩽4, 4-6, and ⩾6 ng/mL) with risk of 14-day mortality, and with the risk of mechanical ventilation in patients that tested positive for SARS-CoV-2.</p><p><strong>Methods: </strong>Observational cohort study of patients presenting with symptoms of COVID-19 at Department of Emergency Medicine, Amager and Hvidovre Hospital, Denmark from March 19th, 2020 to April 3rd, 2020. Plasma suPAR was measured using suPARnostic technologies. Patients were followed for development of mechanical ventilation and mortality for 14 days. Validation of our findings were carried out in a similar sized COVID-19 patient cohort from Mikkeli Central Hospital, Finland.</p><p><strong>Results: </strong>Among 386 patients with symptoms of COVID-19, the median (interquartile range) age was 64 years (46-77), 57% were women, median suPAR was 4.0 ng/mL (2.7-5.9). In total, 35 patients (9.1%) died during the 14 days follow-up. Patients with suPAR ⩽4 ng/mL (N = 196; 50.8%) had a low risk of mortality (N = 2; 1.0%; negative predictive value of 99.0%, specificity 55.3%, sensitivity 95.2%, positive predictive value 17.4%). Among patients with suPAR ⩾6 ng/mL (N = 92; 23.8%), 16 died (17.4%). About 99 patients (25.6%) tested positive for SARS CoV-2 and of those 12 (12.1%) developed need for mechanical ventilation. None of the SARS-CoV-2 positive patients with suPAR ⩽4 ng/mL (N = 28; 38.8%) needed mechanical ventilation or died. The Mikkeli Central Hospital validation cohort confirmed our findings concerning suPAR cut-offs for risk of development of mechanical ventilation and mortality.</p><p><strong>Conclusions: </strong>Patients with symptoms of COVID-19 and suPAR ⩽4 or ⩾6 ng/mL had low or high risk, respectively, concerning the need for mechanical ventilation or mortality. We suggest cut-offs for identification of risk groups in patients presenting to the ED with symptoms of or confirmed COVID-19.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2021-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/21/38/10.1177_11772719211034685.PMC8371731.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39334117","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}
Biomarker InsightsPub Date : 2021-08-14eCollection Date: 2021-01-01DOI: 10.1177/11772719211035643
Megan G Pino, Kelly A Rich, Stephen J Kolb
{"title":"Update on Biomarkers in Spinal Muscular Atrophy.","authors":"Megan G Pino, Kelly A Rich, Stephen J Kolb","doi":"10.1177/11772719211035643","DOIUrl":"10.1177/11772719211035643","url":null,"abstract":"<p><p>The availability of disease modifying therapies for spinal muscular atrophy (SMA) has created an urgent need to identify clinically meaningful biomarkers. Biomarkers present a means to measure and evaluate neurological disease across time. Changes in biomarkers provide insight into disease progression and may reveal biologic, physiologic, or pharmacologic phenomena occurring prior to clinical detection. Efforts to identify biomarkers for SMA, a genetic motor neuron disease characterized by motor neuron degeneration and weakness, have culminated in a number of putative molecular and physiologic markers that evaluate biological media (eg, blood and cerebrospinal fluid [CSF]) or nervous system function. Such biomarkers include <i>SMN2</i> copy number, SMN mRNA and protein levels, neurofilament proteins (NFs), plasma protein analytes, creatine kinase (CK) and creatinine (Crn), and various electrophysiology and imaging measures. <i>SMN2</i> copy number inversely correlates with disease severity and is the best predictor of clinical outcome in untreated individuals. SMN mRNA and protein are commonly measured in the blood or CSF of patients receiving SMA therapies, particularly those aimed at increasing SMN protein expression, and provide insight into current disease state. NFs have proven to be robust prognostic, disease progression, and pharmacodynamic markers for SMA infants undergoing treatment, but less so for adolescents and adults. Select plasma proteins are altered in SMA individuals and may track response to therapy. CK and Crn from blood correlate with motor function and disease severity status and are useful for predicting which individuals will respond to therapy. Electrophysiology measures comprise the most reliable means for monitoring motor function throughout disease course and are sensitive enough to detect neuromuscular changes before overt clinical manifestation, making them robust predictive and pharmacodynamic biomarkers. Finally, magnetic resonance imaging and muscle ultrasonography are non-invasive techniques for studying muscle structure and physiology and are useful diagnostic tools, but cannot reliably track disease progression. Importantly, biomarkers can provide information about the underlying mechanisms of disease as well as reveal subclinical disease progression, allowing for more appropriate timing and dosing of therapy for individuals with SMA. Recent therapeutic advancements in SMA have shown promising results, though there is still a great need to identify and understand the impact of biomarkers in modulating disease onset and progression.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2021-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bb/b8/10.1177_11772719211035643.PMC8371741.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39334119","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}
Biomarker InsightsPub Date : 2021-06-24eCollection Date: 2021-01-01DOI: 10.1177/11772719211027022
Gönül Açıksarı, Mehmet Koçak, Yasemin Çağ, Lütfiye Nilsun Altunal, Adem Atıcı, Fatma Betül Çelik, Furkan Bölen, Kurtuluş Açıksarı, Mustafa Çalışkan
{"title":"Prognostic Value of Inflammatory Biomarkers in Patients with Severe COVID-19: A Single-Center Retrospective Study.","authors":"Gönül Açıksarı, Mehmet Koçak, Yasemin Çağ, Lütfiye Nilsun Altunal, Adem Atıcı, Fatma Betül Çelik, Furkan Bölen, Kurtuluş Açıksarı, Mustafa Çalışkan","doi":"10.1177/11772719211027022","DOIUrl":"https://doi.org/10.1177/11772719211027022","url":null,"abstract":"<p><strong>Background: </strong>The current knowledge about novel coronavirus-2019 (COVID-19) indicates that the immune system and inflammatory response play a crucial role in the severity and prognosis of the disease. In this study, we aimed to investigate prognostic value of systemic inflammatory biomarkers including C-reactive protein/albumin ratio (CAR), prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in patients with severe COVID-19.</p><p><strong>Methods: </strong>This single-center, retrospective study included a total of 223 patients diagnosed with severe COVID-19. Primary outcome measure was mortality during hospitalization. Multivariate logistic regression analyses were performed to identify independent predictors associated with mortality in patients with severe COVID-19. Receiver operating characteristic (ROC) curve was used to determine cut-offs, and area under the curve (AUC) values were used to demonstrate discriminative ability of biomarkers.</p><p><strong>Results: </strong>Compared to survivors of severe COVID-19, non-survivors had higher CAR, NLR, and PLR, and lower LMR and lower PNI (<i>P</i> < .05 for all). The optimal CAR, PNI, NLR, PLR, and LMR cut-off values for detecting prognosis were 3.4, 40.2, 6. 27, 312, and 1.54 respectively. The AUC values of CAR, PNI, NLR, PLR, and LMR for predicting hospital mortality in patients with severe COVID-19 were 0.81, 0.91, 0.85, 0.63, and 0.65, respectively. In ROC analysis, comparative discriminative ability of CAR, PNI, and NLR for hospital mortality were superior to PLR and LMR. Multivariate analysis revealed that CAR (⩾0.34, <i>P</i> = .004), NLR (⩾6.27, <i>P</i> = .012), and PNI (⩽40.2, <i>P</i> = .009) were independent predictors associated with mortality in severe COVID-19 patients.</p><p><strong>Conclusions: </strong>The CAR, PNI, and NLR are independent predictors of mortality in hospitalized severe COVID-19 patients and are more closely associated with prognosis than PLR or LMR.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2021-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/11772719211027022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39173389","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}