Biomarker Insights[JOURNAL]
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200 papers
Moving with the Times: The Health Science Alliance (HSA) Biobank, Pathway to Sustainability.
Quinn CM, Porwal M, Meagher NS … +10 more , Hettiaratchi A, Power C, Jonnaggadala J, McCullough S, Macmillan S, Tang K, Liauw W, Goldstein D, Zeps N, Crowe PJ
Biomark Insights · 2021 · PMID 35173407 · Full text
Human biobanks are recognised as vital components of translational research infrastructure. With the growth in personalised and precision medicine, and the associated expansion of biomarkers and novel therapeutics under...
Human biobanks are recognised as vital components of translational research infrastructure. With the growth in personalised and precision medicine, and the associated expansion of biomarkers and novel therapeutics under development, it is critical that researchers can access a strong collection of patient biospecimens, annotated with clinical data. Biobanks globally are undertaking transformation of their operating models in response to changing research needs; transition from a 'classic' model representing a largely retrospective collection of pre-defined specimens to a more targeted, prospective collection model, although there remains a research need for both models to co-exist. Here we introduce the Health Science Alliance (HSA) Biobank, established in 2012 as a classic biobank, now transitioning to a hybrid operational model. Some of the past and current challenges encountered are discussed including clinical annotation, specimen utilisation and biobank sustainability, along with the measures the HSA Biobank is taking to address these challenges. We describe new directions being explored, going beyond traditional specimen collection into areas involving bioimages, microbiota and live cell culture. The HSA Biobank is working in collaboration with clinicians, pathologists and researchers, piloting a sustainable, robust platform with the potential to integrate future needs.
Query About Validity of uVDBP as a Biomarker of Steroid-Resistant Nephrotic Syndrome.
Aoun AH
Biomark Insights · 2022 · PMID 35153471 · Full text
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Relationship Between Anti-DFS70 Autoantibodies and Oxidative Stress.
Krzemień P, Kasperczyk S, Banach M … +18 more , Kasperczyk A, Dobrakowski M, Tomasik T, Windak A, Mastej M, Catapano A, Ray KK, Mikhailidis DP, Toth PP, Howard G, Lip GY, Tomaszewski M, Charchar FJ, Sattar N, Williams B, MacDonald TM, Penson PE, Jóźwiak JJ
Biomark Insights · 2022 · PMID 35125863 · Full text
BACKGROUND: The anti-DFS70 autoantibodies are one of the most commonly and widely described agent of unknown clinical significance, frequently detected in healthy individuals. It is not known whether the DFS70 autoantibo...
BACKGROUND: The anti-DFS70 autoantibodies are one of the most commonly and widely described agent of unknown clinical significance, frequently detected in healthy individuals. It is not known whether the DFS70 autoantibodies are protective or pathogenic. One of the factors suspected of inducing the formation of anti-DFS70 antibodies is increased oxidative stress. We evaluated the coexistence of anti-DFS70 antibodies with selected markers of oxidative stress and investigated whether these antibodies could be considered as indirect markers of oxidative stress. METHODS: The intensity of oxidative stress was measured in all samples via indices of free-radical damage to lipids and proteins such as total oxidant status (TOS), concentrations of lipid hydroperoxides (LPH), lipofuscin (LPS), and malondialdehyde (MDA). The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid concentration (UA), were also measured, as well as the activity of superoxide dismutase (SOD). Based on TOS and TAS values, the oxidative stress index (OSI) was calculated. All samples were also tested with indirect immunofluorescence assay (IFA) and 357 samples were selected for direct monospecific anti DFS70 enzyme-linked immunosorbent assay (ELISA) testing. RESULTS: The anti-DFS70 antibodies were confirmed by ELISA test in 21.29% of samples. Compared with anti-DFS70 negative samples we observed 23% lower concentration of LPH ( = .038) and 11% lower concentration of UA ( = .005). TOS was 20% lower ( = .014). The activity of SOD was up to 5% higher ( = .037). The Pearson correlation showed weak negative correlation for LPH, UA, and TOS and a weak positive correlation for SOD activity. CONCLUSION: In samples positive for the anti-DFS70 antibody a decreased level of oxidative stress was observed, especially in the case of samples with a high antibody titer. Anti-DFS70 antibodies can be considered as an indirect marker of reduced oxidative stress or a marker indicating the recent intensification of antioxidant processes.
Evaluation of a Prognostic Epigenetic Classification System in Chronic Lymphocytic Leukemia Patients.
Grimm C, Herling CD, Komnidi A … +4 more , Hussong M, Kreuzer KA, Hallek M, Schweiger MR
Biomark Insights · 2022 · PMID 35095271 · Full text
BACKGROUND: Methylation at 5 CpG sites was previously shown to classify chronic lymphocytic leukemia (CLL) into 3 prognostic subgroups. Here, we aimed to validate the marker set in an additional cohort and to evaluate it...
BACKGROUND: Methylation at 5 CpG sites was previously shown to classify chronic lymphocytic leukemia (CLL) into 3 prognostic subgroups. Here, we aimed to validate the marker set in an additional cohort and to evaluate its clinical utility for CLL patient stratification. METHODS: We evaluated this epigenetic marker set in 79 German patients using bisulfite treatment followed by pyrosequencing and classification using a support vector machine-learning tool. RESULTS: The n-CLL, i-CLL, and m-CLL classification was detected in 28 (35%), 10 (13%), and 41 (51%) patients, respectively. Epigenetic grouping was associated with mutational status ( = 2 × 10), isolated ( = 9 × 10), ( = .015), complex karyotype ( = .005), VH-usage, and clinical outcome as time to first treatment ( = 1.4 × 10) and overall survival ( = .003). Multivariate Cox regression analysis identified n-CLL as a factor for earlier treatment hazard ratio (HR), 6.3 (95% confidence interval [CI] 2.4-16.4; = .0002) compared to IGHV mutational status (HR 4.6, 95% CI 1.9-11.3, = .0008). In addition, when comparing the prognostic value of the epigenetic classification system with the IGHV classification, epigenetic grouping performed better compared to IGHV mutational status using Kaplan-Meier estimation and allowed the identification of a third, intermediate (i-CLL) group. Thus, our study confirmed the prognostic value of the epigenetic marker set for patient stratification in routine clinical diagnostics.
Serum Neurofilament Light as a Biomarker of Traumatic Brain Injury in the Presence of Concomitant Peripheral Injury.
Wong KR, O'Brien WT, Sun M … +6 more , Yamakawa G, O'Brien TJ, Mychasiuk R, Shultz SR, McDonald SJ, Brady RD
Biomark Insights · 2021 · PMID 34720579 · Full text
INTRODUCTION: 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...
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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).
Advancing the Care of Pancreatic Cancer Patients: Moving Beyond Just Tumour Tissue.
Kalloger SE, Karasinska JM, Warren C … +2 more , Renouf DJ, Schaeffer DF
Biomark Insights · 2021 · PMID 34658620 · Full text
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 n...
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.
Prognostic Utility of Pretreatment Neutrophil-Lymphocyte Ratio in Advanced Larynx Cancer.
Kotha NV, Voora RS, Qian AS … +5 more , Kumar A, Qiao EM, Stewart TF, Rose BS, Orosco RK
Biomark Insights · 2021 · PMID 34658619 · Full text
PURPOSE: 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...
PURPOSE: 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. METHODS: 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. RESULTS: 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, = .001) and worse CSS (HR 1.46, 95% CI 1.17-1.83, < .001), but not with NCS (HR 0.94, 95% CI 0.75-1.18, = .58). CONCLUSION: 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.
Companion Diagnostics: State of the Art and New Regulations.
Valla V, Alzabin S, Koukoura A … +3 more , Lewis A, Nielsen AA, Vassiliadis E
Biomark Insights · 2021 · PMID 34658618 · Full text
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 consi...
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.
Update on Biomarkers in Spinal Muscular Atrophy.
Pino MG, Rich KA, Kolb SJ
Biomark Insights · 2021 · PMID 34421296 · Full text
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 d...
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 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. 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.
suPAR Cut-Offs for Risk Stratification in Patients With Symptoms of COVID-19.
Altintas I, Eugen-Olsen J, Seppälä S … +13 more , Tingleff J, Stauning MA, El Caidi NO, Elmajdoubi S, Gamst-Jensen H, Lindstrøm MB, Rasmussen LJH, Kristiansen KT, Rasmussen C, Nehlin JO, Kallemose T, Hyppölä H, Andersen O
Biomark Insights · 2021 · PMID 34421295 · Full text
OBJECTIVES: 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...
OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Prognostic Value of Inflammatory Biomarkers in Patients with Severe COVID-19: A Single-Center Retrospective Study.
Açıksarı G, Koçak M, Çağ Y … +6 more , Altunal LN, Atıcı A, Çelik FB, Bölen F, Açıksarı K, Çalışkan M
Biomark Insights · 2021 · PMID 34248354 · Full text
BACKGROUND: 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 aim...
BACKGROUND: 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. METHODS: 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. RESULTS: Compared to survivors of severe COVID-19, non-survivors had higher CAR, NLR, and PLR, and lower LMR and lower PNI ( < .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, = .004), NLR (⩾6.27, = .012), and PNI (⩽40.2, = .009) were independent predictors associated with mortality in severe COVID-19 patients. CONCLUSIONS: 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.
Building Research Support Capacity across Human Health Biobanks during the COVID-19 Pandemic.
Byrne JA, Carpenter JE, Carter C … +4 more , Phillips K, Braye S, Watson PH, Rush A
Biomark Insights · 2021 · PMID 34177256 · Full text
Human health biobanks are forms of research infrastructure that supply biospecimens and associated data to researchers, and therefore juxtapose the activities of clinical care and biomedical research. The discipline of b...
Human health biobanks are forms of research infrastructure that supply biospecimens and associated data to researchers, and therefore juxtapose the activities of clinical care and biomedical research. The discipline of biobanking has existed for over 20 years and is supported by several international professional societies and dedicated academic journals. However, despite both rising research demand for human biospecimens, and the growth of biobanking as an academic discipline, many individual biobanks continue to experience sustainability challenges. This commentary will summarize how the COVID-19 pandemic is creating new challenges and opportunities for both the health biobanking sector and the supporting discipline of biobanking. While the challenges for biobanks may be numerous and acute, there are opportunities for both individual biobanks and the discipline of biobanking to embrace change such that biobanks can continue to support and drive biomedical research. We will therefore describe numerous practical steps that individual biobanks and/or the discipline of biobanking can take to survive and possibly thrive in response to the COVID-19 pandemic.
Effect of Methylprednisolone on Inflammation and Coagulation in Patients with Severe COVID-19: A Retrospective Cohort Study.
Tromp K, van der Zee P, Rokx C … +3 more , van Kampen J, Gommers D, Endeman H
Biomark Insights · 2021 · PMID 34158797 · Full text
Corticosteroids reduced mortality rate in patients with coronavirus disease 2019 (COVID-19). Previously, we hypothesized that corticosteroids mitigate the inflammation response resulting in reduced coagulation and thromb...
Corticosteroids reduced mortality rate in patients with coronavirus disease 2019 (COVID-19). Previously, we hypothesized that corticosteroids mitigate the inflammation response resulting in reduced coagulation and thrombosis. In this retrospective study, we included 27 patients with COVID-19 that received high-dose corticosteroids (methylprednisolone 1000 mg i.v. daily for 3 days) for persistent respiratory failure or an excessive inflammation response. We found that inflammation, coagulation, and ventilation parameters improved significantly after methylprednisolone. The viral loads of SARS-CoV-2 remained stable or decreased. These results provides insight into the reduced mortality rate observed in patients with COVID-19 treated with corticosteroids.
Extracellular Vesicle Proteome of Breast Cancer Patients with and Without Cognitive Impairment Following Anthracycline-based Chemotherapy: An Exploratory Study.
Koh YQ, Ng DQ, Ng CC … +7 more , Boey A, Wei M, Sze SK, Ho HK, Acharya M, Limoli CL, Chan A
Biomark Insights · 2021 · PMID 34103887 · Full text
Cognitive impairment due to cancer and its therapy is a major concern among cancer patients and survivors. Extracellular vesicle (EVs) composition altered by cancer and chemotherapy may affect neurological processes such...
Cognitive impairment due to cancer and its therapy is a major concern among cancer patients and survivors. Extracellular vesicle (EVs) composition altered by cancer and chemotherapy may affect neurological processes such as neuroplasticity, potentially impacting the cognitive abilities of cancer patients and survivors. We investigated the EV proteome of breast cancer patients with and without cognitive impairment following anthracycline-based chemotherapy from longitudinally collected plasma. EVs were cup-shaped and positive for Flotillin-1 and TSG-101. We identified 517 differentially expressed EV proteins between the cognitive impaired and non-impaired groups during and post-chemotherapy. The observed decreased expression of p2X purinoceptor, cofilin-1, ADAM 10, and dynamin-1 in the plasma EVs of the cognitive impaired group may suggest alterations in the mechanisms underlying synaptic plasticity. The reduced expression of tight junction proteins among cognitive-impaired patients may imply weakening of the blood-brain barrier. These EV protein signatures may serve as a fingerprint that underscores the mechanisms underlying cognitive impairment in cancer patients and survivors.
IL-6 and Other Biomarkers associated with Poor Prognosis in a Cohort of Hospitalized Patients with COVID-19 in Madrid.
Donoso-Navarro E, Arribas Gómez I, Bernabeu-Andreu FA
Biomark Insights · 2021 · PMID 34103886 · Full text
OBJECTIVES: There are several published works on the prognostic value of biomarkers in relation to the severity or fatal outcome of coronavirus disease 2019 (COVID-19). In Spain, the second European country in incidence...
OBJECTIVES: There are several published works on the prognostic value of biomarkers in relation to the severity or fatal outcome of coronavirus disease 2019 (COVID-19). In Spain, the second European country in incidence of the disease at the time of data collection, there are few studies that include both laboratory parameters and clinical parameters. Our aim is to study the relationship of a wide series of biomarkers with admission to intensive care and death in a hospital in the Autonomous Community of Madrid (Spain), with special attention to IL-6 due to its role in the systemic inflammatory response associated with a worse prognosis of the disease. METHODS: Data were collected from 546 hospitalized patients with COVID-19. All of them had IL-6 results, in addition to other biochemical and haematological parameters. The difference of the medians for the selected parameters between the groups (ICU vs non-ICU, dead vs survivors) was studied using a Mann-Whitney analysis. The independent variables that predicted death were studied using a Cox proportional hazard regression model. RESULTS: Higher age and blood concentrations of ALT, creatinine, CK, cTnI, LDH, NT-proBNP, CRP, IL-6, leucocyte count and D-dimer together with lower blood concentrations of albumin and lymphocyte count were associated with mortality in univariate analysis. Age, LDH, IL-6 and lymphocyte count remained associated with death in multivariate analysis. CONCLUSIONS: Age, LDH, IL-6 and lymphocyte count, as independent predictors of death, could be used to establish more aggressive therapies in COVID-19 patients.
Circadian, Week-to-Week, and Physical Exercise-Induced Variation of Serum Microfibrillar-Associated Protein 4.
Sækmose SG, Holst R, Lottenburger T … +5 more , Ytting H, Nielsen HJ, Junker P, Schlosser A, Sorensen GL
Biomark Insights · 2021 · PMID 34035648 · Full text
Serum microfibrillar-associated protein 4 (sMFAP4) has been investigated as a biomarker for various diseases and is demonstrated to show significant gradual increase with severity of liver fibrosis. Ideal biomarkers used...
Serum microfibrillar-associated protein 4 (sMFAP4) has been investigated as a biomarker for various diseases and is demonstrated to show significant gradual increase with severity of liver fibrosis. Ideal biomarkers used for disease diagnosis or prognosis should display deviating levels in affected individuals only and be robust to factors unrelated to the disease. Here we show the impact of normal physiological variation of sMFAP4 by characterizing the circadian variation, week-to-week variation, and physical exercise-induced levels. Serum samples from 3 groups of healthy volunteers were drawn: 7 times during a 24-hour period, 5 times during a 3-week period, and before and after a standardized physical exercise challenge. sMFAP4 was determined by AlphaLISA. Statistical analysis was performed using mixed effects modeling of repeated measurements. Circadian variation of sMFAP4 was demonstrated, with time of peak and nadir values depending on age and gender. For males, the peak values were observed during nighttime whereas for females, peak values were observed in the morning. Individual sMFAP4 levels remained stable over a period of 3 weeks and physical exercise inferred a mild negative influence. In conclusion, the circadian sMFAP4 variation was significant, and the levels could be influenced by physical activity. However, these variations were of limited magnitude relative to previously observed disease-induced levels in support of the biomarker potential of sMFAP4.
Multiple Sclerosis Biomarker Discoveries by Proteomics and Metabolomics Approaches.
Jafari A, Babajani A, Rezaei-Tavirani M
Biomark Insights · 2021 · PMID 34017167 · Full text
Multiple sclerosis (MS) is an autoimmune inflammatory disorder of the central nervous system (CNS) resulting in demyelination and axonal loss in the brain and spinal cord. The precise pathogenesis and etiology of this co...
Multiple sclerosis (MS) is an autoimmune inflammatory disorder of the central nervous system (CNS) resulting in demyelination and axonal loss in the brain and spinal cord. The precise pathogenesis and etiology of this complex disease are still a mystery. Despite many studies that have been aimed to identify biomarkers, no protein marker has yet been approved for MS. There is urgently needed for biomarkers, which could clarify pathology, monitor disease progression, response to treatment, and prognosis in MS. Proteomics and metabolomics analysis are powerful tools to identify putative and novel candidate biomarkers. Different human compartments analysis using proteomics, metabolomics, and bioinformatics approaches has generated new information for further clarification of MS pathology, elucidating the mechanisms of the disease, finding new targets, and monitoring treatment response. Overall, omics approaches can develop different therapeutic and diagnostic aspects of complex disorders such as multiple sclerosis, from biomarker discovery to personalized medicine.
The Assessment of the Usefulness of Selected Markers in the Diagnosis of Chronic Kidney Disease in Children.
Będzichowska A, Jobs K, Kloc M … +2 more , Bujnowska A, Kalicki B
Biomark Insights · 2021 · PMID 33958853 · Full text
INTRODUCTION: The kidney deterioration, which starts in childhood often leads to end-stage renal failure in the future. Therefore, searching for an early, sensitive, and specific biomarkers became a paramount for chronic...
INTRODUCTION: The kidney deterioration, which starts in childhood often leads to end-stage renal failure in the future. Therefore, searching for an early, sensitive, and specific biomarkers became a paramount for chronic kidney disease diagnosis. The aim of this study was the assessment of markers: KIM-1, FGF-23, NAG, NGAL, and uromodulin for diagnosis of preclinical phase of the disease in children. PATIENTS AND METHODS: 59 children (15 boys, 44 girls from 6 months to 17 years old) with kidney disorders, which had clinical indications for renoscintigraphy, were included in the study. All patients were divided depending on the result of renoscintigraphy (renal scarring vs normal kidney picture) and depending on the level of estimated glomerular filtration rate (glomerular hyperfiltration vs normal filtration rate). The concentration of uromoduline, KIM-1, FGF-23, NAG, and NGAL in serum and of NGAL and uromoduline in urine were measured in all studied groups. RESULTS: The children with glomerular hyperfiltration had a statistically significantly higher serum values of FGF-23 and NGAL than the children with normal filtration rate ( < .05). There were no statistically significant differences in serum concentrations of tested markers in children with renal scars in comparison to children with normal renal image. There was no statistically significant difference in the concentration of tested markers in urine. CONCLUSIONS: The study confirmed the possible usefulness of FGF-23 and NGAL in detecting the preclinical-stage of renal disease associated with glomerular hyperfiltration in children. The study do not allow to indicate markers, which could be useful in the early diagnosis of kidney damage visible in the scintigraphic examination.
Quality Considerations When Using Tissue Samples for Biomarker Studies in Cancer Research.
Speirs V
Biomark Insights · 2021 · PMID 33958852 · Full text
Tissue obtained from biobanks is frequently employed in biomarker studies. Biomarkers define objective, measurable characteristics of biological and biomedical procedures and have been used as indicators of clinical outc...
Tissue obtained from biobanks is frequently employed in biomarker studies. Biomarkers define objective, measurable characteristics of biological and biomedical procedures and have been used as indicators of clinical outcome. This article outlines some of the steps scientists should consider when embarking on biomarker research in cancer research using samples from biobanks and the importance and challenges of linking clinical data to biological samples.
Cytokine Profiling in Plasma from Patients with Brain Tumors Versus Healthy Individuals using 2 Different Multiplex Immunoassay Platforms.
Bender DE, Schaettler MO, Sheehan KC … +2 more , Johanns TM, Dunn GP
Biomark Insights · 2021 · PMID 33854293 · Full text
We compared the performance of two 96-well multiplex immunoassay platforms in assessing plasma cytokine concentrations in patients with glioblastoma (GBM; n = 27), individuals with melanoma, breast or lung cancer metasta...
We compared the performance of two 96-well multiplex immunoassay platforms in assessing plasma cytokine concentrations in patients with glioblastoma (GBM; n = 27), individuals with melanoma, breast or lung cancer metastases to the brain (n = 17), and healthy volunteers (n = 11). Assays included a bead-based fluorescence MILLIPLEX assay/Luminex (LMX) platform and 4 planar electrochemiluminescence kits from Meso Scale Discovery (MSD). The LMX kit evaluated 21 cytokines and the 3 MSD kits evaluated 20 cytokines in total, with 19 overlapping human cytokines between platforms (GM-CSF, IFNγ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IL-21, IL-23, MIP-1α, MIP-1β, MIP-3α, TNFα). The MSD platform had lower LLoQs (lower limits of quantification) than LMX for 17/19 cytokines, and higher LLoQs for IFN-γ and IL-21. The ULoQs were higher in LMX versus MSD assays for 17/19 shared analytes, but lower than MSD for IL-17A and IL-21. With LMX, all 19 shared analytes were quantifiable in each of 55 samples. Although MSD recombinant protein standard curves indicated lower LLoQs than LMX for most cytokines, MSD detected 7/19 (37%) native analytes in <75% of samples, including 0% detection for IL-21 and 8% for IL-23. The LMX platform categorized identical samples at greater concentrations than the MSD system for most analytes (MIP-1β the sole exception), sometimes by orders of magnitude. This mismatched quantification paradigm was supported by Bland-Altman analysis. LMX identified significantly elevated levels of 10 of 19 circulating cytokines in GBM: GM-CSF, IFN-γ, IL-1β, IL-5, IL-10, IL-17A, IL-21, IL-23, MIP-1α, and MIP-3α, consistent with prior findings and confirming the utility of applying appropriate multiplex immunoassay technologies toward developing a cytokine signature profile for GBM.
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