scholarly journals Biomarkers identified by serum metabolomic analysis to predict biologic treatment response in rheumatoid arthritis patients

Rheumatology ◽  
2019 ◽  
Vol 58 (12) ◽  
pp. 2153-2161 ◽  
Author(s):  
Soshi Takahashi ◽  
Jun Saegusa ◽  
Akira Onishi ◽  
Akio Morinobu
Keyword(s):  
Operating Characteristic ◽  
Area Under The Curve ◽  
Metabolomic Analysis ◽  
Eular Response ◽  
Biologic Treatment ◽  
Discriminative Ability ◽  
Flight Mass Spectrometry ◽  
Tnf Α ◽  
Multiple Biomarkers ◽  
Patient Groups

Abstract Objectives Biologic treatment has recently revolutionized the management of RA. Despite this success, ∼30–40% of the patients undergoing biologic treatment respond insufficiently. The aim of this study was to identify several specific reliable metabolites for predicting the response of RA patients to TNF-α inhibitors (TNFi) and abatacept (ABT), using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS). Methods We collected serum from RA patients with moderate or high disease activity prior to biologic treatment, and obtained the serum metabolomic profiles of these samples using CE-TOFMS. The patients' response was determined 12 weeks after starting biologic treatment, according to the EULAR response criteria. We compared the metabolites between the response and non-response patient groups and analysed their discriminative ability. Results Among 43 total patients, 14 of 26 patients in the TNFi group and 6 of 17 patients in the ABT group responded to the biologic treatment. Of the metabolites separated by CE-TOFMS, 196 were identified as known substances. Using an orthogonal partial least-squares discriminant analysis, we identified five metabolites as potential predictors of TNFi responders and three as predictors of ABT responders. Receiver operating characteristic analyses for multiple biomarkers revealed an area under the curve (AUC) of 0.941, with a sensitivity of 85.7% and specificity of 100% for TNFi, and an AUC of 0.985, with a sensitivity of 100% and specificity of 90.9% for ABT. Conclusion By metabolomic analysis, we identified serum biomarkers that have a high ability to predict the response of RA patients to TNFi or ABT treatment.

scholarly journals Identification of Potential Metabolic Markers of Hypertension in Chinese Children

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Jiahong Sun ◽  
Min Zhao ◽  
Liu Yang ◽  
Xue Liu ◽  
Lucia Pacifico ◽  
...  
Keyword(s):  
Cardiovascular Health ◽  
Area Under The Curve ◽  
Metabolite Profile ◽  
Baseline Survey ◽  
Pediatric Hypertension ◽  
Discriminative Ability ◽  
Metabolic Markers ◽  
Flight Mass Spectrometry ◽  
Ultrahigh Performance Liquid Chromatography ◽  
Age Range

Background. Studies in adults have shown that several metabolites across multiple pathways are strongly associated with hypertension. However, as yet, to our knowledge, no study has investigated such association in childhood. We, therefore, compared the serum metabolite profile of children with normal and elevated blood pressure (BP) to identify potential metabolic markers and pathways that could be useful for the assessment of pediatric hypertension. Methods. The study included 26 hypertensive children (age range, 6–11 years) and 26 age- and sex-matched ones with normal BP, who were recruited from the baseline survey of the Huantai Childhood Cardiovascular Health Cohort Study. Ultrahigh-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry was performed to assess the serum metabolite profile. Logistic regression analysis was used to select significant metabolites associated with hypertension after adjustment for body mass index, waist circumference, and lipid profile. Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaboAnalyst were utilized to search for the potential pathways of metabolites. Results. A total of 45 and 34 metabolites were preliminarily screened in positive and negative modes, respectively (variable importance in the projection (VIP) > 1.0 and P < 0.05 ). After adjustment for the false discovery rate, 7 and 1 differential metabolites in the positive and negative modes, respectively, remained significant (VIP > 1.0 and q < 0.05). These metabolites were mainly involved in amino acid metabolism and glycerophospholipid metabolism. Among these, two significant metabolites including ethanolamine and 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate displayed an area under the curve value of 0.820 (95% confidence interval, 0.688–0.951), with a sensitivity of 0.846 and a specificity of 0.769. Conclusion. The untargeted metabolomics approach effectively identified the differential serum metabolite profile in children with and without hypertension. Notably, two metabolites including ethanolamine and 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate exhibited a good discriminative ability to identify children with hypertension, providing new insights into potential mechanisms of pediatric hypertension.

scholarly journals Salivary IL-8 as a putative predictive biomarker of radiotherapy response in head and neck cancer patients

2021 ◽  
Author(s):  
Sara Principe ◽  
Enrique Zapater-Latorre ◽  
Leo Arribas ◽  
Enrique Garcia-Miragall ◽  
Jose Bagan
Keyword(s):  
Operating Characteristic ◽  
Area Under The Curve ◽  
Predictive Biomarker ◽  
Good Clinical Response ◽  
Receiver Operating Characteristic Curves ◽  
Irradiation Treatment ◽  
Tnf Α ◽  
Irradiation Therapy ◽  
Before And After ◽  
Radiotherapy Treatment

Abstract Objectives Ionizing radiation increases the expression of a number of salivary proteins involved in immunoregulatory networks related to infection, injury, inflammation, and cancer. Our main objective was to analyze whether there are significant differences in salivary cytokines before and after radiotherapy and whether any of them are associated to better outcomes after radiotherapy serving as a potential predictive biomarker of response to the treatment. Materials and methods We analyzed a panel of eight salivary markers (IL-4, IL-6, IL-8, and IL-10; MCP-1; TNF-α; VEGF; and EGF) in a group of HNC patients (N = 30), before and after irradiation treatment pre- and post-RT. We also compared these results with a group of healthy controls (N = 37). In both groups, we used stimulated saliva and we performed immunoassays based on multi-analyte profiling technology (Luminex xMAP). Results In our group of 30 HNC patients, 24 of them showed a good clinical response after radiotherapy treatment while 6 cases did not respond to radiotherapy. The data revealed a post-treatment increase in multiple cytokines in the stimulated saliva of HNC patients; the increases in IL-8 and MCP-1 were statistically significant (p ≤ 0.001 and p ≤ 0.0001, respectively). Analysis of receiver operating characteristic curves indicated the strong potential of IL-8 as a predictive biomarker of RT good outcomes (area under the curve = 0.84; p = 0.018). Conclusions After analyzing the panel of salivary cytokines, IL-8 showed the best association to the response to radiotherapy; in this sense, low IL-8 levels in the saliva of HNC patients before receiving irradiation therapy are associated with positive RT outcomes. Clinical relevance Salivary IL-8 expression in HNC patients undergoing RT may serve as a potential predictive biomarker of response to the treatment.

scholarly journals DOP03 Early change in epithelial neutrophilic infiltrate predicts long-term response to biologics in Ulcerative Colitis

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S042-S043
Author(s):  
N Narula ◽  
E Wong ◽  
J F Colombel ◽  
R Riddell ◽  
J Marshall ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Operating Characteristic ◽  
Multivariate Analyses ◽  
Univariate Analysis ◽  
Area Under The Curve ◽  
Biologic Treatment ◽  
Neutrophilic Infiltrate ◽  
Post Hoc ◽  
Term Response

Abstract Background The prognostic value of histologic scores, grades, and individual histologic sub-components, alone or in combination with endoscopy, for predicting endoscopic improvement (EI) and histo-endoscopic mucosal improvement (HEMI) during maintenance therapy in ulcerative colitis (UC) remains uncertain. Methods Post-hoc analysis of participants from the VARSITY trial (n=734 with histology). Receiver operating characteristic and multi-variate logistic regression analyses were performed to assess whether baseline and/or week 14 assessments for the Robarts Histopathology Index (RHI), Geboes score, or individual histologic sub-components, could predict the achievement of EI and HEMI at week 52. Results RHI and Geboes scores at baseline, and changes in scores at week 14, had fair to poor accuracy for predicting week 52 EI or HEMI (Area Under the Curve [AUC] 0.58–0.67). Among individual sub-components, changes in epithelial neutrophil involvement from baseline to week 14 had the best performance for predicting week 52 EI (AUC 0.83, 95% confidence interval (CI) 0.74–0.91) and HEMI (AUC 0.85, 95% CI 0.76–0.94). On multivariate analyses, improvement of neutrophils in the epithelium was associated with increased odds of week 52 EI (Odds Ratio [OR] 3.63, 95% CI 1.45–9.08, p=0.0059) and HEMI (OR 6.88, 95% CI 3.29–14.36, p&lt;0.0001), and lack of improvement of neutrophils in the epithelium was associated with lack of week 52 EI (OR 0.24, 95% CI 0.12–0.48, p&lt;0.0001) and lack of HEMI (OR 0.03, 95% CI 0.01–0.014, p&lt;0.0001). No other parameters significant on univariate analysis were significant within the multivariate model. Among patients with endoscopic Mayo scores of 2 or 3 at week 14, those who had &gt;50% crypts involved with neutrophils at week 14 were significantly less likely to achieve week 52 EI (18.0%; 31/172 vs. 34.3%; 72/210, p&lt;0.001), HEMI (9.9%; 17/172 vs. 22.4%; 47/210, p=0.001) (Figure 1) and clinical remission (11.0%; 19/172 vs. 23.3%; 49/210, p=0.002). Among patients with endoscopic Mayo scores of 0 or 1 at week 14, those who had &gt;50% crypts involved with neutrophils were significantly less likely to achieve HEMI at week 52 (33%; 4/12 vs. 62.4%; 141/226, p=0.044) (Figure 1). Conclusion Our results on epithelial neutrophilic infiltrate following induction therapy as the only independent predictor for achievement of maintenance EI or HEMI helps clarify the clinical relevance of measuring histologic disease activity in UC. Epithelial neutrophilic infiltrate poses a means to stratify patients according to their likelihood of response to biologic treatment.

scholarly journals Metabolomics and DNA-Based Authentication of Two Traditional Asian Medicinal and Aromatic Species of Salvia subg. Perovskia

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 112
Author(s):  
Monika Bielecka ◽  
Bartosz Pencakowski ◽  
Marta Stafiniak ◽  
Klemens Jakubowski ◽  
Mehdi Rahimmalek ◽  
...  
Keyword(s):  
Dna Barcoding ◽  
High Performance ◽  
Carnosic Acid ◽  
Limited Information ◽  
Metabolomic Analysis ◽  
Separate Species ◽  
Flight Mass Spectrometry ◽  
Aerial Parts ◽  
Central Asian ◽  
Aromatic Species

Subgenus Perovskia of the extended genus of Salvia comprises several Central Asian medicinal and aromatic species, of which S. yangii and S. abrotanoides are the most widespread. These plants are cultivated in Europe as robust ornamentals, and several cultivars are available. However, their medicinal potential remains underutilized because of limited information about their phytochemical and genetic diversity. Thus, we combined an ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS) based metabolomics with DNA barcoding approach based on trnH-psbA and ITS2 barcodes to clarify the relationships between these two taxa. Metabolomic analysis demonstrated that aerial parts are more similar than roots and none of the major compounds stand out as distinct. Sugiol in S. yangii leaves and carnosic acid quinone in S. abrotanoides were mostly responsible for their chemical differentiation, whereas in roots the distinction was supported by the presence of five norditerpenoids in S. yangii and two flavonoids and one norditerpenoid in S. abrotanoides. To verify the metabolomics-based differentiation, we performed DNA authentication that revealed S. yangii and S. abrotanoides to be very closely related but separate species. We demonstrated that DNA barcoding coupled with parallel LC-MS profiling constitutes a powerful tool in identification of taxonomically close Salvia species.

scholarly journals Evaluation of alpha-l-fucosidase for the diagnosis of hepatocellular carcinoma based on meta-analysis

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Lei Xi ◽  
Chunqing Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Operating Characteristic ◽  
Meta Analysis ◽  
Area Under The Curve ◽  
Diagnostic Odds Ratio ◽  
Diagnostic Value ◽  
Receiver Operating Characteristic Curves ◽  
Sensitivity Specificity ◽  
Review Manager

AbstractObjectivesThe main aim of the present study was to assess the diagnostic value of alpha-l-fucosidase (AFU) for hepatocellular carcinoma (HCC).MethodsStudies that explored the diagnostic value of AFU in HCC were searched in EMBASE, SCI, and PUBMED. The sensitivity, specificity, and DOR about the accuracy of serum AFU in the diagnosis of HCC were pooled. The methodological quality of each article was evaluated with QUADAS-2 (quality assessment for studies of diagnostic accuracy 2). Receiver operating characteristic curves (ROC) analysis was performed. Statistical analysis was conducted by using Review Manager 5 and Open Meta-analyst.ResultsEighteen studies were selected in this study. The pooled estimates for AFU vs. α-fetoprotein (AFP) in the diagnosis of HCC in 18 studies were as follows: sensitivity of 0.7352 (0.6827, 0.7818) vs. 0.7501 (0.6725, 0.8144), and specificity of 0.7681 (0.6946, 0.8283) vs. 0.8208 (0.7586, 0.8697), diagnostic odds ratio (DOR) of 7.974(5.302, 11.993) vs. 13.401 (8.359, 21.483), area under the curve (AUC) of 0.7968 vs. 0.8451, respectively.ConclusionsAFU is comparable to AFP for the diagnosis of HCC.

scholarly journals Statistical Assessment of Discrimination Capabilities of a Fractional Calculus Based Image Watermarking System for Gaussian Watermarks

Entropy ◽  
2021 ◽  
Vol 23 (2) ◽  
pp. 255
Author(s):  
Mario Gonzalez-Lee ◽  
Hector Vazquez-Leal ◽  
Luis J. Morales-Mendoza ◽  
Mariko Nakano-Miyatake ◽  
Hector Perez-Meana ◽  
...  
Keyword(s):  
Fractional Calculus ◽  
Roc Curve ◽  
Gaussian Noise ◽  
False Positive ◽  
Operating Characteristic ◽  
Image Watermarking ◽  
Area Under The Curve ◽  
Statistical Assessment ◽  
Watermarking Scheme ◽  
Fractional Equation

In this paper, we explore the advantages of a fractional calculus based watermarking system for detecting Gaussian watermarks. To reach this goal, we selected a typical watermarking scheme and replaced the detection equation set by another set of equations derived from fractional calculus principles; then, we carried out a statistical assessment of the performance of both schemes by analyzing the Receiver Operating Characteristic (ROC) curve and the False Positive Percentage (FPP) when they are used to detect Gaussian watermarks. The results show that the ROC of a fractional equation based scheme has 48.3% more Area Under the Curve (AUC) and a False Positives Percentage median of 0.2% whilst the selected typical watermarking scheme has 3%. In addition, the experimental results suggest that the target applications of fractional schemes for detecting Gaussian watermarks are as a semi-fragile image watermarking systems robust to Gaussian noise.

scholarly journals Snoring: a source of noise pollution and sleep apnea predictor

SLEEP ◽  
2019 ◽  
Vol 43 (6) ◽  
Author(s):  
Mudiaga Sowho ◽  
Francis Sgambati ◽  
Michelle Guzman ◽  
Hartmut Schneider ◽  
Alan Schwartz
Keyword(s):  
Sleep Apnea ◽  
Operating Characteristic ◽  
Area Under The Curve ◽  
Noise Pollution ◽  
Apnea Hypopnea Index ◽  
Sleep Study ◽  
Sound Levels ◽  
Obstructive Sleep ◽  
Single Night ◽  
The Relationship

Abstract Snoring is a highly prevalent condition associated with obstructive sleep apnea (OSA) and sleep disturbance in bed partners. Objective measurements of snoring in the community, however, are limited. The present study was designed to measure sound levels produced by self-reported habitual snorers in a single night. Snorers were excluded if they reported nocturnal gasping or had severe obesity (BMI &gt; 35 kg/m2). Sound was measured by a monitor mounted 65 cm over the head of the bed on an overnight sleep study. Snoring was defined as sound ≥40 dB(A) during flow limited inspirations. The apnea hypopnea index (AHI) and breath-by-breath peak decibel levels were measured. Snore breaths were tallied to determine the frequency and intensity of snoring. Regression models were used to determine the relationship between objective measures of snoring and OSA (AHI ≥ 5 events/h). The area under the curve (AUC) for the receiver operating characteristic (ROC) was used to predict OSA. Snoring intensity exceeded 45 dB(A) in 66% of the 162 participants studied, with 14% surpassing the 53 dB(A) threshold for noise pollution. Snoring intensity and frequency were independent predictors of OSA. AUCs for snoring intensity and frequency were 77% and 81%, respectively, and increased to 87% and 89%, respectively, with the addition of age and sex as predictors. Snoring represents a source of noise pollution in the bedroom and constitutes an important target for mitigating sound and its adverse effects on bed partners. Precise breath-by-breath identification and quantification of snoring also offers a way to risk stratify otherwise healthy snorers for OSA.

Alterations of serum levels of plasminogen, TNF-α, and IDO in granulomatosis with polyangiitis patients

Vascular ◽  
2021 ◽  
pp. 170853812098630
Author(s):  
Dobroslav Kyurkchiev ◽  
Tsvetelina Yoneva ◽  
Adelina Yordanova ◽  
Ekaterina Kurteva ◽  
Georgi Vasilev ◽  
...  
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Renal Involvement ◽  
Clinical Manifestations ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Necrosis Factor Alpha ◽  
Cross Sectional ◽  
Spearman's Rho ◽  
Tnf Α ◽  
Spearman’S Rho

Background Granulomatosis with polyangiitis (GPA) is a representative of vasculitides associated with anti-neutrophil cytoplasmic autoantibodies. “Classical” antibodies directed against proteinase 3 are involved in the pathogenesis and are part of the GPA diagnosis at the same time. Along with them, however, antibodies against Lysosomal-Associated Membrane Protein-2 (LAMP-2) and antibodies directed against plasminogen have been described in GPA. Objectives and methodology: We performed a cross-sectional study enrolling 34 patients diagnosed with GPA. Our study was aimed at looking for correlations between serum levels of LAMP-2 and plasminogen and the clinical manifestations of the GPA. Furthermore, we examined serum levels of tumor necrosis factor-alpha (TNF-α) and its associated indoleamine-pyrrole 2,3-dioxygenase (IDO), as well as we looked for a correlation between these cytokines and the clinical manifestations of GPA. Results The results showed that in GPA, serum plasminogen levels were negatively associated with renal involvement (receiver operating characteristic (ROC) area under the curve (AUC) of 0.78) (95% CI 0.53–0.91), p = 0.035, and the extent of proteinuria, Spearman’s Rho = –0.4, p = 0.015. Increased levels of TNF-α and IDO correlated with disease activity, Spearman’s Rho =0.62, p = 0.001 and Spearman’s Rho = 0.4, p = 0.022, respectively, whereas only TNF-α was increased in severe forms of GPA with lung involvement (ROC AUC of 0.8) (95% CI 0.66–0.94), p = 0.005. Conclusions In this study, we demonstrate the alteration of soluble factors, which play an important role in the pathogenesis of GPA and their relationship with the clinical manifestations of the disease. Our main results confirm the associations of increased secretory TNF-α and some clinical manifestations, and we describe for the first time decreased serum plasminogen levels and their association with renal involvement.

scholarly journals Prognostic Value of Inflammatory Biomarkers in Patients with Severe COVID-19: A Single-Center Retrospective Study

2021 ◽  
Vol 16 ◽  
pp. 117727192110270
Author(s):  
Gönül Açıksarı ◽  
Mehmet Koçak ◽  
Yasemin Çağ ◽  
Lütfiye Nilsun Altunal ◽  
Adem Atıcı ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Hospital Mortality ◽  
Prognostic Value ◽  
Current Knowledge ◽  
Area Under The Curve ◽  
Prognostic Nutritional Index ◽  
Inflammatory Biomarkers ◽  
Single Center ◽  
Discriminative Ability ◽  
Lymphocyte Ratio

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 ( P < .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, P = .004), NLR (⩾6.27, P = .012), and PNI (⩽40.2, P = .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.

scholarly journals Soluble SIGLEC5: A New Prognosis Marker in Colorectal Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3896
Author(s):  
Karla Montalbán-Hernández ◽  
Ramón Cantero-Cid ◽  
Roberto Lozano-Rodríguez ◽  
Alejandro Pascual-Iglesias ◽  
José Avendaño-Ortiz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Operating Characteristic ◽  
Prognostic Markers ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Significant Heterogeneity ◽  
Kaplan Meier ◽  
Prognosis Marker ◽  
Colorectal Cancer Patients ◽  
Healthy Participants

Colorectal cancer (CRC) is the second most deadly and third most commonly diagnosed cancer worldwide. There is significant heterogeneity among patients with CRC, which hinders the search for a standard approach for the detection of this disease. Therefore, the identification of robust prognostic markers for patients with CRC represents an urgent clinical need. In search of such biomarkers, a total of 114 patients with colorectal cancer and 67 healthy participants were studied. Soluble SIGLEC5 (sSIGLEC5) levels were higher in plasma from patients with CRC compared with healthy volunteers. Additionally, sSIGLEC5 levels were higher in exitus than in survivors, and the receiver operating characteristic curve analysis revealed sSIGLEC5 to be an exitus predictor (area under the curve 0.853; cut-off > 412.6 ng/mL) in these patients. A Kaplan–Meier analysis showed that patients with high levels of sSIGLEC5 had significantly shorter overall survival (hazard ratio 15.68; 95% CI 4.571–53.81; p ≤ 0.0001) than those with lower sSIGLEC5 levels. Our study suggests that sSIGLEC5 is a soluble prognosis marker and exitus predictor in CRC.

Sign in / Sign up

Export Citation Format

Share Document