scholarly journals TNF-α Carried by Plasma Extracellular Vesicles Predicts Knee Osteoarthritis Progression

2021 ◽  
Vol 12 ◽  
Author(s):  
Xin Zhang ◽  
Ming-Feng Hsueh ◽  
Janet L. Huebner ◽  
Virginia B. Kraus

ObjectivesTo identify plasma extracellular vesicles (EVs) associated with radiographic knee osteoarthritis (OA) progression.MethodsEVs of small (SEV), medium (MEV) and large (LEV) sizes from plasma of OA participants (n=30) and healthy controls (HCs, n=22) were profiled for surface markers and cytokine cargo by high-resolution flow cytometry. The concentrations of cytokines within (endo-) and outside (exo-) EVs were quantified by multiplex ELISA. EV associations with knee radiographic OA (rOA) progression were assessed by multivariable linear regression (adjusted for baseline clinical variables of age, gender, BMI and OA severity) and receiver operating characteristic (ROC) curve analysis.ResultsBased on integrated mean fluorescence intensity (iMFI), baseline plasma MEVs carrying CD56 (corresponding to natural killer cells) predicted rOA progression with highest area under the ROC curve (AUC) 0.714 among surface markers. Baseline iMFI of TNF-α in LEVs, MEVs and SEVs, and the total endo-EV TNF-α concentration, predicted rOA progression with AUCs 0.688, 0.821, 0.821, 0.665, respectively. In contrast, baseline plasma exo-EV TNF-α (the concentration in the same unit of plasma after EV depletion) did not predict rOA progression (AUC 0.478). Baseline endo-EV IFN-γ and exo-EV IL-6 concentrations were also associated with rOA progression, but had low discriminant capacity (AUCs 0.558 and 0.518, respectively).ConclusionsPlasma EVs carry pro-inflammatory cargo that predict risk of knee rOA progression. These findings suggest that EV-associated TNF-α may be pathogenic in OA. The sequestration of pathogenic TNF-α within EVs may provide an explanation for the lack of success of systemic TNF-α inhibitors in OA trials to date.

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Zahra Rahimi ◽  
Ramin Yaghobi ◽  
Afsoon Afshari ◽  
Jamshid Roozbeh ◽  
Mohammad Javad Mokhtari ◽  
...  

Abstract Background BK virus associated nephropathy (BKVAN) is one of the common causes of graft loss among kidney transplanted recipients (KTRs). The current treatment for BKV nephropathy is decreasing the immunosuppressive regimen in KTRs. Interleukin-27 (IL-27) is a multifunctional cytokine that might be the front-runner of an important pathway in this regard. Therefore, in current study it is tried to evaluate the changes in the expression level of IL-27 and some related molecules, resulting from BKV reactivation in KTR patients. Methods EDTA-treated blood samples were collected from all participants. Patients were divided into two groups, 31 kidney transplant recipients with active and 32 inactive BKV infection, after being monitored by Real time PCR (Taq-Man) in plasma. Total of 30 normal individuals were considered as healthy control group. Real time PCR (SYBR Green) technique is used to determine the expression level of studied genes. Results The results of gene expression comparisons showed that the expression level of IL-27, IFN-γ, TNF-α, TNFR2 and IRF7 genes was significantly higher in inactive group in comparison to active group. The expression level of TLR4 was lower in both active and inactive groups in comparison to control group. ROC curve analysis showed that IL-27 and IRF7 are significantly different amongst other studied genes. Finally, the analyses revealed that the expression level of most of the studied genes (except for TNF-α and TLR4) have significant correlation with viral load. Conclusions Our findings revealed that IL-27, IFN-γ, TNF-α, TNFR2 and IRF7 expression level is higher in inactive group and TLR4 expression level is lower in patients’ groups in comparison to control group. Also, ROC curve analysis showed IL-27 and IRF7 can significantly differentiate studied groups (BKV active vs. inactive). Therefore, these results might help elucidating the pattern in charge of BKV reactivation in kidney transplanted patients.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yuichiro Shimoyama ◽  
Osamu Umegaki ◽  
Noriko Kadono ◽  
Toshiaki Minami

Abstract Objective Sepsis is a major cause of mortality for critically ill patients. This study aimed to determine whether presepsin values can predict mortality in patients with sepsis. Results Receiver operating characteristic (ROC) curve analysis, Log-rank test, and multivariate analysis identified presepsin values and Prognostic Nutritional Index as predictors of mortality in sepsis patients. Presepsin value on Day 1 was a predictor of early mortality, i.e., death within 7 days of ICU admission; ROC curve analysis revealed an AUC of 0.84, sensitivity of 89%, and specificity of 77%; and multivariate analysis showed an OR of 1.0007, with a 95%CI of 1.0001–1.0013 (p = 0.0320).


2021 ◽  
Author(s):  
Naoya Fujita ◽  
Yosuke Ono ◽  
Azusa Sano ◽  
Motohiro Kimata ◽  
Seigo Oyama ◽  
...  

Objective: Conventional diagnostic methods are limited in their ability to differentiate destructive thyroiditis from Graves’ disease. We hypothesised that serum diiodotyrosine (DIT) and monoiodotyrosine (MIT) levels could be biomarkers for differentiating destructive thyroiditis from Graves’ disease. Design: Patients with destructive thyroiditis (n = 13) and Graves’ disease (n = 22) were enrolled in this cross-sectional study. Methods: We assayed the serum DIT and MIT levels using liquid chromatography-tandem mass spectrometry. A receiver operating characteristic (ROC) curve analysis was used to determine the sensitivity and specificity of the serum DIT and MIT levels as biomarkers for differentiating destructive thyroiditis from Graves’ disease. Results: The serum DIT and MIT levels were significantly higher in patients with destructive thyroiditis than in those with Graves’ disease. The ROC curve analysis showed that the serum DIT levels (≥ 359.9 pg/mL) differentiated destructive thyroiditis from Graves’ disease, significantly, with 100.0% sensitivity and 95.5% specificity (P < .001). The diagnostic accuracy of the serum MIT levels (≥119.4 pg/mL) was not as high as that of the serum DIT levels (sensitivity, 84.6%; specificity, 77.3%; P = .001). Conclusions: The serum DIT levels may serve as a novel diagnostic biomarker for differentiating destructive thyroiditis from Graves’ disease.


2019 ◽  
Vol 26 (5) ◽  
pp. 341-350
Author(s):  
Zhao-Juan Er ◽  
Chun-Fang Yin ◽  
Wen-Jing Wang ◽  
Xue-Jun Chen

This study aimed to examine whether stromal cell-derived factor-1 (SDF-1) or C-X-C chemokine ligand 12 (CXCL12) participates in the development of lumbar disc degeneration, as implicated earlier by the level of CXCL12 correlating with this disease. It enrolled 145 patients with symptomatic lumbar intervertebral disc degeneration (IDD) and 130 asymptomatic healthy controls with no indication of IDD. Radiological assessment of the IDD patients was targeted at the lumbar vertebra region, based on Pfirrmann grade. Degeneration of the multifidus and psoas major muscles was evaluated using Goutallier classification. Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores were obtained for assessing the severity of manifestation. The levels of serum CXCL12, IL-6 and TNF-α were determined by ROC curve analysis, resulting in their prognostic value for Pfirrmann grading. Higher levels of serum CXCL12 were found in patients with IDD than in asymptomatic individuals, and were positively related to the Pfirrmann grade as well as multifidus muscle degeneration. Furthermore, serum CXCL12 concentration showed a significant correlation with the VAS and ODI scores. In addition, elevated serum CXCL12 levels were related to serum levels of TNF-α and IL-6. The ROC curve analysis implicated that CXCL12 could function as a biomarker of the early-mediate phase of IDD development. In summary, the serum CXCL12/SDF-1 level is positively related with lumbar IDD and its clinical severity.


2020 ◽  
Vol 76 (1) ◽  
pp. 85-98 ◽  
Author(s):  
Wenjuan Tong ◽  
Xiaoling Zhang ◽  
Jia Luo ◽  
Fushun Pan ◽  
Jinyu Liang ◽  
...  

PURPOSE: To assess the value of conventional ultrasound (US), contrast-enhanced ultrasound (CEUS) and mammography in the diagnosis of breast lesions with calcifications. METHODS: A total of 87 breast lesions with calcification were subjected to US, CEUS and mammography and divided into 3 groups: Group A (all cases), Group A1 (31 cases who underwent US and CEUS first followed by mammography), and Group A2 (56 cases who underwent mammography first followed by US and CEUS). A receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficacy of different methods in different groups. RESULTS: In Group A, the area under the ROC curve (AUROC) of CEUS were 0.937, which were significantly higher than that of mammography (p < 0.05). In Group A1, the AUROC of CEUS were 0.842, which were not significantly different from that of US and mammography (p > 0.05). In Group A2, the AUROC of CEUS were 0.987, which were significantly higher than that of mammography and US (p < 0.05). CONCLUSION: Based on the mammography results, the combination of US and CEUS might improve the diagnostic efficacy in breast lesions with calcification.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Qiaodong Xu ◽  
Yongcong Yan ◽  
Songgang Gu ◽  
Kai Mao ◽  
Jianlong Zhang ◽  
...  

Background. Inflammation is an important hallmark of cancer. Fibrinogen and albumin are both vital factors in systemic inflammation. This study investigated the prognostic value of the fibrinogen/albumin ratio in HCC patients who underwent curative resection. Methods. HCC patients (n=151) who underwent curative resection were evaluated retrospectively. The optimal cutoff value for the fibrinogen/albumin ratio was selected by receiver operating characteristic (ROC) curve analysis. Correlations between preoperative fibrinogen/albumin ratios and clinicopathologic characteristics were analyzed by χ2 test. The area under the receiver operating characteristic curve (AUC) was calculated to compare the prognostic value of the fibrinogen/albumin ratio with other prognostic scores (neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and albumin-bilirubin (ALBI) score). The overall survival (OS) and time to recurrence (TTR) were assessed by the log-rank test and the Cox proportional hazard regression model. Results. An optimal cutoff value of the preoperative fibrinogen/albumin ratio (0.062) was determined for 151 patients who underwent curative resection for HCC via a ROC curve analysis. Fibrinogen/albumin ratio > 0.062 was significantly associated with microvascular invasion, an advanced BCLC stage, and ALBI grade. Multivariate analyses revealed that fibrinogen/albumin ratio was an independent predictor for OS (P=0.003) and TTR (P=0.035). The prognostic ability of fibrinogen/albumin ratio was comparable to other prognostic scores (NLR, PLR, and ALBI score) by AUC analysis. Patients with a fibrinogen/albumin ratio > 0.062 had lower 1-, 3-, and 5-year OS rates (66.0%, 41.8%, and 28.2% versus 81.9%, 69.3%, and 56.1%, resp., P<0.001) and higher 1-, 3-, and 5-year recurrence rates (60.9%, 79.2%, and 90.5% versus 49.5%, 69.1%, and 77.1%, resp., P=0.008) compared with patients with fibrinogen/albumin ratio ≤ 0.062. Conclusion. The preoperative fibrinogen/albumin ratio is an effective prognostic factor for HCC patients who underwent curative resection. An elevated fibrinogen/albumin ratio significantly correlates with poorer survival and a higher risk of recurrence in HCC patients.


2003 ◽  
Vol 30 (1) ◽  
pp. 159-167 ◽  
Author(s):  
O O Faniran ◽  
D G Proverbs

This paper presents the results of a receiver operating characteristic (ROC) curve analysis of the effectiveness of construction planning efforts, based on samples of building projects in Australia and the United Kingdom. The results of the study provide an evaluation of the extent of the effort that must be invested in planning and control activities to achieve success in the performance of construction projects. The study also illustrates the potential application of ROC curve analysis in construction engineering and management research. Planning efforts in a sample of 52 building projects in Australia and 37 building projects in the United Kingdom were evaluated and compared. This study builds on work done in an earlier study in which the concept of optimal planning of construction projects was explored. The ROC curve analysis offers several advantages over the regression methodology employed in the previous optimal planning study. The graphical representation of the relationship between sensitivity and specificity over all possible diagnostic cutoff points provides an insight into the interactions of the variables that was not apparent in the original methodology.Key words: construction planning, project planning, project management, ROC curve analysis, Australia, United Kingdom.


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