scholarly journals Discovery of an autoantibody signature for the early diagnosis of knee osteoarthritis: data from the Osteoarthritis Initiative

2019 ◽  
Vol 78 (12) ◽  
pp. 1699-1705 ◽  
Author(s):  
María Camacho-Encina ◽  
Vanesa Balboa-Barreiro ◽  
Ignacio Rego-Perez ◽  
Florencia Picchi ◽  
Jennifer VanDuin ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Prognostic Model ◽  
Operating Characteristic ◽  
Protein Arrays ◽  
Clinical Model ◽  
Kaplan Meier ◽  
Human Proteins ◽  
Osteoarthritis Initiative

ObjectiveTo find autoantibodies (AAbs) in serum that could be useful to predict incidence of radiographic knee osteoarthritis (KOA).DesignA Nucleic-acid Programmable Protein Arrays (NAPPA) platform was used to screen AAbs against 2125 human proteins in sera at baseline from participants free of radiographic KOA belonging to the incidence and non-exposed subcohorts of the Osteoarthritis Initiative (OAI) who developed or not, radiographic KOA during a follow-up period of 96 months. NAPPA-ELISA were performed to analyse reactivity against methionine adenosyltransferase two beta (MAT2β) and verify the results in 327 participants from the same subcohorts. The association of MAT2β-AAb levels with KOA incidence was assessed by combining several robust biostatistics analysis (logistic regression, Receiver Operating Characteristic and Kaplan-Meier curves). The proposed prognostic model was replicated in samples from the progression subcohort of the OAI.ResultsIn the screening phase, six AAbs were found significantly different at baseline in samples from incident compared with non-incident participants. In the verification phase, high levels of MAT2β-AAb were significantly associated with the future incidence of KOA and with an earlier development of the disease. The incorporation of this AAb in a clinical model for the prognosis of incident radiographic KOA significantly improved the identification/classification of patients who will develop the disorder. The usefulness of the model to predict radiographic KOA was confirmed on a different OAI subcohort.ConclusionsThe measurement of AAbs against MAT2β in serum might be highly useful to improve the prediction of OA development, and also to estimate the time to incidence.

scholarly journals Early T2 changes predict onset of radiographic knee osteoarthritis: data from the osteoarthritis initiative

2014 ◽  
Vol 74 (7) ◽  
pp. 1353-1359 ◽  
Author(s):  
Hans Liebl ◽  
Gabby Joseph ◽  
Michael C Nevitt ◽  
Nathan Singh ◽  
Ursula Heilmeier ◽  
...  
Keyword(s):  
Relaxation Time ◽  
Knee Osteoarthritis ◽  
Case Control ◽  
T2 Relaxation Time ◽  
T2 Relaxation ◽  
Knee Oa ◽  
Osteoarthritis Initiative ◽  
Nested Case Control ◽  
Radiographic Knee Osteoarthritis

ObjectiveTo evaluate whether T2 relaxation time measurements obtained at 3 T MRI predict the onset of radiographic knee osteoarthritis (OA).Materials and methodsWe performed a nested case–control study of incident radiographic knee OA in the Osteoarthritis Initiative cohort. Cases were 50 knees with baseline Kellgren–Lawrence (KL) grade of 0 that developed KL grade of 2 or more over a 4-year period. Controls were 80 knees with KL grade of 0 after 4 years of follow-up. Baseline T2 relaxation time measurements and laminar analysis of T2 in deep and superficial layers were performed in all knee compartments. The association of T2 values with incident OA was assessed with logistic regression and differences in T2 values by case–control status with linear regression, adjusting for age, sex, body mass index (BMI) and other covariates.ResultsBaseline T2 values in all compartments except the medial tibia were significantly higher in knees that developed OA compared with controls and were particularly elevated in the superficial cartilage layers in all compartments. There was an increased likelihood of incident knee OA associated with higher baseline T2 values, particularly in the patella, adjusted OR per 1 SD increase in T2 (3.37 (95% CI 1.72 to 6.62)), but also in the medial femur (1.90 (1.07 to 3.39)), lateral femur (2.17 (1.11 to 4.25)) and lateral tibia (2.23 (1.16 to 4.31)).ConclusionsThese findings suggest that T2 values assessed when radiographic changes are not yet apparent may be useful in predicting the development of radiological tibiofemoral OA.

scholarly journals Inflammatory potential of diet and risk of incident knee osteoarthritis: a prospective cohort study

2020 ◽  
Author(s):  
Qiang Liu ◽  
James R. Hebert ◽  
Nitin Shivappa ◽  
Jianjun Guo ◽  
Ke Tao ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Estimating Equation ◽  
Mediation Analyses ◽  
Knee Oa ◽  
Inflammatory Index ◽  
Symptomatic Knee ◽  
Osteoarthritis Initiative ◽  
Reduce Risk

Abstract Background To examine the relation between inflammatory potential of diet and incident knee osteoarthritis (OA) and the role of BMI in the association of interest. Methods In the Osteoarthritis Initiative, the energy-adjusted dietary inflammatory index (E-DIITM) scores were calculated based on the Block Brief 2000 Food Frequency Questionnaire and categorized into sex-specific quartiles. Outcomes were incident: (1) radiographic knee OA (ROA) (i.e., a KL grade ≥2), (2) symptomatic knee OA (SxOA) (i.e., a combination of a frequent knee pain and ROA). We fitted generalized estimating equation models to examine the association between E-DII scores and incident knee OA. We performed mediation analyses to assess potential mediation by BMI in the DII-OA relation. Results Over a 48-month follow-up period, 232 and 978 knees developed ROA and SxOA, respectively. Compared with the lowest (most anti-inflammatory) E-DII quartile, the odds ratio (OR) of incident ROA for the highest (most pro-inflammatory) E-DII quartile was 1.73 (95% confidence interval (CI): 1.15 to 2.62, Ptrend= 0.007). The corresponding OR for SxOA was 1.43 (95% CI: 1.16 to 1.76, Ptrend = 0.001). The DII-OA association was significantly mediated via BMI with an indirect effect of 1.08 (95% CI: 1.04,1.13) for ROA and 1.13 (95% CI: 1.09, 1.16) for SxOA, accounting for 20.4% and 44.5% of total effect, respectively. Conclusions A higher inflammatory potential of diet increased the risk of knee OA. The association was significantly mediated via BMI. Targeting inflammatory potential of diet may be beneficial to reduce risk of knee OA.

scholarly journals PHOX2B expression in bone marrow and peripheral blood is associated with metastasis and prognosis in patients with neuroblastoma

2020 ◽  
Author(s):  
Hongjun Fan ◽  
Tianyu Xing ◽  
Huimin Hong ◽  
Chao Duan ◽  
Wen Zhao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Clinical Characteristics ◽  
Operating Characteristic ◽  
Neuroblastoma Cells ◽  
Prognostic Analysis ◽  
Kaplan Meier ◽  
Polymerase Chain ◽  
The Relationship

Abstract Background Paired-like homeobox 2B (PHOX2B) is specifically expressed in the nervous system including neuroblastoma cells, but little is known about the clinical significance of the expression of PHOX2B in bone marrow (BM) and peripheral blood (PB) samples of newly diagnosed neuroblastoma patients. Methods The expression of PHOX2B in 276 paired BM and PB samples of neuroblastoma patients at diagnosis was tested by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Then the relationship between PHOX2B level and clinical characteristics including metastasis and prognosis was explored by receiver operating characteristic (ROC) analysis and Kaplan-Meier method. Results We identified the combined expression of PHOX2B in both BM and PB provided a high diagnostic accuracy for metastasis of neuroblastoma patients (AUC = 0.920) with the sensitivity and specificity of 86.7% and 92.9%, respectively. At last, 246 patients were enrolled for prognostic analysis. The median follow-up time was 22 months. Positive expressions of PHOX2B in BM and PB at diagnosis were associated with worse EFS and OS in neuroblastoma patients (P < 0.05). What’s worse, 19.7% (31/157) and 6.4% (10/157) patients with positive expression of PHOX2B in BM and PB samples in low/intermediate-risk group also had shorter EFS and poor OS (P < 0.05). CONCLUSIONS The expressions of PHOX2B in BM and PB were high in patients with unfavorable clinical characteristics. PHOX2B could be an appropriate biomarker for predicting metastasis and prognosis in patients with neuroblastoma.

scholarly journals Identifying the Phenotypic and Temporal Heterogeneity of Knee Osteoarthritis: Data From the Osteoarthritis Initiative

2021 ◽  
Vol 9 ◽  
Author(s):  
Mengjiao Li ◽  
Lan Lan ◽  
Jiawei Luo ◽  
Li Peng ◽  
Xiaolong Li ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Likelihood Ratio ◽  
Statistical Significance ◽  
Temporal Heterogeneity ◽  
Inference Model ◽  
Progression Model ◽  
Osteoarthritis Initiative ◽  
Kellgren And Lawrence ◽  
Distinct Subtype

Objective: Previous studies discussing phenotypic and temporal heterogeneity of knee osteoarthritis (KOA) separately have fatal limitations that either clustering patients with similar severity or assuming all knees have a single common progression pattern, which are unreliable. This study tried to uncover more reliable information on phenotypic and temporal heterogeneity of KOA.Design: Data were from Osteoarthritis Initiative database. Six hundred and seventy-eight unilateral knees that have greater Kellgren and Lawrence (KL) grade than the contralateral knees at baseline and in all follow-up 48 months were included. Measurements of biomarkers at baseline were chosen. Subtype and Stage Inference model (SuStaIn) was applied as a subtype-progression model to identify subtypes, subtype biomarker progress sequences and stages of KOA.Results: This study identified three subtypes which account for 15, 61, and 24% of knees, respectively. Each subtype has distinct subtype biomarker progress sequence. For knees with KL grade 0/1, 2, 3, and 4, they have different distributions on stage and 26, 53, 89, and 95% of them are strongly assigned to subtypes. When assessing whether a knee has KL (grade ≥ 2), subtypes and stages from subtypes-progression model (SuStaIn) are significantly better fitting than those from subtypes-only (mixture of Gaussians) (likelihood ratio = 105.59, p = 2.2 × 10−16) or stages-only (SuStaIn where setting c = 1) (likelihood ratio = 58.04, p = 2.57 × 10−14) model. Stages in subtypes-progression model has greater β than stages-only model. Subtypes from subtypes-progression model have no statistical significance.Conclusions: For subtypes-progression model, stages contain more complete temporal information and subtypes are closer to real OA subtypes.

N9741: Survival update and prognostic factor analysis of oxaliplatin (Ox) and irinotecan (Iri) combinations for metastatic colorectal cancer (MCRC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4067-4067 ◽  
Author(s):  
H. K. Sanoff ◽  
D. J. Sargent ◽  
M. E. Campbell ◽  
R. F. Morton ◽  
C. S. Fuchs ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Prognostic Model ◽  
Performance Status ◽  
Time To Progression ◽  
First Line ◽  
Logistic Regression Models ◽  
Kaplan Meier ◽  
Specific Outcome ◽  
Grade 3

4067 Background: N9741 randomized 1691 patients (pts) to seven 5FU, Ox and Iri containing regimens for MCRC. After 20.4 months median follow-up, FOLFOX and IROX improved time to progression (TTP) and overall survival (OS) compared to IFL. Here we update OS and TTP, and report an analysis of factors prognostic of pt outcome. Methods: 5 yr OS and TTP were calculated by Kaplan-Meier per treatment (rx) arm. Pt factors [rx arm, age, gender, prior adjuvant rx, body mass index (BMI), performance status (PS), number of disease sites (#sites), neutrophil count (ANC), hemoglobin, platelets, bilirubin, alkaline phosphatase (ALK), aspartate aminotransferase (AST)] were assessed for univariate association with OS, TTP, response rate (RR), and any grade =3 toxicity. Associated factors were included in multivariate Cox and logistic regression models. Results: After a median follow-up of 4.3 yrs, FOLFOX treated pts were more likely to live 5 yrs, 9.2% versus 5.4% for IROX (p=.016) and 3.8% for IFL (p<.001). Median TTP was also significantly longer in the FOLFOX arm, 9.2 mo vs 6.5 mo for IROX (p=<.001) and 6.0 mo for IFL (p=<.001). The prognostic model found higher PS, ANC and ALK, and more disease sites were prognostic of worse OS (see table ). Age = 70 was associated with poorer survival (HR death 1.33, p=.03), but not TTP, RR, or grade =3 toxicity. FOLFOX rx was the most powerful prognostic factor for TTP and OS. The odds of grade =3 toxicity were significantly higher in FOLFOX treated pts (OR 1.65, p<.001) and lower in men (OR .63, p<.001). No significant interactions between rx arm and pt factors were present, suggesting no factor examined is predictive of rx-specific outcome. Conclusions: 9% 5 yr OS in MCRC pts treated with first-line FOLFOX sets a new benchmark. We confirmed pre-rx PS, WBC, and ALK are prognostic for OS, though FOLFOX rx was the strongest prognostic factor. No factor was associated with differential outcome or toxicity by rx arm, thus these factors cannot be used to guide rx selection. [Table: see text] [Table: see text]

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