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High Hemoglobin Glycation Index Is Associated With Telomere Attrition Independent of HbA1c, Mediated by TNFα.
Lyu, L, Yu, J, Liu, Y, He, S, Zhao, Y, Qi, M, Ping, F, Xu, L, Li, W, Zhang, H, et al
The Journal of clinical endocrinology and metabolism. 2022;(2):462-473
Abstract
CONTEXT The hemoglobin glycation index (HGI) is correlated with metabolic diseases and inflammation. Whether the HGI is associated with the aging process and how inflammation and oxidative stress affect the relationship remain unclear. OBJECTIVE We aimed to analyze links between the HGI and aging biomarkers, and to explore a potential role of inflammation and oxidative stress in the correlations. METHODS A cross-sectional study of 434 subjects with different glucose intolerances in a rural community was enrolled. The HGI was calculated as the difference between the measured and predicted hemoglobin A1c (HbA1c). The population was categorized into tertiles of the HGI. Telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) determined by polymerase chain reaction assay. Tumor necrosis factor (TNF) α and interleukin (IL) 6, 8-oxo-2'-deoxyguanosine (8-oxo-dG), superoxide dismutase (SOD) activities, and glutathione reductase (GR) were measured. RESULTS Participants in the high HGI group were older and reported a shorter LTL, higher levels of TNFα, SOD activities, and HbA1c. Correlation analyses demonstrated that HGI was correlated with LTL (r = -0.25, P < .001) and TNFα (r = 0.19, P < .001) regardless of HbA1c levels. No relationship was found between HGI and mtDNAcn. HGI (β = -0.238, 95% CI -0.430, -0.046, P = .015) and TNFα (β = -0.02, 95% CI -0.030, -0.014, P < .001) were proved to be correlated with LTL independently, using multiple linear regression analysis. Ordinal logistic regression models showed that compared with subjects the high HGI group, the possibilities of a higher-level LTL was 5.29-fold in the low HGI group (OR 5.29, 95% CI (2.45, 11.41), P < .001), 2.41-fold in the moderate HGI group (OR 2.41, 95% CI 1.35, 4.30, P = .003) after controlling for confounding variables. Mediation analyses indicated that TNFα accounted for 30.39% of the effects of the HGI on LTL. CONCLUSION HGI was negatively related to telomere attrition, independent of HbA1c. TNFα acted as a mediator of the relationship between HGI and LTL.
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Two-year effectiveness and safety of golimumab in ulcerative colitis: An IG-IBD study.
Pugliese, D, Privitera, G, Rogai, F, Variola, A, Viola, A, Laterza, L, Privitera, AC, Allocca, M, Bossa, F, Cappello, M, et al
United European gastroenterology journal. 2021;(1):102-109
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Abstract
BACKGROUND Few data exist regarding the long-term effectiveness of golimumab in ulcerative colitis. No data have been reported on real-world continuous clinical response. OBJECTIVE This study aimed to describe the long-term outcomes in a large cohort of patients on golimumab who had ulcerative colitis. METHODS Consecutive patients with active ulcerative colitis, started on golimumab, were enrolled and prospectively followed up. The primary end point was to evaluate the long-term persistence on golimumab therapy. RESULTS A total of 173 patients with ulcerative colitis were studied. Of these, 79.2% were steroid dependent, and 46.3% were naïve to anti-tumour necrosis factor alpha agents. The median duration of golimumab therapy was 52 weeks (range: 4-142 weeks). The cumulative probability of maintaining golimumab treatment was 47.3% and 22.5% at 54 and 108 weeks, respectively. Biological-naïve status (odds ratio [OR] = 3.02, 95% confidence interval [CI]: 1.44-6.29; p = 0.003) and being able to discontinue steroids at Week 8 (OR = 3.32, 95% CI: 1.34-8.30; p = 0.010) and Week 14 (OR = 2.94, 95% CI: 1.08-8.02; p = 0.036) were associated with longer persistence on therapy. At Week 54, 65/124 (52.4%) postinduction responders were in continuous clinical response. A continuous clinical response was associated with a lower likelihood of golimumab discontinuation throughout the subsequent year of therapy (p < 0.01). Overall, 40 (23.1%) patients were in clinical remission at the last follow-up visit. Twenty-six adverse events were recorded, leading to golimumab withdrawal in 9.2% of patients. CONCLUSIONS Biological-naïve status and not requiring steroids at Weeks 8 and 14 seem to be associated with a longer persistence on golimumab therapy in ulcerative colitis.
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Methylglyoxal, Glycated Albumin, PAF, and TNF-α: Possible Inflammatory and Metabolic Biomarkers for Management of Gestational Diabetes.
Piuri, G, Basello, K, Rossi, G, Soldavini, CM, Duiella, S, Privitera, G, Spadafranca, A, Costanzi, A, Tognon, E, Cappelletti, M, et al
Nutrients. 2020;(2)
Abstract
BACKGROUND In gestational diabetes mellitus (GDM), pancreatic β-cell breakdown can result from a proinflammatory imbalance created by a sustained level of cytokines. In this study, we investigated the role of specific cytokines, such as B-cell activating factor (BAFF), tumor necrosis factor α (TNF-α), and platelet-activating factor (PAF), together with methylglyoxal (MGO) and glycated albumin (GA) in pregnant women affected by GDM. METHODS We enrolled 30 women whose inflammation and metabolic markers were measured at recruitment and after 12 weeks of strict dietetic therapy. We compared these data to the data obtained from 53 randomly selected healthy nonpregnant subjects without diabetes, hyperglycemia, or any condition that can affect glycemic metabolism. RESULTS In pregnant women affected by GDM, PAF levels increased from 26.3 (17.4-47.5) ng/mL to 40.1 (30.5-80.5) ng/mL (p < 0.001). Their TNF-α levels increased from 3.0 (2.8-3.5) pg/mL to 3.4 (3.1-5.8) pg/mL (p < 0.001). The levels of methylglyoxal were significantly higher in the women with GDM (p < 0.001), both at diagnosis and after 12 weeks (0.64 (0.46-0.90) μg/mL; 0.71 (0.47-0.93) μg/mL, respectively) compared to general population (0.25 (0.19-0.28) μg/mL). Levels of glycated albumin were significantly higher in women with GDM (p < 0.001) only after 12 weeks from diagnosis (1.51 (0.88-2.03) nmol/mL) compared to general population (0.95 (0.63-1.4) nmol/mL). CONCLUSION These findings support the involvement of new inflammatory and metabolic biomarkers in the mechanisms related to GDM complications and prompt deeper exploration into the vicious cycle connecting inflammation, oxidative stress, and metabolic results.
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Prevalence of Metabolic Syndrome Among Patients with Psoriasis Treated with TNF Inhibitors and the Effects of Anti-TNF Therapy on Their Lipid Profile: A Prospective Cohort Study.
Botelho, KP, Pontes, MAA, Rodrigues, CEM, Freitas, MVC
Metabolic syndrome and related disorders. 2020;(3):154-160
Abstract
Background: Tumor necrosis factor (TNF) is an important inflammatory cytokine in the pathogenesis of psoriasis and metabolic syndrome (MS). Patients with psoriasis have higher rates of MS; therefore, some authors suggest an MS screening within this population. In addition, TNF inhibitor treatment often modifies the metabolic profiles of these patients. This study describes the epidemiological, clinical, and laboratory characteristics of patients with psoriasis undergoing anti-TNF treatment and evaluates whether anti-TNF treatments influence changes in their metabolic parameters. Methods: A prospective 6-month cohort study followed patients who underwent three consecutive consultations at 0, 3, and 6 months. The sample composed of 83 patients with psoriasis using anti-TNF. Results: The mean age and disease duration of the patients were 48 ± 11 and 16 ± 9 years, respectively. Most patients were men (61.5%). The prevalence of MS was 36%, and high rates of abdominal obesity (59%) and overweight (82%) were observed. Anti-TNF treatment significantly altered total cholesterol levels (195.5 ± 36.17 vs. 183.5 ± 41.23, P = 0.04) and low-density lipoprotein (LDL) cholesterol levels (128.5 ± 31.26 vs. 113 ± 36.31, P = 0.04). This study has some limitations, such as small sample size, brief follow-up period (6 months), patient recruitment from a tertiary-level referral center, and no control group. Conclusions: Patients with psoriasis have high rates of MS, overweight, and obesity, but anti-TNF treatment seems to improve the metabolic profile of these patients by decreasing their total and LDL cholesterol levels.
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Efficacy of autologous bone marrow mesenchymal stem cells in the treatment of knee osteoarthritis and their effects on the expression of serum TNF-α and IL-6.
Li, J, Shao, Q, Zhu, X, Sun, G
Journal of musculoskeletal & neuronal interactions. 2020;(1):128-135
Abstract
OBJECTIVE To investigate the clinical efficacy of autologous bone marrow mesenchymal stem cell (BMSC) transplantation in the treatment of knee osteoarthritis (OA) and its effect on the expression of serum TNF-α and IL-6. METHODS The clinical data of 86 patients with knee OA treated in the Shanghai East Hospital Tongji University from March 2015 to March 2017 were analyzed retrospectively. Observation group (treated with intraarticular injection of autologous BMSC); Control group (treated with arthroscopic debridement and injected with sodium hyaluronate). The patients were followed up for 1 year after treatment, the clinical efficacy was evaluated by the Lysholm Knee Scale (Lysholm), Visual analog scale (VAS), and the expression of serum TNF-α and IL-6 was detected by ELISA. RESULTS The expression of TNF-α and IL-6 at 6 and 12 months after surgery was significantly lower than that before surgery (P<0.05). CONCLUSIONS The Lysholm score and total effective rate of knee OA patients underwent BMSC transplantation are better than that of joint debridement, while the VAS score was lower than that of joint debridement. Meanwhile, BMSC transplantation seems to reduce the postoperative inflammatory reaction.
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Screening for frailty among older patients with cancer using blood biomarkers of inflammation.
Harneshaug, M, Kirkhus, L, Benth, JŠ, Grønberg, BH, Bergh, S, Whist, JE, Rostoft, S, Jordhøy, MS
Journal of geriatric oncology. 2019;(2):272-278
Abstract
INTRODUCTION As frailty is associated with inflammation, biomarkers of inflammation may represent objective measures that could facilitate the identification of frailty. Glasgow prognostic score (GPS), combines C-reactive protein (CRP) and albumin, and is scored from 0 to 2 points. Higher score indicates a higher degree of inflammation. OBJECTIVES To investigate whether (1) GPS is associated with frailty, (2) GPS could be used to screen for frailty, (3) IL-6 and TNF-α add to the accuracy of GPS as a screening tool, and (4) GPS adds prognostic information in frail older patients with cancer. METHODS Prospective, observational study of 255 patients ≥70 years with solid malignant tumours referred for medical cancer treatment. At baseline, frail patients were identified by a modified Geriatric Assessment (mGA), and blood samples were collected. RESULTS Mean age was 76.7 years, 49.8% were frail, and 56.1% had distant metastases. The proportion of frail patients increased with higher GPS (GPS zero: 43.2%, GPS one: 52.7%, GPS two: 94.7%). GPS two was significantly associated with frailty (OR 18.5), independent of cancer type, stage, BMI and the use of anti-inflammatory drugs. The specificity of GPS was high (99%), but the sensitivity was low (14%). Frail patients with GPS two had poorer survival than patients with GPS zero-one. TNF-α and IL-6 did not improve the accuracy of GPS when screening for frailty. CONCLUSION Frailty and GPS two are strongly associated, and GPS two is a significant prognostic factor in frail, older patients with cancer. The inflammatory biomarkers investigated are not suitable screening tools for frailty.
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Differences in carotid atherosclerosis between patients with ankylosing spondylitis treated with tumor necrosis factor-α antagonists and healthy matched controls.
Zardi, EM, Pipita, ME, Giorgi, C, Lichinchi, D, Zardi, DM, Afeltra, A
Medicine. 2018;(27):e11250
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Abstract
An increased vascular risk is present in patients with ankylosing spondylitis (AS). In this report, we evaluate the presence and grade of atherosclerosis in patients with AS, uninterruptedly treated with tumor necrosis factor-α (TNF-α) antagonists for 2 years, in comparison to that in a nontreated group of healthy controls.Fourteen patients with AS and 14 healthy controls underwent carotid sonography to measure intima-media thickness (IMT) and to evaluate the presence of plaque. Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Functional Index scores, erythrocyte sedimentation rate, C-reactive protein, glycemia, total cholesterol, and triglyceride levels were also recorded.Patients with AS showed significantly lower values of mean and maximum IMT at the level of the common carotid (P = .02 and .04, respectively) and the carotid bulb (P = .0006 and .0005, respectively) compared to those of healthy controls. They also had a number of carotid plaques significantly lower than that of healthy controls (P = .02). No differences were found in IMT values at the level of internal carotid between the 2 populations.The significantly lower carotid atherosclerosis found in patients with AS treated with TNF antagonists than in healthy controls shows the important complementary role of this treatment in reducing vascular disease progression probably by decreasing inflammation.
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Microbiota Composition May Predict Anti-Tnf Alpha Response in Spondyloarthritis Patients: an Exploratory Study.
Bazin, T, Hooks, KB, Barnetche, T, Truchetet, ME, Enaud, R, Richez, C, Dougados, M, Hubert, C, Barré, A, Nikolski, M, et al
Scientific reports. 2018;(1):5446
Abstract
Spondyloarthritis (SpA) pathophysiology remains largely unknown. While the association with genetic factors has been established for decades, the influence of gut microbiota is only an emerging direction of research. Despite the remarkable efficacy of anti-TNF-α treatments, non-responders are frequent and no predictive factors of patient outcome have been identified. Our objective was to investigate the modifications of intestinal microbiota composition in patients suffering from SpA three months after an anti-TNF-α treatment. We performed 16S rDNA sequencing of 38 stool samples from 19 spondyloarthritis patients before and three months after anti-TNF-α treatment onset. SpA activity was assessed at each time using ASDAS and BASDAI scores. Some modifications of the microbiota composition were observed after three months of anti-TNF-α treatment, but no specific taxon was modified, whatever the clinical response. We identified a particular taxonomic node before anti-TNF-α treatment that can predict the clinical response as a biomarker, with a higher proportion of Burkholderiales order in future responder patients. This study suggests a cross-influence between anti-TNF-α treatment and intestinal microbiota. If its results are confirmed on larger groups of patients, it may pave the way to the development of predictive tests suitable for clinical practices.
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Impact of treatment with TNF antagonists on total cholesterol in patients with ankylosing spondylitis and psoriatic arthritis.
Maneiro, JR, Souto, A, Gomez-Reino, JJ
Clinical rheumatology. 2017;(5):1167-1172
Abstract
The objective of the study was to analyze the impact of TNF antagonists (TNFa) on the total cholesterol and triglycerides on ankylosing spondylitis (AS) and psoriatic arthritis (PsA). In this single-centre observational study of AS and PsA patients, differences in triglyceride and total cholesterol levels and frequency of hypertriglyceridemia and hypercholesterolemia at 3 and 6 months were analysed in patients treated and not treated with TNFa. General estimation equations and linear regression analysis were used to investigate associations between disease activity and lipid levels and to identify predictors of change. One hundred fifty-seven patients treated, and 157 not treated with TNFa, were included in the study. A transient increase in cholesterol level from baseline to 3 months in TNFa-treated patients was the only statistically significant effect (P < 0.001). Persistent percentages of hypertriglyceridemia and hypercholesterolemia from baseline were significantly higher in not treated than in TNFa-treated patients (P = 0.009 and P = 0.001, respectively). Inverse associations between changes in cholesterol level and Bath Ankylosing Spondylitis Disease Activity Index (P = 0.011) and CRP (P < 0.001), but not Disease Activity Score in 28 Joints (P = 0.095) were found in the whole group. In AS and PsA patients treated with TNFa, mild and transient changes in cholesterol but not in triglyceride levels were associated with changes in disease activity.
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[Effect of tumour necrosis factor α blockade on bone metabolism in chronic inflammatory joint diseases].
Aguilar Del Rey, FJ, García Portales, R, Haro Liger, M, Rodríguez Andreu, J, Casals Sánchez, JL, Pérez González, R
Medicina clinica. 2016;(2):56-62
Abstract
BACKGROUND AND OBJECTIVE To evaluate the effect of anti-TNF treatments on bone mineral density (BMD), bone remodelling markers (BRM) and receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) in patients with chronic inflammatory joint diseases. METHODS A longitudinal prospective study was performed under clinical practice conditions on 31 patients diagnosed of rheumatoid arthritis, psoriatic arthropathy and ankylosing spondylitis who had received treatment with anti-TNF alpha drugs for one year. BMD, OPG and RANKL soluble form (sRANKL) were studied at the onset and end of the study. During the study (0, 3, 6, 9 and 12 month), disease activity (SDAI, BASDAI and CRP), functional capacity (HAQ, BASFI), BRM and vitamin D were studied. RESULTS BMD was not modified after one year of treatment. The patients who took corticosteroids had a mean bone mass loss of 3% in the lumbar spine (±1.6, P=.02). In regards to the BRM, did not experience significant changes over the course of the study. Disease activity, both SDAI (P=.002) and BASDAI (P=.002), decreased. OPG was maintained without changes during the year of treatment while both the sRANKL (0.28±0.22, P=.013) and sRANKL/OPG ratio significantly decreased (0.04±0.03, P=.031). CONCLUSION The patients being treated with anti-TNF did not present with a significant loss of DMO during the study (one year), at the same time experiencing an improvement in disease activity. This protection has been clearer in the responding patients.