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Prognostic value of pre-treatment Naples prognostic score (NPS) in patients with osteosarcoma.
Yang, Q, Chen, T, Yao, Z, Zhang, X
World journal of surgical oncology. 2020;(1):24
Abstract
BACKGROUND This study aimed to evaluate the clinical significance of pre-treatment Naples prognostic score (NPS) in patients with osteosarcoma. METHODS The clinical data of 133 osteosarcoma patients between January 2011 and February 2018 in our hospital was retrospectively collected and analyzed. NPS was calculated from four parameters, including serum albumin level, serum total cholesterol (TC), lymphocyte-to-monocyte ratio (LMR), and neutrophil-to-lymphocyte ratio (NLR). Patients were divided into three groups (group 1-3) based on NPS. The relationships between NPS and clinical features, overall survival (OS), and progression-free survival (PFS) were analyzed. Two prediction models based on NPS and clinical parameters were developed: clinical parameters model (model A), and the combined model of NPS and clinical parameters (model B). Their predictive performances were further evaluated and compared. RESULTS The median follow-up time of this cohort was 46.0 (range, 5-75) months, while the median OS and PFS was 40 (range, 5-75) months and 36 (range, 5-71) months, respectively. NPS was significantly correlated with gender, tumor location, Enneking stage, pathological fracture, local recurrence, and metastasis (all P < 0.05). Variables of NPS, Enneking stage, local recurrence, metastasis, and NLR were confirmed as independent prognostic factors for OS and PFS by univariate and multivariate Cox analysis. Prediction model B obtained larger AUCs for OS and PFS and showed better consistency between nomogram-predicted and actual survival than that of model A at the follow-up time of 1-, 3-, and 5-year. CONCLUSIONS NPS was a novel, reliable, and multidimensional prognostic scoring system with favorable predictive performance for patients with osteosarcoma.
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Incorporation of dynamic segmented neutrophil-to-monocyte ratio with leukocyte count for sepsis risk stratification.
Fang, WF, Chen, YM, Wang, YH, Huang, CH, Hung, KY, Fang, YT, Chang, YC, Lin, CY, Chang, YT, Chen, HC, et al
Scientific reports. 2019;(1):19756
Abstract
The association between sepsis and segmented neutrophil-to-monocyte (SeMo) ratio is unclear. We postulated that an increase in dynamic SeMo ratio measurement can be applied in risk stratification. This retrospective study included 727 consecutive sepsis patients in medical intensive care units (ICUs), including a subpopulation of 153 patients. According to the leukocyte (white blood cell, WBC) count on day 3 (normal range, between 4,000/µL and 12,000/µL) and delta SeMo (value of SeMo ratio on day 3 minus value of SeMo ratio on day 1; normal delta SeMo, <7), patients were grouped into 3 (delta SeMo & WBC tool). The survival lines separated significantly with hazard ratios of 1.854 (1.342-2.560) for the delta SeMo or WBC abnormal group and 2.860 (1.849-4.439) for the delta SeMo and WBC abnormal group compared to the delta SeMo and WBC normal group. Delta SeMo & WBC tool and delta sequential organ failure assessment (SOFA) tool performed better than the other tools (delta SeMo, delta WBC, day 3 WBC, and day 1 WBC). Severity in delta SeMo & WBC tool and delta SeMo tool reflected the immune dysfunction score, cytokine expression, and human leukocyte antigen D-related monocyte expression on day 1 and day 3. There was correspondence between delta SOFA and delta WBC and between delta SeMo and delta cytokine expression. Incorporation of dynamic SeMo ratio with WBC count provides risk stratification for sepsis patients admitted in the ICU.
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Classical monocytes from older adults maintain capacity for metabolic compensation during glucose deprivation and lipopolysaccharide stimulation.
Yarbro, JR, Pence, BD
Mechanisms of ageing and development. 2019;:111146
Abstract
Inflammaging is the chronic low-grade inflammation that occurs with age that contributes to the pathology of age-related diseases. Monocytes are innate immune cells that become dysregulated with age and which can contribute to inflammaging. Metabolism plays a key role in determining immune cell functions, with anti-inflammatory cells primarily relying on fatty acid oxidation and pro-inflammatory cells primarily relying on glycolysis. It was recently shown that lipopolysaccharide (LPS)-stimulated monocytes can compensate for a lack of glucose by utilizing fatty acid oxidation. Given that mitochondrial function decreases with age, we hypothesized that classical monocytes taken from aged individuals would have an impaired ability to upregulate oxidative metabolism along with impaired effector functions. Aging did not impair LPS-induced oxygen consumption rate during glucose deprivation as measured on a Seahorse XFp system. Additionally, aged classical monocytes maintained inflammatory gene expression responses and phagocytic capacity during LPS stimulation in the absence of glucose. In conclusion, aged classical monocytes maintain effector and metabolic functions during glucose deprivation, at least in an ex vivo context.
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Association of the Monocyte to HDL Cholesterol Ratio With Thrombus Burden in Patients With ST-Segment Elevation Myocardial Infarction.
Arısoy, A, Altunkaş, F, Karaman, K, Karayakalı, M, Çelik, A, Ceyhan, K, Zorlu, Ç
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2017;(8):992-997
Abstract
Intracoronary thrombus burden is associated with some adverse events and poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI). Identifying predictors of the intracoronary thrombus burden may contribute to the management of STEMI. In this study, we evaluated whether monocyte count to high-density lipoprotein cholesterol ratio (MHR) is a predictor of intracoronary thrombus burden in patients with STEMI. The study population consisted of 414 patients with STEMI who underwent primary percutaneous coronary intervention (PCI). Angiographic thrombus burden was classified based on thrombolysis in myocardial infarction (TIMI) thrombus grades. The patients were grouped into 2 categories of low thrombus burden and high thrombus burden. The MHR was significantly higher in the high thrombus burden group compared with the low thrombus group (16.0 [9.2-22.1] vs 25.4 [13.5-44.6]; P < .001). In multivariate logistic regression analysis, MHR was an independent predictor of high thrombus burden (odds ratio: 1.067, 95% CI: 1.031-1.105; P < .001). The area under the receiver-operating characteristic curve of the MHR was 0.688 (0.641-0.733; P < .001) to predict high thrombus burden. In conclusion, MHR was independent predictor of high thrombus burden in patients with STEMI who underwent primary PCI.
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Monoclonal antibody against macrophage colony-stimulating factor suppresses circulating monocytes and tissue macrophage function but does not alter cell infiltration/activation in cutaneous lesions or clinical outcomes in patients with cutaneous lupus erythematosus.
Masek-Hammerman, K, Peeva, E, Ahmad, A, Menon, S, Afsharvand, M, Peng Qu, R, Cheng, JB, Syed, J, Zhan, Y, O'Neil, SP, et al
Clinical and experimental immunology. 2016;(2):258-70
Abstract
This study's objective was to assess the effects of PD-0360324, a fully human immunoglobulin G2 monoclonal antibody against macrophage colony-stimulating factor in cutaneous lupus erythematosus (CLE). Patients with active subacute CLE or discoid lupus erythematosus were randomized to receive 100 or 150 mg PD-0360324 or placebo via intravenous infusion every 2 weeks for 3 months. Blood and urine samples were obtained pre- and post-treatment to analyse pharmacokinetics and pharmacodynamic changes in CD14(+) CD16(+) monocytes, urinary N-terminal telopeptide (uNTX), alanine/aspartate aminotransferases (ALT/AST) and creatine kinase (CK); tissue biopsy samples were taken to evaluate macrophage populations and T cells using immunohistochemistry. Clinical efficacy assessments included the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Among 28 randomized/analysed patients, peak/trough plasma concentrations increased in a greater-than-dose-proportional manner with dose increases from 100 to 150 mg. Statistically significant differences were observed between active treatment and placebo groups in changes from baseline in CD14(+) CD16(+) cells, uNTX, ALT, AST and CK levels at most time-points. The numbers, density and activation states of tissue macrophages and T cells did not change from baseline to treatment end. No between-group differences were seen in CLASI. Patients receiving PD-0360324 reported significantly more adverse events than those receiving placebo, but no serious adverse events. In patients with CLE, 100 and 150 mg PD-0360324 every 2 weeks for 3 months suppressed a subset of circulating monocytes and altered activity of some tissue macrophages without affecting cell populations in CLE skin lesions or improving clinical end-points.
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Activation of neutrophils and monocytes by a leukocyte-depleting filter used throughout cardiopulmonary bypass.
Ilmakunnas, M, Pesonen, EJ, Ahonen, J, Rämö, J, Siitonen, S, Repo, H
The Journal of thoracic and cardiovascular surgery. 2005;(4):851-9
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Abstract
OBJECTIVE Cardiopulmonary bypass elicits systemic inflammation. Depletion of circulating leukocytes might alleviate inflammatory response. We studied the effects of a leukocyte-depleting filter on phagocyte activation during cardiopulmonary bypass. METHODS Fifty patients undergoing coronary artery bypass grafting were randomly allocated into an arterial line leukocyte filter group (n = 25) with a Pall LeukoGuard 6 leukocyte-depleting filter (LG6; Pall Biomedical, Portsmouth, United Kingdom) and a control group without any filter (n = 25). Blood sampling took place from arterial line at predetermined time points. In the filter group, the sample was taken immediately before the filter; to evaluate activation at the site, an additional sample was taken immediately after the filter. CD11b/CD18 and L-selectin expressions and basal production of hydrogen peroxide were determined with whole-blood flow cytometry, and plasma lactoferrin level was determined with enzyme-linked immunosorbent assay. RESULTS Neutrophil CD11b expression was higher in the filter group than in the control group (P < .001). Likewise, monocyte CD11b expression, neutrophil hydrogen peroxide production, and lactoferrin plasma levels were all significantly higher, whereas neutrophil and monocyte counts and neutrophil L-selectin expression were all significantly lower in the filter group (all P < .001). At 5 minutes of CPB, CD11b expression increased across the filter on neutrophils (median difference 197 relative fluorescence units, range 45-431 relative fluorescence units, P < .001) and monocytes (median difference 26 relative fluorescence units, range -68-111 relative fluorescence units, P < .001). CONCLUSION The LG6 arterial line leukocyte filter is ineffective in its principal task of diminishing phagocyte activation during cardiopulmonary bypass.
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Decreased tumor necrosis factor-induced adhesion of human monocytes to endothelial cells after moderate alcohol consumption.
Badía, E, Sacanella, E, Fernández-Solá, J, Nicolás, JM, Antúnez, E, Rotilio, D, de Gaetano, G, Urbano-Márquez, A, Estruch, R
The American journal of clinical nutrition. 2004;(1):225-30
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BACKGROUND Moderate alcohol consumption protects against ischemic heart disease, possibly through an antiinflammatory effect. However, little is known about the mechanisms by which alcohol may interfere in the development of atherosclerosis. OBJECTIVE We analyzed the effects of 2 alcoholic beverages with high (red wine) or low (gin) polyphenolic content on human monocyte adhesion to an endothelial cell line (Ea.hy926). DESIGN This was a randomized, crossover trial with 8 healthy men. After a washout period, the subjects received 30 g ethanol/d as red wine or gin for 28 d. Before and after each intervention, a dietary survey and laboratory analysis were performed. Adhesion of human monocytes to endothelial cells was measured in basal and stimulated [by tumor necrosis factor alpha (TNF-alpha)] conditions. Adhesion molecules involved in monocyte-endothelium interactions were determined on the cell surface. RESULTS The mean expression of very late activation antigen 4 on monocytes significantly decreased after red wine intake [by 18% (95% CI: 33%, 3%); P = 0.022]. Monocyte adhesion significantly increased after TNF-alpha stimulation of endothelial cells. This increase, however, was 39% less (95% CI: 48%, 35%; P = 0.049) after gin intake than after the respective washout period and was nearly abolished by red wine intake [96% less than after the respective washout period (95% CI: 142%, 76%); P < 0.001]. The reduction after red wine intake was significantly different from that after gin intake (P = 0.014). CONCLUSIONS TNF-alpha-induced adhesion of monocytes to endothelial cells was virtually abolished after red wine consumption but was only partially reduced after gin consumption. This effect may be due to the down-regulation of adhesion molecules on the monocyte surface.
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Enhanced monocyte expression of tissue factor by oxidative stress in patients with antiphospholipid antibodies: effect of antioxidant treatment.
Ferro, D, Saliola, M, Meroni, PL, Valesini, G, Caroselli, C, Praticò, D, Fitzgerald, GA, Shoenfeld, Y, Violi, F
Journal of thrombosis and haemostasis : JTH. 2003;(3):523-31
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Abstract
In a first study, we performed a cross-sectional analysis of urinary excretion of isoprostanes, IPF(2alpha-III) and (VI), and monocyte tissue factor (TF) antigen and activity between 11 antiphospholipid (APL) antibody-positive patients and 13 APL negative subjects. In a second study, 11 APL positive patients were randomly supplemented either with (n = 6) or without (n = 5) antioxidants (vitamin E at 900 IU day(-1), vitamin C at 2000 mg day(-1)) for 6 weeks. In a third study, TF and superoxide anion were measured in human monocytes incubated with anti-beta(2) glycoprotein 1 (beta(2)GP(1)) or control IgG, either with or without vitamin E. APL-positive patients had higher values of isoprostanes (P < 0.05) and monocyte TF antigen (P = 0.001) and activity (P = 0.0001) than APL-negative subjects. Only in APL positive patients did monocyte TF antigen correlate significantly with IPF(2alpha-III) (rho 0.79; P < 0.003) and IPF(2alpha-VI) (rho = 0.87; P < 0.0001). In patients who received antioxidant supplementation, we found a significant decrease of isoprostanes (P < 0.05) and monocyte TF antigen (P < 0.01) and activity (P < 0.007). In vitro experiments demonstrated that anti-beta(2)GP(1) antibodies dose-dependently enhanced the monocyte production of the superoxide anion and TF, which were significantly inhibited by vitamin E. This study demonstrates that in APL-positive patients, oxidative stress contributes to activate the clotting system via over-expression of monocyte TF. We suggest that anti-beta(2)GP(1) antibodies could play a pivotal role by enhancing the monocyte production of oxygen free radicals.
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Simvastatin inhibits the monocyte expression of proinflammatory cytokines in patients with hypercholesterolemia.
Ferro, D, Parrotto, S, Basili, S, Alessandri, C, Violi, F
Journal of the American College of Cardiology. 2000;(2):427-31
Abstract
OBJECTIVE The purpose of this study was to assess if simvastatin has an anti-inflammatory activity in patients with hypercholesterolemia. BACKGROUND Simvastatin, an inhibitor of 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase, reduced cardiovascular events in patients with myocardial infarction and hypercholesterolemia. METHODS Sixteen patients with polygenic hypercholesterolemia were randomly allocated to diet (n = 8) or diet plus 20 mg/day simvastatin (n = 8) for eight weeks. Before and at the end of treatment period, lipid profile and monocyte expression of tumor necrosis factor-alpha (TNF) and interleukin-1beta (IL-1beta) were measured. RESULTS At baseline no difference in lipid profile and monocyte expression of TNF and IL-1beta were observed between the two groups. In patients allocated to diet alone, no change in lipid profile and monocyte expression of TNF and IL-1beta was seen. In patients with diet plus simvastatin, significant decreases of total cholesterol (-27%, p<0.02), low density lipoprotein-cholesterol (-33%, p<0.02), and monocyte expression of TNF (-49%, p<0.02) and IL-1beta (-35%, p<0.02) were observed. At the end of treatment period, patients treated with simvastatin had lower cholesterol and monocyte TNF and IL-1beta than did patients assigned to diet alone. CONCLUSION This study suggests that simvastatin possesses anti-inflammatory activity via the inhibition of pro-inflammatory cytokines TNF and IL-1beta expressed by monocytes.