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1.
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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2.
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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3.
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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4.
Apheresis buffy coat collection without photoactivation has no effect on apoptosis, cell proliferation, and total viability of mononuclear cells collected using photopheresis systems.
Szczepiorkowski, ZM, Burnett, CA, Dumont, LJ, Abhyankar, SH
Transfusion. 2018;(4):943-950
Abstract
BACKGROUND Extracorporeal photopheresis (ECP) has been approved for the treatment of advanced cutaneous T-cell lymphoma since 1988. While the precise mechanisms resulting in clinical effects are not fully understood, the photoactivation of mononuclear cells (MNCs) using ultraviolet A (UVA) light and methoxsalen is believed to be the predominant initiating process. The effects of MNC passage through the instrument without photoactivation are unknown. The objective of this study was to evaluate the effect of cell processing through the photopheresis instruments on MNCs. STUDY DESIGN AND METHODS Fourteen healthy male subjects underwent one simulated ECP procedure without reinfusion of buffy coats (BCs) in a two-center, open-label, prospective trial. Baseline peripheral blood BC, apheresis-separated untreated BC (BC1), and photoactivated BC (BC2) were evaluated in culture for viability by dye exclusion, apoptosis by annexin V binding, and cell proliferation response to phytohemagglutinin (PHA) stimulation by bromodeoxyuridine (BrdU) incorporation. RESULTS Photoactivation (BC2) resulted in 88% expression of annexin V by Day 1 of culture compared with 37 and 39% for baseline and untreated BC1. Cell viability by propidium iodide exclusion was reduced to 10% in BC2 on Day 1 versus 65 and 60% for baseline and BC1. The proliferative response to PHA stimulation was 97% inhibited in the photoactivated BC2. CONCLUSIONS These results demonstrate that the mechanical processes used for cell separation and processing of the BC in the absence of photoactivation do not induce a significant amount of apoptosis compared to the standard ECP with methoxsalen and UVA photoactivation.
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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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6.
The Effect of Treatment of Denture-related Stomatitis on Peripheral T Cells and Monocytes.
Maciąg, J, Mikołajczyk, T, Matusik, P, Nowakowski, D, Robertson, D, Maciąg, A, Osmenda, G, Cześnikiewicz-Guzik, M
Oral health & preventive dentistry. 2017;(3):259-268
Abstract
PURPOSE Systemic immune activation has been recently linked to chronic inflammatory disorders of the oral cavity, particularly to periodontitis. The purpose of this study was to determine whether treatment of a fungus-induced oral inflammation, namely denture-related stomatitis (DRS), can affect the activation of the systemic immune response. MATERIALS AND METHODS Peripheral blood from patients with denture-related stomatitis caused by Candida albicans infection (n = 15) was collected at three time points: before treatment with nystatin, at the end of therapy and 2 months after finishing therapy. Activation of T cells and monocytes was assessed by flow cytometry. RESULTS The percentages of peripheral lymphocytes, T cells and their subpopulations, as well as monocytes were similar before, immediately following and two months after nystatin treatment. Cells expressing early activation marker CD69 and RANTES C-C chemokine receptor type 5 significantly increased immediately after treatment and returned to baseline levels after two months. Th17 cells, which have been implicated in the pathogenesis of DRS, remained unchanged. Central memory CD4+ subset and intermediate subset of monocytes were lower after therapy and this effect was sustained for two months. CONCLUSION Treatment of denture-related stomatitis does not seem to affect the general state of the cellular components of the immune system. The results suggest a potential proinflammatory effect of the antifungal agent, nystatin. Although transient and not intense, this effect might be of particular clinical importance, because of relationships between inflammation and certain diseases. Further studies are required to clarify this aspect.
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7.
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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Men and women differ in their diurnal expression of monocyte peroxisome proliferator-activated receptor-α in the fed but not in the fasted state.
Wege, N, Schutkowski, A, Boenn, M, Bialek, J, Schlitt, A, Noack, F, Grosse, I, Stangl, GI
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2015;(7):2905-11
Abstract
Peroxisome proliferator-activated receptor-α (PPARα) plays a pivotal role in regulating metabolic response to fasting and is an inhibitor of inflammatory pathways in immune cells. It represents a therapeutic target for treatment of several diseases, mainly hyperlipidemia. To shed light on PPARα expression changes in response to fasting, young healthy male and female volunteers were fed or fasted for 24 hours. Monocytes were analyzed every 2 hours to compile both profiles of mRNA and protein expression of PPARα and its interactive partner, the circadian pacemaker brain and muscle aryl hydrocarbon receptor nuclear translocator like-1 (BMAL1). We found that women change their diurnal expression profiles of PPARα and BMAL1 when switching from the fed to the fasted state, whereas men do not. Interestingly, the PPARα and BMAL1 profiles of men and women in the fed state are different, whereas the profiles in the fasted state are virtually identical. The finding of diametrically opposite responses of male and female PPARα expression in the fed state might have practical implication in human medicine as PPARα activators like fibrates are used for the therapy of chronic lymphocytic leukemia, microvascular complications in diabetes, and kidney diseases.
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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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Long-term (56-week) oral administration of probiotic Enterococcus faecium M-74 decreases the expression of sICAM-1 and monocyte CD54, and increases that of lymphocyte CD49d in humans.
Hlivak, P, Jahnova, E, Odraska, J, Ferencik, M, Ebringer, L, Mikes, Z
Bratislavske lekarske listy. 2005;(4-5):175-81
Abstract
OBJECTIVES To study the effects of long-term probiotic [Enterococcus faecium (EF) M-74 strain] application in humans with respect to adhesion molecules, both soluble forms (sICAM-1, sPECAM-1) and their expression on leukocytes. METHODS Double-blinded randomized and placebo controlled study lasting for 60 weeks. A single capsule containing either 2x10(9) of bacteria EF M-74 with 50 microg of organically bound selenium (E-group) or placebo (P-group) was given to volunteers. Peripheral blood was analyzed for the expression of particular adhesive molecules. RESULTS AND CONCLUSIONS We observed significant changes in CAMs expression in terms of a decrease in sICAM-1, CD54 on monocytes and CD11b on lymphocytes after one-year administration of Enterococcus faecium M-74 in humans. Anti-adhesion-aimed therapeutic modalities may provide the future approach to prevention and treatment of cardiovascular diseases. Application of probiotics may be part of such strategies. (Tab. 2, Fig. 6, Ref. 41.)