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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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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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3.
The comparison of knee osteoarthritis treatment with single-dose bone marrow-derived mononuclear cells vs. hyaluronic acid injections.
Goncars, V, Jakobsons, E, Blums, K, Briede, I, Patetko, L, Erglis, K, Erglis, M, Kalnberzs, K, Muiznieks, I, Erglis, A
Medicina (Kaunas, Lithuania). 2017;(2):101-108
Abstract
OBJECTIVE The aim of this study was to compare treatment methods of the knee joint degenerative osteoarthritis, using autologous bone marrow-derived mononuclear cells and hyaluronic acid injections and observe prevalence of adverse effects in both groups. MATERIALS AND METHODS A prospective randomized controlled clinical trial was carried out. The analysis of pain and changes in osteoarthritis symptoms after a single intra-articular bone marrow-derived mononuclear cell injection into the knee joint in the Kellgren-Lawrence stage II-III osteoarthritis during the 12-month period were performed. The results were compared with the control group treated routinely by hyaluronic acid injections therapy. A therapy group of patients (n=28) received single bone marrow-derived mononuclear cell intra-articular injections. A control group of patients (n=28) was treated with a total of three sodium hyaluronate intra-articular injections each one performed a week apart. The clinical results were obtained using the Knee Osteoarthritis Outcome Score (KOOS) and the Knee Society Score (KSS) before and 3, 6, and 12 months after injection. RESULTS A statistically significant improvement was observed in the mononuclear cell group over the starting point in all scores. At the endpoint at month 12, the KOOS score improved significantly (P<0.05) on the pain subscale (+25.44), activity and daily living subscale (+21.36), quality of life subscale (+28.83), and total KOOS (+18.25). The KSS score also demonstrated a significant improvement on the symptoms subscale (+25.42) and the function subscale (+38.32) (P<0.001). The KOOS symptoms and sports subscales improved without statistical significance. The difference between the control group treated with hyaluronic acid versus the bone marrow-derived mononuclear cells group at time points 6 and 12 months demonstrated a statistically significant (P<0.05) superiority in the KOOS pain subscale over the hyaluronic acid group. In both groups serious adverse effects were not observed. CONCLUSIONS The intra-articular injection of bone marrow-derived mononuclear cells is a safe manipulation with no side effects during the 12-month period. This treatment provides statistically significant clinical improvement between the starting point and 1, 3, 6, and 12 months after. When compared to hyaluronic acid treatment, better pain relief in the long-term period of mononuclear cell group was observed.
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Effects of normoxic and hypoxic exercise regimens on monocyte-mediated thrombin generation in sedentary men.
Wang, JS, Chang, YL, Chen, YC, Tsai, HH, Fu, TC
Clinical science (London, England : 1979). 2015;(4):363-74
Abstract
Exercise and hypoxia paradoxically modulate vascular thrombotic risks. The shedding of procoagulant-rich microparticles from monocytes may accelerate the pathogenesis of atherothrombosis. The present study explores the manner in which normoxic and hypoxic exercise regimens affect procoagulant monocyte-derived microparticle (MDMP) formation and monocyte-promoted thrombin generation (TG). Forty sedentary healthy males were randomized to perform either normoxic (NET; 21% O2, n=20) or hypoxic (HET; 15% O2, n=20) exercise training (60% VO(2max)) for 30 min/day, 5 days/week for 5 weeks. At rest and immediately after HET (100 W under 12% O2 for 30 min), the MDMP characteristics and dynamic TG were measured by flow cytometry and thrombinography respectively. The results demonstrated that acute 12% O2 exercise (i) increased the release of coagulant factor V (FV)/FVIII-rich, phosphatidylserine (PS)-exposed and tissue factor (TF)-expressed microparticles from monocytes, (ii) enhanced the peak height and rate of TG in monocyte-rich plasma (MRP) and (iii) elevated concentrations of norepinephrine/epinephrine, myeloperoxidase (MPO) and interleukin-6 (IL-6) in plasma. Following the 5-week intervention, HET exhibited higher enhancements of peak work-rate and cardiopulmonary fitness than NET did. Moreover, both NET and HET decreased the FV/FVIII-rich, PS-exposed and TF-expressed MDMP counts and the peak height and rate of TG in MRP following the HET. However, HET elicited more suppression for the HE (hypoxic exercise)-enhanced procoagulant MDMP formation and dynamic TG in MPR and catecholamine/peroxide/pro-inflammatory cytokine levels in plasma than NET. Hence, we conclude that HET is superior to NET for enhancing aerobic capacity. Furthermore, HET effectively suppresses procoagulant MDMP formation and monocyte-mediated TG under severe hypoxic stress, compared with NET.
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Upregulation of monocyte tissue factor activity is significantly associated with carotid intima-media thickness in patients with metabolic syndrome.
Nakagomi, A, Sasaki, M, Ishikawa, Y, Shibui, T, Kosugi, M, Endoh, Y, Morikawa, M, Kusama, Y, Atarashi, H, Mizuno, K
Journal of atherosclerosis and thrombosis. 2011;(6):475-86
Abstract
AIMS: Metabolic syndrome (MS) represents a cluster of cardiovascular risk factors and an increased risk of cardiovascular events. The carotid intima-media thickness (CIMT) is correlated with coronary and carotid atherosclerosis, and is a significant predictor of cardiovascular events. Tissue factor (TF) is an initiator of the extrinsic coagulation cascade and is expressed on peripheral blood monocytes and macrophages in atherosclerotic plaques. TF plays important roles in both thrombosis and atherosclerosis. No study has investigated the relationship between monocyte TF activity and CIMT in MS patients. METHODS Peripheral blood mononuclear cells (PBMCs) were collected from 39 normal subjects and 110 patients with MS. The procoagulant activity (PCA) in monocytes was measured using a one-stage clotting assay and is expressed as the mean±SD (mU TF/10(6) PBMCs). RESULTS The PCA in monocytes in MS patients was significantly higher than in normal subjects (86.2 ±69.5 vs. 52.4±9.9 mU TF/10(6) PBMCs, p < 0.001). In multivariate analysis, patient age (β coefficient= 0.373, p < 0.001), high-density lipoprotein cholesterol (β coefficient=-0.307, p = 0.001) and PCA (β coefficient= 0.422, p =0.002) were each significantly and independently associated with CIMT. CONCLUSIONS These data indicate that the upregulation of monocyte TF activity is significantly associated with CIMT in MS patients.
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Disturbed regulation of cholesterol synthesis in monocytes of obese patients with hypercholesterolemia.
Paragh, G, Balogh, Z, Kovács, E, Szabolcs, M, Szabó, J, Csapó, K, Fóris, G
Metabolism: clinical and experimental. 2003;(1):1-6
Abstract
The aim of the present study was to clarify the influence of obesity on the functions of low-density lipoprotein receptors (LDL-R) and 3-hydroxy-3-methylglutarate-coenyzme A (HMG-CoA) reductase both in healthy control subjects and in patients with hypercholesterolemia (HC). Experiments were performed on monocytes of 15 non-obese (C I) and 11 obese (C II) healthy control subjects and on 22 non-obese (HC I) and 26 obese (HC II) patients with HC. [(125)I]LDL was used to determine LDL-R activity by measuring binding and intracellular degradation. The rate of endogenous cholesterol synthesis was measured using [(14)C]acetate incorporation into the cholesterol fraction of monocytes. The binding ability of [(125)I]LDL was identical across all groups. The [(14)C]acetate incorporation in resting monocytes was increased only in obese HC group. The 50-microg/mL LDL protein-induced inhibition of [(14)C]acetate incorporation was significantly diminished (P <.001) in the same group. A strong positive correlation was detected between the [(14)C]acetate incorporation by resting cells and LDL-induced inhibition in all groups except the obese HC group, in which their correlation was negative (P <.001). Furthermore, in the obese HC group, a significant positive correlation was detected between body mass index (BMI) and the basal level of [(14)C]acetate incorporation, whereas a negative correlation was found between BMI and LDL-induced inhibition of [(14)C]acetate incorporation. The present data suggest that in patients with HC the concomitant obesity results in dysregulation of cholesterol homeostasis, which may contribute to the accelerated atherosclerosis.