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Predicting neurological recovery after traumatic spinal cord injury by time-resolved analysis of monocyte subsets.
Heller, RA, Seelig, J, Crowell, HL, Pilz, M, Haubruck, P, Sun, Q, Schomburg, L, Daniel, V, Moghaddam, A, Biglari, B
Brain : a journal of neurology. 2021;(10):3159-3174
Abstract
Monocytes and lymphocytes elicit crucial activities for the regenerative processes after various types of injury. The survival of neurons exposed to mechanical and oxidative stress after traumatic spinal cord injury depends on a multitude of factors. In this study, we sought to evaluate a correlation between remission after traumatic spinal cord injury and the dynamics of monocyte subsets in respect to the lymphocytes' responsive potential, cytokine expression, patterns of trace element concentration and clinical covariates. We examined prospectively 18 (three female, 15 male) patients after traumatic spinal cord injury. Blood samples were drawn at admission and 4 h, 9 h, 12 h, 1 and 3 days as well as 1 and 2 weeks and 1, 2 and 3 months after the trauma. Analysis of cytokines (CCL2, IL-10, enolase 2, CXCL12, TGF-β1, TGF-β2) was performed using a multiplex cytokine panel. Plasma trace element concentrations of selenium, copper and zinc were determined by total reflection X-ray fluorescence analysis; neopterin, selenoprotein P (SELENOP) and ceruloplasmin (CP) by enzyme-linked immunosorbent assay; and selenium binding protein 1 (SELENBP1) by luminometric immunoassay. The responsive potential of lymphocytes was assessed using transformation tests. The monocyte subsets (classical, intermediate, and non-classical) and expression of CD14, CD16, CXCR4 and intracellular IL-10 were identified using a multi-colour flow cytometry analysis. The dynamics of the cluster of intermediate CD14-/CD16+/IL10+/CXCR4int monocytes differed significantly between patients with an absence of neurological remission (G0) from those with an improvement (G1) by 1 or 2 American Spinal Injury Association Impairment Scale (AIS) steps (Kruskal-Wallis Test, P = 0.010, G0 < G1, AIS+: 1 < G1, AIS+: 2) in the first 24 h. These dynamics were associated inversely with an increase in enolase and SELENBP1 14 days after the injury. In the elastic net regularized model, we identified an association between the increase of a subpopulation of intermediate CD14-/CD16+/IL10+/CXCR4int monocytes and exacerbated immune response within 24 h after the injury. These findings were reflected in the consistently elevated response to mitogen stimulation of the lymphocytes of patients with significant neurological remission. Early elevated concentrations of CD14-/CD16+/IL10+/CXCR4int monocytes were related to higher odds of CNS regeneration and enhanced neurological remission. The cluster dynamics of CD14-/CD16+/IL10+/CXCR4int monocytes in the early-acute phase after the injury revealed a maximum of prognostic information regarding neurological remission (mean parameter estimate: 0.207; selection count: 818/1000 repetitions). We conclude that early dynamics in monocyte subsets allow a good prediction of recovery from traumatic spinal cord injury.
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Long-term impact of congenital toxoplasmosis on phenotypic and functional features of circulating leukocytes from infants one year after treatment onset.
de Araújo, TE, Gomes, AO, Coelho-Dos-Reis, JG, Carneiro, ACAV, Machado, AS, Andrade, GMQ, Vasconcelos-Santos, DV, Januário, JN, Peruhype-Magalhães, V, Teixeira-Carvalho, A, et al
Clinical immunology (Orlando, Fla.). 2021;:108859
Abstract
Changes in immune response of children with congenital toxoplasmosis (CT) regarding infection evolution and therapeutic intervention was addressed. Infants with CT presented increased counts of monocytes, CD3-CD16-CD56High, CD3+CD56+ and CD4+ T-cells 1-year after treatment onset (TOXO1-yearAT). Smaller numbers of CD3-CD16-CD56+ and TCRγδ+ T-cells were specifically observed in infants with retinochoroidal lesions (L(+)). When infants were classified based on the baseline status, expansion of CD3-CD16-CD56High and CD4+ T-cells were observed in L(+) who had active, active/cicatricial or cicatricial lesions. Infants who had active or active/cicatricial lesions display augmented numbers of monocytes, CD3-CD16+CD56+, CD3+CD56+, CD8+DR+ and TCRγδ+ T-cells and those with active/cicatricial or cicatricial at baseline displayed increase in CD14+CD64+ monocytes. Moreover, all L(+) had increased IFN-γ+ and IL-10+ CD4+ T-cells, while L(-) had increased ratios of TNF+, IFN-γ+ and IL-4+ NK-cells upon antigen-specific stimulation. Persistent alterations in leukocytes in TOXO1-yearAT suggest long-term sequels in the immune system of infants with CT.
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Monocyte-to-high density lipoprotein cholesterol ratio as a predictor of mortality in patients with transcatheter aortic valve replacement.
Karahan, S, Okuyan, E
European review for medical and pharmacological sciences. 2021;(16):5153-5162
Abstract
OBJECTIVE We aim to evaluate the prognostic value of monocyte-to-high density lipoprotein cholesterol ratio (MHR) in patients undergoing transcatheter aortic valve replacement (TAVR). PATIENTS AND METHODS This was a retrospective observational study and all patients who underwent TAVR for symptomatic and/or severe aortic stenosis between January 2014 and October 2019 were evaluated. Demographic characteristics, clinical features and laboratory data were retrieved from hospital electronic database and patient charts. We evaluated independent predictors of all-cause mortality with logistic regression test. p-value <0.05 was accepted as statistically significant. RESULTS A total of 145 patients (mean age 78.1±7.2 years, 49.7% female) who underwent TAVR were included in the study. The median MHR was 13.73 (interquartile range (IQR) 10.0-25.9). In correlation analysis, MHR positively correlated with only serum CRP level (R: 0.383, p=<0.001). The mortality rates during the observation period were 76.1% and 4.1% in patients who had MHT over and below the median MHR value, respectively (p<0.001). Based on the results of multivariate binary logistic regression analysis, MHR and presence of cerebrovascular accident emerged as independent predictors of all-cause mortality (OR: 1.514, 95% CI:1.231-1.862). CONCLUSIONS This is the first study of the independent predictive ability of MHR in TAVR patients. The strong independent predictive power of MHR possibly stems from the underlying coronary artery disease. Further studies particularly examining the predictive role of MHR on cardiovascular adverse events and cardiovascular death in TAVR patients are needed.
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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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Sex-specific association of monocyte count to high-density lipoprotein ratio with SYNTAX score in patients with suspected stable coronary artery disease.
Xu, W, Guan, H, Gao, D, Pan, J, Wang, Z, Alam, M, Lian, J, Zhou, J
Medicine. 2019;(41):e17536
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Abstract
Recently, the monocyte count to high-density lipoprotein cholesterol ratio (MHR) was found to be associated with the SYNTAX score in patients with both stable coronary artery disease (CAD) and acute coronary syndrome (ACS). The MHR was significantly higher in male patients. However, the sex-specific association of MHR with SYNTAX score in stable CAD was not well explored. Thus, the present study aimed to investigate the association of MHR and presence and severity of CAD evaluated by coronary angiography and the SYNTAX score in males and females.In total, 873 patients who received selective coronary angiography between March 2017 and July 2018 were included in the present study. Patients were divided into 3 groups according to MHR tertiles. The MHR was calculated by dividing the monocyte count by the high-density lipoprotein cholesterol level. CAD was defined as at least 50% diameter stenosis of a major coronary artery, including the right coronary, left main coronary, left anterior descending, and left circumflex arteries. The SYNTAX score was calculated by 2 experienced interventional cardiologists. SYNTAX score ≥23 was defined as a high SYNTAX score.Males showed a significantly higher MHR (12.2 [8.9-15.5] vs 9.3 [6.2-12.1], P < .001), accompanied by a higher prevalence of CAD (68.1% vs 53.4%, P < .001). Male sex remained an independent predictor of elevated MHR after correction for confounding factors (adjusted odds ratio [OR] 3.102, P = .001). The association between MHR and SYNTAX score was confirmed only in male stable patients with CAD (r = 0.113, P = .036). Multivariate logistic regression analysis showed that MHR was an independent predictor of SYNTAX score ≥23 only in male patients with CAD. The receiver-operating characteristic curve showed a predictive value of MHR for high SYNTAX score only in males.A higher MHR in males and a positive correlation of MHR with SYNTAX score were observed only in male stable patients with CAD. Such an easily obtained index may help interventional cardiologists detect high-risk patients before coronary catheterization, but its application may be restricted to males.
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Monocyte-to-high density lipoprotein ratio is associated with a decreased compound muscle action potential amplitude in patients with diabetic axonal polyneuropathy.
Vural, G, Gümüsyayla, Ş
Medicine. 2018;(42):e12857
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Abstract
The monocyte-to-high density lipoprotein ratio (MHR) has recently been implemented as an indicator of inflammation and oxidative stress. The present study characterized MHR in patients with diabetic polyneuropathy (DPN), in which oxidative stress and microvascular damage play a role in pathogenesis, relative to patients with non-DPN, diabetic patients without polyneuropathy, and healthy individuals. We further aimed to evaluate the association between MHR and the decreased compound muscle action potential (CMAP) amplitude of patients with diabetic axonal polyneuropathy.We enrolled 90 patients with DPN, 75 patients with nonDPN, 92 diabetic patients without polyneuropathy, and 67 healthy individuals; The monocyte, high-density lipoprotein cholesterol (HDL-C) values were obtained for all participants and MHR was calculated for each individual. Intergroup comparison was performed. The relationship between MHR and the posterior tibial nerve CMAP amplitudes was examined.Statistically significant negative correlation was observed between MHR and the posterior tibial nerve CMAP amplitudes of patients with DPN. The MHR values of the patients with DPN were significantly higher than those of the patients with non-DPN, diabetic patients without polyneuropathy and the control group.This study demonstrated that diabetic patients with higher MHR values may be more likely to develop polyneuropathy.
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Platelet-Derived MRP-14 Induces Monocyte Activation in Patients With Symptomatic Peripheral Artery Disease.
Dann, R, Hadi, T, Montenont, E, Boytard, L, Alebrahim, D, Feinstein, J, Allen, N, Simon, R, Barone, K, Uryu, K, et al
Journal of the American College of Cardiology. 2018;(1):53-65
Abstract
BACKGROUND Peripheral artery disease (PAD), a diffuse manifestation of atherothrombosis, is a major cardiovascular threat. Although platelets are primary mediators of atherothrombosis, their role in the pathogenesis of PAD remains unclear. OBJECTIVES The authors sought to investigate the role of platelets in a cohort of symptomatic PAD. METHODS The authors profiled platelet activity, mRNA, and effector roles in patients with symptomatic PAD and in healthy controls. Patients with PAD and carotid artery stenosis were recruited into ongoing studies (NCT02106429 and NCT01897103) investigating platelet activity, platelet RNA, and cardiovascular disease. RESULTS Platelet RNA sequence profiling mapped a robust up-regulation of myeloid-related protein (MRP)-14 mRNA, a potent calcium binding protein heterodimer, in PAD. Circulating activated platelets were enriched with MRP-14 protein, which augmented the expression of the adhesion mediator, P-selectin, thereby promoting monocyte-platelet aggregates. Electron microscopy confirmed the firm interaction of platelets with monocytes in vitro and colocalization of macrophages with MRP-14 confirmed their cross talk in atherosclerotic manifestations of PAD in vivo. Platelet-derived MRP-14 was channeled to monocytes, thereby fueling their expression of key PAD lesional hallmarks and increasing their directed locomotion, which were both suppressed in the presence of antibody-mediated blockade. Circulating MRP-14 was heightened in the setting of PAD, significantly correlated with PAD severity, and was associated with incident limb events. CONCLUSIONS The authors identified a heightened platelet activity profile and unraveled a novel immunomodulatory effector role of platelet-derived MRP-14 in reprograming monocyte activation in symptomatic PAD. (Platelet Activity in Vascular Surgery and Cardiovascular Events [PACE]; NCT02106429; and Platelet Activity in Vascular Surgery for Thrombosis and Bleeding [PIVOTAL]; NCT01897103).
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Removing Batch Effects from Longitudinal Gene Expression - Quantile Normalization Plus ComBat as Best Approach for Microarray Transcriptome Data.
Müller, C, Schillert, A, Röthemeier, C, Trégouët, DA, Proust, C, Binder, H, Pfeiffer, N, Beutel, M, Lackner, KJ, Schnabel, RB, et al
PloS one. 2016;(6):e0156594
Abstract
Technical variation plays an important role in microarray-based gene expression studies, and batch effects explain a large proportion of this noise. It is therefore mandatory to eliminate technical variation while maintaining biological variability. Several strategies have been proposed for the removal of batch effects, although they have not been evaluated in large-scale longitudinal gene expression data. In this study, we aimed at identifying a suitable method for batch effect removal in a large study of microarray-based longitudinal gene expression. Monocytic gene expression was measured in 1092 participants of the Gutenberg Health Study at baseline and 5-year follow up. Replicates of selected samples were measured at both time points to identify technical variability. Deming regression, Passing-Bablok regression, linear mixed models, non-linear models as well as ReplicateRUV and ComBat were applied to eliminate batch effects between replicates. In a second step, quantile normalization prior to batch effect correction was performed for each method. Technical variation between batches was evaluated by principal component analysis. Associations between body mass index and transcriptomes were calculated before and after batch removal. Results from association analyses were compared to evaluate maintenance of biological variability. Quantile normalization, separately performed in each batch, combined with ComBat successfully reduced batch effects and maintained biological variability. ReplicateRUV performed perfectly in the replicate data subset of the study, but failed when applied to all samples. All other methods did not substantially reduce batch effects in the replicate data subset. Quantile normalization plus ComBat appears to be a valuable approach for batch correction in longitudinal gene expression data.
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Association of Monocyte-to-HDL Cholesterol Ratio with Slow Coronary Flow is Linked to Systemic Inflammation.
Canpolat, U, Çetin, EH, Cetin, S, Aydin, S, Akboga, MK, Yayla, C, Turak, O, Aras, D, Aydogdu, S
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2016;(5):476-82
Abstract
BACKGROUND Previous studies proposed that both inflammation, oxidative stress, and impaired endothelial dysfunction have a significant role in occurrence of slow coronary flow (SCF). monocyte-to-high density lipoprotein cholesterol ratio (MHR) is a recently emerged indicator of inflammation and oxidative stress, which have been studied only in patients with chronic kidney disease. HYPOTHESIS We aimed to assess the relationship between MHR and SCF. METHODS Patients who had angiographically normal coronary arteries were enrolled in this retrospective study (n = 253 as SCF group and n = 176 as control group). Patients who had corrected thrombolysis in myocardial infarction frame counts (cTFCs) above the normal cutoffs were defined as with SCF. RESULTS The MHR and high-sensitivity C-reactive protein (hsCRP) were significantly higher in the SCF group. In correlation analysis, MHR has a significantly positive correlation with cTFC and serum hsCRP levels (P < .001). In multivariate logistic regression analysis, MHR was found as independently associated with the presence of SCF (odds ratio: 1.24, P < .001). CONCLUSION Higher MHR which indicates an enhanced inflammation and oxidative stress was significantly and independently associated with the presence of SCF. Besides, MHR was positively correlated with serum hsCRP level as a conventional marker for systemic inflammation.
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Subclinical myocyte injury, fibrosis and strain in relationship to coronary plaque in asymptomatic HIV-infected individuals.
Fitch, KV, DeFilippi, C, Christenson, R, Srinivasa, S, Lee, H, Lo, J, Lu, MT, Wong, K, Petrow, E, Sanchez, L, et al
AIDS (London, England). 2016;(14):2205-14
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BACKGROUND Cardiovascular disease (CVD) rates are increased in HIV. The degree to which myocyte injury, strain, and fibrosis occur prior to clinical disease and relate to coronary plaque in HIV is unknown. OBJECTIVE To investigate newer cardiac biomarkers of subclinical myocyte injury [high-sensitivity troponin T (hs-cTnT)], strain (amino terminal proB-type natriutretic peptide), fibrosis (soluble ST2, Galectin-3), and vascular inflammation (oxidized LDL, lipoprotein-associated phospholipase A2) in HIV-infected individuals and non-HIV controls and relate these to coronary plaque by cardiac computed tomography angiography. DESIGN Observational. METHODS Markers were investigated in 155 HIV-infected and 70 non-HIV-infected participants without known CVD and with low traditional CVD risk and related to cardiac computed tomography angiography data. RESULTS Age, sex, and race did not differ between the groups. Hs-cTnT [3.1 (3.0, 6.4) vs. 3.0 (3.0, 4.0) ng/l, P = 0.03], Galectin-3 [13.5 (10.6, 18.1) vs. 11.6 (9.9, 14.5) ng/ml, P = 0.002], and soluble ST2 [31.5 (24.5, 41.5) vs. 28.3 (20.2, 33.5) ng/ml, P = 0.01] were significantly higher in HIV-infected participants vs. CONTROLS Detectable hs-cTnT (seen in 50% of HIV participants) related to the overall presence of plaque [odds ratio (OR) 2.3, P = 0.01] and particularly to coronary calcium (OR for Agatston calcium score > 0, 3.3, P = 0.0008 and OR for calcified plaque 7.4, P = 0.01) in HIV, but not in non-HIV. CONCLUSION Subclinical myocyte injury is observed among young, asymptomatic HIV-infected individuals with low traditional cardiac risk factors. In the setting of HIV infection, the presence of detectable cardiac troponin is strongly associated with coronary plaque, particularly calcified plaque among an asymptomatic group. Future studies are needed to assess if early subclinical injury marked by hs-cTnT predicts plaque progression and cardiac events in HIV.