Clinical usefulness of presepsin and monocyte distribution width (MDW) kinetic for predicting mortality in critically ill patients in intensive care unit.

Background: In this study, we explored the accuracy of two new sepsis biomarkers, monocyte distribution width (MDW) and presepsin (PSP), compared to traditional ones, C-reactive protein (CRP) and Procalcitonin (PCT), to identify sepsis and predict intra-hospital mortality by analyzing their kinetic at different time points during hospitalization stay. Methods: We enrolled 104 patients admitted to the intensive care unit (ICU) of University Hospital "Paolo Giaccone", Palermo. Among these, 30 (29%) had a clinical diagnosis of sepsis. MDW, PCT, CRP, and PSP were evaluated at admission (T0), after 24 h (T24), 48 h (T48), 72 h (T72), at day 5 (T5), and at discharge (TD). Results: Patients with sepsis displayed higher levels of PCT and PSP than patients without sepsis at each timepoint; differently, CRP displayed statistically significant differences only at T0, while MDW only at T0 and T24. Patients with increasing levels of PSP displayed lower median survival time than patients with decreasing levels; differences reached statistical significance only at 48 h (20 vs. 29 days, log rank test, p = 0.046). Interestingly, PSP was an independent predictor of ICU mortality at 48 and 72 h after hospital admission. Also, the kinetic of PSP had prognostic value, with increased values at 48 h after admission being associated with reduced survival. Conclusion: Our findings support the role of PSP and its kinetic as a predictor of ICU mortality.

Monocyte Distribution Width (MDW) as a biomarker of sepsis: An evidenced-based laboratory medicine approach.

Monocyte Distribution Width (MDW) is a new generation cell blood count parameter providing a measure of monocyte anisocytosis. In the last decades, it has emerged as a reliable biomarker of sepsis in the acute setting, especially emergency department, and intensive care unit. MDW has several advantages over commonly used sepsis biomarkers, including low-cost, ease and speed of measurement. The clinical usefulness of MDW has been established in several studies and some clinical laboratory medicines have already implemented it in their routine. In this article, we describe the analytical and clinical features of MDW to guide its appropriate use in clinical practice by integrating the research evidence with real-world laboratory experience. The proper use of a biomarker is critical for improving patients' care and outcome as well as ensuring healthcare quality.

Role of Multiple Vitamin D-Related Polymorphisms in Multiple Sclerosis Severity: Preliminary Findings.

BACKGROUND: Multiple Sclerosis (MS) is a multifactorial disease whose pathogenesis is the result of interaction among genetic, epigenetic, and environmental factors. Among these, a role for vitamin D hypovitaminosis has emerged in recent decades. Vitamin D levels are influenced by both environmental and genetic factors. Single nucleotide polymorphisms (SNPs) in genes codifying for molecules involved in vitamin D metabolism have been associated with an increased risk of developing MS. However, few studies assessed the association of such SNPs with the severity of the disease. The aim of this observational study was to evaluate the potential association among vitamin D status, MS severity, and vitamin D-related SNPs, alone or in combination. METHODS: In a cohort of 100 MS patients, we genotyped 18 SNPs in the following genes: NAD synthetase 1, CYP2R1, vitamin D binding protein, vitamin D receptor, Retinoid X Receptor-α, KLOTHO, CYP24A1, and CYP27A1. Serum 25(OH)D3 levels were measured by high-performance liquid chromatography. Genotyping was performed by real-time polymerase chain reaction or PCR-RFLP. RESULTS: We did not find any association between SNPs, alone or in combination, and MS severity. CONCLUSION: In this study, we make an initial evaluation of the possible influence of several SNPs in vitamin D-related genes on MS severity.

Monocyte distribution width as a biomarker of sepsis in the intensive care unit: A pilot study.

BACKGROUND: Monocyte distribution width has been recently proposed as a sepsis biomarker in the emergency department. The aim of this study was to assess the role of monocyte distribution width as a diagnostic biomarker of sepsis in the intensive care unit. METHODS: In this prospective observational study, we included all consecutive patients admitted to the intensive care unit of the University Hospital "P. Giaccone" of Palermo. Patients were classified into three groups according to Sepsis-3 criteria: (1) patients without sepsis; (2) patients developing sepsis during their hospital stay; (3) patients admitted with sepsis. Monocyte distribution width was measured at admission (groups 1, 2, 3) and daily until the developing of sepsis (group 2) or the end of hospitalization (group 1). RESULTS: Monocyte distribution width was significantly higher in group 3 than group 1 and group 2 (30.9 [25.6-36.0] vs. 20.3 [18.3-23.6] and 21.4 [19.4-25.2]). Among patients belonging to group 2, monocyte distribution width values, measured at the day when sepsis was clinically diagnosed, were significantly higher than those found at admission: 29.4 (26.7-36.0) vs. 21.4 (19.4-25.2), P = 0.001. CONCLUSION: Monocyte distribution width could represent a reliable biomarker of sepsis in the intensive care unit.

Klotho and vitamin D in multiple sclerosis: an Italian study.

INTRODUCTION: Low vitamin D levels have been recognised as an important risk factor for autoimmune diseases, including multiple sclerosis (MS). MS is a multifactorial disease, the pathogenesis of which contributes both to genetic and environmental factors. Polymorphisms in genes codifying molecules involved in vitamin D homeostasis have been associated with hypovitaminosis D. However, the influence of polymorphisms of Klotho, which codify a protein with a pivotal role in vitamin D metabolism, have never been investigated. The aim of this study was to evaluate the association among genetic variants of Klotho, namely rs1207568 and rs9536314, serum 25(OH)D3 levels, and multiple sclerosis (both risk and disease progression). MATERIAL AND METHODS: 107 patients with MS and 133 healthy controls were enrolled in this study. Serum 25(OH)D3 levels and genotyping of Klotho SNPs were evaluated in all participants by high-performance liquid chromatography and real-time polymerase chain reaction, respectively. RESULTS: Allelic and genotypic frequencies did not differ between patients and controls. Concerning rs1207568, we found a trend toward lower serum 25(OH)D3 levels in MS patients with A allele (mutant), both in heterozygosis (AG) and in homozygosis (AA), in comparison to MS patients with G allele in homozygosis (GG) (AG + AA 20.5 ±6.3 µg/l; GG 22.5 ±7.5 µg/l, p = 0.07). CONCLUSIONS: Our findings did not identify a role of Klotho in the genetic susceptibility to MS.

Aging and Neuroinflammatory Disorders: New Biomarkers and Therapeutic Targets.

Chronic neuroinflammation is a common feature of the pathogenic mechanisms involved in various neurodegenerative age-associated disorders, such as Alzheimer's disease, multiple sclerosis, Parkinson's disease, and dementia. In particular, persistent low-grade inflammation may disrupt the brain endothelial barrier and cause a significant increase of pro-inflammatory cytokines and immune cells into the cerebral tissue that, in turn, leads to microglia dysfunction and loss of neuroprotective properties. Nowadays, growing evidence highlights a strong association between persistent peripheral inflammation, as well as metabolic alterations, and neurodegenerative disorder susceptibility. The identification of common pathways involved in the development of these diseases, which modulate the signalling and immune response, is an important goal of ongoing research. The aim of this review is to elucidate which inflammation-related molecules are robustly associated with the risk of neurodegenerative diseases. Of note, peripheral biomarkers may represent direct measures of pathophysiologic processes common of aging and neuroinflammatory processes. In addition, molecular changes associated with the neurodegenerative process might be present many decades before the disease onset. Therefore, the identification of a comprehensive markers panel, closely related to neuroinflammation, could be helpful for the early diagnosis, and the identification of therapeutic targets to counteract the underlying chronic inflammatory processes.

Association between hypovitaminosis D and systemic sclerosis: True or fake?

BACKGROUND: Vitamin D insufficiency/deficiency is considered a major factor triggering and enhancing several autoimmune disorders; hypovitaminosis D has been reported to be common in Systemic Sclerosis (SSc). Previous studies assessing vitamin D insufficiency/deficiency in SSc have been reviewed, and the relation with pathogenesis and clinical features has been examined. CONTENT: Eligibility criteria were: reporting measurement of Vitamin D serum levels in all participants and evaluating adult onset-SSc individuals as patients group. RESULTS: The association between clinical features and low hormone levels is controversial. Manifold data have shown vitamin D insufficiency/deficiency to have a potential role in the pathogenesis of disease, providing inconclusive findings. SUMMARY: Promoting the onset of SSc depends on the interaction between genetics, environment and infections. It remains a sound question whether Vitamin D insufficiency/deficiency is an environment-linked immunological heckler, making infectious agents taking root.

A Risk Score Derived from the Analysis of a Cluster of 27 Serum Inflammatory Cytokines to Predict Long Term Outcome in Patients with Acute Myocardial Infarction: a Pilot Study.

BACKGROUND: The aim of our study was to evaluate the clinical utility and prognostic significance of a cluster of 27 serum cytokines for risk stratification after myocardial infarction. MATERIALS AND METHODS: We enrolled 33 consecutive patients admitted to our institution for acute myocardial infarction and prospectively followed. We evaluated traditional cardiovascular risk factors and assayed, during the acute phase, 27 serum cytokines (IL-1, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL -7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, EOTAXIN, FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1ß, PDGF, RANTES, TNF-α, VEGF) potentially associated with cardiovascular risk. Patients were divided into two groups during follow-up according to the occurrence or absence of adverse cardiovascular events (recurrence of angina, re-infarction, death, need of new revascularization, occurrence of heart failure). We developed an additive risk score by assigning one point for each cytokine that had a value greater than the median value (range 0-27). Cytokines alone and the cytokines score were related to cardiovascular events. RESULTS: Patients with and without major adverse cardiovascular events (MACEs) at follow up had a homogenous distribution of the main cardiovascular risk factors; differences were detected only for sex and age. Patients who experienced MACE had a significantly different distribution of I troponin (p=0.036), IL-8 (p=0.006), IL-13 (p=0.06), IL-10 (p=0.02), IL-17 (p=0.015), IP-10 (p=0.02), MIP-1ß (p=0.05). At univariate analysis, IL -8 (p=0.046 OR 1.13), IL-10 (p=0.05 OR 1.14) and MIP-1ß (p=0.016, OR 1.02) were significantly associated with the occurrence of MACE. This association was not confirmed at multivariate analysis. At the analysis of variance, a higher score was significantly associated with the occurrence of adverse events at follow up (F=5.07, p=0.03). At ROC curve analysis, a score greater than 13 better predicted the occurrence of adverse events at follow-up (AUC 0.72, p=0.03, sensibility 59.1%, specificity 81.8%). CONCLUSIONS: In our study we did not identify a single inflammatory cytokine able to predict adverse events in a long term follow up, whereas the presence of more than 13 cytokines above the median value was useful for risk stratification.

Fetuin-A serum levels are not correlated to kidney function in long-lived subjects.

OBJECTIVES: Serum Fetuin A has been identified as an inhibitor of ectopic calcification. It is reduced in subjects with chronic kidney disease (CKD) and it has been proposed as a potential link between CKD and the higher prevalence of arterial calcification observed in these patients. During aging both the stiffening of arterial wall due to calcification and a decline in kidney function are frequent. The aim of the study is to investigate if Fetuin A serum levels are associated with aging and with AHSG T256S polymorphism. Moreover, we aim at investigate whether serum Fetuin A is correlated to kidney function in this setting of senescence. DESIGN AND METHODS: 256 health long-lived subjects (age 92 [81-100]) were recruited for the study. Serum Fetuin A was evaluated by ELISA, Cystatin C by immune-nephelometry. AHSG T256S was determinated by PCR-RFLP. RESULTS: Serum Fetuin A shows a significant correlation with age (r=0.20; P=0.0048). AHSG TS and SS genotypes are associated to lower levels of serum protein (0.27 [0.19-0.29] g/L vs 0.42 [0.32-0.49] g/L; P<0.027 and 0.34 [0.25-0.41] g/L vs 0.42 [0.32-0.49] g/L; P<0.001, respectively). No significant correlation between Fetuin A and Cystatin C was observed. CONCLUSIONS: Serum Fetuin A increases with age in elder individuals and subjects with the TS or SS AHSG polymorphism have lower levels of the circulating protein. No correlation with kidney function decline was observed. Other mechanisms should be investigated to explain the increase of Fetuin A with age.

C-reactive protein but not soluble CD40 ligand and homocysteine is associated to common atherosclerotic risk factors in a cohort of coronary artery disease patients.

OBJECTIVES: One third to one half of the variation in vascular disease occurrence remains unexplained by traditional risk factors. Since atherosclerosis may, in part, be an inflammatory disease, circulating factors related to inflammation may be predictors of cardiovascular disease. The aim of this study was to evaluate the association between common atherosclerotic risk factors and markers of inflammation. DESIGN AND METHODS: Serum levels of soluble CD40 (sCD40L), high-sensitive C-reactive protein (hs-CRP) and homocysteine (Hcy) were measured in 251 patients selected from a series of 438 subjects affected by previous myocardial infarction, angina or other cardiovascular diseases. RESULTS: sCD40L levels were lower in patients with previous myocardial infarction while no association was observed between sCD40L and Hcy levels and other risk factors. Only hs-CRP levels positively correlated with increased number of risk factors. CONCLUSION: In a setting of patients affected with coronary artery disease no association between sCD40L and homocysteine levels and atherosclerotic risk factors was observed; only hs-CRP showed increased levels according to the number of risk factors. Future studies using larger cohorts will be needed to validate the clinical use of markers of inflammation in the prediction of cardiovascular events.