Monocyte distribution width (MDW) as a screening tool for sepsis in the Emergency Department.

Objectives The diagnosis of sepsis in the Emergency Department (ED) is challenging and a reliable biomarker is needed. The current study aimed to evaluate the diagnostic accuracy of monocyte distribution width (MDW) for the early identification of sepsis in the ED. Methods We performed a large observational study including consecutive adult patients (≥18 years of age) presenting to the ED between September and November 2019, with an order for complete blood count (CBC) evaluation. A total of 2,215 patients were enrolled and classified based on Sepsis-2 criteria as the control group (1,855), infection group (172), Systemic Inflammatory Response Syndrome (SIRS) group (100), and sepsis group (88). Results MDW levels were higher in patients with sepsis than in all other groups (p<0.001). ROC curve analysis showed an optimal diagnostic accuracy of MDW for sepsis prediction at a cut-off point of 23.5, with an AUC of 0.964, sensitivity and specificity of 0.920 and 0.929, respectively. Conclusions Our findings encourage further investigation to validate the use of MDW as a screening tool for the early identification of patients at risk of sepsis in the ED.

Diagnostic accuracy of cerebrospinal fluid biomarkers measured by chemiluminescent enzyme immunoassay for Alzheimer disease diagnosis.

In the last decades, an important role of cerebrospinal fluid (CSF) biomarkers for Alzheimer disease (AD) diagnosis has emerged. The evaluation of the triad consisting of 42 aminoacid-long amyloid-beta peptide (Aß42), total Tau (tTau) and Tau phosphorylated at threonine 181 (pTau) have been recently integrated into the research diagnostic criteria of AD. For a long time, the enzyme-linked immunosorbent assay (ELISA) has represented the most commonly used method for the measurement of CSF biomarkers levels. This study aimed to assess the diagnostic accuracy of CSF biomarkers, namely Aß42, tTau and pTau and their ratio, measured by fully automated CLEIA assay (Lumipulse). We included 96 patients clinically diagnosed as AD (48) and non-AD (48). All CSF biomarkers levels were measured on Lumipulse G1200 fully automated platform (Fujirebio Inc. Europe, Gent, Belgium). Aß42 levels, 42/40 ratio, 42/tTau ratio, 42/PTau ratio were significantly reduced, and tTau and PTau levels were significantly increased in AD patients in comparison with non-AD patients. The receiving operator curve (ROC) analysis showed good diagnostic accuracy of all CSF biomarkers and their ratios for discriminating AD patients from non-AD patients, with 42/40 ratio having the best AUC (0.724, 95%CI 0.619-0.828; p < 0.001). Our findings support the use of CSF biomarkers measured by CLEIA method on a fully automated platform for AD diagnosis.

Non-Skeletal Activities of Vitamin D: From Physiology to Brain Pathology.

Vitamin D is a secosteroid hormone regulating the expression of almost 900 genes, and it is involved in the regulation of calcium and phosphate metabolism, immune response, and brain development. Low blood vitamin D levels have been reported in patients affected by various diseases. Despite a large amount of literature data, there is uncertainty surrounding the role of vitamin D as a serum biomarker in Alzheimer's disease (AD) and Parkinson's disease (PD). Indeed, the lack of internationally recognized 25(OH)D3 reference measurement procedures and standard materials in the past led to unstandardized serum total 25(OH)D3 results among research and clinical care laboratories. Thus, most of the literature studies reported unstandardized data, which are of little use and make it difficult to draw conclusions of the role of vitamin D in AD and PD. This review summarizes the extra-skeletal actions of vitamin D, focusing its role in immunomodulation and brain function, and reports the issue of lacking standardized literature data concerning the usefulness of vitamin D as a biomarker in AD and PD.

Reference interval of monocyte distribution width (MDW) in healthy blood donors.

BACKGROUND: The aim of the study was to accurately establish the reference interval (RI) of monocyte distribution width (MDW) in healthy blood donors by the direct method using different statistical approaches. METHODS: MDW was measured in 486 subjects. RI of MDW was calculated by the non-parametric method, the robust method and, the Harrell-Davis bootstrap method and using different tests to identify potential outliers (Dixon-Reed and Tukey). RESULTS: Lower and upper reference limits of the RI calculated by the non-parametric method were, 16.22 (90%CI 15.78-16.47) - 23.15 (90%CI 22.80-24.10) (without outlier removal), and 16.44 (90%CI 16.21-16.67) - 22.99 (90%CI 22.33-23.22) (after outlier removal). The RIs based on the robust method were, respectively, 16.29-22.98 (without) and 16.50-22.67 (with outlier removal). Finally, the RIs calculated by the Harrell-Davis bootstrap method, without or after outlier removal, were 16.19-23.24 and 16.43-22.93. Thus, the RIs obtained by the three calculation methods were very similar. Additionally, no RI partition was done since no significant gender or age association was found. CONCLUSIONS: Our results support the use of a unique RI of MDW, independently of sex and age.

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.

Vitamin D and the nervous system.

Objective: to summarise the activities that Vitamin D (VD) carries out in the brain and to clarify the potential role of VD in neurological diseases. Methods: a literature research has been performed in Pubmed using the following keywords: 'Vitamin D', 'nervous system', 'brain'. Results: the studies reviewed show that VD contributes to cerebral activity in both embryonic and adult brain, helping the connectivity of neural circuits responsible for locomotor, emotional and reward-dependent behavior. Low VD serum levels have been found in patients affected by Alzheimer Disease, Parkinson Disease, Multiple Sclerosis, Autism Spectrum Disorders, Sleep Disorders and Schizophrenia. Discussion: findings are controversial and should be interpreted with caution, since most of the studies performed have observational study set and few interventional studies are available, producing conflicting results. Overall, it can be stated that the potential role of Vitamin D in neurological diseases is mostly unclear and further randomised controlled trials are needed to understand better whether Vitamin D supplementation treatment can be useful in brain disorders.

Vitamin D in malaria: more hypotheses than clues.

Vitamin D is a secosteroid hormone regulating calcium and phosphate metabolism, immune response and brain development. Low blood 25(OH)D levels have been reported in patients affected by infectious diseases caused by parasites, including malaria. Despite the high effectiveness of antimalarials, malaria is burdened with high morbidity and mortality, and the search for additional therapies is rapidly growing. Furthermore, available preventive measures have proved to be barely effective so far. Finding new prevention and therapy tools is a matter of urgency. Studies on animal models and humans have hypothesized some mechanisms by which the hormone can influence malaria pathogenesis, and the role of Vitamin D supplementation in preventing and treating this disease has been suggested. Few studies on the association between Vitamin D and malaria are available and disagreeing results have been reported. Studies in humans reporting an association between low 25(OH)D circulating levels and Malaria have a small sample size and observational study-set. Randomized controlled trials are needed in order to understand if Vitamin D administration might play a role in preventing and treating malaria.

Establishing the 99th percentile for high sensitivity cardiac troponin I in healthy blood donors from Southern Italy.

INTRODUCTION: The knowledge of high sensitivity cardiac troponin I (hsTnI) distribution in a reference population is mandatory for its introduction in clinical practice. The aim of this study was to define the Upper Reference Limit (URL) of hsTnI measured by Single Molecule Counting technology (SMC) in an accurately selected reference population. MATERIALS AND METHODS: In the study 1140 blood donors were included and selected on the basis of medical history and biomarkers. High sensitivity cardiac troponin I was measured by SMC technology (Clarity, Singulex, Alamed, USA). The 99th percentile was calculated by the non-parametric method according to the Clinical and Laboratory Standard Institute - CLSI C28-A3. RESULTS: The median age was 41 years (IQR: 28 - 50) and 69% were males. The overall 99th percentile was 5 ng/L (90% CI: 4.2 - 5.6). When considering sex-related differences, we found slight differences between the 99th percentile in males and females. Moreover, the 99th percentile trended with age, especially in females. CONCLUSIONS: We defined the 99th percentile of hs-cTnI measured by SMC technology in a highly selected healthy population, with only minor differences between males and females. Our findings provide the basic criteria for the reliable interpretation of hsTnI concentrations measured by the SMC technology in clinical settings.

Standardized measurement of circulating vitamin D [25(OH)D] and its putative role as a serum biomarker in Alzheimer's disease and Parkinson's disease.

The current review provides an overview on the development of 25(OH)D measurement standardization tools over the last three decades and clarifies whether there is a role as a serum biomarker for vitamin D in neurological diseases. In the past, a lack of internationally recognized 25(OH)D reference measurement procedures and reference standard materials led to unstandardized serum total 25(OH)D results among research and clinical care laboratories. The vitamin D Standardization Program (VDSP) has been introduced in 2010 to address this problem, however, vitamin D External Quality Assessment Scheme (DEQAS) reports still show substantial sample- to- sample variability. Further, immunoassays, which are mainly used in clinical care laboratories, display analytical issues, including matrix-effects interferences, which cannot be overcome by the standardization process. Hence, liquid chromatography-tandem mass spectrometry (LC/MS-MS) methods should be used to measure 25(OH)D. Low vitamin D serum levels have been found in patients affected by Alzheimer's disease and Parkinson's disease, suggesting a role for vitamin D as a serum biomarker in these diseases. However, few studies reported 25(OH)D standardized results, thus, no clear evidence on the potential role of 25(OH)D serum levels in these diseases exists.