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Introduction: Several studies have investigated the specific neural correlates of trans people, highlighting mixed results. This study aimed to compare the presence of specific functional connectivity and differences in cognitive profile and hormone levels in trans men diagnosed with gender dysphoria (GD), and a homogeneous group of cisgender men and cisgender women. Methods: A total of 42 participants (19 trans men, 11 cisgender men, and 12 cisgender women) underwent a resting state fMRI and were measured for blood levels of testosterone, estradiol, and progesterone. A neuropsychological battery evaluated executive functions, attention, visual-perceptual ability, verbal fluency, manual preference, and general intelligence. Results: Trans men showed weaker functional connectivity in the precentral gyrus, subcallosal cortex, paracingulate gyrus, temporal pole, and cingulate gyrus than cisgender men (p < 0.01). Trans men performed worse than cisgender men in verbal and visuospatial working memory but similarly to cisgender women (p < 0.05). In trans men, functional connectivity of the precentral gyrus correlated positively with testosterone (r = 0.459, p = 0.064) and negatively with estradiol (r = −0.654, p = 0.004) and progesterone blood levels (r = −0.475, p = 0.054). The cluster involving the subcallosal cortex showed a positive correlation with testosterone (r = 0.718, p = 0.001), and a negative correlation with estradiol (r = −0.602, p = 0.011). The functional connectivity from a cluster involving the paracingulate gyrus showed a positive correlation with testosterone (r = 0.592, p = 0.012). Conclusions: This study highlights the importance of overpassing the binary model by underlining the presence of neural pathways that could represent the peculiarity of the neural profile of people with GD. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) represents the most common form of dementia and affects million people worldwide, with a high social burden and considerable economic costs. AD diagnosis benefits from a well-established panel of laboratory tests that allow ruling-in patients, along with FDG and amyloid PET imaging tools. The main laboratory tests used to identify AD patients are Aβ40, Aβ42, the Aβ42/Aβ40 ratio, phosphorylated Tau 181 (pTau181) and total Tau (tTau). Although they are measured preferentially in the cerebrospinal fluid (CSF), some evidence about the possibility for blood-based determination to enter clinical practice is growing up. Unfortunately, CSF biomarkers for AD and, even more, the blood-based ones, present a few flaws, and twenty years of research in this field did not overcome these pitfalls. The tale even worsens when the issue of treating AD is addressed due to the lack of effective strategies despite the many decades of attempts by pharmaceutic industries and scientists. Amyloid-based drugs failed to stop the disease, and no neuroinflammation-based drugs have been demonstrated to work so far. Hence, only symptomatic therapy is available, with no disease-modifying treatment on hand. Such a desolate situation fully justifies the active search for novel biomarkers to be used as reliable tests for AD diagnosis and molecular targets for treating patients. Recently, a novel group of molecules has been identified to be used for AD diagnosis and follow-up, the nuclei acid-based biomarkers. Nucleic acid-based biomarkers are a composite group of extracellular molecules consisting of DNA and RNA alone or in combination with other molecules, including proteins. This review article reports the main findings from the studies carried out on these biomarkers during AD, and highlights their advantages and limitations. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common form of dementia, characterized by the accumulation of β-amyloid plaques, tau tangles, neuroinflammation, and synaptic/neuronal loss, the latter being the strongest correlating factor with memory and cognitive impairment. Through an in vitro study on a neurons–astrocytes–microglia (NAM) co-culture system, we analyzed the effects of cerebrospinal fluid (CSF) samples from AD and non-AD patients (other neurodegenerative pathologies). Treatment with CSF from AD patients showed a loss of neurofilaments and spheroids, suggesting the presence of elements including CX3CL1 (soluble form), destabilizing the neurofilaments, cellular adhesion processes, and intercellular contacts. The NAM co-cultures were analyzed in immunofluorescence assays for several markers related to AD, such as through zymography, where the expression of proteolytic enzymes was quantified both in cell extracts and the co-cultures' conditioned medium (CM). Through qRT-PCR assays, several genes involved in the formation of β-amyloid plaque, in phosphorylation of tau, and in inflammation pathways and MMP expression were investigated. [ABSTRACT FROM AUTHOR]

Despite Alzheimer's Disease (AD) being known from the times of Alois Alzheimer, who lived more than one century ago, many aspects of the disease are still obscure, including the pathogenesis, the clinical spectrum definition, and the therapeutic approach. Well-established biomarkers for AD come from the histopathological hallmarks of the disease, which are Aβ and phosphorylated Tau protein aggregates. Consistently, cerebrospinal fluid (CSF) Amyloid β (Aβ) and phosphorylated Tau level measurements are currently used to detect AD presence. However, two central biases affect these biomarkers. Firstly, incomplete knowledge of the pathogenesis of diseases legitimates the search for novel molecules that, reasonably, could be expressed by neurons and microglia and could be detected in blood simpler and earlier than the classical markers and in a higher amount. Further, studies have been performed to evaluate whether CSF biomarkers can predict AD onset in Mild Cognitive Impairment (MCI) patients. However, the MCI definition has changed over time. Hence, the studies on MCI patients seem to be biased at the beginning due to the imprecise enrollment and heterogeneous composition of the miscellaneous MCI subgroup. Plasma biomarkers and novel candidate molecules, such as microglia biomarkers, have been tentatively investigated and could represent valuable targets for diagnosing and monitoring AD. Also, novel AD markers are urgently needed to identify molecular targets for treatment strategies. This review article summarizes the main CSF and blood AD biomarkers, underpins their advantages and flaws, and mentions novel molecules that can be used as potential biomarkers for AD. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a scourge for patients, caregivers and healthcare professionals due to the progressive character of the disease and the lack of effective treatments. AD is considered a proteinopathy, which means that aetiological and clinical features of AD have been linked to the deposition of amyloid β (Aβ) and hyperphosphorylated tau protein aggregates throughout the brain, with Aβ and hyperphosphorylated tau representing classical AD hallmarks. However, some other putative mechanisms underlying the pathogenesis of the disease have been proposed, including inflammation in the brain, microglia activation, impaired hippocampus neurogenesis and alterations in the production and release of neurotrophic factors. Among all, microglia activation and chronic inflammation in the brain gained some attention, with researchers worldwide wondering whether it is possible to prevent and stop, respectively, the onset and progression of the disease by modulating microglia phenotypes. The following key points have been established so far: (i) Aβ deposition in brain parenchyma represents repeated stimulus determining chronic activation of microglia; (ii) chronic activation and priming of microglia make these cells lose neuroprotective functions and favour damage and loss of neurons; (iii) quiescent status of microglia at baseline prevents chronic activation and priming, meaning that the more microglia are quiescent, the less they become neurotoxic. Many molecules are known to modulate the quiescent baseline state of microglia, attracting huge interest among scientists as to whether these molecules could be used as valuable targets in AD treatment. The downside of the coin came early with the observation that quiescent microglia do not display phagocytic ability, being unable to clear Aβ deposits since phagocytosis is crucial for Aβ clearance efficacy. A possible solution for this issue could be found in the modulation of microglia status at baseline, which could help maintain both neuroprotective features and phagocytic ability at the same time. Among the molecules known to influence the baseline status of microglia, C-X3-chemokine Ligand 1 (CX3CL1), also known as Fractalkine (FKN), is one of the most investigated. FKN and its microglial receptor CX3CR1 are crucial players in the interplay between neurons and microglia, modulating the operation of some neural circuits and the efficacy and persistence of immune response against injury. In addition, CX3CL1 regulates synaptic pruning and plasticity in the developmental age and in adulthood, when it strongly impacts the hippocampus neurogenesis of the adult. CX3CL1 has an effect on Aβ clearance and tau phosphorylation, as well as in microglia activation and priming. For all the above, CX3CL1/CX3CR1 signalling has been widely studied in relation to AD pathogenesis, and its biochemical pathway could hide molecular targets for novel treatment strategies in AD. This review summarizes the possible role of CX3CL1 in AD pathogenesis and its use as a potential target for AD treatment. [ABSTRACT FROM AUTHOR]

Neuroinflammation plays a fundamental role in the development and progression of neurodegenerative diseases. It could therefore be said that neuroinflammation in neurodegenerative pathologies is not a consequence but a cause of them and could represent a therapeutic target of neuronal degeneration. CX3CL1 and several proteases (ADAMs/MMPs) are strongly involved in the inflammatory pathways of these neurodegenerative pathologies with multiple effects. On the one hand, ADAMs have neuroprotective and anti-apoptotic effects; on the other hand, they target cytokines and chemokines, thus causing inflammatory processes and, consequently, neurodegeneration. CX3CL1 itself is a cytokine substrate for the ADAM, ADAM17, which cleaves and releases it in a soluble isoform (sCX3CL1). CX3CL1, as an adhesion molecule, on the one hand, plays an inhibiting role in the pro-inflammatory response in the central nervous system (CNS) and shows neuroprotective effects by binding its membrane receptor (CX3CR1) present into microglia cells and maintaining them in a quiescent state; on the other hand, the sCX3CL1 isoform seems to promote neurodegeneration. In this review, the dual roles of CX3CL1 and ADAMs/MMPs in different neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (MH), and multiple sclerosis (MS), are investigated. [ABSTRACT FROM AUTHOR]

Alzheimer's Disease (AD) is the most common cause of dementia, having a remarkable social and healthcare burden worldwide. Amyloid β (Aβ) and protein Tau aggregates are disease hallmarks and key players in AD pathogenesis. However, it has been hypothesized that microglia can contribute to AD pathophysiology, as well. Microglia are CNS-resident immune cells belonging to the myeloid lineage of the innate arm of immunity. Under physiological conditions, microglia are in constant motion in order to carry on their housekeeping function, and they maintain an anti-inflammatory, quiescent state, with low expression of cytokines and no phagocytic activity. Upon various stimuli (debris, ATP, misfolded proteins, aggregates and pathogens), microglia acquire a phagocytic function and overexpress cytokine gene modules. This process is generally regarded as microglia activation and implies that the production of pro-inflammatory cytokines is counterbalanced by the synthesis and the release of anti-inflammatory molecules. This mechanism avoids excessive inflammatory response and inappropriate microglial activation, which causes tissue damage and brain homeostasis impairment. Once the pathogenic stimulus has been cleared, activated microglia return to the naïve, anti-inflammatory state. Upon repeated stimuli (as in the case of Aβ deposition in the early stage of AD), activated microglia shift toward a less protective, neurotoxic phenotype, known as "primed" microglia. The main characteristic of primed microglia is their lower capability to turn back toward the naïve, anti-inflammatory state, which makes these cells prone to chronic activation and favours chronic inflammation in the brain. Primed microglia have impaired defence capacity against injury and detrimental effects on the brain microenvironment. Additionally, priming has been associated with AD onset and progression and can represent a promising target for AD treatment strategies. Many factors (genetics, environmental factors, baseline inflammatory status of microglia, ageing) generate an aberrantly activated phenotype that undergoes priming easier and earlier than normally activated microglia do. Novel, promising targets for therapeutic strategies for AD have been sought in the field of microglia activation and, importantly, among those factors influencing the baseline status of these cells. The CX3CL1 pathway could be a valuable target treatment approach in AD, although preliminary findings from the studies in this field are controversial. The current review aims to summarize state of the art on the role of microglia dysfunction in AD pathogenesis and proposes biochemical pathways with possible targets for AD treatment. [ABSTRACT FROM AUTHOR]

Biomarker, kidney, lithiasis, screening, sepsis Keywords: biomarker; kidney; lithiasis; screening; sepsis EN biomarker kidney lithiasis screening sepsis e140 e142 3 07/04/23 20230701 NES 230701 To the Editor, Urosepsis is a life-threatening condition due to an infection in the urogenital system. To date, several biomarkers have been evaluated for early identifying and monitoring sepsis in patients with urolithiasis undergoing surgery. [Extracted from the article]

Alzheimer's disease (AD) is the most common form of cognitive decline worldwide, occurring in about 10% of people older than 65 years. The well-known hallmarks of AD are extracellular aggregates of amyloid β (Aβ) and intracellular neurofibrillary tangles (NFTs) of tau protein. The evidence that Aβ overproduction leads to AD has paved the way for the AD pathogenesis amyloid cascade hypothesis, which proposes that the neuronal damage is sustained by Aβ overproduction. Consistently, AD cerebrospinal fluid (CSF) biomarkers used in clinical practice, including Aβ 1–42, Aβ 1–40, Aβ 42/40 ratio, and pTau, are related to the amyloid hypothesis. Recently, it was suggested that the Aβ deposition cascade cannot fully disclose AD pathogenesis, with other putative players being involved in the pathophysiology of the disease. Among all, one of the most studied factors is inflammation in the brain. Hence, biomarkers of inflammation and microglia activation have also been proposed to identify AD. Among them, CX3 chemokine ligand 1 (CX3CL1) has taken center stage. This transmembrane protein, also known as fractalkine (FKN), is normally expressed in neurons, featuring an N-terminal chemokine domain and an extended mucin-like stalk, following a short intra-cytoplasmatic domain. The molecule exists in both membrane-bound and soluble forms. It is accepted that the soluble and membrane-bound forms of FKN evoke differential signaling within the CNS. Given the link between CX3XL1 and microglial activation, it has been suggested that CX3CL1 signaling disruption could play a part in the pathogenesis of AD. Furthermore, a role for chemokine as a biomarker has been proposed. However, the findings collected are controversial. The current study aimed to describe the cerebrospinal fluid (CSF) levels of CX3XL1 and classical biomarkers in AD patients. [ABSTRACT FROM AUTHOR]

(1) Background: Alpha-synuclein (α-syn) is a presynaptic neuronal protein that regulates several neuronal functions. In recent decades, the role of α-syn as a biomarker of neurodegenerative diseases has been explored, especially in synucleinopathies. However, only a few studies have assessed its role as biomarker in other neurological disorders. The aim of the study was to evaluate cerebrospinal fluid (CSF) α-syn levels in several neurological disorders; (2) Methods: We measured CSF α-syn levels by a commercial ELISA kit in 158 patients classified in the following group: controls, Alzheimer's Disease (AD), cerebrovascular diseases, inflammatory central nervous system diseases, other neurological diseases, Parkinson's Disease (PD), and peripheral neuropathy; (3) Results: Patients with PD showed the lowest and patients with AD the highest levels of CSF α-syn (1372 vs. 2912 pg/mL, respectively, p < 0.001). In AD patients, α-syn levels were significantly associated with tau proteins; (4) Conclusions: α-syn could represent a biomarker of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Monocyte distribution has recently emerged as a promising biomarker of sepsis, especially in acute setting, such as Emergency Department and Intensive Care Unit. This study aimed to evaluate the accuracy of monocyte distribution width (MDW) for early detecting patients with sepsis by performing a systemic review and meta-analysis of published studies. Relevant publications were identified by a systematic literature search on PubMed and Google Scholar from inception to September 07, 2021. Studies were divided into two groups based on the sepsis criteria applied, namely sepsis-2 or sepsis-3. Ten studies including 9,475 individuals, of whom 1,370 with sepsis (742 according Sepsis-2 and 628 according to Sepsis-3), met the inclusion criteria for our meta-analysis. The pooled sensitivity and specificity were 0.789 and 0.777 for Sepsis-2 criteria, 0.838 and 0.704 for Sepsis-3 criteria. MDW represents a reliable biomarker for sepsis screening. [ABSTRACT FROM AUTHOR]

The authors present insights on the possible interplay between vitamin D status and Epstein Barr virus [EBV] infection in the pathogenesis of multiple sclerosis (MS). Topics discussed include the role of vitamin D in brain function during development and in adulthood, metabolism of vitamin D, low vitamin D level as a risk factor for developing MS, and the susceptibility of patients with mononucleosis, which is caused by EBV, to MS onset.

During a severe infection such as coronavirus disease 2019 (COVID-19), the level of almost all analytes can change, presenting a correlation with disease severity and survival; however, a biomarker cannot be translated into clinical practice for treatment guidance until it is proven to have a significant impact. Several studies have documented the association between COVID-19 severity and circulating levels of C-reactive protein (CRP) and interleukin-6, and the accuracy of the CRP level in predicting treatment responses has been evaluated. Moreover, promising findings on prothrombin and D-dimer have been reported. However, the clinical usefulness of these biomarkers in COVID-19 is far from proven. The burst of data generation during this pandemic has led to the publication of numerous studies with several notable drawbacks, weakening the strength of their findings. We provide an overview of the key findings of studies on biomarkers for the prognosis and treatment response in COVID-19 patients. We also highlight the main drawbacks of these studies that have limited the clinical use of these biomarkers. [ABSTRACT FROM AUTHOR]

Objective The aim of the study was to assess the role of midregional proadrenomedullin (MR-proADM) in patients with COVID-19. Methods We included 110 patients hospitalized for COVID-19. Biochemical biomarkers, including MR-proADM, were measured at admission. The association of plasma MR-proADM levels with COVID-19 severity, defined as a requirement for mechanical ventilation or in-hospital mortality, was evaluated. Results Patients showed increased levels of MR-proADM. In addition, MR-proADM was higher in patients who died during hospitalization than in patients who survived (median, 2.59 nmol/L; interquartile range, 2.3–2.95 vs median, 0.82 nmol/L; interquartile range, 0.57–1.03; P <.0001). Receiver operating characteristic curve analysis showed good accuracy of MR-proADM for predicting mortality. A MR-proADM value of 1.73 nmol/L was established as the best cutoff value, with 90% sensitivity and 95% specificity (P <.0001). Conclusion We found that MR-proADM could represent a prognostic biomarker of COVID-19. [ABSTRACT FROM AUTHOR]

In this study, we developed and evaluated the diagnostic accuracy of the Sepsis Index for early sepsis screening in the Emergency Department (ED). Sepsis Index is based on the combination of monocyte distribution width (MDW) and mean monocyte volume (MMV). Sepsis Index≥1 was selected to define sepsis. We tested its diagnostic accuracy in an ED population stratified in four groups: controls, Systemic Inflammatory Response Syndrome (SIRS), infection, and sepsis, according to Sepsis-2 criteria. Patients with sepsis displayed higher median Sepsis Index value than patients without sepsis. At the receiver operating characterictis (ROC) curve analysis for the prediction of sepsis, the area under the curve (AUC) of MDW and Sepsis Index were similar: 0.966 (95%CI 0.947–0.984), and 0.964 (95%CI 0.942–0.985), respectively. Sepsis Index showed increased specificity than MDW (94.7 vs. 90.6%), without any decrease in sensitivity (92.0%). Additionally, LR+ increased from 9.8 (MDW) to 17.4 (Sepsis Index), without any substantial change in LR− (respectively 0.09 vs. 0.08). Finally, PPV increased from 0.286 (MDW) to 0.420 (Sepsis Index). Sepsis Index improves the diagnostic accuracy of MDW alone for sepsis screening. [ABSTRACT FROM AUTHOR]

Objective: Affecting more than 264 million people, depression is a systemic and multifactorial disorder that represents one of the leading causes of illness and disability worldwide. Several studies showed an inflammatory response in depressed patients, including the involvement of both chronic low-grade inflammatory response and activation of cell-mediated immunity. The present study aimed to verify the efficacy of a structured functional therapy program for patients with depressed mood, and to determine whether this program can significantly reduce levels of C-reactive protein. Method: 28 outpatients with depressed mood received 20 individual sessions of Functional therapy. Data about socio-demographic variables, depression, self-esteem, and quality of life were collected; moreover, blood specimens were collected before and after treatment, and CRP measurement was performed by immunoenzymatic method. All measures were administered at baseline, at the end of treatment (i.e., 3 months after baseline), and at follow-up (i.e., 6 months after baseline). Results: A repeated measures ANOVA showed a significant difference after treatment on depression levels, levels of self-esteem, and all dimensions of quality of life, such as physical, psychological, social relationships, and environment. Furthermore, a statistically significant difference on levels of CRP was found. Moreover, at follow-up, improvements were maintained. Conclusions: The study revealed initial evidence of the efficacy of a functional therapy program on treating depression and its psychological and inflammation-related markers. [ABSTRACT FROM AUTHOR]

Background and purpose: To test the hypothesis that total tau (tTau), tau phosphorylated at threonine 181 (pTau) and pTau/tTau ratio in the cerebrospinal fluid (CSF) are diagnostic and prognostic biomarkers of amyotrophic lateral sclerosis (ALS), we performed a retrospective observational study in a large cohort of ALS patients and controls. Methods: We enrolled 196 ALS patients and 91 controls, who included patients with ALS‐mimicking diseases and those with non‐neurodegenerative diseases. All patients underwent lumbar puncture for CSF analysis at the time of the diagnostic evaluation or to first referral. We measured tTau and pTau levels in the CSF by chemiluminescence enzyme immunoassay. Results: Patients with ALS showed significantly higher levels of CSF tTau and a lower pTau/tTau ratio than controls (tTau: 245 vs. 146 pg/ml; p < 0.001; pTau/tTau ratio: 0.12 vs. 0.18; p < 0.001, respectively). No differences in pTau levels were detected. Receiver‐operating characteristic curve analysis showed a good diagnostic accuracy of tTau and pTau/tTau ratio (tTau: area under the curve [AUC] 0.685, 95% confidence interval [CI] 0.616–0.754, p = 0.039; pTau/tTau ratio: AUC 0.777, 95% CI 0.707–0.848, p < 0.001). Among ALS patients, increased tTau levels were associated with advanced age of onset, increased revised amyotrophic lateral sclerosis functional rating scale (ALSFRS‐R) score (ΔFS) rate of progression, and spinal onset. Multivariate analysis showed that in ALS patients, this biomarker was an independent negative predictor of overall survival. Conclusions: Our findings suggest that tTau and pTau/tTau ratio can be diagnostic biomarkers of ALS. In addition, CSF tTau level at diagnosis might play a relevant prognostic role in the disease. [ABSTRACT FROM AUTHOR]

Background In this study, we investigated the possible role of 2 novel biomarkers of synaptic damage, namely, neurogranin and α-synuclein, in Alzheimer disease (AD). Methods The study was performed in a cohort consisting of patients with AD and those without AD, including individuals with other neurological diseases. Cerebrospinal fluid (CSF) neurogranin and α-synuclein levels were measured by sensitive enzyme-linked immunosorbent assays (ELISAs). Results We found significantly increased levels of CSF neurogranin and α-synuclein in patients with AD than those without AD. Neurogranin was correlated with total tau (tTau) and phosphorylated tau (pTau), as well as with cognitive decline, in patients with AD. Receiver operating characteristic (ROC) curve analysis showed good diagnostic accuracy of neurogranin for AD at a cutoff point of 306 pg per mL with an area under the curve (AUC) of 0.872 and sensitivity and specificity of 84.2% and 78%, respectively. Conclusions Our findings support the use of CSF neurogranin as a biomarker of synapsis damage in patients with AD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective In this study, we investigated the roles of presepsin (PSP) and midregional proadrenomedullin (mr-proADM) in children with febrile neutropenia (FN) due to chemotherapy. Methods We assessed 36 FN episodes in 26 children. Patients were classified into bacteremia (B) and fever of unknown origin (FUO) groups. We evaluated PSP and mr-proADM at admission (T0), after 24/48 h (T1), and after 5 days (T2). Results PSP and mr-proADM levels were elevated at T0 and significantly decreased at T2. mr-proADM levels did not significantly differ between the B and FUO groups. PSP levels significantly differed between the B and FUO groups only at T1. Both PSP and mr-proADM levels at T0 were a predictor of length of hospital stay but not of the duration of fever. Finally, receiver operating characteristic curve analysis showed that PSP and mr-proADM had low diagnostic accuracy for blood culture positivity. Conclusion PSP and mr-proADM display poor clinical usefulness for FN in oncologic children. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (Aβ42), 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 Aβ42, 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). Aβ42 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. [ABSTRACT FROM AUTHOR]

Objective To assess the usefulness of the κ free light chain index (κFLCi) as a screening test to identify patients with suspected MS. Methods The study included 56 patients with a request to test for oligoclonal bands (OCBs). OCBs were detected by isoelectric focusing, followed by immunofixation. Cerebrospinal fluid (CSF) and serum κFLC were measured by a turbidimetric assay. Also, the κFLC index (κFLCi) was calculated. Results CSF κFLC levels and κFLCi were significantly higher in patients with multiple sclerosis (MS) than in patients with other neurological diseases (NDs; P <.001 and P <.001, respectively). At the cutoff value of 2.9, the κFLCi detected MS with sensitivity of 97% and specificity of 65%. Overall, 92% patients with κFLCi of 2.9 or greater and who had tested positive for OCBs were diagnosed as having MS. Conclusion Our findings support the use of κFLCi as a screening test when MS is suspected, followed by OCB detection as a confirmatory test for the diagnosis of MS. [ABSTRACT FROM AUTHOR]

The article presents Validation of monocyte distribution width decisional cutoff for sepsis detection in the acute setting. Topics discussed include Sepsis represents an important global health problem associated with a high rate of mortality; and its rapid and accurate detection is critical to promptly start the appropriate treatment reducing worse outcomes and mortality.

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. [ABSTRACT FROM AUTHOR]

Background: The association between glycated albumin (GA) and glycaemic status has not been fully described in patients with advanced chronic kidney disease (CKD) in relation to anaemia. The aim of this study was to evaluate the relationship between GA and fasting plasma glucose (FPG) and HbA1c in patients with advanced CKD and to evaluate the influence of anaemia in such relationship. Materials and methods: Patients with CKD stage 4 or 5 were included in the study. eGFR was calculated by the CKD-EPI creatinine equation. Plasma GA was measured by an enzymatic method. Results: Eighty-one patients were included in the study, 46 (57%) were males; the mean age was 67 ± 14 years. HbA1c was correlated with Hb (r = 0.39; p = .0003), and no significant correlation was detected between plasma GA and serum albumin (p = .82). A significant association between FPG and GA (r2 = 0.41; p < .0001), and between FPG and HbA1c (r2 = 0.42; p < .0001) was detected in the whole study population. Patients with moderate/severe anaemia had lower HbA1c than patients with no anaemia, while both FPG and GA were comparable between the two groups. Multivariate regression analysis showed that GA was a significant predictor of FPG in patients with moderate/severe anaemia while HbA1c did not (r2 = 0.55; p < .0001 for the model). Conclusions: GA, alone or in combination with other biomarkers, can be considered for the evaluation of glycaemic status in patients with advanced CKD and severe anaemia. [ABSTRACT FROM AUTHOR]

Background: Mortality risk and outcome in critically ill patients can be predicted by scoring systems, such as APACHE and SAPS. The identification of prognostic biomarkers, simple to measure upon admission to an intensive care unit (ICU) is an open issue. The aim of this observational study was to assess the prognostic value of plasma mid-regional pro-adrenomedullin (MR-proADM) at ICU admission in non-selected patients in comparison to Acute Physiology and Chronic Health Evaluation II (APACHEII) and Simplified Acute Physiology Score II (SAPSII) scores. Methods: APACHEII and SAPSII scores were calculated after 24 h from ICU admission. Plasma MR-proADM levels were measured by TRACE-Kryptor on admission (T0) and after 24 h (T24). The primary endpoint was intra-hospital mortality; secondary endpoint was length of stay (LOS). Results: One hundred and twenty-six consecutive non-selected patients admitted to an ICU were enrolled. Plasma MR-proADM levels were correlated with LOS (r=0.28; p=0.0014 at T0; r=0.26; p=0.005 at T24). Multivariate analysis showed that T0 MR-proADM was a significant predictor of mortality (odds ratio [OR]: 1.27; 95% confidence interval [95%CI]: 1.03–1.55; p=0.022). Receiver operating characteristic curves analysis revealed that MR-proADM on ICU admission identified non-survivors with high accuracy, not inferior to the one of APACHEII and SAPSII scores (area under the curve [AUC]: 0.71; 95%CI: 0.62–0.78; p=0.0002 for MR-proADM; AUC: 0.71; 95%CI: 0.62–0.79; p<0.0001 for APACHEII; AUC: 0.8; 95%CI: 0.71–0.87; p<0.0001 for SAPSII). Conclusions: Our findings point out a role of MR-proADM as a prognostic tool in non-selected patients in ICUs being a reliable predictor of mortality and LOS and support its use on admission to an ICU to help the management of critically ill patients. [ABSTRACT FROM AUTHOR]