Procalcitonin and community-acquired pneumonia (CAP) in children

The role of procalcitonin (PCT) as a biomarker for sepsis in adults is well documented, while its role in infections affecting neonatal children remains controversial. Among these infections, Community-Acquired pneumonia (CAP) has been studied extensively, because it's the second cause of death in children in developing countries, and one of the most frequent causes of hospitalization in industrialized countries. The PubMed database and the Cochrane Library were used to search for the following keywords: CAP, procalcitonin, children. Thirteen articles were studied to determine the role of PCT in CAP management, specifically its usefulness for distinguishing pneumococcal infections from viral and unknown infections, for predicting severity and the correct antibiotic treatment. This paper focuses on the studies performed to identify the best inflammatory biomarker for CAP management. Although there is an increase in studies confirming the usefulness of PCT in CAP management in children, further studies are needed to have better understanding of its role for pediatric CAP management

Serum Vitamin D as a Biomarker in Autoimmune, Psychiatric and Neurodegenerative Diseases

Vitamin D is a steroid hormone regulating calcium-phosphorus homeostasis, immune response and brain function. In the past thirty years, an increasing number of cohort studies, meta-analyses and randomized controlled trials (RTCs) evaluated the serum levels of 25-hydroxyvitamin D [25(OH)D], which is considered the Vitamin D status biomarker, in patients affected by neurological, psychiatric and autoimmune diseases. Although an association between low 25(OH)D serum levels and the prevalence of these diseases has been found, it is still unclear whether the serum 25(OH)D measurement can be clinically useful as a biomarker for diagnosis, prognosis and predicting treatment response in neurodegeneration, mental illness and immune-mediated disorders. The lack of standardized data, as well as discrepancies among the studies (in the analytical methods, cut-offs, endpoints and study sets), weakened the findings achieved, hindered pooling data, and, consequently, hampered drawing conclusions. This narrative review summarizes the main findings from the studies performed on serum 25(OH)D in neurological, psychiatric and autoimmune diseases, and clarifies whether or not serum 25(OH)D can be used as a reliable biomarker in these diseases

Microglial Activation and Priming in Alzheimer’s Disease: State of the Art and Future Perspectives

Alzheimer's Disease (AD) is the most common cause of dementia, having a remarkable social and healthcare burden worldwide. Amyloid beta (A beta) 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 naive, anti-inflammatory state. Upon repeated stimuli (as in the case of A beta 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 naive, 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

Independent validation of sepsis index for sepsis screening in the emergency department

(1) Background: The early detection of sepsis is still challenging, and there is an urgent need for biomarkers that could identify patients at a high risk of developing it. We recently developed an index, namely the Sepsis Index (SI), based on the combination of two CBC parameters: monocyte distribution width (MDW) and mean monocyte volume (MMV). In this study, we sought to independently validate the performance of SI as a tool for the early detection of patients at a high risk of sepsis in the Emergency Department (ED). (2) Methods: We enrolled all consecutive patients attending the ED with a request of the CBC. MDW and MMV were measured on samples collected in K3-EDTA tubes on the UniCel DxH 900 haematology analyser. SI was calculated based on the MDW and MMV. (3) Results: We enrolled a total of 703 patients stratified into four subgroups according to the Sepsis-2 criteria: control (498), infection (105), SIRS (52) and sepsis (48). The sepsis subgroup displayed the highest MDW (median 27.5, IQR 24.6–32.9) and SI (median 1.15, IQR 1.05–1.29) values. The ROC curve analysis for the prediction of sepsis showed a good and comparable diagnostic accuracy of the MDW and SI. However, the SI displayed an increased specificity, positive predictive value and positive likelihood ratio in comparison to MDW alone. (4) Conclusions: SI improves the diagnostic accuracy of MDW for sepsis screening

Evaluation of anti-sars-cov-2 s-rbd igg antibodies after covid-19 mrna bnt162b2 vaccine

(1) Background: The evaluation of anti-spike protein receptor-binding domain (S-RBD) antibodies represents a useful tool to estimate the individual protection against Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection; (2) Methods: We evaluated anti S-RBD IgG levels by indirect chemiluminescence immunoassay on Maglumi 800 (SNIBE, California) in 2248 vaccinated subjects without previous SARS-CoV-2 infection, 91 vaccinated individuals recovered from COVID-19, and 268 individuals recovered from COVID-19 who had not been vaccinated. Among those who were healthy and vaccinated, 352 subjects performed a re-dosing after about 72 days from the first measurement. (3) Results: Anti S-RBD IgG levels were lower in subjects with previous infection than vaccinated subjects, with or without previous infection (p < 0.001). No difference was observed between vaccinated subjects, with and without previous SARS-CoV-2 infection. Overall, anti-RBD IgG levels were higher in females than males (2110 vs. 1341 BAU/mL; p < 0.001) as well as in subjects with symptoms after vaccination than asymptomatic ones (2085 vs. 1332 BAU/mL; p = 0.001) and lower in older than younger subjects. Finally, a significant decrease in anti-RBD IgG levels was observed within a short period from a complete two-dose cycle vaccination. (4) Conclusions: Our results show an efficacy antibody response after vaccination with age-, timeand sex-related differences

A new tool for sepsis screening in the Emergency Department

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

Comparative analysis of biochip mosaic-based indirect immunofluorescence with enzyme-linked immunosorbent assay for diagnosing myasthenia gravis

Background: The detection of anti-acetylcholine receptor (AChR) and anti-muscle-specific tyrosine kinase (MuSK) antibodies is useful in myasthenia gravis (MG) diagnosis and management. BIOCHIP mosaic-based indirect immunofluorescence is a novel analytical method, which employs the simultaneous detection of anti-AChR and anti-MuSK antibodies in a single miniature incubation field. In this study, we compare, for the first time, the BIOCHIP MG mosaic with conventional enzyme-linked immunosorbent assay (ELISA) in the diagnosis of MG. Methods: A total of 71 patients with MG diagnosis were included in the study. Anti-AChR and anti-MuSK antibodies were measured separately by two different ELISA and simultaneously by BIOCHIP. The results were then compared. Results: The overall concordance between ELISA and BIOCHIP for anti-AChR reactivity was 74%. Cohen’s kappa was 0.51 (95% CI 0.32–0.71), which corresponds to 90% of the maximum possible kappa (0.57), given the observed marginal frequencies. The overall concordance for anti-MuSK reactivity was 84%. Cohen’s kappa was 0.11 (95% CI 0.00–0.36), which corresponds to 41% of the maximum possible kappa (0.27). Conclusion: The overall concordance among assays is not optimal

Foxp3 and gata3 polymorphisms, vitamin d3 and multiple sclerosis

Background: Regulatory T cells (Tregs) alterations have been implicated in the pathogenesis of Multiple Sclerosis (MS). Recently, a crucial role of the X-Linked Forkhead Box P3 (FoxP3) for the development and the stability of Tregs has emerged, and FOXP3 gene polymorphisms have been associated with the susceptibility to autoimmune diseases. The expression of Foxp3 in Tregs is regulated by the transcription factor GATA binding-protein 3 (GATA3) and vitamin D3 . The aim of this retrospective case-control study was to investigate the potential association between FOXP3 and GATA3 genetic variants, Vitamin D3, and MS risk. Methods: We analyzed two polymorphisms in the FOXP3 gene (rs3761547 and rs3761548) and a polymorphism in the GATA3 gene (rs3824662) in 106 MS patients and 113 healthy controls. Serum 25(OH)D3 was also measured in all participants. Results: No statistically significant genotypic and allelic differences were found in the distribution of FOXP3 rs3761547 and rs3761548, or GATA3 rs3824662 in the MS patients, compared with controls. Patients that were homozygous for rs3761547 had lower 25(OH)D3 levels. Conclusions: Our findings did not show any association among FOXP3 and GATA3 SNPs, vitamin D3, and MS susceptibility

Does it Really Make a Difference? Health Care Utilization with Two High Deductible Health Care Plans

Deductibles are commonly used to tame increasing health care costs. Numerous studies find that higher deductibles reduce health care utilization. In this paper we compare utilization in Switzerland between two health care plans with deductibles of 1,500 CHF and 2,500 CHF (1CHF = 1$) per calendar year. While there is a minimum deductible level in Switzerland, individuals are free to increase their deductible and thereby reduce their insurance premium. In order to distinguish between selection and moral hazard we use regional variation in premiums as an instrument. Moreover, we take advantage of a policy change in 2005 that introduced the higher deductible for the first time. The results show that selection leads to considerable differences in utilization between the two groups, while we find no behavioral differences across both groups. If anything health care expenditures are higher for male individuals with the higher deductible, while for females there are no differences between the two deductible levels