Background:VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a severe adult-onset autoinflammatory disease caused by somatic mutations in the X-linked UBA1 gene, most commonly affecting codon 41. Early molecular confirmation is essential, but sequencing-based methods may be limited by turnaround time, cost, and sensitivity for low-level somatic variants. We aimed to validate a rapid, accessible allele-specific real-time PCR assay for detection of the most frequent UBA1 hotspot mutations associated with VEXAS syndrome. Methods:In this prospective monocentric study conducted at the University Hospital "P. Giaccone" (Palermo, Italy), 17 adults were enrolled: six patients with high clinical suspicion of VEXAS syndrome and eleven healthy controls. UBA1 variants c.121A>G, c.121A>C, and c.122T>C were screened using a SYBR Green-based allele-specific real-time PCR kit with mutation-specific reaction mixes and an internal housekeeping control, followed by melting curve analysis for variant discrimination. All PCR-positive samples were confirmed by Sanger sequencing. Results:Allele-specific real-time PCR identified UBA1 mutations in 5/6 (83.3%) suspected VEXAS cases. Sanger sequencing confirmed all real-time PCR-positive results, demonstrating 100% concordance between methods. Conclusion:This allele-specific real-time PCR assay enables rapid and reliable detection of the most common UBA1 codon 41 mutations associated with VEXAS syndrome using standard real-time PCR platforms. The approach provides a practical, cost-effective screening strategy to support timely diagnosis in patients with high clinical suspicion.

BACKGROUND:In this study, we first evaluated the relationship between sTREM2 concentrations in CSF, serum, and plasma of Alzheimer's disease (AD) patients using the newly developed Lumipulse G sTREM2 assay. METHODS:sTREM2 was measured by the fully automated Lumipulse G1200 platform (Fujirebio). Associations and agreement between matrices were assessed using Passing-Bablok regression, Spearman correlation, and Bland-Altman analyses. Sub-analyses explored the influence of disease stage and tau pathology. RESULTS:Median sTREM2 concentrations were highest in CSF, followed by serum and plasma. Serum and CSF sTREM2 levels showed a moderate but significant correlation (ρ = 0.32; p = 0.0012), although regression analysis indicated poor linearity. In contrast, serum and plasma sTREM2 levels were strongly correlated (ρ = 0.74; p < 0.001). The association between CSF and serum sTREM2 levels was independent of total and phosphorylated tau. Notably, a strong CSF-serum correlation was observed in the MCI due to AD group (ρ = 0.74) but was completely lost in overt AD dementia, demonstrating a clear disease stage-dependent relationship. CONCLUSION:CSF and blood sTREM2 capture partly distinct biological processes and show limited overall agreement. While serum and plasma sTREM2 are closely related, they are not interchangeable.

Background: Acute ischemic stroke (AIS) remains a major cause of morbidity and mortality, with an unmet need for reliable blood-based biomarkers. Glial fibrillary acidic protein (GFAP), an astrocytic structural protein, is established in hemorrhagic stroke and traumatic brain injury, but its role in AIS remains incompletely defined. Methods: In this retrospective case-control study, we enrolled AIS patients and healthy controls. Serum GFAP was measured within 24 h using the Lumipulse G1200 automated assay. Stroke severity and outcome were assessed with the National Institutes of Health Stroke Scale (NIHSS) and functional outcome with the modified Rankin Scale (mRS). Associations with clinical measures were explored using Spearman correlation, and diagnostic accuracy was determined by ROC analysis. Results: GFAP levels were significantly higher in AIS patients than controls (median 132.9 vs. 30.0 pg/mL, p < 0.001). The ROC analysis yielded an AUC of 0.88 (95% CI 0.81-0.96). A cutoff of 71 pg/mL achieved 74% sensitivity and 92% specificity, while 150 pg/mL and 32 pg/mL optimized positive and negative predictive values (95% and 96%). GFAP was correlated with stroke severity (NIHSS, ρ = 0.37-0.40, p < 0.001) and disability (mRS, ρ = 0.48-0.49, p < 0.001). No significant differences appeared across TOAST subtypes. Conclusions: Serum GFAP is significantly elevated in AIS and demonstrates strong diagnostic and prognostic value. Integration of GFAP into clinical workflows may enhance early stroke detection and outcome prediction, supporting its role as a promising biomarker in AIS.

Ischemic stroke and its chronic cerebrovascular complications represent significant public health challenges with considerable societal impact. Consequently, healthcare initiatives worldwide are placing greater emphasis on preventing and lowering cerebrovascular risk. Alongside medical therapies, it is now widely recognized that modifying risk factors—many of which are controllable—can substantially reduce the probability of acute cerebrovascular events, up to 33% according to data from trials such as PREDIMED. This modification is often achievable through dietary interventions such as the Mediterranean diet (MedDiet), which positively influences vascular health. The MedDiet, long established as the traditional eating pattern in Mediterranean regions, is an effective means of counteracting factors that jeopardize vascular health and elevate the risk of acute events. To date, there are no narrative reviews that have addressed the impact of the Mediterranean diet on cerebrovascular risk and the consequences of acute cerebrovascular events in terms of disability and neurological functional recovery, focusing on how individual components of the MedDiet, at the molecular level, contribute to the prevention of acute vascular episodes, paving the way for new approaches in the treatment of cerebrovascular patients.

Atrial fibrillation (AF) is the most common arrhythmia in older adults and is associated with an increased risk of cognitive impairment and dementia, even in patients without prior stroke. Nonvitamin K antagonist oral anticoagulants (NOACs) offer a better safety profile than vitamin K antagonists (VKAs), but their cognitive benefit remains uncertain.To assess the impact of NOACs versus VKAs on cognitive decline in elderly AF patients using a machine learning approach.This multicenter prospective cohort study included 983 AF outpatients enrolled between 2008 and 2022 at the Geriatrics Department, University of Catanzaro, and the ProMISE Department, University of Palermo. Stroke and bleeding risks were assessed using CHA2DS2-VASc and HAS-BLED scores. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE). Cognitive decline was defined as a decrease in MMSE score between baseline and follow-up. Patients with prior anticoagulant therapy (OAT), severe dementia, or comorbidities affecting cognition were excluded. Multivariable logistic regression and a random forest classifier were used to assess whether anticoagulant type independently predicted cognitive decline. Class imbalance was addressed using both class-weighted learning and the synthetic minority over-sampling technique (SMOTE), with model performance evaluated through repeated stratified cross-validation and threshold optimization.At baseline, cognitive performance was comparable between groups (p = 0.11). After a mean follow-up of 7.2 ± 3.4 years, MMSE scores declined significantly more in VKA-treated patients (-1.7 vs. -0.3 points, p < 0.001). In logistic regression, NOAC use was independently associated with a lower risk of cognitive decline (odds ratio: 0.322; 95% confidence interval: 0.221-0.469; p < 0.0001). The random forest classifier achieved a mean cross-validated AUC of 0.8719 (standard deviation: 0.0273) and a test-set AUC of 0.880. Threshold adjustment and SMOTE improved sensitivity (recall increased: 0.47-0.84), with a precision-recall AUC of 0.763. Permutation importance analysis identified "OAT" as the top predictor. Predicted probabilities of cognitive decline were significantly higher in VKA users (median = 0.70) than in NOAC users (median = 0.09), confirmed by a Kolmogorov-Smirnov test (KS = 0.385, p < 0.001).NOAC use is associated with a lower predicted probability of cognitive decline, suggesting potential cognitive benefits over VKAs.

Thrombophilia is characterized by a hypercoagulable state that predisposes individuals to venous and arterial thrombotic events, posing significant challenges for clinical evaluation and management. This narrative review critically examines the current landscape of thrombophilia testing, focusing on the utility and limitations of both circulating and genetic biomarkers. Circulating biomarkers—such as D-dimer, antithrombin, protein C, and protein S—offer dynamic insights into the coagulation process yet often suffer from low specificity in varied clinical settings. In contrast, genetic biomarkers, notably Factor V Leiden and the prothrombin G20210A mutation, provide stable risk stratification but are limited by their low prevalence in the general population. Emerging markers, including selectins, Factor VIII, Factor XI, neutrophil extracellular traps, and extracellular vesicles, are also discussed for their potential to refine thrombotic risk assessment. By integrating evidence-based guidelines from international health organizations, this review underscores the need for a personalized approach to thrombophilia evaluation that balances comprehensive risk assessment with the avoidance of over-testing. Such an approach is crucial for optimizing patient outcomes and informing the duration and intensity of anticoagulant therapy.

INTRODUCTION:Some genetic polymorphisms are associated with the risk of stroke, although the individual contribution of such polymorphisms is considered modest. AIMS:To evaluate the frequency of single nucleotide polymorphisms (SNPs) in genes encoding proinflammatory cytokines and coagulation factors in stroke patients, the relationships between the serum levels of the cytokines analyzed with stroke subtypes and prognosis. MATERIAL AND METHODS:A retrospective, cross-sectional, observational, analytical, case-control study. We performed genetic analysis to evaluate various genetic polymorphisms and analyzed cytokine levels at admission. RESULTS:429 patients with ischemic stroke and 195 control subjects without ischemic stroke. Patients with CEI subtype showed significantly higher levels of all the cytokines analyzed, namely, IL-10, TNF-alpha, and IL-6. Logistic regression analysis revealed that higher TNF-α (alpha), IL-6, and IL-1 β levels were significantly associated with the LAAS and CEI subtypes. TNF-α, IL-1, and IL-6 levels were significantly higher in patients with recurrent stroke at follow-up. Of the three polymorphisms in the gene encoding PTSG2, the haplotypes rs6275 and rs20417 showed a different distribution between patients and controls. DISCUSSION:The reported association between ischemic stroke and immunoinflammatory variables agrees with previously reported associations between some proinflammatory and prothrombotic polymorphisms and the risk of ischemic stroke.

BACKGROUND AND AIMS:Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is a key regulator of lipid metabolism and a therapeutic target in cardiovascular disease. Despite its growing clinical relevance, reference intervals (RIs) for circulating PCSK9 are not established, limiting its interpretative utility in clinical and research settings. In this study, we established serum PCSK9 RIs in a healthy adult population, accounting for key demographic and biological variables such as age, sex, and lipid profile. METHODS:We enrolled 132 healthy adult blood donors (88 men, 44 women) aged 18-65 years with normal lipid profiles and no history of cardiovascular, autoimmune, or metabolic disorders. Serum PCSK9 concentrations were measured using a validated ELISA assay. Statistical analyses included assessment of distribution, sex- and age-based stratification, and calculation of RIs using both parametric and robust methods, following CLSI guidelines. RESULTS:The mean serum PCSK9 level was 428 ± 119 ng/mL. PCSK9 values were significantly higher in women compared to men and showed a moderate positive correlation with age (r = 0.36, p < 0.001). RIs for the overall population ranged from 201 to 659 ng/mL (parametric method). Stratified RIs demonstrated notable sex- and age-related differences, reinforcing the need for subgroup-specific interpretation. CONCLUSION:This study provides the first rigorously derived RIs for serum PCSK9 in a healthy Caucasian population. The observed sex- and age-related variations underscore the importance of personalized reference values.

OBJECTIVES:To establish the reference intervals (RIs) of serum glial fibrillary acid protein (GFAP) measured by the fully automated Lumipulse system. METHODS:The study population consisted of 340 healthy individuals, including 251 blood donors and 89 outpatients, with a median age of 56 years. Serum GFAP levels were measured by the Lumipulse G GFAP assay on the fully automated platform Lumipulse G1200 (FUJIREBIO Inc., Tokyo, Japan). GFAP RIs (2.5th and 97.5th percentiles) were calculated for the overall population and stratified by age and sex groups. For the overall population, males, and females partitions, we employed the nonparametric methods, while for the age-and-sex groups we employed the "robust" method, as recommended by CLSI. RESULTS:The RI in the whole population was 10.4-92.0 ng/L. When considering sex differences, females showed higher levels of serum GFAP than males across all age groups. A positive correlation was observed between age and GFAP (Spearman's rho=0.55, p<0.001). Specifically, the biomarker was stable until 60 years, while individuals aged>60 years demonstrated significantly and considerably higher levels than younger age groups. Additionally, in the 50-60 age group, we observed gender-related differences, with females having increased levels than males. CONCLUSIONS:GFAP levels are influenced by both age and sex. Accordingly, we established RIs of serum GFAP, taking into consideration age and sex-related differences.

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and represents a major public health challenge. With increasing life expectancy, the incidence of AD has also increased, highlighting the need for early diagnosis and improved monitoring. Traditionally, diagnosis has relied on clinical symptoms and neuroimaging; however, the introduction of biomarkers has revolutionized disease assessment. Traditional biomarkers, including the Aβ42/Aβ40 ratio, phosphorylated tau (p-Tau181, p-Tau217, and p-Tau231), total tau (t-tau), and neurofilament light chain (NfL), are fundamental for staging AD progression. Updated guidelines introduced the ATX(N) model, which extends biomarker classification to include additional promising biomarkers, such as SNAP-25, YKL-40, GAP-43, VILIP-1, progranulin (PGRN), TREM2, IGF-1, hFABP, MCP-1, TDP-43, and BDNF. Recent advancements have allowed for the detection of these biomarkers not only in CSF but also in plasma and neuron-derived exosomes, offering less invasive and more accessible diagnostic options. This review explores established and emerging biomarkers and emphasizes their roles in early diagnosis, patient stratification, and precision medicine.

INTRODUCTION:Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids, immune cells, and fibrous components within the arterial wall. While traditionally considered a lipid-driven process, growing evidence suggests that immune mechanisms play a central role in all stages of atherogenesis. AREAS COVERED:This review summarizes the most relevant evidence supporting the immunoinflammatory basis of plaque development, progression, and destabilization. Both innate and adaptive immune responses contribute to endothelial dysfunction, immune cell recruitment, cytokine production, and the activation of inflammasome pathways, which amplify vascular inflammation. Crucially, the interplay between inflammation and thrombosis, termed thromboinflammation, plays a pivotal role in plaque instability and clinical events. EXPERT OPINION:We critically examine the limitations of the classic dichotomy between stable and unstable plaques, proposing instead a tripartite classification: active, dormant, and inactive plaques, analogous to the states of volcanic activity. Even clinically 'stable' plaques may exhibit silent yet ongoing immunometabolic and thromboinflammatory activity, contributing to residual cardiovascular risk. Advanced imaging, molecular diagnostics, and inflammation-sensitive biomarkers (e.g. high-sensitivity C-reactive protein, IL-6) can help detect subclinical plaque activity. Finally, the concept of 'thromboinflammaging' emphasizes the impact of age-related immune dysregulation on vascular pathology. This evolving paradigm supports immunomodulation as a cornerstone in precision cardiovascular medicine.

The genetic basis of complex diseases like ischemic stroke probably consists of several predisposing risk factors, such as genes involved in inflammation and thrombotic pathways. Some genetic polymorphisms have been associated with the risk of stroke. Aim: On this basis the aim of this study was to evaluate: - the frequency of some single nucleotide polymorphisms (SNPs) of genes of pro-inflammatory cytokines and coagulation factors in stroke patients; - the relationship between each identified SNP and TOAST stroke subtype; - the relationship between the serum levels of the cytokines analyzed and the diagnostic subtype of ischemic stroke; - the relationship between the serum levels of the analyzed cytokines and stroke prognosis regarding event recurrence, AMI recurrence, and mortality. Materials and methods: All patients aged > 18 years admitted for acute ischemic stroke in the period between 2011 and 2021 were prospectively enrolled. Each patient was subjected to genetic analysis to evaluate various genetic polymorphisms and to the analysis of the levels of cytokines circulating in the different collection times (T0, T1, and T2). Three different biallelic polymorphisms, of the IL-10 gene were identified. Results: 624 subjects were enrolled, including 429 patients with ischemic stroke and 195 controls. Stroke subtype: 47% LAAS, 27% LAC, and 26% CEI. Regarding the immunoinflammatory variables, patients with CEI showed significantly higher levels of serum glucose and all the cytokines analyzed, compared to patients with both LAC and LAAS. Logistic regression analysis revealed that elevated IL-10, TNF-alpha, IL-6, and IL-1beta values are predictive of LAAS and CEI subtypes, respectively. IL-10 levels were lower in patients who developed stroke during follow-up, whereas TNF-alpha, IL-1, and IL-6 levels were significantly higher in patients with recurrent stroke at follow-up, who developed a new vascular event or who experienced death during follow-up. From the analysis of the distribution of the genotypic frequencies of the polymorphisms analyzed, a statistically significant difference emerged between the cases and the controls for all the polymorphisms in the genes of pro-inflammatory cytokines, TPA and PAI-1. These results demonstrated an association between some pro-inflammatory and prothrombotic polymorphisms and the risk of ischemic stroke.

BACKGROUND:Glial Fibrillary Acidic Protein (GFAP) is a well-established biomarker of astrocytes and astrogliosis, a pathological response observed in various neurological diseases. This study aimed to evaluate the diagnostic performance of serum GFAP in Alzheimer's disease (AD), multiple sclerosis (MS), and transthyretin amyloidosis (ATTR) polyneuropathy. METHODS:We performed a retrospective observational study, including 498 participants (337 healthy controls and 161 patients with AD, MS, or ATTR amyloidosis). Serum GFAP levels were measured using the Lumipulse G1200 platform, and statistical analyses were performed to compare levels across disease groups and assess their diagnostic accuracy. RESULTS:GFAP levels were significantly elevated in all neurological disease groups compared to age-matched controls, with the highest levels found in AD (79.4 pg/mL vs. 39.5 pg/mL, p = 2.55 × 10-12). ROC curve analysis revealed that GFAP had strong diagnostic performance for AD (AUC = 0.86), moderate performance for ATTR amyloidosis (AUC = 0.67), and poor performance for MS (AUC = 0.61). CONCLUSIONS:These findings suggest that GFAP is a promising biomarker for AD, reflecting astrocytic activation and neuroinflammatory processes. Its diagnostic utility in ATTR amyloidosis is moderate, while its role in MS remains limited.

Introduction: Neurofilament light chain (NfL) is one of the most important biomarkers in the field of clinical neurochemistry. Several analytical methods have been developed in the last decade. Recently, Fujirebio introduced a ready-to-use assay kit for measuring NfL levels in the cerebrospinal fluid (CSF) on the fully automated LUMIPULSE G System. In this study, we established the decisional cutoffs for CSF NfL. Materials and Methods: We performed a retrospective observational study including patients with cognitive decline. CSF NfL levels were measured by two analytical methods: the NF-light ELISA kit (UmanDiagnostics) and the Lumipulse G1200 fully automated system (Fujirebio). We calculated the cutoffs for the Lumipulse, starting from the consolidated cutoffs of the ELISA method for each age and using the equation obtained by the regression analysis. Results: The study population consisted of 100 patients with cognitive decline. The median levels of CSF NfL measured by Lumipulse and ELISA were 776.5 +/- 772.6 pg/mL and 473.5 +/- 443.5 pg/mL, respectively, significantly different (p < 0.001). The Spearman's rank correlation coefficient was 0.962, indicating a robust positive correlation between the two measurement methods. The equation derived from the Passing-Bablok regression analysis was CSF CLEIA = -61.16 + 1.83 x CSF ELISA. Based on this equation, we defined the decisional cutoff values. Conclusions: Decisional cutoffs are fundamental tools for guiding clinicians to use biomarkers' results and interpretation appropriately. This is the first study establishing the decisional cutoff value of NfL measured by Lumipulse, a fully automated platform widely used in clinical laboratories.

OBJECTIVES:Celiac disease (CD) is a systemic autoimmune disorder triggered by gluten in genetically predisposed individuals. Accurate diagnosis remains challenging due to clinical heterogeneity and reliance on invasive biopsy. This study aimed to evaluate the diagnostic performance of a novel multiparametric membrane-based enzyme immunoassay (AESKUBLOTS®) for the simultaneous detection of IgA antibodies targeting eight CD-related antigens. METHODS:A retrospective, single-centre study was conducted on 180 participants: 80 with CD (30 untreated, 50 on gluten-free diet, GFD), 50 with non-celiac wheat sensitivity (NCWS), and 50 healthy controls (HC). Serum samples were analysed using the AESKU assay. Diagnostic accuracy was assessed via ROC curve analysis and 5-fold cross-validation, examining individual markers and a composite antibody score. RESULTS:The assay demonstrated high diagnostic performance, particularly in untreated CD patients. Anti-tTG neo IgA showed the highest accuracy (AUC=0.93), followed by anti-tTG IgA (AUC=0.92). A composite score of ≥4 positive markers yielded an AUC of 0.99, while ≥6 positive markers achieved 100 % specificity and PPV, with 76.7 % sensitivity. Notably, anti-mTG IgA levels were elevated in all CD patients regardless of diet, suggesting potential utility in monitoring or identifying ongoing mucosal immune activity. CONCLUSIONS:This multiparametric IgA assay offers a sensitive, specific, and non-invasive diagnostic tool for CD. Larger, prospective studies are warranted to confirm the clinical utility and expand the applicability to broader populations.

Direct oral anticoagulants (DOACs) have emerged as a preferred alternative to vitamin K antagonists (VKAs) for the prevention and treatment of thromboembolic disorders, offering improved safety, predictable pharmacokinetics, and ease of administration. Despite these advantages, their use in complex clinical scenarios presents significant challenges that necessitate individualized therapeutic strategies. This comprehensive review explores the efficacy, safety, and limitations of DOAC therapy in special populations, including patients with renal or hepatic impairment, obesity, cancer-associated thrombosis, and antiphospholipid syndrome. Additionally, we examine their role in uncommon thrombotic conditions such as superficial venous thrombosis, embolic stroke of undetermined source, upper extremity vein thrombosis, inferior vena cava thrombosis, pelvic vein thrombosis, and cerebral vein thrombosis. The pharmacokinetic variability of DOACs in renal and hepatic dysfunction requires caution to balance the bleeding and thrombotic risks. In obesity, altered drug distribution and metabolism raise concerns regarding appropriate dosing and therapeutic efficacy. Cancer-associated thrombosis presents a complex interplay of prothrombotic mechanisms, necessitating careful selection of anticoagulant therapy. Furthermore, the use of DOACs in antiphospholipid syndrome remains controversial due to concerns about recurrent thrombotic events. Finally, in some unusual scenarios like inferior vena cava, pelvic vein, and cerebral vein thrombosis, the use of DOACs has scarce evidence. This review aims to guide clinicians in optimizing anticoagulation management in challenging patient populations by synthesizing current evidence and providing practical recommendations.

Objectives Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a rare, progressive neurodegenerative disorder caused by mutations in the transthyretin (TTR) gene. The disease leads to systemic amyloid deposition, primarily affecting the nervous system and, in some cases, the heart. Early diagnosis and monitoring are critical for effective management, yet reliable biomarkers remain limited. This study aimed to investigate the role of serum glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) as biomarkers in ATTRv-PN. Methods A retrospective observational study was conducted at the University Hospital Paolo Giaccone, enrolling ATTRv-PN patients, asymptomatic TTR mutation carriers, and healthy blood donors. Serum GFAP and NfL levels were measured using a fully automated immunoassay (Lumipulse G1200). Results A total of 119 participants were included: ATTRv-PN (n=23), carriers (n=27), and healthy controls (n=69). GFAP levels were significantly elevated in ATTRv-PN patients compared to carriers and healthy controls (p<0.001), with the highest levels observed in individuals with the V122I mutation. The median NfL levels were also significantly elevated in ATTRv-PN patients (30.74 pg/mL) compared to carriers (11.59 pg/mL) and healthy controls (12.86 pg/mL) (p<0.001). Additionally, a significant negative correlation was observed between NfL levels and clinical severity scores, indicating its association with disease severity. Conclusions These findings support the usefulness of serum NfL as a prognostic tool in ATTRv-PN and highlight the potential involvement of astrocyte activation in disease pathology. Further longitudinal studies are needed to validate these biomarkers for clinical application.

BackgroundIn 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.MethodsWe 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).ResultsPatients 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.ConclusionOur findings support the role of PSP and its kinetic as a predictor of ICU mortality.

Cerebrospinal fluid (CSF) core biomarkers of Alzheimer’s disease (AD), including amyloid peptide beta-42 (Aβ42), Aβ42/40 ratio, and phosphorylated tau (pTau), are precious tools for supporting AD diagnosis. However, their use in clinical practice is limited due to the invasiveness of CSF collection. Thus, there is intensive research to find alternative, noninvasive, and widely accessible biological matrices to measure AD core biomarkers. In this study, we measured AD core biomarkers in saliva and plasma by a fully automated platform. We enrolled all consecutive patients with cognitive decline. For each patient, we measured Aβ42, Aβ40, and pTau levels in CSF, saliva, and plasma by Lumipulse G1200 (Fujirebio). We included forty-two patients, of whom 27 had AD. Levels of all biomarkers significantly differed in the three biofluids, with saliva having the lowest and CSF the highest levels of Aβ42, Aβ40, and pTau. A positive correlation of pTau, Aβ42/40 ratio, and pTau/Aβ42 ratio levels in CSF and plasma was detected, while no correlation between any biomarker in CSF and saliva was found. Our findings suggest that plasma but not saliva could represent a surrogate biofluid for measuring core AD biomarkers. Specifically, plasma Aβ42/40 ratio, pTau/Aβ42 ratio, and pTau could serve as surrogates of the corresponding CSF biomarkers.