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This document discusses the potential use of serum protein electrophoresis (SPE) as a screening tool for alpha-1 antitrypsin deficiency (AATD), a heritable condition that can lead to pulmonary and hepatic diseases. The study, conducted in four Italian hospitals, found that using the alpha1-globulin band in SPE can effectively detect AATD variants. The authors suggest that implementing SPE for population screening could lead to early intervention and improved outcomes for AATD patients. However, they note that SPE is not a diagnostic tool and cannot differentiate between different AATD variants or clinical phenotypes. Further research is needed to understand the clinical relevance of these findings. [Extracted from the article]

Aim: To evaluate, in a large population, differences in HDL levels between subjects with acute phase reaction (APR) and subjects without different HDL decreases depending on disease causing APR and correlations between HDL and APR parameters. Materials & methods: In 902 patients we retrospectively evaluated alpha-2-globulins, white blood cells, C-reactive protein (CRP) and lipid profiles. APR was defined by CRP >1.5 mg/dl. Patients were reselected in seven subsets: infections, rheumatic diseases, neoplasms, cerebro-cardiovascular diseases, traumatic/mental disorders, endocrine/metabolic diseases and controls. Results: Subjects with APR showed significantly lower HDL-C (age and gender adjusted). Subset 'infections' showed the lowest HDL-C values and the highest CRP values. HDL-C had inverse significant correlation with all APR parameters. At stepwise regression analysis gender, albumin, TG and CRP were independent predictors of HDL-C. Conclusion: Our data produced the observation that subjects with APR show HDL-C levels lower than non-APR subjects to a large and heterogeneous population. HDL-C levels decrease in a different manner on the basis of the disease causing APR, maybe depending on inflammation intensity. [ABSTRACT FROM AUTHOR]

Summary: To slow down the coronavirus disease 2019 (COVID‐19) pandemic an unequalled vaccination campaign was initiated. Despite proven efficacy and safety, a rare but potentially fatal complication of adenoviral‐vector vaccines, called vaccine‐induced immune thrombotic thrombocytopenia (VITT), has emerged the pathogenesis of which seems to be related to the development of platelet‐activating anti‐platelet factor 4 (PF4) antibodies. While a few studies have evaluated the incidence of anti‐PF4 positivity in anti‐severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) vaccine recipients, to date no studies have assessed whether an antiplatelet immunological response develops and if this associates with platelet and blood clotting activation. We carried out a prospective study in healthy subjects who received the first dose of ChAdOx1 or Ad26.COV2.S or BNT162b2 vaccines to evaluate platelet‐specific and non‐specific immune response and in vivo platelet activation and blood clotting activation. Individuals receiving ChAdOx1 and, less so, Ad26.COV2.S developed with high frequency auto‐ or alloantiplatelet antibodies, increased circulating platelet‐derived microvesicles and soluble P‐selectin associated with mild blood clotting activation. Our study shows that an immunological reaction involving platelets is not uncommon in individuals receiving anti‐SARS‐CoV‐2 vaccination, especially after ChAdOx1 and Ad26.COV2.S, and that it associates with in vivo platelet and blood clotting activation. [ABSTRACT FROM AUTHOR]

The kappa index (K-Index), calculated by dividing the cerebrospinal fluid (CSF)/serum kappa free light chain (KFLC) ratio by the CSF/serum albumin ratio, is gaining increasing interest as a marker of intrathecal immunoglobulin synthesis. However, data on inter-laboratory agreement of these measures is lacking. The aim was to assess the concordance of CSF and serum KFLC measurements, and of K-index values, across different laboratories. KFLC and albumin of 15 paired CSF and serum samples were analyzed by eight participating laboratories. Four centers used Binding Site instruments and assays (B), three used Siemens instruments and assays (S), and one center used a Siemens instrument with a Binding Site assay (mixed). Absolute individual agreement was calculated using a two-way mixed effects intraclass correlation coefficient (ICC). Cohen's kappa coefficient (k) was used to measure agreement on positive (≥5.8) K-index values. There was an excellent agreement in CSF KFLC measurements across all laboratories (ICC (95% confidence interval): 0.93 (0.87–0.97)) and of serum KFLC across B and S laboratories (ICC: 0.91 (0.73–0.97)), while ICC decreased (to 0.81 (0.53–0.93)) when including the mixed laboratory in the analysis. Concordance for a positive K-Index was substantial across all laboratories (k = 0.77) and within S laboratories (k = 0.71), and very good (k = 0.89) within B laboratories, meaning that patients rarely get discordant results on K-index positivity notwithstanding the testing in different laboratories and the use of different platforms/assays. [ABSTRACT FROM AUTHOR]

Background: Elevated peripheral levels of different cytokines and chemokines in subjects with Alzheimer's disease (AD), as compared with healthy controls (HC), have emphasized the role of inflammation in such a disease. Considering the cross-talking between the central nervous system and the periphery, the inflammatory analytes may provide utility as biomarkers to identify AD at earlier stages.Objective: Using an advanced statistical approach, we can discriminate the interactive network of cytokines/chemokines and propose a useful tool to follow the progression and evolution of AD, also in light of sex differences.Methods: A cohort of 289 old-age subjects was screened for cytokine and chemokine profiling, measured in plasma, after a thorough clinical and neuropsychological evaluation. A custom algorithm based on Fisher linear discriminant analysis was applied to ascertain a classification signature able to discriminate HC from mild cognitive impairment (MCI) and AD.Results: We observed that a joint expression of three proteins (a "signature" composed by IFN-α2, IL-1α, TNFα) can discriminate HC from AD with an accuracy of 65.24%. Using this signature on MCI samples, 84.93% of them were classified as "non-HC". Stratifying MCI samples by sex, we observed that 87.23% of women were classified as "non-HC", and only 57.69% of males. Indeed, in a scatter plot of IFN-α2 and IL-1α, the HC group was better separated from MCI and AD in women as compared with men.Conclusion: These findings suggest that AD is accompanied by a peripheral inflammatory response that can already be present in MCI subjects, thus providing a mean for detecting this at-risk status and allow an anticipated intervention. [ABSTRACT FROM AUTHOR]

• Evusheld should be considered an integration, not a substitute, of vaccination against SARS-CoV-2. • To date, pre-exposure prophylaxis with tixagevimab-cilgavimab (300 + 300 mg) is mandatory. • The threshold defining protection on antibody neutralisation efficacy was an NT-Abs titre of 8. Tixagevimab-cilgavimab has been approved as primary pre-exposure prophylaxis in immunocompromised patients as support or replacement for vaccination, even though the Omicron variant of concern (VOC) was spreading at the time. The aim of our study was to evaluate the post-injection neutralising activity (NT 90 -Abs titre) against the Omicron BA.5 variant in fully vaccinated immunocompromised patients. NT 90 -Abs titres against BA.5 and 20A.EU1 as well as anti-spike and anti-receptor-binding domain IgG were evaluated 0, 14, and 30 d after tixagevimab-cilgavimab administration. The primary end point was NT 90 -Abs titres ≥ 80 against BA.5 in ≥ 25% of patients, and the secondary end point was NT 90 -Abs titres ≥ 1280 against 20A.EU1 in >50% of patients on day 14. At baseline, 35.2%, 37.02%, and 32.5% of booster vaccinated patients exhibited undetectable levels of anti-S and anti-RBD IgG antibodies such as NT 90 -Abs titres against A20.EU1. Moreover, 35 patients (61.5%) had undetectable NT 90 -Abs titres against BA.5. On day 14, IgG anti-S and anti-RBD levels were 3880 BAU/mL and 776.6 AU/mL, respectively. Only 12.5% of patients met a NT 90 -Abs titres ≥ 80 against BA.5, whereas the median NT 90 -Abs titre against 20A.EU1 was 1280. NT 90 -Abs titres against BA.5 were 64-fold lower than those against A20.EU1. Four patients (7.5%) had a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the 3 months after treatment, all with a time gap between the booster vaccination and injection. To date, tixagevimab-cilgavimab cannot be considered a substitute for vaccination but may be a useful supporting therapy if the recommended dose for pre-exposure prophylaxis is doubled. [ABSTRACT FROM AUTHOR]

Objective: To delineate thromboelastographic profiles of the premature infants with and without intracranial hemorrhage during the first 21 days of life. Methods: In this study, 49 premature infants (24 female; 25 male) were consecutively admitted at our neonatal intensive care unit during a 6 months period were subject to thromboelastography and standard coagulation assessments at birth and weekly up to 21 days. Sixteen out of 49 infants developed intracranial hemorrhage at birth. Results: The test results of 127/196 were considered eligible for analysis. Overall significant changes of the main thromboelastographic parameters were observed shortly after birth. Newborns with intracranial hemorrhage showed increased thromboelastogram-defined thrombin generation (shorter R and time to maximum amplitude times) from birth onward, suggesting a hypercoagulable state. No significant differences concerning thromboelastographic and coagulation assays parameters were found at birth between infants with and without intracranial hemorrhage, except for higher plasma D-Dimer concentration (p = 0.002) in the former infants. Finally, a positive correlation between clot lysis time and gestational age (Spearman's rho = 0.502,p = 0.002) was observed. Conclusions: Thromboelastographic profiles of the premature infants suggest an effective hemostatic function during the first post-natal weeks. Further study is needed to determine whether thromboelastography may be more useful than coagulation assays to reflect the bleeding risk of the premature infants. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid (CSF) free light chains (FLC) may be an alternative biomarker to oligoclonal bands (OCB) in multiple sclerosis (MS). Herein, we compared the diagnostic accuracy of CSF OCB and FLC and we tested the prognostic value of FLC in a cohort of 64 MS patients and 106 controls. A κ-index >7.83 was more sensitive but less specific than OCB in discriminating MS patients from controls. Additionally, a κ-index >10.61 performed better than OCB in the discrimination between MS and controls with inflammatory neurological diseases (p <.001). In clinically isolated syndrome (CIS) patients, a κ-index >10.61 significantly predicted time to conversion to MS (p =.020). κ-index might be a valid alternative to OCB as a diagnostic biomarker for MS and might also be a prognostic marker in CIS. Unlabelled Image • κ-index is more sensitive and less specific than OCB for MS diagnosis. • κ-index performs better than OCB in discriminating MS from other inflammatory neurological diseases. • κ-index correlates with different disease characteristics in MS. • κ-index predicts disease activity in early MS patients. [ABSTRACT FROM AUTHOR]