Repeated iv anti-CD20 treatment in multiple sclerosis: Long-term effects on peripheral immune cell subsets.

Objective: Repeated intravenous administration of anti-CD20 depleting monoclonal antibodies 6 months apart is among the highly effective treatment options in multiple sclerosis (MS). Here, we aimed to investigate peripheral immune cell subset depletion kinetics following either rituximab (RTX) or ocrelizumab (OCR) infusions in people with MS (pwMS).

Methods: We studied pwMS treated de-novo with either RTX (n = 7) or OCR (n = 8).

Efficiency, efficacy and subjective user satisfaction of alternative laboratory report formats. An investigation on behalf of the Working Group for Postanalytical Phase (WG-POST), of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM).

Objectives: Although laboratory result presentation may lead to information overload and subsequent missed or delayed diagnosis, little has been done in the past to improve this post-analytical issue. We aimed to investigate the efficiency, efficacy and user satisfaction of alternative report formats.

Methods: We redesigned cumulative (sparkline format) and single reports (improved tabular and z-log format) and tested these on 46 physicians, nurses and medical students in comparison to the classical tabular formats, by asking standardized questions on general items on the reports as well as on suspected diagnosis and follow-up treatment or diagnostics.

Acidification of 24-hour urine in urolithiasis risk testing: An obsolete relic?

Background: Recommendations on the optimal preservation of 24 h urine for the metabolic work-up in urolithiasis patients are very heterogeneous. In case two such tests with different storage condition recommendations are being analysed, multiple collections would be needed, challenging especially elderly and very young patients. We therefore aimed to evaluate the stability of urine constituents under different storage conditions.

Long-term immunological consequences of anti-CD20 therapies on humoral responses to COVID-19 vaccines in multiple sclerosis: an observational study.

Background: Anti-CD20 therapies induce pronounced B-cell depletion and blunt humoral responses to vaccines. Recovery kinetics of anti-CD20 therapy-mediated cellular and humoral effects in people with multiple sclerosis (pwMS) are poorly defined.

Objective: To investigate the duration of the anti-CD20 treatment-induced effects on humoral responses to COVID-19 vaccines.

Cladribine Alters Immune Cell Surface Molecules for Adhesion and Costimulation: Further Insights to the Mode of Action in Multiple Sclerosis.

Cladribine (CLAD) is a deoxyadenosine analogue prodrug which is given in multiple sclerosis (MS) as two short oral treatment courses 12 months apart. Reconstitution of adaptive immune function following selective immune cell depletion is the presumed mode of action. In this exploratory study, we investigated the impact of CLAD tablets on immune cell surface molecules for adhesion (CAMs) and costimulation (CoSs) in people with MS (pwMS).

Tetravalent Influenza Vaccine Is Not Associated With Neuroaxonal Damage in Multiple Sclerosis Patients.

Background: Efficacy of vaccines and disease activity linked to immunization are major concerns among people with multiple sclerosis (pwMS).

Objective: To assess antibody responses to seasonal influenza antigens and vaccine-associated neuroaxonal damage utilizing serum neurofilament light chain (sNfL) in pwMS receiving dimethyl fumarate (DMF).

Methods: In this prospective study, the 2020/2021 seasonal tetravalent influenza vaccine was administered to 20 pwMS treated with DMF and 15 healthy controls (HCs).

The CXCL13/CXCR5-chemokine axis in neuroinflammation: evidence of CXCR5+CD4 T cell recruitment to CSF.

Background: C-X-C chemokine ligand 13 (CXCL13) is frequently elevated in cerebrospinal fluid (CSF) in a variety of inflammatory central nervous system (CNS) diseases, has been detected in meningeal B cell aggregates in brain tissues of multiple sclerosis patients, and proposedly recruits B cells into the inflamed CNS. Besides B cells also follicular helper T (Tfh) cells express the cognate receptor C-X-C chemokine receptor type 5 (CXCR5) and follow CXCL13 gradients in lymphoid tissues. These highly specialized B cell helper T cells are indispensable for B cell responses to infection and vaccination and involved in autoimmune diseases.

Laboratory Demand Management Strategies-An Overview.

Inappropriate laboratory test selection in the form of overutilization as well as underutilization frequently occurs despite available guidelines. There is broad approval among laboratory specialists as well as clinicians that demand management strategies are useful tools to avoid this issue. Most of these tools are based on automated algorithms or other types of machine learning.

Presentation and formatting of laboratory results: a narrative review on behalf of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group "postanalytical phase" (WG-POST).

In laboratory medicine, much effort has been put into analytical quality in the past decades, making this medical profession one of the most standardized with the lowest rates of error. However, even the best analytical quality cannot compensate for errors or low quality in the pre or postanalytical phase of the total testing process. Guidelines for data reporting focus solely on defined data elements, which have to be provided alongside the analytical test results.

Long-term peripheral immune cell profiling reveals further targets of oral cladribine in MS.

Objectives: To expand the knowledge about the immunological consequences of cladribine (CLAD), a pulsed immune reconstitution therapy approved for active multiple sclerosis (MS), beyond the known short-term effects on peripheral immune cell subsets.

Methods: In this study, we characterized depletion and restitution kinetics as well as cytokine profiles of peripheral immune cell subsets in 18 patients with MS following treatment with oral CLAD. The methods involved blood collection prior to CLAD and every three months over a period of 24 months, and extensive characterization of various immune cells subsets by multiparametric flow cytometry.

Influence of dabigatran on pro-inflammatory cytokines, growth factors and chemokines - Slowing the vicious circle of coagulation and inflammation.

Aims: Blood coagulation is one of the most important host-defending mechanisms in vivo by maintaining the blood pressure after injury. However, besides maintaining homeostasis, blood coagulation and the contributing factors are directly linked to pathological conditions, such as thromboembolism and inflammation, leading to cardiovascular diseases, among others. As anti-inflammatory drugs may reduce cardiovascular events, we hypothesized in this study that the direct thrombin inhibitor dabigatran may reduce cytokine, growth factor and chemokine expression in vitro.

Errors within the total laboratory testing process, from test selection to medical decision-making - A review of causes, consequences, surveillance and solutions.

Laboratory analyses are crucial for diagnosis, follow-up and treatment decisions. Since mistakes in every step of the total testing process may potentially affect patient safety, a broad knowledge and systematic assessment of laboratory errors is essential for future improvement. In this review, we aim to discuss the types and frequencies of potential errors in the total testing process, quality management options, as well as tentative solutions for improvement.

The clinically effective use of cardiac markers by restructuring laboratory profiles at Cardiology wards.

Background: Laboratory overutilization is associated with diagnostic error and potential patient risk. We applied a demand management strategy in collaboration with the local Department of Cardiology to reduce the cardiac markers high-sensitive troponin T (hsTropT) and N-terminal pro brain natriuretic peptide (NTproBNP) in laboratory ordering profiles (LOPs). The present study aimed to retrospectively evaluate the implemented strategies.

Reducing the probability of falsely elevated HbA1c results in diabetic patients by applying automated and educative HbA1c re-testing intervals.

Introduction: Too frequent HbA1c measurements may lead to unnecessary treatment modifications of diabetic patients. The aim of this study was to estimate the percentage of falsely elevated HbA1c results in two hospitals, Landeskrankenhaus/Uniklinikum Salzburg (LKH) and Landesklinik St. Veit (STV), as well as to retrospectively investigate the effect of an automated and an educative 60-day re-testing interval (RTI).

Chemokine CXCL13 in serum, CSF and blood-CSF barrier function: evidence of compartment restriction.

Background And Purpose: Elevation of the chemokine CXCL13 in CSF frequently occurs during active and acute CNS inflammatory processes and presumably is associated with B cell-related immune activation. Elevation levels, however, vary a lot and "leaking" of CXCL13 from blood across dysfunctional brain barriers is a possible source. The aim was to clarify the relation between CXCL13 concentrations in CSF, CXCL13 concentrations in serum and blood-CSF barrier (BCSFB) function for a correct interpretation of the intrathecal origin of CXCL13.

Inappropriate use of laboratory tests: How availability triggers demand - Examples across Europe.

Introduction: The appropriate use of laboratory diagnostics is increasingly at stake. The aim of this study was to depict some paradigmatic examples of under- and overutilization, as well as possible solutions across Europe.

Methods: We collected six examples from five European countries where a rise or decline of orders for specific laboratory parameters was observed after organizational changes but without evidence of changes in patient collective characteristics as source of this variation.

Beyond LNB: Real life data on occurrence and extent of CSF CXCL13 in neuroinflammatory diseases.

To evaluate occurrence and extent of CSF CXCL13 elevations beyond Lyme neuroborreliosis, we investigated CXCL13 in an unselected patient cohort with neuroinflammatory disease. From March 2016 to March 2017, 180 in-patients with CSF pleocytosis were categorized into following groups: pyogenic CNS infections, aseptic meningoencephalitis, neuroimmunological diseases, and reactive pleocytosis. We provide evidence that CXCL13 elevation occurs at variable extent in the majority of neuroinflammatory diseases.

Development and Characterization of the Neuroregenerative Xanthohumol C/Hydroxypropyl-β-cyclodextrin Complex Suitable for Parenteral Administration.

The chroman-like chalcone Xanthohumol C, originally found in hops, was demonstrated to be a potent neuroregenerative and neuroprotective natural product and therefore constitutes a strong candidate for further pharmaceutical research. The bottleneck for experiments is the low water solubility of this chalcone. Consequently, we developed and validated a suitable formulation enabling administration.

Heparin and citrate additive carryover during blood collection.

Background Published evidence on the risk of additive carryover during phlebotomy remains elusive. We aimed to assess potential carryover of citrated and heparinized blood and the relative volume needed to bias clinical chemistry and coagulation tests. Methods We simulated standardized phlebotomies to quantify the risk of carryover of citrate and heparin additives in distilled water, using sodium and lithium as surrogates.

The endogenous cardiotonic steroid Marinobufagenin and decline in estimated glomerular filtration rate at follow-up in patients with arterial hypertension.

Background: Marinobufagenin (MBG) is an endogenous cardiotonic steroid (CTS) that inhibits the Na+/K+-ATPase. Human MBG is significantly increased in end-stage renal disease and immunization against MBG attenuates cardiovascular fibrosis in a rat model of uremic cardiomyopathy. Mineralocorticoid antagonists (MRA) block MBG binding sites and decrease proteinuria in chronic kidney disease (CKD) patients.

Cerebrospinal fluid CXLC13 indicates disease course in neuroinfection: an observational study.

Background: The chemokine CXCL13 is an intensively investigated biomarker in Lyme neuroborreliosis (LNB). Its role in other neuroinfections is increasingly recognized but less clear.

Objective: To determine the significance of CXCL13 in established central nervous system (CNS) infections other than LNB by matching cerebrospinal fluid (CSF) CXCL13 elevations with severity of the disease course.