Very low doses of rituximab in autoimmune hemolytic anemia-an open-label, phase II pilot trial.

Introduction: Although rituximab is approved for several autoimmune diseases, no formal dose finding studies have been conducted. The amount of CD20+ cells differs significantly between autoimmune diseases and B-cell malignancies. Hence, dose requirements of anti-CD20 therapies may differ accordingly.

The factor XI/XIa antibody abelacimab combined with enoxaparin inhibits filter clotting in hemodialysis circuits ex vivo.

Drugs targeting factor XI may offer an alternative to heparin for preventing blood clotting in extracorporeal circulation. We investigated the effects of abelacimab, a novel monoclonal antibody targeting factor XI. We collected whole blood samples into two bags (each 240 ml, control group: enoxaparin 1.

Efficacy and safety of asunercept, a CD95L-selective inhibitor, in hospitalised patients with moderate-to-severe COVID-19: ASUNCTIS, a multicentre, randomised, open-label, controlled, phase 2 trial.

Background: The phase 2 ASUNCTIS study assessed the efficacy and safety of asunercept, a fully human CD95 (Fas) ligand-binding protein, in hospitalised patients with moderate-to-severe coronavirus disease (COVID-19) to assess the clinical benefit of CD95 ligand inhibition in this viral disease.

Methods: In this open-label, multicentre, randomised, controlled, phase 2 trial, patients with COVID-19-induced pneumonia and respiratory deterioration were randomly assigned (1:1:1:1) in 12 Russian and Spanish hospitals using an interactive web-response system to receive standard of care (SOC) or SOC plus weekly asunercept 25 mg, 100 mg, or 400 mg, administered intravenously for up to 4 weeks, or until hospital discharge or death. The randomisation was stratified according to the respiratory support methods at the time of enrolment, corresponding to categories 4-6 of a clinical severity assessment scale comprising 9 levels that was recommended by the World Health Organization (WHO) at the time of the study.

Torque Teno Virus Control by the Classical Pathway of Complement Activation-A Retrospective Analysis From a First-in-Human Trial Utilizing Sutimlimab.

Torque Teno virus (TTV) load is linked with the functionality of its host's immune system and has been proposed as a potential monitoring tool for immune-modulating therapy. However, the immunological mechanisms of TTV control are incompletely understood. To assess the effect of the classical complement pathway on TTV, 64 healthy volunteers and 10 kidney transplant recipients treated with the anti-C1s antibody sutimlimab were analyzed for serum TTV copy numbers (c/mL) by qPCR.

Prospective Trial on the Pharmacokinetics of Clopidogrel in Hemodialysis Patients.

Introduction: Hemodialysis patients (HDPs) exhibit extensive cardiovascular risk. The widely prescribed anti-platelet agent clopidogrel is metabolically activated by cytochrome enzymes, which may be impaired by uremia and chronic low-grade inflammation, typically present in HDPs. We conducted a prospective multicenter study to investigate the pharmacokinetics and pharmacodynamics of clopidogrel in HDPs and healthy volunteers (HVs).

Macronutrient Intake during Complementary Feeding in Very Low Birth Weight Infants Comparing Early and Late Introduction of Solid Foods: A Secondary Outcome Analysis.

Very low birth weight (VLBW) infants may require enhanced nutrition, even during complementary feeding. However, there are limited data on macronutrient intake during this period, particularly concerning the individual timing of the introduction of solid foods in a representative VLBW infant population. This prospective observational study analyzed macronutrient intake in VLBW infants with a gestational age < 32 weeks based on whether solid foods were introduced early (<17 weeks corrected age (CA)) or late (≥17 weeks corrected age) Nutritional intake was analyzed using a 24 h recall at 6 weeks CA and 3-day dietary records at 12 weeks, 6, 9, and 12 months CA.

Micronutrient Intake during Complementary Feeding in Very Low Birth Weight Infants Comparing Early and Late Introduction of Solid Foods: A Secondary Outcome Analysis.

The complementary feeding period is crucial for addressing micronutrient imbalances, particularly in very low birth weight (VLBW) infants. However, the impact of the timing of solid food introduction on micronutrient intake in a representative VLBW population remains unclear. : This prospective, observational study investigated micronutrient intake during complementary feeding in VLBW infants categorized based on whether solids were introduced early (<17 weeks corrected age (CA)) or late (≥17 weeks CA).

Association of Electrocardiogram Findings With Clinical Outcomes in Patients With Chronic Coronary Syndrome: An Analysis of the ISCHEMIA Trials.

Objective: We aimed to investigate the association of electrocardiogram (ECG) findings with outcomes in patients with chronic coronary syndrome.

Methods: This secondary analysis of the ISCHEMIA and ISCHEMIA-CKD trials divided patients with chronic coronary syndrome into two groups, those with a normal ECG tracing and abnormal ECG tracing. Repolarization abnormalities included ST-segment depression ≥ 0.

Pharmacokinetics and pharmacodynamics of low doses of recombinant tissue plasminogen activator to establish a model for biosimilarity comparisons.

Background: Recombinant tissue plasminogen activator (rt-PA) is a thrombolytic agent and essential in emergency medical care. Given recent supply shortages, the availability of biosimilar products is an urgent medical need. However, biosimilarity trials are difficult to perform in critically ill patients.

Sustained improvements in patient-reported outcomes after long-term sutimlimab in patients with cold agglutinin disease: results from the CADENZA study open-label extension.

Background: Cold agglutinin disease (CAD) is a rare subtype of autoimmune haemolytic anaemia characterised by classical complement pathway-mediated haemolysis, fatigue, and poor quality of life (QoL). Sutimlimab, a C1s inhibitor, rapidly halted haemolysis, and improved patient-reported outcomes (PROs) in patients with CAD in two phase 3 trials (CARDINAL and CADENZA). Here we report PROs from the CADENZA open-label extension (Part B).

Reproducibility of LPS-Induced ex vivo Cytokine Response of Healthy Volunteers Using a Whole Blood Assay.

Introduction: Lipopolysaccharide (LPS) stimulation of human whole blood ex vivo has been widely used to investigate human innate immune responses. However, there are uncertainties regarding the reproducibility and reliability of this assay.

Methods: In this prospective, single-center study, cytokine responses (interleukin 8, interferon-α, interferon-γ, interleukin 10, interleukin 1-β, interleukin 6, and tumor necrosis factor-α) to ex vivo whole blood LPS stimulation were assessed in 12 healthy volunteers.

Introduction of Solid Foods in Preterm Infants and Its Impact on Growth in the First Year of Life-A Prospective Observational Study.

The aim of this study was to investigate whether age at introduction of solid foods in preterm infants influences growth in the first year of life. This was a prospective observational study in very low birth weight infants stratified to an early (<17 weeks corrected age) or a late (≥17 weeks corrected age) feeding group according to the individual timing of weaning. In total, 115 infants were assigned to the early group, and 82 were assigned to the late group.

Fluid management for sepsis-induced hypotension in patients with advanced chronic kidney disease: a secondary analysis of the CLOVERS trial.

Background: Early fluid management in patients with advanced chronic kidney disease (CKD) and sepsis-induced hypotension is challenging with limited evidence to support treatment recommendations. We aimed to compare an early restrictive versus liberal fluid management for sepsis-induced hypotension in patients with advanced CKD.

Methods: This post-hoc analysis included patients with advanced CKD (eGFR of less than 30 mL/min/1.

Kinetic Modeling for BT200 to Predict the Level of Plasma-Derived Coagulation Factor VIII in Humans.

Lack of Factor VIII (FVIII) concentrates is one of limiting factors for Hemophilia A prophylaxis in resource-limited countries. Rondaptivon pegol (BT200) is a pegylated aptamer and has been shown to elevate the level of von Willebrand Factor (VWF) and FVIII in previous studies. A population pharmacokinetic model for BT200 was built and linked to the kinetic models of VWF and FVIII based on reasonable assumptions.

Thromboelastography in acute immunologic reactions: a prospective pilot study.

Background: Biomarkers of fibrinolysis are elevated during acute immunologic reactions (allergic reactions and angioedema), although it is unclear whether fibrinolysis is associated with disease severity.

Objectives: We investigated a possible association between maximum lysis (ML) measured by thromboelastography and the severity of acute immunologic reactions.

Methods: We recruited patients with acute immunologic reactions at a high-volume emergency department.

Landiolol for refractory ventricular fibrillation in out-of-hospital cardiac arrest: A randomized, double-blind, placebo-controlled, pilot trial.

Background: Out-of-hospital cardiac arrest (OHCA) complicated by refractory ventricular fibrillation (VF) is associated with poor outcome. Beta-1-receptor selective blockade might overcome refractory VF and improve survival. This trial investigates the efficacy and safety of prehospital landiolol in OHCA and refractory VF.

A Randomized Phase 2 Trial of Felzartamab in Antibody-Mediated Rejection.

Background: Antibody-mediated rejection is a leading cause of kidney-transplant failure. The targeting of CD38 to inhibit graft injury caused by alloantibodies and natural killer (NK) cells may be a therapeutic option.

Methods: In this phase 2, double-blind, randomized, placebo-controlled trial, we assigned patients with antibody-mediated rejection that had occurred at least 180 days after transplantation to receive nine infusions of the CD38 monoclonal antibody felzartamab (at a dose of 16 mg per kilogram of body weight) or placebo for 6 months, followed by a 6-month observation period.

Preterm Infants on Early Solid Foods and Neurodevelopmental Outcome-A Secondary Outcome Analysis of a Randomized Controlled Trial.

There are no evidence-based recommendations regarding the introduction of solid foods in preterm infants. The objective of this study was to investigate whether age at the introduction of solid foods affects neurodevelopmental outcomes. This study focuses on analyzing secondary outcomes from a prospective trial involving very low birth weight infants who were randomly assigned to either an early (10-12th week corrected age) or a late (16-18th week corrected age) complementary feeding group.