A-SURE: intra-patient comparison of prophylactic effectiveness of a recombinant factor VIII Fc fusion protein versus standard half-life factor VIII in hemophilia A.

Background: Despite recent advances, factor replacement therapy remains a cornerstone in hemophilia A treatment. Efmoroctocog alfa, a recombinant FVIII Fc fusion protein (rFVIIIFc), has an extended half-life allowing higher FVIII levels and less frequent dosing than standard half-life (SHL) products, without increasing factor consumption.

Methods: A-SURE was a 24-month prospective, non-interventional study assessing real-world effectiveness of rFVIIIFc prophylaxis.

Safety and immunogenicity of investigational tuberculosis vaccine M72/AS01 in people living with HIV in South Africa: an observer-blinded, randomised, controlled, phase 2 trial.

Background: M72/AS01 is a recombinant fusion protein vaccine candidate derived from two Mycobacterium tuberculosis antigens (Mtb32A and Mtb39A) and AS01 adjuvant. We evaluated safety and immunogenicity of M72/AS01 in people living with HIV in South Africa.

Methods: In this observer-blinded, randomised, controlled, phase 2 trial, participants aged 16-35 years with well controlled HIV were enrolled from urban, semi-urban, and semi-rural settings in South Africa, including sites with high tuberculosis and HIV prevalence, as well as agricultural and mining communities.

ARTEMISIA: a mechanistic study of a novel Janus kinase 1 inhibitor to advance molecular understanding and precision medicine in asthma.

Background: Patients with uncontrolled asthma despite the use of inhaled corticosteroids (ICS), may have a variety of biological pathways driving their airway inflammation. Londamocitinib (AZD4604), a selective, inhaled, Janus kinase 1 inhibitor, has been designed to target a broad inflammatory cytokine profile including those classically unresponsive to ICS. The ARTEMISIA mechanistic study aims to provide a clear understanding of the pathways impacted by londamocitinib in the lung, determine how this impact is reflected in the nose and periphery, and identify candidate biomarkers of londamocitinib-treatment response in asthma.

Characteristics and management of follicular events and contact dermatitis in patients using tapinarof cream for the treatment of atopic dermatitis or plaque psoriasis.

Provide insights into the incidence, pre-sentation and management of follicular events and contact dermatitis in patients with plaque psoriasis or atopic dermatitis (AD) treated with tapinarof cream 1%. Key clinical trial publications for tapinarof were reviewed and augmented with the authors' opinions based on real-world clinical experience. In the PSOARING and ADORING trials, discontinuation rates due to follicular events and contact dermatitis were low and most patients did not require dose modifications or treatment interruptions.

Gene therapy and genome editing for lipoprotein disorders.

Genetic factors play a critical role in the development of lipoprotein disorders, which significantly contribute to atherosclerotic cardiovascular disease (ASCVD). Traditional management of these conditions has relied on lipid-lowering therapies, which require lifelong adherence. Recent advancements in gene addition and editing technologies offer novel and potentially transformative approaches for treating lipoprotein disorders by targeting the relevant genetic pathways for each disease.

Intracardiac echocardiography versus transesophageal echocardiography guidance on left atrial appendage occlusion in patients with atrial fibrillation: A systematic review and meta-analysis.

Background: Intracardiac echocardiography (ICE) is an innovative technique that has emerged as an alternative to transesophageal echocardiography (TEE) to guide the implantation of a left atrial appendage occlusion (LAAO) device in patients with nonvalvular atrial fibrillation (AF) who cannot tolerate anticoagulants.

Purpose: We aim to review the clinical efficacy and safety of ICE compared to TEE to guide the implantation of LAAO devices in patients with AF.

Methods: We conducted comprehensive searches across PubMed, CENTRAL, Web of Science, Scopus, and EMBASE until March 2024.

Use of 5% Topical Minoxidil Application for Telogen Effluvium: An Open-Label Single-Arm Clinical Trial.

Telogen effluvium (TE) is an acute and diffuse hair loss due to an abnormal increase in telogen hair follicles in response to external or internal factors. Recently, TE attracts global interest as a major cause of hair loss as a sequela of COVID-19. Typically, hair shedding in TE is expected to cease around 3-6 months from the onset with spontaneous hair regrowth, once the triggering factor is eliminated.

Simple observation as a management option for early-stage Coats disease.

Purpose: To assess observation as first-line management option in early-stage Coats disease.

Methods: This retrospective study analyzed records of patients diagnosed with Coats disease at a single tertiary pediatric retina center from 2017 to 2025. Patients with Stage 2A or less were included.

A Comparison of SGLT2 or DPP-4 Inhibitor Monotherapy vs Placebo for Type 2 Diabetes in Adolescents vs Young Adults.

Context: There is an unmet need for type 2 diabetes (T2D) treatments in addition to metformin and insulin for adolescents. This is due to the challenges of monotherapy in youth with T2D and need for treatment escalation to maintain glycemic control in youth generally more so than in young adults.

Objective: We assessed the efficacy and safety of sodium-glucose co-transporter-2 (SGLT2) or dipeptidyl peptidase-4 (DPP-4) inhibitor monotherapies in adolescents and young adults with T2D not on active therapy.

Effect of corrections for renal function on plasma phosphorylated tau performance for Alzheimer's disease.

BackgroundBlood-based biomarkers (BBMs), including plasma phosphorylated tau (pTau), have been considered as a promising, less-invasive tool for detecting Alzheimer's disease (AD) pathology in real-world applications. Plasma pTau levels are known to be elevated in individuals with chronic kidney disease, which may require caution when corrected for renal function since it alters testing performance-decreased sensitivity and increased specificity.ObjectiveWe aimed to quantify how correcting for renal function affects BBM test performance.

Exploratory Analysis of Practical Predictive Indices for the Efficacy of Mogamulizumab in Patients With Aggressive Adult T-Cell Leukemia-Lymphoma.

An exploratory analysis of past clinical trials was conducted to propose a predictive scoring system for the efficacy of mogamulizumab, an anti-CC chemokine receptor 4 (CCR4) antibody, based on easily measurable parameters. Factors affecting progression-free survival (PFS) were investigated using data from three clinical trials (NCT00920790, NCT01626664, and NCT01173887) and one clinical study (UMIN000013294) conducted in patients with relapsed/refractory (R/R) or untreated CCR4-positive aggressive adult T-cell leukemia-lymphoma (ATL) receiving mogamulizumab treatment. Twelve routinely measured clinical parameters and three calculated indices-lymphocyte-to-neutrophil count ratio, platelet-to-lymphocyte count ratio, and lymphocyte-to-monocyte count ratio (LMR)-were selected as variables.

Long-term safety analysis of pooled data for tislelizumab as monotherapy or in combination with chemotherapy in patients with advanced cancers.

Background: Tislelizumab, an anti-programmed cell death protein 1 monoclonal antibody, has demonstrated efficacy and safety in solid tumors. This analysis evaluates its long-term safety.

Patients And Methods: A retrospective analysis was performed on data from 8 randomized phase III clinical trials involving patients with advanced gastrointestinal (GI) or lung cancers who received tislelizumab.

Phase 1 study and population PK/PD modeling of long-acting growth hormone, GB08, to guide pediatric dosing.

Objective: Growth hormone deficiency (GHD) requires long-term treatment, but daily injections and adverse effects of current therapies often pose adherence challenges in children. GB08, a novel Fc-GH, leverages the extended half-life of Fc-fusion proteins to reduce injection frequency with potential for improved safety. This study evaluates the safety, immunogenicity, pharmacokinetics, and pharmacodynamics profiles of GB08 in healthy adults.

Measurable residual disease (MRD) as a surrogate end point for clinical drug approval in acute myeloid leukemia (AML): Perspectives from the MRD Partnership and Alliance in AML Clinical Treatment Consortium.

Despite advances in acute myeloid leukemia (AML) treatment, significant unmet medical needs remain. Surrogate end points for overall survival can accelerate the approval of novel therapies. Measurable residual disease (MRD) is a promising surrogate end point candidate, providing a sensitive and quantitative assessment of disease burden.

Pivmecillinam for Treatment of Uncomplicated Urinary Tract Infection: New Efficacy Analysis.

Background: In April 2024-over 40 years after its first approval in Europe-pivmecillinam received approval from the United States Food and Drug Administration (FDA) for the treatment of uncomplicated urinary tract infection (uUTI) in women aged ≥18 years, caused by susceptible isolates of Escherichia coli, Proteus mirabilis, and Staphylococcus saprophyticus. Herein, we describe the reanalysis from previously published clinical trials, conducted in accordance with current FDA efficacy criteria, which formed the basis for this regulatory approval.

Methods: Of 14 studies reviewed, 3 randomized, controlled trials offered suitable subject-level data from patients with uUTI treated with 185 mg pivmecillinam 3 times daily for 3-7 days.

Challenges and opportunities in assessing right ventricular structure and function: a Roadmap for standardization, clinical implementation and research.

Given its crucial role in determining patient symptoms and outcomes in various cardiopulmonary diseases, the thorough and accurate assessment of right ventricular function is essential for both diagnosis and ongoing patient monitoring. In the era of precision medicine, a more detailed characterization of patients with cardiopulmonary diseases is needed, especially with the emergence of novel pharmacological and device-based therapies, such as transcatheter tricuspid valve intervention, gene therapy in patients with cardiomyopathy and anti-obesity interventions for patients with heart failure. Precise and reproducible quantification of right ventricular morphology and function are crucial for risk stratification, the selection of different therapies for the appropriate patients and the evaluation of treatment outcomes.

Impact of Fortified Malt-Based Food on Immunity Outcomes in School Children in India: Cluster Randomized Controlled Trial.

Background: Nutritional inadequacy and consequent diminished immunity among school-age children is a public health problem in India. Nutrition interventional studies using a cluster randomized controlled trial (RCT) design can avoid ethical issues inherent in double-blind individual RCTs in children involving daily administration of an empty-calorie placebo.

Objective: We tested the hypothesis that daily administration of a fortified malt-based food (FMBF), a multinutrient supplement, would improve immunity outcomes against common infectious diseases, nutritional status, and gut health in Indian school-age children by using a cluster RCT design.

Q-TWiST Analysis to Assess Benefit-Risk of Sacituzumab Govitecan in Previously Treated Patients With Metastatic Triple-Negative Breast Cancer.

Purpose: In ASCENT, sacituzumab govitecan (SG) showed significantly longer overall survival and progression-free survival than chemotherapy of physician's choice with similar rates of treatment-emergent adverse events (TEAEs) in previously treated patients with metastatic triple-negative breast cancer (mTNBC). We assessed the benefit-risk of SG versus chemotherapy by integrating patient preferences (health utilities) with clinical benefits in this analysis.

Methods: Quality-adjusted Time Without Symptoms of disease progression or Toxicity of treatment (Q-TWiST) methodology was used to compare treatments where survival was partitioned into three health states using the intention-to-treat ASCENT population: (1) toxicity (grade ≥3 TEAE after random assignment and before disease progression), (2) TWiST (progression-free period without grade ≥3 TEAE), and (3) relapse (disease progression until death or end of follow-up, whichever came first).

Phase 1b study of the anti-CD38 antibody mezagitamab in patients with relapsed/refractory multiple myeloma.

This phase 1b trial aimed to determine the safety, tolerability, and preliminary efficacy of mezagitamab, a subcutaneously administered anti-CD38 monoclonal antibody, in patients with relapsed/refractory multiple myeloma (RRMM). Eligible patients had received ≥3 prior lines of treatment, including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and a steroid, or ≥2 prior lines in which 1 included a PI + IMiD, and were refractory or intolerant to ≥1 IMiD and ≥1 PI. Fifty patients were enrolled: 44 received mezagitamab monotherapy (dose-escalating cohorts at 45-1200 mg) and 6 received mezagitamab 300 mg in combination with pomalidomide plus dexamethasone.

Efficacy and Safety of Finerenone in Asian Patients with Type 2 Diabetes and Chronic Kidney Disease: A FIDELITY Analysis.

Introduction: In FIDELITY, a prespecified pooled analysis of the phase III FIDELIO-DKD and FIGARO-DKD trials, finerenone reduced the risk of cardiovascular (CV) and kidney events versus placebo in patients with type 2 diabetes and chronic kidney disease, on optimized renin-angiotensin system blockade. This FIDELITY post hoc subanalysis explores the efficacy and safety of finerenone in Asian patients.

Methods: For this subanalysis, efficacy outcomes included a CV composite (time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney composite (kidney failure, sustained ≥57% estimated glomerular filtration rate [eGFR] decrease from baseline over ≥4 weeks or renal death) outcome.

A Randomized, Double-Blind Crossover Study of Change in Post-Dose Lung Function with Hydrofluoroolefin-1234ze, a Next-Generation Propellant for Metered Dose Inhalers, in Participants with Asthma.

Pressurized metered dose inhalers (pMDIs) currently contain propellants with relatively high global warming potential (GWP), such as hydrofluoroalkane-134a (HFA-134a). Hyrofluoroolefin-1234ze (HFO-1234ze) is a near-zero GWP propellant in development for use in future pMDIs. This Phase IIIb, multicenter, randomized, double-blind, single-dose crossover study aimed to assess post-dose lung function and clinical manifestations of bronchospasm following single doses of HFA-134a and HFO-1234ze via pMDI (four inhalations with no active drugs) in participants with well or partially controlled asthma.

Untangling "dissolved" drug species from various formulations of a poorly soluble drug: Sampling methods, mechanistic insights, and IVIVC.

Our study aimed to both provide comprehensive mechanistic enlightenment of the dissolution, supersaturation, and precipitation behavior of different formulations using various sampling approaches, as well as evaluate the predictive capabilities by in vitro in vivo correlation (IVIVC). In vitro two-stage dissolution tests, that simulate the transfer from gastric to intestinal phases, using four different formulations at two dose strengths of the poorly water-soluble and weakly basic drug emodepside were performed. During the two-stage dissolution tests, five different sampling approaches were employed simultaneously (in situ 2 derivative UV spectroscopy, benchtop centrifugation, filtration, nanofiltration, and microdialysis).

Reinterventions and medical costs after tetralogy of Fallot repair: a retrospective cohort study using health insurance claims in Japan.

Background: Reinterventions after congenital heart disease surgery include not only reoperations but also medical catheter interventions, and the details of these treatment realities are often unclear. This study aimed to elucidate the medical and surgical reinterventions and associated medical costs after the tetralogy of Fallot (TOF) repair using Japanese health insurance claims data.

Methods And Results: We analyzed reinterventions and medical costs from insurance claims data of patients who underwent TOF repair between 2005 and 2021.