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.

Clinical utility of companion diagnostic biomarker results below the limit of detection in comprehensive genomic profiling of patients with advanced non-small cell lung cancer.

Background: When the limit of blank (LoB) of comprehensive genomic profiling (CGP) for a given biomarker is acceptably demonstrated (ie, α ≤ 0.05 or LoB equal to zero), biomarkers detected below the assay limit of detection (LoD) can be reported with a high degree of confidence. However, it is unknown whether variants detected below LoD have clinical utility.

Revealing the Patient Perspective: Evolution of Patient-Reported Outcome Measures in Botulinum Toxin Studies in Aesthetic Medicine.

Background: OnabotulinumtoxinA has been licensed for the treatment of upper facial lines for over 20 years. Patient benefits extend well beyond correction of the lines themselves-including positive effects on confidence, self-esteem, feelings of attractiveness, and age appearance. Regulatory bodies recommend that patient-reported outcomes (PROs) are routinely included in registrational studies to ensure the patient perspective is considered.

Real-world characteristics, treatment patterns, and outcomes of patients with 2 or more LOTs for CLL/SLL in the United States.

The development of targeted agents for chronic lymphocytic leukemia (CLL) has transformed the treatment paradigm for patients with CLL. Because of this evolving treatment landscape, contemporaneous evidence was needed related to US treatment patterns and outcomes among patients treated in the real-world. Using COTA's electronic health records-based database, we examined characteristics, treatment patterns, and outcomes of patients receiving ≥2 lines of therapy (LOTs).

Investigating the expression of HERV-K env, np9, gag, and rec in bladder cancers.

Objective: Bladder cancer (BCa) has become a growing concern worldwide, highlighting the importance of early detection and new treatment methods. Recent studies have shown that viruses from the HERV family play a significant role in the development of various cancers and can act as early diagnostic biomarkers. Although hypomethylation of HERV-K has been proven in bladder cancer, no studies have yet explored the role of HERV-K oncogenes such as env, gag, np9, and rec.

Current practices on the measurement of electrocardiogram and hemodynamic parameters in non-rodent species in regulatory safety assessment studies.

Introduction: Cardiovascular (CV) parameters such as blood pressure (BP), electrocardiogram (ECG), and heart rate (HR) are recorded in non-rodent non-clinical safety studies to support drug development. However, measurement quality varies depending on the methodology used, including restraint-based or telemetry (implanted or jacketed) techniques. Measurement quality, in this context, refers to the sensitivity and reliability of CV measurements in affecting baseline values of measured CV parameters and in detecting pharmacological effects.

A phase 3, randomized trial to evaluate lot-to-lot consistency of V116, an adult-specific pneumococcal conjugate vaccine (STRIDE-4).

Background: Streptococcus pneumoniae infection can lead to community-acquired pneumonia and invasive pneumococcal disease (IPD), conditions associated with substantial morbidity and mortality. V116 (Merck & Co., Inc.

Phase I Study of the Anti-interleukin 33 Fragment Antigen-Binding Region RO7303359 in Geographic Atrophy Secondary to Age-Related Macular Degeneration.

Purpose: Interleukin (IL) 33 is a potent proinflammatory cytokine and a potential target in age-related macular degeneration (AMD) pathophysiology. This study evaluated RO7303359, an anti-IL-33 fragment antigen-binding region (Fab) targeting the IL-33/serum stimulation-2 (ST2) pathway, in patients with geographic atrophy (GA) secondary to AMD.

Design: Phase I, open-label, multicenter, single-dose, dose-escalation study.

Safety Evaluation of Topical Products Containing Live Cultures and Ferment of Cutibacterium Acnes Subspecies Defendens Strain XYCM42 in Individuals Predisposed to Acne Vulgaris.

Background: For individuals with acne-prone skin, identifying a topical regimen that does not lead to progression of their inflammatory issues often poses a challenge. A topical skin probiotic regimen containing a specific strain of subspecies , XYCM42, has been shown to be beneficial in improving skin health and appearance in individuals with generally healthy skin, but the use of the skin probiotic has not been sufficiently assessed in individuals with acne-prone skin.

Objective: The purpose of this study was to evaluate the safety and efficacy of daily application of a topical skin biome care regimen containing a living subsp.

A phase 1 study evaluating the safety, tolerability, and pharmacokinetics of the porcupine inhibitor, AZD5055.

Excessive Wnt signaling contributes to the development of fibrotic diseases and cancer. Here, we report the findings of a phase 1 study evaluating AZD5055, an orally administered porcupine inhibitor, which inhibits Wnt signaling. The primary objective was to evaluate the safety and tolerability of AZD5055 in healthy volunteers.

A Randomized Phase I Trial Evaluating Safety and Pharmacokinetics of Single and Multiple Ascending Doses of Eclitasertib, a RIPK1 Inhibitor, in Healthy Participants.

Introduction: Receptor-interacting protein kinase 1 (RIPK1) is a master regulator of inflammation and necroptotic cell death and is implicated in the pathogenesis of several inflammatory and neurodegenerative diseases. This first-in-human study assessed the safety, pharmacokinetic (PK) and pharmacodynamic (PD) properties of eclitasertib, a selective, peripherally-restricted, oral inhibitor of RIPK1.

Methods: This 2-part Phase I trial enrolled healthy participants aged 18-55 years.

Taste Profile and Relative Bioavailability of Tovorafenib Powder for Oral Suspension and Food Effect of the Tovorafenib Tablet in Healthy Participants.

A pediatric-friendly powder for oral suspension (PfOS) of tovorafenib, a type II RAF inhibitor, was developed for patients with difficulty swallowing tablets. This open-label, randomized, phase 1 study (QSC205140) evaluated the taste/palatability of PfOS formulations (n = 12), the relative bioavailability of the PfOS versus tablet formulation, and the food effect on tablets (n = 12) in healthy participants. Tovorafenib was initially administered at 300 mg and reduced to 100 mg due to musculoskeletal adverse events (AEs).

Finerenone According to Frailty in Heart Failure: A Prespecified Analysis of the FINEARTS-HF Randomized Clinical Trial.

Importance: Patients with frailty are often perceived to have a less favorable benefit-risk profile for novel therapies and therefore may be less likely to receive these.

Objective: To examine the efficacy and safety of finerenone, compared with placebo, according to frailty status in patients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) or with HF and preserved ejection fraction (HFpEF).

Design, Setting, And Participants: This was a prespecified secondary analysis of a phase 3 randomized clinical trial, the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF), conducted across 653 sites in 37 countries.

Economic Burden of Postsurgical Chronic Hypoparathyroidism: A US Medicare Claims Retrospective Analysis.

Introduction: Approximately 75% of hypoparathyroidism (HypoPT) cases result from removal of or injury to parathyroid glands during anterior neck surgery. HypoPT persisting 6 months following surgery carries a significant economic burden. This study aims to describe the economic burden of postsurgical chronic HypoPT in the Medicare population.

Zabedosertib, a novel interleukin-1 receptor-associated kinase-4 inhibitor, shows a favorable pharmacokinetic and safety profile across multiple phase 1 studies.

Introduction: Zabedosertib, the interleukin-1 receptor-associated kinase-4 (IRAK4) inhibitor, is in clinical development as an oral therapeutic for immune-mediated inflammatory diseases and was thoroughly investigated in several phase 1 studies in healthy male volunteers.

Methods: Pharmacokinetics, safety, and tolerability of zabedosertib were characterized in two clinical phase 1 studies with single oral doses up to 480 mg and multiple oral doses up to 200 mg twice daily over 10 consecutive days. The absolute oral bioavailability was determined in a third study using the intravenous microtracer methodology.

Anti-OX40 antibody BAT6026 in patients with advanced solid tumors: A multi-center phase I study.

BAT6026 is a fully human IgG1 OX40 monoclonal antibody. This was a multicenter, open-label, dose escalation, and dose expansion phase I study of BAT6026 conducted in patients with advanced solid tumors who failed standard treatment. Patients received BAT6026 injections ranging from 0.

Efficacy and safety of drospirenone as a progestin-only pill in Japanese women: A phase III study.

Aim: To evaluate the efficacy and safety of 4 mg of drospirenone (DRSP), a progestin-only pill (POP), for contraception in Japanese women.

Methods: This was a multicenter, open-label, single-arm study. The dosing period of DRSP was 13 cycles, each lasting for 28 days.

Interlaboratory study to assess precision and reproducibility of the meningococcal antigen surface expression (MEASURE) assay to quantify factor H binding protein expression at the surface of meningococcal serogroup B strains.

Background: The serum bactericidal antibody using human complement (hSBA) assay, the accepted surrogate measure of meningococcal vaccine efficacy, is limited by human sera and complement requirements. Pfizer developed and validated the flow-cytometry-based Meningococcal Antigen Surface Expression (MEASURE) assay to quantify surface-expressed factor H binding protein (fHbp) levels on intact meningococci. Surface expression of fHbp is correlated with hSBA assay killing by MenB-fHbp (Trumenba)-induced antibody, meaning the MEASURE assay can be used to predict meningococcal serogroup B (MenB) strain susceptibility to antibodies elicited by MenB-fHbp.

A Pooled Analysis of Datopotamab Deruxtecan in Patients With EGFR-Mutated NSCLC.

Background: This exploratory analysis assessed datopotamab deruxtecan (Dato-DXd) in pretreated patients with advanced or metastatic NSCLC and EGFR mutations.

Methods: Data were pooled from the phase II TROPION-Lung05 (NCT04484142) and phase III TROPION-Lung01 (NCT04656652) trials. Patients with EGFR-mutated advanced or metastatic NSCLC, who had received previous targeted therapies and platinum-based chemotherapy, received Dato-DXd 6 mg/kg (TROPION-Lung05) or were randomized to Dato-DXd 6 mg/kg or docetaxel 75 mg/m (TROPION-Lung01) once every 3 weeks.

Phase I study of H3B-6545 in patients with estrogen receptor-positive breast cancer.

Background: This phase I study (NCT04568902) evaluated a novel selective estrogen receptor (ER)-α covalent antagonist (H3B-6545) at doses of 300-450 mg in Japanese women with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative, advanced/metastatic breast cancer (mBC).

Patients And Methods: This study consisted of three parts. In the dose-escalation (DE) part, two dose levels [300 and 450 mg once daily (QD)] were evaluated.

First-in-human phase I/II, open-label study of mRNA-2416 alone or combined with durvalumab in patients with advanced solid tumors and ovarian cancer.

Background: mRNA-2416 is a novel lipid nanoparticle-encapsulated messenger RNA (mRNA) encoding human OX40 ligand (OX40L) for intratumoral (Itu) injection. OX40L plus immune checkpoint inhibitor (ICI) increased preclinical antitumor activity, thus mRNA-2416 plus ICI may potentiate antitumor activity.

Methods: This first-in-human, phase I/II, open-label, multicenter study examined the safety, tolerability, and efficacy of mRNA-2416 alone (arm A) or with durvalumab (arm B) in patients with advanced solid tumors or lymphoma (NCT03323398).

Safety and effectiveness of empagliflozin in Japanese patients with heart failure: a 1-year post-marketing surveillance study stratified by age.

Background: The sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin is approved in Japan for the treatment of heart failure (HF) with reduced left ventricular ejection fraction (HFrEF) and HF with preserved left ventricular ejection fraction (HFpEF). We conducted a post-marketing surveillance study of empagliflozin for HF in Japan.

Research Design & Methods: This was a 1-year prospective, multicenter, observational study of patients with chronic HF who had not previously received empagliflozin.

LiGeR-HN phase III trials of petosemtamab + pembrolizumab and petosemtamab monotherapy in recurrent or metastatic HNSCC.

Patients with recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC) have limited treatment options and a dismal prognosis, especially when their cancer is resistant to standard treatments like anti-programmed cell death protein 1 and platinum-based therapies. Petosemtamab - a human, common light chain, bispecific antibody with enhanced antibody-dependent cellular cytotoxicity targeting epidermal growth factor receptor (EGFR) and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) - demonstrated antitumor activity in r/m HNSCC. In many tumor types, including HNSCC, EGFR is an oncogenic driver, while LGR5 is upregulated.

Complete Genome Sequencing of a G3P[14] Rabbit Rotavirus.

Group A rotaviruses (RVAs) are a major cause of acute dehydrating diarrhea in infants and young animals worldwide. In rabbits, RVAs are associated with enteric disease, likely in combination with other pathogens. We report the identification and characterization of a lapine RVA strain in an Italian rabbit breeding farm.

Efficacy and Safety of Finerenone in Heart Failure With Preserved Ejection Fraction: A FINE-HEART Analysis.

Background: Pooling data from participants with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) from all completed outcomes trials evaluating finerenone to date may enhance understanding of its safety and efficacy in this high-risk and heterogeneous population.

Objectives: In this prespecified participant-level pooled analysis of the FIDELIO-DKD, FIGARO-DKD, and FINEARTS-HF trials (FINE-HEART), we evaluated the safety and efficacy of finerenone in individuals with HFmrEF/HFpEF.

Methods: The treatment effects of finerenone vs placebo on cardiovascular death or heart failure hospitalization were evaluated using Cox proportional hazards regression models stratified by trial.