The Voxelotor Effect: Decreased Affinity for New Drugs for Sickle Cell Disease?

Voxelotor (OXBRYTA) was abruptly withdrawn from the global market in September 2024. Clinicians and patients were not prepared for this, and the sudden discontinuation has caused much consternation, uncertainty, and loss of trust.

A pharmacokinetic-pharmacodynamic analysis of l-glutamine for the treatment of sickle cell disease: Implications for understanding the mechanism of action and evaluating response to therapy.

The mechanisms of action of l-glutamine for the treatment of sickle cell disease (SCD) are not well understood and there are no validated clinical biomarkers to assess response. We conducted a three-week, dose-ascending trial of glutamine and measured the pharmacokinetic (PK) exposure parameters, peak concentration (C) and area under the curve (AUC). We used a panel of biomarkers to investigate the pharmacodynamics (PD) of glutamine and studied PK-PD relationships.

Differing Susceptibilities to Certain Microbicidal Chemistries among Three Representative Enveloped Viruses.

Three lipid-enveloped viruses (bovine viral diarrhea virus [BVDV], vaccinia virus, and severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) were evaluated in side-by-side liquid inactivation efficacy studies of low pH (3.0 to 3.1) treatment and of the non-formulated microbicidal actives sodium hypochlorite (100 ppm), ethanol (70%), quaternary ammonium compound BTC 835 (100 ppm), and peracetic acid (100 ppm).

A Population Pharmacokinetic Analysis of L-Glutamine Exposure in Patients with Sickle Cell Disease: Evaluation of Dose and Food Effects.

Background And Objective: L-Glutamine is a treatment for children and adults with sickle cell disease. A comprehensive evaluation of the pharmacokinetics of L-glutamine in sickle cell disease has not been conducted. We aimed to assess the effects of long-term dosing, multiple dose levels, and food intake on L-glutamine exposure in patients with sickle cell disease compared to normal participants.

Feasibility of Electronic Medication Monitoring Among Adolescents and Emerging Adults with Sickle Cell Disease.

Purpose: To examine the feasibility of using MEMS bottles to assess adherence among adolescents and emerging adults with sickle cell disease.

Patients And Methods: Eighteen non-Hispanic Black participants with HbSS (M = 17.8 years; 61% male) were given a MEMS bottle to store hydroxyurea (n = 14) or deferasirox (n = 4).

The secondary injury cascade after spinal cord injury: an analysis of local cytokine/chemokine regulation.

After spinal cord injury, there is an extensive infiltration of immune cells, which exacerbates the injury and leads to further neural degeneration. Therefore, a major aim of current research involves targeting the immune response as a treatment for spinal cord injury. Although much research has been performed analyzing the complex inflammatory process following spinal cord injury, there remain major discrepancies within previous literature regarding the timeline of local cytokine regulation.

Return visit rates after an emergency department discharge for children with sickle cell pain episodes.

Background: High return visit rates after hospitalization for people with sickle cell disease (SCD) have been previously established. Due to a lack of multicenter emergency department (ED) return visit rate data, the return visit rate following ED discharge for pediatric SCD pain treatment is currently unknown.

Procedure: A seven-site retrospective cohort study of discharged ED visits for pain by children with SCD was conducted using the Pediatric Emergency Care Applied Research Network Registry.

Identification of HPV16 E1 and E2-specific T cells in the oropharyngeal cancer tumor microenvironment.

Background: High-risk human papillomavirus (HPV) is a primary cause of an increasing number of oropharyngeal squamous cell carcinomas (OPSCCs). The viral etiology of these cancers provides the opportunity for antigen-directed therapies that are restricted in scope compared with cancers without viral components. However, specific virally-encoded epitopes and their corresponding immune responses are not fully defined.

Correction: Comprehensive Immunoprofiling of High-risk Oral Proliferative and Localized Leukoplakia.

[This corrects the article DOI: 10.1158/2767-9764.CRC-21-0060.

Using the consolidated framework for implementation research to identify recruitment barriers and targeted strategies for a shared decision-making randomized clinical trial in pediatric sickle cell disease.

Background/aims: Recruitment is often a barrier in clinical trials that include minoritized populations, such as individuals with sickle cell disease. In the United States, the majority of people with sickle cell disease identify as Black or African American. In sickle cell disease, 57% of the United States trials that ended early did so due to low enrollment.

Implementation of CYP2D6-guided opioid therapy at Cincinnati Children's Hospital Medical Center.

Purpose: We describe the implementation of CYP2D6-focused pharmacogenetic testing to guide opioid prescribing in a quaternary care, nonprofit pediatric academic medical center.

Summary: Children are often prescribed oral opioids after surgeries, for cancer pain, and occasionally for chronic pain. In 2004, Cincinnati Children's Hospital Medical Center implemented pharmacogenetic testing for CYP2D6 metabolism phenotype to inform codeine prescribing.

Iron status and burden of anemia in children with recessive dystrophic epidermolysis bullosa.

Background And Objectives: To describe the prevalence, severity, and management of anemia in a cohort of children with recessive dystrophic epidermolysis bullosa (RDEB) and to highlight the use of soluble transferrin receptor (sTfR) to diagnose iron deficiency in this chronic inflammatory state.

Methods: We studied a cohort of 114 patients with RDEB followed at a pediatric hospital-based Epidermolysis Bullosa Center from 2010 to 2020; data were prospectively tracked in a comprehensive clinical database that captured all visits, laboratory tests, iron infusions, and transfusions. The primary outcome was occurrence of anemia, which was assessed by age and sex, with and without transfusion support.

Safety and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, in children with SCD: a V114-023 (PNEU-SICKLE) study.

Sickle cell disease (SCD) is an inherited red blood cell disease that results in a multitude of medical complications, including an increased risk of invasive disease caused by encapsulated bacteria, such as Streptococcus pneumoniae. Pneumococcal vaccines have contributed to a significant reduction in pneumococcal disease (PD) in children and adults, including those with SCD. This phase 3 study evaluated the safety and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), in children with SCD.

Consensus definition of essential, optimal, and suggested components of a pediatric sickle cell disease center.

Sickle cell disease (SCD) requires coordinated, specialized medical care for optimal outcomes. There are no United States (US) guidelines that define a pediatric comprehensive SCD program. We report a modified Delphi consensus-seeking process to determine essential, optimal, and suggested elements of a comprehensive pediatric SCD center.

Early initiation of disease-modifying therapy can impede or prevent diffuse myocardial fibrosis in sickle cell anemia.

Cardiovascular disease is a major cause of mortality in patients with sickle cell disease (SCD). Niss et al previously reported that cardiac magnetic resonance in 25 patients showed universal myocardial fibrosis, which they correlated with increased extracellular volume fraction (ECV). In the current study, they compared patients with SCD who were treated with hydroxyurea or transfusion at age <6 years to a group of patients with SCD without therapy.

Early hydroxyurea use is neuroprotective in children with sickle cell anemia.

Children with sickle cell disease (SCD) who began hydroyxurea before age five years scored no differently on a measure of cognitive funciton than age, sex, and race-matched unaffected peers.

An Immersive Virtual Reality Curriculum for Pediatric Hematology Clinicians on Shared Decision-making for Hydroxyurea in Sickle Cell Anemia.

Although hydroxyurea (HU) is an effective treatment for sickle cell anemia, uptake remains low. Shared decision-making (SDM) is a recommended strategy for HU initiation to elicit family preferences; however, clinicians lack SDM training. We implemented an immersive virtual reality (VR) curriculum at 8 pediatric institutions to train clinicians on SDM that included counseling virtual patients.

Clinical Utility of the Addition of Molecular Genetic Testing to Newborn Screening for Sickle Cell Anemia.

Sickle cell disease (SCD) is a group of related yet genetically complex hemoglobinopathies. Universal newborn screening (NBS) for SCD is performed in the United States and many other nations. Classical, protein-based laboratory methods are often adequate for the diagnosis of SCD but have specific limitations in the context of NBS.