Cerebral Hemodynamic Responses to Disease-Modifying and Curative Sickle Cell Disease Therapies.

Background And Objectives: Sickle cell disease (SCD) is a hemoglobinopathy resulting in hemoglobin-S production, hemolytic anemia, and elevated stroke risk. Treatments include oral hydroxyurea, blood transfusions, and hematopoietic stem cell transplantation (HSCT). Our objective was to evaluate the neurologic relevance of these therapies by characterizing how treatment-induced changes in hemoglobin (Hb) affect brain health biomarkers.

Children with sickle cell disease and fever but no respiratory symptoms: Is a chest x-ray needed?

Background: The National Heart, Lung, and Blood Institute (NHLBI) defines acute chest syndrome (ACS) as a new infiltrate on chest x-ray (CXR) and at least 1 of the following: fever (≥38.5C), hypoxia, or respiratory symptoms. NHLBI expert consensus recommends a CXR in patients with sickle cell disease (SCD) who have fever and respiratory symptoms.

Sociodemographic and Clinical Factors Predictive of Poor Health-Related Quality of Life of Children with Sickle Cell Anemia in The Gambia.

Children with sickle cell anemia (SCA) experience recurrent vaso-occlusive crises and complications, significantly impacting their health-related quality of life (HRQoL). This study determined HRQoL in 130 children aged 5 -15 years with SCA in The Gambia, compared to 130 age- and sex-matched hemoglobin AA (HbAA) children. HRQoL was measured using the Pediatric Quality of Life Inventory (PedsQL), with scores below 69.

Nationwide survey on awareness of consanguinity and genetic diseases in Saudi Arabia: challenges and potential solutions to reduce the national healthcare burden.

Background: Consanguineous marriage is a major contributing factor for many genetic diseases and a burden to the healthcare system and national economy due to costly long-term care. Earlier studies highlighted the significantly limited awareness of the higher prevalence of genetic disease due to consanguinity even among the educated Arabs. In Saudi Arabia, more than 50% of marriages are between first cousins.

Screening and Impact of Neuropathic Pain in Young Individuals With Sickle Cell Disease.

Objective: To assess the frequency of neuropathic pain (NP) and its impact in young patients with sickle cell disease (SCD).

Methods: We used the ID-Pain (ID-P) questionnaire and a bedside clinical sensory testing (CST) as screening tools for NP and performed sensory nerve conduction study (SNCS) for all the participants. The impact of pain was assessed using Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires and Pediatric Quality of Life Inventory (PedsQL) SCD module.

Unwanted or negative treatment reactions in digital psychological interventions for adolescents with chronic pain.

Objective: Reports of pain clinical trials evaluating psychological treatments often lack sufficient details on the potential and actual harm resulting from intervention. We aimed to understand how frequent and intense treatment reactions, conceptualized as unwanted symptoms, were in three clinical trials of digital Cognitive Behavioral Therapy (CBT) for adolescents with: (1) chronic primary pain, (2) sickle cell disease, and (3) chronic pancreatitis. We also aimed to understand any differences by demographic and clinical variables.

Direct delivery of Cas-embedded cytosine base editors as ribonucleoprotein complexes for efficient and accurate editing of clinically relevant targets.

Recently, cytosine base editors (CBEs) have emerged as a promising therapeutic tool for specific editing of single nucleotide variants and disrupting specific genes associated with disease. Despite this promise, the currently available CBEs have the significant liabilities of off-target and bystander editing activities, partly due to the mechanism by which they are delivered, causing limitations in their potential applications. In this study, we engineered optimized, soluble and stable Cas-embedded CBEs (CE_CBEs) that integrate several recent advances, which were efficiently formulated for direct delivery into cells as ribonucleoprotein (RNP) complexes.

Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells.

Gene editing the BCL11A erythroid enhancer is a validated approach to fetal hemoglobin (HbF) induction for β-hemoglobinopathy therapy, though heterogeneity in edit allele distribution and HbF response may impact its safety and efficacy. Here, we compare combined CRISPR-Cas9 editing of the BCL11A +58 and +55 enhancers with leading gene modification approaches under clinical investigation. Dual targeting of the BCL11A +58 and +55 enhancers with 3xNLS-SpCas9 and two single guide RNAs (sgRNAs) resulted in superior HbF induction, including in sickle cell disease (SCD) patient xenografts, attributable to simultaneous disruption of core half E-box/GATA motifs at both enhancers.

Safety and Tolerability of Intravenous Lidocaine Infusions as Opioid Adjunct for Children Hospitalized With Sickle Cell Vaso-Occlusive Pain.

Sickle cell disease (SCD) vaso-occlusive episode (VOE) pain is treated with opioids, and non-opioid adjuvants may reduce pain severity without opioid side effects. We retrospectively investigated the safety and tolerability of intravenous lidocaine infusions as an adjunct to opioids in children and adolescents during VOE hospitalizations. In 2 years, lidocaine was administered in 64.

Relationships Between Markers of Iron Status and Hematological Parameters in Patients With Sickle Cell Disease.

Based on the relationship between the intracellular concentration of sickle hemoglobin S (HbS) and the delay that occurs prior to the onset of sickling following deoxygenation, targeting the intracellular HbS concentration is a recognized therapeutic approach for sickle cell disease (SCD). We and others have shown that restricting iron by dietary or pharmacologic means improves hematologic parameters, inflammation, and organ damage in mouse models of SCD. Clinical evidence corroborating these findings is confined to case reports and small case series studies, none of which account for treatment or -thalassemia.

The prevalence of opioid misuse diagnostic codes in children with sickle cell disease.

Hospitalized patients with sickle cell disease (SCD) may use opioid medications for both acute and chronic pain management. Use of these medications may unintentionally generate diagnostic codes for opioid misuse including "opioid use," "opioid abuse," and "opioid dependence," which connote a behavioral problem or addiction. In this study, we sought to compare diagnostic codes for opioid misuse amongst hospitalized patients with and without SCD.

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.

The role of miR-129-5p in regulating γ-globin expression and erythropoiesis in β-thalassemia.

The regulation of γ-globin expression is crucial due to its beneficial effects on diseases like β-thalassemia and sickle cell disease. B-cell lymphoma/leukemia 11A (BCL11A) is a significant suppressor of γ-globin, and microRNAs (miRNAs) targeting BCL11A have been shown to alleviate this suppression. In our previous high-throughput sequencing, we identified an 11.

Association of Unmet Social Needs With Disease-Related Outcomes in Pediatric Patients With Sickle Cell Disease.

Background: Social determinants of health (SDoH) are socioeconomic factors that influence health and well-being, though when unmet can greatly contribute to health disparities. Individuals with sickle cell disease (SCD) are at increased risk of mortality, disability, and healthcare utilization. However, there are limited data linking specific social needs with disease outcomes in this population.

Estimation of HbA1c Levels in Transfusion-Dependent Thalassemia Patients in Comparison With Normal Healthy Individuals.

Introduction HbA1c values used for diagnosing and treating diabetes can be affected by factors such as red blood cell lifespan, hemolysis, red cell transfusion, and the presence of minor Hb species like HbA2 and HBF in hemoglobinopathies like sickle cell disease, homozygous HbC disease, HbSC disease, and β-thalassemia. This study aims to compare HbA1c levels in transfusion-dependent thalassemia (TDT) patients and healthy individuals. Materials and methods This is a cross-sectional comparative study.

End-of-life care for people with sickle cell disease: barriers to and facilitators of high-quality care.

End-of-life (EOL) care is a critical part of sickle cell disease (SCD) management. However, barriers to high-quality EOL care remain, including (1) disease-related barriers (prior opioid exposure, risk of vaso-occlusive crises, chronic conditions with conflicting needs, and limitations of receiving disease-directed therapy on hospice); (2) communication-related barriers (challenges of identifying and responding to religious and spiritual concerns, limited health literacy, and previous health care system experience); (3) systemic issues (social determinants of health, structural racism, and mistrust of the medical system). However, palliative care and interdisciplinary collaboration can overcome many of these barriers.

Practical guide for disease-modifying medication management of children and adolescents with sickle cell disease.

Hydroxyurea has historically been the sole disease-modifying medication (DMM) for sickle cell disease (SCD). However, 3 newer DMMs, L-glutamine, voxelotor, and crizanlizumab, were approved for children and adolescents with SCD since 2017. Despite their emergence, treatment barriers, including access, affordability, and nonadherence, limit the optimization of DMMs in the clinical setting.

Sickle cell disease in India: the journey and hope for the future.

India, the most populous nation in the world, also has a high frequency of the sickle hemoglobin (HbS) allele globally. The Arab Indian HbS haplotype in India is characterized by a relatively high percentage of fetal Hb, with widely varying frequencies of α-thalassemia. Hence, sickle cell disease (SCD) in India was perceived to be mild.

BCL11A +58/+55 enhancer-editing facilitates HSPC engraftment and HbF induction in rhesus macaques conditioned with a CD45 antibody-drug conjugate.

Editing the +58 region of the BCL11A erythroid enhancer has shown promise in treating β-globin disorders. To address variations in fetal hemoglobin (HbF) response, we investigated editing both +58 and +55 enhancers. Rhesus macaques transplanted with edited hematopoietic stem/progenitor cells (HSPCs) following busulfan conditioning exhibited durable, high-level (∼90%) editing frequencies post transplantation with sustained HbF reactivation over 4 years, without hematological perturbations.