A5065976686- Hemoglobinopathies and Related Disorders
- Iron Metabolism and Disorders
- Blood groups and transfusion
- Erythrocyte Function and Pathophysiology
- Blood properties and coagulation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cardiovascular Function and Risk Factors
- Virus-based gene therapy research
- Prenatal Screening and Diagnostics
- Folate and B Vitamins Research
- Blood disorders and treatments
- Acute Myeloid Leukemia Research
- Bone and Joint Diseases
- Food Security and Health in Diverse Populations
- Adolescent and Pediatric Healthcare
- CRISPR and Genetic Engineering
- Platelet Disorders and Treatments
- Immunodeficiency and Autoimmune Disorders
- Chronic Lymphocytic Leukemia Research
- RNA modifications and cancer
- Cell death mechanisms and regulation
- Caveolin-1 and cellular processes
- Hemoglobin structure and function
- Cardiovascular Disease and Adiposity
- Muscle and Compartmental Disorders
University of Cincinnati Medical Center
2016-2024
Cincinnati Children's Hospital Medical Center
2015-2024
University of Cincinnati
2018-2021
Abstract Hydroxyurea is FDA‐approved and now increasingly used for children with sickle cell anemia (SCA), but dosing strategies, pharmacokinetic (PK) profiles, treatment responses individual patients are highly variable. Typical weight‐based step‐wise escalation to maximum tolerated dose (MTD) leads predictable laboratory clinical benefits, often takes 6 12 months achieve. The Therapeutic Response Evaluation Adherence Trial (TREAT, NCT02286154) was a single‐center study designed...
Significance Sickle cell anemia (SCA) is a common monogenic disorder associated with significant morbidity and mortality high incidence of unexplained sudden death in young adults. With the prevention infections, there an increasing appreciation for cardiopulmonary complications cardiac phenotype that cannot be solely attributed to chronic anemia. We used mouse models SCA iron-deficient show distinct functional, pathological, ultrastructural, molecular features causing unique restrictive...
Hemolysis is a key feature of sickle cell anemia (HbSS). Direct quantitation hemolysis could be used as an objective outcome in clinical trials new therapeutics for HbSS and would also enable better human studies the pathogenesis complications that are ostensibly hemolysis‐related, such pulmonary hypertension. However, contemporary have only surrogate markers rather than direct measurements RBC survival. We directly quantified by measuring survival age cohort RBCs labeled with stable...
Hereditary spherocytosis (HS) is the most common red blood cell membrane (RBC) disorder causing hereditary hemolytic anemia. Patients with HS have defects in genes coding ankyrin (ANK1), band 3 (SLC4A1), protein 4.2 (EPB42), and (SPTA1) or -spectrin (SPTB). Severe recessive commonly due to biallelic SPTA1 mutations. -spectrin produced excess normal erythroid cells, therefore SPTA1-associated ensues mutations significant decrease of expression from both alleles. In this study, we...
Abstract Sickle cell nephropathy results in chronic kidney disease (CKD), which is associated with significant morbidity and mortality sickle anemia (SCA). Albuminuria an early manifestation of nephropathy; however, little known about progression albuminuria or its correlation glomerular filtration rate (GFR) decline CKD. We studied 303 SCA participants a prospective, multicenter, longitudinal study. collected steady-state urine serum samples yearly assessed albumin/creatinine ratio (ACR),...
Nephropathy is a common and progressive complication of sickle cell anemia (SCA). In SCA mice, we found that hyperangiotensinemia in the absence hypertension underlies nephropathy, its downregulation by losartan, an angiotensin-II-receptor-1 blocker, reduced albuminuria progression nephropathy. Therefore, performed phase-2 trial oral given for 6 months, to explore whether it children adults with SCA. Participants were allocated groups defined class baseline urinary albumin-to-creatinine...
Summary Hydroxyurea (hydroxycarbamide) is an effective treatment for sickle cell anaemia (SCA), but clinical responses depend primarily upon the degree of fetal haemoglobin (HbF) induction and heterogeneity HbF expression across erythrocytes. The number characteristics HbF‐containing cells (F‐cells) are not assessed by traditional measurements. Conventional hydroxyurea dosing (e.g. fixed doses or low starting with stepwise escalation) produces a moderate heterocellular induction, haemolysis...
Abstract Through the use of genetic sequencing, molecular variants driving autoimmunity are increasingly identified in patients with chronic and refractory immune cytopenias. With goal discovering that predispose to pediatric thrombocytopenia (ITP) or increase risk for disease, we conducted a genome-wide association study large multi-institutional cohort ITP. A total 591 were genotyped using an Illumina Global Screening Array BeadChip. Six met significance comparison between children ITP...
Abstract Background Left ventricular diastolic dysfunction (DD) is an independent risk factor for mortality in sickle cell anemia (SCA) and associated with increased extracellular volume (ECV) on cardiac MRI (CMR). Exercise impairment common SCA, but its causes prognostic value are not well understood. Objective To study the effects of DD ECV cardiopulmonary exercise test (CPET) patients SCA. Methods Results As part a prospective to characterize cardiomyopathy SCA (NCT02410811), 20 children...
Abstract Increased extracellular volume (ECV) by CMR is a marker of interstitial myocardial fibrosis and associated with diastolic dysfunction in sickle cell anemia (SCA). Left atrial (LA) stiffness contribute to the development heart failure other settings. We aimed evaluate LA function associations ECV, tricuspid regurgitation jet velocity (TRV) exercise abnormalities SCA. In prospective study, individuals SCA underwent CMR, echocardiography test. ECV was measured using MOLLI sequence....
Abstract Background Sickle cell disease (SCD) is a severe and devastating hematological disorder that affects over 100,000 persons in the USA millions worldwide. Hydroxyurea primary disease-modifying therapy for SCD, with proven benefits to reduce both short-term long-term complications. Despite well-described inter-patient variability pharmacokinetics (PK), pharmacodynamics, optimal dose, hydroxyurea traditionally initiated at weight-based dose subsequent conservative escalation strategy...
Without early initiation of disease-modifying therapy, the acute and chronic complications sickle cell anemia (SCA) begin in childhood progress throughout life. Hydroxyurea is a safe effective medication that reduces or prevents most SCA-related complications. Despite recommendations to prescribe hydroxyurea for all children with SCA as young 9 months, utilization remains low.We completed retrospective review hydroxyurea-prescribing practices associated clinical outcomes at our institution...
Abstract Lymphopenia is common in adults who have had a Fontan operation although its aetiology and clinical implications remain unknown. Previous work suggests an association between lymphopenia both liver disease splenomegaly. The objective of this study was to assess the prevalence with circulation evaluate associations risk factors outcomes. Using retrospective cohort design, we studied 73 adult patients (age 25.0 ± 8.4 years) complete blood count abdominal imaging performed. Patients...