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.

Cerebral Oxygen Metabolic Stress in Children and Adults With Large Vessel Vasculopathy Due to Sickle Cell Disease.

Background And Objectives: Large vessel vasculopathy (LVV), or moyamoya syndrome, increases the risk of stroke in patients with sickle cell disease (SCD), yet effective treatments are lacking. In atherosclerotic carotid disease, previous studies demonstrated elevated oxygen extraction fraction (OEF) as a predictor of ipsilateral stroke. In a SCD cohort, we examined hemispheric hemodynamic and oxygen metabolic dysfunction as tissue-based biomarkers of cerebral ischemic risk in patients with LVV.

Intracranial aneurysms in sickle cell disease are associated with hemodynamic stress and anemia.

Although hemodynamic stress plays a key role in aneurysm formation outside of sickle cell disease (SCD), its role is understudied in patients with SCD. We hypothesized that tissue-based markers of hemodynamic stress are associated with aneurysm presence in a prospective SCD cohort. Children and adults with SCD, with and without aneurysms, underwent longitudinal brain magnetic resonance imaging/magnetic resonance angiography (MRA) to assess cerebral blood flow (CBF) and oxygen extraction fraction (OEF).

Resting-state MRI reveals spontaneous physiological fluctuations in the kidney and tracks diabetic nephropathy in rats.

The kidneys maintain fluid-electrolyte balance and excrete waste in the presence of constant fluctuations in plasma volume and systemic blood pressure. The kidneys perform these functions to control capillary perfusion and glomerular filtration by modulating the mechanisms of autoregulation. An effect of these modulations are spontaneous, natural fluctuations in glomerular perfusion.

Education Liaison improves implementation of school accommodations for students with sickle cell disease.

Background: Children with sickle cell disease (SCD) have lower academic attainment than healthy peers. Many benefit from neuropsychological testing (NPT) and educational accommodations, including Individualized Education Programs (IEPs) and Section 504 plans (504s). Despite medical barriers to academic attainment, many children with SCD do not receive indicated NPT or accommodations.

Cerebral revascularization surgery reduces cerebrovascular events in children with sickle cell disease and moyamoya syndrome: Results of the stroke in sickle cell revascularization surgery retrospective study.

Background: Recent studies suggest that cerebral revascularization surgery may be a safe and effective therapy to reduce stroke risk in patients with sickle cell disease and moyamoya syndrome (SCD-MMS).

Methods: We performed a multicenter, retrospective study of children with SCD-MMS treated with conservative management alone (conservative group)-chronic blood transfusion and/or hydroxyurea-versus conservative management plus surgical revascularization (surgery group). We monitored cerebrovascular event (CVE) rates-a composite of strokes and transient ischemic attacks.

Organ function indications and potential improvements following curative therapy for sickle cell disease.

Curative therapies for sickle cell disease include allogeneic hematopoietic stem cell transplantation (HSCT) and gene-modified autologous stem cell transplantation. HSCT has been used for 30 years with success measured by engraftment, symptom control, graft-vs-host disease (GVHD) risk, organ toxicity, and immune reconstitution. While human leukocyte antigen-matched sibling donor (MSD) transplants have excellent outcomes, alternate donor transplants (unrelated/haploidentical) are just beginning to overcome GVHD and engraftment hurdles to match MSD.

Infantile-onset Pompe disease complicated by sickle cell anemia: Case report and management considerations.

Infantile-onset Pompe disease (IOPD) is a rare, severe disorder of lysosomal storage of glycogen that leads to progressive cardiac and skeletal myopathy. IOPD is a fatal disease in childhood unless treated with enzyme replacement therapy (ERT) from an early age. Sickle cell anemia (SCA) is a relatively common hemoglobinopathy caused by a specific variant in the hemoglobin beta-chain.

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.

Normalization of cerebral hemodynamics after hematopoietic stem cell transplant in children with sickle cell disease.

Children with sickle cell disease (SCD) demonstrate cerebral hemodynamic stress and are at high risk of strokes. We hypothesized that curative hematopoietic stem cell transplant (HSCT) normalizes cerebral hemodynamics in children with SCD compared with pre-transplant baseline. Whole-brain cerebral blood flow (CBF) and oxygen extraction fraction (OEF) were measured by magnetic resonance imaging 1 to 3 months before and 12 to 24 months after HSCT in 10 children with SCD.

Silent Infarcts, White Matter Integrity, and Oxygen Metabolic Stress in Young Adults With and Without Sickle Cell Trait.

Background: Individuals with sickle cell anemia have heightened risk of stroke and cognitive dysfunction. Given its high prevalence globally, whether sickle cell trait (SCT) is a risk factor for neurological injury has been of interest; however, data have been limited. We hypothesized that young, healthy adults with SCT would show normal cerebrovascular structure and hemodynamic function.

Cerebral oxygen metabolic stress is increased in children with sickle cell anemia compared to anemic controls.

Patients with sickle cell anemia (SCA) experience cerebral metabolic stress with an increase in oxygen extraction fraction (OEF) to compensate for reduced oxygen carrying capacity due to anemia. It remains unclear if anemia alone drives this metabolic stress. Using MRI, we collected voxel-wise OEF measurements to test our hypothesis that OEF would be elevated in anemic controls without SCA (AC) compared to healthy controls (HC), but OEF would be even higher in SCA compared to AC.

A Case Series of Kawasaki Disease in Children With Sickle Cell Disease.

Prompt recognition and treatment of presumed bacterial infection in febrile children with sickle cell disease is necessary due to splenic dysfunction and impaired immune response. However, fever may be a manifestation of a noninfectious process, and health care providers must consider alternative sources. We describe 2 cases of children with sickle cell disease and persistent fevers, ultimately diagnosed with Kawasaki disease.

Neurologic and Cognitive Outcomes in Sickle Cell Disease from Infancy through Adolescence.

Children with sickle cell disease (SCD) are at risk for neurologic and cognitive complications beginning in early childhood. Current treatment for SCD focuses on primary prevention of complications, such as hydroxyurea for prevention of pain and acute chest syndrome, and chronic transfusion therapy for children who are at high risk for strokes. In this article, the prevalence, pathophysiology, and available interventions to prevent and treat neurologic and cognitive complications of SCD will be reviewed.

Epstein-Barr virus-induced sickle hepatopathy.

Sickle hepatopathy comprises a spectrum of disorders that vary in severity. Intravascular sickling and sinusoidal occlusion are the principal drivers of sickle hepatopathy, but infection or autoimmunity can act as triggers. We describe two cases of acute sickle hepatopathy initiated by primary Epstein-Barr virus (EBV) infection, a previously unreported association.

Abatacept is effective as GVHD prophylaxis in unrelated donor stem cell transplantation for children with severe sickle cell disease.

We report results of a phase 1 multicenter stem cell transplantation (SCT) trial from HLA-matched (n = 7) or one-antigen-mismatched (n = 7) unrelated donors (URD) using bone marrow or cord blood as stem cell source, following reduced-intensity conditioning (RIC) in severe sickle cell disease (SCD). Conditioning included distal alemtuzumab, fludarabine, and melphalan (matched donors), with thiotepa (mismatched donors). Abatacept, a selective inhibitor of T cell costimulation, was added to tacrolimus and methotrexate as graft-versus-host disease (GVHD) prophylaxis to offset GVHD risks, and was administered for longer duration in bone marrow recipients than in cord blood recipients because of increased incidence of chronic GVHD with bone marrow.

Higher executive abilities following a blood transfusion in children and young adults with sickle cell disease.

Individuals with sickle cell disease (SCD) experience cognitive deficits; however, it remains unclear whether medical treatments for SCD improve cognition. Given that executive abilities are typically impaired in individuals with SCD, they were the focus of the current study. Our primary hypothesis was that executive abilities would be higher acutely soon after a blood transfusion in children and young adults with SCD.

Hydroxyurea reduces cerebral metabolic stress in patients with sickle cell anemia.

Chronic transfusion therapy (CTT) prevents stroke in selected patients with sickle cell anemia (SCA). We have shown that CTT mitigates signatures of cerebral metabolic stress, reflected by elevated oxygen extraction fraction (OEF), which likely drives stroke risk reduction. The region of highest OEF falls within the border zone, where cerebral blood flow (CBF) nadirs; OEF in this region was reduced after CTT.