Background: SCD-related complications result in significant declines in health-related quality of life and other patient-reported outcomes (PROs). However, PROs are not routinely monitored in the SCD-clinic setting. Hydroxyurea reduces complications, decreases hospitalizations and improves PROs in SCD patients. Yet hydroxyurea adherence remains suboptimal, especially among adolescents and young adults (AYA) with SCD. No previous studies have addressed the relationship between hydroxyurea adherence and PROs. Objectives: To assess the feasibility of evaluating PROs and hydroxyurea adherence in AYA with SCD in the outpatient setting, and 2) To explore the relationship between PROs and hydroxyurea adherence. Design/Method: A cross-sectional survey was administered on electronic tablets to 34 AYA (12-22 years old, all genotypes) on steady state hydroxyurea in our SCD clinic from January through December 2015. PROs were assessed by Patient Reported Outcomes Measurement Information System (PROMIS) – Computerized Adaptive Testing (CAT), and hydroxyurea adherence was assessed using the Modified Morisky Adherence Scale-8. Results: At survey time, participants (52% male, 89% Black, 89% Hb SS, mean 15±3.3 years) had taken hydroxyurea at a mean dose of 32.5±4.9 mg/kg/day for an average of 15±8.6 months, most commonly for recurrent pain. All patients approached agreed to participate and successfully completed all assessments during their clinic visits, meeting our feasibility criterion of a >=85% completion rate. The average time to complete PROMIS-CAT was 61±30 seconds/instrument. Participants with low hydroxyurea adherence, compared to moderate/high adherence, had significantly worse mean fatigue (54.4 vs. 33.5, p<0.001) and depression (48.4 vs. 34.4, p=0.04) scores. Participants with fetal hemoglobin (Hb F) <10%, compared to >=10%, had significantly worse mean fatigue (60 vs. 47.4, p=0.03) and peer relationship (58.5 vs. 45.7, p=0.006) scores. Mean PROs scores did not correlate with mean Hb, Hb F, hydroxyurea dose or duration. Abstract source

Background: Cardiopulmonary and renal complications are major causes of morbidity and mortality in sickle cell anemia (SCA). Recently, we have observed that SCA is characterized by a unique cardiomyopathy, with features of both restrictive physiology (diastolic dysfunction, disproportionate left atrial (LA) enlargement and normal systolic function) and an anemia-related hyperdynamic state with ventricular enlargement. Restrictive physiology could lead to secondary elevation in tricuspid regurgitant jet velocity (TRV) and exercise intolerance, independent of pulmonary artery hypertension. Albuminuria is an early manifestation of sickle nephropathy. Albuminuria has been correlated with echocardiography-estimated pulmonary hypertension using TRV as a surrogate measure. Whether the sickle cardiomyopathy correlates with nephropathy is unknown. Design/Method: Echocardiograms were performed in individuals with SCA (SS and Sβ0-thalassemia) participating in a clinical trial of losartan for sickle nephropathy. We analyzed baseline (pre-losartan) results and correlated the cardiac phenotype with urine albumin-to-creatinine ratio (UACR), 6-minute walk distance (6MWD) and hematological markers. Albuminuria was defined as UACR ≥ 30 mg/g. Results: Thirty-six SCA patients were included (mean age 24.1y; 53% female). Fifteen had normal UACR (mean±SEM 9.2±1.5 mg/g) while 21 patients had albuminuria (UACR 373±87 mg/g). Patients with albuminuria had worse diastolic function indicated by the early-to-late ratio of mitral inflow velocities, E/A (1.81±0.1 vs 2.3±0.1, P=0.018), and septal annular velocities, e’/a’ (1.5±0.2 vs 2.4±0.2, P<0.001), and significantly larger LA volumes (57.2±3.1 vs 38.9±3.7 ml, P<0.001). Systolic function was normal and similar in both groups (shortening fraction 36.9±2% vs 36.7±1.5%, P=0.94). Patients with albuminuria had significantly lower hemoglobin (8.3±0.3 vs 9.2±0.3 g/dL, P=0.04); however, there was no difference in TRV, LV mass, LV diameter or reticulocyte count between groups. 6MWD correlated significantly with the diastolic measures E/A and septal e’/a’ (P=0.013 and P=0.015, respectively). Patients with albuminuria had significantly shorter 6MWD (1182±78 vs 1472±86 ft, P=0.018). Abstract source

Background: Chronic inflammation, coagulation activation and oxidative stress are increasingly recognized as the major determining factors of acute and chronic clinical manifestations of sickle cell disease (SCD). Several lines of evidence indicate that the anti-inflammatory, anti-aggregatory and anti-oxidant long chance omega-3 fatty acids (n-3) could be a safe and effective modifying therapy for SCD. Objectives: To demonstrate the clinical and biochemical effects of n-3 fatty acids (DHA and EPA) treatment on SCD. Design/Method: One hundred forty patients with homozygous SCD (aged 2-24) were randomly assigned and received, daily, 1 (age 2–4 y), 2 (age 5–10 y), 3 (age 11–16), or 4 (age >17 y) omega-3 capsules containing 277.8 mg docosahexaenoic (DHA) and 39.0 mg eicosapentaenoic (EPA) or placebo for 1 year. The rates of clinical vaso-occlusive crisis, hemolytic events, blood transfusion rate, were assessed. The effect of n-3 treatment on markers of inflammation, blood cells adhesion, oxidative stress, coagulation and intravascular hemolysis was investigated. Results: Omega-3 treatment reduced the median rate of clinical vaso-occlusive events (P> 0.0001), severe anemia (P > 0.05), blood transfusion (0.05), white blood cell count (P> 0.05), plasma lactate dehydrogenase (LDH) , nuclear factor-kappa B (NF-κB) gene expression in buffy coat, expression of monocyte integrin and D-dimer (p>0.05). Omega-3 fatty acid group had significantly higher vitamin E plasma levels. Treatment with n-3 had no significant effect on plasma hs-CRP and plasma plasma tumor necrosis factor-α (TNF-α), (p>0.05). Conclusion: These findings suggest that treatment with omega-3 fatty acids can be an effective therapeutic option for patents with sickle cell disease. Abstract source

Splenectomy is the mainstay of long-term management of sickle cell disease (SCD) patients with frequent splenic sequestration crisis. However, it exposes patients to increased risk of infections, which remain major concern for both patients and clinicians. Dendritic cells (DC) play a key role in priming immune responses against infections. To date, limited information is available about DC subsets and their clinical relevance in splenectomised children with SCD. A total of 57 SCD children who underwent open splenectomy were prospectively enrolled. Twenty eight age- and sex-matched healthy children were recruited as controls. The indication of splenectomy was based on the history of patients, clinical examination, hematological and radiological findings. The circulating DC subsets including plasmacytoid DC (pDC) and myeloid DC (mDC) were phenotypically identified by the expression of HLA-DR, CD123, CD11c, Lin and CD1d surface markers using 8-color flow cytometry. The B cell subsets were characterized by the positive staining with CD19, CD24 and CD38 surface markers. Comparisons among study groups were performed using unpaired t test, while the Spearman’s correlation was used to assess associations. Compared to healthy controls, splenectomised children exhibited significantly lower levels of pDC (P=0.02). Similarly, levels of mDC were significantly reduced in splenectomised children compared to healthy controls (0.009). Interestingly, levels of pDC expressing CD1d, a non-classical molecule that is critical for generating cytokines from innate cells, were significantly reduced in splenectomised children compared to healthy controls (P<0.001). Levels of memory B cells, but not total and naïve B cells, were also significantly lower in splenectomised children compared to healthy controls (P=0.02). The levels of pDC and mDC were weakly associated with memory B cells (r=0.41, P=0.04), but not with age, total hemoglobin levels at phlebotomy, baseline haemoglobin F, time since splenectomy, hydroxyurea therapy and clinical severity. Abstract source

A recent article in the New England Journal of Medicine presented the results of a phase 2 clinical trial that found positive results for the efficacy and safety of crizanlizumab, a novel pharmaceutical agent currently in pipeline development by Selexys Pharmaceuticals. The drug, designed to block the underlying mechanism of acute painful crisis in patients suffering from sickle-cell disease, could be one of the first and most effective medications of its kind. For all the details on the Phase 2 research, read the original Practical Pain Management report. In this commentary, Leonard B. Goldstein, DDS, PhD, and colleagues review the research and provide their own opinion on the prospect of a novel pharmaceutical agents for patients suffering from sickle cell disease.   Abstract source

Beatrice Gee, M.D., FAAP is an interim associate director for translational science in Cardiovascular Research Institute. She is the the Professor of Pediatrics at Morehouse School of Medicine in Atlanta, Georgia, and practices medicine at the Georgia Sickle Cell Center at Grady Hospital. In 2003 she received a major grant to study the arterial narrowing in sickle cell disease that can cause strokes in young children. Dr. Gee’s lab focuses on dissecting mechanisms leading to cerebral artery stenosis in young children with sickle cell anemia. Specialties: - Sickle Cell - Hematology - Oncology Online profile

Jerlym S. Porter is an Associate Member of Psychology in St. Jude Children's Research Hospital. Education: MPH – Northwestern University PhD – Virginia Commonwealth University MS – Virginia Commonwealth University BA – University of Virginia Research Interests: - Issues related to the transition process from pediatric care to adult care for patients with sickle cell disease - Psychosocial factors impacting health promotion, treatment adherence and disease management Online profile

Katie Wu is a Clinical Research Coordinator at Policy Lab at Children’s Hospital of Philadelphia (CHOP). She works as a qualitative and quantitative research team member on several program evaluation projects, including an evaluation of a new therapeutic model for improving parental-child attachment for mothers enrolled in substance use treatment programs. Ms. Wu previously worked as a community health worker for CHOP’s adult care and transition team where she worked with patients who were transitioning from pediatric to adult care to build their self-management and self-advocacy skills. She also previously worked on several transition to adulthood research and quality improvement projects. Katie received her bachelor’s degree in biology and her Master of Public Health from University of Pennsylvania.   Online profile

James Eckman, MD, is emeritus professor of the Department of Hematology and Medical Oncology and held appointments as professor of medicine and adjunct professor of pediatrics in medical genetics at Emory University School of Medicine. He was committed to establishing a sickle cell program at Grady Memorial Hospital, and after intensive state lobbying for funding in 1984, became medical director of the world's first 24-hour comprehensive acute care sickle cell center. Dr. Eckman's other interest is in public health services for individuals with genetic diseases. He has championed newborn screening for sickle cell disease on a local and national level. His work has saved the lives of many sickle cell children who would have died from pneumococcal sepsis if timely preventive care with oral penicillin prophylaxis was not started. He serves as a member of several local and national committees and acts as an advocate to continue awareness and support of these programs. Dr. Eckman has broad research experience in basic science, translational research, clinical research and clinical trials. These have included studies of red cell metabolism; sickle erythrocyte endothelial interactions; coagulation activation with sickle complications; psychological and social complications from sickle cell disease; drug and chemotherapy of sickle complications; pain assessment and management; and bone marrow transplantation in sickle disease. Online profile

Dr. Raymona Lawrence serves as the Director of Research for the Sickle Cell Community Consortium. She has dedicated her career to community engagement and the elimination of health inequities and health disparities as they relate to African Americans living in rural populations—especially those with chronic diseases such as sickle cell disease. Her research and practice focus on discovering how healthcare delivery systems, public health, formal and informal community organizations, and participants come together to more effectively address health inequities/disparities in rural areas as well as how research related to community capacity can contribute to addressing health disparities.Dr. Lawrence is currently serving as an Assistant Professor of Community Health in the Jiann Ping Hsu College of Public Health at Georgia Southern University (GSU). Dr. Lawrence holds both a DrPH in Community Health Behavior and Education and an MPH in Community Health from GSU. Online profile