Elliott Vichinsky, MD diagnoses and treats children with blood disorders, cancers and tumors. He founded and directs the largest hemoglobinopathy center of sickle cell disease and thalassemia in North America. The center is dedicated to developing therapy to treat and cure the 200,000 infants born worldwide each year with sickle cell or thalassemia. He has been instrumental in implementing newborn screening programs for blood diseases in California and throughout the world. He is working with the World Health Organization in studying the worldwide public health problem of thalassemia and sickle cell disease. Dr. Vichinsky was responsible for the development of the Blood and Marrow Transplantation Program, which has cured hundreds of children who had sickle cell anemia, thalassemia, and various cancers. He has developed techniques that make blood safer for chronically transfused patients. These patients often suffer from iron overload as a result of either transfusion therapy or genetic mutations. Iron overload causes thousands of deaths each year. Dr. Vichinsky has been an international leader in developing drugs to remove excess iron and non-invasive equipment to measure iron in the body. Online profile

Background: The sickling of red blood cells causes a constellation of musculoskeletal, cardiovascular, and pulmonary manifestations. A 32-year-old gentleman with sickle cell anemia (SCA) had been suffering from recurrent acute chest syndrome (ACS). Aim. To examine the effects of inspiratory muscle training (IMT) on pulmonary functions, respiratory and peripheral muscle strength, functional exercise capacity, and quality of life in this patient with SCA. Methods: Functional exercise capacity was evaluated using six-minute walk test, respiratory muscle strength using mouth pressure device, hand grip strength using hand-held dynamometer, pain using Visual Analogue Scale, fatigue using Fatigue Severity Scale, dyspnea using Modified Medical Research Council Scale, and health related quality of life using European Organization for Research and Treatment of Cancer QOL measurement. Results: A significant improvement has been demonstrated in respiratory muscle strength, functional exercise capacity, pain, fatigue, dyspnea, and quality of life. There was no admission to emergency department due to acute chest syndrome in the following 12 months after commencing regular erythrocytapheresis. Conclusion: This is the first report demonstrating the beneficial effects of inspiratory muscle training on functional exercise capacity, respiratory muscle strength, pain, fatigue, dyspnea, and quality of life in a patient with recurrent ACS. Abstract source Full text Full text (PMC)

Cynthia Gipson is a family advocate for sickle cell disease at Howard University Hospital, Pediatric & Child Health. Online profile

Dr. Howard is Professor of Pediatrics and Director of Hematology Section at University of Alabama. Dr. Howard hails from North Carolina, graduated from the University of North Carolina at Chapel Hill in Chemistry, and received his MD degree from the Johns Hopkins University School of Medicine (JHUSOM). Dr. Howard's primary clinical interest is general hematology with a focus on sickle cell disease (SCD), hemophilia and red and white blood cell defects. Dr. Howard's research career interests and experience include an NIH funded basic research program focused on assembly and regulation of the molecular motor in neutrophils; his clinical research focuses on neurological abnormalities, health care delivery, and novel therapies for SCD.  Currently he is institutional PI for NHLBI studies (The Baby Hydroxyurea Trial, Co-PI on the JHU/UAB Basic and Translational Research Program, The JHU Priapism Project), NINDS grants (The Silent Infarct Transfusion Trial, Hydroxyurea for Silent Infarcts in Sickle Hemoglobinopathies), and HRSA projects (Sickle Cell Treatment Demonstration Project) and industry sponsored trials of a novel pneumococcal vaccine. He, in collaboration with Lee Hilliard MD, founded and developed the Children and Youth Sickle Network (The CYSNTM), a network of regional, comprehensive SCD clinics focused on prevention of SCD morbidity and mortality. Online profile

Dr. Paschal is Associate Professor of medicine and Program Director of hematology/oncology fellowship program at UAB School of Medicine. She received her medical degree from the University of South Florida in Tampa. Dr.  Paschal completed her Internal Medicine Residency and her Hematology/Oncology Fellowship training at Vanderbilt University Medical Center in Nashville. Her main focus is on benign hematology including coagulation and sickle cell disease. Specialties- Hematology/Oncology Conditions and Treatments-

• Acute Myelogenous Leukemia
• Chronic Lymphocytic Leukemia (CLL)
• Chronic Myelogenous Leukemia
• Hemoglobinopathies
• Hemostasis
• Infusion Therapy
• Non-Malignant Hematology
• Thrombosis

  Online profile

OBJECTIVE: This qualitative study sought to learn from young adults with sickle cell disease (SCD) about their experience leaving pediatric care and perspective on what makes a successful transition. METHODS: Fifteen young adults with SCD who had left pediatric care within the previous five years participated in focus groups led by a trained moderator. Transcripts were analyzed using grounded theory. RESULTS: Four main themes emerged from the analysis: facilitators of transition (meeting the adult provider prior to transfer, knowing what to expect, gradually taking over disease self-management and starting the process early), barriers to transition (negative perceived attitude of adult staff, lack of SCD specific knowledge by both patients and staff, and competing priorities interfering with transition preparation), what young adults wished for in a transition program (opportunities to meet more staff prior to transfer, more information about the differences between pediatric and adult care, learning from a peer who has been through the process, more SCD teaching, and flexibility in transition preparation) and how they define a successful transition (gradually assuming responsibility for self-management of their SCD). CONCLUSION: Our findings present unique opportunities to learn from young adults with SCD about ways to improve current transition programs. Abstract source Full text Full text (PMC)

BACKGROUND: A high level of evidence exists to suggest that negative attitudes held by clinicians toward persons with sickle cell disease serve as important barriers to the delivery of high quality care to this patient population. Little is known, though, about the characteristics of clinicians that may be predictive of these negative attitudes. METHODS: During spring and summer 2009, we conducted a randomized controlled trial to test an intervention to improve clinician attitudes toward persons with sickle cell disease. Participating clinicians completed questionnaires regarding their demographic characteristics and their attitudes toward sickle cell patients. Principal clinician characteristics of interest included their race, professional discipline (nurse/physician), and the amount of their recent exposure to sickle cell patients in pain. Secondary analyses from this trial are presented here. MAIN FINDINGS: Asian clinicians reported more negative attitudes towards these patients than did Black or White clinicians, nurses reported more negative attitudes than physicians, and clinicians with the greatest levels of recent exposure to sickle cell patients in pain reported more negative attitudes than did clinicians with lower levels of recent exposure. CONCLUSIONS: Our findings could facilitate the development of tailored educational resources needed to improve the quality of care delivered to persons with sickle cell disease, a national priority for sickle cell efforts. Abstract source Full text

Although the primary origin of sickle cell disease is a hemoglobin disorder, many types of cells contribute considerably to the pathophysiology of the disease. The adhesion of neutrophils to activated endothelium is critical in the pathophysiology of sickle cell disease and targeting neutrophils and their interactions with endothelium represents an important opportunity for the development of new therapeutics. We focused on endothelin-1, a mediator involved in neutrophil activation and recruitment in tissues, and investigated the involvement of the endothelin receptors in the interaction of neutrophils with endothelial cells. We used fluorescence intravital microscopy analyses of the microcirculation in sickle mice and quantitative microfluidic fluorescence microscopy of human blood. Both experiments on the mouse model and patients indicate that blocking endothelin receptors, particularly ETB receptor, strongly influences neutrophil recruitment under inflammatory conditions in sickle cell disease. We show that human neutrophils have functional ETB receptors with calcium signaling capability, leading to increased adhesion to the endothelium through effects on both endothelial cells and neutrophils. Intact ETB function was found to be required for tumor necrosis factor α-dependent upregulation of CD11b on neutrophils. Furthermore, we confirmed that human neutrophils synthesize endothelin-1, which may be involved in autocrine and paracrine pathophysiological actions. Thus, the endothelin-ETB axis should be considered as a cytokine-like potent pro-inflammatory pathway in sickle cell disease. Blockade of endothelin receptors, including ETB, may provide major benefits for preventing or treating vaso-occlusive crises in sickle cell patients. Abstract source Full text Full text (PMC)

Overt ischaemic stroke is one of the most devastating complications in children with sickle cell disease (SCD). The compensatory response to anaemia in SCD includes an increase in cerebral blood flow (CBF) by accessing cerebrovascular dilatory reserve. Exhaustion of dilatory reserve secondary to anaemic stress may lead to cerebral ischaemia. The purpose of this study was to investigate CBF and cerebrovascular reactivity (CVR) using magnetic resonance imaging (MRI) in children with SCD and to correlate these with haematological markers of anaemia. Baseline CBF was measured using arterial spin labelling. Blood-oxygen level-dependent MRI in response to a CO2 stimulus was used to acquire CVR. In total, 28 children with SCD (23 not on any disease-modifying treatment, 5 on chronic transfusion) and 22 healthy controls were imaged using MRI. Transfusion patients were imaged at two time points to assess the effect of changes in haematocrit after a transfusion cycle. In children with SCD, CBF was significantly elevated compared to healthy controls, while CVR was significantly reduced. Both measures were significantly correlated with haematocrit. For transfusion patients, CBF decreased and CVR increased following a transfusion cycle. Lastly, a significant correlation was observed between CBF and CVR in both children with SCD and healthy controls. Abstract source Full text

BACKGROUND: We tried to understand whether or not there are lowered prevalences of terminal consequences of sickle cell diseases (SCDs) with tonsilectomy. METHODS: All cases with SCDs were taken into the study. RESULTS: The study included 334 patients (164 females). There were 27 cases with tonsilectomy and 307 cases without. The mean ages, female ratios, and prevalences of associated thalassemia minors and smoking were similar in both groups (P>0.05 for all). Although the white blood cell and platelet counts of peripheric blood were higher in patients without tonsilectomy, the mean hematocrit value was lower in them, but the differences were nonsignificant probably due to the small sample size of the tonsilectomy group (P>0.05 for all). Similarly, although the painful crises per year, digital clubbing, leg ulcers, pulmonary hypertension, chronic obstructive pulmonary disease, rheumatic heart disease, avascular necrosis of bone, cirrhosis, stroke, and mortality were higher in cases without tonsilectomy, the differences were nonsignificant probably due to the same reason again (P>0.05 for all). CONCLUSION: There may be an inverse relationship between prevalence of tonsilectomy and severity of SCDs, and the tonsils may act as chronic inflammatory foci accelerating the chronic endothelial damage all over the body in such patients. Abstract source Full text