Background: The exact causes of intracranial aneurysms (IAs) are still unknown. However, certain diseases are known to be associated with IAs. Objective: To analyze the differences in IA characteristics in the general population and in individuals with sickle-cell disease (SCD). Methods: We systematically searched PubMed, Scopus, Web of Science, and Cochrane Library for Data on SCD patients with IAs. We compared IA characteristics of SCD patients with those from 2451 healthy IA carriers from our observational cohort. Results: 129 SCD patients with IAs were identified in 42 studies. The SCD patient cohort was characterized by younger age (mean 27.1 vs 54.9 years, p<0.0001) and lower female prevalence (57.7% vs 68.4%, p=0.0177). The prevalence (47% vs 34.5%, p=0.004) and the number (3.02 vs 2.56 IAs/patient, p=0.004) of multiple IAs were also higher in the SCD cohort. Unruptured IAs (3.27 vs 6.16 mm, p<0.0001), but not ruptured IAs (7.8 vs 7.34 mm, p=0.9086) were significantly smaller in the SCD cohort. In addition, IAs were more frequently located in the internal carotid artery (45% vs 29%, p<0.0001) or posterior circulation (43% vs 20%, p<0.0001). Higher age (>=30 years, p=0.007), IA size >=7 mm (p=0.008), and location in posterior circulation (p=0.01) were independently associated with subarachnoid hemorrhage in SCD. Conclusion: There is a distinct demographic and radiographic pattern of IA in SCD. Risk factors for IA rupture in SCD are mostly congruent with those in healthy individuals. Abstract source

Background: Acute vaso-occlusive pain episodes in sickle cell disease (SCD) are associated with increased rates of hospitalization and early mortality. Despite the observation that women have higher rates of acute vaso-occlusive pain episodes than men, sex-specific risk factors for acute vaso-occlusive pain have not been identified. We tested the hypothesis that acute vaso-occlusive pain is temporally associated with the onset of menstruation in women with SCD. Methods: Initially, using a cross-sectional study design, we administered questionnaires, including validated measures of SCD pain frequency and severity within the last 30 days, as well as menstrual symptoms in a discovery group (n = 103). We then confirmed our findings by administering the same questionnaires online in a replication group (n = 118). A validated questionnaire was used to define dysmenorrhea. Results: In the initial discovery group, 28% (29 of 103) reported acute vaso-occlusive pain episodes temporally associated with menstruation, and 72% (74 of 103) did not. Of the 29 reporting acute vaso-occlusive pain associated with menstruation, 90% (26) and 10% (3) did and did not meet criteria for dysmenorrhea, respectively. In the replication group, 36% (43 of 118) reported acute vaso-occlusive pain temporally associated with menstruation. Of the 43 reporting acute vaso-occlusive pain associated with menstruation, 60% (26) and 40% (17) did and did not meet criteria for dysmenorrhea, respectively. Conclusions: In both the discovery and replication groups, we demonstrate that acute vaso-occlusive pain is temporally associated with the onset of menstruation that women with SCD can distinguish from dysmenorrhea. Abstract source

Background: Children with Sickle Cell Disease (SCD) show endocrine complications and metabolic alterations. The physiopathology of these conditions is not completely understood: iron overload due to chronic transfusions, ischemic damage, and inflammatory state related to vaso-occlusive crises may be involved. Aims of this study were to evaluate the growth pattern, endocrine complications, and metabolic alterations and to detect the relationship between these conditions and the SCD severity in affected children and adolescents. Methods: Fifty-two children and adolescents with SCD [38 homozygous sickle hemoglobin (HbSS) and 14 heterozygous sickle hemoglobin (HbSC); age range 3-18 years] were recruited. Anthropometric [height, body mass index (BMI), arm span, sitting height, target height (TH), and pubertal status] and laboratory [blood cell counts, hemolysis indices, metabolic and nutritional status indices and hormonal blood levels] data were evaluated. The SCD severity was defined according to hematological and clinical parameters. Results: Height-SDS adjusted for TH and BMI-SDS were significantly higher in HbSC children than in HbSS ones. Forty-eight out of 52 patients (92%) had at least one metabolic and/or endocrine alteration: insufficiency/deficiency of vitamin D (84.7%), insulin resistance (11.5%), growth hormone deficiency (3.8%), subclinical hypothyroidism (3.8%), and hypogonadism (1.9%). Levels of vitamin D were significantly and negatively correlated with clinical indicators of the SCD severity. Subjects with HbSS genotype show significant lower levels of both insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein 3 than children with HbSC. In the study population IGF-1 values were significantly and positively correlated with Hb and negatively with lactate dehydrogenase. Conclusions: Metabolic alterations and endocrine complications are very common in children and adolescents with SCD. A regular follow-up is necessary to identify subjects at risk for complications to precociously start an appropriate treatment and to improve the quality of life of SCD patients. Abstract source Full text

Sickle cell disease (SCD), an inherited blood disorder that primarily affects individuals of African descent, is associated with serious medical complications as well as numerous social-environmental risk factors. These social-environmental factors are linked to long-standing social inequities, such as financial hardship and racial discrimination, both of which impact cognitive and behavioral functioning in youth. Previous research on the relationship between social-environmental risk and psychological functioning has primarily relied on non-modifiable, unidimensional measures of socioeconomic status (SES), such as income and parental education, as a proxy for social-environmental risk. The current study aimed to address the limitations associated with typical SES-type measures by comparing the unique and shared association of SES and more targeted and modifiable social-environmental factors (e.g., parent and family functioning) with specific areas of cognitive and behavioral adjustment in pediatric SCD. Seventy children ages 4-8 years old and their parents completed measures of social-environmental risk and psychological adjustment. Exploratory factor analysis indicated parent and family functioning measures were largely independent of SES. Parent and family functioning predicted phonological processing and ADHD symptoms above and beyond SES alone. In addition, the predictive ability of social-environmental risk factors appears to vary by genotype severity for measures of social functioning and math problem-solving ability. Future studies are needed to explore more specific and well-supported models of modifiable social-environmental risk and the relative impact of social-environmental risk on cognitive and behavioral functioning. Abstract source

Objectives: Women with sickle cell disease (SCD) are living longer as a result of advances in the care of their underlying disease. With the population growing of women living with SCD, reproductive health issues in this population have become an emphasized area of medical care. We sought to describe current patterns of contraception use, menstruation, and quality-of-life (QOL) measures in women with SCD. Methods: Using a cross-sectional study design, we administered paper surveys at two academic medical centers to women aged 10 to 55 years with SCD to capture current contraceptive use, characteristics of menstrual cycles, and QOL metrics. Results: Of the 103 women who participated, 12.7% (13/102) experienced a duration of menses >7 days (defined here as prolonged menstrual bleeding). Approximately half of women (51.5%, 53/103) used some form of contraception, with depot medroxyprogesterone acetate injections and condoms being the most common. During their last menstrual periods, women with both dysmenorrhea and prolonged menstrual bleeding (6.9%, 7/102) were more likely to experience more days of poor QOL, with more nights with sleep disturbance (P = 0.001) and more days with trouble taking care of themselves (P = 0.003), as well as being unable to do things they previously enjoyed (P = 0.001), compared with those with neither phenomenon (28.2%, 29/103). Conclusions: Dysmenorrhea and prolonged menstrual bleeding negatively affect the QOL of women with SCD. Menstrual histories and preventive measures for menstruation-related morbidity should be incorporated into routine evaluations of women with SCD. Abstract source

Objective: More effective transitions and transfers of young people with sickle cell disease (SCD) into the adult healthcare setting is a focus of both primary care and specialty care medical organizations. Effective transition and transfer requires six core elements: establishing a policy, tracking progress, administering transition readiness assessments, planning for adult care, transferring to adult care, and integrating into an adult practice. We developed a program using these six core elements. The objective of our report was to assess the development and implementation of this program. Methods: We used the six core elements to develop and implement a program at Virginia Commonwealth University for children and adolescents with SCD to transition to adult health care. Results: We assessed individuals' differences by age and grade, their independent living skills, their feelings about moving to adult care; tallied and analyzed several assessment scales; and assessed transfer success and patient retention. Conclusions: The principles and lessons we learned in developing and implementing this program over 5 years, accompanied by caring, flexible, and dedicated care team members, often can overcome even severe barriers to care transitions. Abstract source

Importance: In children with sickle cell anemia (SCA), high transcranial Doppler (TCD) velocities are associated with stroke risk, which is reduced by chronic transfusion. Whether matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) can reduce velocities in patients with SCA is unknown. Objective: To determine the association of MSD-HSCT with TCD velocities as a surrogate for the occurrence of ischemic stroke in children with SCA. Design, Setting, and Participants: Nonrandomized controlled intervention study conducted at 9 French centers. Patients with SCA were enrolled between December 2010 and June 2013, with 3-year follow-up ending in January 2017. Children with SCA were eligible if younger than 15 years, required chronic transfusions for persistently elevated TCD velocities, and had at least 1 sibling without SCA from the same 2 parents. Families agreed to HLA antigen typing and transplantation if a matched sibling donor was identified or to standard care in the absence of a matched sibling donor. Exposures: MSD-HSCT (n = 32), compared with standard care (n = 35) (transfusions for ≥1 year with potential switch to hydroxyurea thereafter), using propensity score matching. Main Outcomes and Measures: The primary outcome was the highest time-averaged mean of maximum velocities in 8 cerebral arteries, measured by TCD (TCD velocity) at 1 year. Twenty-five of 29 secondary outcomes were analyzed, including the highest TCD velocity at 3 years and normalization of velocities (<170 cm/s) and ferritin levels at 1 and 3 years. Results: Sixty-seven children with SCA (median age, 7.6 years; 35 girls [52%]) were enrolled (7 with stroke history). In the matched sample, highest TCD velocities at 1 year were significantly lower on average in the transplantation group (129.6 cm/s) vs the standard care group (170.4 cm/s; difference, -40.8 cm/s [95% CI, -62.9 to -18.6]; P < .001). Of the 25 analyzed secondary end points, 4 showed significant differences, including the highest TCD velocity at 3 years (112.4 cm/s in the transplantation group vs 156.7 cm/s in the standard care group; difference, -44.3 [95% CI, -71.9 to -21.1]; P = .001); normalization rate at 1 year (80.0% in the transplantation group vs 48.0% in the standard care group; difference, 32.0% [95% CI, 0.2% to 58.6%]; P = .045); and ferritin levels at 1 year (905 ng/mL in the transplantation group vs 2529 ng/mL in the standard care group; difference, -1624 [95% CI, -2370 to -879]; P < .001) and 3 years (382 ng/mL in the transplantation group vs 2170 ng/mL in the standard care group; difference, -1788 [95% CI, -2570 to -1006]; P < .001). Conclusions and Relevance: Among children with SCA requiring chronic transfusion because of persistently elevated TCD velocities, MSD-HSCT was significantly associated with lower TCD velocities at 1 year compared with standard care. Further research is warranted to assess the effects of MSD-HSCT on clinical outcomes and over longer follow-up. Abstract source

Dr. Hatoon Ezzat received her medical degree in 1995, and pursued specialist training in internal medicine and hematology. She obtained certification in internal medicine and hematology from the American Board of Internal Medicine (ABIM) and is a fellow of the Royal College of Physicians and Surgeons of Canada. She plays an active role in clinical research, and her major medical interests are hemoglobinopathies, including thalassemia and sickle-cell anemia. Dr. Hatoon Ezzat had obtained Master of Science in Hemoglonbinopathy from University College London in England and currently is the director of the Provincial Adult Hemoglobinopathy Program of British Columbia and the director of the Provincial Home Hemosiderosis (Iron Chelation) Program of British Columbia. She is associated with University of British Columbia as a Clinical Assistant Professor. Dr. Hatoon Ezzat plays an active role in clinical research. She had published in the field of Lymphoma and HIV and her most recent work is on liver iron overload and iron chelation therapy.   Representative Publications: Utility of Transient Elastography in Estimating Hepatic Iron Concentration in Comparison to Magnetic Resonance Imaging in Patients Who are Transfusion-Dependent: A Canadian Center Experience Improved survival in HIV-associated diffuse large B-cell lymphoma with the addition of rituximab to chemotherapy in patients receiving highly active antiretroviral therapy Improved survival in red blood cell transfusion dependent patients with primary myelofibrosis (PMF) receiving iron chelation therapy HIV-Associated Burkitt Lymphoma: Good Efficacy and Tolerance of Intensive Chemotherapy Including CODOX-M/IVAC with or without Rituximab in the HAART Era Online profile

Dr. Stephen Nelson completed his Board Certification in Hematology and Oncology, Pediatric from American Board of Pediatrics. He attended medical school and completed his pediatric residency at Eastern Virginia Medical School in Norfolk, Virginia. His pediatric hematology/oncology fellowship was completed at Duke University Medical Center in Durham, North Carolina. He joined the hematology/oncology program at Children's of Minnesota in 1993. He is the co-director of the Vascular Anomalies Center. His interests include caring for patients with sickle cell disease and working to decrease racial health care disparities.   Representative Publications: Graph theory analysis reveals how sickle cell disease impacts neural networks of patients with more severe disease Hydroxyurea use in young infants with sickle cell disease Whole blood tissue factor procoagulant activity is elevated in patients with sickle cell disease Weekend very high-dose intravenous deferoxamine in children with transfusional iron overload Emergency management of sickle cell disease complications: review and practice guidelines Online profile

La anemia falciforme es un trastorno heredado que afecta las células rojas de la sangre. La anemia falciforme afecta a más de 72.000 personas en los Estados Unidos. La mayoría de los afectados son africano-americanos pero otros tienen antepasados árabes, asiáticos, caribeños, indios y mediterráneos además de sudamericanos y centroamericanos. Las formas más comunes de anemia falciforme son talasemia SS, talasemia SC y talasemia beta S. Otras formas, más raras, incluyen la enfermedad SD-Punjab, SO-Árabe, S-Lepore y SE. La anemia falciforme es una condición de por vida y puede provocar problemas graves de salud. Las complicaciones pueden incluir episodios de dolor que se llaman crisis, anemia (cuando falta hemoglobina), daño a los órganos, infecciones, problemas con los pulmones, úlceras en las piernas, daño a los huesos y ataques cerebrales.   Abstract source