Objective: The prevalence of type 2 diabetes (T2D) is rapidly increasing in sub-Saharan Africa, where sickle cell trait (SCT) is also frequent. Although SCT is generally considered a benign condition, evidence suggests that SCT could exaggerate vascular dysfunction in T2D. However, it remains unclear whether SCT could increase the risk of the development of T2D complications. Therefore, this study was conducted to determine whether T2D complications were more prevalent among Senegalese individuals with SCT and T2D than among those with T2D only. Research Design and Methods: Rates of hypertension, retinopathy, peripheral neuropathy, peripheral artery disease, and impaired renal function as well as arterial stiffness, blood rheology, and concentrations of plasma advanced glycation end products (AGEs) and cytokines were compared between groups of Senegalese individuals with combined SCT and T2D (T2D-SCT) (n = 60), T2D (n = 52), SCT (n = 53), and neither T2D nor SCT (control) (n = 56). Human aortic endothelial cell (HAEC) expression of inflammatory and adhesion factors was measured after treatment with tumor necrosis factor-α and subjects' plasma. Effects of AGE inhibition or tiron on HAEC expression of E-selectin were measured. Results: Retinopathy, hypertension, and reduced renal function were more prevalent, and arterial stiffness, blood viscosity at high shear rates, and thixotropic index were higher, in the SCT group compared with the other groups. Multivariable analysis showed that plasma AGE concentration was significantly associated with arterial stiffness. E-selectin expression was elevated in HAECs treated with T2D-SCT plasma compared with the other groups, but AGE inhibition reversed this. Conclusions: SCT could potentially augment the risk of the development of T2D-related complications, including retinopathy, nephropathy, and hypertension. Abstract source Full text

Sickle Cell Disease (SCD) is an increasing global health problem and presents significant challenges to European health care systems. Newborn screening (NBS) for SCD enables early initiation of preventive measures and has contributed to a reduction in childhood mortality from SCD. Policies and methodologies for NBS vary in different countries, and this might have consequences for the quality of care and clinical outcomes for SCD across Europe. A two-day Pan-European consensus conference was held in Berlin in April 2017 in order to appraise the current status of NBS for SCD and to develop consensus-based statements on indications and methodology for NBS for SCD in Europe. More than 50 SCD experts from 13 European countries participated in the conference. This paper aims to summarise the discussions and present consensus recommendations which can be used to support the development of NBS programmes in European countries where they do not yet exist, and to review existing programmes. Abstract source Full text

Objective: Due to incomplete management of vaso-occlusive pain episodes (VOE) in patients with sickle cell disease (SCD), we sought to determine if immersive VR would be feasible for inpatients. Secondarily, we hypothesized that a single VR session would improve the VOE pain experience. Procedures: Consecutive patients with SCD eight years and older admitted for VOE were offered one 15-minute VR session, utilizing a relaxing underwater world specifically created for pediatric patients and to minimize potential simulator side effects. Safety and acceptability were evaluated with a brief survey before and after the session. Pain was evaluated utilizing the validated adolescent pediatric pain tool (APPT). Survey data and pain scores were analyzed using Wilcoxon signed-rank test as the data were nonnormally distributed. Results: Thirty patients, 21 female, with a median age of 16 years were enrolled, the majority having hemoglobin SS disease. The VR session had no reported side effects; all patients requested VR again in the future. Median pain intensity (pre-VR 7.3 [interquartile range, IQR, 6.1, 8.8], post-VR 5.8 [4.7, 7.9]), number of affected body areas (pre-VR 3.0 [2.0, 7.8], post-VR 2.0 [0, 4.8]), and qualitative measures including sensory, affective, evaluative, and temporal pain domains were all statistically reduced (i.e., P =<0.01). Conclusions: VR therapy was feasible in a cohort of patients with SCD admitted for VOE. In addition to standard therapies, VR may help reduce the pain experience with SCD VOE. Further study is required to determine the impact of VR therapy on opioid usage and length of stay in hospital. Abstract source Full text

Swee Lay Thein is the Chief of the Sickle Cell Branch of the National Heart, Lung, and Blood Institute, NIH. She was educated in both Malaysia and the United Kingdom. She completed her specialist training in hematology at the U.K. Royal Postgraduate Medical School, Hammersmith, and the Royal Free Hospital, London. In 1982, she joined the U.K. Medical Research Council Molecular Hematology Unit in Oxford where she held various positions, including clinical training fellow, Wellcome Senior Fellow in Clinical Science, senior clinical scientist, and honorary consultant hematologist. Dr. Thein was appointed in 2000 to the position of professor of molecular hematology and consultant hematologist at King’s College London, and served as clinical director of the Red Cell Centre in King’s College Hospital. Dr. Thein joined the NHLBI in spring 2015 as Senior Investigator and Chief of the institute’s newly formed Sickle Cell Branch. Dr. Thein was Chair of the European Hematology Association’s scientific working group for red blood cells and iron disorders from 2011–2014 and has also has been instrumental in organizing scientific and educational conferences on red blood cell disorders for the European Hematology Association and European School of Hematology. Dr. Thein’s research explores the underlying genetic mechanisms affecting the formation of fetal hemoglobin, which could lead to new ways to reduce the severity of sickle cell disease complications, including pain.   Representative Publications: Intergenic variants of HBS1L-MYB are responsible for a major quantitative trait locus on chromosome 6q23 influencing fetal hemoglobin levels in adults Voxelotor treatment of a patient with sickle cell disease and very severe anemia HBS1L-MYB intergenic variants modulate fetal hemoglobin via long-range MYB enhancers Online profile

Dr. Benz graduated from Harvard Medical School in 1973 and received his training at Brigham and Women's Hospital and the National Institutes of Health. He is president and CEO emeritus of Dana-Farber Cancer Institute, director emeritus and principal investigator of Dana-Farber/Harvard Cancer Center, and a member of the Governing Board of Dana-Farber/Children's Cancer Center. He is also a clinical hematologist and an active NIH-funded investigator. He is the Richard and Susan Smith Distinguished Professor of Medicine, Professor of Pediatrics, Professor of Genetics, Harvard Medical School. Dr. Benz is an internationally recognized hematologist and an active National Institutes of Health-funded Investigator. His laboratory studies focus on molecular regulation and functions of membrane cytoskeletal proteins that were originally discovered in the red blood cell. He has authored more than 300 peer reviewed articles, reviews, chapters, and abstracts. He is Co-editor of “Hematology: Principles and Practice,” which received the First Place Award for Textbooks from the British Medical Journal and of the “Oxford Textbook of Medicine,” for which he and his colleagues received the Royal Society of Authors Textbook Award. He is an Associate Editor of the New England Journal of Medicine.   Representative Publications: Molecular genetics of the sickling syndromes: evolution of new strategies for improved diagnosis Protein 4.1R Exon 16 3' Splice Site Activation Requires Coordination among TIA1, Pcbp1, and RBM39 during Terminal Erythropoiesis Newborn screening for α-thalassemia--keeping up with globalization An erythroid differentiation-specific splicing switch in protein 4.1R mediated by the interaction of SF2/ASF with an exonic splicing enhancer Learning about genomics and disease from the anucleate human red blood cell Online profile

Clayton Andrews is a 35-year-old patient with Sickle Cell Disease, residing in Augusta GA. Clayton is an LAPC and graduate from Troy University with a Master of Science in Counseling and Psychology. He is currently completing his licensure as a behavioral health counselor, as well as pursuing his Doctorate to further expand his effectiveness. He and his wife of eight years have three daughters, all of whom have Sickle Cell Trait and a 12-year-old son. Clayton is the Chair and co-founder of the Sickle Cell Champions Association, a mentoring organization geared and designed for the guidance and empowerment of young males with Sickle Cell Disease into their transition into adulthood. Clayton’s ultimate objective is to become a positive influence and mentor to his peers in the Sickle Cell Community and advocating for young males with this disease. Clayton’s works include his involvement in the S.C.C.A. “Mentoring Workshop” in August 2016, Panel Presentation of the “Safety Response System, Phase I” for Georgia Department of Human Services in 2013 and self-designed training presentation of “The Proper Acquisition and Assessment of Safety Resources in Child Protective Services (2010).” Online profile

Background: Although sickle cell trait (SCT) is largely a benign carrier state, it may increase risk for certain clinical outcomes. Purpose: To evaluate associations between SCT and clinical outcomes in children and adults. Data Sources: English-language searches of PubMed, CINAHL, the Cochrane Library, Current Contents Connect, Scopus, and Embase (1 January 1970 to 30 June 2018) and bibliographies of review articles. Study Selection: Observational controlled studies (published in English) in children or adults that examined an association between SCT and any of 24 clinical outcomes specified a priori in the following 6 categories: exertion-related injury; renal, vascular, pediatric, and surgery- or trauma-related outcomes; and overall mortality. Data Extraction: A single reviewer extracted study data, which was checked by another; 2 reviewers independently assessed study quality; and strength of evidence was assessed by consensus. Data Synthesis: Of 7083 screened studies, 41 met inclusion criteria. High-strength evidence supported a positive association between SCT and risk for pulmonary embolism, proteinuria, and chronic kidney disease. Moderate-strength evidence supported a positive association between SCT and exertional rhabdomyolysis and a null association between SCT and deep venous thrombosis, heart failure or cardiomyopathy, stroke, and pediatric height or weight. Absolute risks for thromboembolism and rhabdomyolysis were small. For the remaining 15 clinical outcomes, data were insufficient or strength of evidence was low. Limitation: Publication bias was possible, and high-quality evidence was scant. Conclusion: Sickle cell trait is a risk factor for a few adverse health outcomes, such as pulmonary embolism, kidney disease, and exertional rhabdomyolysis, but does not seem to be associated with such complications as heart failure and stroke. Insufficient data or low-strength evidence exists for most speculated complications of SCT. Abstract source Full text

Background: Exercise could be a triggering factor for vaso-occlusive crises in patients with sickle-cell disease. We aimed to investigate whether a patient-adapted training programme of moderate endurance exercise could be safe and beneficial for patients with sickle-cell disease. Methods: We did a multicentre, prospective, open-label, randomised controlled trial at four university hospitals in France. Eligible patients were older than 18 years, with an HbSS or S/β0-thalassaemia genotype, and with no severe chronic complications. All patients underwent cardiopulmonary exercise tests (CPETs) on a stationary bicycle with cardiac, pulmonary, laboratory, and muscle parameter evaluations at the start and end of the study period. We randomly assigned patients (1:1) to the training group (three 45-min exercise sessions per week, for 8 weeks) or the control group (no lifestyle changes) using a central computer-generated randomisation list. During baseline evaluation, patients and researchers were masked to group assignment; randomisation was done after completion of the baseline evaluation to minimise bias. The primary outcome was difference in power output at a blood lactate concentration of 4 mmol/L during CPET between baseline and the end of the 8-week training period. Patients were analysed on a per-protocol basis, excluding those who missed more than 20% of the training sessions or had other major protocol violations. This trial is registered with ClinicalTrials.gov, number NCT02571088, and is completed. Findings: Between Sept 8, 2014, and Dec 11, 2015, 40 patients were enrolled (20 to each group). After exclusion of seven patients (one pregnancy, one appendicitis, one protocol violation, two lost to follow-up, and two incompatibilities with work schedule), 33 patients were analysed (15 in the training group, 18 in the control group). At the 8-week follow-up, the absolute change from baseline in mean power output at 4 mmol/L blood lactate was 7•2 W (SD 8•7) in trained patients (from 70•4 W [SD 16•2] at baseline to 77•6 W [15•1] at end of intervention) compared with -0•3 W (9•4) in controls (from 66•2 W [13•8] to 65•9 W [15•6]; mean difference between groups 7•3 W [95% CI 0•7-13•8], p=0•031). No adverse events requiring hospital admission occurred in the training group, whereas five occurred in the control group: four (20%) vaso-occlusive crises (one complicated by an acute chest syndrome), and one (6%) viral infection with isolated chest pain (hazard ratio 0•143 [95% CI 0•024-0•827; p=0•029). Interpretation: Moderate-intensity endurance-exercise training seems to be safe for adults with sickle-cell disease without severe chronic complications and significantly improved their functional capacity, especially for exercise levels close to those needed for daily activities. Our findings support consideration of endurance-exercise training as a novel therapeutic strategy for patients with sickle-cell disease. Funding: Société Française de Cardiologie and Institut National du Sport, de l'Expertise et de la Performance (INSEP) Abstract source Full text

Metabolic syndrome (MetS) is a key risk factor for cardiovascular disease (CVD) incidence and all-cause mortality. MetS prevalence among adults with sickle cell disease (SCD) is not well known. We report initial findings from a cross-sectional study that examined MetS risk factors within a cohort of adults living with SCD. 50 adult SCD participants (ages 21-66 years; 72% female) completed demographic and health behavior surveys, health-related family and personal histories, and anthropometric and laboratory measurements. Descriptive and inferential statistics were used to summarize and compare CVD risk factors, stratified in separate analyses by SCD genotype and sex. Triglyceride, blood pressure, and fasting glucose levels were within normal limits. 78% of the cohort reported moderate to high physical activity. However, 46% of this cohort was overweight and dietary saturated fat intake exceeded both the national average (11%) and US Dietary Guidelines (<10%). 14.3% of the cohort fulfilled criteria for MetS with large waist circumference and reduced HDL levels prominently accounting for this status. We evaluated the prevalence of MetS in a cohort of adults living with SCD. Our findings suggest that increased attention to eating habits and physical activity may generate new approaches for decreasing cardiovascular morbidity in SCD. Abstract source Full text

Background: This study aimed to evaluate the preliminary validation and application of a pain screening tool to identify biopsychosocial risk factors for chronic pain in pediatric sickle cell disease (SCD) and classify youth with SCD into prognostic risk groups. Method: Youth presenting to a pediatric SCD clinic completed the Pediatric Pain Screening Tool (PPST), a brief 9-item self-report questionnaire developed for rapid identification of risk in youth with pain complaints. Youth also completed a battery of standardized patient-reported outcomes, including pain characteristics, pain burden, functional disability, pain interference, depressive symptoms, pain catastrophizing, and fear of pain. Healthcare utilization was extracted from medical chart review. Results: Seventy-three 8- to 18-year-olds (94% Black, 57% female) with SCD participated. The PPST demonstrated discriminant validity that ranged from fair to excellent (area under the curves (AUC) = 0.74-0.93, P values < 0.001) for identifying significant pain frequency, disability, pain interference, and psychosocial distress. Receiver operating characteristic curve analyses indicated that previously established cutoff scores were appropriate for the SCD sample. Participants were classified into low-risk (28.8%), medium-risk (38.4%), and high-risk (32.9%) groups, with significant group differences across measures, F(18, 116) = 6.67, P < 0.001. The high-risk group reported significantly higher pain intensity, pain frequency, pain burden, functional disability, pain interference, and depressive symptoms relative to both low-risk and medium-risk groups (P values < 0.005). Conclusions: The high-risk group demonstrated a pain and psychosocial profile consistent with chronic SCD pain. The PPST may be useful for efficiently identifying youth with chronic SCD pain or those at risk of poor outcomes. Abstract source Full text