Endari treatment ameliorates sickle cell-related disruption in intestinal barrier functions and is associated with prolonged survival in sickle cell mice.

BACKGROUND: Endari (L-glutamine) is a conditional amino acid that reduces the frequency of vaso-occlusive crisis (VOC) in sickle cell disease (SCD). AIM: To investigate whether Endari could ameliorate intestinal barrier function and improve survival outcomes in SCD. METHODS: We treated female Townes SCD mice with Endari and evaluated their intestinal barrier functions by measuring the recovery of orally administered fluorescein isothiocyanate (FITC)-conjugated dextran 4 kDa in serum, and serum intestinal fatty acid binding proteins (iFABP) and lipopolysaccharide (LPS) concentrations by ELISA. We also explored the impact the Endari has on the survival of the SCD mice that underwent repeated experimentally-induced VOC. RESULTS: Compared to SCD mice treated with water only, Endari-treated mice showed improved intestinal barrier functions, with decrease in the barrier permeability and reduction in the translocation of lipopolysaccharides from the intestinal lumen into the circulation. These changes occurred after only 4 weeks of Endari treatment. Improved intestinal barrier function was also associated with prolonged survival in Endari-treated SCD mice after repeated experimentally-induced VOC. CONCLUSION: Our findings provide the evidence supporting the beneficial effects of Enadri in improving intestinal barrier function and associated survival outcomes in SCD.

Proliferative Sickle Cell Retinopathy: A Patient and a Physician's Perspective on Quality of Life and Quality of Eye Care.

The impact of visual impairment in the context of sickle cell disease is poorly understood. Despite the significant advancements over the past three decades in retinal imaging and in the understanding of molecular mechanisms that drive retinal neovascularization, there has been little improvement in the management of proliferative sickle cell retinopathy. This article is co-authored by a patient impacted by proliferative sickle cell retinopathy. She highlights her personal experience of sight loss from proliferative sickle cell retinopathy and the impact on her daily life and mental health. Subsequent to diagnosis and management of proliferative sickle cell retinopathy, she continues to live with irreversible sight loss and provides crucial insight from a patient's perspective into the broad lack of high-quality educational materials online and lack of understanding of the disease within the clinical community. This article aims to provide a strong narrative to emphasize the need for further qualitative and quantitative research in this area, to bring about the holistic step-change required to improve visual outcomes and eyecare for people with sickle cell disease.

Bloodless management of significantly elevated transcranial Doppler velocity value in a Jehovah's witness child with sickle cell disease: A tertiary centre experience-A case report.

BACKGROUND: Effective management of complications in sickle cell disease (SCD), such as stroke prevention, often necessitates the use of blood transfusions. However, individuals who adhere to the religious tenets of Jehovah's Witnesses strictly abstain from accepting blood transfusions, thereby presenting a formidable challenge in clinical decision-making. CASE REPORT: This is a case of a 3 year old child Jehovah's Witness who was found to have significantly elevated transcranial Doppler (TCD) velocity values between 193 and 203 cm/s, following routine screening. This was an otherwise clinically stable child, whose mother was diligently ensuring he had adequate medical care. Ideally, a prophylactic exchange blood transfusion program would have been commenced immediately but was not done due to due to the lack of consent from the caregiver. Patient was initially on hydroxyurea at 15 mg/kg and self medicating on omega 3 supplements and astymin syrup. Further elevation of TCD velocity upto 242 cm/s after a repeat testing, necessitated graduated increase of the dosage of hydroxyurea to 35 mg/kg to optimize its therapeutic effect, and discontinuation of omega 3 fatty acids and replacement of astymin with folic acid, vitamin C and B complex. Following these adjustments, the TCD dropped to below 190 cm/s reducing the risk of stroke in the child. CONCLUSION: This case report demonstrates the successful implementation of a bloodless management strategy for stroke prevention in a Jehovah's Witness child with SCD. This study contributes to the existing literature by providing valuable insights and practical guidance for healthcare providers facing similar ethical and medical dilemmas.

Acupuncture as a Complementary Treatment for Leg Ulcers in Sickle-Cell Disease.

Background: Sickle-cell diseases (SCD) are a group of hereditary disorders in which a specific mutation in the gene that encodes the hemoglobin ß chain leads to formation of an anomalous hemoglobin molecule (HbS) with high polymerization power. This leads to sickling of erythrocytes in situations of low oxygen tension, such as in microcirculation, resulting in peripheral microvasculature occlusion, chronic hemolysis, inflammation, and damage to several target organs. Malleolar ulcers are among the most-debilitating complications of the disease, as they are associated with significant pain, secondary infections, and social impact due to their aesthetic impairment. There are no completely satisfactory therapeutic options for this complication; local healing agents, antibiotics, and dressings are used, with high rates of recurrence and complications, such as osteomyelitis and even limb amputation. Case: This case study evaluated the effect of Traditional Chinese Medicine techniques on chronic malleolar ulcers in a 49-year-old male patient. Ten sessions of systemic acupuncture (combinations involving Source, Master, Energetic Action, and Extraordinary Vessels points), auriculotherapy, and dressing with magnets were conducted. Results: Although the primary outcome sought was not reached (decrease in ulcer diameters), this patient had great reduction of local pain, a decrease in limb edema, and important reduction of his inflammatory condition, reflected in his decreasing blood levels of C-reactive protein. Conclusions: These results show that acupuncture should be considered as an important auxiliary treatment for SCD complications.

DHA and EPA in Sickle Cell Disease Favor Clinical Improvement and Contribute to Better Quality of Life: A Qualitative Systematic Review.

BACKGROUND: Sickle cell disease is a severe genetic disorder, and searching for therapeutic strategies is indispensable for prolonged and improved life for people affected by this condition. OBJECTIVE: This qualitative systematic review aimed to highlight the therapeutic potential of omega- 3 (n-3) in people with sickle cell disease. METHODS: The search was performed by combining sickle cell disease and n-3 descriptors in DeCS/ MeSH databases, including Scopus, PubMed, ScienceDirect, Web of Science, and Virtual Health Library. The risk of bias assessment in the primary studies was performed using the Cochrane risk of bias tool for randomized controlled trials. The evidence quality was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. RESULTS: From the 187 records identified, seven were selected for data collection. Based on the evidence, n-3 supplementation contributes to lower activation of pro-inflammatory biomarkers, improves the concentration of docosahexaenoic and eicosapentaenoic acids in the erythrocyte membrane, provides better hemostatic response, and helps in vaso-occlusive crisis, pain episodes, and hospitalization reduction. CONCLUSION: The findings suggest that n-3 adjuvant therapy favors the clinical and general aspects of people with sickle cell disease.

Pain screening in youth with sickle cell disease: A quality improvement study.

BACKGROUND: Youth with sickle cell disease (SCD) face several challenges as they age, including increased pain frequency, duration, and interference. The purpose of this study was to (i) determine the feasibility of routine pain screening; (ii) identify and describe various clinical pain presentations; and (iii) understand preferences/resources related to engaging in integrative health and medicine (IHM) modalities within an outpatient pediatric SCD clinic. METHODS: During routine outpatient visits, patients aged 8-18 completed measures of pain frequency, duration, and chronic pain risk (Pediatric Pain Screening Tool [PPST]). Participants screening positive for (i) persistent or chronic pain or (ii) medium or high risk for persistent symptoms and disability on the PPST were asked to complete measures of pain interference, pain catastrophizing, and interest in/resources for engaging in IHM modalities. RESULTS: Between March 2022 and May 2023, 104/141 (73.8%) patients who attended at least one outpatient visit were screened. Of these 104 (mean age 12.46, 53.8% female, 63.5% HbSS), 34 (32.7%) reported persistent or chronic pain, and 48 (46.2%) reported medium or high risk for persistent symptoms and disability. Patients completing subsequent pain screening measures reported a mean pain interference T-score of 53.2 ± 8.8 and a mean pain catastrophizing total score of 24.3 ± 10.2. Patients expressed highest interest in music (55.6%) and art therapy (51.9%) and preferred in-person (81.5%) over virtual programming (22.2%). CONCLUSIONS: Comprehensive pain screening is feasible within pediatric SCD care. Classifying patients by PPST risk may provide a means of triaging patients to appropriate services to address pain-related psychosocial factors.

Improvement in Cardiac Morphology Demonstrated by Cardiac Magnetic Resonance Imaging and Echocardiography after Haploidentical Hematopoietic Cell Transplantation in Adults with Sickle Cell Disease.

Cardiopulmonary complications account for approximately 40% of deaths in patients with sickle cell disease (SCD). Diffuse myocardial fibrosis, elevated tricuspid regurgitant jet velocity (TRV) and iron overload are all associated with early mortality. Although HLA-matched sibling hematopoietic cell transplantation (HCT) offers a potential cure, less than 20% of patients have a suitable donor. Haploidentical HCT allows for an increased donor pool and has recently demonstrated improved safety and efficacy. Our group has reported improved cardiac morphology via echocardiography at 1 year after HCT. Here we describe the first use of cardiac magnetic resonance imaging (CMR), the gold standard for measuring volume, mass, and ventricular function, to evaluate changes in cardiac morphology post-HCT in adults with SCD. We analyzed baseline and 1-year data from 12 adults with SCD who underwent nonmyeloablative haploidentical peripheral blood HCT at the National Institutes of Health. Patients underwent noncontrast CMR at 3 T, echocardiography, and laboratory studies. At 1 year after HCT, patients showed marked improvement in cardiac chamber morphology by CMR, including left ventricular (LV) mass (70.2 to 60.1 g/m2; P = .02) and volume (114.5 to 90.6 mL/m2; P = .001). Furthermore, mean TRV normalized by 1 year, suggesting that HCT may offer a survival benefit. Fewer patients had pathologically prolonged native myocardial T1 times, an indirect marker of myocardial fibrosis at 1 year; these data showed a trend toward significance. In this small sample, CMR was very sensitive in detecting cardiac mass and volume changes after HCT and provided complementary information to echocardiography. Notably, post-HCT improvement in cardiac parameters can be attributed only in part to the resolution of anemia; further studies are needed to determine the roles of myocardial fibrosis reversal, improved blood flow, and survival impact after HCT for SCD.

Low vitamin B12 blood levels in sickle cell disease: Data from a large cohort study in Tanzania.

Sickle cell disease (SCD) is associated with high rates of undernutrition and stunting. Undernutrition in combination with chronic haemolysis may lead to deficiencies in micronutrients necessary for erythropoiesis. Here we examined selected levels of ferritin, vitamins B2 , B6 , B9 and B12 , and vitamin C that were measured in blood samples from 820 SCD patients from Tanzania with no history of hospital admission, infections or painful episodes in the previous 30 days. We studied children (0-8 years), early adolescents (9-14 years), late adolescents (15-17 years) and adults (≥18 years). Severely low levels of vitamin B12 were observed across the four age groups. Despite the lowered vitamin B12 concentrations, total homocysteine concentrations were normal across both genders in all age groups. We found no significant gender-related differences between the other measured micronutrients. In this large SCD population, spanning the whole life cycle, a low level of vitamin B12 was consistently found across both genders and all age groups. Given the pivotal role of vitamin B12 in cellular metabolism, particularly in erythropoiesis, more studies are required to unravel how to better detect clinically relevant vitamin B12 deficiency among SCD patients, and thus to identify more precisely those who need supplementation of vitamin B12 .

Bridging the Access Gap for Comprehensive Sickle Cell Disease Management Across Sub-Saharan Africa: Learnings for Other Global Health Interventions?

Background: Sickle cell disease (SCD) is a major unresolved global health issue, with the highest disease burden in sub-Saharan African countries; yet, SCD care has not proportionally reached patients in these regions, and the disease has received limited attention in the past. Addressing the burden of SCD in sub-Saharan Africa requires a holistic, collaborative approach to ensure solutions are both comprehensive - i.e., cover the entire continuum of care from early diagnosis to treatment - and sustainable - i.e., are co-created and co-owned with local partners and integrated into existing local systems to enable long-term independence without the need for continuous external support. Objective: We outline a set of recommendations for enhancing the provision of comprehensive healthcare for prevalent diseases in resource-constraint settings, gathered from the Novartis Africa SCD Program, that could serve as 'blueprint' for public-private partnerships to tackle global health priorities. Methods: The Novartis Africa SCD program was initiated with the aim to bridge access gaps to SCD care and provide comprehensive and innovative treatment solutions for SCD, especially in SSA where the disease burden is highest. The Program was first inaugurated in 2019 in Ghana through a public-private partnership with the Ministry of Health of the Government of Ghana, the Ghana Health Service, and the Sickle Cell Foundation of Ghana. Through engagement with these partners, as well as with support from other organizations with complementary competencies and resources, several targeted solutions were implemented to help strengthen the healthcare ecosystem to allow for comprehensive SCD management. Learnings from these interventions are highlighted as best practice consideration as a catalyst and to activate more public-private actors for this neglected global health issue. Findings and Conclusions: A solid understanding of the access barriers to comprehensive care has to be acquired by listening to and learning from patients, civil society, and local experts. Access barriers need to be addressed at multiple levels, i.e., by not only making medicines available and affordable, but also by strengthening healthcare systems, building capacity, and fostering local research and development. Partnerships across governmental, public, academic, non-profit, and private organizations are needed to secure political will, pool resources, gather expertise with understanding of the local context, and allow integration into all levels of existing local healthcare structures and the wider society.

Precision, integrative medicine for pain management in sickle cell disease.

Sickle cell disease (SCD) is a prevalent and complex inherited pain disorder that can manifest as acute vaso-occlusive crises (VOC) and/or chronic pain. Despite their known risks, opioids are often prescribed routinely and indiscriminately in managing SCD pain, because it is so often severe and debilitating. Integrative medicine strategies, particularly non-opioid therapies, hold promise in safe and effective management of SCD pain. However, the lack of evidence-based methods for managing SCD pain hinders the widespread implementation of non-opioid therapies. In this review, we acknowledge that implementing personalized pain treatment strategies in SCD, which is a guideline-recommended strategy, is currently fraught with limitations. The full implementation of pharmacological and biobehavioral pain approaches targeting mechanistic pain pathways faces challenges due to limited knowledge and limited financial and personnel support. We recommend personalized medicine, pharmacogenomics, and integrative medicine as aspirational strategies for improving pain care in SCD. As an organizing model that is a comprehensive framework for classifying pain subphenotypes and mechanisms in SCD, and for guiding selection of specific strategies, we present evidence updating pain research pioneer Richard Melzack's neuromatrix theory of pain. We advocate for using the updated neuromatrix model to subphenotype individuals with SCD, to better select personalized multimodal treatment strategies, and to identify research gaps fruitful for exploration. We present a fairly complete list of currently used pharmacologic and non-pharmacologic SCD pain therapies, classified by their mechanism of action and by their hypothesized targets in the updated neuromatrix model.

The Effectiveness of Common Interventions in the Management of Sickle Cell Disease in Primary Care Settings: A Review.

Sickle cell disease (SCD), a chronic condition that affects men and women equally, continues to present a public health burden in the United States due to its associated morbidity and complications. Despite advances in medical knowledge and the design of novel therapies for managing the disease, its burden remains compounded because of increasing rates of immigration arising from global displacements and economic unrest in many countries. We thus conducted a comprehensive literature review of publications from 2000 to 2022 to gather guidelines on managing SCD, with a search through four databases, PubMed, Embase, Google Scholar, and Cochrane; 42 articles met the final inclusion criteria after the full-text article screening process. In the United States healthcare system, primary care physicians (PCPs) are generally providers who cater to the lifelong management of chronic medical conditions, SCD not being an exception. While more SCD patients now present to primary care clinics, many PCPs still lack the confidence and adequate experience necessary to manage the condition effectively. The gap created by the shortage of PCPs extensively equipped to provide comprehensive SCD care leads to poor health outcomes for patients. It is imperative now more than ever to continue to raise awareness about this condition at the provider level, to ensure that patients receive well-rounded care to improve their quality of life and clinical outcomes. Providing up-to-date knowledge about existing and novel therapies and/or modalities of SCD treatment would undoubtedly equip the PCPs with self-assurance to manage the condition adeptly. Thus, we explore various public health interventions such as hydroxyurea therapy, pneumococcal vaccination, penicillin therapy, iron chelation therapy, and clinical decision support tools that have been implemented in primary healthcare settings and shown to be effective in improving SCD care. We also discuss recent advancements that can lead to improved outcomes for SCD patients in the future.

Erythrocytapheresis in Children and Young Adults with Hemoglobinopathies and Iron Overload in Need of Iron Chelation Therapy.

Limited data regarding erythrocytapheresis in children, adolescents, and young adults have been published. The aim of this study was to evaluate erythrocytapheresis, either as a standalone therapy or in combination with iron chelation therapy, in children and young adults with hemoglobinopathies in whom current iron chelation therapy is not sufficient in decreasing the iron overload during management. We retrospectively analysed erythrocytapheresis in 19 patients with hemoglobinopathies in need of iron chelation therapy diagnosed with sickle cell disease (SCD) or ß-thalassemia major. Patients were divided into (1) a case cohort who received erythrocytapheresis alone or in combination with iron chelation therapy and (2) a control cohort who received oral iron chelation therapy alone. Serum ferritin and haemoglobin levels were compared at five different time points over a one-year period. In the erythrocytapheresis cohort, there was a significant decrease in serum ferritin (p < 0.001). In the iron chelation therapy alone cohort, there was no significant decrease in serum ferritin over time (p = 0.156). Comparing the evolution of median serum ferritin between therapy with erythrocytapheresis and iron chelation therapy showed a statistically significant difference (p = 0.008). Patients with ß-thalassemia major receiving erythrocytapheresis showed a greater reduction in serum ferritin compared to patients without (p = 0.036). A difference could not be shown between the erythrocytapheresis and iron chelation single therapies (p = 0.100). This study showed an overall significant reduction in serum ferritin in patients with hemoglobinopathies treated with erythrocytapheresis in addition to iron chelation. A clinical, although not statistical, trend of higher haemoglobin levels was maintained. Erythrocytapheresis in paediatric patients with ß-thalassemia major was as effective in decreasing ferritin levels as in previously reported studies with SCD. Erythrocytapheresis is a promising therapy for treating and preventing transfusion-related iron overload.

Longer length peripheral catheters in sickle cell treatment: a more efficient and cost-effective care pathway.

Patients with sickle cell disease require frequent venous access for red blood cell exchange transfusions to manage their condition. Such frequent access can lead to scar tissue formation, increased pain on insertion, and difficult vascular access for the patients. Previous attempts at achieving successful venous access for patients with difficult venous access has been made with central venous lines, usually femoral lines, which required a large amount of nursing input and resulted in anxiety and pain on insertion for patients. In this article, the author reports on a new pathway with a longer-length peripheral intravenous catheter that reduces the nursing time burden during line insertion, requires less equipment and, crucially, results in a less painful procedure for patients. The increased efficiency of the pathway resulted in a cost saving of £149 per insertion, and patient feedback revealed that the longer-length catheter was preferred over femoral lines.

Evidence-based interventions for reducing sickle cell disease-associated morbidity and mortality in sub-Saharan Africa: A scoping review.

Objective: Sickle cell disease is a lifelong illness affecting millions of people globally, but predominantly burdensome in sub-Saharan Africa, where most affected children do not live to adulthood, despite available evidence-based interventions that reduce the disease burden in high-income countries. Method: We reviewed studies evaluating evidence-based interventions that decrease sickle cell disease-related morbidity and mortality among children living in sub-Saharan Africa. We used the Joanna Briggs scoping review methodological framework and grouped identified evidence-based interventions into preventative pharmacotherapeutic agents, newborn screening and comprehensive healthcare, disease-modifying agents, nutritional supplementation, systemic treatment, supportive agents and patient/carer/population education. Results: We included 36 studies: 18 randomized controlled trials, 11 observational studies, 5 before-and-after studies and 2 economic evaluation studies, with most of the studies performed in West African countries. Included studies suggest evidence-based interventions effectively to reduce the common morbidities associated with sickle cell disease such as stroke, vaso-occlusive crisis, acute chest syndrome, severe anaemia and malaria infection. Evidence-based interventions also improve survival among study participants. Specifically, our review shows hydroxyurea increases haemoglobin and foetal haemoglobin levels, a finding with practical implications given the challenges with blood transfusion in this setting. The feasibility of implementing individual interventions is hampered by challenges such as affordability, accessibility and the availability of financial and human resources. Conclusion: Our review suggests that regular use of low-dose hydroxyurea therapy, sulphadoxine-pyrimethamine chemoprophylaxis, L-arginine and Omega-3 fatty acid supplementation and establishment of specialist stand-alone sickle cell clinics could reduce the sickle cell disease-associated morbidity and mortality in sub-Saharan Africa countries.

Current challenges and new approaches to implementing optimal management of sickle cell disease in sub-Saharan Africa.

Sickle cell disease (SCD) is the most common life-threatening monogenic disorder in the world. The disease is highly prevalent in malaria endemic areas with over 75% of patients residing in Sub-Saharan Africa (SSA). It is estimated that, without proper care, up to 90% of children with SCD will not celebrate their fifth birthday. Early identification and enrolment into comprehensive care has been shown to reduce the morbidity and mortality related with SCD complications. However, due to resource constraints, the SSA is yet to implement universal newborn screening programs for SCD. Furthermore, care for patients with SCD in the region is hampered by the shortage of qualified healthcare workers, lack of guidelines for the clinical management of SCD, limited infrastructure for inpatient and outpatient care, and limited access to blood and disease modifying drugs such as Hydroxyurea which contribute to poor clinical outcomes. Curative options such as bone marrow transplant and gene therapy are expensive and not available in many SSA countries. In addressing these challenges, various initiatives are ongoing in SSA which aim to enhance awareness on SCD, improve patient identification and retention to care, harmonize the standards of care for SCD, improve the skills of healthcare workers and conduct research on pertinent areas in SCD in the SSA context. Fortifying these measures is paramount to improving the outcomes of SCD in SSA.

Evaluation of treatment patterns, healthcare resource utilization and cost of illness for sickle cell disease in Ghana: a private medical insurance claims database study.

BACKGROUND: Sickle cell disease (SCD) is a major public health concern in sub-Saharan Africa, accounting for nearly 75% of the global disease burden. The current analysis evaluated patient characteristics, treatment patterns, healthcare resource utilization (HCRU) and associated costs in patients with SCD based on a Private Medical Insurance Database in Ghana. METHODS: This retrospective longitudinal cohort study was conducted using an e-claims database from Ghana (01 January 2015 to 31 March 2021). Patients were stratified by age (0 month to < 2 years, ≥ 2 years to ˂6 years, ≥ 6 years to < 12 years, ≥ 12 years to < 16 years; ≥16 years), vaso-occlusive crisis (VOC) (< 1, ≥ 1 to < 3, and ≥ 3 per year), and continuous enrolment. Study outcomes related to patient characteristics, comorbidities, treatment pattern, HCRU were evaluated for pre- and post-index period (index period was between July 2015 to March 2020). Descriptive analysis was used to analyse different study variables. RESULTS: The study included 2,863 patients (mean age: 20.1 years; Min age: 0; Max age: 83; females 56.1%). Overall, 52.2% (n = 1,495) of SCD patients were ≥ 16 years and 17.0% (n = 486) were in the ≥ 2 to ˂6-years age group. The majority of patients aged ≥ 16 years (62.5%) in the database did not have reported VOC episodes, 35.9% of patients had 1 to 3 VOCs per year and 1.5% had ≥ 3 VOCs per year during the follow-up period. Consultation-based prevalence of SCD was 0.5% [95% confidence interval (CI): 0-1.3%] - 1.4% [CI: 0.6-2.2%]. Malaria, upper respiratory tract infection (URTI) and sepsis were the common complications of SCD. Analgesics were the most frequently prescribed medications followed by anti-infectives, hematinics, and antimalarials. Hydroxyurea, a routine standard of care for SCD was under-utilized. SCD patients had median cost incurred for consultation/hospital services of $11.3 (Interquartile range [IQR] $6.2 - $27.2). For patients with VOC, maximum median cost was incurred for medications ($10.9 [IQR $5.0-$32.6]). Overall median healthcare cost was highest for individuals with ≥ 3 VOCs per year during the follow-up period ($166.8 [IQR $70.3-$223.5]). CONCLUSION: In this retrospective private insurance claims database analysis, SCD imposes a significant healthcare burden, especially in patients with VOC. There is a need for reimbursed treatment options that could reduce the long-term burden associated with SCD and VOC.

Potential inflammatory targets in the integrative health care of patients with sickle cell disease.

Inflammation plays an integral role in the complications of sickle cell disease (SCD), which can lead to vaso-occlusive crisis and extreme pain. SCD is accompanied by numerous complications, including cardiovascular disease, cognitive decline and endothelial dysfunction, contributing to mortality. As disease severity increases with age, the present study aimed to assess if age is also correlated with a definite pattern of progression of the two inflammatory markers, high-sensitivity C-reactive protein (hsCRP) and total homocysteine (tHCY). The findings of the present study could lead to an improved understanding of the threshold levels of these inflammatory markers and timely interventions to delay complications. In an observational study, levels of hsCRP and tHCY were analyzed in 70 patients (35 male and 35 female patients) with SCD aged between 5 and 16 years. hsCRP levels were in the high-risk range in 64.29% (n=45) of all male and female patients. A sex-wise distribution showed that, of the 35 male patients, 74.28% (n=26) were in the high-risk range, and of the 35 female patients, 54.28% (n=19) were in the high-risk range. An age-wise distribution showed that of the 41 patients in the 5-10-years age group, 70.73% (n=29), were in the high-risk range. In comparison, of the 29 patients in the 11-16-years age group, 55.17% (n=16) were in the high-risk range. tHCY levels were observed to be in the normal range in 98.57% (n=69) of all children, as compared with 1.43% (n=1) in the high-risk range. Furthermore, a sex-wise distribution showed that female patients in the high-risk group of hsCRP had higher concentrations of tHCY as compared with the male patients in that risk group. An age-wise distribution of hsCRP concentration also showed that the risk of CVD in patients in the 11-16-years age group was higher with increased concentrations of tHCY. A weak negative correlation was observed between age and hsCRP concentrations (r-value=-0.280; P=0.026) and a weak positive correlation was detected between tHCY and age (r-value=0.259; P=0.036). In conclusion, the results of the present study indicated that higher levels of hsCRP could be a useful marker in children with SCD, and levels of tHCY may be an adjunct marker as the disease progresses with age.

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. OBJECTIVE: We hypothesize that a dedicated Education Liaison (EL) embedded in the SCD team increases implementation of NPT and accommodations. STUDY DESIGN: This retrospective study included children aged 5-20 years with SCD receiving care at a single center from 2017 through 2020. Univariate analysis and multiple logistic regression were performed. RESULTS: Total 316 children with SCD were included. At baseline, 52.8% had accommodations (IEP: 24.4%, 504: 38.0%). The EL interacted with 62.0% of children. Children with EL contact were more likely to undergo NPT (odds ratio [OR]: 5.385), have an IEP (OR: 4.580), and have a 504 (OR: 2.038) (p < .001 for all). At the end of the study period, 64.6% had accommodations (IEP: 33.5%, 504: 54.4%), which increased from baseline (p < .001 for all). EL interaction was associated with overt or silent stroke history (OR: 1.911), acute chest syndrome history (OR: 2.257), hospitalizations since age 5 (OR: 3.216), and hospitalization for vaso-occlusive pain since age 5 (OR: 2.226) (p < .001 for all). CONCLUSION: EL interaction improves access to NPT and educational accommodations among children with SCD. SCD centers should incorporate ELs in comprehensive care teams to improve access to appropriate educational accommodations.

Use of Compartmental Modeling and Retinol Isotope Dilution to Determine Vitamin A Stores in Young People with Sickle Cell Disease Before and After Vitamin A Supplementation.

BACKGROUND: Suboptimal plasma retinol concentrations have been documented in US children with sickle cell disease (SCD) hemoglobin SS type (SCD-HbSS), but little is known about vitamin A kinetics and stores in SCD. OBJECTIVES: The objectives were to quantify vitamin A total body stores (TBS) and whole-body retinol kinetics in young people with SCD-HbSS and use retinol isotope dilution (RID) to predict TBS in SCD-HbSS and healthy peers as well as after vitamin A supplementation in SCD-HbSS subjects. METHODS: Composite plasma [13C10]retinol response data collected from 22 subjects with SCD-HbSS for 28 d after isotope ingestion were analyzed using population-based compartmental modeling ("super-subject" approach); TBS and retinol kinetics were quantified for the group. TBS was also calculated for the same individuals using RID, as well as for healthy peers (n = 20) and for the subjects with SCD-HbSS after 8 wk of daily vitamin A supplements (3.15 or 6.29 µmol retinol/d [900 or 1800 µg retinol activity equivalents/d]). RESULTS: Model-predicted group mean TBS for subjects with SCD-HbSS was 428 µmol, equivalent to ∼11 mo of stored vitamin A; vitamin A disposal rate was 1.3 µmol/d. Model-predicted TBS was similar to that predicted by RID at 3 d postdosing (mean, 389 µmol; ∼0.3 µmol/g liver); TBS predictions at 3 compared with 28 d were not significantly different. Mean TBS in healthy peers was similar (406 µmol). RID-predicted TBS for subjects with SCD-HbSS was not significantly affected by vitamin A supplementation at either dose. CONCLUSIONS: Despite differences in plasma retinol concentrations, TBS was the same in subjects with SCD-HbSS compared with healthy peers. Because 56 d of vitamin A supplementation at levels 1.2 to 2.6 times the Recommended Dietary Allowance did not increase TBS in these subjects with SCD-HbSS, further work will be needed to understand the effects of SCD on retinol metabolism. This trial was registered as NCT03632876 at clinicaltrials.gov.

Iron profile of pregnant sickle cell anemia patients in Odisha, India

ABSTRACT Introduction: During pregnancy, the iron requirement increases to meet the optimal growth of the fetus and prevent iron deficiency anemia-related complications in the mother. However, in sickle cell disease (SCD) primarily due to repeated blood transfusions and hemolysis-induced recycling of iron, its supplementation during pregnancy remains questionable and may be harmful. Methods: Twenty-five pregnant women with homozygous SCD and 25 pregnant women with normal hemoglobin variants were included as cases and control, respectively. Pregnancy and sickle cell anemia (SCA) were diagnosed using standard protocols. The serum iron, serum ferritin, total iron-binding capacity (TIBC), percentage transferrin saturation and C-reactive protein were estimated, as per the manufacturer's protocol. The complete blood count was performed. The unpaired 't-test' was performed using the SPSS v23.0 and the principal component analysis (PCA) was performed using the online software MetaboAnalyst for statistical analysis. Main Results: The studied cases had significantly lower mean hemoglobin and higher mean corpuscular volume (MCV), compared to controls. The mean serum-iron, serum-ferritin and percentage transferrin-saturation in the cases were significantly higher than that of the controls, while the TIBC was lower in the cases (p < 0.0001). The mean level of serum iron, ferritin, percentage transferrin saturation and TIBC were 309.44 ± 122.40mcg/dl, 860.36 ± 624.64ng/ml, 42.6 ± 17.30% and 241.32 ± 96.30 mcg/dl, respectively, in the cases and 95.36 ± 41.90mcg/dl, 122.28 ± 49.70ng/ml, 15.83 ± 3.10% and 492.6 ± 149.40mcg/dl in the controls, respectively. Higher MCV, mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) with lower hemoglobin (Hb) were noted in the cases. The PCA revealed that the cases were more heterogeneous in terms of the variability of the iron status and hematological indices than the controls. Conclusion: The current study shows iron sufficiency in most cases of pregnancy with SCA and suggests that evaluation of iron status must be made before initiating iron prophylaxis in pregnant women with SCA, especially in regions having a high prevalence of sickle cell hemoglobinopathy.