Management Of Sickle Cell Disease Research Articles

Towards genomic medicine: a tailored next-generation sequencing panel for hydroxyurea pharmacogenomics in Tanzania

BackgroundPharmacogenomics of hydroxyurea is an important aspect in the management of sickle cell disease (SCD), especially in the era of genomic medicine. Genetic variations in loci associated with HbF induction and drug metabolism are prime targets for hydroxyurea (HU) pharmacogenomics, as these can significantly impact the therapeutic efficacy and safety of HU in SCD patients.MethodsThis study involved designing of a custom panel targeting BCL11A, ARG2, HBB, HBG1, WAC, HBG2, HAO2, MYB, SAR1A, KLF10, CYP2C9, CYP2E1 and NOS1 as potential HU pharmacogenomics targets. These genes were selected based on their known roles in HbF induction and HU metabolism. The panel was designed using the Illumina Design Studio (Illumina, San Diego, CA, USA) and achieved a total coverage of 96% of all genomic targets over a span of 51.6 kilobases (kb). This custom panel was then sequenced using the Illumina MiSeq platform to ensure high coverage and accuracy.ResultsWe are reporting a successfully designed Illumina (MiSeq) HU pharmacogenomics custom panel encompassing 51.6 kilobases. The designed panel achieved greater than 1000x amplicon coverage which is sufficient for genomic analysis.ConclusionsThis study provides a valuable tool for research in HU pharmacogenomics, especially in Africa where SCD is highly prevalent, and personalized medicine approaches are crucial for improving patient outcomes. The custom-designed Illumina (MiSeq) panel, with its extensive coverage and high sequencing depth, provides a robust platform for studying genetic variations associated with HU response. This panel can contribute to the development of tailored therapeutic strategies, ultimately enhancing the management of SCD through more effective and safer use of hydroxyurea.

Healthcare Professionals’ Knowledge, Attitude, Practices of Assessment, and Management of Sickle-Cell Disease: A Meta-Aggregative Review

Abstract: Background: Sickle Cell Disease (SCD) presents significant health challenges globally. Despite its prevalence in diverse geographical regions, there is a paucity of literature synthesizing evidence on healthcare professionals’ knowledge, attitudes, and practices (KAP) toward SCD assessment and management. This meta-aggregative review systematically examined and synthesized existing qualitative research to elucidate healthcare professionals’ KAP regarding SCD assessment and management. Methods: This meta-aggregative review followed Aromataris and Pearson’s guidelines and the PRISMA framework for systematic review reporting. The search was conducted in Scopus, PubMed, Embase, CINAHL Web of Science, Google Scholar, Dimensions AI, and HINARI. Quality appraisal was performed using the Joanna Briggs Institute tool. Results: Healthcare professionals (HCPs) demonstrate varying levels of KAP toward SCD assessment and management. Studies reveal low-to-moderate levels of general knowledge among HCPs, with nurses often exhibiting poorer understanding than physicians. Deficiencies in awareness of specific interventions, such as chemoprophylaxis and prenatal diagnosis, are noted, along with gaps in SCD assessment and diagnosis, particularly in pain management and premarital screening. Attitudes toward SCD patients vary, and practices reveal inconsistencies and deficiencies, including inadequate nutritional counseling and barriers in emergency departments. However, interventions aimed at improving HCPs’ KAP show promise in enhancing understanding and attitudes toward SCD, suggesting potential avenues for improvement. Conclusions: Educational initiatives targeted at both student nurses and practicing healthcare providers, coupled with the implementation of standardized protocols and guidelines, can enhance knowledge acquisition and promote consistent, high-quality care delivery. Future studies should improve the quality of their methods in this area of study.

Concomitant sickle cell disease and systemic lupus erythematosus: A single-center case series.

Sickle cell disease (SCD) and systemic lupus erythematosus (SLE) are two uncommon disorders each characterized by multisystemic manifestations. Individuals with SCD exhibit abnormalities in the complement pathway, which may predispose patients to develop autoimmune disorders such as SLE. As many manifestations of SLE mimic those of SCD, diagnosis and therapeutic management of SLE in a patient with known SCD may be delayed. In this study, we describe our institutional experience of diagnosing and managing concomitant SCD and SLE. We offer insights into the complex interplay between these conditions to enhance early recognition and effective management of concurrent SCD and SLE.

Bridging Gaps: A Quality Improvement Project for the Continuing Medical Education on Stick (CMES) Program.

Aimed at bridging the gap in continuing medical education (CME) resource availability in low- and middle-income countries (LMICs), the "Continuing Medical Education on Stick" (CMES) program introduces two technological solutions: a universal serial bus (USB) drive and the CMES-Pi computer facilitating access to monthly updated CME content without data cost. Feedback from users suggests a lack of content on tropical infectious diseases (IDs) and content from a Western perspective, which may be less relevant in LMIC settings. This quality improvement project was intended to identify areas for improvement of the CMES database to better meet the educational needs of users. We compared the CMES content with the American Board of Emergency Medicine (ABEM) Exam content outline to identify gaps. The curriculum map of the CMES library, encompassing content from 2019 to 2024, was reviewed. An anonymous survey was conducted among 47 global users to gather feedback on unmet educational needs and suggestions for content improvements. All healthcare workers who were members of the CMES WhatsApp group were eligible to participate in the survey. The curriculum map included 2,572 items categorized into 23 areas. The comparison with the ABEM outline identified gaps in several clinical areas, including procedures, traumatic disorders, and geriatrics, which were represented -5%, -5%, and -4% in the CMES library compared with the ABEM outline, respectively. Free responses from users highlighted a lack of content on practical skills, such as electrocardiogram (ECG) interpretation and management of tropical diseases. Respondents identified emergency medical services (EMS)/prehospital care (81%), diagnostic imaging (62%), and toxicology/pharmacology (40%) as the most beneficial areas for clinical practice. In response to feedback from users, new content was added to the CMES platform on the management of sickle cell disease and dermatologic conditions in darkly pigmented skin. Furthermore, a targeted podcast series called "ID for Users of the CMES Program (ID4U)" has been launched, focusing on tropical and locally relevant ID, with episodes now being integrated into the CMES platform. The project pinpointed critical gaps in emergency medicine (EM) content pertinent to LMICs and led to targeted enhancements in the CMES library. Ongoing updates will focus on including more prehospital medicine, diagnostic imaging, and toxicology content. Further engagement with users and education on utilizing the CMES platform will be implemented to maximize its educational impact. Future adaptations will consider local relevance over the ABEM curriculum to better serve the diverse needs of global users.

Anti-sickling effect of Vigna subterranean (L.) Verdc on sickle cell beta thalassemia

Sickle cell disease affects millions of people worldwide and has been recognized as a global health concern by WHO. Presently, there is no cure for sickle cell disease. Treatment options which include bone marrow, stem cell transplantation, blood transfusions, and hydroxyurea are not only expensive but have their side effects. Medicinal plants are often employed in the treatment of diseases because of the therapeutic effects of the secondary metabolites in them. Vigna subterranean an important leguminous crop in Africa, is used in some parts of the world for the treatment and management of sickle cell disease. However, there are no established link between the use of Vigna subterranean and their pharmacological effects. The present study investigated the therapeutic effect of Vigna subterranean on a variant of sickle cell disease known as sickle cell beta thalassemia. Parameters such as reversibility test, polymerization test, osmotic fragility test, deoxygenation test, beta synthesis and oxy-haemoglobin concentration were used to study the anti-sickling potentials of sickle cell beta thalassemia. The result showed that the plant extract reversed the sickled cells, reduced the rate of polymerization, maintained the stability of the cell membrane, increased beta globin synthesis and increased the oxy-haemoglobin concentration. This suggests that Vigna subterranean possesses anti-sicking properties and could be used as an effective therapeutic for the treatment and management of sickle cell beta thalassemia.

Revolutionary breakthrough: FDA approves CASGEVY™, the first CRISPR/Cas9 gene therapy for sickle cell disease

Sickle Cell Disease (SCD) is a hereditary hemoglobinopathy resulting from a β-globin chain mutation that causes abnormal hemoglobin (HbS) polymerization and leads to severe complications. Current treatment options primarily focus on symptom management, with limited curative potential. Recently, Casgevy, the first CRISPR/Cas9-based gene therapy for SCD, has received breakthrough FDA approval. Clinical trials have shown that Casgevy administered to patients aged ≥ 12 years enables precise modifications in hematopoietic stem cells, resulting in elevated fetal hemoglobin (HbF) levels and a significant reduction in vaso-occlusive events. Unlike conventional treatments, this therapy offers a curative approach and eliminates the need for recurrent transfusions and transplants, thereby improving the quality of life of patients with SCD. Casgevy has emerged as a beacon of hope for SCD patients and signifies a potential paradigm shift in SCD management due to its safety, curative potential, and transformative impact, positioning it as a groundbreaking intervention. Nevertheless, ethical considerations surrounding CRISPR technology and regulatory frameworks must be addressed to ensure responsible application and equitable access to this one-time gene editing therapy. As we celebrate this scientific advancement, sustained interdisciplinary collaboration and ethical scrutiny are essential to navigating the evolving landscape of CRISPR technology in medicine. This review aims to provide a detailed insight into the application of Casgevy, challenges associated with its application, future prospects of this therapy, and its comparison with existing treatment options for SCD.

Clinical Practice Patterns in Sickle Cell Disease Treatment: Disease-modifying and Potentially Curative Therapies.

Therapeutic options for sickle cell disease (SCD) have increased recently as well as the development of updated national guidelines. It is not known how these options are being offered or to what degree guidelines are incorporated into clinical practice. This study aimed to describe practice patterns for pediatric hematologists regarding the use of disease-modifying and potentially curative therapies for SCD. A 9-section, cross-sectional electronic survey was disseminated during a 3-month period via SurveyMonkey, to members of the American Society of Pediatric Hematology/Oncology Hemoglobinopathy Special Interest Group (ASPHO HSIG). A total of 88 physician members of the ASPHO HSIG were surveyed. Ninety percent of respondents (72/80) start hydroxyurea routinely in patients with HbSS and HbSβ 0 thalassemia, regardless of disease severity. Laboratory monitoring was recommended every 3 months for stable dosing in 63.8% (51/80). New therapies were recommended for patients on hydroxyurea who were still experiencing SCD complications: L-glutamine 68.5% (37/54) or crizanlizumab 93.1% (54/58). Voxelotor was recommended for patients on hydroxyurea with low hemoglobin in 65.1% (43/66) of cases. Matched sibling transplant was considered for any disease severity by 55.1% (38/69). Gene therapy trials are offered on-site by 29% (20/69). Our study demonstrated the enhanced utilization of hydroxyurea while revealing the unexplored potential of other disease-modifying therapies in SCD. These findings underscore the importance of continued knowledge acquisition about the long-term efficacy of new medical therapies and addressing barriers to the use of proven therapies and guide the development of future studies of optimal SCD management.

A Mixed-Methods Evaluation of a Project ECHO Program for the Evidence-Based Management of Sickle Cell Disease.

Sickle cell disease (SCD) is a group of chronic, genetic disorders of the red blood cells with significant gaps in access to evidence-based clinical care. Sickle Treatment and Outcomes Research in the Midwest (STORM), a provider network, utilized Project ECHO (Extension for Community Health Outcomes), a telementoring model, to deliver evidence-based education about SCD management. The purpose of this mixed-methods study is to evaluate the utility of Project ECHO as an educational strategy for healthcare providers treating children and adults with SCD. Annual evaluations were administered to STORM TeleECHO participants from 2016 to 2021. Survey data showed a statistically significant change in self-reported provider confidence in the ability to provide care for adult patients with SCD; identify suitable candidates for disease-modifying therapies; and confidence to prescribe disease-modifying therapies. Participants who attended at least 10 sessions were invited to participate in a semi-structured interview. Qualitative data were analyzed using thematic analysis and several themes emerged about the benefits, including (1) increased confidence, (2) integrated best-practice care, (3) connection to provider network and access to experts, (4) high-quality educational presentations and (5) opportunities for collaboration and a sense of community. This suggests that Project ECHO is accessible and leads to increased confidence in providers caring for individuals with SCD. Overall, participant knowledge gains successfully demonstrated the utility of Project ECHO as an educational resource for providers.

Folic Acid in the Treatment of Sickle Cell Disease: A Systematic Review.

Sickle cell disease (SCD) is a group of inherited genetic disorders that is caused by a mutation in the gene that codes for hemoglobin subunit β. This systematic review aimed to evaluate the effect of folic acid in the treatment of SCD patients. We retrieved 3730 articlesfrom PubMed, PubMed Central, Google Scholar, and ScienceDirect databases. We employed a search technique that involved framing keywords, such asfolic acid, folate, and sickle cell illness, and the MedicalSubject Headings (MeSH) strategy in PubMed. We chose research articles that had been published during the last 10 years, as well as case reports, systematic reviews and meta-analyses, literature reviews, randomized controlled trials, and observational studies. Exclusion criteria included paid full-text articles, abstracts, non-English studies, and patients who do not have SCD.The 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria were used in the design of our systematic review. It was found that the majority of SCD patients were receiving regular folic acid supplements and that their plasma folate levels were either increased or within normal range, with no discernible impact on other clinical outcomes such as hemoglobin levels, infections, or pain crises. SCD patients produce more red blood cells than healthy individuals, and nearly all SCD patients receive daily folic acid supplements. On the other hand, not enough information is available on folic acid's potential benefits in the management of SCD; thus, there is a need for more large clinical trials.

Assessing the Clinical Outcomes of Voxelotor Treatment in Patients with Sickle Cell Disease

The results of Voxelotor treatment in Sickle Cell Disease, as assessed through clinical outcomes, demonstrated its efficacy in reducing hemolysis and improving hemoglobin levels. This effect can be attributed to Voxelotor's inhibition of HbS polymerization, thereby restoring the deformability and compliance of sickle RBCs. Our mathematical model provided mechanistic insights into how altered rheological properties of sickle RBCs impact their flow dynamics in microcirculation. Specifically, we observed that Voxelotor-induced improvements in RBC deformability and compliance lead to enhanced plasma film height in capillaries, promoting smoother blood flow and reducing the risk of vaso-occlusive events. We established a direct relationship between the molecular mechanism of Voxelotor action and its clinical outcomes. The mathematical model served as a bridge, elucidating how Voxelotor-induced changes in sickle RBC mechanics translate to improved microcirculatory flow and reduced vaso-occlusion. This holistic understanding not only validates the therapeutic efficacy of Voxelotor but also underscores the importance of considering biomechanical factors in evaluating treatment outcomes in SCD. Furthermore, this study highlighted the relevance of microfluidics based diagnostic tools in assessing the efficacy of Voxelotor treatment. By leveraging insights from our mathematical model, microfluidics devices can be designed to mimic physiological conditions and effectively evaluate the deformability of sickle RBCs before and after treatment. This integrated approach not only facilitates the development of personalized therapeutic interventions but also accelerates the translation of novel treatments, such as Voxelotor, from preclinical studies to clinical practice for the management of Sickle Cell Disease. Int. J. Appl. Sci. Biotechnol. Vol 12(1): 46-53.

Pre-transfusion compatibility tests in Malagasy sickle cell patients

Introduction: Blood transfusion is a key component of sickle cell disease management. However, iterative transfusions of labile blood products for sickle cell patients increase the risk of anti-erythrocyte alloimmunization. It is usual to perform pre-transfusion compatibility tests in order to check ABO compatibility and to detect the possible existence of irregular antibodies in patients against the donor's antigens. Methods: This is a prospective and descriptive study dealing with pre-transfusion compatibility tests over a 3-month period, from September 2018 to November 2018, at the Regional Blood Transfusion Centre (CRTS) of Analamanga Region, the capital of Madagascar. Results: We included 33 out of 113 patients during the study period. Compatibility test was positive in 21.21%, of all tested samples. Major and minor compatibility tests were positive alone respectively in 6.25% and 12.50%. And both were positive in 3.12%. The self-test was positive in 3.03% with a positive direct antiglobulin test. Positive compatibility tests were more frequent in patients who received more than two transfusions. Compatible blood bag for the patient was found after testing 2 donor pockets in 27.27% of cases, and after testing 3 pockets in 3.03%. Conclusion: Pre-transfusion compatibility tests are essential and have to be performed systematically on each blood bag before any transfusion. They are used to identify the presence of alloantibodies and provide compatible blood products to patients.

Understanding Knowledge, Attitude, and Practices towards Sickle Cell Disease among Adult Outpatients: Insights from Lira Regional Referral Hospital, Northern Uganda

This study investigates the knowledge, attitude, and practices (KAP) regarding sickle cell disease (SCD) among adult outpatients at Lira Regional Referral Hospital (LRRH) in Northern Uganda. Employing a descriptive cross-sectional qualitative approach, data were collected from 100 adult patients aged 18 years and above attending the general outpatient department (OPD) at LRRH. Results revealed a substantial level of awareness of SCD among respondents, predominantly sourced from healthcare facilities and media outlets. While many recognized SCD as hereditary, misconceptions regarding its etiology and symptoms were evident. Notably, there was a knowledge gap regarding the treatability of SCD. Attitudes towards marrying individuals with SCD were predominantly negative, reflecting concerns about genetic transmission. However, there was a positive inclination towards premarital SCD testing. Regarding practices, reliance on medical facilities for SCD treatment was predominant, with minimal engagement with alternative therapies. Recommendations include sustained awareness campaigns, integration of SCD prevention and control initiatives, and further research to elucidate regional SCD prevalence determinants. Efforts to enhance male involvement in SCD advocacy and capacity building among healthcare providers are advocated to optimize SCD management and prevention strategies within the community. Keywords: Knowledge, Attitude, Practices, Sickle Cell Disease, Outpatients

Attitude and Behavior of Parents of Children With Sickle Cell Disease Toward the Disease: An Observational Study in Saudi Arabia.

Sickle cell disease (SCD) is a significant hematological disorder affecting populations worldwide, with a notable prevalence in certain regions of Saudi Arabia. Despite extensive screening programs, there is a critical need for improved public health education to enhance understanding and management of SCD. This study examines the relationship between the attitudes and behaviors of parents toward their children's disease and its management. We conducted a cross-sectional observational study at the King Fahd Medical Research Center in Jeddah. This research encompassed children aged 5-16 years with SCD and their parents. Comprehensive questionnaires assessed sociodemographic data, attitudes toward SCD, and behavioral responses to the illness and treatment. The study included 66 parents, predominantly in the age range of 30-39 years and earning below 5000 Saudi Riyals, who exhibited varying attitudes towards SCD, with a majority questioning the availability of a cure and expressing caution towards new treatments. Despite a cautious approach to invasive treatments, parents relied on information from healthcare providers. Attitudes towards treatment showed significant differences based on gender and education level, with females and less-educated parents exhibiting more hesitancy towards new treatment and blood transfusions. The study indicates that while parents show a positive and proactive attitude toward SCD, there is hesitancy towards new and invasive treatments, reflecting the need for continued educational support. The results underscore the importance of tailored healthcare communication strategies to address the diverse needs of families affected by SCD.

Enhancing the Management of Pediatric Sickle Cell Disease by Integrating Functional Evaluation to Mitigate the Burden of Vaso-Occlusive Crises

Sickle cell disease (SCD) imposes a significant health burden, particularly in low- and middle-income countries where healthcare professionals and resources are scarce. This opinion paper delves into the management strategies employed for vaso-occlusive crises (VOCs) in pediatric patients with SCD, advocating for the adoption of a transformative strategy. We explore the integration of functional assessment approaches into existing procedures, highlighting the potential of technology-assisted rehabilitation, including wearable sensors and digital biomarkers, to enhance the effectiveness of managing and preventing VOCs. Rehabilomics, as a comprehensive framework, merges rehabilitation-related data with biomarkers, providing a basis for personalized therapeutic interventions. Despite the promising advantages of these approaches, persistent obstacles such as the limited availability of rehabilitation programs, especially in resource-limited settings, pose challenges. This paper underscores the importance of a collaborative strategy to effectively address the unique obstacles faced by patients with SCD. This collaborative approach involves improving accessibility to rehabilitation services, incorporating technology-supported therapy, and fostering focused research endeavors. The primary objective of this comprehensive approach is to enhance the overall care of SCD patients, with a specific focus on preventing VOCs, as well as providing tailored (neuro)rehabilitation services in resource-limited settings. By examining the current state of SCD management and proposing transformative strategies, this opinion paper seeks to inspire collective action and collaboration to improve outcomes for pediatric SCD patients globally.

Knowledge and practices of sickle cell disease among healthcare providers in Kinshasa, Democratic Republic of the Congo.

In Kinshasa, Democratic Republic of Congo, there is a low evocation of the diagnosis of sickle cell disease (SCD) by first-level healthcare providers (HCPs), most likely because of poor knowledge of the disease. To assess the levels of knowledge and practices of SCD and to identify determinants of the practices among primary HCPs. Healthcare facilities in Selembao health zone in Kinshasa, Democratic Republic of the Congo. A cross-sectional study of HCPs randomly selected through a two-stage sampling design. Data were collected using a pre-tested interviewer-administered questionnaire. Univariate and bivariate analysis were done to describe the levels of knowledge and practices of SCD. Factors associated with better practices on SCD were determined using multiple linear regression. The threshold for statistical significance wasp˂ 0.05. A total of 318 HCPs, which included 80 physicians and 238 nurses, participated in the study. The participants showed different scores on the components of the knowledge. All the participants showed poor practices on SCD. Multiple linear regression retained overall knowledge of SCD as a significant predictor of better practice for physicians. Knowledge of SCD and duration of work experience were significant predictors of better practices among nurses. The practices of healthcare providers on SCD were far from optimal. These practices were significantly associated with knowledge and experience of healthcare providers.Contribution:This study highlighted the need for continuing professional education to enhance the management of SCD in the setting.

Comprehensive Care in Sickle Cell Disease.

Despite advancements in sickle cell disease (SCD) management, individuals with SCD continue to face greater degrees of mortality, disability, and health care barriers compared with their healthy peers. Comprehensive care includes essential elements such as newborn screening, key immunizations, penicillin prophylaxis, and consistent health screening for common complications. Pediatricians should be familiar with treatment options for SCD to offer informed education to both patients and their families. By providing guided and comprehensive care, pediatricians have the potential to enhance both the quantity and quality of life for individuals living with SCD. [Pediatr Ann. 2024;53(2):e43-e46.].

INVITRO MEMBRANE PROTECTION EFFECT OF AGERATUM CONYZOIDES METHANOLIC EXTRACT ON HUMAN SICKLED CELLS

Hemolytic anemia caused by membrane damage is the major objective of treating sickle cell anemia in both mainstream and alternative medicine, which is a characteristic hallmark of the disease.One plant that is reportedly utilized in traditional medicine to treat sickle cell anemia is ageratum conyzoides. Prelimnary phytochemical investigation were carried out according to the standard protocols. In vitro spectrophotometric analysis was used to assess the methanolic extract of A. conyzoides' capacity to shield sickle red blood cells from lysis. Preliminary phytochemical screening of crude extracts of leaf, stem and root of Ageratum conyzoides tested positive for the presence of phytochemicals such as alkaloids, flavonoids, tannins, cardiac glycosides, saponins, steroids and triterpenes. The leaf extract caused significant (P<0.05) membrane protection with the value of 24.13±0.47% at 2.5mg/ml concentration, while the stem extract produced a significant (P<0.05) protective effect with the value of 29.13±0.47% at 2.5mg/ml.The root also gave a significant (P<0.05) membrane protective effect of 40.73±1.04% at 2.5mg/ml. These finding clearly support the traditional usage of A. conyzoides in the management of sickle cell anemia by demonstrating the functions that the plant's leaves, stem, and roots play in membrane protection.

Point-of-care detection of hydroxyurea drug in serum using a supramolecular enzyme mimetic

The sole approved therapeutic drug for sickle cell disease management is provided by hydroxyurea, requiring its precise detection and monitoring in biological matrices such as human blood serum for personalized treatment. Herein, we introduce a direct colorimetric detection method for hydroxyurea in serum using a metallo-supramolecular assembly called Vesi-ImCu that mimics the peroxidase enzyme. The Vesi-ImCu enzyme mimetic comprises a catalytically active copper center coordinated to synthetic imidazole containing surfactant and iminodiacetic acid capping moieties. By leveraging the peroxidase-like activity of Vesi-ImCu, we have demonstrated that it catalyzes the efficient production of nitric oxide from hydroxyurea that reacts with the Griess reagent, producing an intense pink color. This approach enables the naked-eye detection of hydroxyurea, with notable efficacy even in complex biological matrices such as human blood serum. The Vesi-ImCu suprazyme-based approach offers several advantages, including high sensitivity (limit of detection of 75 µM), clinically relevant dynamic range of hydroxyurea detection, minimum batch-to-batch variation, and the ability to perform mobile phone-based quantification. To our knowledge, this is the first report on direct colorimetric quantification of HU in serum. With its visual detection ability, high-end equipment-free quantification, user-friendliness and portability, the present enzyme mimetic holds great promise for point-of-care detection applications.

Red Blood Cells as Therapeutic Target to Treat Sickle Cell Disease.

Significance: Sickle cell disease (SCD) is the most common inherited diathesis affecting mostly underserved populations globally. SCD is characterized by chronic pain and fatigue, severe acute painful crises requiring hospitalization and opioids, strokes, multiorgan damage, and a shortened life span. Symptoms may appear shortly after birth, and, in less developed countries, most children with SCD die before attaining age 5. Hematopoietic stem cell transplant and gene therapy offer a curative therapeutic approach, but, due to many challenges, are limited in their availability and effectiveness for a majority of persons with SCD. A critical unmet need is to develop safe and effective novel targeted therapies. A wide array of drugs currently undergoing clinical investigation hold promise for an expanded pharmacological armamentarium against SCD. Recent Advances: Hydroxyurea, the most widely used intervention for SCD management, has improved the survival in the Western world and more recently, voxelotor (R-state-stabilizer), l-glutamine, and crizanlizumab (anti-P-selectin antibody) have been approved by the Food and Drug Administration (FDA) for use in SCD. The recent FDA approval emphasizes the need to revisit the advances in understanding the core pathophysiology of SCD to accelerate novel evidence-based strategies to treat SCD. The biomechanical breakdown of erythrocytesis, the core pathophysiology of SCD, is associated with intrinsic factors, including the composition of hemoglobin, membrane integrity, cellular volume, hydration, andoxidative stress. Critical Issues and Future Directions: In this context, this review focuses on advances in emerging nongenetic interventions directed toward the therapeutic targets intrinsic to sickle red blood cells (RBCs), which can prevent impaired rheology of RBCs to impede disease progression and reduce the sequelae of comorbidities, including pain, vasculopathy, and organ damage. In addition, given the intricate pathophysiology of the disease, it is unlikely that a single pharmacotherapeutic intervention will comprehensively ameliorate the multifaceted complications associated with SCD. However, the availability of multiple drug options affords the opportunity for individualized therapeutic regimens tailored to specific SCD-related complications. Furthermore, it opens avenues for combination drug therapy, capitalizing on distinct mechanisms of action and profiles of adverse effects.

Computing Sickle Erythrocyte Health Index on quantitative phase imaging and machine learning

Sickle cell disease (SCD) is a genetic disorder characterized by abnormal hemoglobin and deformation of red blood cells (RBCs), leading to complications and reduced life expectancy. This study developed an in vitro assessment, the Sickle Erythrocyte Health Index, using quantitative phase imaging (QPI) and machine learning to model the health of RBCs in people with SCD. The health index combines assessment of cell deformation, sickle-shaped classification, and membrane flexibility to evaluate erythrocyte health. Using QPI and image processing, the percentage of sickle-shaped cells and membrane flexibility were quantified. Statistically significant differences were observed between individuals with and without SCD, indicating the impact of underlying pathophysiology on erythrocyte health. Additionally, sodium metabisulfite led to an increase in sickle-shaped cells and a decrease in flexibility in the sickle cell blood samples. Based on these findings, two approaches were used to calculate the Sickle Erythrocyte Health Index: one using hand-crafted features and one using learned features from deep learning models. Both indices showed significant differences between non-SCD and SCD groups and sensitivity to changes induced by sodium metabisulfite. The Sickle Erythrocyte Health Index has important clinical implications for SCD management and could be used by providers when making treatment decisions. Further research is warranted to evaluate the clinical utility and applicability of the Sickle Erythrocyte Health Index in diverse patient populations.