Decreased risk of underdosing with continuous infusion versus intermittent administration of cefotaxime in patients with sickle cell disease and acute chest syndrome.

OBJECTIVE: Underdosing of antibiotics is common in patients with sickle cell disease (SCD). We hypothesized that in critically-ill patients with SCD receiving cefotaxime during acute chest syndrome, the continuous infusion may outperform the intermittent administration in achieving pharmacokinetic/pharmacodynamic targets. DESIGN: Prospective before-after study. SETTINGS: Intensive-care unit of a French teaching hospital and sickle cell disease referral center. PATIENTS: Sixty consecutive episodes of severe acute chest syndrome in 58 adult patients with sickle cell disease. INTERVENTIONS: Patients were treated with intermittent administration during the first period (April 2016 -April 2018) and with continuous infusion during the second period (May 2018 -August 2019). MEASUREMENTS AND MAIN RESULTS: We included 60 episodes of acute chest syndrome in 58 patients (29 [25-34] years, 37/58 (64%) males). Daily dose of cefotaxime was similar between groups (59 [48-88] vs. 61 [57-64] mg/kg/day, p = 0.84). Most patients (>75%) presented a glomerular hyperfiltration with no difference between groups (p = 0.25). More patients had a cefotaxime trough level ≥2 mg/L with continuous infusion than intermittent administration: 28 (93%) vs. 5 (16%), p<0.001. The median residual concentration was higher in the continuous infusion than intermittent administration group: 10.5 [7.4-13.3] vs. 0 [0-0] mg/L, p<0.001. No infection relapse was observed in the entire cohort. Hospital length of stay was similar between groups. CONCLUSION: As compared to intermittent administration, continuous infusion of cefotaxime maximizes the pharmacokinetic/pharmacodynamic parameters in patients with SCD. The clinical outcome did not differ between the two administration methods; however, the study was underpowered to detect such a difference.

Poor Sleep Quality in Jamaican Adults With Sickle Cell Disease: Prevalence, Risk Factors, and Association With Quality of Life.

Poor sleep and chronic illnesses have a bidirectional relationship where presence of one can worsen the other. Sickle cell disease (SCD) is associated with significant morbidity and early mortality. In this study, we examine sleep quality, its predictors, and its association with quality of life in Jamaican adults with SCD. This cross-sectional study evaluated 177 well adult SCD patients for sleep quality using The Pittsburgh Sleep Quality Index (PSQI) and quality of life using the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me). Multiple linear regression models examined the predictors of poor sleep quality. The mean global PSQI score was 6.9 (SD 4.2) with 56.5% having poor sleep quality. Women had significantly worse scores for sleep efficiency (p 0.005), sleep latency (p 0.03) and higher use of sleeping medications (p 0.02). Those overweight/obese had significantly worse subjective sleep quality (p 0.001) and sleep efficiency (p 0.05). In multivariate regression analysis, overweight individuals had poorer sleep quality (OR: 2.9; 95% C.I.: 1.07, 7.88) than those with normal weight whereas those unemployed and looking for a job had lower prevalence of poor sleep quality (OR 0.2; 95% C.I.: 0.05, 0.77) compared to employed individuals. Participants with good sleep quality had significantly better functioning in all 5 domains of the ASCQ-Me. In conclusion, persons with SCD who are overweight or obese are at increased risk of poor sleep which can negatively affect quality of life. Patient populations and healthcare providers will need to manage the emerging burden of overweight/obesity.

Genetic Variants Associated with the Risk of Stroke in Sickle Cell Anemia: Systematic Review and Meta-Analysis.

Sickle cell anemia (SCA) is the most common cause of stroke in children. As it is a rare disease, studies investigating the association with complications like stroke in SCD have small sample sizes. Here, we performed a systematic review and meta-analysis of the studies exploring an association of genetic variants with stroke to get a better indication of their association with stroke. PubMed and Google Scholar were searched to identify studies that had performed an association analysis of genetic variants for the risk of stroke in SCA patients. After screening of eligible studies, summary statistics of association analysis with stroke and other general information were extracted. Meta-analysis was performed using the fixed effect method on the tool METAL and forest plots were plotted using the R program. The random effect model was performed as a sensitivity analysis for loci where significant heterogeneity was observed. 407 studies were identified using the search term and after screening 37 studies that cumulatively analyzed 11,373 SCA patients were included. These 37 studies included a total of 2,222 SCA patients with stroke, predominantly included individuals of African ancestry (N = 16). Three of these studies performed whole exome sequencing while 35 performed single nucleotide-based genotyping. Though the studies reported association with 132 loci, meta-analyses could be performed only for 12 loci that had data from two or more studies. After meta-analysis we observed that four loci were significantly associated with risk for stroke: -α3.7 kb Alpha-thalassemia deletion (P = 0.00000027), rs489347-TEK (P = 0.00081), rs2238432-ADCY9 (P = 0.00085), rs11853426-ANXA2 (P = 0.0034), and rs1800629-TNF (P = 0.0003396). Ethnic representation of regions with a high prevalence of SCD like the Mediterranean basin and India needs to be improved for genetic studies on associated complications like stroke. Larger genome-wide collaborative studies on SCD and associated complications including stroke need to be performed.

An assessment of the psychometric properties of the Coping Strategies Questionnaire - Sickle Cell Disease (CSQ-SCD) among adults in the United States.

BACKGROUND: Previous studies have reported conflicting factor structures of the Coping Strategies Questionnaire - Sickle Cell Disease (CSQ-SCD). This study examined the psychometric properties of the CSQ-SCD among adults with SCD in the United States. METHODS: This study implemented a cross-sectional study design with web-based self-administered surveys. Individuals with SCD were recruited via an online panel. Psychometric properties, including factorial and construct validity, and internal consistency reliability, of the CSQ-SCD were assessed. RESULTS: A total of 196 adults with SCD completed the survey. Confirmatory factor analysis (CFA), using maximum likelihood estimation and the 13 subscale scores as factor indicators, supported a three-factor model for the CSQ-SCD compared to a two-factor model. Model fit statistics for the three-factor model were: Chi-square [df] = 227.084 [62]; CFI = 0.817; TLI = 0.770; RMSEA [90% CI] = 0.117 [0.101-0.133]; SRMR = 0.096. All standardized factor loadings (except for the subscales isolation, resting, taking fluids, and praying and hoping) were > 0.5 and statistically significant, indicating evidence of convergent validity. Correlations between all subscales (except praying and hoping) were lower than hypothesized; however, model testing revealed that the three latent factors, active coping, affective coping, and passive adherence coping were not perfectly correlated, suggesting discriminant validity. Internal consistency reliabilities for the active coping factor (α = 0.803) and affective coping factor (α = 0.787) were satisfactory, however, reliability was inadequate for the passive adherence coping factor (α = 0.531). Given this overall pattern of results, a follow-up exploratory factor analysis (EFA) was also conducted. The new factor structure extracted by EFA supported a three-factor structure (based on the results of a parallel analysis), wherein the subscale of praying and hoping loaded on the active coping factor. CONCLUSIONS: Overall, the CSQ-SCD was found to have less than adequate psychometric validity in our sample of adults with SCD. These results provide clarification around the conflicting factor structure results reported in the literature and demonstrate a need for the future development of a SCD specific coping instrument.

Sickle Cell Disease Phenotypes and Obstructive Sleep Apnea; Are They Related?

OBJECTIVE: This study aims to compare the polysomnographic features between Arab-Indian and Benin phenotypes of sickle cell disease (SCD). MATERIALS AND METHODS: This prospective cross-sectional study was conducted in the Children's Hospital at King Fahad MedicalCity, in Riyadhwhere childrenwere recruited fromthe pediatric hematology clinic and pediatric sleepmedicine. All families were approached and patients who met the inclusion criteria and agreed to participate were included in the study. RESULTS: Eighty four children (37 of whom were females) with SCD were included in the study. Their median (interquartile) age was 9 (6.65, 11) years and their body mass index z score was -1.45 (-2.195, -1.45). The evidence of obstructive sleep apnea (OSA) was more prominent in the Benin phenotype (66.7%) in comparison to those of the Arab-Indian (35.2%) phenotype ( p = 0.006). Additionally, 56.7% of Benin had moderate to severe OSA whereas Arab-Indian had 18% with a ( p = 0.0003). Controlling for other factors, the odds ratio (confidence interval) of having OSA in Benin phenotype was 4.68 (1.42-15.38) times higher as compared to Arab-Indian phenotype. CONCLUSION: The risk of having OSA as well as the severity of OSA is higher in Benin phenotype as compared to Arab-Indian phenotype which indicates the presence of potential OSA risk factors other than the SCD itself.

Age-related Morphofunctional Changes in Sickle Cell Mice Bone Marrow Mesenchymal Stromal Cells.

BACKGROUND AND OBJECTIVES: Bone marrow mesenchymal stromal cells (BM-MSCs) are key elements of the hematopoietic niche and participate in the regulatory mechanisms of hematopoietic stem cells (HSCs). Hematological diseases can affect MSCs and their functions. However, the dysregulations caused by sickle cell disease (SCD) are not fully elucidated. This work explored changes in BM-MSCs and their relationship with age using sickle cell mice (Townes-SS). MATERIALS AND METHODS: BM-MSCs were isolated from Townes-SS, and control groups 30- and 60-day-old Townes-AA and C57BL/6 J. RESULTS: The BM-MSCs showed no morphological differences in culture and demonstrated a murine MSC-like immunophenotypic profile (Sca-1+, CD29+, CD44+, CD90.2+, CD31-, CD45-, and CD117-). Subsequently, all BM-MSCs were able to differentiate into adipocytes and osteocytes in vitro. Finally, 30-day-old BM-MSCs of Townes-SS showed higher expression of genes related to the maintenance of HSCs (Cxcl12, Vegfa, and Angpt1) and lower expression of pro-inflammatory genes (Tnfa and Il-6). However, 60-day-old BM-MSCs of Townes-SS started to show expression of genes related to reduced HSC maintenance and increased expression of pro-inflammatory genes. CONCLUSION: These results indicates age as a modifying factor of gene expression of BM-MSCs in the context of SCD.

A Novel Mechanistic Model for Future Research in the Elements of the ERAS Program in Patients With Sickle Cell Disease.

Enhanced recovery after surgery (ERAS) is a patient-centered, evidence-based, multidisciplinary team-developed approach to a surgical stress response that is implemented to optimize physiological function and facilitate recovery for the best possible outcomes from surgery. Although there are currently well-known published guidelines for the perioperative management of patients with sickle cell disease, there are currently no specific and evidencebased ERAS protocols that address the needs of these patients. A novel mechanistic model has recently been found that could change ERAS protocols for patients with sickle cell disease with regard to a current preoperative carbohydrate loading drink recommendation, nutrition and intravenous fluid management. ERAS has great benefits for most patient populations, but emerging research suggests that patients with sickle cell disease may process and respond differently to varying concentrations of serum glucose and serum cations (hyperglycemia and hypertonic states). This adverse response involves actin, a cytoskeletal protein, in the red blood cell and how increased hemoglobin glycosylation may lead to a malfunction in this protein and a transition to vaso-occlusive crises in patients with sickle cell disease. Further research is warranted with this new mechanistic model to develop more meticulous and customized perioperative management plans to address risk mitigation in patients with sickle cell disease.

[Transition in sickle cell disease - recommendations of the transition initiative sickle cell disease]. / Transition bei der Sichelzellkrankheit ­ Empfehlungen der Transitionsinitiative Sichelzellkrankheit.

Sickle cell disease is a rare, but complex multi-systemic disorder with high need of interdisciplinary and specialized care and new structural requirements. Besides care of those chronically sick patients, transition process is a vulnerable phase which highly influences further treatment. To make matters worse, patients often have migration background with subsequent communication problems. A national guidance for a standardized transition process is lacking in Germany. In context of a structured consensus process, the "transition initiative sickle cell disease" developed specific recommendations for a structured transition of sickle cell patients on the basis of the S3 transition guideline of the DGfTM. These recommendations should improve this vulnerable process in this complex disease to ensure adequate further treatment and to avoid acute and chronic complications but also mental, social or job-related issues. Besides improvement of quality of life, medical treatment and survival, health economic aspects arise. Documents were developed to support and facilitate the transition process and are available under www.sichelzellkrankheit.info/transition/.

Translational Research and Health Equity: Gene Therapies for Sickle Cell Disease as a Case Study.

In August of 2023, the National Academies of Science, Engineering, and Medicine published a timely report titled "Toward Equitable Innovation in Health and Medicine: A Framework." Here, we review some of the key contributions of the report, focusing on two dimensions of equity: input equity and deployment equity. We then use the example of new gene therapies to treat sickle cell disease (SCD) as a case study of input and deployment equity in translational research. The SCD case study illustrates the need for a kind of translational bioethics with deep understanding of lived experiences and clinical realities as well as a high degree of economic and policy sophistication.

Multi-center study on mortality in children, and adults with sickle cell anemia-risk factors and causes of death.

Sickle cell disease (SCD) is a major public health burden worldwide with increasing morbidity and mortality. The study evaluates the risk factors associated with mortality in SCD patients, between the years 2006 and 2020 at three hospitals in Oman. The analysis includes clinical manifestations, haematological, biochemical, and radiological parameters, use of antibiotics, and blood and exchange transfusions. Our cohort included 123 patients (82 males, 41 females), with a median age of 27 (Interquartile Range 21-35 years). SCD related complications included acute chest syndrome (ACS) in 52.8%, splenic sequestration in 21.1%, right upper quadrant syndrome in 19.5%, more than > 6 VOC/year in 17.9%, and stroke in 13.8%. At the terminal admission, patients had cough, reduced O2 saturation, crepitation and fever in 24.4%, 49.6%, 53.6% and 68.3% respectively. Abnormal chest X-ray and chest CT scan were seen in 57.7%, and 76.4% respectively. Laboratory parameters showed a significant drop in hemoglobin (Hb) and platelet counts from baseline, with a significant rise in WBC, LDH and CRP from baseline (p < 0.05, Wilcoxon Signed Ranks test). All patients received antibiotics, whereas, 95.9% and 93.5% received simple blood transfusions, and exchange transfusions respectively, and 66.6% required non-invasive ventilation. Among the causes of death, ACS is seen in 32 (26%), sepsis in 49 (40%), and miscellaneous in 42 (34%). Sudden death was seen in 32 (26%) of patients. Male gender, with low HbF, rapid drop in Hb and platelet, and increased in WBC, LDH, ferritin, and CRP, correlated significantly with mortality in this cohort.

Prevalence and predictors of iron deficiency anaemia among children with sickle cell disease in Dodoma, Tanzania: a cross-sectional study.

BACKGROUND: Patients with sickle cell disease (SCD) are prone to iron profile derangements. This study aimed to determine the prevalence of iron deficiency anaemia (IDA) and their predictors among children with SCD aged between 6 months and 14 years. Assessment of the prevalence of IDA and its predictors helps to understand ways of alleviating the magnitude of the problem so as to prevent possible complications such as shortness of breath and chest pain. METHODS: This was a cross-sectional analytical hospital-based study which included 174 patients with SCD attending SCD clinics at St. Gema hospital and Dodoma regional referral hospital in Dodoma city from October 2020 to March 2021. The cut-off points for detection of IDA was serum ferritin level < 30 µg/L and low mean corpuscular volume (MCV) for age. Data were analyzed using SPSS software version 25.0. Multivariate logistic regression analysis was used to determine the predictors of IDA. P-value less than 0.05 was considered significant. RESULTS: The prevalence of IDA in this study was (16.1%, n = 28). Family income of less than 70,000/= TZS/month (AOR = 2.2, 95% CI = 1.07-2.49, p = 0.023), being transfused with blood less than 3 times from the time of being diagnosed with SCD (AOR = 5.5, 95% CI = 1.03-8.91, p = 0.046), and eating red meat at least once per month (AOR = 3.60, 95% CI = 1.37-9.46, p = 0.010) remained the independent predictors of IDA in multivariate regression analysis. CONCLUSION: The findings of this study have shown that, support of families with children suffering from SCD in terms of financial support for improving medical services including optimal blood transfusion and affordability of diet which is rich in iron such as red meat is imperative.

Acute care utilization among individuals with sickle cell disease and related cardiopulmonary and renal complications.

Cardiopulmonary and renal end organ (CPR) complications are associated with early mortality among individuals with sickle cell disease (SCD). However, there is limited knowledge regarding acute care utilization for individuals with SCD and CPR complications. Our objective was to determine the prevalence of CPR complications in a state specific SCD population and compare acute care utilization among individuals with and without CPR complications. We leveraged 2017-2020 data for individuals with SCD identified by the Sickle Cell Data Collection program in Wisconsin. The prevalence of CPR complications is determined for distinct age groups. Generalized linear models adjusted for age compared the rate of acute care visits/person/year among individuals who had cardiopulmonary only, renal only, both cardiopulmonary and renal, or no CPR complications. There were 1378 individuals with SCD, 52% females, mean (SD) age 28.3 (18.5) years; 48% had at least one CPR complication during the study period. The prevalence of CPR complications was higher in adults (69%) compared to pediatric (15%) and transition (51%) groups. Individuals with SCD and cardiopulmonary complications had higher acute visit rates than those without CPR complications (5.4 (IQR 5.0-5.8) vs 2.4 (IQR 2.1-2.5), p <0.001)). Acute care visit rates were similar between individuals with SCD who had renal only complications and no CPR complications (2.7 (IQR 2.5-3.0) vs 2.4 (2.1-2.5), p = 0.24). The high acute care visit rates, especially for those with cardiopulmonary complications, warrant further investigation to understand risk factors for CPR complications, the underlying reasons and identify effective disease management strategies.

Effect of nutritional supplementation on bone mineral density in children with sickle cell disease: protocol for an open-label, randomised controlled clinical trial.

INTRODUCTION: Children with sickle cell disease show a significant decrease in bone mineral density, an increase in resting energy expenditure of more than 15%, a decrease in fat and lean mass as well as a significant increase in protein turnover, particularly in bone tissue. This study aims to evaluate the effectiveness of an increase in food intake on bone mineral density and the clinical and biological complications of paediatric sickle cell disease. METHODS AND ANALYSIS: The study is designed as an open-label randomised controlled clinical trial conducted in the Paediatrics Unit of the Orléans University Hospital Centre. Participants aged 3-16 years will be randomly divided into two groups: the intervention group will receive oral nutritional supplements (pharmacological nutritional hypercaloric products) while the control group will receive age-appropriate and gender-appropriate nutritional intake during 12 months. Total body less head bone mineral density will be measured at the beginning and the end of the trial. A rigorous nutritional follow-up by weekly 24 hours recall dietary assessment and planned contacts every 6 weeks will be carried out throughout the study. A school absenteeism questionnaire, intended to reflect the patient's school productivity, will be completed by participants and parents every 3 months. Blood samples of each patient of both groups will be stocked at the beginning and at the end of the trial, for future biological trial. Clinical and biological complications will be regularly monitored. ETHICS AND DISSEMINATION: The protocol has been approved by the French ethics committee (Comité de Protection des Personnes Sud-Ouest et Outre-Mer 2, Toulouse; approval no: 2-20-092 id9534). Children and their parents will give informed consent to participate in the study before taking part. Results will be disseminated through peer-reviewed journals or international academic conferences. TRIAL REGISTRATION NUMBER: NCT04754711.

[Population characterization of mutations for sickle cell anemia and its treatment: One step towards personalized medicine for the disease]. / Caracterización poblacional de mutaciones relevantes para la Anemia Falciforme y su tratamiento: Un paso hacia la personalización de la enfermedad.

Sickle cell anemia (SCA) is the most common genetic disease worldwide. There are countries with massive public health programs for early detection of this condition. In the literature, several specific haplotypes or single-base polymorphic variants (SNPs) have been associated with the SCA prognosis. OBJECTIVE: To demonstrate the significant correlation of SNPs relevant to the diagnosis and prognosis of SCA among different ethnic groups. METHODOLOGY: we analyzed population frequencies and correlations of several SNPs related to the prognosis of SCA (i.e., baseline fetal hemoglobin levels), response to hydroxyurea treatment, and response to other drugs used in the SCA treatment, collected from validated genomic databases among different ethnic groups. RESULTS: The calculation of the Hardy-Weinberg equilibrium and the logistic regression was successful in classifying the ethnic groups as African (0 = 0.78, 1 = 0.89), and with a lower efficiency as American (AMR) (0 = 0.88, 1 = 0.00), East Asian (EAS) (0 = 0.80, 1 = 0.00), European (EUR) (0 = 0.79, 1 = 0.00), and South Asian (SAS) (0 = 0.80, 1 = 0.00). CONCLUSIONS: The results extend those from previous reports and show that the profile of most of the SNPs studied presented statistically significant distributions among general ethnic groups, pointing to the need to carry out massive early screening of relevant SNPs for SCA in patients diagnosed with this disease. It is concluded that the application of a broad mutation detection program will lead to a more personalized and efficient response in the treatment of SCA.

Validating evidence for the knowledge, management and involvement of dentists in a dental approach to sickle-cell disease.

This study validated the content of an instrument designed to assess the knowledge, involvement (attitudes) and management (practice) of dentists relative to sickle-cell disease (KAPD-SCD). The instrument consisted of five domains composed of a total of thirteen items: I. Dentist's self-assessment relative to sickle-cell disease; II. Dentist's knowledge of the repercussions of sickle-cell disease on the stomatognathic system; III. Dentist's knowledge of the complications of sickle-cell disease in the stomatognathic system; IV. Dentist's knowledge concerning the dental management of sickle-cell disease patients; and V. Dentist's involvement in an approach to sickle-cell disease. Twelve experts assigned scores to each item of the instrument. The criteria were clarity, understanding and appropriateness, leaving open fields for comments. Descriptive and content analyses of the data were made. Each expert analyzed 39 assessment units. The percentages considered for agreement were high (>80%), medium (70%-80%), or low (<70%), and each item was maintained or revised according to the percentage observed. There was high consensus in 74% of the assessment units (the corresponding items were maintained), medium consensus in 24% of them (the corresponding items were revised), and disagreement in 2% of them, namely as regards the "appropriateness" of item 5 ("Are there oral complications in sickle-cell disease?"), which was revised. The final version of the instrument had 16 items for different applications such as in the clinical care program, teaching program, or research program, with different cut-off scores for each application. In conclusion, the level of agreement among experts showed evidence of the content validity of the instrument.

Serum iron Profile of Patients with Sickle Cell Disease and its Association with Socio-demographic Characteristics and Duration of Diagnosis.

BACKGROUND: Sickle cell anemia is the most common hemoglobinopathy in the world. The study aimed to evaluate the iron profile and its association with socio-demographic characteristics in patients with sickle cell disease. METHODS: A hospital-based descriptive cross-sectional study was conducted to know the iron profile and its socio-demographic association in patients with sickle cell disease. RESULTS: The average serum iron, TIBC, and transferrin saturation were 16.75 ± 6.40 mcgMole/L, 69.46 ± 16.94 mcg/dl and 25.15 ± 12.51% respectively. The serum ferritin ranged from 10.00 to 3000.00 ng/ml. The proportion of participants with normal serum iron, TIBC, serum ferritin, and transferrin saturation were 86.10%, 0.00%, 33.90% and 36.40% respectively. All of the participants of this study had low TIBC (1005), and more than half of the participants had elevated serum ferritin (56.40%). CONCLUSIONS: Iron overload is a common complication of sickle cell disease. There was no association of age and sex with iron profile. The TIBC variation between the Chaudhary ethnic group compared to other ethnic groups signifies the ethnic role in the iron profile.

Assessment of hypoxemia among young adults with sickle cell anaemia in steady state in southwestern Nigeria: a crosssectional study.

OBJECTIVES: Hypoxia is a known feature of sickle cell anaemia (SCA) which results from chronic anaemia and recurrent vaso-occlusive crisis (VOC) which can cause tissue ischaemia that leads to an end organ damage. The hallmark of SCA is chronic anaemia and recurrent vaso-occlusive crisis. The aim of this study is to compare the oxygen saturation of sickle cell anaemic individuals with the normal haemoglobin type (Hb AA) control and also to determine the prevalence of hypoxemia among SCA. RESULTS: Two-hundred and twenty-two (136 Hb SS and 86 Hb AA) participated in the study. The mean ± SD of age (years), oxygen saturation (%) and pulse rate (bpm) of participants with sickle cell anaemia and Hb AA control were 21.85 ± 3.04 and 22.14 ± 3.18 (t = 0.701, p = 0.436), 95.21 ± 3.02 and 98.07 ± 0.81 (t=-8.598, p < 0.0001) and 77.10 ± 9.28 and 73.16 ± 8.52 (t = 3.173, p = 0.002) respectively. The prevalence of hypoxemia among SCA participants was 47.1%. Prevalence of hypoxemia in males with SCA was 60.9% while 39.1% of the females had hypoxemia.

Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent ß-Thalassemia.

In 2020, Emmanuelle Charpentier and Jennifer Doudna were awarded the Nobel Prize in Chemistry for their research on the endonuclease, clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated protein 9 (CRISPR-Cas9) method for DNA editing. On 16 November 2023, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) was the first to approve the CRISPR-Cas9 gene editing therapy, Casgevy (exagamglogene autotemcel), for the treatment of patients with transfusion-dependent b-thalassemia and the treatment of sickle cell disease in patients aged ≥12 years with recurrent vaso-occlusive crises. On 8 December 2023, the US Food and Drug Administration (FDA) approved both Casgevy and Lyfgenia (lovotibeglogene autotemcel) for patients with sickle cell disease. On 15 December 2023, the European Medicines Agency (EMA) approved Casgevy for sickle cell disease and transfusion-dependent ß-thalassemia. This Editorial aims to present an update on the landmark first regulatory approvals of CRISPR-Cas9 for patients with sickle cell disease and transfusion-dependent b-thalassemia and the potential challenges for therapeutic gene (DNA) editing.