Search Results (334)

Background: Quality care of individuals with sickle cell disease (SCD) is dependent upon education of the providers on their care team. Previous studies demonstrate lack of resident and provider comfort regarding care of patients with SCD, yet none have assessed these in medical students. Objective: This study aims to evaluate the adequacy of the research instrument for measuring medical students’ knowledge, confidence, and comfort regarding SCD and related complications prior to wider distribution. Methods: A self-assessment survey was distributed to medical students at two universities to evaluate their knowledge, confidence, and comfort in general SCD topics, in all clinical settings, and regarding common complications. Results: Of the 98 responses, knowledge (p < 0.001) and confidence (p = 0.02) were significantly different between topics, including epidemiology and genetics, pathophysiology, and treatment options. For “treatment options”, there were significant differences in knowledge (p = 0.02) and confidence (p = 0.02) between medical students at different levels of training. Students felt least knowledgeable and least comfortable with care of pregnant women and most knowledgeable and most comfortable with acute pain management. Caring for patients with specific SCD-related conditions increased knowledge and comfort across all domains. Conclusions: This instrument was adequate for measuring knowledge, confidence, and comfort in caring for those with SCD across all clinical settings. We identified a lack of knowledge, confidence, and comfort regarding treatment for those with SCD starting early in medical careers, which improves after caring for patients with various complications. Thus, educating and providing SCD patient experiences is crucial for medical student management confidence related to SCD. Full article

Microfluidic methods are an important tool for studying the microrheology of blood and the mechanical properties of blood cells—erythrocytes, leukocytes, and platelets. In patients with diabetes, hypertension, obesity, sickle cell anemia, or cerebrovascular or peripheral vascular diseases, hemorheological alterations are commonly observed. These include increased blood viscosity and red blood cell (RBC) aggregation, along with reduced RBC deformability. Such disturbances significantly contribute to impaired microcirculation and microvascular perfusion. In blood vessels, abnormal hemorheological parameters can elevate resistance to blood flow, exert greater mechanical stress on the endothelial wall, and lead to microvascular complications. Among these parameters, erythrocyte deformability is a potential biomarker for diseases including diabetes, malaria, and cancer. This review highlights recent advances in microfluidic technologies for in vitro assays of RBC deformability and aggregation, as well as leukocyte aggregation and adhesion. It summarizes the core principles of microfluidic platforms and the experimental findings related to hemodynamic parameters. The advantages and limitations of each technique are discussed, and future directions for improving these devices are explored. Additionally, some aspects of the modeling of the microrheological properties of blood cells are considered. Overall, the described microfluidic systems represent promising tools for investigating erythrocyte mechanics and leukocyte behavior. Full article

Sickle cell disease (SCD) is a prevalent genetic disorder caused by a mutation in the beta-globin gene. Hyperhemolysis (HS) is a severe complication involving the rapid destruction of both transfused and endogenous red blood cells, commonly found in SCD. This literature review explores the clinical presentation, diagnosis, pathogenesis, and management of HS in SCD. HS can manifest acutely or in a delayed manner, complicating diagnosis due to overlapping symptoms and varying reticulocyte responses. Immunohematological assessments often reveal delayed positivity in direct antiglobulin tests and antibody screens. HS typically presents severe anemia, jaundice, hemoglobinuria, and hemodynamic instability. Diagnostic markers include elevated bilirubin and lactate dehydrogenase levels alongside a reduced reticulocyte count. The management of HS is primarily empirical, with no clinical trials to support standardized treatment protocols. First-line treatments involve steroids and intravenous immunoglobulins (IVIG), which modulate immune responses and mitigate hemolysis. Refractory cases may require additional agents such as rituximab, eculizumab, tocilizumab, and, in some instances, plasma exchange or erythropoietin-stimulating agents. Novel therapeutic approaches, including bortezomib and Hemopure, have shown promise but require further investigation. Current management strategies are empirical, underscoring the need for robust clinical trials to establish effective treatment protocols that ultimately improve outcomes for SCD patients experiencing HS. Full article

Background: One of the major challenges for children and adolescents with sickle cell disease (SCD) is academic performance. Objectives: Our study aimed to evaluate the academic performance of children and adolescents with SCD in Benin and compare it to the academic performance of their healthy siblings and paediatric comparisons. Furthermore, we aimed to explore the associations between socio-demographic factors, clinical characteristics, and depressive symptoms, and the academic performance of children and adolescents with SCD. Methods: The study was a cross-sectional study that used convenient sampling. Academic scores were collected during the 2021–2022 academic year. Patients with SCD and paediatric comparisons were recruited during routine hospital consultations. The Children’s Depression Inventory (CDI-S) tool was used to assess depressive symptoms. We compared academic performance scores (ranging from 0 to 20) using independent t-tests and explored associations through linear regression analyses. Results: This study included 209 participants: 100 patients with SCD (aged 6 to 17 years), 46 siblings, and 63 paediatric comparisons. The academic performance of patients with SCD (mean academic score = 13.29) was similar to that of the combined comparison group (mean academic score = 12.8, p = 0.196). Younger patients showed poorer academic performance (coef = −0.169, p = 0.019), and depressive symptoms (‘pessimism’, ‘self-hate’, ‘lack of friends’, and ‘fatigue’) were associated with poorer academic performance as well. Patients with SCD who were treated in Benin performed academically as well as their healthy siblings and peers. Conclusions: Children and adolescents with SCD performed on par academically with their healthy siblings and peers. While overall depressive symptoms were not significantly associated with academic performance, certain symptoms were more common among lower-performing students and should therefore be explored in greater detail. Full article

Sickle cell disease (SCD) is the most common hemoglobinopathy, caused by a mutation in the β-globin gene of hemoglobin. It predisposes patients to painful Vaso-occlusive crises (VOC) and multi-organ dysfunctions. The disease exhibits significant phenotypic variability, making it challenging to predict severity and outcomes. This study aimed to characterize the whole blood gene expression profile of Bahraini SCD patients, identifying differentially expressed genes during steady-state (n = 10) and VOC (n = 10) compared to healthy controls (n = 8). Analysis revealed 2073 and 3363 dysregulated genes during steady-state and VOC, respectively, compared to controls, with 1078 genes differentially expressed during VOC versus steady-state. Gene Ontology (GO) enrichment analysis highlighted significant deregulation in immune and hematopoietic pathways, including down-regulation of critical genes for immune modulation and hematopoietic balance. Notably, the transcription factor RUNX3, involved in immune cell differentiation and inflammation, was among the 668 down-regulated genes. RUNX3 was four-fold down-regulated in microarray analysis, three-fold in PCR, and showed a mean protein concentration of 11.13 pg/mL during VOC compared to 457.93 pg/mL during steady-state (p < 0.01). These findings suggest that RUNX3 may serve as a potential biomarker for VOC. Future large-scale validation, additional proteomic studies, and functional investigations are recommended to confirm its clinical utility and significance. Full article

Background: PP-007 (SANGUINATE^®, PEGylated carboxyhemoglobin, bovine) is under development to treat conditions of ischemia/hypoxia. Hemorrhagic/hypovolemic shock (H/HVS) becomes a life-threatening comorbidity due in part to hypotension and hypoxia. Blood transfusions are indicated, but supply and compatibility issues may limit subject access or when blood is not an option due to religious restriction or concern for clinical complications. PP-007 is universally compatible with an effective hydrodynamic radius and colloidal osmotic pressure facilitating perfusion without promoting extravasation. Methods: A review of previous clinical trials was performed and revealed an Open-Label Phase 1 safety study of acute severe anemia (hemoglobin ≤ 5 g/dL) in adult (≥18 y) patients unable to receive red blood cell transfusion (NCT02754999). Primary outcomes included safety events with secondary efficacy measures of organ function and survival at 1, 14, and 28 days. Additionally, a retrospective review of published, peer-reviewed case reports was performed, evaluating the administration of Sanguinate for Expanded Access in those patient populations where blood was not an option over the past 12 years. Results: A total of 103 subjects were enrolled in the Phase I safety study with significant co-morbidities that most commonly included hypertension (n = 43), acute and chronic kidney disease (n = 38), diabetes mellitus (n = 29), gastrointestinal bleeds (n = 18), and sickle cell disease (n = 13). Enrollment characteristics included decreased hemoglobin and severe anemia (mean baseline hemoglobin of 4.2 g/dL). Treatments included an average of three infusions [range 1–17]. Secondary efficacy measures were mean Hb levels, respiratory support, and vasopressor requirements, all demonstrating clinically relevant improvements. Fourteen additional cases were identified in the literature. Though one patient died due to pre-treatment conditions, all patients but one were discharged home in stable condition. Conclusion: Collectively, these observations are encouraging and provide support for the continued evaluation of PP-007 in advanced clinical trials in severe anemia including H/HVS. The review of published case reports underscored the potential of Sanguinate to reduce early mortality. Adverse effects included transient hypertension, lethargy, dizziness, and troponin elevation. These findings highlight the need for continued research and funding of blood alternatives to improve outcomes when standard blood transfusions are unavailable or contraindicated. Full article

Background/Objectives: Children with sickle cell disease (SCD) often experience limited access to care, contributing to poor health outcomes. Patient-level predictors and outcomes associated with telehealth use among Medicaid-enrolled children with SCD remain unknown. This study aims to (1) analyze telehealth trends before and during the pandemic (March 2020–March 2022), (2) identify patient-level predictors of telehealth use, (3) assess its association with care continuity and health outcomes, and (4) identify physician specialties involved in telehealth visits. Methods: Using Texas Medicaid claims (March 2017–March 2022), we conducted a retrospective analysis of children aged 1–18 with ≥3 SCD-related claims. Monthly trends in outpatient visits (in-person and telehealth) were visualized from March 2019 to March 2022. Multivariable regression models examined predictors of telehealth use and associations with ≥10 hydroxyurea fills, emergency department (ED) visits, and hospitalizations, adjusting for age, sex, regions with SCD clinics, and prior healthcare utilization. Results: Among 903 included patients (mean [SD] age = 10.4 [4.1], 52.6% male), 59.4% had ≥1 telehealth visits between March 2019 and March 2022. Telehealth use peaked between March 2020 and May 2020, then gradually declined. Children with ≥10 SCD-related outpatient visits 1 year before the lockdown (March 2019–February 2020) had 77.4% higher odds of using telehealth compared to those with 0–4 visits (OR = 1.774, 95% CI = 1.281–2.457, p = 0.0006), while controlling for sociodemographic characteristics. However, SCD-related telehealth use during the pandemic was not associated with either ≥10 hydroxyurea fills or reduced ED visits. Prior healthcare utilization remained a strong predictor of both outcomes. The majority of telehealth visits were conducted at multispecialty clinics (74%). Conclusions: Telehealth use surged early in the pandemic but later declined among Texas Medicaid-enrolled children with SCD. Children with high healthcare needs adopted telehealth, but this did not impact care continuity or extensive healthcare utilization. While maintaining telehealth access, other measures should be implemented to improve access and outcomes for this vulnerable population. Full article

Background: Sickle cell disease (SCD) is associated with high physical and psychosocial burden among patients and their families. Hydroxyurea (HU) improves health-related quality of life by preventing SCD complications. Despite its availability, HU is underutilised in Tanzania. Perceived self-efficacy for appropriate medication use influences medication usage among individuals with chronic illnesses. We studied factors associated with caregivers’ perceived self-efficacy for appropriate use of HU and its association with HU usage among children with SCD in Dar-es-Salaam. Methods: We conducted a cross-sectional study from May to August 2023. We enrolled 374 caregivers of children with SCD from two regional and two national hospitals. We adapted the self-efficacy for appropriate medication use scale, a multidimensional perceived social support scale, and a patient health questionnaire for assessment of self-efficacy, social support, and depressive symptoms, respectively. Results: Three-quarters of caregivers had high perceived self-efficacy scores for medication use. Attending national hospitals, high social support, and absence of depressive symptoms were positively associated with perceived self-efficacy (adjusted beta coefficient aβ 2.3, 95% CI 0.5–4.2; aβ 9, 95% CI 7.1–10.9; and aβ 5.3, 95% CI 2.8–7.8, respectively). Caregivers with high self-efficacy were 5.3 times more likely to give HU to their children compared with those with low self-efficacy (incidence rate ratio 5.3, 95% CI 3.3–8.3). Conclusions: Hospital levels and psychosocial factors influence caregivers’ perceived self-efficacy for appropriate HU use. We recommend targeted interventions to enhance psychosocial support among caregivers to increase caregivers’ perceived self-efficacy and HU utilization among children with SCD in Tanzania. Full article

Sickle cell disease (SCD) affects millions globally, with approximately 0.26% of the Saudi population impacted. Despite standard treatments, patients frequently experience vaso-occlusive crises (VOCs). This retrospective observational study evaluated the real-world effectiveness of L-glutamine (Endari^®) in reducing SCD-related complications in the Saudi population, where data remain limited. Patients aged five and older who received L-glutamine from June 2019 to June 2023 were included. The primary endpoint was VOC frequency through week 48. Descriptive statistics and paired t-tests compared outcomes before and after treatment. Fifteen patients (median age 12 years, 53% female) met the inclusion criteria; all were on maximum tolerated hydroxyurea. Eleven completed 48 weeks, showing a median VOC reduction from 4 to 3 (p = 0.44). Hospital stay duration remained unchanged (median 7 days, p = 0.72). Laboratory parameters were largely stable, except for a 61.9% increase in reticulocyte count (p = 0.03). The estimated annual treatment cost exceeded SAR 2 million (USD ~547,840). L-glutamine did not produce statistically significant improvements in VOC frequency, though numerical trends were observed. Given the small sample size and limited statistical power, the findings are exploratory. Larger, well-powered, multicenter studies are needed to confirm L-glutamine’s potential benefits in this population. Full article

Sickle cell disease (SCD) is a common genetic disorder affecting up to 2.6% of the population in Saudi Arabia. SCD results in severe disability, reduced quality of life, extensive use of medical resources, increased economic burden, and a high likelihood of increased mortality. Red blood cell transfusion remains a cornerstone in the management of SCD complications. This position paper highlights the current state of SCD management within the Kingdom of Saudi Arabia. Despite the advantages of automated red blood cell exchange (aRBCX) and guideline recommendations, its use remains limited. In practice, aRBCX is used for a variety of indications, including acute management and prophylaxis of stroke, systemic fat embolism, severe forms of acute chest syndrome, preoperative management, hematopoietic stem cell transplantation, hepatic crisis, and priapism. However, aRBCX is underutilized in pregnancy. Common gaps identified by the advisory panel include the absence of standardized national guidelines, limited access to aRBCX, issues with vascular access, lack of equipment, and insufficient staff training. Another limitation to the use of aRBCX is the higher blood requirements compared to other blood transfusion modalities. These factors contribute to geographical disparities in the management of SCD and suboptimal patient outcomes. To address these issues, the advisory panel recommended developing and implementing evidence-based national guidelines, expanding access to aRBCX, enhancing health staff education and training, and establishing a robust national SCD registry. By prioritizing these recommendations, we can help streamline SCD care, reduce practice variation, and nationalize sickle cell disease management in Saudi Arabia to improve patient care. Full article

Background: Sickle cell disease (SCD) significantly impacts diverse racial groups, particularly African American and Hispanic persons, who experience notable disparities in healthcare outcomes. Despite the extensive literature on SCD, studies focusing on in-hospital racial inequities remain limited. Methods: We conducted a retrospective analysis using the National Inpatient Sample (NIS) from 2016 to 2020, identifying adult hospitalizations for SCD (HbSS genotype). Hospitalizations were categorized by race—White, African American, Hispanic, and other, and analyzed for demographic variables, admission types, disposition outcomes, and complications. Statistical analyses included chi-square tests and multivariate logistic regression, adjusting for confounders. Results: Of the 1,089,270 identified hospitalizations, 90.31% were African American. African American and Hispanic patients exhibited significantly higher non-elective admissions compared to Whites (77.81%). In-hospital mortality was highest among Hispanics (0.82%). Multivariate regression analysis revealed that African Americans and others had higher odds of prolonged hospital stays (Adjusted Odds Ratio (AOR): 1.30 and 1.20, respectively). African Americans and Hispanics also had increased risks of in-hospital complications of SCD. Conclusions: This study highlights substantial racial disparities in SCD hospitalizations, with African Americans and Hispanics facing poorer outcomes compared to Whites. Hispanics also demonstrated increased mortality. These findings underscore the need for targeted healthcare interventions to address racial inequities in SCD management and improve outcomes for all affected populations. Full article

Sickle cell disease (SCD) is a group of recessive diseases caused by the β^S sickling mutation of HBB in homozygosity or in compound heterozygosity with other pathogenic HBB mutations. Patients with severe SCD typically experience painful vaso-occlusive crises and other pain-related phenomena, including acute chest syndrome, priapism, dactylitis, avascular necrosis, and splenic sequestration and infarction. High variability of pain-related phenomena per SCD genotype indicates genetic disease modifiers (GDMs) as pathology determinants and, thus, as critical to prognosis, treatment choice, and therapy development. Articles likely holding genetic information for SCD pain phenomena were identified in PubMed and SCOPUS for article quality assessment and extraction of corresponding GDMs and observations indicative of development areas in our understanding of SCD GDMs. This process led to the initial selection of 183 articles matching the search terms, which, after two-step selection, resulted in the inclusion of 100 articles for content analysis and of significant findings for GDMs from 37 articles. Published data point to gender effects and to 51 GDM SNVs, deletions, and regions, including globin genes and significant overrepresentation of gene ontology pathways related, e.g., to oxidative stress, hypoxia, and regulation of blood pressure. Analyzed articles further pointed to additional candidate GDMs affecting SCD VOC and pain phenomena and to potential confounding factors for GWAS analyses. We found that despite the critical importance of VOC and pain phenomena for SCD pathology, corresponding clinically relevant genetic insights are held back by a shortage of large-scale, systematic multi-ethnic efforts, as undertaken by the INHERENT Network. Full article

Acute chest syndrome (ACS) is among the most serious complications of sickle cell disease (SCD). While the pathogenesis of ACS is incompletely understood, endothelial damage and microvascular occlusion are critical components. Our previous studies have implicated small extracellular vesicles in the plasma of subjects with SCD in causing endothelial dysfunction. This suggested that microRNAs within these small EVs might be responsible for endothelial damage. The sequencing of microRNAs in small EVs from the plasma of subjects with SCD revealed that several miRNAs were differentially expressed between subjects with and without ACS history, including let-7c-5p. In a replication cohort, plasma let-7c-5p levels were quantified via RT-qPCR. The baseline plasma let-7c-5p level was twofold higher in patients without previous ACS. Furthermore, we observed a positive correlation between let-7c-5p levels and time to subsequent ACS events. These findings suggest a role for let-7c-5p in endothelial disruption underlying ACS pathogenesis. It may also serve as a novel biomarker for ACS detection and the prediction of disease progression. Full article

Background/Objectives: Antimicrobial resistance (AMR) is increasingly rising due to antimicrobial overuse and misuse. In sickle cell disease (SCD) care, frequent antibiotic use drives the rapid emergence of AMR, threatening treatment options and patient lives. This systematic review synthesizes data on AMR with regard to SCD patients for the first time. Methods: A comprehensive database search for articles published in English was conducted in PubMed, Scopus, ScienceDirect, and Web of Science, with no restriction set for the year of publication. The DerSimonian–Laird method was applied to derive the pooled prevalence, while the Mantel–Haenszel method was used to calculate the pooled odds ratio. Results: A total of 18 eligible studies covering 3220 SCD patients published between 1996 and 2024 were included in this review. The common bacterial pathogens reported in the included studies were Streptococcus pneumoniae (10 studies), Staphylococcus aureus (10 studies), and Escherichia coli (4 studies). For S. aureus, the pooled resistance was highest for penicillins (ampicillin = 100%; penicillin = 93.64%; and amoxicillin = 77.82%) followed by cefuroxime (51.23%). The pooled prevalence of methicillin-resistant S. aureus (MRSA) was 19.30%. SCD patients had 2.89 and 2.47 times higher odds of being colonized or infected with penicillin-resistant and erythromycin-resistant S. aureus strains, respectively. For S. pneumoniae, resistance prevalence was highest for co-trimoxazole (81.1%), followed by penicillin (47.08%). The pooled prevalence of multidrug-resistant (MDR) S. pneumoniae isolates was 32.12%. The majority of the studies included (n = 14, 77.8%) were of moderate quality according to the modified STROBE checklist. Conclusions: This review reveals a high prevalence of AMR with regard to SCD patients. SCD patients have an increased risk of resistance to penicillin and co-trimoxazole across several bacterial pathogens. The limited geographical distribution of the included studies underscores the urgent need for expanded AMR research on the subject, especially in regions with high SCD burden. Full article

Background and Objectives: Priapism is a condition characterized by a prolonged erection lasting over four hours, either independent of or following sexual stimulation. The primary treatment goal for ischemic and non-ischemic priapism is timely and appropriate intervention in order to preserve erectile function and penile length. This study aims to evaluate the management of recurrent ischemic priapism in sickle cell disease (SCD) patients in an endemic region and compare it with ischemic priapism of other etiologies. Materials and Methods: Patients admitted to our hospital with a diagnosis of priapism between January 2010 and June 2024 were retrospectively reviewed. The patients were divided into two groups: ischemic priapism due to SCD and ischemic priapism due to other etiologies. Patient characteristics, treatment management, and the need for penile prosthesis (PP) were compared. Results: A total of 40 ischemic priapism patients were included in the study; 20 of them had SCD and the other 20 had priapism cases due to different etiologies. In the SCD priapism group, the rate of comorbidity and previous history of priapism were significantly (p < 0.05) higher than in the other etiologies of priapism group. Similarly, in the SCD priapism group, the hospital admission time and the rate of fibrosis findings in MRI (magnetic resonance imaging) were significantly (p < 0.05) higher than in the other priapism groups. The PP implantation rate in the SCD priapism group was found to be significantly (p < 0.05) higher than in the other priapism group. Conclusions: This study highlights the importance of early intervention and patient awareness in SCD-related ischemic priapism, recommending educational programs to improve symptom recognition and prevent complications. Full article