Partial Splenic Embolization in Paediatric Sickle Cell Disease Patients with Hypersplenism.

PURPOSE: To assess the safety and efficacy of partial splenic embolization (PSE) to reduce the need of transfusions and improve hematologic parameters in patients with hypersplenism and sickle cell disease (SCD). MATERIAL AND METHODS: This prospective study includes 35 homozygous hemoglobin S patients with SCD and hypersplenism who underwent PSE from 2015 until 2021 in Kinshasa. Patients were evaluated, before and after PSE (1, 3 and 6 months), using clinical, laboratory and ultrasonographic methods. PSE was performed with the administration of gelatin sponge particles embolizing 60-70% of the splenic parenchyma. RESULTS: The mean age was 10 (± 4) years and (21/35, 60%) were male. After PSE Leucocytes decreased at 3 months (16 692.94 vs 13 582.86, p = 0.02) and at six months Erythrocytes increased 2 004 000 vs. 2 804 142 (p < 0.001), Platelets increased (168 147 vs. 308 445, p < 0.001) and Hemoglobin increased (5.05 g/dL vs. 6.31 g/dL, p < 0.001) There was a significant dicrease in the need of transfusions from 6 (2-20) before PSE to 0.06 (0-1) after PSE (p < 0.001). The most frequent complication was splenic rupture (4/35, 11.4%), seen only and in all patients with hypoechogenic nodules at baseline. CONCLUSION: PSE is a safe procedure in patients with SCD and hypersplenism, that do not have hypoechogenic nodules in the spleen. PSE improves the hematological parameters and reduces the frequency of blood transfusions.

Consanguineous marriages, premarital screening, and genetic testing: a survey among Saudi university students.

Background: Marriage among cousins or close relatives, i.e., consanguinity, is prevalent in many parts of the world, especially the Muslim world. Across civilizations, cultural norms, religious beliefs, and economic factors affect consanguineous marriages (CMs); however, such marriages have social, genetic, and health repercussions. The present study investigated the university students' attitudes regarding CMs and factors influencing their attitudes at King Abdulaziz University (KAU), Jeddah, Kingdom of Saudi Arabia (KSA). Methods: This cross-sectional prospective study was conducted at KAU Jeddah in 2023. The questionnaire was distributed via electronic media (Emails, Facebook Messenger & WhatsApp). The convenience sampling technique was used to select participants, and descriptive and inferential statistics were used to analyze the data on SPSS-26. Results: A total of 1707 university students were part of the study (females, 1,198, 70.2%; males, 509, 29.8%). Almost half of the participants, 819 (48.0%), had parents with CMs. Most of the participants, 1,391 (81.5%), had CMs in the family. Half of the participants disagreed that parents consider marriage stable due to high compatibility and the same social relationship before and after marriage. About one-third of respondents said parents believe family marriage transmits cultural values and continuity and keeps wealth in the family. More than three-fourths of the participants stated that if marriage is arranged with first cousins, they will opt for genetic analysis (82.5%) and premarital counseling (85.2%). The personal attitudes of females (p < 0.001), undergraduate (p = 0.02), and health sciences students (p = 0.02) were more positive than their counterparts. Males (OR = 0.41; p < 0.001) and non-health sciences students (OR = 0.68; p = 0.01) were less likely to have significant positive attitudes than their counterparts. Among participants who had CM parents, males (OR = 0.397; p < 0.001) and non-health sciences students (OR = 0.60; p = 0.01) and urban residents (OR = 0.59; p = 0.01) had significantly lower odds of having a positive attitude than their counterparts. Conclusion: The practice of CMs is still prevalent in Saudi culture, with almost half of the participants having CM parents and the majority reporting these marriages in their families. Personal attitudes toward CMs were extremely positive. Most students prefer genetic testing and premarital counseling if marrying first cousins. Gender, faculty, parental income, and educational background influenced participants' attitudes.

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.

SARS-CoV-2 with Influenza B Coinfection in a Patient with Sickle Cell HbSC Presenting with Painful Crisis: A Case Report.

Sickle cell disease is a hereditary red blood cell disorder characterized by hemolytic anemia, particularly in association with stress. As they grow, most children with sickle cell anemia undergo auto-splenectomy, making them vulnerable to serious infections. Patients with sickle cell disease infected with the SARS-CoV-2 virus are reported to have an increased risk for hospitalization, thrombosis, and other complications compared to non-sickle cell patients. Influenza infection in patients with sickle cell is associated with increased morbidity. Patients with sickle cell HbSC are reported to have a milder form of the disease than HbSS. Coinfection with SARS-CoV-2 and influenza B is rarely reported in patients with hematologic diseases, including sickle cell hemoglobinopathy. We are reporting an unusual case of a patient with sickle cell HbSC with co-infection of SARS-CoV-2 and influenza B with a favorable outcome.

Dental Management of a Child With Sickle Cell Anemia: A Case Report.

Sickle cell disease (SCD) has been identified as one of the most prevalent genetic conditions. It alters the shape and function of red blood cells. This brief case report presents a case of a five-year-old male with sickle cell disease who complained of pain in the left mandibular region due to deep proximal caries. Before dental management, a complete fitness evaluation was performed with the help of a pediatrician, followed by informed consent. Dental management includes pulpectomy followed by stainless steel crown placement and Glass ionomer cement (GIC) restoration for superficial caries. Other oral manifestations were observed, including a smooth tongue and mucosal pallor. It was concluded that dentists and health professionals should be knowledgeable of the general and oral anomalies that can be present in individuals with sickle cell anemia in order to take preventive action and implement effective management.

Prevalence of Duffy null and its impact on hydroxyurea in young children with sickle cell disease in the United States.

Consistent with studies showing a high prevalence of the Duffy null phenotype among healthy Black Americans, this retrospective study found that Duffy null was present in >75% of a young and contemporary cohort of children with sickle cell disease (SCD) in the United States. Despite the potential for this phenotype to impact absolute neutrophil counts, hydroxyurea (HU) dosing, and outcomes, it was not associated with being prescribed a lower HU dose or having increased acute SCD visits early in the HU treatment course. Future studies are needed to confirm these findings in older children with SCD.

Description of a national, multi-center registry of patients with sickle cell disease and SARS-CoV-2 infection: Data from the Pediatric COVID-19 United States Registry.

Children with sickle cell disease (SCD) are at risk of complications from viral infections, including SARS-CoV-2. We present the clinical characteristics and outcomes of pediatric patients with SCD from the Pediatric COVID-19 United States Registry who developed acute COVID-19 due to SARS-CoV-2 infection (n = 259) or multisystem inflammatory syndrome in children (MIS-C; n = 4). Nearly half of hospitalized children with SCD and SARS-CoV-2 infection required supplemental oxygen, though children with SCD had fewer intensive care (ICU) admissions compared to the general pediatric and immunocompromised populations. All registry patients with both SCD and MIS-C required ICU admission. Children with SCD are at risk of severe disease with SARS-CoV-2 infection, highlighting the importance of vaccination in this vulnerable population.

Guarding Health: A Comprehensive Review of Nosocomial Infections in Sickle Cell Anemia, a Multifaceted Approach to Prevention.

This comprehensive review explores the complex dynamics of nosocomial infections in individuals with sickle cell anemia (SCA) and advocates for a collaborative strategy to enhance prevention. SCA patients, marked by compromised immunity and susceptibility to infections, face unique challenges that necessitate tailored preventive measures. The review underscores the importance of vaccination, antibiotic prophylaxis, education, and environmental hygiene in mitigating the risk of nosocomial infections. Addressing socioeconomic factors, healthcare system limitations, patient-related issues, and cultural considerations is imperative for effective prevention. The call to action emphasizes the pivotal roles of healthcare professionals, policymakers, researchers, and community engagement in implementing targeted interventions. By fostering a collective effort, this review envisions an improved landscape for infection prevention in SCA patients, enhancing their overall health outcomes and quality of life.

Influence of hydroxyurea on tubular phosphate handling in sickle cell nephropathy.

OBJECTIVE: This study aims to evaluate the markers of tubular phosphate handling in adults with sickle cell anemia (SCA) and the influence of hydroxyurea (HU), the degree of anemia and Hb F concentration on these markers. METHODS: Eighty-eight steady state SCA patients in outpatient follow-up in Fortaleza, Ceara, Brazil and 31 healthy individuals were included in this study. Vitamin D (25OHD) was measured by enzyme-bound fluorescence assay, intact parathyroid hormone (iPTH) by electrochemiluminescence, and serum and urinary phosphate and creatinine by colorimetric methods. Details of Hb F and HU use were obtained from clinical records. Tubular reabsorption of phosphate (TRP) and maximum tubular reabsorption of phosphate (MTRP) were calculated. SCA patients were stratified according to the use of HU, degree of anemia and percentage of Hb F. The significance level was set for p-values <0.05. RESULTS: Compared to controls the 25OHD level (25 ± 11 vs. 30 ± 9 pg/mL) was lower in SCA, while serum phosphate and MTRP were higher (3.86 ± 0.94 vs. 3.46 ± 0.72 and 3.6 ± 1.21 vs. 3.21 ± 0.53, respectively). There was no significant difference in iPTH, TRP and phosphaturia. Serum phosphate showed correlation with TRP (r = 0.32; p-value = 0.008) and MTRP (r = 0.9; p-value <0.001) in SCA. Patients taking HU, especially those with Hb F >10 % presented reduced serum phosphate levels, and TRP and MTRP rates. Those with mild anemia presented reduced serum phosphate levels and MTRP rates. CONCLUSION: Serum phosphate levels and renal phosphate reabsorption rate were increased in SCA. HU use, high Hb F concentration and total Hb were associated with better control of tubular phosphate handling markers.

Transcranial Doppler ultrasound velocities in a population of unstudied African children with sickle cell anemia.

The greatest burden of sickle cell anemia (SCA) globally occurs in sub-Saharan Africa, where significant morbidity and mortality occur secondary to SCA-induced vasculopathy and stroke. Transcranial Doppler ultrasound (TCD) can grade the severity of vasculopathy, with disease modifying therapy resulting in stroke reduction in high-risk children. However, TCD utilization for vasculopathy detection in African children with SCA remains understudied. The objective was to perform a prospective, observational study of TCD findings in a cohort of children with SCA from the Democratic Republic of the Congo, Zambia, and Malawi. A total of 770 children aged 2-17 years without prior stroke underwent screening TCD. A study was scored as low risk when the time-averaged maximum of the mean (TAMMX) in the middle cerebral artery or terminal internal carotid artery was <170 cm/s but >50 cm/s, conditional risk when 170-200 cm/s, and high risk when >200 cm/s. Low-risk studies were identified in 604 children (78%), conditional risk in 129 children (17%), and high risk in three children (0.4%). Additionally, 34 (4%) were scored as having an unknown risk study (TAMMX <50 cm/s). Over the course of 15 months of follow-up, 17 children (2.2%) developed new neurologic symptoms (six with low-risk studies, seven with conditional risk, and four with unknown risk). African children with SCA in this cohort had a low rate of high-risk TCD screening results, even in those who developed new neurologic symptoms. Stroke in this population may be multifactorial with vasculopathy representing only one determinant. The development of a sensitive stroke prediction bundle incorporating relevant elements may help to guide preventative therapies in high-risk children.

Sterile inflammation induces vasculopathy and chronic lung injury in murine sickle cell disease.

Murine sickle cell disease (SCD) results in damage to multiple organs, likely mediated first by vasculopathy. While the mechanisms inducing vascular damage remain to be determined, nitric oxide bioavailability and sterile inflammation are both considered to play major roles in vasculopathy. Here, we investigate the effects of high mobility group box-1 (HMGB1), a pro-inflammatory damage-associated molecular pattern (DAMP) molecule on endothelial-dependent vasodilation and lung morphometrics, a structural index of damage in sickle (SS) mice. SS mice were treated with either phosphate-buffered saline (PBS), hE-HMGB1-BP, an hE dual-domain peptide that binds and removes HMGB1 from the circulation via the liver, 1-[4-(aminocarbonyl)-2-methylphenyl]-5-[4-(1H-imidazol-1-yl)phenyl]-1H-pyrrole-2-propanoic acid (N6022) or N-acetyl-lysyltyrosylcysteine amide (KYC) for three weeks. Human umbilical vein endothelial cells (HUVEC) were treated with recombinant HMGB1 (r-HMGB1), which increases S-nitrosoglutathione reductase (GSNOR) expression by ∼80%, demonstrating a direct effect of HMGB1 to increase GSNOR. Treatment of SS mice with hE-HMGB1-BP reduced plasma HMGB1 in SS mice to control levels and reduced GSNOR expression in facialis arteries isolated from SS mice by ∼20%. These changes were associated with improved endothelial-dependent vasodilation. Treatment of SS mice with N6022 also improved vasodilation in SS mice suggesting that targeting GSNOR also improves vasodilation. SCD decreased protein nitrosothiols (SNOs) and radial alveolar counts (RAC) and increased GSNOR expression and mean linear intercepts (MLI) in lungs from SS mice. The marked changes in pulmonary morphometrics and GSNOR expression throughout the lung parenchyma in SS mice were improved by treating with either hE-HMGB1-BP or KYC. These data demonstrate that murine SCD induces vasculopathy and chronic lung disease by an HMGB1- and GSNOR-dependent mechanism and suggest that HMGB1 and GSNOR might be effective therapeutic targets for reducing vasculopathy and chronic lung disease in humans with SCD.

Comparative transcriptomic analysis of circulating endothelial cells in sickle cell stroke.

Ischemic stroke (IS) is one of the most impairing complications of sickle cell anemia (SCA), responsible for 20% of mortality in patients. Rheological alterations, adhesive properties of sickle reticulocytes, leukocyte adhesion, inflammation and endothelial dysfunction are related to the vasculopathy observed prior to ischemic events. The role of the vascular endothelium in this complex cascade of mechanisms is emphasized, as well as in the process of ischemia-induced repair and neovascularization. The aim of the present study was to perform a comparative transcriptomic analysis of endothelial colony-forming cells (ECFCs) from SCA patients with and without IS. Next, to gain further insights of the biological relevance of differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction network (PPI) construction and in silico prediction of regulatory factors were performed. Among the 2469 DEGs, genes related to cell proliferation (AKT1, E2F1, CDCA5, EGFL7), migration (AKT1, HRAS), angiogenesis (AKT1, EGFL7) and defense response pathways (HRAS, IRF3, TGFB1), important endothelial cell molecular mechanisms in post ischemia repair were identified. Despite the severity of IS in SCA, widely accepted molecular targets are still lacking, especially related to stroke outcome. The comparative analysis of the gene expression profile of ECFCs from IS patients versus controls seems to indicate that there is a persistent angiogenic process even after a long time this complication has occurred. Thus, this is an original study which may lead to new insights into the molecular basis of SCA stroke and contribute to a better understanding of the role of endothelial cells in stroke recovery.

ANALYSIS OF THE APPROACH TO SICKLE CELL ANEMIA IN NATURAL SCIENCE TEXTBOOKS / ANÁLISIS DEL ABORDAJE DE LA ANEMIA FALCIFORME EN LOS LIBROS DE TEXTO DE CIENCIAS NATURALES / ANÁLISE DA ABORDAGEM SOBRE A ANEMIA FALCIFORME EM LIVROS DIDÁTICOS DE CIÊNCIAS DA NATUREZA

This work aimed to analyze the Sickle Cell Anemia (SCA) approach in Natural Sciences textbook collections approved in 2021 National Textbook and Teaching Material Program (PNLD) for High School. The focus of these analyses was: the racial discourse associated with SCA and scientific racism; health approaches; and adequacy from a clinical-scientific point of view. To this end, the content analysis proposed by Bardin was adopted, involving textbooks floating reading, the creation or adaptation of categories and indicators for analysis, the material description and the interpreting the data collected. The data was compared with previous analyses of the approach to SCA in biology textbooks from the 2012 and 2015 PNLD. The approach to SCA, when it did occur in the current collections, was linked to natural selection, without focusing on racial issues, and based on a molecular description. There was a silencing of the approach to SCA in relation to the findings of previous research. In addition, biomedical and reductionist approaches to SCA continued to predominate, disregarding socio-political and historical aspects related to the disease.

El objetivo de este estudio fue analizar el abordaje de la Anemia Falciforme (AF) en las colecciones de Ciencias Naturales y sus Tecnologías aprobadas en el Programa Nacional de Libros de Texto y Material Didáctico (PNLD) 2021 para la enseñanza media. El foco de ese análisis fue: el discurso racial asociado a la Anemia Falciforme y el racismo científico; los abordajes de salud; y la adecuación del punto de vista clínico-científico. Para ello, se adoptó el análisis de contenido propuesto por Bardin, que implica la lectura flotante de las colecciones, la creación o adaptación de categorías e indicadores para el análisis, la descripción del material y la interpretación de los datos. Los datos se compararon con análisis anteriores sobre el abordaje de la AF en los libros de texto de biología de los PNLD de 2012 y 2015. La aproximación a la AF, cuando se producía en las colecciones actuales, estaba vinculada a la selección natural, sin centrarse en cuestiones raciales, y basada en una descripción molecular. Hubo un silenciamiento del abordaje de la AF en relación a los hallazgos de investigaciones anteriores. Además, siguieron predominando los enfoques biomédicos y reduccionistas de la AF, sin tener en cuenta los aspectos sociopolíticos e históricos relacionados con la enfermedad.

Este trabalho objetivou analisar a abordagem sobre a Anemia Falciforme (AF) nas coleções de Ciências da Natureza e Suas Tecnologias aprovadas no Programa Nacional do Livro e do Material Didático (PNLD) de 2021 para o Ensino Médio. Os focos desta análise foram: o discurso racial associado a AF e ao racismo científico; as abordagens de saúde; e a adequação do ponto de vista clínico-científico. Para tanto, adotou-se a análise de conteúdo proposta por Bardin, envolvendo a leitura flutuante das coleções, a criação ou a adaptação de categorias e indicadores para análise, a descrição do material e a interpretação dos dados. Os dados foram comparados com análises anteriores sobre a abordagem da AF em livros didáticos de biologia do PNLD de 2012 e de 2015. A abordagem da AF, quando ocorreu nas coleções atuais, esteve atrelada a seleção natural, sem pautar questões raciais, e a partir de uma descrição molecular. Observou-se um silenciamento na abordagem sobre a AF em relação aos achados de pesquisas anteriores. Além disso, manteve-se a predominância de abordagens biomédicas e reducionistas sobre a AF, desconsiderando aspectos sociopolíticos e históricos relacionados a doença.

Minor physical anomalies including palatal rugae pattern and palatal dimensions in children with sickle cell disease: A cross-sectional analytical study.

Background: Sickle cell disease (SCD) is the most common hereditary hemoglobinopathy, which delays growth leading to an altered skeleton and craniofacial pattern. Palatal rugae patterning has been considered the regulator of the development of the palate. The purpose of the research work was to study the morphology of the palate, rugae pattern, and its dimensions in SCD children and compare them with healthy normal children, and to evaluate its role as minor physical anomalies (MPAs). Methods: A cross-sectional case-control study was designed as per STROBE guidelines. The sample comprised 50 children diagnosed with sickle cell disease (Group SCD) and 50 normal healthy children as control (Group C) belonging to the same age group (10-18 years). Dental impressions were made, followed by the pouring of dental casts. The length of the palatal rugae was measured and categorized into primary (>5 mm), secondary (3 mm-5 mm), and fragmentary rugae (<3 mm). The shape of each primary palatal rugae was identified and categorized as curved, wavy, straight, circular and non-specific. Linear and angular measurements of the palatal rugae patterns and palatal dimensions (width, height, area) were measured and recorded. Results: The total number of palatal rugae and fragmentary rugae was lesser in Group SCD than in Group C (p < 0.05). The depth of the palate was significantly increased, whereas the area of the palate significantly decreased in Group SCD. Conclusions: The children with SCD showed distinctive palatal rugae patterns and dimensions when compared with normal healthy children that can be attributed as potential MPAs for sickle cell disease. Children with SCD had an under-developed palatal rugae pattern with a deep, narrow and small palate when compared to healthy children.The dimensions of the palatal rugae pattern in SCD showed reduced distance between the incisive papilla and the first and last rugae, indicating a further decrease in the anteroposterior dimensions of the palate. These findings may aid in the early diagnosis and prevention of malocclusion in children with SCD by appropriate interceptive orthodontic treatment.

Acute Chest Syndrome: A Bibliometric Analysis of the Top 100 Most Cited Articles.

Acute chest syndrome (ACS) is a major cause of morbidity and mortality in patients with SCD (SCD). The analysis of research productivity and trends in ACS may serve as a valuable guide for investigators, institutions, and funding agencies to plan the future directions of research. The current review aims to evaluate the productivity and trends of publications related to ACS in adults by analyzing the top 100 most cited articles. A bibliometric analysis of the top 100 most cited articles related to ACS in adults was conducted on May 20, 2021. The Scopus database was searched to identify the top-cited articles. The following term was applied: "acute chest syndrome" in the fields of title, abstract, and keyword. The most cited article received a total of 776 citations, while the least cited received a total of 10 citations. Over half of the identified articles received 35 citations or less. The articles originated in 12 different countries; the overwhelming majority of articles originated in the United States (n = 75), with small contributions from developing countries with a high prevalence of sickle cell disease. Blood and American Journal of Hematology published the largest number of articles, with nine articles each. The Author "Vichinsky, E.P." has the largest contribution with a total of 10 articles. The plethora of the highly cited articles were Observational studies, while randomized controlled trials were represented by seven articles. The present study demonstrates that research in ACS may be receiving less attention than it should. Therefore, research empowerment and adequate funding are of paramount importance to improve research productivity and quality. Additionally, more collaborative efforts should be encouraged to reduce the gap between developed and developing countries.

Adverse pregnancy, fetal and neonatal outcomes in women with sickle cell disease in a Middle Eastern country.

BACKGROUND: Sickle cell disease in pregnancy is associated with high maternal and fetal mortality. However, studies reporting pregnancy, fetal, and neonatal outcomes in women with sickle cell disease are extremely limited. OBJECTIVES: The objectives of the study are to determine whether women with sickle cell disease have a greater risk of adverse pregnancy, fetal, and neonatal outcomes than women without sickle cell disease and identify the predictors of adverse pregnancy, fetal, and neonatal outcomes in women with sickle cell disease. DESIGN: A retrospective pair-matched case-control study was conducted to compare 171 pregnant women with sickle cell disease to 171 pregnant women without sickle cell disease in Muscat, Sultanate of Oman. METHODS: All pregnant Omani women with sickle cell disease who delivered between January 2015 and August 2021 at Sultan Qaboos University Hospital and Royal Hospital, who were either primipara or multipara and who had a gestational age of 24-42 weeks, were included as patients, whereas women who had no sickle cell disease or any comorbidity during pregnancy, who delivered within the same timeframe and at the same hospitals, were recruited as controls. The data were retrieved from electronic medical records and delivery registry books between January 2015 and August 2021. RESULTS: Women with sickle cell disease who had severe anemia had increased odds of (χ2 = 58.56, p < 0.001) having adverse pregnancy outcomes. Women with sickle cell disease had 21.97% higher odds of delivering a baby with intrauterine growth retardation (χ2 = 17.80, unadjusted odds ratio = 2.91-166.13, p < 0.001). Newborns born to women with sickle cell disease had 3.93% greater odds of being admitted to the neonatal intensive care unit (χ2 = 16.80, unadjusted odds ratio = 1.97-7.84, p < 0.001). In addition, the children born to women with sickle cell disease had 10.90% higher odds of being born with low birth weight (χ2 = 56.92, unadjusted odds ratio = 5.36-22.16, p < 0.001). Hemoglobin level (odds ratio = 0.17, p < 0.001, 95% confidence interval = 0.10-3.0), past medical history (odds ratio = 7.95, p < 0.001, 95% confidence interval = 2.39-26.43), past surgical history (odds ratio = 17.69, p < 0.001, 95% confidence interval = 3.41-91.76), and preterm delivery (odds ratio = 9.48, p = 0.005, 95% confidence interval = 1.95-46.23) were identified as predictors of adverse pregnancy, fetal, and neonatal outcomes in women with sickle cell disease. CONCLUSION: As pregnant women with sickle cell disease are at increased risk for pregnancy, fetal, and neonatal adverse outcomes; improved antenatal surveillance and management may improve the outcomes.

Characterization of a cohort of Angolan children with sickle cell anemia treated with hydroxyurea.

BACKGROUND: Sickle Cell Anemia (SCA) is a monogenic disease, although its severity and response to treatment are very heterogeneous. OBJECTIVES: This study aims to characterize a cohort of Angolan children with SCA and evaluate their response to hydroxyurea (HU) treatment and the potential side effects and toxicity. METHODS: The study enrolled 215 patients between 3 and 12 years old before and after the administration of HU, at a fix dose of 20 mg/kg/day for 12 months. RESULTS: A total of 157 patients started HU medication and 141 of them completed the 12-month treatment. After initiating HU treatment, the frequency of clinical events decreased (transfusions 53.4 %, hospitalizations 47.1 %). The response to HU medication varied among patients, with some experiencing an increase in fetal hemoglobin (HbF) of <5 %. The mean increase in HbF was 11.9 %, ranging from 1.8 % to 31 %. Responders to HU treatment were 57 %, inadequate responders 38.7 % and non-adherent 4.2 %. No clinical side effects related to HU were reported. Hematological toxicities were transient and reversible. Children naïve to HU and with lower HbF reported higher number of hospitalizations caused by malaria infection. During HU treatment, the frequency of malaria episodes did not appear to be affected by HbF levels. CONCLUSIONS: the present study provided a valuable contribution to the understanding of the clinical and laboratory profiles of Angolan children with SCA. These findings support the evidence that the implementation of prophylactic measures and treatment with HU is associated with increased survival in children with SCA.

Impact of maternal depression on malnutrition treatment outcomes in older children with sickle cell anemia.

BACKGROUND: Malnutrition and sickle cell anemia (SCA) result in high childhood mortality rates. Although maternal depression is an established risk factor for malnutrition in younger children, little is known about its impact on treatment response in children with malnutrition. We aimed to determine the relationship, if any, between maternal depression scores and malnutrition treatment outcomes in older children with SCA. METHODS: We conducted a planned ancillary study to our randomized controlled feasibility trial for managing severe acute malnutrition in children aged 5-12 with SCA in northern Nigeria (NCT03634488). Mothers of participants completed a depression screen using the Patient Health Questionnaire (PHQ-9).We used a multivariable linear regression model to describe the relationship between the baseline maternal PHQ-9 score and the trial participant's final body mass index (BMI) z-score. RESULTS: Out of 108 mother-child dyads, 101 with maternal baseline PHQ-9 scores were eligible for inclusion in this analysis. At baseline, 25.7% of mothers (26 of 101) screened positive for at least mild depression (PHQ-9 score of 5 or above). The baseline maternal PHQ-9 score was negatively associated with the child's BMI z-score after 12 weeks of malnutrition treatment (ß=-0.045, p = 0.041). CONCLUSIONS: Maternal depressive symptoms has an impact on malnutrition treatment outcomes. Treatment of malnutrition in older children with sickle cell anemia should include screening for maternal depression and, if indicated, appropriate maternal referral for depression evaluation and treatment. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov (#NCT03634488) on January 30, 2018, https://clinicaltrials.gov/study/NCT03634488 .

In vitro delayed response to dihydroartemisinin of malaria parasites infecting sickle cell erythocytes.

BACKGROUND: Decreased efficacy of artemisinin-based combination therapy (ACT) for Plasmodium falciparum malaria has been previously reported in patients with sickle cell disease (SCD). The main purpose of this study was to investigate the in vitro susceptibility of isolates to dihydro-artemisinin (DHA) to provide a hypothesis to explain this treatment failure. METHODS: Isolates were collected from patients attending health centres in Abidjan with uncomplicated P. falciparum malaria. The haemoglobin type has been identified and in vitro drug sensitivity tests were conducted with the ring stage assay and maturation inhibition assay. RESULTS: 134 isolates were obtained. Parasitaemia and haemoglobin levels at inclusion were lower in patients with haemoglobin HbSS and HbSC than in patients with normal HbAA. After ex vivo RSA and drug inhibition assays, the lowest rate of parasitic growth was found with isolates from HbAS red cells. Conversely, a significantly higher survival rate of parasites ranging from 15 to 34% were observed in isolates from HbSS. Isolates with in vitro reduced DHA sensitivity correlate with lower RBC count and haematocrit and higher parasitaemia at inclusion compared to those with isolates with normal DHA sensitivity. However, this decrease of in vitro sensitivity to DHA was not associated with Kelch 13-Propeller gene polymorphism. CONCLUSION: This study highlights an in vitro decreased sensitivity to DHA, for isolates collected from HbSS patients, not related to the Pfkelch13 gene mutations. These results are in line with recent studies pointing out the role of the redox context in the efficacy of the drug. Indeed, SCD red cells harbour a highly different ionic and redox context in comparison with normal red cells. This study offers new insights into the understanding of artemisinin selective pressure on the malaria parasite in the context of haemoglobinopathies in Africa.

Massive spontaneous subdural hemorrhage mimicking dural venous thrombosis in a sickle cell adolescent, a rare case report.

INTRODUCTION: Sickle cell disease is one of the most common hemoglobinopathies in Africa. Tanzania alone accounts for about 11,000 sickle cell births annually making it one of the most common disorders in eastern Africa. The affected individuals are prone to several complications since childhood as a result of the defective hemoglobin structure, these include neurological complications such as ischemic stroke due to hypercoagulability state caused by the disease. Spontaneous intracranial hemorrhage such as subdural hemorrhage in the absence of predisposing factors such as trauma, anticoagulant use, or recent blood transfusions is rare. As reported in the previous literature. CASE PRESENTATION: We report a rare case of acute spontaneous subdural hemorrhage in an adolescent sickle cell patient of African descent. DISCUSSION: Initial management including early referral and medical treatment is crucial for cases that are suspicious of intracranial hemorrhage. These cases are more common to be missed in resource-limited settings where there are a limited number of neurosurgery interventions. CONCLUSION: Although few reported cases of spontaneous intracranial hemorrhage in sickle cell patients are reported, it is important to be vigilant as a clinician wherever a sickle cell patient presents with signs of increased intracranial pressure without a history of trauma such as in our patient and order an urgent brain imaging to rule out spontaneous hemorrhagic events which may lead to fatal consequences if missed out.