UNASSIGNED: This case-control study investigated the mode of leukocyte function in sickle cell anemia (SCA) to delineate the underlying immunopathology for early diagnosis and mitigate the increased bacterial infection risk in this patient population.
UNASSIGNED: In total, 90 participants comprising 24 hemoglobin (Hb)-AA, 22 Hb-AS, 23 steady state Hb-SS and 21 vaso-occlusive crisis state Hb-SS subjects were recruited for this study. The subjects were further divided into the following six groups: Hb-AA and Hb-AS subjects as control groups, Hb-SS subjects at steady state, Hb-SS subjects in a vaso-occlusive crisis state, Hb-SS subjects undergoing medication (Meds), and Hb-SS subjects undergoing medication plus blood transfusion (Meds/BT) group, respectively. Hematological analysis, Hb electrophoresis, leukocyte ratios, and leukocyte functional assays were assessed with standard methods, and interleukin 8 (IL-8) and L-selectin levels were evaluated using enzyme-linked immunosorbent assays.
UNASSIGNED: Total leukocyte and monocyte counts were increased in the Hb-SS groups compared to the control groups. However, the Hb-SS groups had lower lymphocyte counts than the other groups (p < 0.005). Leukocyte viability was increased in the SCA groups, while phagocytic activities and oxidative respiratory burst were both reduced in the SCA groups (p < 0.005). Increased IL-8 levels were observed in all SCA groups (p < 0.05), whereas L-selectin levels of the Hb-SS steady and Hb-SS on Meds groups were decreased compared to the other groups (p < 0.05). The neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were higher in the SCA groups than the control groups (p < 0.05).
UNASSIGNED: Impaired leukocyte phagocytic and oxidative respiratory burst activities constitute altered leukocyte function in SCA, which can increase their susceptibility to infections and the risk of mortality, especially during the crisis state. Novel therapeutic approaches can be tailored specifically to enhance these leukocyte functions and mitigate the increased infection risk in SCA.
UNASSIGNED: بحثت دراسة الحالات والشواهد هذه في وضع وظائف الكريات البيضاء في فقر الدم المنجلي لتحديد الأمراض المناعية الأساسية للتشخيص المبكر والتخفيف من خطر العدوى البكتيرية المتزايدة في هذه الفئة من المرضى.
UNASSIGNED: تسعون مشاركا يضمون 24 هيموجلوبين-أ أ و22 هيموجلوبين-أ س و23 حالة ثابتة من هيموجلوبين-س س و21 حالة أزمة انسداد الأوعية الدموية هيموجلوبين-س س تم استقطابهم لهذه الدراسة. تم تصنيف الموضوعات أيضا إلى ست مجموعات، أي موضوعات هيموجلوبين-أ أ وموضوعات هيموجلوبين-أ س كمجموعات مراقبة، موضوعات هيموجلوبين-س س في حالة مستقرة، موضوعات هيموجلوبين-س س في حالة أزمة انسداد الأوعية الدموية، موضوعات هيموجلوبين-س س الخاضعة للأدوية، ومجموعة هيموجلوبين-س س التي تخضع للعلاج بالإضافة إلى مجموعة نقل الدم على التوالي. تم تقييم تحليل الدم، والرحلان الكهربائي للهيموجلوبين، ونسب الكريات البيضاء، والمقايسات الوظيفية للكريات البيضاء باستخدام الطرق القياسية، وتم تقييم مستويات انترليوكن-8 و إل-سيليكتن باستخدام إليزا.
UNASSIGNED: تم زيادة إجمالي عدد الكريات البيضاء والوحيدات في مجموعات هيموجلوبين-س س مقارنة بمجموعات التحكم. ومع ذلك، كان لدى مجموعات هيموجلوبين-س س عدد أقل من الخلايا الليمفاوية مقارنة بالمجموعات الأخرى. تمت زيادة صلاحية كريات الدم البيضاء في مجموعات فقر الدم المنجلي، في حين تم تقليل أنشطة البلعمة والانفجار التنفسي التأكسدي في مجموعات فقر الدم المنجلي. لوحظت زيادة في مستويات انترليوكن-8 في جميع مجموعات فقر الدم المنجلي، ومع ذلك انخفضت مستويات إل-سيليكتن لـ هيموجلوبين-أ س الثابت و هيموجلوبين-أ س في مجموعات الأدوية مقارنة بالمجموعات الأخرى. تم العثور على نسبة العدلات إلى الخلايا اللمفاوية، ونسبة الخلايا الليمفاوية الوحيدة ونسبة الصفائح الدموية إلى الخلايا الليمفاوية لمجموعات فقر الدم المنجلي أعلى من مجموعات التحكم.
UNASSIGNED: يشكل خلل أنشطة البلعمة والانفجار التنفسي التأكسدي لكريات الدم البيضاء في مجموعات مرض فقر الدم المنجلي، مما قد يزيد من قابليتها للإصابة بالعدوى وخطر الوفاة، خاصة أثناء حالة الأزمة. يمكن تصميم الأساليب العلاجية الجديدة خصيصا لتعزيز وظائف كريات الدم البيضاء هذه والتخفيف من خطر الإصابة المتزايد في مرض فقر الدم المنجلي.

Sickle cell anemia (SCA) is a genetically inherited hemoglobinopathy characterized by the abnormal morphology of red blood cells, resulting in vaso-occlusive events and diverse clinical complications. Recent investigations have unveiled a novel dimension in understanding SCA severity through the lens of eosinophilic dialogues. This review article synthesizes current knowledge on the molecular intricacies of eosinophils in the context of SCA, exploring their biology, molecular markers, and interactions with other cellular components. Eosinophil-mediated inflammation and oxidative stress are dissected to elucidate their impact on the disease course. Furthermore, the review evaluates potential therapeutic interventions and outlines future directions in this burgeoning field. The term \"Eosinophilic Dialogues\" encapsulates the multifaceted molecular exchanges that influence SCA severity, presenting a promising avenue for targeted interventions and improved clinical outcomes. This review serves as a comprehensive resource for researchers, clinicians, and healthcare practitioners engaged in unraveling the complex pathophysiology of SCA and exploring novel therapeutic avenues.

Background Sickle cell anemia (SCA) results in various complications, necessitating continuous daily care and placing burdens on caregivers. Objectives This study aims to assess the burden on family caregivers of children with SCA and its associated factors. Materials and methods This analytical cross-sectional study was conducted in Madinah City, Saudi Arabia. We included family caregivers of children with SCA who were registered and treated at the Maternity and Child Hospital in King Salman Medical City. Data were collected from all registered files of children who received treatment for SCA. Data from participants was obtained using the validated Arabic version of the Zarit Burden Interview (ZBI). Descriptive statistics, chi-square tests, independent sample t-tests, and multivariate regression analysis were used in the statistical analysis. Results Overall, 124 caregivers participated out of 166 (response rate: 74.7%), among which 83 (66.9%) were fathers, 72 (58.1%) were aged ≥40 years, 96 (77.4%) held Saudi nationality, and 62 (50%) had a monthly income of <5000 SAR. The average daily caregiving hours were 5±4 hours, and 30 (24.2%) of children were diagnosed with associated physical or psychological diseases. The Zarit Burden Interview score indicated that 45 (36.3%) of caregivers reported no burden, whereas 51 (41.1%), 22 (17.7%), and 6 (4.8%) reported mild, moderate, and severe burden, respectively. Factors contributing to the burden included being a mother, low financial resources, non-Saudi nationality, children diagnosed with associated physical or psychological diseases, and caregiving hours. Conclusions The burden on SCA caregivers was higher for caregivers who were mothers, non-Saudis, those with lower income, and children with physical or psychological diseases, as well as more caregiving hours. Enhancing the overall well-being of families affected by the SCA burden involves creating targeted interventions and comprehensive support programs.

Sickle cell disease (SCD) is an inherited blood disorder marked by homozygosity of hemoglobin S, which is a defective hemoglobin caused by a missense mutation in the β-globin gene. However, clinical phenotypes of SCD vary among patients. To investigate genetic variants associated with various clinical phenotypes of SCD, we genotyped DNA samples from 520 SCD subjects and used a genome-wide association study (GWAS) approach to identify genetic variants associated with phenotypic features of SCD. For HbF levels, the previously reported 2p16.1 locus (BCL11A) reached genome significance (rs1427407, P = 8.58 × 10-10) in our GWAS as expected. In addition, we found a new genome-wide significance locus at 15q14 (rs8182015, P = 2.07 × 10-8) near gene EMC7. GWAS of acute chest syndrome (ACS) detected a locus (rs79915189, P = 3.70 × 10-8) near gene IDH2 at 15q26.1. The SNP, rs79915189, is also an expression quantitative trait locus (eQTL) of IDH2 in multiple tissues. For vasoocclusive episode (VOE), GWAS detected multiple significant signals at 2p25.1 (rs62118798, P = 4.27 × 10-8), 15q26.1 (rs62020555, P = 2.04 × 10-9) and 15q26.3 (rs117797325, P = 4.63 × 10-8). Our findings provide novel insights into the genetic mechanisms of SCD suggesting that common genetic variants play an important role in the presentation of the clinical phenotypes of patients with SCD.

The Middle Eastern prevalence of sickle cell anemia, a genetic disorder that affects red blood cells, necessitates additional research. On a molecular level, we sought to identify and sort the oral microbiota of healthy individuals and those with sickle cell anemia. Furthermore, it is crucial to comprehend how changes in the genetic makeup of the oral microbiota impact the state of sickle cell anemia. Using next-generation sequencing, the 16S rRNA amplicon was examined using saliva samples from 36 individuals with sickle cell anemia and healthy individuals. These samples were obtained from sickle cell anemia patients (18 samples) and healthy control participants (controls, 18 samples). Various analyses are conducted using bioinformatic techniques to identify distinct species and their relative abundance. Streptococcus, followed by Fusobacterium nucleatum, Prevotella, and Veillonella were the most prevalent genera of bacteria in the saliva of the SCA and non-SCA individuals according to our findings. Rothia mucilaginosa, Prevotella scoposa, and Veillonella dispar species were the dominant species in both sickle cell anemia and non-sickle cell anemia subjects. Streptococcus salivarius, Actinomyces graevenitzii, Actinomyces odontolyticus, and Actinomyces georgiae spp. were the most prevalent bacterial spp. in the studied SCA cases. The sequencing of the 16S rRNA gene yielded relative abundance values that were visualized through a heatmap analysis. Alterations in the oral microflora\'s constitution can significantly affect the susceptibility of sickle cell anemia patients to develop more severe health complications. Salivary diagnosis is a potential tool for predicting and preventing oral microbiome-related diseases in the future.

暂无摘要。

Intravenous mercury poisoning is a rare but severe medical emergency, often resulting from accidental exposure or intentional self-harm. We present the case of a 30-year-old male with a history of sickle cell anemia who presented with high-grade fever, vomiting, giddiness, and breathlessness following intravenous mercury self-administration. Diagnostic challenges included distinguishing symptoms of acute mercury toxicity from those of his chronic condition of sickle cell trait. Markedly elevated serum mercury levels confirmed the diagnosis, with high-resolution computed tomography (HRCT) imaging studies revealing mercury deposits and alveolar lung injury. Management involved antidote of mercury poisoning, including non-invasive ventilation and transfusions, with consultations from multiple specialties. The patient demonstrated significant clinical improvement and was discharged with scheduled follow-ups. This case underscores the complexity of diagnosing and managing intravenous mercury poisoning, highlighting the importance of a comprehensive multidisciplinary approach for optimal patient outcomes.

Sickle Cell Anemia (SCA) is a hereditary blood disorder characterized by the presence of abnormal hemoglobin, leading to the formation of sickle-shaped red blood cells. While extensive research has unraveled many aspects of the genetic and molecular basis of SCA, the role of telomere dynamics in disease progression remains a relatively unexplored frontier. This review seeks to provide a comprehensive examination of telomere biology within the context of SCA, aiming to elucidate its potential impact on molecular aging and the progression of the disease. The impact of oxidative stress on telomere dynamics in SCA is explored, with a particular focus on how increased reactive oxygen species (ROS) may contribute to accelerated telomere shortening and genomic instability. Furthermore, the potential relationship between telomere dysfunction and cellular senescence in SCA is investigated, shedding light on how telomere dynamics may contribute to the premature aging of cells in this population. The review concludes by summarizing key findings and proposing potential therapeutic strategies targeting telomere dynamics to mitigate disease progression in SCA. It also identifies gaps in current understanding and suggests avenues for future research, emphasizing the importance of further investigating telomere biology to advance our understanding of molecular aging and disease progression in Sickle Cell Anemia. This comprehensive exploration of telomere dynamics in SCA offers insights into potential mechanisms of molecular aging and disease progression, paving the way for targeted therapeutic interventions and improved disease management.

Sickle cell anemia (SCA) is a multisystem disease, associated with increased risk for infection and thromboembolic disease, and pregnancy is a stressor for patients with SCA. In general, coronavirus disease 2019 (COVID-19) infection in SCA is associated with a favorable outcome. Literature of pregnancy in SCA with COVID is scarce. We report a case series study of pregnant women with SCA, who are confirmed positive for COVID-19 from May 2020 to March 2021. These patients showed generally mild-to-moderate disease and presented predominantly with fever and painful crisis. They showed a significant drop in Hb from baseline, and they received low-molecular-weight heparin prophylaxis (LMWH) and blood transfusion. The outcome of pregnancy is satisfactory, although the mean birth weight was significantly lower than that reported from the same SCA population.

Red blood cells (RBCs) become sickle-shaped and stiff under hypoxia as a consequence of hemoglobin (Hb) polymerization in sickle cell anemia. Distinguishing between sickle cell disease and trait is crucial during the diagnosis of sickle cell disease. While genetic analysis or high-performance liquid chromatography (HPLC) can accurately differentiate between these two genotypes, these tests are unsuitable for field use. Here, we report a novel microscopy-based diagnostic test called ShapeDx™ to distinguish between disease and trait blood in less than 1 h. This is achieved by mixing an unknown blood sample with low and high concentrations of a chemical oxygen scavenger and thereby subjecting the blood to slow and fast hypoxia, respectively. The different rates of Hb polymerization resulting from slow and fast hypoxia lead to two distinct RBC shape distributions in the same blood sample, which allows us to identify it as healthy, trait, or disease. The controlled hypoxic environment necessary for differential Hb polymerization is generated using an imaging microchamber, which also reduces the sickling time of trait blood from several hours to just 30 min. In a single-blinded proof-of-concept study conducted on a small cohort of clinical samples, the results of the ShapeDx™ test were 100% concordant with HPLC results. Additionally, our field studies have demonstrated that ShapeDx™ is the first reported microscopy test capable of distinguishing between sickle cell disease and trait samples in resource-limited settings with the same accuracy as a gold standard test.