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PloS One 2024Despite the huge burden of sickle cell disease (SCD) among Nigerian children, the burden and outcome of respiratory illnesses remain undocumented. Thus, we aimed to...
Burden and outcome of respiratory morbidities among children and adolescents with sickle cell disease-A retrospective review of emergency presentations in some Nigerian tertiary institutions.
BACKGROUND
Despite the huge burden of sickle cell disease (SCD) among Nigerian children, the burden and outcome of respiratory illnesses remain undocumented. Thus, we aimed to describe the spectrum and outcome of respiratory illnesses among SCD childrenand adolescentadmissions in ten Nigerian tertiary hospitals.
METHOD
A retrospective review of the SCD admission records of children and adolescents with a confirmed diagnosis of respiratory illnesses from 2012 to 2021 in ten tertiary health facilities across five geopolitical zones in Nigeria was conducted. The data, collectedbetween March and June 2023, included the age, sex, diagnosis, complications, duration and outcome of hospitalization.
RESULTS
Of the 72,333 paediatric admissions, 7,256 (10.0%) had SCD; the proportion of SCD from the total admission ranged from 2.1 to 16.3% in the facilities. Of the 7,256 children and adolescents with SCD, 1,213 (16.7%) had respiratory morbidities. Lower respiratory disease was the most common (70.0%) respiratory entity and the majority were pneumonia (40.1.0%), followed by acute chest syndrome (26.7%). Seventeen (1.4%) patients died; all had lower respiratory diseases [(acute chest syndrome ACS (11, 64.7%), pneumonia; 5, 29.4%, and asthma (1, 5.9%). Based on the proportion of deaths among overall SCD, the 17 death cases contributed 9.4% (95% CI 5.9 to 14.5). Factors associated with deaths included duration of hospitalization less than 72 hours and lower respiratory tract diseases.
CONCLUSION
Sickle cell disease is a major contributor to hospitalization among Nigerian children and adolescents, with high respiratory morbidity and mortality. Pneumonia and acute chest syndrome were associated with mortality, andthe highest risk of death within the first 72 hours.
Topics: Humans; Anemia, Sickle Cell; Adolescent; Child; Nigeria; Male; Female; Retrospective Studies; Tertiary Care Centers; Child, Preschool; Infant; Hospitalization; Respiratory Tract Diseases; Acute Chest Syndrome; Cost of Illness
PubMed: 38753737
DOI: 10.1371/journal.pone.0303323 -
Scientific Reports May 2024This pilot study focusing on Sickle Cell Anemia (SCA) patients offers a comprehensive and integrative evaluation of respiratory, cardiovascular, hemodynamic, and...
This pilot study focusing on Sickle Cell Anemia (SCA) patients offers a comprehensive and integrative evaluation of respiratory, cardiovascular, hemodynamic, and metabolic variables during exercise. Knowing that diastolic dysfunction is frequent in this population, we hypothesize that a lack of cardiac adaptation through exercise might lead to premature increase in blood lactate concentrations in SCA patients, a potential trigger for acute disease complication. SCA patients were prospectively included in PHYSIO-EXDRE study and underwent a comprehensive stress test with a standardized incremental exercise protocol up to 4 mmol L blood lactate concentration (BL4). Gas exchange, capillary lactate concentration and echocardiography were performed at baseline, during stress test (at ∼ 2 mmol L) and BL4. The population was divided into two groups and compared according to the median value of percentage of theoretical peak oxygen uptake (% ) at BL4. Twenty-nine patients were included (42 ± 12 years old, 48% of women). Most patients reached BL4 at low-intensity exercise [median value of predicted power output (W) was 37%], which corresponds to daily life activities. The median value of % at BL4 was 39%. Interestingly, diastolic maladaptation using echocardiography during stress test along with hemoglobin concentration were independently associated to early occurrence of BL4. As BL4 occurs for low-intensity exercises, SCA patients may be subject to acidosis-related complications even during their daily life activities. Beyond assessing physical capacities, our study underlines that diastolic maladaptation during exercise is associated with an early increase in blood lactate concentration.
Topics: Humans; Anemia, Sickle Cell; Male; Female; Adult; Diastole; Middle Aged; Exercise Tolerance; Exercise Test; Pilot Projects; Echocardiography; Adaptation, Physiological; Lactic Acid; Prospective Studies; Oxygen Consumption; Exercise
PubMed: 38750085
DOI: 10.1038/s41598-024-61689-w -
Revista Da Associacao Medica Brasileira... 2024The ability to cause death is the definitive measure of an infectious disease severity, particularly one caused by a novel pathogen like severe acute respiratory...
OBJECTIVE
The ability to cause death is the definitive measure of an infectious disease severity, particularly one caused by a novel pathogen like severe acute respiratory syndrome-CoV-2 (COVID-19). This study describes sickle cell disease-related mortality issues during the COVID-19 pandemic in Brazil.
METHODS
The provisional 2020 mortality data originated from the public databases of the Mortality Information System and were investigated using the multiple-cause-of-death methodology.
RESULTS
In 2020, 688 sickle cell disease-related deaths occurred, of which 422 (61.3%) had an underlying cause of death and 266 (38.7%) had an associated cause of death. Furthermore, 98 COVID-19-related deaths occurred, of which 78 were underlying cause of death among sickle cell disease associated (non-underlying) cause of death. Sickle cell disease-related deaths occurred mostly among young adults aged 25-49 years. COVID-19 deaths occurred at ages older than among sickle cell disease-related deaths. Majority of deaths happened in the southeast (42.3%) and northeast regions (34.0%), while COVID-19 deaths prevailed in the northeast region (42.9%). Regarding overall deaths, the leading underlying cause of death was sickle cell disease itself, followed by infectious and parasitic diseases (14.8%), owing to COVID-19 deaths, and diseases of the circulatory system (8.9%). Next, in males, diseases of the digestive system (4.8%) occurred, while, in females, maternal deaths succeeded, included in the chapter on pregnancy, childbirth, and the puerperium, accounting for 5.9% of female deaths. The leading overall associated (non-underlying) cause of deaths were septicemias (29.4%), followed by respiratory failure (20.9%), pneumonias (18.3%), and renal failure (14.7%).
CONCLUSION
In Brazil, COVID-19 deaths produced trend changes in sickle cell disease-related causes of death, age at death, and regional distribution of deaths in 2020.
Topics: Humans; COVID-19; Anemia, Sickle Cell; Brazil; Adult; Female; Middle Aged; Male; Cause of Death; Young Adult; SARS-CoV-2; Adolescent; Child; Pandemics; Aged; Child, Preschool; Age Distribution
PubMed: 38747879
DOI: 10.1590/1806-9282.20231466 -
Molecular Therapy. Methods & Clinical... Jun 2024A major limitation of gene therapy for sickle cell disease (SCD) is the availability and access to a potentially curative one-time treatment, due to high treatment...
A major limitation of gene therapy for sickle cell disease (SCD) is the availability and access to a potentially curative one-time treatment, due to high treatment costs. We have developed a high-titer bifunctional lentiviral vector (LVV) in a vector backbone that has reduced size, high vector yields, and efficient gene transfer to human CD34 hematopoietic stem and progenitor cells (HSPCs). This LVV contains locus control region cores expressing an anti-sickling β-globin gene and two microRNA-adapted short hairpin RNA simultaneously targeting and transcripts to maximally induce fetal hemoglobin (HbF) expression. This LVV induces high levels of anti-sickling hemoglobins (HbA + HbF), while concurrently decreasing sickle hemoglobin (HbS). The decrease in HbS and increased anti-sickling hemoglobin impedes deoxygenated HbS polymerization and red blood cell sickling at low vector copy per cell in transduced SCD patient CD34 cells differentiated into erythrocytes. The dual alterations in red cell hemoglobins ameliorated the SCD phenotype in the SCD Berkeley mouse model . With high titer and enhanced transduction of HSPC at a low multiplicity of infection, this LVV will increase the number of patient doses of vector from production lots to decrease costs and help improve accessibility to gene therapy for SCD.
PubMed: 38745893
DOI: 10.1016/j.omtm.2024.101254 -
American Journal of Men's Health 2024Dyslipidemia is linked to various health complications, including cardiovascular disease and inflammation. This study aimed to assess the association between smoking and...
Dyslipidemia is linked to various health complications, including cardiovascular disease and inflammation. This study aimed to assess the association between smoking and lipid profile in the Tabari cohort population. Data from the Tabari Cohort Study involving 4,149 men were analyzed. A standardized questionnaire collected smoking history, while blood samples measured lipid levels and anthropometric measurements were recorded. Statistical analysis utilized chi-square tests and logistic regression, adjusting for potential confounders. The prevalence of smoking was 893 (21.52%; urban: 20.6%, mountainous: 23.8%, significant level: .024). The adjusted odds ratio (OR) of low high-density lipoprotein (HDL) among smokers 1.48 (95% confidence interval [CI]: 1.25-1.77, < .001) was the same as non-smokers. The adjusted OR of high low-density lipoprotein (LDL) in men with 1 to 10, 11 to 20, and more than 20 cigarettes per day was 0.95 (95% CI: 0.73-1.25), 1.30 (95% CI: 0.99-1.71), and 2.64 (95% CI: 1.32-5.27) and low HDL was equal to 1.34 (95% CI: 1.06-1.68), 1.61 (95% CI: 1.26-2.05), and 2.24 (95% CI: 1.13-4.42) compared with non-smokers, respectively. The study findings indicate that smoking is associated with lower HDL levels, even after adjusting for potential confounders. The odds of low HDL and high LDL increases with higher smoking intensity. The low HDL and high LDL levels in individuals smoking over 20 cigarettes/day, respectively, show a 2.24-fold and a 2.64-fold increased odds compared to non-smokers. These findings highlight the importance of smoking cessation in relation to lipid profiles and related health risks.
Topics: Humans; Male; Middle Aged; Adult; Smoking; Aged; Dyslipidemias; Cohort Studies; Iran; Lipids; Prevalence; Risk Factors; Surveys and Questionnaires
PubMed: 38742733
DOI: 10.1177/15579883241249655 -
BMC Pediatrics May 2024Thalassemias represent some of the most common monogenic diseases worldwide and are caused by variations in human hemoglobin genes which disrupt the balance of synthesis...
BACKGROUND
Thalassemias represent some of the most common monogenic diseases worldwide and are caused by variations in human hemoglobin genes which disrupt the balance of synthesis between the alpha and beta globin chains. Thalassemia gene detection technology is the gold standard to achieve accurate detection of thalassemia, but in clinical practice, most of the tests are only for common genotypes, which can easily lead to missing or misdiagnosis of rare thalassemia genotypes.
CASE PRESENTATION
We present the case of an 18-year-old Chinese female with abnormal values of routine hematological indices who was admitted for genetic screening for thalassemia. Genomic DNA was extracted and used for the genetic assays. Gap polymerase chain reaction and agarose gel electrophoresis were performed to detect HBA gene deletions, while PCR-reverse dot blot hybridization was used to detect point mutations in the HBA and HBB genes. Next-generation sequencing and third-generation sequencing (TGS) were used to identify known and potentially novel genotypes of thalassemia. We identified a novel complex variant ααα/-α in a patient with rare alpha-thalassemia.
CONCLUSIONS
Our study identified a novel complex variant that expands the thalassemia gene variants spectrum. Meanwhile, the study suggests that TGS could effectively improve the specificity of thalassemia gene detection, and has promising potential for the discovery of novel thalassemia genotypes, which could also improve the accuracy of genetic counseling. Couples who are thalassemia carriers have the opportunity to reduce their risk of having a child with thalassemia.
Topics: Humans; alpha-Thalassemia; Female; Adolescent; High-Throughput Nucleotide Sequencing; Genotype; Genetic Testing; Point Mutation; Hemoglobins, Abnormal
PubMed: 38741052
DOI: 10.1186/s12887-024-04811-1 -
Journal of Medicine and Life Jan 2024Sickle cell disease (SCD) is the most common monogenic disorder, although the diversity and heterogenicity of clinical presentations render estimations of disease...
Sickle cell disease (SCD) is the most common monogenic disorder, although the diversity and heterogenicity of clinical presentations render estimations of disease severity unpredictable. This cross-sectional study aimed to determine if laboratory markers could serve as indicators of SCD severity. We enrolled 90 adult patients with SCD with a mean age of 32.33 ± 11.84 years from the eastern province of Saudi Arabia, where SCD is more common than in other regions. Our study revealed a positive significant association between the number of hospitalizations and emergency visits with white blood cells (WBC) (R = 0.241, R = 0.207), respectively. Similarly, positive significant associations were found between the number of hospitalizations and emergency visits with platelets (R = 0.393, R = 0.276), respectively. Conversely, negative significant relationships were found between the number of hospitalizations and emergency visits (ER) with hemoglobin (Hb) F (R = -0.268, R = -0.263), respectively. Additionally, significant negative relationships were found between Hb F (R = -0.223) and the frequency of ICU admission. Only the number of hospitalizations and emergency visits annually were significantly predicted with values of 0.021 and 0.038, respectively. Moreover, an increase in WBC was found to significantly increase the chance of undergoing splenectomy by 23.02%. SCD is a multisystemic disease with heterogeneous clinical presentations and disease severity. Inflammatory markers are valuable tools for better risk stratification and could be translated into developing new therapeutic strategies and modifying the treatment paradigm.
Topics: Humans; Anemia, Sickle Cell; Cross-Sectional Studies; Adult; Male; Female; Severity of Illness Index; Saudi Arabia; Biomarkers; Hospitalization; Young Adult; Middle Aged; Emergency Service, Hospital
PubMed: 38737665
DOI: 10.25122/jml-2023-0397 -
Journal of Blood Medicine 2024Sickle cell disease is an inherited blood disorder which can lead to severe complications, particularly in the cardiovascular and respiratory systems, potentially...
BACKGROUND
Sickle cell disease is an inherited blood disorder which can lead to severe complications, particularly in the cardiovascular and respiratory systems, potentially resulting in arrhythmias, pulmonary hypertension (PH), and cardiomegaly. This study aims to investigate the risk of PH and arrhythmias in adult SCD patients.
METHODS
Retrospective analysis of medical records from King Abdulaziz University Hospital (KAUH) for patients with SCD aged 15 and above between 2009 and 2021. The study included 517 patients, with echocardiograms and electrocardiograms assessed according to the European Society of Cardiology/the European Respiratory Society (ESC/ERS) guidelines for categorizing PH risk (low, moderate, high) and detecting arrhythmias. Data analysis employed the Statistical Package for the Social Sciences (SPSS), utilizing quantitative and qualitative data representation. Multivariate logistic regression identified independent risk factors with odds ratios at a 95% confidence interval (CI).
RESULTS
Among participants, 50.3% were male, with a total sample average age of 34.45 ± 9.28 years. Results indicated that 1.4% of patients experienced arrhythmias, 3.7% had a moderate PH risk, and 3.3% were classified as high PH risk. Logistic regression revealed significant independent risk factors for PH and arrhythmia in patients with SCD, with chronic kidney disease (CKD) carrying the highest odds (26.4 times higher odds of PH and 15.36 times higher odds of arrhythmias).
CONCLUSION
Patients with SCD are at risk for developing PH and various arrhythmias but are often underdiagnosed. Key risk factors for PH included CKD, liver cirrhosis, and pre-existing cardiac conditions. Arrhythmias were significantly associated with CKD and pre-existing cardiac conditions. To mitigate these risks, we recommend involving a multidisciplinary healthcare team in the care of adult patients with SCD. Future prospective studies are advised for early detection of PH and arrhythmias in hemoglobinopathy patients, potentially reducing mortality.
PubMed: 38737582
DOI: 10.2147/JBM.S455564 -
BMC Veterinary Research May 2024Hydrops fetalis (HF) is fluid accumulation in fetus body cavities and subcutaneous tissue. The condition has been described in various farm and companion animal species,...
BACKGROUND
Hydrops fetalis (HF) is fluid accumulation in fetus body cavities and subcutaneous tissue. The condition has been described in various farm and companion animal species, including dogs. Most of cases result from a heart defect. Exact nature of this defect is rarely clarified.
CASE PRESENTATION
A newborn, male French bulldog puppy with severe HF underwent a full anatomopathological examination to diagnose the primary cause of HF. Based on the anatomopathological examination, fetal ultrasound, and micro-computed tomography, transposition of the great arteries with hypoplasia of the ascending aorta, aortic arch interruption, ostium secundum atrial septal defect, severe tricuspid valve dysplasia, as well as hypoplasia of pulmonary vessels and lungs were diagnosed.
CONCLUSIONS
This is the first report of HF caused by severe, complex congenital heart defects with concurrent pulmonary vessel and lung hypoplasia.
Topics: Animals; Hydrops Fetalis; Male; Lung; Dog Diseases; Dogs; Heart Defects, Congenital; X-Ray Microtomography; Animals, Newborn
PubMed: 38734649
DOI: 10.1186/s12917-024-04060-5 -
International Journal of Molecular... Apr 2024Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD), affecting 6-10% of adult SCD patients. Various mechanisms... (Review)
Review
Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD), affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of this disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is currently focused on the potential role of genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the transforming growth factor-beta (TGF-β) pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future, as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield reliable results that will allow a better understanding of SCD-related PH as a part of the disease's clinical spectrum. This review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.
Topics: Humans; Anemia, Sickle Cell; Hypertension, Pulmonary; Polymorphism, Genetic; Genetic Predisposition to Disease
PubMed: 38732015
DOI: 10.3390/ijms25094792