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Journal of Multidisciplinary Healthcare 2024This retrospective study evaluated nutritional status and body composition changes in paediatric β-thalassemia (β-TM) patients before and after hematopoietic stem cell...
Nutritional and Body Composition Changes in Paediatric β-Thalassemia Patients Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Study Using Bioelectrical Impedance Analysis.
OBJECTIVE
This retrospective study evaluated nutritional status and body composition changes in paediatric β-thalassemia (β-TM) patients before and after hematopoietic stem cell transplantation (HSCT), using bioelectrical impedance analysis (BIA), and explored their relationship with HSCT outcomes.
METHODS
A cohort of 40 paediatric β-TM patients undergoing allogeneic HSCT was assessed for their nutritional status, anthropometric parameters, including body mass index (BMI), weight, and height, and body composition parameters pre-and post-HSCT, focusing on BIA measurements, including intracellular water (ICW), extracellular water (ECW), fat mass (FAT), fat-free mass (FFM), Skeletal Muscle Mass (SMM), soft Lean Mass (SLM), percent body fat (PBF), Body Cell Mass (BCM), Phase angle (PA) and muscle balance pre- and post-HSCT. Post-HSCT clinical outcomes, including acute graft-vs-host disease (aGVHD), engraftment time, oral mucositis (OM), sinusoidal obstruction syndrome (SOS), and diarrhoea in relation to nutrition status after HSCT were analysed.
RESULTS
After HSCT, 28.21% experienced diminished nutritional status, with 71.43% of those who were wasting before HSCT showing diminished nutritional status, significantly higher than the normal group (18.75%, P = 0.012). Anthropometric changes included significant weight reduction (87.5%, 22.15 ± 7.46 vs 20.74 ± 6.57, P < 0.001) and BMI decrease (90%, 15.19 ± 1.70 vs 14.05 ± 1.48, P < 0.001). Body composition parameters, which are FFM, SMM, SLM, ICW, ECW, BCM, and PA (18.26 ± 5.71 vs 17.27 ± 5.19, 8.68 ± 3.30 vs 7.93 ± 3.02, 17.11 ± 5.28 vs 16.06 ± 4.84, 8.19 ± 2.54 vs 7.62 ± 2.31, 5.15 ± 1.58 vs 4.94 ± 1.47, 11.74 ± 3.63 vs 10.92 ± 3.32, 4.42 ± 0.50 vs 3.90 ± 0.57, respectively, P < 0.001) analysis revealed significant decreases. No significant differences in clinical outcomes were observed based on nutritional status.
CONCLUSION
Paediatric β-TM patients undergoing HSCT exhibit significant changes in nutrition status and body composition, emphasizing the need for focused attention on malnourished children who are more prone to diminished nutritional status. Comprehensive BIA aids in understanding the impact, urging consideration for extended follow-up and larger cohorts in future research.
PubMed: 38751668
DOI: 10.2147/JMDH.S463796 -
Asian Journal of Neurosurgery Mar 2024The role of some biomarkers such as S100 beta (S100B) has been somewhat known in determining the severity of primary acute spinal cord injury (SCI), and today, it...
The role of some biomarkers such as S100 beta (S100B) has been somewhat known in determining the severity of primary acute spinal cord injury (SCI), and today, it has been the basis of various relevant studies. Therefore, this study estimates the S100B level in serum and cerebrospinal fluid (CSF) in patients with spinal injuries. This was a descriptive-analytic study. In this study, 31 patients with acute SCI referred to Sari Imam Khomeini Hospital, Iran, were recruited. Patients were divided into two groups of complete and incomplete SCI according to the American Spinal Injury Association (ASIA). The S100B concentrations in serum and CSF levels were compared between the two groups. There was only significant positive correlation between S100B CSF concentration and complete SCI based on the ASIA criterion, meaning that in cases of complete SCI the S100B CSF concentration was significantly increased correlation coefficient (CC) (cc = 0.529 and = 0.002). Based on the results of serum S100B protein concentration, 14.70 ng/dL with a sensitivity of 66.7% and specificity of 55% was determined as cutoff for complete SCI. Also, about the CSF S100B protein level variable, concentration of 342.18 ng/dL with 100% sensitivity and 64% specificity was determined as cutoff for complete injury. The results of this unique study have shown that S100B were useful markers for predicting the prognosis of patients with acute SCI and cutoff points determined for serum and especially CSF concentrations can differentiate complete and incomplete SCI.
PubMed: 38751401
DOI: 10.1055/s-0043-1771323 -
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 -
Therapeutic Advances in Hematology 2024Secondary failure of platelet recovery (SFPR) is a common complication that influences survival and quality of life of patients with β-thalassemia major (β-TM) after...
Development of a nomogram to predict the risk of secondary failure of platelet recovery in patients with β-thalassemia major after hematopoietic stem cell transplantation: a retrospective study.
BACKGROUND
Secondary failure of platelet recovery (SFPR) is a common complication that influences survival and quality of life of patients with β-thalassemia major (β-TM) after hematopoietic stem cell transplantation (HSCT).
OBJECTIVES
A model to predict the risk of SFPR in β-TM patients after HSCT was developed.
DESIGN
A retrospective study was used to develop the prediction model.
METHODS
The clinical data for 218 β-TM patients who received HSCT comprised the training set, and those for another 89 patients represented the validation set. The least absolute shrinkage and selection operator regression algorithm was used to identify the critical clinical factors with nonzero coefficients for constructing the nomogram. Calibration curve, C-index, and receiver operating characteristic curve assessments and decision curve analysis (DCA) were used to evaluate the calibration, discrimination, accuracy, and clinical usefulness of the nomogram. Internal and external validation were used to test and verify the predictive model.
RESULTS
The nomogram based on pretransplant serum ferritin, hepatomegaly, mycophenolate mofetil use, and posttransplant serum albumin could be conveniently used to predict the SFPR risk of thalassemia patients after HSCT. The calibration curve of the nomogram revealed good concordance between the training and validation sets. The nomogram showed good discrimination with a C-index of 0.780 (95% CI: 70.3-85.7) and 0.868 (95% CI: 78.5-95.1) and AUCs of 0.780 and 0.868 in the training and validation sets, respectively. A high C-index value of 0.766 was reached in the interval validation assessment. DCA confirmed that the nomogram was clinically useful when intervention was decided at the possibility threshold ranging from 3% to 83%.
CONCLUSION
We constructed a nomogram model to predict the risk of SFPR in patients with β-TM after HSCT. The nomogram has a good predictive ability and may be used by clinicians to identify SFPR patients early and recommend effective preventive measures.
PubMed: 38737005
DOI: 10.1177/20406207241245190 -
Clinical Case Reports May 2024This case report and literature review examine the use of a relatively novel agent in a transfusion-dependent beta-thalassemia patient with extramedullary hematopoiesis...
KEY CLINICAL MESSAGE
This case report and literature review examine the use of a relatively novel agent in a transfusion-dependent beta-thalassemia patient with extramedullary hematopoiesis (EMH). It examines the benefits and risks associated with its use and reviews the available literature while highlighting the drug's results in our patient with a higher risk profile.
ABSTRACT
Beta thalassemia can be complicated by EMH, which causes different symptoms based on location and size. Luspatercept is a new agent approved for transfusion-dependent thalassemia and Non-transfusion-dependent thalassemia (NTDT). Still, its use in patients with EMH was not well studied, and literature showed an increased risk of EMH expansion or development of new masses after its use. We discuss, in this case, the results of luspatercept treatment in a patient with transfusion-dependent thalassemia who is considered high risk for its use due to the patient's specific characteristics (history of symptomatic intrathoracic EMH, previous splenectomy, refusal to use antithrombotic medications). While also highlighting the benefits of using luspatercept regarding decreasing the iron overload and improving hemoglobin levels and examining how it was used safely to manage a transfusion-dependent thalassemia patient with an extramedullary hematopoiesis mass with no adverse events of note.
PubMed: 38736568
DOI: 10.1002/ccr3.8795 -
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 -
Journal of Clinical Medicine Apr 2024: in β-thalassemia, important clinical complications are caused by the presence of free α-globin chains in the erythroid cells of β-thalassemia patients. These free...
Increased Expression of α-Hemoglobin Stabilizing Protein (AHSP) mRNA in Erythroid Precursor Cells Isolated from β-Thalassemia Patients Treated with Sirolimus (Rapamycin).
: in β-thalassemia, important clinical complications are caused by the presence of free α-globin chains in the erythroid cells of β-thalassemia patients. These free α-globin chains are present in excess as a result of the lack of β-globin chains to bind with; they tend to aggregate and precipitate, causing deleterious effects and overall cytotoxicity, maturation arrest of the erythroid cells and, ultimately, ineffective erythropoiesis. The chaperone protein α-hemoglobin-stabilizing protein (AHSP) reversibly binds with free α-globin; the resulting AHSP-αHb complex prevents aggregation and precipitation. Sirolimus (rapamycin) has been previously demonstrated to induce expression of fetal hemoglobin and decrease the excess of free α-globin chain in the erythroid cells of β-thalassemia patients. The objective of this study was to verify whether sirolimus is also able to upregulate AHSP expression in erythroid precursor cells (ErPCs) isolated from β-thalassemia patients. the expression of AHSP genes was analyzed by measuring the AHSP mRNA content by real-time quantitative PCR (RT-qPCR) and the AHSP protein production by Western blotting. AHSP gene expression was found to be higher in ErPCs of β-thalassemia patients in comparison to ErPCs isolated from healthy subjects. In addition, AHSP expression was further induced by treatment of β-thalassemia ErPCs with sirolimus. Finally, AHSP mRNA was expressed at an increased level in ErPCs of sirolimus-treated β-thalassemia patients participating in the NCT03877809 Sirthalaclin clinical trial. this exploratory study suggests that AHSP expression should be considered as an endpoint in clinical trials based on sirolimus.
PubMed: 38731008
DOI: 10.3390/jcm13092479 -
Anemia 2024Anemia, a global health concern, affects one-fourth of the global population, particularly women. In Indonesia, its prevalence is 23.7%, with 32.0% among 15-24...
BACKGROUND
Anemia, a global health concern, affects one-fourth of the global population, particularly women. In Indonesia, its prevalence is 23.7%, with 32.0% among 15-24 year-olds. Factors include poor nutrition, infectious diseases, chronic diseases, inherited disorders, and inadequate healthcare access. This study aimed to investigate anemia prevalence and its etiology among medical students from Jakarta.
METHODS
This study was a descriptive research with a cross-sectional approach. Undergraduate students aged 18-23 years old were selected and consented to participate by a consecutive nonrandom sampling methods. Laboratory blood data were evaluated (including Hb, MCV, MCH, HbA, and ferritin levels) and DNA was isolated to confirm the type of thalassemia carrier.
RESULTS
In total, 140 medical students, mainly female, were recruited. Anemia was found in 13.6% (11.4% had low MCV and/or MCH), and 16.5% had low MCV and/or MCH without anemia. Hb electrophoresis revealed high HbA values, suggesting the HbE variant (2.1%), and -thalassemia carrier (0.7%). DNA analysis confirmed the cd26 mutation and heterozygous IVS1nt5. Among those without anemia, 5% had , while in the group with anemia, 1.4% had (with coexistent IDA), 3.6% had , and 0.7% had .
CONCLUSION
DNA analysis can identify specific mutations associated with alpha-thalassemia, distinguishing between iron deficiency anemia and the alpha-thalassemia trait. Thalassemia screening should involve low MCV and/or MCH values as the first step (stage 1), followed by Hb analysis (stage 2) and DNA analysis (stage 3). In common areas, a combination of Hb and DNA testing is best. However, healthcare professionals must diagnose and treat thalassemia, as proper management relies on accurately identifying the underlying condition.
PubMed: 38716362
DOI: 10.1155/2024/4215439 -
Practical Laboratory Medicine Mar 2024Hemoglobin A1c has been widely used to diagnose and monitor diabetes. However, the accuracy of HbA analysis can be significantly affected by hemoglobin variants, leading...
BACKGROUND
Hemoglobin A1c has been widely used to diagnose and monitor diabetes. However, the accuracy of HbA analysis can be significantly affected by hemoglobin variants, leading to falsely low or elevated levels and misdiagnosis or inappropriate diabetes management.
CASE REPORT
In this study, we present the case of a 23-year-old man with undetectable HbA levels during his annual checkup by high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE). To investigate the reason for HbA absence, Sanger sequencing, multiplex ligation-dependent probe amplification assay (MLPA), long-read single molecule real-time sequencing (SMRT) and MALDI-TOF mass spectrometry (MS) were performed, and the proband was identified as compound heterozygous of β-thalassemia with Hb G-Taipei (HBB:c.68A > G) and Hb Lepore-Boston-Washington (NG_000007.3:g.63632_71046del).
CONCLUSION
The combination of these molecular technologies including MLPA, long-read SMRT sequencing and MALDI-TOF MS is beneficial for identifying rare hemoglobin variants. This case also provides essential evidence for uncovering the effect of compound heterozygosity for Hb Lepore-Boston-Washington and Hb G-Taipei on hematological phenotypes and HbA analysis.
PubMed: 38715657
DOI: 10.1016/j.plabm.2024.e00379 -
International Journal of General... 2024We evaluated the long-term safety and efficacy of thalidomide in the treatment of transfusion-dependent β-thalassemia (TDT).
OBJECTIVE
We evaluated the long-term safety and efficacy of thalidomide in the treatment of transfusion-dependent β-thalassemia (TDT).
METHODS
Fifty patients with TDT were treated with thalidomide and followed-up for 5 years. Thalidomide at a 50 mg dose was administered once a day after dinner. The dose was increased to 150 mg/d after 3 d if well tolerated. After 1 year of treatment, the hemoglobin (Hb) level was stabilized at its maximum, and thalidomide was gradually reduced and maintained at the minimum dose. The hematological response, transfusion dependence, and haemolytic indicators were assessed.
RESULTS
At 9 month of follow-up, 38 (76%) patients achieved an excellent response, 1 (2%) a good response, 4(8%) a minor response, and 7(14%) did not show a response. The overall response rate was 86%. At 9 months, the Hb level increased from 79.0 ± 13.2 g/L at baseline to 99.0 ± 13.7g/L (<0.001). Patients who achieved excellent response continued to show an increase in Hb levels during follow-up. At 48 months, the mean Hb level was 98.99 ± 10.3g/L; 21 patients (84.0%) became transfusion independent. Thalidomide was reduced and maintained to 25 mg/d in three of these patients. Moreover, five patients completed 60 months of follow-up, and with a mean Hb level of 99.8 ± 6.7g/L. During follow-up, grade 1-2 adverse drug reactions were noted; however, no grade 3 or higher adverse event was reported. However, no decrease in hemolytic indicators was observed.
CONCLUSION
Thalidomide was well tolerated in the long term, while it significantly improved Hb levels and reduced the transfusion burden.
PubMed: 38711824
DOI: 10.2147/IJGM.S462991