Chelation Therapy Research Articles

The Diagnostic Performance of Serum Glycosylated Ferritin in Patients Undergoing Regular Blood Transfusion: An Indicator of Iron Overload to Initiate Iron Chelation Therapy.

Background and objective Serum ferritin concentration and transferrin saturation are commonly employed to estimate body iron but are non-specific to iron overload. Glycosylated ferritin may be primarily elevated in cases of iron overload in patients undergoing regular blood transfusions. In this study, we aimed to estimate glycosylated ferritin and determine its cutoff values for iron overload in patients receiving blood transfusions regularly. We also endeavored to the examine correlation between serum ferritin and glycosylated ferritin in patients receiving regular blood transfusions. Methods We conducted a cross-sectional study involving 17 patients undergoing regular blood transfusions in the Department of Medical Oncology/Hematology, who had already received ≥10 transfusions without any iron chelation therapy or acute inflammation. All participants were evaluated based on a questionnaire to gather relevant medical details. Serum iron, ferritin, glycosylated ferritin, and unsaturated iron-binding capacity (UIBC) were estimated. Total iron-binding capacity (TIBC) and transferrin saturation were also calculated. Results Participants were divided into two groups based on transferrin saturation (≥50% as a reference for iron overload). The group with transferrin saturation ≥50% had significantly higher levels of serum ferritin, glycosylated ferritin, and iron, compared to the group with transferrin saturation <50%. Glycosylated ferritin showed a positive correlation with ferritin (rho=0.80) and transferrin saturation (rho=0.64), which was statistically significant. UIBCand TIBCshowed a negative association with glycosylated ferritin. The correlation of glycosylated ferritin with units of blood transfusion (Spearman's rho=0.60) was found to be better than that of serum ferritin (Spearman's rho=0.52). Conclusions Based on our findings, glycosylated ferritin could be a potential marker for transfusion-related iron overload. The optimal cutoff value for iron overload using serum glycosylated ferritin level was >587.55 ng/mL. Further extensive studies withlarger sample sizes will substantiate the role of glycosylated ferritin in predicting post-transfusion iron overload.

Abstract Tu011: Targeted chelation therapy decreases Cryopyrin/NLRP3 expression and acts as senomorphic in Chronic Kidney Disorder induced Vascular Calcification.

Background: The high phosphate (P) microenvironment caused by mineral imbalance in chronic kidney disease (CKD) has been reported to induce osteogenic changes in healthy Vascular Smooth Muscle Cells (VSMCs), leading to the calcification of arteries. We have previously shown that EDTA therapy can reverse calcification of the arteries in a rat model of CKD. This study investigated whether global mineral imbalance observed during CKD can initiate senescent changes in the aorta. We focused on NLRP3 as an intracellular source of SASP and evaluated if chelation therapy with EDTA has senotherapeutic potential. Methods: We used an early-stage adenine diet-based rodent model of CKD to evaluate whether senescent cells accumulate prior to vascular calcification. For validation studies, we adopted an ex-vivo approach, wherein we cultured aortic rings under high phosphate conditions for different durations to simulate the early and late stages of vascular calcification. Further, to test the efficacy of chelation therapy, EDTA loaded- human serum albumin nanoparticles tagged with anti-elastin antibody- Flexibzumab (EL-EDTA -NPs) were successfully targeted to the site of calcification in the aorta in a progressive CKD rodent model. Results: Using a flow-cytometry-based approach to detect senescent cells based on SA-βGal activity, we evidence the presence of senescent cells that accumulate in the aorta prior to calcific changes as observed using micro-CT and histopathology in the in vivo model of vascular calcification. Further, we show that targeted chelation therapy with EDTA NPs acts as senomorphic and decreases NLRP3 inflammasome formation. The EL-EDTA-NPs decreased mineral deposits in arteries and thus altered the local immune microenvironment, secretion of growth factors, and proteases within the aortic tissue, identified as SASP. Conclusion: For the first time, the current study reports that the accumulation of senescent cells occurs before calcification and provides an opportunity to analyze the potential role of senescence in the pathological progression of vascular calcification. Additionally, these findings emphasize the role of altered Ca and Pi microenvironment observed during CKD in initiating senescent changes via NLRP3 activation in the aorta. Furthermore, these findings highlight the potential of a targeted EDTA delivery approach to modulate tissue micro-environment selectively by decreasing Ca deposition and SASP in the aorta.

Surgical Management of Iatrogenic Mercury Poisoning From Subcutaneous Injection Into the Arm.

Mercury, an element with threats of severe toxic insult to humans and no biological function, has a surprisingly extensive record of human exposure. Regardless of hesitancies toward its harmfulness, it has been historically identified with an almost supernatural power to provide protection from evil and sickness, give good fortune, lend aid in athletic undertakings, or even allow one to achieve immortality. Mercury poisoning is an iatrogenic disease even today as people attempt to achieve these effects through volitional injections into their body by practitioners. Although an uncommon practice in the United States, awareness of patient presentation after volitional injections of elemental mercury is necessary for appropriate treatment of these patients. We aim to increase awareness of the cultural practice of subcutaneous injections of mercury, as it is uncommonly seen in the United States, to contribute a broader understanding to the patient's medical presentation and describe an approach and the impact of medical and surgical intervention. In this report, we describe a rare case of elemental mercury poisoning secondary to volitional subcutaneous injection to the arm. Initial management of care through chelation therapy and monitoring of renal and serum mercury levels in addition to symptoms of systemic spread was overseen by an internal medicine physician and poison control. Surgical intervention via full-thickness excision of the visible mercury to the right arm followed by local flap and skin grafting reconstruction was performed. Mercury poisoning from intentional subcutaneous administration is an uncommon patient presentation in the United States; however, knowledge of management of this rare condition is important for effective management of iatrogenic mercury toxicity.

Skin complications during iron chelation therapy for beta-thalassemia: overview and treatment approach.

Thalassemia is an inherited genetic disorder of hemoglobin that affects a large population worldwide, and it is estimated that between 50,000 and 60,000 infants with thalassemia are born each year. The most common treatment for thalassemia is blood transfusion, which leads to iron overload. This in itself is a serious clinical condition, and is commonly managed with iron chelation therapy. However, iron chelators can cause various skin complications, including hyperpigmentation, skin rash, itching, and photosensitivity. These skin side effects can impact patients' quality of life. Therefore, this article provides a comprehensive overview of skin complications caused by iron chelators, along with a proposed comprehensive approach to their management in patients with beta-thalassemia. Key strategies include patient education, regular skin assessment, sun protection measures, symptomatic relief with topical corticosteroids and antihistamines, and consideration of treatment modification if severe complications occur. Collaboration between hematologists and dermatologists, along with psychological support and regular follow-up, is an essential component of this multidisciplinary approach. By implementing these strategies, healthcare providers can optimize skin care for patients with beta-thalassemia treated with iron chelators and improve their quality of life.

MRI changes of the pituitary gland and brain in Thalassemia major: A comprehensive review of clinical implications

Introduction: Thalassemia major is a genetic disorder characterized by chronic anemia requiring frequent blood transfusions, leading to iron overload in various organs, including the pituitary gland and brain. MRI is a pivotal tool in assessing the extent of iron deposition and its clinical consequences in these patients. Objective: To summarize the MRI findings related to pituitary and brain changes in thalassemia major and to elucidate their clinical implications based on existing literature. Methods: A comprehensive review of the literature was conducted, focusing on studies that employed MRI to investigate pituitary and brain changes in patients with thalassemia major. Data extracted from these studies included the number of patients, MRI findings, and associated clinical outcomes. Results: The review included studies published between 1998 and 2022. Key findings are as follows: Pituitary Gland Changes: Multiple studies reported reduced pituitary gland volume and signal intensity, correlating with hypogonadotropic hypogonadism (HH) and delayed puberty. Specific MRI metrics such as pituitary-to-fat signal intensity ratios (SIRs) and pituitary-R2 values were elevated in patients with HH, indicating significant iron overload. Brain Changes: Increased brain T2* values indicative of iron overload was observed. Clinical Associations: The MRI findings were consistently associated with various endocrinal abnormalities, including hypogonadism, short stature, delayed puberty, and growth hormone deficiency. Severe pituitary iron deposition and volume loss were predictive of hypogonadism. Specific studies highlighted the independent progression of iron overload in different organs, emphasizing the importance of organ-specific MRI evaluation. Additional Findings: Notably, iron chelation therapy showed potential benefits in reversing some of the endocrinal and cardiac complications associated with iron overload. Discussion and Conclusions: MRI is a valuable diagnostic tool for detecting iron overload in the pituitary gland and brain in thalassemia major patients. The findings from various studies highlight significant clinical implications, including hypogonadotropic hypogonadism, delayed puberty, and growth hormone deficiency. Regular MRI assessments, along with appropriate chelation therapy, are crucial in managing and mitigating these complications. Further research is needed to establish standardized MRI protocols and improve early diagnosis and treatment outcomes in thalassemia major.

Deferasirox adherence in patients with thalassemia: Exploring the association with patient knowledge and ferritin levels

In this study, data from 171 patients with thalassemia were analyzed. There was high variability in ferritin levels among patients, with a median of 2290 ng/mL. The median Morisky adherence score was 4, and 75% of the patients had low adherence levels to deferasirox. There were no significant correlations between the adherence score and patients’ sociodemographic data. However, a significant positive correlation was noted between the adherence score and the knowledge score of the patients. Ferritin levels were significantly and negatively correlated with the adherence score, as demonstrated by the highest ferritin level observed among patients with low levels of adherence. In conclusion, a low level of adherence to deferasirox was noted among patients with thalassemia. Adherence levels were directly associated with patients’ knowledge of the disease and its therapy, while ferritin levels were inversely linked to adherence levels. Thus, tailored and effective strategies are needed to optimize chelation therapy and patient outcomes.

Hubungan Transfusi Darah Berulang dan Kepatuhan Konsumsi Obat Kelasi Besi dengan Kadar Ferritin pada Pasien Thalasemia di Kota Depok

Repeated transfusions cause iron overload in β thalassemia patients. Therefore, iron chelation therapy is needed to reduce the amount of ferritin and ions in the blood. Compliance with iron chelation therapy is one of the factors that affect the patient's serum ferritin level. This study aims to determine the relationship between repeated blood transfusions and consumption of iron chelating drugs with serum ferritin levels of β thalassemia patients at Depok City Hospital in 2021. This research is a retrospective cohort study. The initial population was 112 people, sampling was carried out using the non-probability method and obtained 69 people who met the inclusion and exclusion criteria. This research was conducted from January 2021 to December 2021 in three medical record installations at Depok City Hospital. Respondents who rarely did repeated blood transfusions were 42 (60.9%), respondents who adhered to taking iron chelation drugs were 45 (65.2%), and respondents who had high ferritin levels were 43 (62.3%). There is a relationship between repeated blood transfusions and ferritin levels in thalassemia patients in Depok City in 2021. There is a relationship between adherence to taking iron chelating drugs and ferritin levels in thalassemia patients in Depok City in 2021. It is recommended that clinicians continue to provide a deeper understanding to parents or the patient's family to continue to carry out regular chelation therapy and check serum ferritin levels regularly.

Comparison of R2* and FerriScan liver iron concentration (LIC) quantification in the clinical classification of Iron overload states

PurposeThis study assessed the clinical classification performance of an R2*-based MRI technique for LIC quantification relative to FerriScan, with intra-patient FerriScan LIC uncertainty taken into account. The variabilities of R2* and FerriScan LIC were also assessed. Materials and methodsThis was an ethics approved retrospective study, performed on patients undergoing chelation treatment for iron overload. 126 patients (69 women, 57 men), with an age of 42 +/− 16 years (range 19–86 years) were included. FerriScan and R2* MRI at 1.5 T were performed as part of a routine liver iron assessment protocol. For R2* MRI, a commercially available pulse sequence and reconstruction implementation was used, together with a previously derived calibration curve to convert R2* to LIC. Clinical classifications arising from R2*-derived LIC estimates were compared to those based on FerriScan. The accuracy and precision of the R2* technique was calculated. The variabilities of FerriScan- and R2*-derived estimates of LIC were compared with a Wilcoxon Signed Rank test. Significance was set at the 95% confidence level. ResultsThe precision of R2* ranged from 0.59 to 0.92, with an overall accuracy of 72%. When intra-patient FerriScan LIC uncertainty was considered, precision and accuracy increased to >94% and 97% respectively. The R2*-LIC variability (=17%) was significantly lower than the FerriScan-LIC variability (34%) at the 95% confidence level (p < 10−3). ConclusionMRI R2*-based LIC estimates provided a similar clinical classification as FerriScan. The intra-patient uncertainty of R2*-based LIC estimates was significantly lower than FerriScan.

Modeling Plutonium Decorporation in a Female Nuclear Worker Treated with Ca-DTPA after Inhalation Intake.

The present work models plutonium (Pu) biokinetics in a female former nuclear worker. Her bioassay measurements are available at the US Transuranium and Uranium Registries. The worker was internally exposed to a plutonium-americium mixture via acute inhalation at a nuclear weapons facility. She was medically treated with injections of 1 g Ca-DTPA on days 0, 5, and 14 after the intake. Between days 0 and 20, fecal and urine samples were collected and analyzed for 239Pu and 241Am. Subsequently, she was followed up for bioassay monitoring over 14 y, with additional post-treatment urine samples collected and analyzed for 239Pu. The uniqueness of this dataset is due to the availability of: (1) both early and long-term bioassay data from a female with plutonium intake; (2) data on chelation therapy for a female; and (3) fecal measurement results. Chelation therapy with Ca- and/or Zn-salts of DTPA is known to aid in reducing the internal radiation dose by enhancing the excretion of plutonium and americium from the body. Such enhancement affects plutonium biokinetics in the human body, posing a challenge to the internal dose assessment. The current radiation dose assessment practice is to exclude the data affected by Ca-DTPA from the analysis. The present analysis is the first to explicitly model the chelation-affected bioassay data in a female by using a newly developed chelation model. Thus, the bioassay data collected during and after the Ca-DTPA administrations were used for biokinetic modeling and dose assessment. The Markov Chain Monte Carlo method was used to investigate model parameter uncertainty, based on the bioassay data and assumed prior probability distributions. A χ2/nData (number of data points) ≈ 1 was observed in this study, which indicates self-consistency of the data with the model. Results of this study show that the worker's 239Pu intake was 12 Bq, with a committed effective dose to the whole-body of 1.2 mSv and a committed equivalent dose to the bone surfaces, liver, and lungs of 37.8, 9.1, and 0.8 mSv, respectively. This study also discusses the worker's dose reduction due to chelation treatment.

Clinical burden and healthcare resource utilization associated with managing transfusion-dependent β-thalassemia in France

Objective To describe the clinical burden and healthcare resource utilization associated with managing transfusion-dependent β-thalassemia (TDT) in France. Methods We used the French National Health Data System (système national des données de santé) to identify eligible patients from January 1, 2012, to March 1, 2019. Inclusion criteria were a diagnosis of β-thalassemia, ≥8 red blood cell (RBC) transfusion episodes per year in ≥2 consecutive years following the diagnosis, and ≥1 year of follow-up data. Patients were excluded if medical records showed evidence of sickle cell disease, α-thalassemia, hereditary persistence of fetal hemoglobin, or hematopoietic stem cell transplant. Clinical complications, mortality, treatment use, and healthcare resource utilization were evaluated. Results Overall, 331 eligible patients with TDT were identified. Mean age was 26.1 (standard deviation [SD]: 18.0) years, and 50.5% were male. Common clinical complications were endocrine (26.0%), hepatobiliary (22.7%), and cardiopulmonary (18.7%). Fifteen (4.5%) patients died during follow-up, with a mortality rate of 1.16 deaths per 100 person-years (mean age of death: 52.5 years [SD: 22]). Patients had a mean of 13.5 (SD: 5.2) RBC transfusion episodes and 11.2 (SD: 5.3) iron chelation therapy treatments per year. Healthcare resource utilization was substantial, with a mean of 14.8 inpatient hospitalizations (including 13.8 mean inpatient day cases) and 16.9 outpatient prescriptions per patient per year. Conclusions Patients with TDT in France experience significant clinical complications, elevated mortality, and substantial healthcare resource utilization driven by frequent RBC transfusion episodes and inpatient hospitalizations. These results reinforce the need for disease-modifying therapies for this patient population.

Plasma amino acid profiles in thalassaemia major with iron overload

Introduction: Iron overload in thalassaemia major patients mainly occurs due to periodic transfusions. When iron exceeds transferrin capacity, non-transferrin bound iron accumulates and causes tissue damage, including in the gastrointestinal tract, resulting in impaired enterocyte function and amino acid absorption. The aim of this study was to evaluate amino acid profiles in patients with thalassaemia major after repeated transfusions and chelation. Methods: Whole blood amino acids were analysed from dried blood spots using liquid chromatography tandem mass spectrometry. This study consisted of two parts: a cross-sectional and a cohort study in thalassaemia-β-major patients. In the cross-sectional study, amino acid profiles were analysed in 219 thalassaemia patients who received routine transfusion and chelation therapy, and 60 healthy control subjects. The cohort study included 21 subjects, from whom blood samples were taken at pre-transfusion, 1-day posttransfusion, one and three months post-chelation to evaluate changes in amino acid levels. Results: There were significant differences between amino acid levels in thalassaemia subjects and controls. Positive correlations were found between serum iron and transferrin with age, also between transferrin with proline, valine, phenylalanine, aspartic acid, and glutamic. Phenylalanine and aspartic acid were significantly lower in subjects with transferrin lower than 180 µg/dL. Significant correlations were found between haemoglobin with essential and non-essential amino acid groups. From the cohort study, significant changes were observed in glycine, alanine, leucine, and aspartic acid. Conclusion: Amino acid profiles in thalassaemia patients differed compared to healthy controls, even after transfusion and chelation. Phenylalanine and aspartic acid were significantly lower in subjects with low transferrin levels.

STUDY OF THE LONG-TERM EFFECTS OF DIABETES ON THE OVERALL HEALTH AND QUALITY OF LIFE IN THALASSEMIA PATIENTS

Thalassemia is a genetic blood disorder characterized by chronic anemia, requiring regular blood transfusions and chelation therapy. Diabetes mellitus is a common complication in thalassemia patients, primarily due to iron overload affecting the pancreas. This study investigates the long-term effects of diabetes on the overall health and quality of life in thalassemia patients. The research aims to understand how diabetes exacerbates complications associated with thalassemia and to identify strategies for improved management and care. The study includes a cohort of thalassemia patients with diabetes, compared to a control group of thalassemia patients without diabetes. Parameters assessed include glycemic control, incidence of diabetes-related complications, and overall health markers such as liver function, cardiovascular health, and renal function. Quality of life is measured using standardized questionnaires addressing physical, emotional, and social well-being. Preliminary findings indicate that thalassemia patients with diabetes have a significantly higher incidence of comorbid conditions, including cardiovascular disease and renal impairment (De Sanctis et al., 2016). Additionally, the quality of life in these patients is notably lower, with increased reports of fatigue, pain, and psychological distress (Haines et al., 2013). Effective management of diabetes in thalassemia patients, through regular monitoring and tailored treatment plans, is crucial in mitigating these adverse effects and improving patient outcomes (Farmaki et al., 2006). This study underscores the importance of integrated care approaches for thalassemia patients with diabetes, emphasizing the need for multidisciplinary teams to address the complex interplay of these conditions. Further research is needed to develop targeted interventions that can enhance the long-term health and quality of life for this vulnerable patient population. Results: study indicated that plant extracts exhibited higher inhibition than antibiotics. The minimum inhibitory concentration (MIC) while the results of the lowest inhibitory concentration of carvacrol for the bacterial species under study showed that it had an effect at a concentration of 615 µg/ml against Escherichia coli, 307.5 µg/ml for the species Corynebacterium stratium, Morganella morganii and Pseudomonas aeruginosa, and the least effect was 76.875 µg/ml on Staphylococcus aureus, it gave less results than the antibiotic used Carvacrol (Absorbance was measured at Wavelength 600) .

Copper impairs the intestinal barrier integrity in Wilson disease

In Wilson disease (WD), liver copper (Cu) excess, caused by mutations in the ATPase Cu transporting beta (ATP7B), has been extensively studied. In contrast, in the gastrointestinal tract, responsible for dietary Cu uptake, ATP7B malfunction is poorly explored. We therefore investigated gut biopsies from WD patients and compared intestines from two rodent WD models and from human ATP7B knock-out intestinal cells to their respective wild-type controls.We observed gastrointestinal (GI) inflammation in patients, rats and mice lacking ATP7B. Mitochondrial alterations and increased intestinal leakage were observed in WD rats, Atp7b−/− mice and human ATP7B KO Caco-2 cells. Proteome analyses of intestinal WD homogenates revealed profound alterations of energy and lipid metabolism. The intestinal damage in WD animals and human ATP7B KO cells did not correlate with absolute Cu elevations, but likely reflects intracellular Cu mislocalization. Importantly, Cu depletion by the high-affinity Cu chelator methanobactin (MB) restored enterocyte mitochondria, epithelial integrity, and resolved gut inflammation in WD rats and human WD enterocytes, plausibly via autophagy-related mechanisms.Thus, we report here before largely unrecognized intestinal damage in WD, occurring early on and comprising metabolic and structural tissue damage, mitochondrial dysfunction, and compromised intestinal barrier integrity and inflammation, that can be resolved by high-affinity Cu chelation treatment.

Cardiac Disease in Egyptian Thalassemia Major and Sickle Cell Disease Adolescents in relation to Vitamin D Status Using Echocardiogram &amp; Ultrafast Magnetic Resonance Imaging

Abstract Background Cardiovascular complications are well recognized in patients with β-thalassemia major (β-TM) and sickle cell disease (SCD). Vitamin D deficiency is prevalent in patients with transfusion-dependent thalassemia and there is an association between vitamin D deficiency and both left ventricular function and iron overload in thalassemia. However, the relationship between vitamin D and cardiac iron is not well studied in Egypt and the role of vitamin D in cardiac disease in SCD and β-TM needs to be assessed. Aim To assess vitamin D status in children and adolescents with SCD and β-TM in relation to cardiac complications using echocardiography and cardiac magnetic resonance (CMR) T2*. Methods Forty-one patients with SCD and 35 patients with β-TM without symptomatic cardiac disease were studied stressing on history of splenectomy and transfusion history. Markers of hemolysis, serum ferritin and vitamin D levels were measured. Liver iron concentration (LIC) was assessed by magnetic resonance imaging (MRI). Screening for cardiovascular abnormalities was performed by the non-invasive Doppler echocardiography and CMR was used to assess myocardial iron overload. Results Echocardiography showed that cardiac functions were significantly impaired in β-TM patients compared with SCD while the frequency of pulmonary hypertension risk (elevated TRV ≥2.5 m/sec) was consistent between both β-TM and SCD groups. Cardiac T2* (which reflects cardiac iron overload) was significantly lower while myocardial iron concentration (MIC) was significantly higher in β -TM patients compared with SCD group. Vitamin D levels were decreased in both SCD and β-TM patients than control levels; however, SCD patients had significantly lower vitamin D levels. Low vitamin D levels were significantly associated withincreased risk of pulmonary hypertension in the SCD group while In β-TM group, vitamin D levels were significantly lower in patients with cardiac disease and those with serum ferritin levels ≥ 2500 µg/L. A significant evidence of diastolic dysfunction was found in SCD and β-TM patients who had low serum vitamin D level &amp;lt; 20 ng/mL. Vitamin D levels were negatively correlated to serum ferritin and LIC while positively correlated to cardiac T2*. Conclusion Low vitamin D levels were associated with cardiopulmonary dysfunction in adolescents with SCD and β-TM. Vitamin D deficiency in those patients was linked to cardiac iron overload leading to iron induced cardiomyopathy. Proper chelation therapy is mandatory to improve cardiac disease, iron overload and consequently, vitamin D status in β-TM patients.

The influence of the pre-addition of semi-dry and dry slaked lime during the purification of flue gas on the subsequent chelation and solidification treatment of MSWI fly ash

Incineration is a main way to dispose the municipal solid waste (MSW) in China, but municipal solid waste incineration (MSWI) fly ash will negatively impact the environment and human health as containing high content of heavy metals. This study aimed to investigate the influence of the pre-addition of dry/semi-dry slaked lime during the purification of flue gas on the subsequent chelation and solidification treatment of fly ash. This study has found that semi-dry slaked lime had more effect on the solidification rate of heavy metals in MSWI fly ash compared to the pre-addition of the dry slaked lime. As the dosage of semi-dry slaked lime increased, the solidification rate of Zn and Ba increased to 100 %, while the solidification rate of Cr decreased to as low as 0 %. However, the effect of the dosage of semi-dry slaked lime on the other heavy metals (Cu, Pb, Cd, Ni) showed a complex trend. This study underscores the importance of the pre-addition of slaked lime during the purification of flue gas in influencing subsequent chelation and solidification treatment of MSWI fly ash. It provides valuable insights into optimizing lime dosage to enhance heavy metal stabilization, contributing to more effective and sustainable waste management practices.

Clinical Profile, Laboratory Characteristics and Treatment of Wilson’s Disease in Children from Western India

To study the clinical profile and laboratory characteristics and treatment of children with Wilson’s disease (WD). The current study was done at Department of pediatrics, Sir Padampat Institute of Neonatology and Pediatric Health, Sawai Man Singh Medical College, Jaipur. It was an observational study and institution ethics committee approved the study. Patients visiting the outpatient department or admitting in wards with clinical presentation suggestive of WD were enrolled in the study after obtaining a valid informed written consent. Patients subjected to detailed clinical history and physical examination. All patients subjected to routine blood count, biochemistry including liver function tests and specific laboratory investigations. They underwent ophthalmological examination. Ultrasonography abdomen and liver biopsy performed in enrolled patients. Magnetic resonance imaging brain carried out in patients with neurological WD. Ferenci score was calculated for each of the patients. Total 50 patients were included in the study. Mean age at the time of diagnosis was 9.4 years with delay of 11 months after onset of symptoms. Male is to female ratio was 2/1. Hepatic manifestation were seen in 76% patients and 24% patients presented with neurological disease. Kayser-Fleischer ring was seen in 44% patients with hepatic disease and 83% patients with neurological disease. Twenty-four hour urinary copper was more than 2 time of upper limit of normal in all patients. Fifty-four percent patients showed improvement with chelation therapy and 9 patients died during the study period. WD in children has varied clinical manifestation and early diagnosis is necessary for good prognosis. It requires wide range of tests as genetic testing is not easily available. Acute liver failure has high mortality. Early chelation therapy reverses the clinical and biochemical abnormalities.

Correlation between plasma biochemical parameters and cardio-hepatic iron deposition in thalassemia major patients

Introduction Major Thalassemia patients suffer from iron overload and organ damage, especially heart and liver damage. Early diagnosis and treatment with a chelator can reduce the complications and mortality of iron overload. Therefore, we aimed to investigate the biochemical and hematological predictors as an alternative and indirect indicator of iron deposition in heart and liver cells in comparison with the MRI T2* method as the gold standard. Material and method MRI T2* was evaluated in the heart and liver tissues of 62 major beta-thalassemia patients undergoing regular transfusion and chelator therapy. Biochemical and hematological factors were also measured, including serum ferritin, serum electrolytes, liver enzymes, hemoglobin, blood glucose, and serum magnesium. The correlation between these factors was assessed using statistical evaluations. Result Serum ferritin had a positive and significant correlation with liver siderosis based on MRI T2* (p-value = .015), and no significant association was observed with cardiac siderosis (p-value = .79). However, there was a significant positive correlation between cardiac iron deposition and fasting blood sugar level (p-value = −.049), and plasma level of liver enzymes (alanine aminotransferase (ALT) (p-value = .001), aspartate aminotransferase (AST ((p-value = .01)). Moreover, there was a significant negative correlation between cardiac iron overload and plasma magnesium level (p-value = .014). According to MRI T2*, there was no significant correlation between cardiac and hepatic iron overload (p value = .36). Conclusion An increase in blood sugar or liver enzymes and a decrease in serum magnesium was associated with an increase in cardiac iron overload based on MRI T2*. Liver iron overload based on MRI T2* had a significant correlation with serum ferritin.

Correlation between Serum Ferritin and Thyroid Hormones Level in Children with Thalassemia

Background: Thalassemia is a group of hereditary blood disorder characterized by reduced or absent globin chain synthesis resulting in transfusion dependent anaemia and iron overload. Due to regular blood transfusion and inadequate chelation therapy patient develop multiorgan dysfunction. Objectives: To find any correlation between serum ferritin and thyroid hormones level in children with transfusion dependent thalassemia. Methods: This cross-sectional study was carried out in the department of Paediatrics and department of Medicine, Sylhet MAG Osmani Medical College Hospital between June, 2021 to May, 2022, on one hundred children with transfusion dependent thalassemia who were on more than 12 times blood transfusion but did not take any chelation therapy and whose serum ferritin level were &gt; 1000 ng/ml. Assessment of their thyroid hormones level and statistically its correlation with serum ferritin were done. Result: A total of 53 (53%) male and 47 (47%) female were included in this study. The mean age of the patients was 9.47 ±3.63 years. Mean serum ferritin was 1980±1126.19 ng/ml, mean serum TSH was 3.55±2.08 µIU/ml, mean serum free T4 was 1.10±0.18 ng/ml, mean serum free T3 was 3.64±0.37 pg/ml. Subclinical hypothyroidism and euthyroid were found in 20 patients (20%) and 80 patients (80%) respectively. No overt hypothyroidism or hyperthyroidism were found. Mean serum ferritin in subclinical hypothyroid and euthyroid were 2407±995.37 ng/ml and 1875.59±1131.18 ng/ml respectively which difference was statistically significant (P value &lt;0.05). Scattered diagram was done and it showed linear correlation between serum ferritin and serum TSH of subclinical hypothyroid group. No linear correlation was found between serum ferritin and F.T3 and F.T4 on scattered diagram. Positive (Pearson) correlation was found between serum ferritin and serum TSH of subclinical hypothyroid group and strong positive (Pearson) correlation (r=0.74, P=0.02) was found between them. Conclusion: This study showed that good percentages of children with transfusion dependent thalassemia are suffering from subclinical hypothyroidism. There is positive correlation between serum ferritin level and subclinical hypothyroidism.

Analysis of how Serum Ferritin and the Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) are correlated to Hepatic MRI T2* Findings in Children with Beta-Thalassemia Major

Background: Iron overload is a major complication in patients with beta-thalassemia major. Excessive iron accumulation leads to organ dysfunction. The regular assessment of iron is crucial to effectively manage iron overload in these patients. This study evaluated the correlation between serum ferritin levels, the Aspartate Aminotransferase-to-Platelet Ratio Index (APRI), and hepatic MRI T2* findings in children with beta-thalassemia major. Materials and Methods: This retrospective analytical study was conducted at Shahid Sadoughi Hospital in Yazd in 2023. The research population comprised all the children under the age of 15 with beta-thalassemia major who had undergone multiple blood transfusions (at least ten units of blood). Results: The participants in this study were 70 children with beta-thalassemia major, including 35 males and 35 females. Their mean age was 3.52 ± 10.76 years. The mean relaxation time of liver MRI T2* was 4.42 ± 4.91 ms. The participants also had the APRI score of 0.55 ± 1.90, the aspartate aminotransferase (AST) level of 23.82 ± 36.29, and the serum ferritin level of 285.01 ± 3244.04 (ng/mL). Based on MRI T2* results, 30% of the patients had a severe liver iron overload, 27.1% had a moderate overload, 21.4% had a severe overload, 18.6% had a mild overload, and 2.9% had near-normal iron levels.The AST level demonstrated a significant association with the type of chelation treatment (P = 0.003). The duration of blood transfusion (in years) showed a strong positive correlation with the patients' age (Pearson's coefficient = 0.996). Conclusion: This study indicates the elevated serum ferritin levels and APRI scores in patients with beta-thalassemia major, most of whom have abnormal MRI T2* findings. However, no significant correlation was observed between the APRI score, serum ferritin level, and MRI T2* results.

Comorbidities and complications in adult and paediatric patients with pyruvate kinase deficiency: Analysis from the Peak Registry.

Pyruvate kinase (PK) deficiency, a rare, congenital haemolytic anaemia caused by mutations in the PKLR gene, is associated with many clinical manifestations, but the full disease burden has yet to be characterised. The Peak Registry (NCT03481738) is an observational, longitudinal registry of adult and paediatric patients with PK deficiency. Here, we described comorbidities and complications in these patients by age at most recent visit and PKLR genotype. As of 13 May 2022, 241 patients were included in the analysis. In total, 48.3% had undergone splenectomy and 50.5% had received chelation therapy. History of iron overload (before enrolment/during follow-up) was common (52.5%), even in never-transfused patients (20.7%). Neonatal complications and symptoms included jaundice, splenomegaly and hepatomegaly, with treatment interventions required in 41.5%. Among adults, osteopenia/osteoporosis occurred in 19.0% and pulmonary hypertension in 6.7%, with median onset ages of 37, 33 and 22 years, respectively. Biliary events and bone health problems were common across PKLR genotypes. Among 11 patients who had thromboembolic events, eight had undergone prior splenectomy. Patients with PK deficiency may have many complications, which can occur early in and throughout life. Awareness of their high disease burden may help clinicians better provide appropriate monitoring and management of these patients.