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Caspian Journal of Internal Medicine 2023Growth retardation is a long-term complication in pediatric transfusion-dependent thalassemias (TDTs), presented as short-stature and upper body segment shortening. The...
BACKGROUND
Growth retardation is a long-term complication in pediatric transfusion-dependent thalassemias (TDTs), presented as short-stature and upper body segment shortening. The cause of this condition was chronic hypoxia, iron overload, endocrinopathy, inadequate transfusion, and iron chelation. We analyze the relationship between ferritin level and growth status of pediatric TDTs.
METHODS
This was a cross-sectional study on pediatric TDTs aged 2-18 years old at Dr. Soetomo General Academic Hospital Surabaya, Indonesia conducted in 2020. They required blood transfusion every 2-4 weeks. We evaluated the ratio of upper/lower body segments, weight for age Z-score (WAZ), height for age Z-score (HAZ), and body mass index (BMI) Z-score, based on CDC growth chart as growth status parameters. Serum ferritin was checked every three months to determine iron overload and iron chelation (deferiprone, deferasirox and deferoxamine). We used Spearman correlation and Mann-Whitney U test to analyze between variables (α=0.05).
RESULTS
We enrolled 15/29 males with median age 10.5 years. Serum Ferritin had negative correlation with the ratio of upper/lower body segments (rho=-0.552; P=0.002), but not for HAZ (rho=-0.078; P=0.694), WAZ (rho=-0.186; P=0.342), BMI Z-score (rho=-0.089; P=0.653) especially if serum ferritin was above 2500 µ/L. In deferiprone group (n=8), the WAZ (P=0.034) and BMI Z-score (P=0.031) were lower; but the ratio of upper/lower body segments was greater (P=0.039) than the deferasirox group.
CONCLUSION
Growth retardation was more visible in pediatric TDTs with high ferritin and in deferiprone group. The height and the ratio of upper/lower body segments of the body were more affected.
PubMed: 37520873
DOI: 10.22088/cjim.14.3.425 -
British Journal of Haematology Sep 2022Regular transfusion and chelation therapy produces increased life expectancy in thalassaemic patients who may develop new complications. Since few data are available...
Regular transfusion and chelation therapy produces increased life expectancy in thalassaemic patients who may develop new complications. Since few data are available regarding hypercalciuria in β-thalassaemia major (TM), the aim of our study was to evaluate its prevalence, risk factors and clinical consequences. We enrolled 176 adult TM patients followed at the Center of Thalassemia of Ferrara. Hypercalciuria was defined by a calciuria of 4 mg/kg/day or more in a 24-h urine sample. Anamnestic, biochemical and radiological data were collected. Hypercalciuria prevalence was reported in 69.3% of patients (females 52.5%). Hypercalciuric (HC) patients used deferasirox (DFX) more often than normocalciuric (NC) patients (47.5% vs 29.6%; p < 0.05). In HC subjects plasma parathyroid hormone (PTH) (24.1 ± 10.4 vs 30.1 ± 13.2 pg/ml) and phosphate levels (3.6 ± 0.5 vs 3.8 ± 0.7 mg/dl) were lower, whereas serum calcium (9.6 ± 0.4 vs 9.4 ± 0.4 mg/dl) and urinary 24-h phosphaturia (0.9 ± 0.4 vs 0.6 ± 0.3 g/day) were higher as compared to NC patients (p < 0.05 for all comparisons). Supplementation with oral calcium and cholecalciferol was similar between the groups. A higher rate of kidney stones was present in HC (14.8%) versus NC patients (3.7%) (p < 0.05). Hypercalciuria is a frequent complication in adequately treated adult TM patients. Hypercalciuria prevalence is increased in DFX users whereas haemoglobin level or calcium supplements play no role. A significant proportion of HC patients developed kidney stones.
Topics: Adult; Calcium; Female; Humans; Hypercalciuria; Kidney Calculi; Prevalence; Risk Factors; beta-Thalassemia
PubMed: 35768889
DOI: 10.1111/bjh.18345 -
BioMed Research International 2023The primary aim of this study was to evaluate the prevalence of iron overload and the real-world clinical effectiveness of the iron chelation therapies (ICTs) in Syrian... (Observational Study)
Observational Study
OBJECTIVES
The primary aim of this study was to evaluate the prevalence of iron overload and the real-world clinical effectiveness of the iron chelation therapies (ICTs) in Syrian patients with transfusion-dependent beta thalassemia major (BTM) prior to and during the ongoing Syrian conflict.
METHODS
This single-center, two-stage observational study was conducted at Homs National Thalassemia Center (HNTC) prior to (2009) and during (2019) the armed conflict. The prevalence and the severity of iron overload, as well as the effectiveness of four iron chelation regimens, were assessed using serum ferritin (SF) concentrations as a means of monitoring in two cohorts of BTM patients receiving deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), or a combination of DFO and DFP therapy in both years. Statistical analyses encompassed one-way ANOVA, Kruskal-Wallis, Mann-Whitney , and chi-square (2) tests for the comparisons of the variables and the frequencies between the two cohorts and subgroups.
RESULTS
We included all eligible BTM patients at HNTC in 2009 ( = 205) and 2019 ( = 172). Only 84 patients from the 2009 cohort were accessible in 2019. Our findings revealed that 98% and 89% of the patients had iron overload ( ≥ 1500 ng/mL) and comparable elevated median SF concentrations (3868 and 3757 ng/mL) in 2009 and 2019, respectively ( = 0.275). Furthermore, patients on DFO demonstrated the poorest control of iron overload and the highest SF concentrations (4319 and 5586 ng/mL), whereas those on DFX achieved superior outcomes and the lowest SF concentrations (3355 and 2152 ng/mL) in both years. Twenty-six patients from the 2019 cohort received no ICT for six years (from 2012 to 2018) and experienced extremely severe iron overload with SF levels ranging between 4481 and 16,000 ng/mL.
CONCLUSIONS
Our findings prove a high prevalence of iron overload and suboptimal chelation outcomes in Syrian BTM patients, both prior to and during the ongoing armed conflict, despite the provision of free ICTs at HNTC. Poor adherence and older age of patients may explain the unfavorable outcomes of DFO and (DFO+DFP) regimens, whereas younger age and higher socioeconomic status may have contributed to the lowest SF and superior outcomes in patients on DFX. This study also demonstrates the crucial role of the National Thalassemia Centers, namely HNTC, in providing health services to BTM patients in times of peace and conflict.
Topics: Humans; Animals; Cricetinae; beta-Thalassemia; Prevalence; Syria; Analysis of Variance; Iron Overload; Mesocricetus
PubMed: 37743972
DOI: 10.1155/2023/8911518 -
Internal Medicine (Tokyo, Japan) Jul 2020The patient was a 64-year-old man presented with difficulty in walking, articulation, and swallowing, as well as cognitive impairment. He had refractory microcytic... (Review)
Review
The patient was a 64-year-old man presented with difficulty in walking, articulation, and swallowing, as well as cognitive impairment. He had refractory microcytic anemia and diabetes mellitus. His serum levels of iron, copper, and ceruloplasmin were low. Magnetic resonance imaging suggested iron deposition in the basal ganglia, thalami, cerebellar dentate nuclei, and cerebral and cerebellar cortices. He was diagnosed with aceruloplasminemia after a ceruloplasmin gene analysis. Iron chelation therapy with deferasirox improved his anemia and cerebellar symptoms, which included dysarthria and limb ataxia. The present study and previous reports indicate that cerebellar symptoms with aceruloplasminemia might respond to deferasirox in less than one year.
Topics: Adult; Anemia, Iron-Deficiency; Ceruloplasmin; Copper; Deferasirox; Female; Humans; Iron; Iron Chelating Agents; Iron Metabolism Disorders; Male; Middle Aged; Neurodegenerative Diseases; Treatment Outcome; Young Adult
PubMed: 32238721
DOI: 10.2169/internalmedicine.4178-19 -
Caspian Journal of Internal Medicine 2022Beta-thalassemia major patients typically require chronic transfusion and iron-chelating agents to reduce serum iron overload. Osveral is an available Iranian brand name...
Two trade names of deferasirox (Osveral® and Exjade®) in reduction of iron overload parameters in major beta-thalassemia patients: A randomized open labeled clinical trial.
BACKGROUND
Beta-thalassemia major patients typically require chronic transfusion and iron-chelating agents to reduce serum iron overload. Osveral is an available Iranian brand name of deferasirox used by majority of thalassemic patients. The aim of this study was to compare the efficacy of Osveral vs. Exjade in major beta- thalassemia patients.
METHODS
In this randomized clinical trial, all patients received a single daily dose of 30 mg/kg either of Osveral or Exjade for 6 months. Primary outcome was the mean of bimonthly changes in serum ferritin concentration and secondary outcomes included mean changes of heart and liver MRI T2* after a year.
RESULTS
Finally, 80 patients completed the study. The mean serum ferritin level at the end of sixth month significantly decreased in Osveral and Exjade groups (p<0.01). After a year, means cardiac MRI T2* in Osveral group were changed from 25.9±9.6 ms to 25.4±9.7 ms and in Exjade group from 24.8±9.2 ms to 26.9±5.9 ms, with no significant difference (P=0.43). Mean liver MRI T2* for Osveral and Exjade groups were 8.6±6.4 ms (baseline 6.3±4.7) and 6.3±4 ms (baseline 4.9±3.5), respectively and there was no significant difference between two study arms (P=0.1).
CONCLUSION
Osveral decreased significantly the serum ferritin level and improved heart and liver iron overload as efficient as Exjade. It can be a suitable cost-effective alternative agent in beta-thalassemia major patients.
PubMed: 35178209
DOI: 10.22088/cjim.13.1.61 -
Antibiotics (Basel, Switzerland) Sep 2023with difficult-to-treat resistance has been designated as an urgent or serious threat by the CDC in the United States; therefore, novel antibacterial drugs and...
with difficult-to-treat resistance has been designated as an urgent or serious threat by the CDC in the United States; therefore, novel antibacterial drugs and combination strategies are urgently needed. The sensor kinase RoxS is necessary for the aerobic growth of . This study aimed to screen candidate RoxS inhibitors and evaluate their efficacy in treating multi-drug-resistant and extensively drug-resistant in combination with meropenem and amikacin to identify promising combination strategies. RoxS protein structures were constructed using homology modeling and potential RoxS inhibitors, including Ezetimibe, Deferasirox, and Posaconazole, were screened from the FDA-approved ZINC drug database using molecular docking and molecular dynamics simulations. MIC and checkerboard assays were used to determine the in vitro antimicrobial efficacy of the three drugs in combination with antibiotics. The results of in vitro experiments showed an additive effect of 100 μg/mL Deferasirox or 16 μg/mL Posaconazole in combination with meropenem and a synergistic effect of 1.5 μg/mL Deferasirox and amikacin. In summary, these three drugs are potential inhibitors of RoxS, and their combination with meropenem or amikacin is expected to reverse the resistance of , providing new combination strategies for the treatment of clinically difficult-to-treat
PubMed: 37760718
DOI: 10.3390/antibiotics12091422 -
Oncotarget Jul 2021Pediatric acute myeloid leukemia (AML) represents 20% of total childhood leukemia diagnoses and is characterized by poor prognosis with a long-term survival rate around...
Pediatric acute myeloid leukemia (AML) represents 20% of total childhood leukemia diagnoses and is characterized by poor prognosis with a long-term survival rate around the 50%, when patients are properly treated. The standard treatment for pediatric AML currently consists in a combination of cytarabine (Ara-C) and antracycline. Iron plays an important role in cancer development and progression. Targeting iron and its metabolism mediators could be a novel therapeutic strategy in cancer.Deferasirox (DFX) inhibits cancer cell proliferation and its use as an antiblastic drug could be suggested. Eltrombopag (ELT), a thrombopoietin receptor agonist used in immunethrombocytopenia, shows anticancer properties related to its emerging iron chelating properties. We compare the anticancer effect of classically used cytarabine with DFX and ELT effects in a pediatric AML cell line, THP-1, in order to identify innovative and more effective therapeutic strategies. ELT and DFX reduce intracellular iron concentration by inhibiting its uptake and by promoting its release. In particular, even though further investigations are needed to better understand the extact underlying action mechanisms, we demonstrated that ELT improves cytarabine antineoplastic activity in pediatric AML cell line.
PubMed: 34262648
DOI: 10.18632/oncotarget.28000 -
Pharmaceutics Sep 2021Pancreatic cancer is a malignant disease with high mortality and poor prognosis due to lack of early diagnosis and low treatment efficiency after diagnosis. Although...
Pancreatic cancer is a malignant disease with high mortality and poor prognosis due to lack of early diagnosis and low treatment efficiency after diagnosis. Although Gemcitabine (GEM) is used as the first-line chemotherapeutic drug, chemoresistance is still the major problem that limits its therapeutic efficacy. Here in this study, we developed a specific M1 macrophage-derived exosome (M1Exo)-based drug delivery system against GEM resistance in pancreatic cancer. In addition to GEM, Deferasirox (DFX) was also loaded into drug carrier, M1Exo, in order to inhibit ribonucleotide reductase regulatory subunit M2 (RRM2) expression via depleting iron, and thus increase chemosensitivity of GEM. The M1Exo nanoformulations combining both GEM and DFX significantly enhanced the therapeutic efficacy on the GEM-resistant PANC-1/GEM cells and 3D tumor spheroids by inhibiting cancer cell proliferation, cell attachment and migration, and chemoresistance to GEM. These data demonstrated that M1Exo loaded with GEM and DFX offered an efficient therapeutic strategy for drug-resistant pancreatic cancer.
PubMed: 34575569
DOI: 10.3390/pharmaceutics13091493 -
Journal of Clinical Medicine Apr 2022The aim of this study is the evaluation of the safety and the efficacy of long-term combination therapy deferasirox plus desferrioxamine and deferasirox plus deferiprone...
The aim of this study is the evaluation of the safety and the efficacy of long-term combination therapy deferasirox plus desferrioxamine and deferasirox plus deferiprone in a large group of transfusion-dependent thalassemia patients with high values of serum ferritin and/or magnetic resonance, indicative of severe liver and cardiac iron accumulation. Sixteen adults with transfusion-dependent thalassemia were treated simultaneously with deferasirox plus desferrioxamine, while another 42 patients (seven children) were treated with deferasirox plus deferiprone. The hepatic and cardiac iron overload was assessed prior to treatment and then annually with magnetic resonance imaging, and the serum ferritin was measured monthly. Adverse events were checked at each transfusion visit. The safety of both the combinations was consistent with established monotherapies. Both treatments were able to decrease the serum ferritin and liver iron concentration over time, depending on the level of compliance with therapy. Cardiac iron measured as R2* did not significantly change in patients treated with deferasirox plus desferrioxamine. Most patients with MRI indicative of myocardial siderosis at the beginning of treatment reached normal values of cardiac iron at the last determination if treated with deferasirox plus desferrioxamine. The greatest limitation of these therapies was low patient adherence to the two drugs, which is not surprising considering that the need for an intensive chelation is generally linked to previous issues of compliance.
PubMed: 35407617
DOI: 10.3390/jcm11072010 -
BMJ Case Reports Jul 2020A 33-year-old male presenting with subacute abdominal pain was found to have hyperbilirubinaemia, hypokalaemia and hyponatraemia. This was in the setting of...
A 33-year-old male presenting with subacute abdominal pain was found to have hyperbilirubinaemia, hypokalaemia and hyponatraemia. This was in the setting of transitioning between deferasirox iron chelator formulations, from dispersible tablets to film-coated tablets for ongoing treatment of chronic iron overload secondary to transfusion requirement for beta-thalassemia major. A liver biopsy demonstrated acute cholestasis with patchy confluent hepatocellular necrosis and mild to moderate microvesicular steatosis. Based on the histological, biochemical and clinical findings, the diagnosis of hepatotoxicity and Fanconi-like syndrome was made. The patient improved clinically and biochemically with cessation of the deferasirox film-coated tablets and supportive management. To our knowledge, this is the first case report of hepatotoxicity and Fanconi-like syndrome occurring due to deferasirox film-coated tablets with previous tolerance of dispersible deferasirox tablets. It is important to raise clinical awareness of this potentially severe complication.
Topics: Adult; Chemical and Drug Induced Liver Injury, Chronic; Deferasirox; Fanconi Syndrome; Humans; Iron Chelating Agents; Male; beta-Thalassemia
PubMed: 32646935
DOI: 10.1136/bcr-2020-234542