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Hemoglobin Sep 2021As a cause of chronic blood transfusions, iron overload is an important issue in β-thalassemia (β-thal) patients that leads to multiple organ dysfunctions. This is an... (Meta-Analysis)
Meta-Analysis Review
As a cause of chronic blood transfusions, iron overload is an important issue in β-thalassemia (β-thal) patients that leads to multiple organ dysfunctions. This is an updated meta-analysis conducted to summarize the existing evidence of the prevalence of hypothyroidism (HT) among patients with transfusion-dependent (TDT) and non transfusion-dependent β-thal (NTDT) and for the first time we meta-analyzed the relationship between ferritin level and HT. This systematic review and meta-analysis were done according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. We searched databases including Web of Science (ISI), Scopus, PubMed, Embase, and Scholar. The quality of the included studies was assessed based on the Newcastle-Ottawa scale (NOS) checklist. Meta-analysis was done using Stata statistical software. The pooled prevalence of total HT, subclinical HT, and overt HT among β-thal patients was 13.25 [95% confidence interval (95% CI): 10.29-16.21; 11.84, 95% CI: 8.43-15.25 and 12.46, 95% CI: 1.05-23.87], respectively. The prevalence of total HT was 16.22% (95% CI: 12.36-20.08) in TDT and 7.22% (95% CI: 3.66-10.78) in NTDT patients. Serum ferritin (SF) levels were significantly lower in euthyroid compared to hypothyroid patients [standard mean difference (SMD) -2.15 (95% CI: -3.08, -1.21, value <0.001]. The prevalence of HT was higher in TDT compared to NTDT patients. Moreover, our results showed a significant association of high serum ferritin (SF) levels with hypothyroidism in β-thal patients. Both of these findings highlight the importance of prevention measures and timely diagnosis and management of iron overload in β-thal patients.
Topics: Cross-Sectional Studies; Ferritins; Humans; Hypothyroidism; Iron Overload; Prevalence; beta-Thalassemia
PubMed: 34806533
DOI: 10.1080/03630269.2021.2003382 -
The Cochrane Database of Systematic... Nov 2023Beta-thalassaemia is an inherited blood disorder that reduces the production of haemoglobin. The most severe form requires recurrent blood transfusions, which can lead... (Review)
Review
BACKGROUND
Beta-thalassaemia is an inherited blood disorder that reduces the production of haemoglobin. The most severe form requires recurrent blood transfusions, which can lead to iron overload. Cardiovascular dysfunction caused by iron overload is the leading cause of morbidity and mortality in people with transfusion-dependent beta-thalassaemia. Iron chelation therapy has reduced the severity of systemic iron overload, but removal of iron from the myocardium requires a very proactive preventive strategy. There is evidence that calcium channel blockers may reduce myocardial iron deposition. This is an update of a Cochrane Review first published in 2018.
OBJECTIVES
To assess the effects of calcium channel blockers plus standard iron chelation therapy, compared with standard iron chelation therapy (alone or with a placebo), on cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia.
SEARCH METHODS
We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books, to 13 January 2022. We also searched ongoing trials databases and the reference lists of relevant articles and reviews.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of calcium channel blockers combined with standard chelation therapy versus standard chelation therapy alone or combined with placebo in people with transfusion-dependent beta thalassaemia.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included six RCTs (five parallel-group trials and one cross-over trial) with 253 participants; there were 126 participants in the amlodipine arms and 127 in the control arms. The certainty of the evidence was low for most outcomes at 12 months; the evidence for liver iron concentration was of moderate certainty, and the evidence for adverse events was of very low certainty. Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may have little or no effect on cardiac T2* values at 12 months (mean difference (MD) 1.30 ms, 95% confidence interval (CI) -0.53 to 3.14; 4 trials, 191 participants; low-certainty evidence) and left ventricular ejection fraction (LVEF) at 12 months (MD 0.81%, 95% CI -0.92% to 2.54%; 3 trials, 136 participants; low-certainty evidence). Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may reduce myocardial iron concentration (MIC) after 12 months (MD -0.27 mg/g, 95% CI -0.46 to -0.08; 3 trials, 138 participants; low-certainty evidence). The results of our analysis suggest that amlodipine has little or no effect on heart T2*, MIC, or LVEF after six months, but the evidence is very uncertain. Amlodipine plus standard iron chelation compared with standard iron chelation (alone or with placebo) may increase liver T2* values after 12 months (MD 1.48 ms, 95% CI 0.27 to 2.69; 3 trials, 127 participants; low-certainty evidence), but may have little or no effect on serum ferritin at 12 months (MD 0.07 μg/mL, 95% CI -0.20 to 0.35; 4 trials, 187 participants; low-certainty evidence), and probably has little or no effect on liver iron concentration (LIC) after 12 months (MD -0.86 mg/g, 95% CI -4.39 to 2.66; 2 trials, 123 participants; moderate-certainty evidence). The results of our analysis suggest that amlodipine has little or no effect on serum ferritin, liver T2* values, or LIC after six months, but the evidence is very uncertain. The included trials did not report any serious adverse events at six or 12 months of intervention. The studies did report mild adverse effects such as oedema, dizziness, mild cutaneous allergy, joint swelling, and mild gastrointestinal symptoms. Amlodipine may be associated with a higher risk of oedema (risk ratio (RR) 5.54, 95% CI 1.24 to 24.76; 4 trials, 167 participants; very low-certainty evidence). We found no difference between the groups in the occurrence of other adverse events, but the evidence was very uncertain. No trials reported mortality, cardiac function assessments other than echocardiographic estimation of LVEF, electrocardiographic abnormalities, quality of life, compliance with treatment, or cost of interventions.
AUTHORS' CONCLUSIONS
The available evidence suggests that calcium channel blockers may reduce MIC and may increase liver T2* values in people with transfusion-dependent beta thalassaemia. Longer-term multicentre RCTs are needed to assess the efficacy and safety of calcium channel blockers for myocardial iron overload, especially in younger children. Future trials should also investigate the role of baseline MIC in the response to calcium channel blockers, and include a cost-effectiveness analysis.
Topics: Child; Humans; beta-Thalassemia; Calcium Channel Blockers; Iron Overload; Iron; Cardiomyopathies; Amlodipine; Iron Chelating Agents; Ferritins; Edema
PubMed: 37975597
DOI: 10.1002/14651858.CD011626.pub3 -
European Journal of Neurology Mar 2021Several studies suggested a role or iron in the pathogenesis or Parkinson's disease (PD), and substantia nigra iron concentrarions have been found increased in PD.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
Several studies suggested a role or iron in the pathogenesis or Parkinson's disease (PD), and substantia nigra iron concentrarions have been found increased in PD. However, the results on cerebrospinal (CSF) and serum/plasma iron levels in PD patients have been controversial. The aim of this systematic review and meta-analysis was to establish the CSF and serum/plasma levels of iron and iron-related proteins (ferritin, transferrin, lactoferrin, haptoglobin, and hepcidine) levels, and the urine levels of iron, in patients with PD.
METHODS
Four databases (PubMed, EMBASE, MedLine, and Web of Science - Core Collection) were reviewed for studies published from 1966 to October 5, 2020. References of interest were identified. A meta-analysis of eligible studies was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines, using the R software package meta.
RESULTS
A non-significant trend towards higher CSF iron levels and marginally significantly lower serum/plasma iron levels was observed in patients with PD compared with age- and sex-matched controls. CSF and serum/plasma ferritin and transferrin concentrations, and serum/plasma lactoferrin and haptoglobin concentrations did not differ significantly between PD patients and controls.
CONCLUSION
The findings of this study suggest an association between decreased serum/plasma iron levels and, possibly, higher CSF iron levels with risk of PD.
Topics: Ferritins; Humans; Iron; Parkinson Disease; Substantia Nigra
PubMed: 33098743
DOI: 10.1111/ene.14607 -
Reviews in Medical Virology Sep 2023Serum ferritin levels serves as biomarkers in many inflammatory and infectious diseases. This current systematic review and meta-analysis evaluated whether serum... (Meta-Analysis)
Meta-Analysis Review
Serum ferritin levels serves as biomarkers in many inflammatory and infectious diseases. This current systematic review and meta-analysis evaluated whether serum ferritin levels are associated with severe dengue and its utility as a biomarker of disease severity. Literature searches were conducted in PubMed, Scopus, ScienceDirect, the Cochrane library, and Google Scholar. A total of 18 studies examining the serum ferritin levels in dengue cases in the context of disease severity (nine studies having dengue classification as non-severe vs. severe dengue cases, and nine studies having dengue classification as dengue without warning signs (DwoWS), dengue with warning signs (DwWS), and severe dengue cases) were included and the quality of the studies was assessed using the Quality in Prognostic Factor Studies tool. The meta-analysis was performed using STATA software to calculate the effect size as a standardized mean difference (SMD) or Hedges 'g' for the continuous outcome. Higher serum ferritin levels were found in severe dengue cases compared to non-severe cases [SMD (Hedges 'g') 4.05 (95% C.I. 2.09-6.00), (I = 98.8%)]. In the second group, DwWS cases showed high serum ferritin levels compared to DwoWS [SMD 2.01 (95% C.I. 0.92-3.10), (I = 97.89%)], and severe dengue cases showed higher levels of serum ferritin compared to DwWS [SMD 2.66 (95% C.I. 1.72-4.48), (I = 98.78%)] and DwoWS cases [SMD 6.65 (95% C.I. 1.72-11.59), (I = 99.78%]. Subgroup analysis for the country of study (India vs. others), ferritin testing methods, and ferritin measurement day revealed testing method as a significant contributor to heterogeneity. To conclude, the present study suggests serum ferritin as a prognostic marker for dengue disease severity. Multi-centric studies involving a large number of dengue patients with a uniform case definition accounting for all the confounding variables might help in determining a universal cut-off value to discriminate between non-severe and severe dengue.
Topics: Humans; Severe Dengue; Prognosis; Biomarkers; Patient Acuity; Ferritins; Dengue
PubMed: 37347209
DOI: 10.1002/rmv.2468 -
Clinical Nutrition ESPEN Oct 2023Iron deficiency anemia (IDA) is one of the leading causes of anemia, globally. Oral vitamin C enhances iron absorption and is commonly prescribed with iron for anemia... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Iron deficiency anemia (IDA) is one of the leading causes of anemia, globally. Oral vitamin C enhances iron absorption and is commonly prescribed with iron for anemia patients. Considering the lack of evidence to support this practice, we conducted this systematic review and meta-analysis to determine the treatment efficacy of experimental studies where oral vitamin C or ascorbate was given as co-intervention with iron compared to providing only iron among participants with anemia of all ages.
METHODOLOGY
A comprehensive strategy was used to search literature from PubMed, Cochrane and Google Scholar. Experimental studies conducted among participants with lab-confirmed anemia at baseline, with "oral ascorbic acid or vitamin C given as co-intervention with iron" as intervention and "only oral iron" as the comparator, and reported the outcomes hemoglobin or ferritin, were selected. Random-effects model was used to estimate standardized mean differences or odds ratio of outcomes, and sensitivity analyses were done. Sub-group and meta-regression analyses were conducted to evaluate the reasons for heterogeneity (PROSPERO number: CRD42022306612).
RESULTS
Of the total nine studies included in the review, seven studies with 905 participants were included for meta-analysis. The pooled estimate for standardized mean difference (SMD) of hemoglobin (g/dL) and Serum Ferritin (mcg/L) for intervention-type ferrous ascorbate were 0.44 (95% C.I.: -0.30, 1.26) and 0.03 (95% C.I.: -0.68, 0.73) respectively, and were not statistically significant. The pooled estimate for SMD of hemoglobin (g/dL) and Serum Ferritin (mcg/L) for intervention type 'oral iron and vitamin C' was 0.11 (95% C.I.: -0.05, 0.28) and -0.90 (95% C.I.: -1.09, -0.72) respectively, and were not statistically significant.
CONCLUSION
The SMD of hemoglobin or serum ferritin between the intervention group were not significantly favouring the intervention when the intervention group was ferrous ascorbate or oral iron and vitamin C, and the methodological quality of evidence of these effect measures was very low. This necessitates studying the treatment efficacy of oral vitamin C or ascorbate when given with oral iron for participants with anemia in future clinical trials.
Topics: Humans; Ascorbic Acid; Iron; Vitamins; Anemia; Ferritins; Treatment Outcome
PubMed: 37739692
DOI: 10.1016/j.clnesp.2023.07.081 -
International Journal of Molecular... Oct 2022The characteristic epigenetic profile of periodontitis found in peripheral leukocytes denotes its impact on systemic immunity. In fact, this profile not only stands for... (Review)
Review
The characteristic epigenetic profile of periodontitis found in peripheral leukocytes denotes its impact on systemic immunity. In fact, this profile not only stands for periodontitis as a low-grade inflammatory disease with systemic effects but also as an important source of potentially valuable clinical biomarkers of its systemic effects and susceptibility to other inflammatory conditions. Thus, we aimed to identify relevant genes tested as epigenetic systemic biomarkers in patients with periodontitis, based on the DNA methylation patterns and RNA expression profiles in peripheral immune cells. A detailed protocol was designed following the Preferred Reporting Items for Systematic Review and Meta-analysis -PRISMA guideline. Only cross-sectional and case-control studies that reported potential systemic biomarkers of periodontitis in peripheral immune cell types were included. DNA methylation was analyzed in leukocytes, and gene expression was in polymorphonuclear and mononuclear cells. Hypermethylation was found in TLR regulators genes: , , , , , , and in early stages of periodontitis, while advanced stages presented hypomethylation of these genes. , , , and genes were differentially expressed in lymphocytes and monocytes of subjects with poorly controlled diabetes mellitus, dyslipidemia, and periodontitis in comparison with controls. The gene was differentially overexpressed in periodontitis and dyslipidemia. Peripheral blood neutrophils in periodontitis showed differential expression in 163 genes. Periodontitis showed an increase in ceruloplasmin gene expression in polymorphonuclears in comparison with controls. Several genes highlight the role of the epigenetics of peripheral inflammatory cells in periodontitis that could be explored in blood as a source of biomarkers for routine testing.
Topics: Biomarkers; Ceruloplasmin; Cross-Sectional Studies; DNA Methylation; Dyslipidemias; Gene Expression; Humans; Myeloid Differentiation Factor 88; Periodontitis; RNA
PubMed: 36233348
DOI: 10.3390/ijms231912042 -
Birth Defects Research Oct 2022Congenital anomalies affect over 2% of pregnancies, with congenital heart disease (CHD) the most common. Understanding of causal factors is limited. Micronutrients are... (Review)
Review
BACKGROUND
Congenital anomalies affect over 2% of pregnancies, with congenital heart disease (CHD) the most common. Understanding of causal factors is limited. Micronutrients are essential trace elements with key roles in growth and development. We aimed to investigate whether maternal micronutrient deficiencies increase the risk of fetal CHD through systematic review of published literature.
METHOD
We performed a systematic review registered at PROSPERO as CRD42021276699. Ovid-MEDLINE, Ovid-EMBASE, and Cochrane Library were searched from their inception until September 7, 2021. Case control trials were included with a population of biological mothers of fetuses with and without CHD. The exposure was maternal micronutrient level measured in pregnancy or the postpartum period. Data extraction was performed by one author and checked by a second. Risk of bias assessment was performed according to the Scottish Intercollegiate Guidelines Network guidance. We performed a narrative synthesis for analysis.
RESULTS
726 articles were identified of which 8 met our inclusion criteria. Final analysis incorporated data from 2,427 pregnancies, 1,199 of which were complicated by fetal CHD assessing 8 maternal micronutrients: vitamin D, vitamin B12, folate, vitamin A, zinc, copper, selenium, and ferritin. Studies were heterogenous with limited sample sizes and differing methods and timing of maternal micronutrient sampling. Definitions of deficiency varied and differed from published literature. Published results were contradictory.
CONCLUSION
There is not enough evidence to confidently conclude if maternal micronutrient deficiencies increase the risk of fetal CHD. Further large-scale prospective study is required to answer this question.
Topics: Copper; Female; Ferritins; Folic Acid; Heart Defects, Congenital; Humans; Malnutrition; Maternal Nutritional Physiological Phenomena; Micronutrients; Observational Studies as Topic; Pregnancy; Selenium; Trace Elements; Vitamin A; Vitamin B 12; Vitamin D; Zinc
PubMed: 35979646
DOI: 10.1002/bdr2.2072 -
Journal of Child Neurology Mar 2023Febrile seizures are the most common type of seizure in children under the age of 5, and a number of risk factors for this condition have been identified. Several... (Meta-Analysis)
Meta-Analysis
Febrile seizures are the most common type of seizure in children under the age of 5, and a number of risk factors for this condition have been identified. Several studies have examined the connection between iron deficiency anemia and febrile seizures in children, with inconsistent results. As a result, the authors sought to determine the precise link between iron deficiency anemia and its indices (mean corpuscular volume, serum iron, total iron-binding capacity, and ferritin) in conjunction to febrile seizures. A systematic literature search from several databases (PubMed, Europe PMC, ScienceDirect) was conducted from database inception until November 30, 2022. Studies were eligible if they investigated the relationship of the iron deficiency anemia and the aforementioned indices with the likelihood of febrile seizures. This meta-analysis comprised 20 case-control studies with a total of 3856 participants. Our study revealed that iron deficiency anemia, low mean corpuscular volume, low serum iron, high total iron-binding capacity, and low ferritin were associated with the incremental risk of developing febrile seizures, with the odds ratios ranging from 1.24 to 1.59. Moreover, diagnostic test accuracy meta-analysis indicated that low serum ferritin level had the highest overall area under the curve value amid other iron deficiency anemia indices regarding our outcomes of interest. This study suggest that iron deficiency anemia and poor iron indices are associated with increased risk of febrile seizures in children.
Topics: Child; Humans; Iron; Anemia, Iron-Deficiency; Seizures, Febrile; Ferritins; Case-Control Studies
PubMed: 37125415
DOI: 10.1177/08830738231170333 -
Frontiers in Public Health 2022Hepcidin has been identified as a systemic iron-regulatory hormone. Recent studies have suggested that iron metabolism disorders may be involved in the pathogenesis of... (Meta-Analysis)
Meta-Analysis
BACKGROUNDS
Hepcidin has been identified as a systemic iron-regulatory hormone. Recent studies have suggested that iron metabolism disorders may be involved in the pathogenesis of acute respiratory distress syndrome and multiple organ dysfunction in coronavirus disease 2019 (COVID-19).
OBJECTIVES
To re-evaluate the hepcidin-related iron metabolism parameters and explore the relationship between hepcidin-mediated iron dysmetabolism and COVID-19 severity.
METHODS
COVID-19 is classified as mild and moderate as non-severe, severe and critical as severe. A meta-analysis was conducted. Four bibliographic databases were comprehensively searched up to December 31st 2021.
RESULTS
Six unique studies with data from 477 COVID-19 patients were included. Compared to non-severe cases, severe cases had higher hepcidin (standardized mean difference (SMD), -0.39; 95% Confidence Interval (CI) [-0.76, -0.03]; = 0.03) and ferritin (SMD, -0.84; 95% CI [-1.30, -0.38]; = 0.0004). In five out of six studies, a total of 427 patients were tested for serum iron, and there were significant differences in their levels between severe and non-severe cases (SMD, 0.22; 95% CI [0.02, 0.41]; = 0.03). A total of 320 patients from four out of six studies were tested for transferrin saturation, and the statistical difference was not significant (SMD, 0.06; 95% CI [-0.17, 0.28]; = 0.64).
CONCLUSION
Severe COVID-19 cases had higher serum levels of hepcidin and ferritin, and lower serum iron, without significant differences in transferrin saturation. Further studies are needed to verify whether targeting the hepcidin-mediated iron metabolism axis may influence the outcome and treatment of COVID-19.
Topics: COVID-19; Ferritins; Hepcidins; Humans; Iron; Transferrin
PubMed: 35558525
DOI: 10.3389/fpubh.2022.881412 -
Cerebrovascular Diseases (Basel,... 2022Hemorrhagic transformation (HT) is a complication that occurs spontaneously or after thrombolysis in acute ischemic stroke (AIS) and can increase morbidity and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hemorrhagic transformation (HT) is a complication that occurs spontaneously or after thrombolysis in acute ischemic stroke (AIS) and can increase morbidity and mortality. The association of biomarkers with the risk of HT has been variably reported. We conducted a systematic review of the literature and meta-analysis and sought to compare blood biomarkers associated with HT and its subtypes by evaluating its predictability and correlation with outcome in AIS.
METHODS
The study protocol was registered in the PROSPERO database (CRD42020201334) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Among 2,230 articles identified from Cochrane Library, PubMed, and Web of Science databases, 30 quality-appraised articles were found eligible. Meta-analysis was conducted for matrix metalloproteinase-9 (MMP-9), cellular fibronectin (c-Fn), ferritin, S100 calcium-binding protein B (S100B), and neutrophil-lymphocyte ratio (NLR). We also reviewed biomarkers for correlation with the functional outcome at 90 days from stroke onset (poor outcome modified Rankin scale >2).
RESULTS
The pooled diagnostic odds ratio (DORpooled) was the highest for baseline c-Fn levels (299.253 [95% CI, 20.508-4,366.709]), followed by MMP-9 (DORpooled, 29.571 [95% CI 17.750-49.267]) and ferritin (DORpooled, 24.032 [95% CI 2.557-225.871]). However, wide confidence intervals for ferritin and c-Fn suggested lesser reliability of the markers. Patients with MMP-9 levels ≥140 ng/mL were 29.5 times at higher risk of developing symptomatic HT after AIS (area under the curve = 0.881). S100B (DORpooled, 6.286 [95% CI, 1.861-21.230]) and NLR (DORpooled, 5.036 [95% CI, 2.898-8.749]) had lower diagnostic accuracies. Among the markers not included for meta-analysis, caveolin-1, thrombin-activated fibrinolysis inhibitor, plasminogen activator inhibitor-1, and soluble ST2 were highly sensitive. Elevated levels of MMP-9, ferritin, and NLR were found to be associated with poor functional outcomes and mortality.
CONCLUSION
Of the 5 biomarkers, there was enough evidence that MMP-9 has higher diagnostic accuracy for predicting the risk of HT before thrombolysis. MMP-9, ferritin, and NLR also predicted poor short-term outcomes.
Topics: Biomarkers; Brain Ischemia; Ferritins; Hemorrhage; Humans; Ischemic Stroke; Matrix Metalloproteinase 9; Prognosis; Reproducibility of Results; Stroke
PubMed: 34569521
DOI: 10.1159/000518570