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PloS One 2021To describe the laboratory parameters and biomarkers of the cytokine storm syndrome associated with severe and fatal COVID-19 cases. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To describe the laboratory parameters and biomarkers of the cytokine storm syndrome associated with severe and fatal COVID-19 cases.
METHODS
A search with standardized descriptors and synonyms was performed on November 28th, 2020 of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, LILACS, and IBECS to identify studies of interest. Grey literature searches and snowballing techniques were additionally utilized to identify yet-unpublished works and related citations. Two review authors independently screened the retrieved titles and abstracts, selected eligible studies for inclusion, extracted data from the included studies, and then assessed the risk of bias using the Newcastle-Ottawa Scale. Eligible studies were those including laboratory parameters-including serum interleukin-6 levels-from mild, moderate, or severe COVID-19 cases. Laboratory parameters, such as interleukin-6, ferritin, hematology, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer, were extracted from the studies. Meta-analyses were conducted using the laboratory data to estimate mean differences with associated 95% confidence intervals.
DATA SYNTHESIS
The database search yielded 9,620 records; 40 studies (containing a total of 9,542 patients) were included in the final analysis. Twenty-one studies (n = 4,313) assessed laboratory data related to severe COVID-19 cases, eighteen studies (n = 4,681) assessed predictors for fatal COVID-19 cases and one study (n = 548) assessed laboratory biomarkers related to severe and fatal COVID-19 cases. Lymphopenia, thrombocytopenia, and elevated levels of interleukin-6, ferritin, D-dimer, aspartate aminotransferase, C-Reactive-Protein, procalcitonin, creatinine, neutrophils and leucocytes were associated with severe and fatal COVID-19 cases.
CONCLUSIONS
This review points to interleukin-6, ferritin, leukocytes, neutrophils, lymphocytes, platelets, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer as important biomarkers of cytokine storm syndrome. Elevated levels of interleukin-6 and hyperferritinemia should be considered as red flags of systemic inflammation and poor prognosis in COVID-19.
Topics: Biomarkers; C-Reactive Protein; COVID-19; Cytokine Release Syndrome; Ferritins; Humans; Interleukin-6; Leukocytes; SARS-CoV-2; Severity of Illness Index
PubMed: 34185801
DOI: 10.1371/journal.pone.0253894 -
Clinical Biochemistry Jul 2024The goal of this review was to investigate the levels of pro-inflammatory markers such as Tumour necrosis factor-α (TNF-α) Interlukin-6 (IL-6), C-reactive protein... (Meta-Analysis)
Meta-Analysis
The goal of this review was to investigate the levels of pro-inflammatory markers such as Tumour necrosis factor-α (TNF-α) Interlukin-6 (IL-6), C-reactive protein (CRP), Transforming growth factor-β1 (TGF-β1) and ferritin in pre-eclamptic and normotensive pregnant women. Using PubMed, ProQuest and Google Scholar databases, a literature search was carried out and case-control studies showing associations between inflammatory markers and preeclampsia in pregnancy published between 2010 and 2023 were included. The risk of bias was assessed by using the Newcastle Ottawa quality assessment scale. A random effect meta-analysis was performed and pooled difference in means with 95 % CI were reported. All statistical analyses were performed using R software. Out of 660 articles, 25 articles were included in the systematic review. The differences in means for TGF-β1, CRP, ferritin and TNF-α levels between the preeclamptic women and normotensive women were 2.37 pg/mL [95 % CI: -1.66,6.39], 5.62 mg/L [95 % CI: -4.11,15.36], 32.93 ng/mL [95 % CI: -7.66,58.19] and 13.67 pg/mL [95 % CI: 4.20,23.14] respectively which showed moderate increase. The pooled differences in means for hs-CRP and IL-6 levels between the preeclamptic and normotensive women were 3.20 mg/L [95 % CI: 0.27,6.12] and 17.64 pg/mL [95 % CI: -8.36,43.64] respectively which showed significant increase. Sub-group analysis showed significant differences for CRP, ferritin and TNF-α levels across ethnicities. Meta-analysis demonstrates an increase in the maternal circulating levels of inflammatory markers such as hs-CRP, IL-6 and showed moderate increase in TGF-β1, CRP, ferritin, TNF-α markers among women affected by preeclampsia compared to those with normotensive pregnancies.
Topics: Female; Humans; Pregnancy; Biomarkers; C-Reactive Protein; Ferritins; Inflammation; Interleukin-6; Pre-Eclampsia; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha
PubMed: 38876455
DOI: 10.1016/j.clinbiochem.2024.110778 -
The Journal of Nutrition May 2021The interaction between dietary (and supplementary) divalent ions has been a long-standing issue in human nutrition research. Developing an optimal calcium and iron... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The interaction between dietary (and supplementary) divalent ions has been a long-standing issue in human nutrition research. Developing an optimal calcium and iron supplementation recommendation requires detailed knowledge of the potential trade-offs between: 1) the clinical effects of concurrent intake on iron absorption and hematological indices; and 2) the potentially negative effects of separated ingestion on adherence to iron and/or calcium supplements. Human clinical studies have examined the effects of calcium intake on iron status, but there are no meta-analyses or recent reviews summarizing the findings.
OBJECTIVES
To synthesize peer-reviewed, human, randomized, and cross-over studies on effects of calcium consumption on iron indices without age, gender, or any other restrictions.
METHODS
Weighted mean differences for total, heme, and nonheme iron absorption (%) and serum ferritin (μg/L) were obtained from pooled analysis of the highest daily calcium intake compared to the lowest daily calcium intake.
RESULTS
The negative effect of calcium intake was statistically significant in short-term iron absorption studies, but the effect magnitude was low [weighted mean difference (WMD) = -5.57%; 95% CI: -7.09 to -4.04]. The effect of calcium on the iron status was mixed. The inverse dose-response association of calcium intake with the serum ferritin concentration was significant (P value = 0.0004). There was, however, no reduction in the hemoglobin concentration (WMD = 1.22g/L; 95% CI: 0.37-2.07).
CONCLUSIONS
The existing body of studies is insufficient to make recommendations with high confidence due to heterogeneity in designs, limitations of ferritin as an iron biomarker, and a lack of intake studies in pregnant women. Prescribing separation of prenatal calcium and iron supplements in free-living individuals is unlikely to affect the anemia burden. There is a need for effectiveness trials comparing the effects of prescribing separated intake to concurrent intake, with functional endpoints as primary outcomes and adherence to each supplement as intermediate outcomes.
Topics: Calcium; Cross-Over Studies; Diet; Ferritins; Humans; Iron
PubMed: 33758936
DOI: 10.1093/jn/nxaa437 -
The Pan African Medical Journal 2024Chronic kidney disease (CKD) is commonly complicated by anemia. Treating dialysis-dependent patients with anemia, including daprodustat and other inhibitors of prolyl... (Meta-Analysis)
Meta-Analysis Comparative Study Review
Chronic kidney disease (CKD) is commonly complicated by anemia. Treating dialysis-dependent patients with anemia, including daprodustat and other inhibitors of prolyl hydroxylase of hypoxia-inducible factor, recombinant human erythropoietin (rhEPO), and iron supplements. We conducted this study to test our postulation; daprodustat is superior to rhEPO and other conventional treatments respecting efficacy and safety parameters. We made systematic search through PubMed, Web of Science, Scopus, and Cochrane. Seven unique trials were eventually included for systematic review; six of them with a sample size of 759 patients entered our network meta-analysis (NMA). Daprodustat 25-30 mg was associated with the greatest change in serum hemoglobin (MD=1.86, 95%CI= [1.20; 2.52]), ferritin (MD= -180.84, 95%CI= [-264.47; -97.20]), and total iron binding capacity (TIBC) (MD=11.03, 95%CI= [3.15; 18.92]) from baseline values. Dialysis-dependent patients with anemia had a significant increment in serum Hemoglobin and TIBC and a reduction in serum ferritin, in a dose-dependent manner, when administered daprodustat.
Topics: Humans; Anemia; Renal Dialysis; Hemoglobins; Renal Insufficiency, Chronic; Glycine; Ferritins; Barbiturates; Network Meta-Analysis; Erythropoietin; Recombinant Proteins; Dose-Response Relationship, Drug; Iron
PubMed: 38828426
DOI: 10.11604/pamj.2024.47.114.37278 -
Neurosurgical Review Jun 2022Hydrocephalus is a common complication of hemorrhagic stroke and has been reported to contribute to poor neurological outcomes. Herein, we aimed to investigate the... (Meta-Analysis)
Meta-Analysis Review
Hydrocephalus is a common complication of hemorrhagic stroke and has been reported to contribute to poor neurological outcomes. Herein, we aimed to investigate the validity of cerebrospinal fluid (CSF) data in predicting shunt-dependent hydrocephalus (SDHC) in patients with hemorrhagic stroke. PubMed, CENTRAL, and Embase databases were searched for relevant studies published through July 31, 2021. The 16 studies with 1505 patient included those in which CSF data predicted risk for SDHC and reports on CSF parameters in patients in whom SDHC or hydrocephalus that was not shunt-dependent developed following hemorrhagic stroke. We appraised the study quality using Newcastle-Ottawa Scale and conducted a meta-analysis of the pooled estimates of the CSF predictors. The meta-analysis revealed three significant CSF predictors for shunt dependency, i.e., higher protein levels (mean difference [MD] = 32.09 mg/dL, 95% confidence interval [CI] = 25.48-38.70, I = 0%), higher levels of transforming growth factor β1 (TGF-β1; MD = 0.52 ng/mL, 95% CI = 0.42-0.62, I = 0%), and higher ferritin levels (MD = 108.87 µg/dL, 95% CI = 56.68-161.16, I = 36%). The red blood cell count, lactate level, and glucose level in CSF were not significant in predicting SDHC in patients with hemorrhagic stroke. Therefore, higher protein, TGF-β1, and ferritin levels in CSF are significant predictors for SDHC in patients with hemorrhagic stroke. Measuring these CSF parameters would help in the early recognition of SDHC risk in clinical care.
Topics: Cerebrospinal Fluid Shunts; Ferritins; Hemorrhagic Stroke; Humans; Hydrocephalus; Subarachnoid Hemorrhage; Transforming Growth Factor beta1
PubMed: 35015193
DOI: 10.1007/s10143-022-01731-5 -
Clinical and Translational Science Mar 2023Experimental exposure of healthy volunteers to the T-cell dependent neoantigen keyhole limpet hemocyanin (KLH) permits the evaluation of immunomodulatory investigational... (Review)
Review
Experimental exposure of healthy volunteers to the T-cell dependent neoantigen keyhole limpet hemocyanin (KLH) permits the evaluation of immunomodulatory investigational medicinal product (IMP) pharmacology prior to the recruitment of patient populations. Despite widespread use, no standardized approach to the design and conduct of such studies has been agreed. The objective of this systematic review was to survey the published literature where KLH was used as a challenge agent, describing methodology, therapeutic targets addressed, and pharmacodynamic outcome measures. We searched MEDLINE, EMBASE, clinicaltrials.gov, and Cochrane CENTRAL for studies using KLH challenge in humans between January 1, 1994, and April 1, 2022. We described key study features, including KLH formulation, dose, use of adjuvants, route of administration, co-administered IMPs, and end points. Of 2421 titles and abstracts screened, 46 met the inclusion criteria, including 14 (31%) early phase trials of IMP, of which 10 (71%) targeted T-cell co-stimulation. IMPs with diverse mechanisms demonstrated modulation of the humoral response to KLH, suggesting limited specificity of this end point. Two early phase IMP studies (14%) described the response to intradermal re-challenge (delayed type hypersensitivity). Challenge regimens for IMP assessment were often incompletely described, and exhibited marked heterogeneity, including primary KLH dose (25-fold variation: 100-2500 mcg), KLH formulation, and co-administration with adjuvants. Methodological heterogeneity and failure to exploit the access to tissue-level mechanism-relevant end points afforded by KLH challenge has impaired the translational utility of this paradigm to date. Future standardization, characterization, and methodological development is required to permit tailored, appropriately powered, mechanism-dependent study design to optimize drug development decisions.
Topics: Humans; Pharmaceutical Preparations; T-Lymphocytes; Hemocyanins; Adjuvants, Immunologic
PubMed: 36420645
DOI: 10.1111/cts.13457 -
BMJ Open Jun 2024This systematic review and meta-analysis aimed to comprehensively assess the impact of weekly iron-folic acid supplementation (WIFAS) on the nutrition, health and... (Meta-Analysis)
Meta-Analysis
Weekly iron-folic acid supplementation and its impact on children and adolescents iron status, mental health and school performance: a systematic review and meta-analysis in sub-Saharan Africa.
OBJECTIVE
This systematic review and meta-analysis aimed to comprehensively assess the impact of weekly iron-folic acid supplementation (WIFAS) on the nutrition, health and educational outcomes of children and adolescents in sub-Saharan Africa.
DESIGN
A systematic review and meta-analysis was used.
DATA SOURCES
Five databases, namely, MEDLINE, Scopus, Web of Science, Cochrane Library and Google Scholar, were systematically searched for relevant articles up to 23 August 2023.
ELIGIBILITY CRITERIA
It was focused on randomised controlled trials involving children and adolescents in sub-Saharan Africa, exploring the effects of iron supplementation on various outcomes, such as serum ferritin and haemoglobin levels, anaemia, mental health and school performance.
DATA EXTRACTION AND SYNTHESIS
The Joanna Briggs Institute Critical Appraisal tools were used for quality assessment, with two independent reviewers thoroughly evaluating each paper. Using the Cochrane risk of bias tool, we evaluated the certainty of evidence such as the risk of bias, inconsistency, indirectness, imprecision and publication bias.
RESULTS
A systematic review of 10 articles revealed that WIFAS significantly increased serum ferritin levels in adolescent girls (Hedge's g=0.53, 95% CI 0.28 to 0.78; heterogeneity I=41.21%, p<0.001) and haemoglobin levels in school-aged children (Hedge's g=0.37, 95% CI 0.01 to 0.73; heterogeneity I=91.62%, p<0.001). The analysis further demonstrated a substantial reduction in the risk of anaemia by 20% (risk ratio=0.8, 95% CI 0.69 to 0.93; heterogeneity I=28.12%, p<0.001).
CONCLUSION
WIFAS proved effective in enhancing serum ferritin and haemoglobin concentrations and lowering the risk of anaemia in school-aged children and adolescents compared with a placebo. Similarly, there are not enough studies to examine the effects of WIFAS on school performance. However, information regarding mental health problems, mortality and potential side effects remains insufficient.
PROSPERO REGISTRATION NUMBER
CRD42023397898.
Topics: Humans; Child; Adolescent; Dietary Supplements; Africa South of the Sahara; Mental Health; Iron; Folic Acid; Ferritins; Anemia, Iron-Deficiency; Hemoglobins; Randomized Controlled Trials as Topic; Female; Nutritional Status
PubMed: 38862227
DOI: 10.1136/bmjopen-2024-084033 -
Reviews in Medical Virology Jan 2022It has been demonstrated that lactoferrin (LF) plays a role in host defence, but evidence on its potential antiviral property from clinical studies is fragmented. Our... (Review)
Review
It has been demonstrated that lactoferrin (LF) plays a role in host defence, but evidence on its potential antiviral property from clinical studies is fragmented. Our systematic review aimed at identifying the effects of orally administered LF against virus infections. The systematic search was conducted on PubMed, Scopus, Web of Science, BioRxiv.org and ClinicalTrials.gov from database inception to 7th January 2021. Eligible articles investigated any virus family and provided data on the effects of orally administered LF of any origin in the prevention and/or management of confirmed viral infections in people of any age. A narrative synthesis of the results was performed. Quality was assessed with the Cochrane Risk-Of-Bias and ROBINS-1 tools. A total of 27 records were included, nine of which were registered protocols. We found data on Flaviviridae (n = 10), Retroviridae (n = 3), Coronaviridae (n = 2), Reoviridae (n = 2) and Caliciviridae (n = 1). Most published trials were at high risk of bias. The findings were heterogeneous across and within viral families regarding virological, immunological and biological response, with no clear conclusion. Some weak but positive results were reported about decrease of symptom severity and duration, or reduction in viral loads. Despite high tolerability, the effects of LF as oral supplement are still inconsistent, both in preventing and managing viral infections. Small sample sizes, variety in recruitment and treatment protocols, and low study quality may have contributed to such heterogeneity. Better-designed studies are needed to further investigate its potential benefits against viral infections, including SARS-CoV-2.
Topics: Anti-Infective Agents; COVID-19; Humans; Lactoferrin; SARS-CoV-2; Virus Diseases
PubMed: 34133812
DOI: 10.1002/rmv.2261 -
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 -
Clinical Chemistry and Laboratory... Feb 2024Dysregulation of hepcidin-iron axis is presumed to account for abnormal iron status in patients with chronic liver disease (CLD). Our aim is to determine the effect of... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Dysregulation of hepcidin-iron axis is presumed to account for abnormal iron status in patients with chronic liver disease (CLD). Our aim is to determine the effect of specific etiologies of CLD and of cirrhosis on serum hepcidin levels.
METHODS
PubMed, Embase, Web of Science were searched for studies comparing serum hepcidin levels in patients with CLD to that in controls using enzyme-linked immunosorbent assay. The study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Guidelines. Statistical analysis was carried out with STATA using random effects model to calculate the mean difference (MD) between two groups.
RESULTS
Hepcidin levels were significantly lower in subjects with hepatitis C virus (16 studies) [MD -1.6 (95 % CI: -2.66 to -0.54), p<0.01] and alcoholic liver disease (3 studies) [MD -0.84 (95 % CI: -1.6 to -0.07), p=0.03] than controls. Serum hepcidin was significantly higher in subjects with non-alcoholic fatty liver disease (12 studies) [MD 0.62 (95 % CI: 0.21 to 1.03), p<0.01], but did not differ in subjects with hepatitis B and controls (eight studies) [MD -0.65 (95 % CI: -1.47 to 0.16), p=0.12]. Hepcidin levels were significantly lower in patients with cirrhosis of any etiology (four studies) [MD -1.02 (CI: -1.59 to -0.45), p<0.01] vs. controls (CI: confidence interval).
CONCLUSIONS
Serum hepcidin levels are altered in common forms of CLD albeit not in a consistent direction. Additional study is needed to determine how changes in hepcidin levels are related to dysregulation of iron metabolism in CLD.
Topics: Humans; Hepcidins; Ferritins; Liver Cirrhosis; Iron; Non-alcoholic Fatty Liver Disease
PubMed: 37540837
DOI: 10.1515/cclm-2023-0540