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European Journal of Epidemiology Aug 2020Iron metabolism and anemia may play an important role in multiple organ dysfunction syndrome in Coronavirus disease 2019 (COVID-19). We conducted a systematic review and... (Meta-Analysis)
Meta-Analysis
Iron metabolism and anemia may play an important role in multiple organ dysfunction syndrome in Coronavirus disease 2019 (COVID-19). We conducted a systematic review and meta-analysis to evaluate biomarkers of anemia and iron metabolism (hemoglobin, ferritin, transferrin, soluble transferrin receptor, hepcidin, haptoglobin, unsaturated iron-binding capacity, erythropoietin, free erythrocyte protoporphyrine, and erythrocyte indices) in patients diagnosed with COVID-19, and explored their prognostic value. Six bibliographic databases were searched up to August 3rd 2020. We included 189 unique studies, with data from 57,563 COVID-19 patients. Pooled mean hemoglobin and ferritin levels in COVID-19 patients across all ages were 129.7 g/L (95% Confidence Interval (CI), 128.51; 130.88) and 777.33 ng/mL (95% CI, 701.33; 852.77), respectively. Hemoglobin levels were lower with older age, higher percentage of subjects with diabetes, hypertension and overall comorbidities, and admitted to intensive care. Ferritin level increased with older age, increasing proportion of hypertensive study participants, and increasing proportion of mortality. Compared to moderate cases, severe COVID-19 cases had lower hemoglobin [weighted mean difference (WMD), - 4.08 g/L (95% CI - 5.12; - 3.05)] and red blood cell count [WMD, - 0.16 × 10 /L (95% CI - 0.31; - 0.014)], and higher ferritin [WMD, - 473.25 ng/mL (95% CI 382.52; 563.98)] and red cell distribution width [WMD, 1.82% (95% CI 0.10; 3.55)]. A significant difference in mean ferritin levels of 606.37 ng/mL (95% CI 461.86; 750.88) was found between survivors and non-survivors, but not in hemoglobin levels. Future studies should explore the impact of iron metabolism and anemia in the pathophysiology, prognosis, and treatment of COVID-19.
Topics: Anemia; Betacoronavirus; Biomarkers; COVID-19; COVID-19 Testing; Clinical Laboratory Techniques; Coronavirus; Coronavirus Infections; Erythropoietin; Ferritins; Hemoglobins; Hepcidins; Humans; Iron; Pandemics; Pneumonia, Viral; Receptors, Transferrin; SARS-CoV-2; Transferrin
PubMed: 32816244
DOI: 10.1007/s10654-020-00678-5 -
Renal Failure Dec 2023This meta-analysis aims to assess the efficacy and safety of roxadustat in treating anemia patients with dialysis-dependent (DD) chronic kidney disease (CKD). (Meta-Analysis)
Meta-Analysis
BACKGROUND
This meta-analysis aims to assess the efficacy and safety of roxadustat in treating anemia patients with dialysis-dependent (DD) chronic kidney disease (CKD).
METHODS
We comprehensively searched 5 databases for randomized controlled trials (RCTs) investigating roxadustat for anemia in DD-CKD patients. RevMan 5.0 was used to extract and synthesize data for meta-analysis.
RESULTS
Ten different RCTs (9 studies) and 5698 DD-CKD patients with anemia were included. Our findings revealed that when compared to the erythropoiesis-stimulating agents (ESAs) group, the roxadustat group showed increased hemoglobin levels [MD (Mean Difference) 0.25 g/dL (95%CI 0.14 g/dL to 0.36 g/dL), < 0.00001] and improved iron-utilization by increasing serum iron [MD 1.85 µmol/L], total iron binding capacity [MD 35.73 µg/dL], transferrin saturation [MD 1.19%], and transferrin level [MD 0.40 g/L]. In addition, we found that roxadustat significantly decreased the low-density lipoprotein-cholesterol [MD -0.39 mmol/L] and total cholesterol [MD -0.6 mmol/L]. In patients with a C-reactive protein level that exceeds the upper limit of the normal range, hemoglobin levels were higher for roxadustat than for ESAs [MD 0.39 g/dL]. Treatment-emergent adverse events, treatment-emergent serious adverse events, and major adverse cardiovascular events were not significantly different between the two groups.
CONCLUSIONS
The hemoglobin levels of DD-CKD patients were significantly increased and not affected by the inflammatory state after roxadustat treatment. Roxadustat also improved iron utilization, and it was not associated with higher treatment-emergent adverse events, treatment-emergent serious adverse events, and major adverse cardiovascular events when compared to ESAs.
Topics: Humans; Renal Dialysis; Anemia; Iron; Cholesterol, LDL; Glycine; Hematinics; Cardiovascular Diseases; Transferrins; Hemoglobins
PubMed: 37489561
DOI: 10.1080/0886022X.2023.2195011 -
The Turkish Journal of Pediatrics 2023Anemia is a common nutritional problem in children, especially those under five. Lactoferrin (Lf) as a supplement in treating iron deficiency anemia (IDA) has been... (Review)
Review
BACKGROUND
Anemia is a common nutritional problem in children, especially those under five. Lactoferrin (Lf) as a supplement in treating iron deficiency anemia (IDA) has been studied, but its results in children have not been reviewed. This review aims to evaluate the effect of lactoferrin on children with IDA.
METHODS
PubMed, ProQuest, EBSCO and Ovid databases were searched using a variation of keywords: lactoferrin, anemia, and children. The literature selected must be clinical trial-based in design. The years of the studies published were limited to 2012 and 2022.
RESULTS
Eleven studies were included in the final systematic review, consisting of 10 randomized controlled trials (RCTs) and 1 non-randomized trial. Serum ferritin (SF) and hemoglobin (Hb) were found to be increased in groups treated with Lf or a combination of Lf and elemental iron compared to iron only or placebo supplementation. Adverse events such as constipation, vomiting, anorexia, and abdominal pain were found; particularly, a significant decrease in constipation is seen in Lf-treated groups.
CONCLUSIONS
This study supports Lf as a superior treatment for IDA in children regarding the improvement in hematological and iron indices and fewer adverse effects.
Topics: Child; Humans; Abdominal Pain; Anemia, Iron-Deficiency; Constipation; Iron; Lactoferrin
PubMed: 37661669
DOI: 10.24953/turkjped.2022.670 -
International Journal of Molecular... Mar 2023Iron deficiency (ID) in conjunction with heart failure (HF) poses a challenge for clinicians and is associated with worse HF outcomes. Treatment of ID with IV iron... (Review)
Review
Iron deficiency (ID) in conjunction with heart failure (HF) poses a challenge for clinicians and is associated with worse HF outcomes. Treatment of ID with IV iron supplementation for patients with HF has demonstrated benefits in quality of life (QoL) and HF-related hospitalizations. The aim of this systematic review was to summarize the evidence linking iron metabolism biomarkers with outcomes in patients with HF to assist in the optimal use of these biomarkers for patient selection. A systematic review of observational studies in English from 2010 to 2022 was conducted using PubMed, with keywords of "Heart Failure" and respective iron metabolism biomarkers ("Ferritin", "Hepcidin", "TSAT", "Serum Iron", and "Soluble Transferrin Receptor"). Studies pertaining to HF patients, with available quantitative data on serum iron metabolism biomarkers, and report of specific outcomes (mortality, hospitalization rates, functional capacity, QoL, and cardiovascular events) were included, irrespective of left ventricular ejection fraction (LVEF) or other HF characteristics. Clinical trials of iron supplementation and anemia treatment were removed. This systematic review was conducive to formal assessment of risk of bias via Newcastle-Ottawa Scale. Results were synthesized based on their respective adverse outcomes and iron metabolism biomarker(s). Initial and updated searches identified 508 unique titles once duplicates were removed. The final analysis included 26 studies: 58% focused on reduced LVEF; age range was 53-79 years; males composed 41-100% of the reported population. Statistically significant associations of ID were observed with all-cause mortality, HF hospitalization rates, functional capacity, and QoL. Increased risk for cerebrovascular events and acute renal injury have also been reported, but these findings were not consistent. Varying definitions of ID were utilized among the studies; however, most studies employed the current European Society of Cardiology criteria: serum ferritin < 100 ng/mL or the combination of ferritin between 100-299 ng/mL and transferrin saturation (TSAT) < 20%. Despite several iron metabolism biomarkers demonstrating strong association with several outcomes, TSAT better predicted all-cause mortality, as well as long-term risk for HF hospitalizations. Low ferritin was associated with short-term risk for HF hospitalizations, worsening functional capacity, poor QoL, and development of acute renal injury in acute HF. Elevated soluble transferrin receptor (sTfR) levels were associated with worse functional capacity and QoL. Finally, low serum iron was significantly associated with increased risk for cardiovascular events. Considering the lack of consistency among the iron metabolism biomarkers for association with adverse outcomes, it is important to incorporate additional biomarker data, beyond ferritin and TSAT, when assessing for ID in HF patients. These inconsistent associations question how best to define ID to ensure proper treatment. Further research, potentially tailored to specific HF phenotypes, is required to optimize patient selection for iron supplementation therapy and appropriate targets for iron stores replenishment.
Topics: Humans; Male; Anemia, Iron-Deficiency; Quality of Life; Stroke Volume; Ventricular Function, Left; Iron; Iron Deficiencies; Ferritins; Heart Failure; Biomarkers; Receptors, Transferrin
PubMed: 36982717
DOI: 10.3390/ijms24065645 -
Immunity, Inflammation and Disease Aug 2023Lactoferrin is a versatile protein with important modulatory functions in inflammation and immune response. This glycoprotein can bind and sequester iron and LPS,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lactoferrin is a versatile protein with important modulatory functions in inflammation and immune response. This glycoprotein can bind and sequester iron and LPS, thereby intervening in certain signaling pathways and biological processes. In the present meta-analysis, we aimed to pool experimental data regarding the immunomodulatory effects of lactoferrin and its derived peptides on the NF-κB signaling pathway.
MATERIALS
We searched PubMed, Google Scholar, and Web of Science databases and obtained all related articles published before April 2022. Finally, 25 eligible studies were selected, and their reports were analyzed.
METHODS
We used Review Manager Version 5.2 to compute the standardized mean difference (SMD) and its 95% confidence interval. In addition, the source of heterogeneity was explored using meta-regression and sensitivity analysis. The symmetry of the funnel plot and Egger's test were also used to evaluate publication bias utilizing Comprehensive Meta-Analysis Version 2.
RESULTS
Comparing the group of cells and animals exposed to lipopolysaccharide alone with the group that received pretreatment with lactoferrin and its derivatives, we observed significant reductions in TNF-α, IL-1 beta, and IL-6 levels by 8.73 pg/mL, 2.21 pg/mL, and 3.24 pg/mL, respectively, in the second group. Additionally, IKK-β, p-IκB, and NF-κB (p65) levels were significantly lower by 7.37-fold, 15.02-fold, and 3.88-fold, respectively, in various cells and tissues.
CONCLUSION
Based on the results of this meta-analysis, lactoferrin and its derived peptides can be considered potent prophylactic and therapeutic candidates against inflammation-associated diseases by targeting the NF-kB pathway.
Topics: Animals; NF-kappa B; Lactoferrin; Signal Transduction; Peptides; Inflammation; Lipopolysaccharides; Immunity
PubMed: 37647433
DOI: 10.1002/iid3.972 -
International Journal of Molecular... Jan 2024Alzheimer's Disease (AD) is the most common neurodegenerative disease which manifests with progressive cognitive impairment, leading to dementia. Considering the... (Meta-Analysis)
Meta-Analysis Review
Alzheimer's Disease (AD) is the most common neurodegenerative disease which manifests with progressive cognitive impairment, leading to dementia. Considering the noninvasive collection of saliva, we designed the systematic review to answer the question "Are salivary biomarkers reliable for the diagnosis of Alzheimer's Disease?" Following the inclusion and exclusion criteria, 30 studies were included in this systematic review (according to the PRISMA statement guidelines). Potential biomarkers include mainly proteins, metabolites and even miRNAs. Based on meta-analysis, in AD patients, salivary levels of beta-amyloid42 and p-tau levels were significantly increased, and t-tau and lactoferrin were decreased at borderline statistical significance. However, according to pooled AUC, lactoferrin and beta-amyloid42 showed a significant predictive value for salivary-based AD diagnosis. In conclusion, potential markers such as beta-amyloid42, tau and lactoferrin can be detected in the saliva of AD patients, which could reliably support the early diagnosis of this neurodegenerative disease.
Topics: Humans; Alzheimer Disease; Neurodegenerative Diseases; Lactoferrin; MicroRNAs; Biomarkers
PubMed: 38256241
DOI: 10.3390/ijms25021168 -
The Cochrane Database of Systematic... May 2023Neonates who have undergone gastrointestinal surgery are particularly susceptible to infectious complications in the postoperative period. This may be due in part to... (Review)
Review
BACKGROUND
Neonates who have undergone gastrointestinal surgery are particularly susceptible to infectious complications in the postoperative period. This may be due in part to disruption of the integrity of the gut and its altered intestinal microflora. Lactoferrin is a whey protein found in milk and is an important innate mammalian defence mechanism. Lactoferrin has been reported to have antimicrobial and anti-inflammatory properties. It has also been reported to help establish a healthy gut microflora and aid in the intestinal immune system. Lactoferrin supplementation has been reported to decrease sepsis in preterm infants. There may be a role for lactoferrin to reduce the incidence of sepsis, thus reducing morbidity and mortality and improving enteral feeding in postoperative term neonates.
OBJECTIVES
The primary objective of this review was to evaluate the efficacy of administering lactoferrin on the incidence of sepsis and mortality in term neonates after gastrointestinal surgery. The secondary objective was to assess the impact of administering lactoferrin on time to full enteral feeds, the intestinal microflora, duration of hospital stay, and mortality before discharge in the same population.
SEARCH METHODS
The Cochrane Neonatal Information Specialist searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase Ovid, CINAHL, the WHO ICTRP and ClinicalTrials.gov trials registries. The date of the last search was February 2023. There were no restrictions to language, publication year or publication type. We checked references of potentially relevant studies and systematic reviews.
SELECTION CRITERIA
We planned to include randomised controlled trials that studied infants born at 37 or more weeks of gestation who had one or more episodes of gastrointestinal surgery within 28 days of birth, and compared administration of lactoferrin with a placebo.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures. We planned to use the GRADE approach to assess the certainty of evidence for each outcome.
MAIN RESULTS
We identified no published randomised controlled studies that assessed the efficacy of lactoferrin for the postoperative management of term neonates following gastrointestinal surgery.
AUTHORS' CONCLUSIONS
There is currently no evidence available from randomised controlled trials to show whether lactoferrin is effective or ineffective for the postoperative management of term neonates after gastrointestinal surgery. There is a need for randomised controlled trials to be performed to assess the role of lactoferrin in this setting.
Topics: Animals; Humans; Infant, Newborn; Digestive System Surgical Procedures; Infant, Premature; Lactoferrin; Milk; Sepsis
PubMed: 37233609
DOI: 10.1002/14651858.CD012218.pub2 -
Journal of Diabetes Investigation Jul 2020Iron metabolism can directly or indirectly affect the occurrence and development of type 2 diabetes. This meta-analysis and systematic review aimed to analyze the... (Meta-Analysis)
Meta-Analysis
AIMS/INTRODUCTION
Iron metabolism can directly or indirectly affect the occurrence and development of type 2 diabetes. This meta-analysis and systematic review aimed to analyze the association between serum iron metabolism indicators and type 2 diabetes.
MATERIALS AND METHODS
The databases PubMed and Embase were searched for studies on the correlations between serum iron metabolism indicators (iron, ferritin, transferrin, hepcidin and soluble transferrin receptor) and type 2 diabetes since January 2006. Relevant data were extracted from the included studies, and meta-analysis was carried out.
RESULTS
A total of 12 case-control and cohort studies were analyzed. Of the 12 studies, 11 described the correlation between serum ferritin levels and type 2 diabetes. The median and high serum ferritin concentrations were significantly associated with the risks of type 2 diabetes (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.08-1.33 and OR 1.43, 95% CI 1.29-1.59, respectively). However, the low concentration was not correlated with the risk of type 2 diabetes (OR 0.99, 95% CI 0.89-1.11). No significant association was observed between serum soluble transferrin receptor and type 2 diabetes, whereas the soluble transferrin receptor-to-ferritin ratio was significantly inversely related to the risk of type 2 diabetes in the median and high ratio subgroups (OR 0.71, 95% CI 0.51, 0.99 and OR 0.65, 95% CI 0.45-0.95).
CONCLUSIONS
The elevated serum ferritin was one of the risk factors for type 2 diabetes, and soluble transferrin receptor-to-ferritin ratio was inversely related to the risk of type 2 diabetes. A systematic review showed that serum transferrin and hepcidin might be directly or indirectly related to the development of diabetes.
Topics: Aged; Case-Control Studies; Cohort Studies; Diabetes Mellitus, Type 2; Female; Ferritins; Hepcidins; Humans; Male; Middle Aged; Odds Ratio; Receptors, Transferrin; Risk Factors
PubMed: 31975563
DOI: 10.1111/jdi.13216 -
BMJ Global Health Feb 2023WHO guidelines on iron supplementation among children call for further research to identify the optimal schedule, duration, dose and cosupplementation regimen. (Meta-Analysis)
Meta-Analysis
Oral iron supplementation and anaemia in children according to schedule, duration, dose and cosupplementation: a systematic review and meta-analysis of 129 randomised trials.
INTRODUCTION
WHO guidelines on iron supplementation among children call for further research to identify the optimal schedule, duration, dose and cosupplementation regimen.
METHODS
A systematic review and meta-analysis of randomised controlled trials was undertaken. Randomised controlled trials providing ≥30 days of oral iron supplementation versus placebo or control to children and adolescents aged <20 years were eligible. Random-effects meta-analysis was used to summarise the potential benefits and harms of iron supplementation. Meta-regression was used to estimate iron effect heterogeneity.
RESULTS
129 trials with 201 intervention arms randomised 34 564 children. Frequent (3-7/week) and intermittent (1-2/week) iron regimens were similarly effective at decreasing anaemia, iron deficiency and iron deficiency anaemia (p heterogeneity >0.05), although serum ferritin levels and (after adjustment for baseline anaemia) haemoglobin levels increased more with frequent supplementation. Shorter (1-3 months) versus longer (7+ months) durations of supplementation generally showed similar benefits after controlling for baseline anaemia status, except for ferritin which increased more with longer duration of supplementation (p=0.04). Moderate-dose and high-dose supplements were more effective than low-dose supplements at improving haemoglobin (p=0.004), ferritin (p=0.008) and iron deficiency anaemia (p=0.02), but had similar effects to low-dose supplements for overall anaemia. Iron supplementation provided similar benefits when administered alone or in combination with zinc or vitamin A, except for an attenuated effect on overall anaemia when iron was cosupplemented with zinc (p=0.048).
CONCLUSIONS
Weekly and shorter duration iron supplementation at moderate or high doses might be optimal approaches for children and adolescents at risk of deficiency.
TRIAL REGISTRATION NUMBER
CRD42016039948.
Topics: Adolescent; Child; Humans; Iron; Anemia, Iron-Deficiency; Anemia; Ferritins; Dietary Supplements; Zinc; Randomized Controlled Trials as Topic
PubMed: 36849195
DOI: 10.1136/bmjgh-2022-010745 -
BMC Infectious Diseases Mar 2024Coronavirus disease 2019 (COVID-19) is frequntly accompanied by venous thromboembolism (VTE), and its mechanism may be related to the abnormal inflammation and immune... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Coronavirus disease 2019 (COVID-19) is frequntly accompanied by venous thromboembolism (VTE), and its mechanism may be related to the abnormal inflammation and immune status of COVID-19 patients. It has been proved that interleukin-6 (IL-6), ferritin and lactate dehydrogenase (LDH) may play an important role in the occurrence of VTE in COVID-19 infection. But whether they can server as predictors for VTE in COVID-19 is still unclear. In this study, we performed a systematic review and meta-analysis to compare IL-6, ferritin and LDH in VTE and non-VTE COVID-19 patients in order to shed light on the prevention and treatment of VTE.
METHODS
Related literatures were searched in PubMed, Embase, Web of Science, Google Scholar, China National Knowledge Infrastructure (CNKI), WANGFANG. COVID-19 patients were divided into VTE group and non-VTE group. Meta-analysis was then conducted to compare levels of IL-6, ferritin and LDH between the two groups.
RESULTS
We finally included and analyzed 17 literatures from January 2019 to October 2022. There was a total of 7,035 COVID-19 patients, with a weighted mean age of 60.01 years. Males accounted for 62.64% and 61.34% patients were in intensive care unit (ICU). Weighted mean difference (WMD) of IL-6, ferritin and LDH was 31.15 (95% CI: 9.82, 52.49), 257.02 (95% CI: 51.70, 462.33) and 41.79 (95% CI: -19.38, 102.96), respectively. The above results indicated that than compared with non-VTE group, VTE group had significantly higher levels of IL-6 and ferritin but similar LDH.
CONCLUSION
This systematic review and meta-analysis pointed out that elevated levels of IL-6 and ferritin were significantly possitive associated with VTE, thus could be used as biological predictive indicators of VTE among COVID-19 patients. However, no association was found between level of LDH and VTE. Therefore, close monitoring of changes in IL-6 and ferritin concentrations is of great value in assisting clinicans to rapidly identify thrombotic complications among COVID-19 patients, hence facilitating the timely effective managment. Further studies are required in terms of the clinical role of cytokines in the occurrence of VTE among COVID-19 infection, with more reliable systematic controls and interventional trials.
Topics: Male; Humans; Middle Aged; COVID-19; Interleukin-6; Venous Thromboembolism; Ferritins; L-Lactate Dehydrogenase
PubMed: 38493138
DOI: 10.1186/s12879-024-09205-3