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Recombinant human erythropoietin plus methylprednisolone versus methylprednisolone in treatment of acute spinal cord injury：protocol for a systematic review and meta-analysis
Fang, M., Zhou, J., Huang, S., Zhang, Y., He, Y., Zeng, Y., Song, Y.
BMJ open. 2022;12(12):e056689
Abstract
INTRODUCTION Recent studies in animal models indicate that recombinant human erythropoietin (rHuEPO) is very effective in enhancing neurological recovery after spinal cord injury (SCI). We described a protocol aimed at evaluating the efficacy of rHuEPO plus methylprednisolone (MP) compared with MP alone in improving neurological function of patients with SCI in randomised controlled trials (RCTs). METHODS AND ANALYSIS This study aims to explore the effect of rHuEPO combined with MP on neurological function in patients with SCI through a meta-analysis. To this end, the authors will search eight research databases for data retrieval: MEDLINE, China National Knowledge Infrastructure, Wan Fang, China Biology Medicine dis, Web of Science, PubMed, Cochrane and Embase for RCTs on SCI in any language. The primary outcome will be the American Spinal Injury Association score at the time of follow-up. The secondary outcomes will be the WHOQOL-100 instrument score, neurophysiological state and related factors. Two authors will independently search literature records, scan titles, abstracts and full texts, collect data, and assess materials for risk of bias. Stata V.14.0 will be used for statistical analysis. ETHICS AND DISSEMINATION This research is exempt from ethics approval because the work is carried out on published documents. We will disseminate this protocol in scientific conferences and a peer-reviewed journal. PROSPERO REGISTRATION NUMBER CRD42021260688.
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Targeting Pro-Oxidant Iron with Deferoxamine as a Treatment for Ischemic Stroke: Safety and Optimal Dose Selection in a Randomized Clinical Trial
Millán M, DeGregorio-Rocasolano N, Pérez de la Ossa N, Reverté S, Costa J, Giner P, Silva Y, Sobrino T, Rodríguez-Yáñez M, Nombela F, et al
Antioxidants (Basel, Switzerland). 2021;10(8)
Abstract
A role of iron as a target to prevent stroke-induced neurodegeneration has been recently revisited due to new evidence showing that ferroptosis inhibitors are protective in experimental ischemic stroke and might be therapeutic in other neurodegenerative brain pathologies. Ferroptosis is a new form of programmed cell death attributed to an overwhelming lipidic peroxidation due to excessive free iron and reactive oxygen species (ROS). This study aims to evaluate the safety and tolerability and to explore the therapeutic efficacy of the iron chelator and antioxidant deferoxamine mesylate (DFO) in ischemic stroke patients. Administration of placebo or a single DFO bolus followed by a 72 h continuous infusion of three escalating doses was initiated during the tPA infusion, and the impact on blood transferrin iron was determined. Primary endpoint was safety and tolerability, and secondary endpoint was good clinical outcome (clinicalTrials.gov NCT00777140). DFO was found safe as adverse effects were not different between placebo and DFO arms. DFO (40-60 mg/Kg/day) reduced the iron saturation of blood transferrin. A trend to efficacy was observed in patients with moderate-severe ischemic stroke (NIHSS > 7) treated with DFO 40-60 mg/Kg/day. A good outcome was observed at day 90 in 31% of placebo vs. 50-58% of the 40-60 mg/Kg/day DFO-treated patients.
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Efficacy and safety of high and low dose recombinant human erythropoietin on neurodevelopment of premature infants: A meta-analysis
Qin N, Qin H
Medicine. 2021;100(18):e25805
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Abstract
BACKGROUND To evaluate the effect of recombinant human erythropoietin (rhEPO) in nervous system of premature infants including different dosage. METHODS The multiple databases like Pubmed, Embase, Cochrane databases and China National Knowledge Database were used to search for the relevant studies, and full-text articles involved in the evaluation on effect of rhEPO for neurodevelopment among premature infants. Review Manager 5.2 was adopted to estimate the effects of the results among selected articles. Forest plots, sensitivity analysis and bias analysis for the articles included were also conducted. RESULTS Finally, 10 eligible studies were eventually satisfied the included criteria. The results showed that rhEPO was much higher than placebo group in composite cognitive score (MD = 5.89, 95% confidential interval {CI} [1.95, 9.82], P = .003; I2 = 89%), there was no significant difference between rhEPO and placebo groups (RR = 0.93, 95% CI [0.60, 1.43], P = .74; I2 = 51%) and no difference in neurodevelopmental impairment between rhEPO and placebo was insignificant (RR = 0.55 95% CI [0.30, 1.02], P = .06). Composite cognitive score in high dose rhEPO was much higher than placebo group (MD = 10.39, 95% CI [8.84, 11.93], P < .0001, I2 = 0%) and low dose rhEPO also had higher composite cognitive score than placebo group (MD = 2.58, 95% CI [0.80, 4.37], P = .004, I2 = 11%). Limited publication bias was observed in this study. CONCLUSION Recombinant human erythropoietin might be a promotor for neurodevelopment among premature infants with limited adverse events.
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Lactoferrin versus iron hydroxide polymaltose complex for the treatment of iron deficiency anemia in children with cerebral palsy: a randomized controlled trial
Omar OM, Assem H, Ahmed D, Abd Elmaksoud MS
European journal of pediatrics. 2021
Abstract
Iron deficiency anemia (IDA) is common among children with cerebral palsy (CP), and studies on the efficacy of lactoferrin (Lf) in the treatment of IDA are limited. This study aimed to compare the efficacy of Lf with that of iron hydroxide polymaltose complex (IPC) in the treatment of IDA in children with CP. This randomized controlled study, conducted at Alexandria University Children's Hospital, enrolled 70 children aged 1-10 years with CP and IDA; 35 children randomly received IPC, whereas the other 35 received Lf. Four children withdrew from the study; thus, only 66 children were analyzed (32 in the IPC group and 34 in the Lf group). At baseline, the hemoglobin level and other blood parameters were similar between the two intervention groups. After four weeks of treatment, both the IPC and Lf groups showed significant improvements in hemoglobin (Hb), serum ferritin (SF), serum iron, total iron-binding capacity, mean corpuscular volume, and mean corpuscular hemoglobin from baseline. Upon comparing the two treatment groups, adjusted mean Hb and SF changes in the Lf group were significantly higher than that of the IPC group (p =0.001and p= 0.033, respectively), and constipation was less likely to occur in the Lf group than the IPC group (p = 0.049 ).Conclusion: Lactoferrin is effective and superior to IPC as an oral iron replacement therapy in children with CP and IDA, as it has fewer side effects. What is Known: • Lactoferrin (LF) is a natural glycoprotein capable of treating iron deficiency anemia (IDA). • Studies on the efficacy of Lf in the treatment of IDA in children with cerebral palsy (CP) are limited. What is New? • This trial compared the efficacy of Lf and iron hydroxide polymaltose complex (IPC) as treatments of IDA in children with CP. • Lf is effective and even better than IPC as a treatment of IDA in children with CP, as it has fewer side effects.
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Erythropoietin monotherapy for neuroprotection after neonatal encephalopathy in low-to-middle income countries: a systematic review and meta-analysis
Ivain P, Montaldo P, Khan A, Elagovan R, Burgod C, Morales MM, Pant S, Thayyil S
Journal of perinatology : official journal of the California Perinatal Association. 2021;41(9):2134-2140
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Abstract
OBJECTIVE We examined whether erythropoietin monotherapy improves neurodevelopmental outcomes in near-term and term infants with neonatal encephalopathy (NE) in low-middle income countries (LMICs). METHODS We searched Pubmed, Embase, and Web of Science databases to identify studies that used erythropoietin (1500-12,500 units/kg/dose) or a derivative to treat NE. RESULTS Five studies, with a total of 348 infants in LMICs, were retrieved. However, only three of the five studies met the primary outcome of death or neuro-disability at 18 months of age or later. Erythropoietin reduced the risk of death (during the neonatal period and at follow-up) or neuro-disability at 18 months or later (p < 0.05). Death or neuro-disability occurred in 27.6% of the erythropoietin group and 49.7% of the comparison group (risk ratio 0.56 (95% CI: 0.42-0.75)). CONCLUSION The pooled data suggest that erythropoietin monotherapy may improve outcomes after NE in LMICs where therapeutic hypothermia is not available.
PICO Summary
Population
Near-term and term infants with neonatal encephalopathy in low-middle income countries (5 studies, n= 348).
Intervention
Erythropoietin or one of its analogues.
Comparison
Placebo or usual care.
Outcome
Erythropoietin reduced the risk of death (during the neonatal period and at follow-up) or neuro-disability at 18 months or later. Death or neuro-disability occurred in 27.6% of the erythropoietin group and 49.7% of the comparison group (risk ratio 0.56).
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Efficacy and tolerability of intravenous iron for patients with restless legs syndrome: evidence from randomized trials and observational studies
Yang X, Yang B, Ming M, Li S, Wang F, Zhu Z, Ji C, Long J, Hu F, Xu Z, et al
Sleep medicine. 2019
Abstract
OBJECTIVE Restless legs syndrome (RLS) is a common neurological disorder of unclear pathophysiology that appears to involve an iron deficiency in the brain. Some studies, but not others, suggest that intravenous injection of iron can reduce RLS severity. METHOD The databases Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed were searched for randomized controlled trials, cohort studies and case-control studies of intravenous iron therapy to treat RLS. Eligible studies were meta-analyzed using Stata 12.0. RESULTS This analysis indicated that IV iron was more efficacious than placebo in treating RLS (OR: 4.71,95%CI 4.21-5.21,p < 0.0001). According to sub-group analysis, either IV ferric carboxymaltose (FCM) or iron sucrose was more efficacious than placebo in treating RLS. Adverse events did not differ significantly between patients receiving intravenous iron or placebo (OR 1.68, 95%CI 0.92-3.07, p = 0.093). The present study also indicated after accepting IV iron treatment the IRLS score in RLS patients decreased (OR = 6.75,95%CI 4.02-9.49, p < 0.0001). The subgroup analysis showed that IV iron dextran, iron sucrose, and FCM could alleviate the IRLS score. CONCLUSION The available evidence suggests that intravenous iron is effective and tolerable for patients with RLS regardless of peripheral iron status.
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Iron supplementation for restless legs syndrome - A systematic review and meta-analysis
Avni T, Reich S, Lev N, Gafter-Gvili A
European journal of internal medicine. 2019
Abstract
BACKGROUND Iron supplementation, is recommended for the treatment of restless legs syndrome (RLS). We gathered evidence for the efficacy and safety of iron supplementation for RLS. METHODS A systematic review and meta-analysis of randomized controlled trials that compared iron supplementation versus no iron for patients with RLS was performed. Multiple databases were searched. The primary outcome was the effect of iron on the International Restless Legs Syndrome score (IRLSS) at 4weeks after treatment. For dichotomous data, risk ratios (RR) with 95% confidence intervals (CIs) were estimated and pooled. For continuous data, weighted mean differences (WMD) were calculated. RESULTS Ten trials fulfilled the inclusion criteria. Iron therapy was associated with a significant decrease of the IRLSS of -3.55 [95% CI (-5.41) - (-1.68)] points and an increase in the percentage of patients with improvement of the IRLSS score, RR of 2.16 [95% CI 1.56-2.98]. IV FCM was associated with improvement in both the IRLSS (WMD of -2.79 (95% CI (-4.62) - (-0.96), 4 trials, I(2)=0%) and on the RLS-QOL by WMD of 8.67 (95% CI 1.68-15). Iron was associated with an increased rate of adverse events RR 2.04 (95% CI 1.46-2.85), which were not severe and not associated with increased rate of treatment discontinuation. CONCLUSION Iron supplementation is associated with improvement of the IRLSS score. Our meta-analysis supports the use of iron, oral or IV, as effective therapy for patients with RLS. Further studies should assess subgroups of patients most likely to benefit from iron supplementation.
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Colony stimulating factors (including erythropoietin, granulocyte colony stimulating factor and analogues) for stroke
Bath PM, Sprigg N, England T
Cochrane Database of Systematic Reviews. 2013;6:CD005207.
Abstract
BACKGROUND Colony stimulating factors (CSFs), also called haematopoietic growth factors, regulate bone marrow production of circulating red and white cells, and platelets. Some CSFs also mobilise the release of bone marrow stem cells into the circulation. CSFs have been shown to be neuroprotective in experimental stroke. OBJECTIVES To assess (1) the safety and efficacy of CSFs in people with acute or subacute ischaemic or haemorrhagic stroke, and (2) the effect of CSFs on circulating stem and blood cell counts. SEARCH METHODS We searched the Cochrane Stroke Group Trials Register (last searched September 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 4), MEDLINE (1985 to September 2012), EMBASE (1985 to September 2012) and Science Citation Index (1985 to September 2012). In an attempt to identify further published, unpublished and ongoing trials we contacted manufacturers and principal investigators of trials (last contacted April 2012). We also searched reference lists of relevant articles and reviews. SELECTION CRITERIA We included randomised controlled trials recruiting people with acute or subacute ischaemic or haemorrhagic stroke. CSFs included stem cell factor (SCF), erythropoietin (EPO), granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage-colony stimulating factor (M-CSF, CSF-1), thrombopoietin (TPO), or analogues of these. The primary outcome was functional outcome at the end of the trial. Secondary outcomes included safety at the end of treatment, death at the end of follow-up, infarct volume and haematology measures. DATA COLLECTION AND ANALYSIS Two review authors (TE and NS) independently extracted data and assessed trial quality. We contacted study authors for additional information. MAIN RESULTS We included a total of 11 studies involving 1275 participants. In three trials (n = 782), EPO therapy was associated with a significant increase in death by the end of the trial (odds ratio (OR) 1.98, 95% confidence interval (CI) 1.19 to 3.3, P = 0.009) and a non-significant increase in serious adverse events. EPO significantly increased the red cell count with no effect on platelet or white cell count, or infarct volume. Two small trials of carbamylated EPO have been completed but have yet to be reported. We included eight small trials (n = 548) of G-CSF. G-CSF was associated with a non-significant reduction in early impairment (mean difference (MD) -0.4, 95% CI -1.82 to 1.01, P = 0.58) but had no effect on functional outcome at the end of the trial. G-CSF significantly elevated the white cell count and the CD34+ cell count, but had no effect on infarct volume. Further trials of G-CSF are ongoing. AUTHORS' CONCLUSIONS There are significant safety concerns regarding EPO therapy for stroke. It is too early to know whether other CSFs improve functional outcome.
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Neuroprotective effects of erythropoietin in acute ischemic stroke
Asadi B, Askari GR, Khorvash F, Bagherpur A, Mehrabi F, Karimi M, Ghasemi M, Najjaran A
International Journal of Preventive Medicine. 2013;4((Suppl 2):):S306-12.
Abstract
BACKGROUND Ischemic brain strokes consisttwo-thirdsof strokesand their complications bear a lot of disability for patient and society. In this study, we seek for effect of Erythropoietin on ischemic brain stroke's outcomes according to National Institutes of Health Stroke Scale (NIHSS) changes. METHODS This study is a RCT (randomized clinical trial). All patients with focal neurologic deficit with primary suspicion of brain stroke undergone neuroimaging evaluations. After confirmation of new ischemic brain stroke, the patients with inclusion criteria'srandomized into two groups of cases and controls. NIHSS was defined for each patient and all patients received a routine treatment protocol. Erythropoietin 16,000 IU as a bolus intravenous dose was given to case patients as soon as neuroimaging study confirmed new ischemic stroke and continued as 8000 IU each 12 h up to total dose of 56,000 IU during 3 days. Patients re-evaluated at days 14 and 28 and NIHSS was assessed by another neurologist blinded to patient's group. Finally, NIHSS changes of both groups compared with each other's. RESULTS Evaluations revealed that in days14 and 28 during follow-up, Erythropoietin was effective in NIHSS (P= 0.0001). This effect was of value in level of consciousness Commands (P= 0.024), facial palsy (P= 0.003), motor arm (P= 0.0001), motor leg (P= 0.0001), sensory (P= 0.009), and best language (P= 0.023). CONCLUSIONS Administration of high-dose erythropoietin in first 24 h can be effective on reduction of ischemic stroke complication. A larger scale clinical trial is warranted.
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Erythropoietin in Friedreich ataxia: no effect on frataxin in a randomized controlled trial
Mariotti C, Fancellu R, Caldarazzo S, Nanetti L, Bella D, Plumari M, Lauria G, Cappellini MD, Duca L, Solari A, et al
Movement Disorders. 2012;27((3):):446-9.
Abstract
BACKGROUND Friedreich ataxia is a rare disease caused by GAA-trinucleotide-repeat expansions in the frataxin gene, leading to marked reduction of qualitatively normal frataxin protein. Recently, human recombinant erythropoietin was reported to increase frataxin levels in patients with Friedreich ataxia. METHODS We performed a 6-month, randomized placebo-controlled, double-blind, dose-response pilot trial to assess the safety and efficacy of erythropoietin in increasing frataxin levels. Sixteen adult patient with Friedreich ataxia were randomly assigned to erythropoietin (n = 11) or matching placebo (n = 5). All patients continued Idebenone treatment (5 mg/kg/day). Treatment consisted of a 6-month scaling-up phase, in which erythropoietin was administered intravenously at the following doses: 20,000 IU every 3 weeks, 40,000 IU every 3 weeks, and 40,000 IU every 2 weeks. RESULTS Erythropoietin treatment was safe and well tolerated, but did not result in any significant hematological, clinical, or biochemical effects in Friedreich ataxia patients.
