Baseline Ferritin Levels Research Articles

Surrogate Thresholds for Iron Chelation in Patients with Hematological Malignancies

Background: The reference standard for evaluating the magnitude of body iron overload is measurement of the liver iron concentration (LIC). Until recently, the conventional clinical method for measuring LIC was through analysis of biopsy specimens considered the “gold standard” of LIC measurement. To counter the shortcomings of liver biopsy, several noninvasive techniques have been applied to estimate LIC. The spin-density projection-assisted (SDPA) R2-MRI (FerriScan) technique has been recently validated to estimate LIC. There are reports in the literature that ferritin levels in patients with hematological malignancies (HM) may not correlate sufficiently with LIC. We conducted R2-MRI Ferriscan sequencing in consecutive patients with HM followed in our center to better evaluate the diagnostic value of ferritin levels and packed red blood cell (pRBC) transfusions for iron overload.Methods: HM patients with a history of transfusion requirement were evaluated for inclusion in the study within the Liver Iron Cutino Network (Licnet) project. Patients were excluded if they had contraindications to MRI assessment (heart pacemaker, metallic foreign body or devices, and claustrophobia). Demographics and HM disease data were collected, together with ferritin levels and transfusion requirement. R2 LIC measures by FerriScan were defined as indicating normal/marginally high iron load for values 0 to <3, mild liver iron overload for values 3 to < 7, moderate between 7 and 15 and severe if >15. Correlations and the generation of receiver operating characteristic (ROC) curves were performed to test the diagnostic power of ferritin levels and volume of transfused blood (ml/kg in the preceeding 12 months) to indicate moderate-severe iron overload.Results: 28 patients (20 males) of mean age 62, SD 17 years with HM (myelodysplastic syndromes N=14; acute myeloid leukemia N=7, of which 5 post-transplant; acute lymphoblastic leukemia post-transplant N=2; aplastic anemia N=2; non Hodgkin lymphoma N=1; chronic lymphocytic leukemia N=1; erythroblastopenia N=1) were evaluated. Median baseline ferritin levels were 1617 (interquartile range 1185-2360). Mean R2 values were 10.9, SD 10.1 mg/kg. Three patients had normal or marginally high LIC, 12 patients had mild overload, 6 patients moderate and 7 patients severe overload. Both ferritin levels and amount of blood volume transfused in the preceding 12 months correlated well with R2 measures (Spearman rho=0.478, p=0.10 and r=0.509, p=0.006, respectively). However, neither ferritin levels nor transfusions correlated with R2 MRI in patients with normal-mild iron overload while the correlations were confirmed and highly significant in patients with moderate-severe iron overload (r=0.692, p=0.009 and r= 0.754, p=0.003, respectively). ROC curves denied the diagnostic power of ferritin levels and confirmed transfusions to indicate moderate to severe liver iron overload (Figure 1), indicating that 37 ml/kg/year (about 14 units of pRBC) has a sensitivity of 77% and a specificity of 80% to predict moderate-severe iron overloadConclusions: We confirm that, though ferritin levels do generally correlate with LIC, they are not to be considered an appropriate surrogate marker for iron overload in HM. R2 MRI sequencing is valuable to diagnose the state of LIC. The results of this study indicate that as soon as an HM patient begins to receive regular transfusions, since the probability of developing moderate-severe iron overload is high, it is warranted not to await high ferritin levels, nor a large number of pRBC units, to initiate iron chelation. [Display omitted] DisclosuresOliva:Celgene: Consultancy; La Jolla: Consultancy; Amgen Inc.: Consultancy; Novartis: Consultancy; Janssen: Consultancy.

Oral Ferric Maltol for the Treatment of Iron-Deficiency Anemia in Patients With CKD: A Randomized Trial and Open-Label Extension

Iron-deficiency anemia is common in patients with chronic kidney disease (CKD) not requiring kidney replacement therapy (KRT). We evaluated effects of oral iron replacement therapy with ferric maltol in these patients. Phase 3, double-blind, randomized, placebo-controlled trial (AEGIS-CKD) and open-label extension. Adults with stage 3 or 4 CKD and iron-deficiency anemia at 30 US centers. Oral ferric maltol at 30mg or placebo twice daily for 16 weeks (2:1 randomization) followed by ferric maltol at 30mg twice daily for up to 36 weeks (all patients). Change from baseline in hemoglobin (primary end point at week 16), ferritin, transferrin saturation, and serum iron; safety. 167 patients were randomized (ferric maltol, n=111; placebo, n=56). At week 16, hemoglobin had increased significantly with ferric maltol versus placebo (least-squares mean difference: 0.5±0.2 [SE] g/dL; 95% CI, 0.1-0.9; P=0.01). Ferritin, transferrin saturation, and serum iron increased with ferric maltol but declined with placebo (all P<0.05). Hemoglobin levels were sustained up to week 52 in patients continuing ferric maltol and increased in patients switching from placebo to ferric maltol. The most frequent adverse events were gastrointestinal (randomized phase: 41% vs 30% [ferric maltol vs placebo]; open-label phase: 56% vs 46%, respectively). Adverse events led to treatment withdrawal in 7 patients (6%) receiving ferric maltol and 5 patients (9%) receiving placebo during double-blind treatment, and 11 patients (9%) during the open-label extension. Heterogeneity in baseline ferritin levels; high proportion of female participants; single-arm open-label extension. Ferric maltol was associated with statistically significant (week 16) and sustained (up to week 52) increases in hemoglobin and iron indices in patients with CKD and iron deficiency, and was well tolerated during treatment for up to 52 weeks. Funded by Shield Therapeutics (UK) Ltd. Registered at ClinicalTrials.gov with study number NCT02968368.

Comparative efficacy and safety of intravenous ferric carboxymaltose and iron sucrose for iron deficiency anemia in obstetric and gynecologic patients: A systematic review and meta-analysis.

Introduction:Iron deficiency anemia (IDA) is common among obstetric and gynecologic patients. This systematic review aimed to assess the comparative efficacy and safety of commonly used intravenous (IV) iron formulations, ferric carboxymaltose (FCM), and iron sucrose (IS) in the treatment of IDA in obstetric and gynecologic patients.Methods:We systematically searched PubMed, EMBASE, Cochrane CENTRAL, and Google Scholar for eligible randomized controlled trials (RCTs) comparing IV iron replacement using FCM and IS up to October 2019. The primary outcome was to compare the efficacy of FCM and IS, assessed by measuring serum hemoglobin (Hb) and ferritin levels before and after iron replacement. The secondary outcome was to compare the safety of FCM and IS, assessed by the incidence of adverse events during iron replacement. The meta-analysis was performed using RevMan 5.3.Results:We identified 9 RCTs with 910 patients (FCM group, n = 456; IS group, n = 454). Before iron replacement, FCM and IS group patients had similar baseline Hb (mean difference [MD], 0.04 g/dL; 95% confidence interval [CI], −0.07 to 015; I2 = 0%; P = 0.48) and ferritin levels (MD, −0.42 ng/mL; 95% CI, −1.61 to 0.78; I2 = 45%; P = 0.49). Following iron replacement, patients who received FCM had higher Hb (MD, 0.67; 95% CI, 0.25–1.08; I2 = 92%; P = 0.002) and ferritin levels (MD, 24.41; 95% CI, 12.06–36.76; I2 = 75%; P = 0.0001) than patients who received IS. FCM group showed a lower incidence of adverse events following iron replacement than IS group (risk ratio, 0.53; 95% CI, 0.35–0.80; I2 = 0%; P = 0.003). Serious adverse events were not reported in any group.Conclusion:FCM group showed better efficacy in increasing Hb and ferritin levels and a favorable safety profile with fewer adverse events compared with IS group for IDA treatment among obstetric and gynecologic patients. However, this meta-analysis was limited by the small number of RCTs and high heterogeneity.Trial registration:The review was prospectively registered with the International Prospective Registry of Systematic Reviews (https://www.crd.york.ac.uk/prospero/, registration number CRD42019148905).

Baseline and follow-up serum ferritin level as a prognostic factor in coronavirus disease 2019-infected patients

Objective In the past few months, WHO declared coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 as a major pandemic, with increasing number of discovered cases and mortalities in all countries. Up till now, there are a lot of controversial data on its pathogenesis, possible complications, prognostic factors, and available preventive and/or therapeutic options. A series of fast growing research studies are being conducted aiming at studying prognostic criteria that may predict the disease severity and possible outcomes and hence plan of management either home or hospital management. Patients and methods Our cohort study included 73 COVID-19-confirmed positive cases by nasopharyngeal swab/reverse transcriptase PCR to evaluate correlation between serum ferritin levels (baseline and follow-up samples at day 7), as well as C-reactive protein levels and severity of clinical presentation of COVID-19-infected patients. Results Our results have demonstrated a statistically significant difference between mild (n=40) and moderate cases (n=33) regarding baseline ferritin level (P=0.00); however; no significant difference was detected among ferritin changes during the course of the disease (P=0.744), and also, no statistically significant difference in ferritin changes was found among mild and moderate severity groups (P=0.942). Finally, the only significant predictors of clinical severity were baseline ferritin and C-reactive protein levels according to multivariate analysis model (P=0.014 and =0.000, respectively). Conclusions The current study added further evidence to suggest baseline serum ferritin as an index of severity in COVID-19 and could have a prognostic effect; however, we cannot rely on follow-up serum ferritin during treatment and the course of the disease to predict outcome of the disease, and it may be misleading.

Slower response to treatment of iron-deficiency anaemia in pregnant women infected with HIV: a prospective cohort study.

Antenatal anaemia is associated with increased peripartum transfusion requirement in South Africa. We studied whether HIV was associated with the response to treatment of iron-deficiency anaemia. Prospective cohort study. Hospital-based antenatal anaemia clinic in South Africa. Equal-sized cohorts of pregnant women testing positive for HIV (HIV+) and testing negative for HIV (HIV-) with iron-deficiency anaemia. Haemoglobin trajectories of women with confirmed iron-deficiency anaemia (ferritin<50ng/ml) were estimated from the initiation of iron supplementation using mixed-effects modelling, adjusted for baseline HIV status, ferritin level, maternal and gestational ages and time-varying iron supplementation. Haemoglobin trajectories. Of 469 women enrolled, 51% were HIV+, 90% of whom were on antiretroviral therapy (with a mean CD4+ lymphocyte count of 403cells/mm3 ). Anaemia diagnoses did not differ by HIV status. A total of 400 women with iron-deficiency anaemia were followed during treatment with oral or intravenous (6%) iron therapy. In multivariable analysis, haemoglobin recovery was 0.10g/dl per week slower on average in women who were HIV+ versus women who were HIV- (P=0.001), 0.01g/dl per week slower in women with higher baseline ferritin (P<0.001) and 0.06g/dl per week faster in women who were compliant with oral iron therapy (P=0.002). Compared with women who were HIV-, women who were HIV+ with iron-deficiency anaemia had slower but successful haemoglobin recovery with iron therapy. Earlier effective management of iron deficiency could reduce the incidence of peripartum blood transfusion. Among pregnant women with iron-deficiency anaemia in South Africa, HIV slows haemoglobin recovery in response to oral iron therapy.

Association of Serum Hepcidin Levels with Aerobic and Resistance Exercise: A Systematic Review.

Background: Prevalence of iron deficiency is commonly reported among athletic population groups. It impairs physical performance due to insufficient oxygen delivery to target organs and low energy production. This is due to the high demand of exercise on oxygen delivery for systemic metabolism by the erythrocytes in the blood. Hepcidin, the key regulator of iron homeostasis, decreases to facilitate iron efflux into the circulation during enhanced erythropoiesis. However, acute anaemia of exercise is caused by increased hepcidin expression that is induced by stress and inflammatory signal. The study aimed to systematically review changes in serum hepcidin levels during resistance and aerobic exercise programmes. Methods: A systemic literature search from 2010 to April 2020 across seven databases comprised of Cochrane library, PubMed, Web of Science, Scopus, Embase, MEDLINE, and OpenGrey. The primary outcome was increased or decreased serum hepcidin from baseline after the exercise activity. Risks of bias were evaluated by using the National Institutes of Health (NIH) for quality assessment of before and after different exercise programmes. Results: Overall, twenty-three studies met the inclusion criteria. Out of the 23 studies, 16 studies reported significantly exercise-induced serum hepcidin elevation. Of the 17 studies that evaluated serum interleukin (IL)-6 levels, 14 studies showed significant exercise-induced serum IL-6 elevation. Changes in exercise-induced serum hepcidin and IL-6 levels were similar in both resistance and endurance exercise. Significant correlations were observed between post-exercise hepcidin and baseline ferritin levels (r = 0.69, p < 0.05) and between post-exercise hepcidin and post-exercise IL-6 (r = 0.625, p < 0.05). Conclusion: Resistance and endurance training showed significant increase in serum hepcidin and IL-6 levels in response to exercise. Baseline ferritin and post-exercise IL-6 elevation are key determining factors in the augmentation of hepcidin response to exercise.

Use of Convalescent Plasma Therapy in Severe Coronavirus Disease 2019: The Yale-New Haven Health System Experience

Use of Convalescent Plasma Therapy in Severe Coronavirus Disease 2019: The Yale-New Haven Health System Experience

Low-Dose Maintenance Intravenous Iron Therapy Can Prevent Anemia in Children with End-Stage Renal Disease Undergoing Chronic Hemodialysis

Iron deficiency anemia is common in children with end-stage renal disease (ESRD) on long-term hemodialysis receiving erythropoiesis-stimulating agents. One approach to maintain the iron profile and hemoglobin levels is maintenance therapy with regular low doses of intravenous (IV) iron after initial iron repletion therapy; however, evidence for the benefits of this approach is lacking. This study evaluated the effect of IV iron maintenance therapy on anemia in children on regular hemodialysis. This retrospective cohort study included 41 pediatric ESRD patients with normal hemoglobin and iron status who underwent regular hemodialysis at the Pediatric Dialysis Unit of Cipto Mangunkusumo Hospital, Indonesia, between January 2015 and April 2019. Among these, 21 received IV iron maintenance therapy with two doses of 2 mg/kg of IV iron sucrose every 2 weeks (the treatment group) and 20 did not (the comparison group). Changes in hemoglobin and transferrin saturation were assessed after 6 weeks of observation and compared between the two groups. There was a significant reduction in the mean hemoglobin level compared with the baseline level in the comparison group (21 g/L; 95% CI, 9.3–33 g/L; p=0.001) but not in the treatment group (0.7 g/L; 95% CI, −6.6–8 g/L; p=0.84). The risk of anemia was lower in the treatment group (relative risk = 0.42; 95% CI, 0.22–0.79; p=0.003). Although majority of the patients had high baseline ferritin level, this study indicates that in our setting, ferritin may not be a reliable parameter to review the iron status, as it can be affected by chronic inflammation. Hence, the decision to start IV iron maintenance therapy in patients with hyperferritinemia should consider the patient's clinical condition and morbidity. To conclude, the coadministration of IV iron maintenance therapy is beneficial for maintaining hemoglobin levels and preventing anemia in children with ESRD who are undergoing regular hemodialysis, have achieved the target hemoglobin levels, and have normal iron status.

1001 Intravenous Ferric Carboxymaltose For Restless Legs Syndrome In Children And Adolescents

Abstract Introduction Substantial scientific evidence implicates brain iron deficiency in the pathophysiology of restless legs syndrome (RLS). Current clinical guidelines recommend oral and intravenous iron (IV) in the treatment of both adult and pediatric RLS but studies using ferric carboxymaltose (FCM) are lacking in children and adolescents. Methods Retrospective case series of children and adolescents with RLS treated with IV FCM who had serum ferritin levels &amp;lt;50 μg/L. Patients were offered a single dose of IV FCM, 15 mg/kg if weighting &amp;lt;50 kg or 750 mg if weighting &amp;gt;50 kg. Iron profile, serum ferritin, and severity assessment by the International Restless Legs Study Group severity scale (IRLS) were collected pre- and post-infusion. Clinical Global Impression Scale (CGI) was used instead of the IRLS for children. Phosphorus level and adverse effects were assessed post-infusion in all patients. Age and sex-matched children with RLS treated with oral iron supplementation (mean dosage 1.5±0.62 mg/kg/day) were included as a comparison group. Results Twenty-eight subjects (15 females, mean age 11.5 years, SD 4.23) and 24 controls were included. Baseline ferritin levels were not significantly different from those of controls but increased significantly from 13.9±7.02 to 112.9±12.00 μg/L after 8 weeks from infusion (p&amp;lt;0.000001), when they were also significantly higher than control values (34.2±21.64 μg/mL, p&amp;lt;0.000001). Transferrin saturation increased from 22.8±9.77% to 31.7±6.81% (p&amp;lt;0.0001), total iron binding capacity decreased from 366.7±51.32 to 302.0±37.83 μg/dL (p&amp;lt;0.0000035). RLS was reported to be resolved or improved in all children treated with IV iron (vs. 62.5% of controls) while none of them reported no change (vs. 37.5% of controls; Chi-square test 9.84, p&amp;lt;0.002). IRLS Score decreased in adolescents from 30.7±22.68 to 3.2±4.21 (p&amp;lt;0.000008) while CGI-I was “very much improved” in six children and “much improved” in four. Side effects were reported in 17.8% of patients treated IV and 20.8% controls (Chi-square 0.0169, p=0.897). FCM side effects included lightheadedness and gastrointestinal discomfort. Post IV phosphorus levels were normal in all participants. Conclusion This open-label, observational and retrospective study indicates that FCM IV infusion is an effective treatment for pediatric RLS with higher efficacy than oral iron supplementation. Support

P658 A pooled analysis of serum phosphate measurements and transient decreased phosphate levels in 45 interventional trials with ferric carboxymaltose

Abstract Background ECCO guidelines acknowledge the limitations of oral iron for iron deficiency anaemia in IBD and recommend first-line IV iron in patients with active disease. Ferric carboxymaltose (FCM) is approved for iron deficiency when oral iron is ineffective/inappropriate. FCM has shown benefit in RCTs, and as with other IV irons, is known to cause a transient decrease in serum phosphate (PO4), which in most cases is asymptomatic. The aim of this pooled analysis was to characterise the frequency, duration, risk factors, and clinical signs of hypophosphataemia (HP) across 45 interventional trials with FCM. Methods 15,080 subjects were included (FCM n = 8,245; controls n = 6,835). 12,683 had post-baseline serum PO4 measurements (FCM n = 6,879), which were pooled by time-point, clinical characteristics, dose, and iron parameters. Serum PO4 thresholds were: 2.5–&amp;lt;4.5 mg/dl (normal), 2.0–&amp;lt;2.5 mg/dl (mild decrease), 1–&amp;lt;2.0 mg/dl (moderate), and &amp;lt;1 mg/dl (severe). Logistic regression analysis was used to identify predictors of HP. MedDRA terms were interrogated for reported and potential clinical signs of HP. Results 2,760 FCM subjects (40.1%) with normal PO4 at baseline developed HP (PO4 &amp;lt;2.5 mg/dl) on study. PO4 levels normalised in 1,705 subjects (61.8%); mean time to normalisation (±SD) was 40.7 days (±35.31). PO4 normalisation during follow-up did not occur in 177 subjects (0.06%). Independent risk factors for moderate/severe HP within 12 weeks of treatment included treatment setting (gastroenterology or neurology vs. women’s health), lower baseline ferritin level, maximum single-dose, advanced age, lower weight at baseline (all p &amp;lt; 0.0001), multiple doses vs. single dose (p = 0.0003), and higher cumulative dose (p = 0.0005). ‘Hypophosphataemia’ as a MedDRA term was approximately 10-fold more frequent with FCM than controls (2.2% vs. 0.2% with other IV irons). Potential clinical signs of HP were not more frequent with FCM vs. controls (Table) and were not associated with nadir levels of serum PO4. 4 of 49 FCM subjects (8.2%) who had nadir PO4 below 1 mg/dl had a potential clinical sign of HP, vs. 126/1,569 (8.0%) with 1–&amp;lt;2.0 mg/dl, 113/1,229 (9.2%) with 2.0–&amp;lt;2.5 mg/dl and 411/4,032 (10.2%) with ≥2.5 mg/dl. Among subjects with PO4 &amp;lt;2.5 mg/dl, serious cardiac disorders classified as potentially related to HP occurred in 14 FCM subjects (0.5%), 1 (0.7%) other IV iron, and 2 (4.4%) oral iron. Conclusion HP is recognised as a common adverse drug reaction with FCM as with several other IV iron preparations. This analysis shows that the transient decreases in PO4 levels were more frequent in patients receiving multiple and/or large doses of FCM but were not associated with an increased rate of potential signs/symptoms of HP.

604 Outcomes of Long-Term Follow-Up in Patients With Iron Deficiency Anemia and Initial Negative Upper Endoscopy, Colonoscopy, and Video Capsule Endoscopy

INTRODUCTION: Iron Deficiency Anemia (IDA) occurs in 2-5% of adults and requires workup including upper esophagogastroduodenoscopy (EGD) and/or colonoscopy.1 However, in 10-41% of patients a source of bleeding is not identified,2–5 which requires investigation of the small bowel using video capsule endoscopy (VCE). This study aims to determine the long-term outcomes in patients with IDA and a pan endoscopy-negative IDA, which entails negative EGD, colonoscopy and VCE. METHODS: Medical records at the VA NY Harbor were queried for patients with IDA and having an EGD, colonoscopy, and VCE between 2005-2015. Anemia was defined as hemoglobin less than 13 g/dL in men and 12 g/dL in women; IDA was confirmed using serum ferritin less than 100 ng/mL. Exclusion criteria included underlying causes for IDA such as pre-menopausal women or history of ulcerative colitis. Biographical, laboratory and endoscopic data were obtained. Baseline hemoglobin and ferritin levels were recorded, and subsequently followed at 1, 3, and 6-year intervals. RESULTS: A total of 7,000 records were reviewed, 311 patients had EGD, colonoscopy and VCE; 67 of these patients were excluded. Of the remaining patients, 99 patients (13 females, 86 males) had a negative initial workup and were included in analysis. The mean age was 68.2 (±11.1). IDA resolved in 37 (37.4%) patients, 49 (49.5%) patients had persistent anemia, and 13 (13.1%) patients had recurrent anemia. Of the 99 patients with negative workup, 80 (80.8%) patients went on to have subsequent EGD, colonoscopy or VCE. 62 (62.6%) patients had subsequent EGD with 12 (19.4%) patients having positive findings such as gastric ulcers. 64 (64.7%) patients had subsequent colonoscopies, 7 (10.9%) of these patients had positive findings such as chronically bleeding hemorrhoids. 18 (18.2%) patients had subsequent VCEs, and 5 (27.8%) of these patients had findings such as angioectasias. CONCLUSION: Our findings are consistent with previous reports suggesting that the majority of elderly patients who have an initial negative workup for IDA tend to have favorable outcomes. 21 of 80 patients (26.25%) had some findings on subsequent workup to explain IDA, however those findings were benign. In addition to previous published data, our study highlights the significance of VCE as a tool for identifying a bleeding source. Our study also emphasizes the need for randomized control studies to determine the optimal workup strategy for patients with initially negative bidirectional endoscopy and VCE.

Association between serum ferritin levels and clinical outcomes in maintenance hemodialysis patients: a retrospective single-center cohort study

BackgroundFerritin is a well-known marker of iron deficiency anemia, but the target in maintenance hemodialysis (MHD) patients remains controversial. This study examined the association between baseline ferritin levels and clinical outcomes.MethodsWe retrospectively collected the data of outpatients on MHD for 5 years at St. Luke’s International Hospital from July 2009. Patients with baseline ferritin levels of > 100 ng/mL in June 2009 were defined as the high-ferritin (HF) group and the remaining patients as the low-ferritin (LF) group. The primary endpoint was all-cause mortality. The secondary endpoints included cardiovascular events and infection-related hospitalizations. Log-rank test and Cox proportional hazard analysis were performed.ResultsOf 116 patients (age, 65.4 ± 13.4 years, 70% males), 29 (25%) and 87 (75%) belonged to the HF and LF groups, respectively. During the follow-up period of 1825 (interquartile range 819–1825) days, 38 patients (23 in the HF and 15 in the LF groups) died. According to the Kaplan–Meier survival curves, the HF group had significantly poor survival compared with the LF group (p = 0.0089). After adjusting for age, sex, vintage of hemodialysis, C-reactive protein levels, and history of cardiovascular events, the hazard ratio (HR) for the HF group was 2.49 (95% confidence interval (CI), 1.21–5.12). The multivariate analysis of cardiovascular events revealed a similar result with statistical significance (HR 2.69; 95% CI 1.12–6.46). Infection-related hospitalizations did not exhibit any statistically significant difference.ConclusionsIn MHD patients, ferritin levels > 100 ng/mL is associated with increased rates of all-cause mortality and cardiovascular events.

Predictive value of iron parameters in neurocritically ill patients.

BackgroundIron, an essential mineral for human body, has the potential to cause toxicity at high levels. Previous studies have shown inconsistent predictive value of iron parameters in critically ill patients. Thus, we aimed to evaluate the performance of iron parameters in outcome prediction of neurocritically ill patients.MethodsRetrospective data were collected from patients admitted to the neurocritical care unit (NCU) of a tertiary teaching hospital between August 2016 and January 2017. The iron parameters were obtained at NCU admission. Primary endpoints were short‐term (30‐day) mortality and long‐term (6‐month) poor outcome, with the latter defined as modified Rankin Scale of 4–6. The predictive value of variables was determined with univariate and multivariate logistic analysis. A further subanalysis was conducted in patients stratified by the level of estimated glomerular filtration rate (eGFR).ResultsOf 103 eligible patients, the etiology included stroke (58.2%, N = 60), central nervous system infection (13.6%, N = 14), and other neurologic disorders (28.2%, N = 29). The correlation analysis showed that the increase in ferritin, as well as the reduction in transferrin and total iron‐binding capacity, had strong correlation with C‐reactive protein, procalcitonin, duration of NCU stay, Acute Physiology and Chronic Health Evaluation II score, and Sequential Organ Failure Assessment score. In a further subanalysis of 75 patients with eGFR ≥ 60 ml/min/1.73 m2, twelve (16.0%) patients died within 30 days and 39 (52.0%) patients achieved good follow‐up outcome data. In the multivariate logistic regression analysis, we identified baseline ferritin level as an independent predictor of short‐term mortality (OR: 1.002; 95% CI: 1.000–1.003; p = 0.008) and long‐term functional outcome (OR: 1.002; 95% CI: 1.000–1.004; p = 0.031).ConclusionsSerum ferritin level at admission could be used as an independent predictor of short‐term mortality and long‐term functional outcome in neurocritically ill patients with eGFR ≥ 60 ml/min/1.73 m2.

The Effect of HCV Treatment With DAA on Iron Overload and Ferritin Levels: A Case Series

Introduction: Patients with chronic hepatitis C (CHC) are at increased risk for iron overload. Studies showed that chronic HCV patients treated with Pegylated Interferon (PEG-IFN) and who achieved sustained virologic response recovered from impaired hepcidin secretion leading to iron overload. Other studies showed that Hepatitis C virus-induced oxidative stress suppresses hepcidin expression [2,3]. HCV treatment has been transformed with the availability of direct acting anti-virals (DAAs), and SVR rates now exceed 90%. In this series, we report all patients in our practice with CHC who had an elevated serum ferritin or iron prior to treatment with DAAs and compare with levels after treatment with DAAs. To our knowledge, this is the first case series reporting outcomes in patients with high baseline iron and/or ferritin in the DAA era.2859_A Figure 1. No Caption available.Methods: We included all patients who were referred to our hepatology clinic for HCV treatment and evaluation. Data from patients who had ferritin level > 400 at the initial evaluation were collected. Results: There were 12 patients with high ferritin and/or iron/iron sat levels who met the criteria. Average age was 59 ±8 years. There were 9 (75%) males. A decrease in the levels of iron was noticed in 11/12 individuals. The average decrease in iron after treatment was 69.27 (range of 8 -149). The average decrease in ferritin was 648.25 (figure 1, table 1). 7 patients (58.3%) were alcohol users and 6 of them had quit drinking. 10 (83.33%) achieved SVR. 1 patient had compound C282Y-H63D heterozygote mutation and 2 patients had H63D homozygous mutation. Conclusion: Patients with CHC with elevated baseline iron level and/or ferritin level treated with DAAs saw a significant decrease in their iron, iron saturation and ferritin levels within a short period even in patients with hemochromatosis mutations. Whether this decrease was because of clinical factors, viral factors, genetic factors or an interplay between all three needs to be further investigated. Long term studies are needed to determine the clinical impact of decreasing iron/ferritin levels in these patients.

Evaluation of changes in ferritin levels during sucroferric oxyhydroxide treatment.

BackgroundA sub-analysis of a Phase III study was conducted to identify factors that might predict increased ferritin levels during long-term sucroferric oxyhydroxide (SO) treatment in hemodialysis patients.MethodsThe open-label, multicenter, Phase III study assessed the efficacy and safety of SO 750–3000 mg/day for 52 weeks in Japanese patients with chronic renal failure and hyperphosphatemia. A total of 125 of 161 patients from the Phase III trial, and who had data for ferritin levels after 28 weeks of SO treatment, were evaluated.ResultsBaseline ferritin was the strongest contributor (P < 0.0001) to ferritin increases during SO treatment. By Week 28, there were significant differences (P < 0.05/3) in ferritin increases between patients with higher [quartile 4 (Q4)] versus lower (Q1, Q2 and Q3) baseline ferritin. An erythropoiesis-stimulating agent dosage reduction was observed in patients with the lowest baseline ferritin level (Q1), and only slight reductions were noted in the other patient subsets. SO dosages administered to patients in baseline ferritin quartiles Q2, Q3 and Q4 were comparable throughout the study with slight fluctuations. SO dosages in Q1 were considerably lower than those in the other quartiles.ConclusionsIn summary, of the baseline variables found to predict increased ferritin, and changes in iron-related parameters, during SO treatment in Japanese chronic kidney disease patients undergoing hemodialysis, baseline ferritin was the most relevant variable.

Efficacy of canagliflozin against nonalcoholic fatty liver disease: a prospective cohort study.

SummaryBackgroundNonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease worldwide and is characterized by insulin resistance, hepatic steatosis and often prediabetes or diabetes. Canagliflozin, a selective sodium glucose cotransporter 2 inhibitor, is a new oral anti‐diabetic drug that reduces hyperglycaemia by promoting urinary glucose excretion. Glycosuria produced by canagliflozin is associated with weight loss, mainly due to reduced fat volume and improve insulin resistance. Reduced body weight and improvement of insulin resistance by canagliflozin may be an effective treatment for NAFLD.MethodsThirty‐five patients with NAFLD (17 men and 18 women) were enrolled and administered canagliflozin (100 mg). Body weight and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma‐glutamyl transferase (γ‐GTP), low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, triglycerides (TG), blood sugar (BS), glycated haemoglobin (HbA1C), uric acid (UA) and ferritin, and fibrosis‐4 (FIB‐4) index values were measured at baseline and at 3‐month and 6‐month follow‐up visits.ResultsBody weight and serum levels of AST, ALT, γ‐GTP, TG, UA, HbA1C, BS and ferritin decreased significantly after 3 and 6 months of canagliflozin treatment. Serum BS levels and FIB‐4 index values decreased slightly following 3 months of treatment; these results reached significance after 6 months. Reduced serum ALT levels at 6 months were significantly correlated with baseline HbA1C and ferritin levels. Moreover, a significant correlation between reduced body weight and serum ALT levels was observed at 6 months. Decreased serum ALT levels were significantly correlated with decreased serum ferritin at 6 months.ConclusionsCanagliflozin significantly reduced the serum levels of BS, HbA1C, TG, UA and ferritin, as well as FIB‐4 index values and body weight, with improved liver function. Sodium glucose cotransporter 2 inhibitors may be an important therapeutic modality for improving liver injury in NAFLD patients.

Ferritin level prospectively predicts hepatocarcinogenesis in patients with chronic hepatitis B virus infection.

Previous studies have detected a higher level of ferritin in patients with hepatocellular carcinoma (HCC), but a potential causal association between serum ferritin level and hepatocarcinogenesis remains to be clarified. Using a well-established prospective cohort and longitudinally collected serial blood samples, the association between baseline ferritin levels and HCC risk were evaluated in 1,152 patients infected with hepatitis B virus (HBV), a major risk factor for HCC. The association was assessed by Cox proportional hazards regression model using univariate and multivariate analyses and longitudinal analysis. It was demonstrated that HBV patients who developed HCC had a significantly higher baseline ferritin level than those who remained cancer-free (188.00 vs. 108.00 ng/ml, P<0.0001). The patients with a high ferritin level (≥200 ng/ml) had 2.43-fold increased risk of HCC compared to those with lower ferritin levels [hazard ratio (HR), 2.43; 95% confidence interval, 1.63–3.63]. A significant trend of increasing HRs along with elevated ferritin levels was observed (P for trend <0.0001). The association was still significant after multivariate adjustment. Incorporating ferritin into the α-fetoprotein (AFP) model significantly improved the performance of HCC prediction (the area under the curve from 0.74 to 0.77, P=0.003). Longitudinal analysis showed that the average ferritin level in HBV patients who developed HCC was persistently higher than in those who were cancer-free during follow-up. HCC risk reached a peak at approximately the fifth year after baseline ferritin detection. Moreover, stratified analyses showed that the association was noted in both males and females, and was prominent in patients with a low AFP value. In short, serum ferritin level could independently predict the risk of HBV-related HCC and may have a complementary role in AFP-based HCC diagnosis. Future studies are warranted to validate these findings and test its clinical applicability in HCC prevention and management.

Does Iron Supplementation Improve Performance in Iron-Deficient Nonanemic Athletes?

Context:Supplementing iron-deficient nonanemic (IDNA) athletes with iron to improve performance is a trend in endurance sports.Objectives:To investigate the benefits of iron on performance, identify a ferritin level cutoff in IDNA athletes, and determine which iron supplementation regimens are most effective.Data Sources:A search of the PubMed, CINAHL, Embase, ERIC, and Cochrane databases was performed in 2014 including all articles. Citations of pertinent review articles were also searched. In 2017, the search was repeated.Study Selection:Inclusion criteria comprised studies of level 1 to 3 evidence, written in the English language, that researched iron supplementation in nonanemic athletes and reported performance outcomes.Study Design:Systematic review.Level of Evidence:Level 3.Data Extraction:The search terms used included athletic performance, resistance training, athletes, physical endurance, iron, iron deficiency, supplement, non-anemic, low ferritin, ferritin, ferritin blood level, athletes, and sports.Results:A total of 1884 studies were identified through the initial database search, and 13 were identified through searching references of relevant review articles. A subsequent database search identified 46 studies. Following exclusions, 12 studies with a total of 283 participants were included. Supplementing IDNA athletes with iron improved performance in 6 studies (146 participants) and did not improve performance in the other 6 studies (137 participants). In the 6 studies that showed improved performance with iron supplementation, all used a ferritin level cutoff of ≤20 μg/L for treatment. Additionally, all studies that showed improved performance used oral iron as a supplement.Conclusion:The evidence is equivocal as to whether iron supplementation in IDNA athletes improves athletic performance. Supplementing athletes with ferritin levels <20 μg/L may be more beneficial than supplementing athletes with higher baseline ferritin levels.

The effectiveness of intravenous iron for iron deficiency anemia in gastrointestinal cancer patients: a retrospective study.

Background:Knowledge of the role of intravenous iron without the use of additional erythropoietic stimulating agents in anemic cancer patients is limited. This study evaluated the effect of ferric carboxymaltose (FCM) in a group of digestive oncology (DIO) patients and aimed to differentiate therapy response according to different types of iron deficiency (ID) anemia.Methods:In this retrospective study, we identified DIO patients who were receiving FCM and had eligible baseline and follow-up hemoglobin (Hb) levels that did not require red blood cell transfusion. Subgroup analyses examined adequately versus inadequately treated patients and low (<100 µg/L) vs. high (>100 µg/L) baseline ferritin levels. Inadequate treatment was defined as administration of an insufficient dose of FCM, based on the modified Ganzoni formula.Results:A total of 414 patients were receiving FCM, of whom 41 were excluded because of transfusion and another 70 because of unknown or inadequate baseline iron status. Thus, the study group consisted of 303 patients. Follow-up serum levels were evaluated after a median of 4 weeks. Overall, the median change between baseline and follow-up Hb was 0.5 (interquartile range [IQR]: -0.1–1.6) g/dL. No significant difference in this change was found between the adequately and inadequately dosed groups. The median change in Hb was significantly greater in the low baseline ferritin group than in the high baseline ferritin group: 1.2 (IQR: 0.3–2.2) vs. 0.4 (IQR: -0.3–1.4) g/dL, respectively; P=0.004.Conclusions:Intravenous administration of iron in DIO patients with ID anemia leads to a significant increase in Hb. Moreover, differentiating between the types of ID anemia based on ferritin levels could be applied to predict therapy response, although better biomarkers are needed.

Effect of iron supplementation on iron stores and total body iron after whole blood donation.

Understanding the effect of blood donation and iron supplementation on iron balance will inform strategies to manage donor iron status. A total of 215 donors were randomized to receive ferrous gluconate daily (37.5 mg iron) or no iron for 24 weeks after blood donation. Iron stores were assessed using ferritin and soluble transferrin receptor. Hemoglobin (Hb) iron was calculated from total body Hb. Total body iron (TBI) was estimated by summing iron stores and Hb iron. At 24 weeks, TBI in donors taking iron increased by 281.0 mg (95% confidence interval [CI], 223.4-338.6 mg) compared to before donation, while TBI in donors not on iron decreased by 74.1 mg (95% CI, -112.3 to -35.9; p < 0.0001, iron vs. no iron). TBI increased rapidly after blood donation with iron supplementation, especially in iron-depleted donors. Supplementation increased TBI compared to controls during the first 8 weeks after donation: 367.8 mg (95% CI, 293.5-442.1) versus -24.1 mg (95% CI, -82.5 to 34.3) for donors with a baseline ferritin level of not more than 26 ng/mL and 167.8 mg (95% CI, 116.5-219.2) versus -68.1 mg (95% CI, -136.7 to 0.5) for donors with a baseline ferritin level of more than 26 ng/mL. A total of 88% of the benefit of iron supplementation occurred during the first 8 weeks after blood donation. Donors on iron supplementation replaced donated iron while donors not on iron did not. Eight weeks of iron supplementation provided nearly all of the measured improvement in TBI. Daily iron supplementation after blood donation allows blood donors to recover the iron loss from blood donation and prevents sustained iron deficiency.