Association of Estimated Total Body Iron with All-Cause Mortality in Japanese Hemodialysis Patients: The Miyazaki Dialysis Cohort Study.

Iron deficiency/excess may be associated with worse prognosis in patients undergoing hemodialysis. This study ascertained the association of the estimated total body iron (TBI) with mortality in patients receiving hemodialysis. Multicenter clinical data collected in the Miyazaki Dialysis Cohort Study from 943 patients receiving hemodialysis were analyzed after stratification into tertile categories by baseline TBI-estimated as the heme iron plus iron storage from ferritin levels. The primary outcome was a 5-year all-cause mortality; hazard ratios of the TBI-all-cause mortality association were estimated using Cox models adjusted for potential confounders, including clinical characteristics, laboratory, and drug data, wherein patients with high TBI were the reference category. The receiver operating characteristic (ROC) curve analyses of TBI, serum ferritin levels, and transferrin saturation were performed to predict all-cause mortality; a total of 232 patients died during the follow-up. The low TBI group (<1.6 g) had significantly higher hazard ratios of mortality than the high TBI group (≥2.0 g). As ROC curve analyses showed, TBI predicted mortality more accurately than either levels of serum ferritin or transferrin saturation. Lower TBI increases the mortality risk of Japanese hemodialysis patients, and further studies should examine whether iron supplementation therapy that avoids low TBI improves prognosis.

Investigation on the feasibility of large-volume autologous red blood cells donation: A pilot trial in a small cohort of Chinese.

BACKGROUND: Preoperative autologous blood donation (PAD) is used for elective surgical procedures with a predictable blood loss. But a downward trend in PAD is due to the fact that patients with preoperative whole blood donation or two-unit red cell apheresis cannot avoid receiving allogenic blood during intensive surgery. To improve the clinical application of PAD, this study explores the feasibility of large-volume autologous red blood cells (RBCs) donation by a pilot trial in a small cohort of Chinese. METHODS: This was a single-center, prospective study and 16 male volunteers were enrolled from May to October in 2020. Each volunteer donated 627.25 ± 109.74 mL (mean ± SD) RBC with apheresis machine or manually, and received 800 mg of intravenous iron in four divided doses. Blood pressure, oxygen saturation (SpO2 ), respiratory rate and heart rate were monitored throughout the procedure. The RBC count, hemoglobin (Hb) concentration, hematocrit (Hct), reticulocyte count, erythropoietin (Epo), serum iron, total iron binding capacity (TIBC), transferrin saturation, transferrin, and ferritin were dynamically detected and analyzed before and 8 weeks after blood donation. RESULTS: There was no differences in SpO2 , systolic and diastolic blood pressure before and after blood collection (P ≥ .05). The heart rate and respiratory rate after donation were slightly lower than those before (P < .05). The level of RBC, Hb concentration and Hct fell to a nadir on Day 3 (pre-donation vs post-donation on Day 3: RBC 4.81 ± 0.36*1012 /L vs 3.65 ± 0.31, P < .05; Hb 148.59 ± 11.92 g/L vs 113.19 ± 10.43 g/L, P < .05; Hct 44.08 ± 3.06% vs 33.38 ± 2.57%, P < .05) and recovered to the pre-donation levels at the eighth week post donation (pre-donation vs post-donation at the eighth week: RBC 4.81 ± 0.36*1012 /L vs 4.84 ± 0.34*1012 /L, P ≥ .05; Hb 148.59 ± 11.92 g/L vs 150.91 ± 11.75 g/L, P ≥ .05; Hct 44.08% ± 3.06% vs 43.86 ± 3.06%, P ≥ .05). Epo and the reticulocyte count reached the peak values on Days 1 and 7, respectively (Epo: D0 15.30 ± 7.47 mlU/ML vs D1 43.26 ± 10.52 mlU/ML, P < .05; reticulocyte count: D0 0.07 ± 0.02*109 /L vs D7 0.17 ± 0.04*109 /L, P < .05). The red cell net profits on Day 7, the second, fourth and eighth week postdonation were 160.39 ± 144.33 mL, 387.59 ± 128.74 mL, 530.95 ± 120.37 mL, and 614.18 ± 120.10 mL, and accounted for 27.47% ± 24.70%, 63.75% ± 24.91%, 86.20% ± 22.99%, and 99.20% ± 19.19% of RBC donation, respectively. The levels of serum iron, serum ferritin, and transferrin saturation increased during the first week because of the supplement of intravenous iron, and then gradually decreased and declined to the baseline at the end of the study period at the eighth week. CONCLUSIONS: The large-volume autologous RBCs donation of 600 mL is proved safe in our study. Combination support of normal saline to maintain blood volume and intravenous iron supplementation may ensure the safety and effectiveness of large-volume RBC apheresis.

[Evaluation of serum iron as a predictor of a hemoglobin response to injectable iron treatment in chronic hemodialysis patients]. / Évaluation du fer sérique comme facteur prédictif d'une réponse de l'hémoglobine au traitement par fer injectable chez les patients hémodialysés chroniques.

BACKGROUND: The detection and correction of iron deficiency are essential for the treatment of anemia in chronic hemodialysis patients. The aim of our study was to assess the ability of serum iron to predict hemoglobin response to intravenous iron supplementation in hemodialysis patients. METHODS: It is a retrospective study in 91 hemodialysis patients during 2016 at Clermont-Ferrand University Hospital for whom intravenous iron supplementation had been started. A responder patient was defined as an increase in hemoglobin greater than or equal to 1 g/dL/month and/or a decrease in the dose of erythropoiesis stimulating agent after two months of iron supplementation. RESULTS: In responding patients, serum iron was significantly lower (6.7 ± 2.7 µmol/L) compared to non-responding patients (8.9±2.9 µmol/L; P<0.001). The positive response to iron supplementation was significantly associated with low serum iron (odds ratio = 0.58 [0.42-0.81]; P=0.002) in a logistic regression model taking into account ferritin, transferrin saturation coefficient, dose variation monthly iron and erythropoiesis stimulating agent and the duration of dialysis. The area under the receiver operating characteristic curve of serum iron, ferritin and transferrin saturation coefficient to predict the response to iron supplementation were 0.72, 0.51 and 0.64, respectively (serum iron versus ferritin [P=0.006] and serum iron versus transferrin saturation coefficient [P=0.04]). The sensitivity for serum iron below 7.5 µmol/L was better than that for ferritin below 86 ng/mL (P<0.001) and the specificity for serum iron below 7.5 µmol/L was better than that for TSC less than 19% (P=0.02). CONCLUSION: Serum iron below 7.5 µmol/L can predict the success of the response to iron supplementation in chronic hemodialysis patients.

Acute Administration of Bioavailable Curcumin Alongside Ferrous Sulphate Supplements Does Not Impair Iron Absorption in Healthy Adults in a Randomised Trial.

Ferrous sulphate (FS) is a cost effective, readily available iron supplement for iron deficiency (ID). The pro-oxidant effect of oral ferrous iron is known to induce inflammation, causing gastric side-effects and resulting in poor compliance. Curcumin is a potent antioxidant and has also been shown to exhibit iron chelation in-vitro, although it is not established whether these effects are retained in-vivo. The aim of this study was therefore to assess the influence of a formulated bioavailable form of curcumin (HydroCurcTM; 500 mg) on acute iron absorption and status in a double blind, placebo-controlled randomized trial recruiting 155 healthy participants (79 males; 26.42 years ± 0.55 and 76 females; 25.82 years ± 0.54). Participants were randomly allocated to five different treatment groups: iron and curcumin placebo (FS0_Plac), low dose (18 mg) iron and curcumin placebo (FS18_Plac), low dose iron and curcumin (FS18_Curc), high dose (65 mg) iron and curcumin placebo (FS65_Plac), and high dose iron and curcumin (FS65_Curc). Participants were provided with the supplements according to their relevant treatment groups at baseline (0 min), and blood collection was carried out at 0 min and at 180 min following supplementation. In the treatment groups, significant difference was observed in mean serum iron between baseline (0 min) and at end-point (180 min) (F (1, 144) = 331.9, p < 0.0001) with statistically significant intra-group increases after 180 min (p < 0.0001) in the FS18_Plac (8.79 µmol/L), FS18_Curc (11.41 µmol/L), FS65_Plac (19.09 µmol/L), and FS65_Curc (16.39 µmol/L) groups. A significant difference was also observed between the two time points in serum TIBC levels and in whole blood haemoglobin (HGB) in the treatment groups, with a significant increase (1.55%/2.04 g/L) in HGB levels from baseline to end-point observed in the FS65_Curc group (p < 0.05). All groups receiving iron demonstrated an increase in transferrin saturation (TS%) in a dose-related manner, demonstrating that increases in serum iron are translated into increases in physiological iron transportation. This study demonstrates, for the first time, that regardless of ferrous dose, formulated curcumin in the form of HydroCurc™ does not negatively influence acute iron absorption in healthy humans.

Genetically Predicted Serum Iron Status Is Associated with Altered Risk of Systemic Lupus Erythematosus among European Populations.

BACKGROUND: Observational epidemiological studies have reported an inconsistent relation between iron status and risk of systemic lupus erythematosus (SLE). Moreover, it remains uncertain whether the observed association is causal or due to confounding or reverse causality. OBJECTIVES: We aimed to investigate the association between serum iron status and risk of SLE using a 2-sample Mendelian randomization (MR) approach. METHODS: Genetic instruments for iron status including serum iron, log-transformed ferritin, transferrin saturation, and transferrin were identified from a large-scale genome-wide association study (GWAS) performed by the Genetics of Iron Status Consortium among 48,972 individuals of European ancestry (55% female). Three independent single nucleotide polymorphisms (rs1800562, rs1799945, and rs855791) concordantly related with 4 iron status biomarkers were selected as instrumental variables. Summary statistics of SLE were obtained from a publicly available GWAS of 4036 patients with SLE and 6959 controls of European descent. The MR study was conducted using the inverse-variance weighted (IVW) method, supplemented with MR-Egger regression and simple- and weighted-median methods. Leave-one-out analysis was further performed to test the robustness of our findings. ORs with 95% CIs were calculated. RESULTS: Genetically predicted iron status was associated with altered risk of SLE, with ORs of 0.79 (95% CI: 0.66, 0.94), 0.54 (95% CI: 0.34, 0.85), 0.82 (95% CI: 0.71, 0.94), and 1.36 (95% CI: 1.06, 1.76) per 1-SD increase in iron, log-transformed ferritin, transferrin saturation, and transferrin using the IVW method, respectively. MR-Egger regression did not indicate potential pleiotropic bias. Sensitivity analyses produced similar findings, suggesting the robustness of the association. CONCLUSIONS: Our study suggested that high iron status may be associated with a reduced risk of SLE among European populations. Further studies are warranted to elucidate the mechanism underlying the protective role of iron against susceptibility to SLE.

[A real-world study to evaluate a peptidic oral supplement in adults with altered intestinal function after parenteral nutrition]. / Un estudio en la vida real para evaluar un suplemento oral peptídico en adultos con alteración de la función intestinal tras la nutrición parenteral.

INTRODUCTION: Objectives: in routine clinical practice many disorders are found that can disrupt the sequence of reactions in digestion and absorption, leading to malnutrition and requiring the use of oral nutritional supplements (ONS). The objective of our study was to evaluate in a real world setting the use of and compliance with a peptide-based ONS in malnourished adult patients with intestinal compromise after more than 14 days of parenteral nutrition. Material and methods: the study was carried out in 44 malnourished patients who required total parenteral nutrition for at least 14 days without using the oral route during their hospital stay. All patients were administered, on an outpatient basis, 1 brick per day of Vital 1.5® for 12 weeks. At the beginning of treatment and after the intervention period evaluated, the following variables were collected: weight, height, body mass index (BMI), global subjective assessment test, nutritional biochemistry, 3-day nutritional survey, adverse effects generated by the formula, and completion rate. Results: 44 patients were enrolled. Mean age was 70.4 ± 10.4 years (20 women & 24 men). After the intervention the following parameters had increased: BMI (0.51 ± 0.1 kg/m2; p = 0.02), weight (1.4 ± 0.3 kg; p = 0.03), prealbumin (3.5 ± 4.1 mg/dl; p = 0.01), albumin (1.3 ± 0.1 mg/dl; p = 0.03), and transferrin (71.5 ± 24.1 mg/dl; p = 0.02). Dietary intake of the ONS represented 14.4 % of the diet's total caloric intake at 3 months, 17.5 % of carbohydrates, 12.9 % of proteins, and 12.3 % of fats. Mean compliance was 87.7 ± 7.2 % of the prescribed intakes. In relation to the nutritional situation, at the beginning of the study, 52.3 % (n = 23) of patients were in the global subjective assessment test in category B (moderate malnutrition or nutritional risk), and 47.7 % (n = 21) in category C (severe malnutrition). After the intervention, 75 % of patients were in category A (n = 33), 13.6 % (n = 6) in category B, and 11.4 % (n = 5) in category C. Conclusions: the use of a peptide-based ONS with short-chain triglycerides in outpatients showed a beneficial effect on biochemical and anthropometric parameters, and improved the nutritional status of patients with high compliance and good tolerance rates.

INTRODUCCIÓN: Objetivos: en la práctica clínica habitual existen multitud de situaciones y patologías que pueden interrumpir la digestión y la absorción intestinal, cursando con desnutrición y requiriendo el uso de suplementos orales nutricionales (SON). El objetivo de nuestro estudio fue evaluar, en el contexto de la vida real, el uso de un SON basado en péptidos, y el cumplimiento con el mismo, en pacientes adultos desnutridos con compromiso intestinal tras más de 14 días de nutrición parenteral. Material y métodos: el estudio se realizó en 44 pacientes desnutridos que requirieron nutrición parenteral total al menos 14 días, sin utilización de la vía oral durante el ingreso hospitalario. Se les administró de manera ambulatoria 1 brik al día de Vital 1.5® para su consumo durante 12 semanas. Al inicio del tratamiento y tras el periodo de intervención se les recogieron las variables siguientes: peso, talla, IMC, test de valoración subjetiva global, bioquímica nutricional, encuesta nutricional, efectos adversos generados por la fórmula y cumplimentación. Resultados: se incluyeron 44 pacientes con una edad media de 70,4 ± 10,4 años (20 mujeres/24 hombres). Tras la intervención aumentaron el IMC (0,51 ± 0,1 kg/m2; p = 0,02), el peso (1,4 ± 0,3 kg; p = 0,03), la prealbúmina (3,5 ± 4,1 mg/dl; p = 0,01), la albúmina (1,3 ± 0,1 mg/dl; p = 0,03) y la transferrina (71,5 ± 24,1 mg/dl; p = 0,02). La toma del SON represento a los 3 meses un 14,4 % del aporte calórico total de la dieta, un 17,5 % de los hidratos de carbono, un 12,9 % de las proteínas y un 12,3 % de las grasas. La cumplimentación media del grupo fue del 87,7 ± 7,2 % de las tomas prescritas. En relacion a la situacion nutricional, a la entrada del estudio un 52,3 % (n = 23) de los pacientes presentaban en el test de valoración subjetiva global la categoría B (malnutrición moderada o riesgo nutricional) y un 47,7 % (n = 21) la categoría C (desnutrición severa). Tras la intervención, un 75 % de los pacientes presentaban la categoría A (buena situación nutricional (n = 33), un 13,6 % (n = 6) de los pacientes presentaban la categoría B y un 11,4 % (n = 5) la categoría C. Conclusiones: la utilización de un suplemento peptídico con triglicéridos de cadena corta en pacientes ambulatorios tras haber recibido una nutrición parenteral total muestra un efecto beneficioso sobre los parametros bioquímicos y antropométricos, y la situación nutricional, con una alta cumplimentación y buena tolerancia.

Genetically predicted iron status and life expectancy.

BACKGROUND & AIMS: Systemic iron status affects multiple health outcomes, however its net effect on life expectancy is not known. We conducted a two-sample Mendelian randomization (MR) study to investigate the association of genetically proxied iron status with life expectancy. METHODS: Using genetic data from 48,972 individuals, we identified three genetic variants as instrumental variables for systemic iron status. We obtained genetic associations of these variants with parental lifespan (n = 1,012,240) and individual survival to the 90th vs. 60th percentile age (11,262 cases and 25,483 controls). We used the inverse-variance weighted method to estimate the effect of a 1-standard deviation (SD) increase in genetically predicted serum iron on each of the life expectancy outcomes. RESULTS: We found a detrimental effect of genetically proxied higher iron status on life expectancy. A 1-SD increase in genetically predicted serum iron corresponded to 0.70 (95% confidence interval [CI] -1.17, -0.24; P = 3.00 × 10-3) fewer years of parental lifespan and had odds ratio 0.81 (95% CI 0.70, 0.93; P = 4.44 × 10-3) for survival to the 90th vs. 60th percentile age. We did not find evidence to suggest that these results were biased by pleiotropic effects of the genetic variants. CONCLUSIONS: Higher systemic iron status may reduce life expectancy. The clinical implications of this finding warrant further investigation, particularly in the context of iron supplementation in individuals with normal iron status.

On the trail of blood doping-microRNA fingerprints to monitor autologous blood transfusions in vivo.

Autologous blood doping refers to the illegal re-transfusion of any quantities of blood or blood components with blood donor and recipient being the same person. The re-transfusion of stored erythrocyte concentrates is particularly attractive to high-performance athletes as this practice improves their oxygen capacity excessively. However, there is still no reliable detection method available. Analyzing circulating microRNA profiles of human subjects that underwent monitored autologous blood transfusions seems to be a highly promising approach to develop novel biomarkers for autologous blood doping. In this exploratory study, we randomly divided 30 healthy males into two different treatment groups and one control group and sampled whole blood at several time points at baseline, after whole blood donation and after transfusion of erythrocyte concentrates. Hematological variables were recorded and analyzed following the adaptive model of the Athlete Biological Passport. microRNA profiles were examined by small RNA sequencing and comprehensive multivariate data analyses, revealing microRNA fingerprints that reflect the sampling time point and transfusion volume. Neither individual microRNAs nor a signature of transfusion-dependent microRNAs reached superior sensitivity at 100% specificity compared to the Athlete Biological Passport (≤11% 6 h after transfusion versus ≤44% 2 days after transfusion). However, the window of autologous blood doping detection was different. Due to the heterogenous nature of doping, with athletes frequently combining multiple medications in order to both gain a competitive advantage and interfere with known testing methods, the true applicability of the molecular signature remains to be validated in real anti-doping testings.

Vitamin D in dysphagic patients who have undergone endoscopic gastrostomy for long-term enteral feeding.

OBJECTIVE: Vitamin D plays a major role in biological processes. Its deficiency is associated with increased morbidity and mortality. Patients who have undergone endoscopic gastrostomy (PEG) present with protein-energy malnutrition, and may be at risk for Vitamin D deficiency, due to their age, less sunlight exposure and lower dietary intake. We aimed to determine the prevalence of hypovitaminosis D in PEG-patients, its change under PEG-feeding, and its relationship with serum proteins and risk factors for Vitamin D deficiency. METHODS: This was a prospective observational study, over 4 weeks, after gastrostomy. Data were collected at the initial PEG procedure (T0), and after 4 weeks (T1). Initial evaluation included age, gender, underlying disorder, NRS-2002, BMI, serum albumin, transferrin and Vitamin D. At T1 we assessed Vit. D, albumin, and transferrin. Vitamin D was performed with Electrochemiluminescence through Elecsys 2010 assay. Patients were fed with blended homemade meals. RESULTS: 200 patients (118 males), 22-92 years of age, were studied. There were initial low values for Vit. D (181), albumin (96), transferrin (121), and BMI (124). A correlation was found between Vit. D and serum albumin (r=0.49, p=0.005) but not with transferrin (r=0.26, p=0.195). At T1 the subgroup who had Vit. D levels assessed (n=48) was part of the initial study group maintained low levels of Vitamin D despite nutritional intervention. CONCLUSION: We recommend systematic Vitamin D supplementation of PEG fed patients using homemade meals or at least screening for hypovitaminosis D as a routine part of their care.

Anemia of Chronic Diseases: Wider Diagnostics-Better Treatment?

Anemia of chronic diseases is a condition that accompanies a specific underlying disease, in which there is a decrease in hemoglobin, hematocrit and erythrocyte counts due to a complex process, usually initiated by cellular immunity mechanisms and pro-inflammatory cytokines and hepcidin. This is the second most common type of anemia after iron deficiency anemia in the world. Its severity generally correlates with the severity of the underlying disease. This disease most often coexists with chronic inflammation, autoimmune diseases, cancer, and kidney failure. Before starting treatment, one should undertake in-depth diagnostics, which includes not only assessment of complete blood count and biochemical parameters, but also severity of the underlying disease. The differential diagnosis of anemia of chronic diseases is primarily based on the exclusion of other types of anemia, in particular iron deficiency. The main features of anemia of chronic diseases include mild to moderate lowering of hemoglobin level, decreased percentage of reticulocyte count, low iron and transferrin concentration, but increased ferritin. Due to the increasingly better knowledge of the pathomechanism of chronic diseases and cancer biology, the diagnosis of this anemia is constantly expanding with new biochemical indicators. These include: the concentration of other hematopoietic factors (folic acid, vitamin B12), hepcidin, creatinine and erythropoietin. The basic form of treatment of anemia of chronic diseases remains supplementation with iron, folic acid and vitamin B12 as well as a diet rich in the above-mentioned hematopoietic factors. The route of administration (oral, intramuscular or intravenous) requires careful consideration of the benefits and possible side effects, and assessment of the patient's clinical status. New methods of treating both the underlying disease and anemia are raising hopes. The novel methods are associated not only with supplementing deficiencies, but also with the administration of drugs molecularly targeted to specific proteins or receptors involved in the development of anemia of chronic diseases.

Iron metabolism imbalance at the time of listing increases overall and infectious mortality after liver transplantation.

BACKGROUND: Liver transplantation (LT) is the best treatment for patients with liver cancer or end stage cirrhosis, but it is still associated with a significant mortality. Therefore identifying factors associated with mortality could help improve patient management. The impact of iron metabolism, which could be a relevant therapeutic target, yield discrepant results in this setting. Previous studies suggest that increased serum ferritin is associated with higher mortality. Surprisingly iron deficiency which is a well described risk factor in critically ill patients has not been considered. AIM: To assess the impact of pre-transplant iron metabolism parameters on post-transplant survival. METHODS: From 2001 to 2011, 553 patients who underwent LT with iron metabolism parameters available at LT evaluation were included. Data were prospectively recorded at the time of evaluation and at the time of LT regarding donor and recipient. Serum ferritin (SF) and transferrin saturation (TS) were studied as continuous and categorical variable. Cox regression analysis was used to determine mortality risks factors. Follow-up data were obtained from the local and national database regarding causes of death. RESULTS: At the end of a 95-mo median follow-up, 196 patients were dead, 38 of them because of infections. In multivariate analysis, overall mortality was significantly associated with TS > 75% [HR: 1.73 (1.14; 2.63)], SF < 100 µg/L [HR: 1.62 (1.12; 2.35)], hepatocellular carcinoma [HR: 1.58 (1.15; 2.26)], estimated glomerular filtration rate (CKD EPI Cystatin C) [HR: 0.99 (0.98; 0.99)], and packed red blood cell transfusion [HR: 1.05 (1.03; 1.08)]. Kaplan Meier curves show that patients with low SF (< 100 µg/L) or high SF (> 400 µg/L) have lower survival rates at 36 mo than patients with normal SF (P = 0.008 and P = 0.016 respectively). Patients with TS higher than 75% had higher mortality at 12 mo (91.4% ± 1.4% vs 84.6% ± 3.1%, P = 0.039). TS > 75% was significantly associated with infection related death [HR: 3.06 (1.13; 8.23)]. CONCLUSION: Our results show that iron metabolism imbalance (either deficiency or overload) is associated with post-transplant overall and infectious mortality. Impact of iron supplementation or depletion should be assessed in prospective study.

Impact of Transferrin Saturation on All-Cause Mortality in Patients on Maintenance Hemodialysis.

BACKGROUND: Transferrin saturation (TSAT) is an index that represents the iron-binding capacity of transferrin, which is the main transport protein for iron, and is widely used to evaluate iron status. OBJECTIVE: To evaluate the prognostic importance of TSAT in Japanese patients on maintenance hemodialysis (MHD). METHODS: A total of 398 patients on MHD were recruited and divided into 3 groups on the basis of their baseline TSAT levels (<20, 20-40, and >40%). RESULTS: There was no difference in the proportion of patients on erythropoiesis-stimulating agents or iron supplements between the 3 groups. During a mean follow-up period of 52.2 ± 1 6.3 months, 130 patients died of cardiovascular causes (n = 63, 15.8%) or infection (n = 47, 11.8%). Compared with the reference group (TSAT 20-40%), patients with a TSAT <20% had a significantly higher all-cause mortality rate (6.44 vs. 9.55 events per 100 patient-years, p = 0.0452). Kaplan-Meier analysis showed that all-cause mortality rate was significantly higher in patients with TSAT <20% than in the other 2 groups (p = 0.0353). CONCLUSIONS: Low TSAT was a significant independent risk factor for all-cause mortality in a cohort of Japanese patients on MHD. The findings of this study suggest that the adverse clinical outcomes in patients with low TSAT can be partly attributed to infection-related iron deficiency.

Iron intake, body iron status, and risk of breast cancer: a systematic review and meta-analysis.

BACKGROUND: Iron has been shown to promote breast carcinogenesis in animal models through generation of oxidative stress and interaction with estrogen. Heme iron, which is found exclusively in animal-sourced foods, is suggested to have a more detrimental effect. Epidemiological evidence of the association between iron and breast cancer risk remains inconclusive and has not been comprehensively summarized. This systematic review and meta-analysis evaluated associations between both iron intake and body iron status and breast cancer risk. METHODS: Four electronic databases (MEDLINE, EMBASE, CINAHL, and Scopus) were searched up to December 2018 for studies assessing iron intake and/or biomarkers of iron status in relation to breast cancer risk. Using random-effects meta-analyses, pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated comparing the highest vs. lowest category of each iron measure. Dose-response meta-analyses were also performed to investigate linear and nonlinear associations. RESULTS: A total of 27 studies were included in the review, of which 23 were eligible for meta-analysis of one or more iron intake/status measures. Comparing the highest vs. lowest category, heme iron intake was significantly associated with increased breast cancer risk, with a pooled RR of 1.12 (95% CI: 1.04-1.22), whereas no associations were found for dietary (1.01, 95% CI: 0.89-1.15), supplemental (1.02, 95% CI: 0.91-1.13), or total (0.97, 95% CI: 0.82-1.14) iron intake. Associations of iron status indicators with breast cancer risk were generally in the positive direction; however, a significant pooled RR was found only for serum/plasma levels (highest vs. lowest) of iron (1.22, 95% CI: 1.01-1.47), but not for ferritin (1.13, 95% CI: 0.78-1.62), transferrin saturation (1.16, 95% CI: 0.91-1.47), or total iron-binding capacity (1.10, 95% CI: 0.97-1.25). In addition, a nonlinear dose-response was observed for heme iron intake and serum iron (both Pnonlinearity < 0.05). CONCLUSIONS: Heme iron intake and serum iron levels may be positively associated with breast cancer risk. Although associations were modest, these findings may have public health implications given the widespread consumption of (heme) iron-rich foods. In light of methodological and research gaps identified, further research is warranted to better elucidate the relationship between iron and breast cancer risk.

Intravenous Iron in Patients Undergoing Maintenance Hemodialysis.

BACKGROUND: Intravenous iron is a standard treatment for patients undergoing hemodialysis, but comparative data regarding clinically effective regimens are limited. METHODS: In a multicenter, open-label trial with blinded end-point evaluation, we randomly assigned adults undergoing maintenance hemodialysis to receive either high-dose iron sucrose, administered intravenously in a proactive fashion (400 mg monthly, unless the ferritin concentration was >700 µg per liter or the transferrin saturation was ≥40%), or low-dose iron sucrose, administered intravenously in a reactive fashion (0 to 400 mg monthly, with a ferritin concentration of <200 µg per liter or a transferrin saturation of <20% being a trigger for iron administration). The primary end point was the composite of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, or death, assessed in a time-to-first-event analysis. These end points were also analyzed as recurrent events. Other secondary end points included death, infection rate, and dose of an erythropoiesis-stimulating agent. Noninferiority of the high-dose group to the low-dose group would be established if the upper boundary of the 95% confidence interval for the hazard ratio for the primary end point did not cross 1.25. RESULTS: A total of 2141 patients underwent randomization (1093 patients to the high-dose group and 1048 to the low-dose group). The median follow-up was 2.1 years. Patients in the high-dose group received a median monthly iron dose of 264 mg (interquartile range [25th to 75th percentile], 200 to 336), as compared with 145 mg (interquartile range, 100 to 190) in the low-dose group. The median monthly dose of an erythropoiesis-stimulating agent was 29,757 IU in the high-dose group and 38,805 IU in the low-dose group (median difference, -7539 IU; 95% confidence interval [CI], -9485 to -5582). A total of 320 patients (29.3%) in the high-dose group had a primary end-point event, as compared with 338 (32.3%) in the low-dose group (hazard ratio, 0.85; 95% CI, 0.73 to 1.00; P<0.001 for noninferiority; P=0.04 for superiority). In an analysis that used a recurrent-events approach, there were 429 events in the high-dose group and 507 in the low-dose group (rate ratio, 0.77; 95% CI, 0.66 to 0.92). The infection rate was the same in the two groups. CONCLUSIONS: Among patients undergoing hemodialysis, a high-dose intravenous iron regimen administered proactively was superior to a low-dose regimen administered reactively and resulted in lower doses of erythropoiesis-stimulating agent being administered. (Funded by Kidney Research UK; PIVOTAL EudraCT number, 2013-002267-25 .).

Synergistic effect of galacto oligosaccharides and iron fortificants on serum iron, ferritin, transferrin and total iron binding capacity levels in anemic rats.

Iron deficiency anemia is one of the leading public health issues being faced by the global population currently. The present research was an attempt to determine the synergistic effect of Galacto Oligosaccharides and iron fortificants on serum iron, serum ferritin, serum transferrin and total iron binding capacity in anemic rats. To serve the purpose, eight different types of fortified feed were prepared with varying concentrations of Iron Fortificants (NaFeEDTA and FeSO4) while the varying dosage of galacto oligosaccharides was dissolved separately in water to be fed to anemic rats. Afterwards, animal trials were conducted for twelve weeks to determine the efficacy of Galacto Oligosaccharides & iron fortificants based feed against the aforementioned parameters. The results of the study suggested that both serum iron and serum ferritin levels were significantly improved when anemic rats were fed with iron and Galacto Oligosaccharides fortified feed. It was also observed that the levels of serum transferrin and total iron binding capacity steadily decreased over the study duration. It can be concluded that Galacto Oligosaccharides helped enhance the absorption of iron in anemic rats, reflected by increase in serum iron and serum ferritin levels and decrease in serum transferrin and total iron binding capacity.

Iron Bisglycinate Chelate and Polymaltose Iron for the Treatment of Iron Deficiency Anemia: A Pilot Randomized Trial.

BACKGROUND: Iron Deficiency Anemia (IDA) is a major public health problem worldwide. Iron Bisglycinate Chelate (FeBC) and polymaltose iron (FeP) are used for the treatment of IDA and exhibit good tolerability with a low incidence of adverse effects. However, these compounds have important differences in their structures and bioavailability. OBJECTIVE: To compare the efficacy of oral supplementation with FeBC and FeP in anemic children. METHODS: In this double-blind study, children aged 1 to 13 years who were diagnosed with IDA were randomly divided into two groups: i) FeBC, supplemented with iron bisglycinate chelate, and ii) FeP, supplemented with polymaltose iron (3.0 mg iron/kg body weight/day for 45 days for both groups). RESULTS: Both treatments resulted in significant increases in hemoglobin levels, Mean Corpuscular Volume (MCV) and Cell Distribution Width (RDW) and in a reduction of transferrin levels, relative to initial values. However, only FeBC treatment significantly increased ferritin and Mean Corpuscular Hemoglobin (MCH) levels. A significant negative correlation was observed between the increase in ferritin and initial hemoglobin levels in the FeBC group, indicating that the absorption of FeBC is regulated by the body iron demand. CONCLUSION: These results provide preliminary evidence to suggest a greater efficacy of FeBC than FeP in increasing iron stores.

Iron deficiency associates with deterioration in several symptoms independently from hemoglobin level among chronic hemodialysis patients.

BACKGROUND: While iron deficiency (ID) is a frequent cause of anemia in hemodialysis patients, the clinical impact of ID without anemic level of hemoglobin remains unclear. As such, this study was designed to clarify the manifestations of ID itself in subjects on hemodialysis. METHODS: Maintenance hemodialysis patients achieving target hemoglobin levels (≥ 10.0g/dL) under treatment in our clinic were stratified for comparison from three perspectives: ID (transferrin saturation [TSAT] < 20% or ferritin < 100ng/mL) vs non-ID, level of TSAT (< or ≥ 20%), and level of serum ferritin concentration (< or ≥ 100ng/mL). The severity of frequent symptoms was determined by a self-rating symptom score questionnaire, and the rate of those with severe manifestations was calculated for each symptom. Significant difference was examined between groups; univariate and adjusted multivariate odds ratios and 95% confidence intervals were obtained by logistic regression. RESULTS: Among 154 subjects selected for analysis, the ratio of severe arthralgia and fatigue was significantly higher in the ID group (n = 94) compared to the non-ID group (n = 60), in both univariate and adjusted multivariate analyses. Moreover, in multivariate analysis, low TSAT was significantly associated with exacerbation of pain during vascular access puncture and intradialytic leg cramps, while low serum ferritin concentration was related to significant increase in severe arthralgia, fatigue, intradialytic headache and leg cramps. CONCLUSIONS: ID was identified as a risk factor regarding severity of several symptoms even without low hemoglobin level among chronic hemodialysis patients, and supplementation of iron was considered efficacious for improving critical symptoms affecting those undergoing maintenance dialysis.

Efficient preparation of surface imprinted magnetic nanoparticles using poly (2-anilinoethanol) as imprinting coating for the selective recognition of glycoprotein.

In view of the significance of glycoprotein biomarkers for early clinical diagnostics and treatments of diseases, it is essential to develop efficient and selective enrichment approaches for glycoproteins. Molecularly imprinted polymers (MIPs) have found important applications for separation and enrichment of glycoproteins. In this study, we use boronate affinity-based controllable oriented surface imprinting to prepare glycoprotein-imprinted magnetic nanoparticles. A glycoprotein was first immobilized onto the surface of boronic acid functionalized magnetic nanoparticles by boronate affinity. Subsequently, self-polymerization of 2-anilinoethanol was carried out to form thin imprinting coating on the magnetic nanoparticles surface with appropriate thickness. After removing the template with an acidic solution containing sodium dodecyl sulfate, 3D cavities complementary to the template were efficiently formed in the imprinting layer. The imprinting coating was highly hydrophilic and presented limited residual boronic acid, thus non-specific binding was avoided. Using horseradish peroxidase as a model target, the effects of imprinting conditions on the properties and performance of the prepared MIPs were investigated. The obtained MIPs exhibited several highly favorable features, including excellent specificity, high binding strength and low binding pH. The MIPs were successfully applied to the analysis of transferrin (TRF) in human serum.

Parâmetros hematológicos e bioquímicos de bezerros neonatos da raça Holandesa tratados com ferro suplementar / Hematological and biochemical parameters of neonatal Holstein calves supplemented with iron

A deficiência de ferro em bezerros neonatos está associada ao desenvolvimento de anemia, que favorece o aparecimento de outras enfermidades como pneumonia e diarreia. Avaliou-se o efeito da suplementação de ferro sobre o eritrograma, teores séricos de ferro, ceruloplasmina e transferrina, bem como o potencial para toxicidade do protocolo utilizado por meio da avaliação dos teores de ureia, creatinina e enzimas hepáticas. Para tal avaliação foram utilizados 40 bezerros neonatos da raça Holandesa, alocados em cinco grupos experimentais com oito animais em cada grupo, que foram submetidos aos seguintes protocolos: administração intramuscular de 5mL de solução fisiológica estéril no 5º dia de idade (grupo controle G1), e administração intramuscular de 5mL de ferro dextrano 10% nos seguintes momentos: no 5º dia de idade (G2); no 5o e no 20º dias de idade (G3); no 5o e no 30º dias de idade (G4) e no 5o, 20o e 45º dias de idade (G5). Foram coletadas amostras de sangue até 8 horas após o nascimento e aos 5, 10, 20, 30, 60 e 90 dias de idade para realização do eritrograma, avaliação dos teores séricos de ferro, ceruloplasmina, transferrina, ureia, creatinina, bilirrubina total e direta, e das atividades das enzimas aspartato aminotransferase (AST), fosfatase alcalina (ALP) e gamaglutamiltransferase (GGT). Os animais que receberam ferro suplementar apresentaram menor oscilação nos parâmetros eritrocitários, embora os animais do grupo controle não tenham desenvolvido anemia. Notou-se também aumento, embora não significativo, nos teores séricos de ferro e das proteínas de fase aguda ceruloplasmina e transferrina, cuja atividade está relacionada ao metabolismo desse mineral. Os teores séricos de ureia, creatinina, bilirrubina total e direta e as atividades das enzimas GGT, AST e ALP não foram influenciados pelos protocolos de administração de ferro suplementar. Os protocolos de tratamento empregados não ocasionaram hepatoxidade ou nefrotoxidade aos animais. Concluiu-se que a suplementação com ferro dextrano por via parenteral em bezerros que recebem outras dietas que não apenas leite não traz benefícios que justifiquem sua indicação, embora sejam necessários mais estudos que avaliem a influência da suplementação com ferro sobre o tempo necessário para a recuperação, custos com o tratamento e impacto sobre a vida produtiva dos animais na idade adulta.(AU)

Iron deficiency in newborn calves is associated with the development of anemia, which favors the development of other infirmities such as pneumonia and diarrhea. The present study evaluated the effect of iron supplementation on erythrogram, serum levels of iron, ceruloplasmin and tranferrin, as well as potential toxicity of the protocol used by means of evaluation of urea, creatinine and hepatic enzyme activities. 40 newborn Holstein calves were allocated into 5 experimental groups comprising 8 calves each, which were subjected to the following treatment protocols: intramuscular administration of 5mL of sterile saline on the 5th day of age (control group G1), intramuscular administration of 5mL of 10% dextran iron in the following moments: on the 5th day of age (G2); on the 5th and in the 20th day of age (G3); on the 5th and 30th day of age (G4); on the 5th, 20th and 45th days of age (G5). Blood samples were taken until 8 hours after birth and with 5, 10, 20, 30, 60, and 90 days of age, and subjected to hemogram, evaluation of serum levels of iron, ceruloplasmin, transferrin, urea, creatinine, total and direct bilirrubin, and serum activities of aspartate aminotransferase (AST), alcaline phosphatase (ALP), and gamma-glutamyltransferase (GGT). Calves that received iron supplementation at any time presented less variation in the erythrocyte parameters, although calves in the control group did not develop anemia. Serum concentration of iron and acute phase protein ceruloplasmin and transferrin, which activities are related to iron metabolism, also increased, although not significantly. Serum levels of urea, creatinine, bilirubins and activities of AST, ALP, and GGT were not influenced by the administration protocols used in this experiment. The results of the experiment led to the conclusion that the supplementation with parenteral dextran iron in calves that receive diets other than exclusive milk does not bring sufficient advantages to be indicated, although more studies are necessary to evaluate the influence of iron supplementation on the outcome of infections in newborn calves, especially its influence on cost of treatment, time necessary for discharge and impact on its productive life.(AU)