Iron distribution in different tissues of homozygous Mask (msk/msk) mice and the effects of oral iron treatments.

Iron-refractory iron deficiency anemia (IRIDA) is an autosomal recessive disorder caused by genetic mutations on TMPRSS6 gene which encodes Matriptase2 (MT2). An altered MT2 cannot appropriately suppress hepatic BMP6/SMAD signaling in case of low iron, hence hepcidin excess blocks dietary iron absorption, leading to a form of anemia resistant to oral iron supplementation. In this study, using the IRIDA mouse model Mask, we characterized homozygous (msk/msk) compared to asymptomatic heterozygous (msk/wt) mice, assessing the major parameters of iron status in different organs, at different ages in both sexes. The effect of carbonyl iron diet was analyzed as control iron supplementation being used for many studies in mice. It resulted effective in both anemic control and msk/msk mice, as expected, even if there is no information about its mechanism of absorption. Then, we mainly compared two forms of oral iron supplement, largely used for humans: ferrous sulfate and Sucrosomial iron. In anemic control mice, the two oral formulations corrected hemoglobin levels from 11.40 ± 0.60 to 15.38 ± 1.71 g/dl in 2-4 weeks. Interestingly, in msk/msk mice, ferrous sulfate did not increase hemoglobin likely due to ferroportin/hepcidin-dependent absorption, whereas Sucrosomial iron increased it from 11.50 ± 0.60 to 13.53 ± 0.64 g/dl mainly in the first week followed by a minor increase at 4 weeks with a stable level of 13.30 ± 0.80 g/dl, probably because of alternative absorption. Thus, Sucrosomial iron, already used in other conditions of iron deficiency, may represent a promising option for oral iron supplementation in IRIDA patients.

Iron Deficiency in Chronic Kidney Disease: Updates on Pathophysiology, Diagnosis, and Treatment.

Anemia is a complication that affects a majority of individuals with advanced CKD. Although relative deficiency of erythropoietin production is the major driver of anemia in CKD, iron deficiency stands out among the mechanisms contributing to the impaired erythropoiesis in the setting of reduced kidney function. Iron deficiency plays a significant role in anemia in CKD. This may be due to a true paucity of iron stores (absolute iron deficiency) or a relative (functional) deficiency which prevents the use of available iron stores. Several risk factors contribute to absolute and functional iron deficiency in CKD, including blood losses, impaired iron absorption, and chronic inflammation. The traditional biomarkers used for the diagnosis of iron-deficiency anemia (IDA) in patients with CKD have limitations, leading to persistent challenges in the detection and monitoring of IDA in these patients. Here, we review the pathophysiology and available diagnostic tests for IDA in CKD, we discuss the literature that has informed the current practice guidelines for the treatment of IDA in CKD, and we summarize the available oral and intravenous (IV) iron formulations for the treatment of IDA in CKD. Two important issues are addressed, including the potential risks of a more liberal approach to iron supplementation as well as the potential risks and benefits of IV versus oral iron supplementation in patients with CKD.

Consumption of Sinlek Rice Drink Improved Red Cell Indices in Anemic Elderly Subjects.

Iron fortifications are used for the treatment of iron-deficiency anemia; however, iron dosing may cause oxidative damage to the gut lumen. Thai Sinlek rice is abundant in iron and contains phytochemicals. We aimed at evaluating the effect of an iron-rice (IR) hydrolysate drink (100 mL/serving) on neurological function, red cell indices and iron status in elders. Healthy elderly subjects were divided into three non-anemic groups and one anemic group. The non-anemic groups consumed one WR (2 mg iron/serving) and two IR drinks (15 and 27 mg iron/serving) (groups A, B and D, respectively), while the anemic group consumed one IR drink (15 mg iron serving) (group C) every day for 30 days. There were no significant differences in the MMSE Thai 2002 and PHQ9 test scores for members of all groups, while the nutrition scores and body weight values of group D subjects were significantly increased. Hemoglobin (Hb) and mean corpuscular hemoglobin concentrations increased significantly only in group C. Serum iron and transferrin saturation levels tended to increase in group A, while these levels were decreased in members of group C. Serum antioxidant activity levels were increased in all groups, and were highest in group C. Thus, consumption of an IR drink for 15 days functioned to increase Hb and antioxidant capacity levels in anemic elders.

N-Heterocyclic Carbene Iron Complexes as Anticancer Agents: In Vitro and In Vivo Biological Studies.

Cisplatin and its derivatives are commonly used in chemotherapeutic treatments of cancer, even though they suffer from many toxic side effects. The problems that emerge from the use of these metal compounds led to the search for new complexes capable to overcome the toxic side effects. Here, we report the evaluation of the antiproliferative activity of Fe(II) cyclopentadienyl complexes bearing n-heterocyclic carbene ligands in tumour cells and their in vivo toxicological profile. The in vitro antiproliferative assays demonstrated that complex Fe1 displays the highest cytotoxic activity both in human colorectal carcinoma cells (HCT116) and ovarian carcinoma cells (A2780) with IC50 values in the low micromolar range. The antiproliferative effect of Fe1 was even higher than cisplatin. Interestingly, Fe1 showed low in vivo toxicity, and in vivo analyses of Fe1 and Fe2 compounds using colorectal HCT116 zebrafish xenograft showed that both reduce the proliferation of human HCT116 colorectal cancer cells in vivo.

Reticulocyte Hemoglobin Content (Ret He): A Simple Tool for Evaluation of Iron Status in Childhood Cancer.

BACKGROUND: Cancer-related anemia is a common complication of cancer and its treatment that may be mediated by nutritional deficiency or inflammatory cytokines inhibiting erythropoiesis. AIM: We evaluated the value of reticulocyte hemoglobin content (Ret He) as a marker of iron availability for erythropoiesis in childhood cancer and the impact of oral iron supplementation on hematologic parameters in patients with low Ret He. MATERIALS AND METHODS: This prospective study included 100 pediatric patients with cancer on chemotherapy who were screened for the presence of anemia. Patients with anemia underwent testing for complete blood count including Ret He on Sysmex XE 2100 and assessment of reticulocyte count, serum iron, serum ferritin, transferrin saturation, total iron-binding capacity, and C-reactive protein. Patients were classified according to their level of Ret He into normal or low Ret He using a cutoff level of 28 pg. Patients with low Ret He were subjected to 6 weeks' treatment with oral ion and were followed up with complete blood count and iron profile. RESULTS: Thirty-one (77.5%) patients had normal Ret He, and 9 (22.5%) had low Ret He. Ret He was positively correlated with red cell indices, but not with iron parameters. After oral iron supplementation, a significant increase in hemoglobin, reticulocyte count, and iron was found. CONCLUSIONS: We suggest that Ret He could be used as an easy and affordable tool for the assessment of iron deficiency anemia in childhood cancer during chemotherapy treatment. A trial of oral iron in patients with low Ret He may be useful to correct the associated anemia.

Factors influencing safety and efficacy of intravenous iron-carbohydrate nanomedicines: From production to clinical practice.

Iron deficiency is an important subclinical disease affecting over one billion people worldwide. A growing body of clinical records supports the use of intravenous iron-carbohydrate complexes for patients where iron replenishment is necessary and oral iron supplements are either ineffective or cannot be tolerated by the gastrointestinal tract. A critical characteristic of iron-carbohydrate drugs is the complexity of their core-shell structure, which has led to differences in the efficacy and safety of various iron formulations. This review describes parameters influencing the safety and effectiveness of iron-carbohydrate complexes during production, storage, handling, and clinical application. We summarized the physicochemical and biological assessments of commercially available iron carbohydrate nanomedicines to provide an overview of publicly available data. Further, we reviewed studies that described how subtle differences in the manufacturing process of iron-carbohydrate complexes can impact on the physicochemical, biological, and clinical outcomes of original product versus their intended copies or so-called iron "similar" products.

A case of dystonia with polycythemia and hypermanganesemia caused by SLC30A10 mutation: a treatable inborn error of manganese metabolism.

BACKGROUND: Manganese is a critical trace element that not only has antioxidant properties, but also is essential for various metabolic pathways and neurotransmitters production. However, it can be toxic at high levels, particularly in the central nervous system. Manganese intoxication can be acquired, but an inherited form due to autosomal-recessive mutations in the SLC30A10 gene encoding a Mn transporter protein has also been reported recently. These mutations are associated with significant failure of manganese excretion and its storage in the liver, brain (especially basal ganglia), and other peripheral tissues, resulting in toxicity. CASE PRESENTATION: A 10-year-old boy from consanguineous parents presented with a history of progressive truncal instability, gait difficulty, and frequent falls for 2 months. He had dystonia, rigidity, ataxia, dysarthria, bradykinesia and a plethoric skin. Investigations showed polycythemia, low serum iron and ferritin levels, and increased total iron binding capacity. A brain MRI revealed symmetric hyperintensities in the basal ganglia and dentate nucleuses on TI images that were suggestive of brain metal deposition together with clinical manifestations. Serum calcium and copper levels were normal, while the manganese level was significantly higher than normal values. There was no history of environmental overexposure to manganese. Genetic testing showed a homozygous missense mutation in SLC30A10 (c.C1006T, p.His336Tyr) and Sanger sequencing confirmed a homozygous state in the proband and a heterozygous state in the parents. Regular treatment with monthly infusions of disodium calcium edetate and oral iron compounds resulted in decreased serum manganese and hemoglobin levels to normal values, significant resolution of MRI lesions, and partial improvement of neurological symptoms during 6 months of follow-up. CONCLUSION: The syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by SLC30A10 mutation is a treatable inherited metal deposition syndrome. The patient may only have pure neurological without hepatic manifestations. Although this is a rare and potentially fatal inborn error of metabolism, early diagnosis and continuous chelation therapy might improve the symptoms and prevent disease progression.

Guideline No. 389-Medical Management of Symptomatic Uterine Leiomyomas - An Addendum.

OBJECTIVES: The aim of this guideline is to provide clinicians with an update to the 2015 Clinical Practice Guideline on the Management of Uterine Fibroids. As new information and evidence has become available since 2015, the Gynaecology Clinical Practice Committee of the Society for Obstetricians and Gynaecologists of Canada has determined that an addendum to that document was necessary to inform members about treatment modalities for uterine fibroids. OUTCOMES: Implementation of this guideline update should optimize the decision-making process of women and their health care providers in proceeding with further investigation or therapy for uterine leiomyomas, having considered the disease process and available treatment options and reviewed the risks and anticipated benefits. EVIDENCE: Published literature was retrieved through searches of PubMed, CINAHL, and Cochrane Systematic Reviews in February 2015 to April 2018, using appropriate controlled vocabulary (uterine fibroids, myoma, leiomyoma, myomectomy, myolysis, heavy menstrual bleeding, and menorrhagia) and key words (myoma, leiomyoma, fibroid, myomectomy, uterine artery embolization, hysterectomy, heavy menstrual bleeding, menorrhagia). The reference lists of articles identified were also searched for other relevant publications. Results were restricted to systematic reviews, randomized controlled trials or controlled clinical trials, and observational studies. There were no date limits, but results were limited to English or French language materials. Searches were updated on a regular basis and incorporated in the guideline to April 2018. Most of the unpublished data have not been evaluated scientifically. The product monograph was also reviewed up to December 31st, 2018. BENEFITS, HARMS, AND COSTS: The majority of fibroids are asymptomatic and require no intervention or further investigations. For symptomatic fibroids such as those causing menstrual abnormalities (e.g., heavy, irregular, and prolonged uterine bleeding), iron deficiency anemia, or bulk symptoms (e.g., pelvic pressure/pain, obstructive symptoms), hysterectomy is a definitive solution. However, it is not the preferred solution for women who wish to preserve fertility and/or their uterus. The selected treatment should be directed towards an improvement in symptomatology and quality of life. The cost of the therapy to the health care system and to women with fibroids must be interpreted in the context of the cost of untreated disease conditions and the cost of ongoing or repeat investigative or treatment modalities. VALUES: The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care.

Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD).

BACKGROUND: Phosphate binders are used to reduce positive phosphate balance and to lower serum phosphate levels for people with chronic kidney disease (CKD) with the aim to prevent progression of chronic kidney disease-mineral and bone disorder (CKD-MBD). This is an update of a review first published in 2011. OBJECTIVES: The aim of this review was to assess the benefits and harms of phosphate binders for people with CKD with particular reference to relevant biochemical end-points, musculoskeletal and cardiovascular morbidity, hospitalisation, and death. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 12 July 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs of adults with CKD of any GFR category comparing a phosphate binder to another phosphate binder, placebo or usual care to lower serum phosphate. Outcomes included all-cause and cardiovascular death, myocardial infarction, stroke, adverse events, vascular calcification and bone fracture, and surrogates for such outcomes including serum phosphate, parathyroid hormone (PTH), and FGF23. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion and extracted study data. We applied the Cochrane 'Risk of Bias' tool and used the GRADE process to assess evidence certainty. We estimated treatment effects using random-effects meta-analysis. Results were expressed as risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI) or mean differences (MD) or standardised MD (SMD) for continuous outcomes. MAIN RESULTS: We included 104 studies involving 13,744 adults. Sixty-nine new studies were added to this 2018 update.Most placebo or usual care controlled studies were among participants with CKD G2 to G5 not requiring dialysis (15/25 studies involving 1467 participants) while most head to head studies involved participants with CKD G5D treated with dialysis (74/81 studies involving 10,364 participants). Overall, seven studies compared sevelamer with placebo or usual care (667 participants), seven compared lanthanum to placebo or usual care (515 participants), three compared iron to placebo or usual care (422 participants), and four compared calcium to placebo or usual care (278 participants). Thirty studies compared sevelamer to calcium (5424 participants), and fourteen studies compared lanthanum to calcium (1690 participants). No study compared iron-based binders to calcium. The remaining studies evaluated comparisons between sevelamer (hydrochloride or carbonate), sevelamer plus calcium, lanthanum, iron (ferric citrate, sucroferric oxyhydroxide, stabilised polynuclear iron(III)-oxyhydroxide), calcium (acetate, ketoglutarate, carbonate), bixalomer, colestilan, magnesium (carbonate), magnesium plus calcium, aluminium hydroxide, sucralfate, the inhibitor of phosphate absorption nicotinamide, placebo, or usual care without binder. In 82 studies, treatment was evaluated among adults with CKD G5D treated with haemodialysis or peritoneal dialysis, while in 22 studies, treatment was evaluated among participants with CKD G2 to G5. The duration of study follow-up ranged from 8 weeks to 36 months (median 3.7 months). The sample size ranged from 8 to 2103 participants (median 69). The mean age ranged between 42.6 and 68.9 years.Random sequence generation and allocation concealment were low risk in 25 and 15 studies, respectively. Twenty-seven studies reported low risk methods for blinding of participants, investigators, and outcome assessors. Thirty-one studies were at low risk of attrition bias and 69 studies were at low risk of selective reporting bias.In CKD G2 to G5, compared with placebo or usual care, sevelamer, lanthanum, iron and calcium-based phosphate binders had uncertain or inestimable effects on death (all causes), cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification. Sevelamer may lead to constipation (RR 6.92, CI 2.24 to 21.4; low certainty) and lanthanum (RR 2.98, CI 1.21 to 7.30, moderate certainty) and iron-based binders (RR 2.66, CI 1.15 to 6.12, moderate certainty) probably increased constipation compared with placebo or usual care. Lanthanum may result in vomiting (RR 3.72, CI 1.36 to 10.18, low certainty). Iron-based binders probably result in diarrhoea (RR 2.81, CI 1.18 to 6.68, high certainty), while the risks of other adverse events for all binders were uncertain.In CKD G5D sevelamer may lead to lower death (all causes) (RR 0.53, CI 0.30 to 0.91, low certainty) and induce less hypercalcaemia (RR 0.30, CI 0.20 to 0.43, low certainty) when compared with calcium-based binders, and has uncertain or inestimable effects on cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification. The finding of lower death with sevelamer compared with calcium was present when the analysis was restricted to studies at low risk of bias (RR 0.50, CI 0.32 to 0.77). In absolute terms, sevelamer may lower risk of death (all causes) from 210 per 1000 to 105 per 1000 over a follow-up of up to 36 months, compared to calcium-based binders. Compared with calcium-based binders, lanthanum had uncertain effects with respect to all-cause or cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification and probably had reduced risks of treatment-related hypercalcaemia (RR 0.16, CI 0.06 to 0.43, low certainty). There were no head-to-head studies of iron-based binders compared with calcium. The paucity of placebo-controlled studies in CKD G5D has led to uncertainty about the effects of phosphate binders on patient-important outcomes compared with placebo.It is uncertain whether the effects of binders on clinically-relevant outcomes were different for patients who were and were not treated with dialysis in subgroup analyses. AUTHORS' CONCLUSIONS: In studies of adults with CKD G5D treated with dialysis, sevelamer may lower death (all causes) compared to calcium-based binders and incur less treatment-related hypercalcaemia, while we found no clinically important benefits of any phosphate binder on cardiovascular death, myocardial infarction, stroke, fracture or coronary artery calcification. The effects of binders on patient-important outcomes compared to placebo are uncertain. In patients with CKD G2 to G5, the effects of sevelamer, lanthanum, and iron-based phosphate binders on cardiovascular, vascular calcification, and bone outcomes compared to placebo or usual care, are also uncertain and they may incur constipation, while iron-based binders may lead to diarrhoea.

[Iron, a "miralcle cure" for chronic cardiac insufficiency?] / Eisen, ein Wundermittel bei Herzinsuffizienz?

Anemia and chronic heart failure are frequent comorbidities in geriatric patients. In approximately one third of older adults the cause of the anemia is an iron, vitamin B12 and/or folate deficiency and in another third a chronic inflammatory process is present. In the case of iron deficiency a differentiation must be made between the absolute and functional forms. Although in functional iron deficiency ferritin, as a parameter of iron metabolism, is within the normal range or can even be higher, an iron-deficient erythropoiesis is present. In cardiac insufficiency a chronic inflammatory process is assumed. According to the recent guidelines of the Deutsche Gesellschaft für Kardiologie (DGK, German Cardiac Society) and European Society of Cardiology (ESC) a routine contol of the iron status should be performed and, if necessary, initiation of adequate supplementation is recommended.

Distinct in vitro Complement Activation by Various Intravenous Iron Preparations.

BACKGROUND: Intravenous (IV) iron preparations are widely used in the treatment of anemia in patients undergoing hemodialysis (HD). All IV iron preparations carry a risk of causing hypersensitivity reactions. However, the pathophysiological mechanism is poorly understood. We hypothesize that a relevant number of these reactions are mediated by complement activation, resulting in a pseudo-anaphylactic clinical picture known as complement activation-related pseudo allergy (CARPA). METHODS: First, the in-vitro complement-activating capacity was determined for 5 commonly used IV iron preparations using functional complement assays for the 3 pathways. Additionally, the preparations were tested in an ex-vivo model using the whole blood of healthy volunteers and HD patients. Lastly, in-vivo complement activation was tested for one preparation in HD patients. RESULTS: In the in-vitro assays, iron dextran, and ferric carboxymaltose caused complement activation, which was only possible under alternative pathway conditions. Iron sucrose may interact with complement proteins, but did not activate complement in-vitro. In the ex-vivo assay, iron dextran significantly induced complement activation in the blood of healthy volunteers and HD patients. Furthermore, in the ex-vivo assay, ferric carboxymaltose and iron sucrose only caused significant complement activation in the blood of HD patients. No in-vitro or ex-vivo complement activation was found for ferumoxytol and iron isomaltoside. IV iron therapy with ferric carboxymaltose in HD patients did not lead to significant in-vivo complement activation. CONCLUSION: This study provides evidence that iron dextran and ferric carboxymaltose have complement-activating capacities in-vitro, and hypersensitivity reactions to these drugs could be CARPA-mediated.

Management of anemia in patients with congestive heart failure.

Anemia is an independent risk factor for adverse patient outcomes. There are no guidelines for management of anemia in patients with congestive heart failure (CHF), despite its high incidence. Four objectives were defined by the International Anemia Management and Clinical Outcomes Expert Panel (AMCO), a multinational group of interdisciplinary experts identified by the Society for the Advancement of Blood Management (SABM) to: determine the prevalence of anemia in outpatients; to determine the prevalence of hospital-acquired anemia; to assess the impact of anemia management on clinical outcomes such as quality of life and functional status; and to provide recommendations for primary care physicians and specialists for the diagnosis, evaluation, and management of anemia in patients with CHF. Anemia and iron deficiency were confirmed to be highly prevalent in patients with CHF. Intravenous iron therapy improves anemia, cardiac function and exercise tolerance, leading to improvement in quality of life. Anemia management has been demonstrated to be cost-effective. Clinical care pathways to manage anemia in patients with CHF are recommended as best practices in order to improve patient outcomes. Am. J. Hematol. 92:88-93, 2017. © 2016 Wiley Periodicals, Inc.

Five-Year Period Prevalence and Characteristics of Anemia in a Large US Inflammatory Bowel Disease Cohort.

BACKGROUND: Anemia is a common manifestation of inflammatory bowel disease (IBD), but its prevalence in the United States is not well defined. Aim of this study was to determine the prevalence and characteristics of anemia in IBD patients who were followed in a US referral center. MATERIALS AND METHODS: Demographic, clinical, laboratory, and treatment data from a prospective, consented longitudinal IBD registry between the years 2009 and 2013 were analyzed. Disease activity was evaluated using Harvey-Bradshaw index in Crohn's disease (CD) and ulcerative colitis (UC) activity index in UC as well as C-reactive protein and erythrocyte sedimentation rate. Anemia was defined based on the World Health Organization criteria. RESULTS: A total of 1821 IBD patients (1077 with CD, 744 with UC, median age 43.8 y, 51.9% female) were included. The 5-year period prevalence of anemia in IBD patients was 50.1%, (CD: 53.3% vs. UC: 44.7%, P=0.001). In multivariate logistic regression analysis, anemia was associated with surgery for IBD [odds ratio (OR)=2.77; 95% confidence interval (CI), 2.21-3.48; P<0.0001], female gender (OR=1.29; 95% CI, 1.04-1.61; P=0.02), C-reactive protein (OR=1.26; 95% CI, 1.16-1.37; P<0.0001), erythrocyte sedimentation rate (OR=1.02; 95% CI, 1.01-1.03; P=0.0002), and use of biologics (OR=2.00; 95% CI, 1.58-2.52; P=0.0001) or immunomodulators (OR=1.51; 95% CI, 1.21-1.87; P=0.0003). Iron replacement therapy was administered to 46.8% of the anemic patients. CONCLUSION: Anemia has a high period prevalence in IBD patients followed at a tertiary center. Anemia is more common in CD than in UC, is associated with disease activity, and in current practice is undertreated.

Considerations and challenges in defining optimal iron utilization in hemodialysis.

Trials raising concerns about erythropoiesis-stimulating agents, revisions to their labeling, and changes to practice guidelines and dialysis payment systems have provided strong stimuli to decrease erythropoiesis-stimulating agent use and increase intravenous iron administration in recent years. These factors have been associated with a rise in iron utilization, particularly among hemodialysis patients, and an unprecedented increase in serum ferritin concentrations. The mean serum ferritin concentration among United States dialysis patients in 2013 exceeded 800 ng/ml, with 18% of patients exceeding 1200 ng/ml. Although these changes are broad based, the wisdom of these practices is uncertain. Herein, we examine influences on and trends in intravenous iron utilization and assess the clinical trial, epidemiologic, and experimental evidence relevant to its safety and efficacy in the setting of maintenance dialysis. These data suggest a potential for harm from increasing use of parenteral iron in dialysis-dependent patients. In the absence of well powered, randomized clinical trials, available evidence will remain inadequate for making reliable conclusions about the effect of a ubiquitous therapy on mortality or other outcomes of importance to dialysis patients. Nephrology stakeholders have an urgent obligation to initiate well designed investigations of intravenous iron in order to ensure the safety of the dialysis population.

[Study of parenteral iron use in a health facility and its impact in terms of hospital economics]. / Étude de l'usage du fer injectable en établissement de santé et de son impact en terme d'économie hospitalière.

INTRODUCTION: Administration of parenteral iron is a mainstay of iron deficiency treatment. Evaluation and control of this element is an issue for healthcare facilities. Study of parenteral iron use is thus to be evaluated in its impact in terms of hospital economics. MATERIALS AND METHODS: Parenteral iron administrations that took place on 2014 in our healthcare facility were retrospectively identified by pharmacists. Following data were extracted from Pharma™ and Crossway™ softwares: indication, diagnostic coding and total dose of iron received. They were then compared to the summary of product characteristics. RESULTS: Of 198 analyzed prescriptions, iron deficiency was known or suspected for 97% of patients. However, the total dose of iron administered was not in compliance for three quarters of prescriptions. Sixty-eight percent of patients appear under-dosed. Administration's traceability was found for two-thirds. Eighty-five hospital discharges did not have the right coding and 34 stays were charged like an external act instead sessions. Financial loss for the hospital is estimated at 49,300 euros. DISCUSSION AND CONCLUSION: As part of improving practice, close pharmaceutical monitoring of parenteral iron prescribed dosing regimen is essential. Effective communication with the medical information department and regular awareness raising of prescribers should also allow to give more value to this act. Hospital economics is a real tool to aid decision-making.

Synthesis of Iron Nanometallic Glasses and Their Application in Cancer Therapy by a Localized Fenton Reaction.

Metallic glasses and cancer theranostics are emerging fields that do not seem to be related to each other. Herein, we report the facile synthesis of amorphous iron nanoparticles (AFeNPs) and their superior physicochemical properties compared to their crystalline counterpart, iron nanocrystals (FeNCs). The AFeNPs can be used for cancer theranostics by inducing a Fenton reaction in the tumor by taking advantage of the mild acidity and the overproduced H2 O2 in a tumor microenvironment: Ionization of the AFeNPs enables on-demand ferrous ion release in the tumor, and subsequent H2 O2 disproportionation leads to efficient (.)OH generation. The endogenous stimuli-responsive (.)OH generation in the presence AFeNPs enables a highly specific cancer therapy without the need for external energy input.

PREECLAMPSIA AND IRON EXCHANGE. ARE THERE ANY COMMON PATTERNS?

THE AIM: Detarmination of correlation between the level ofserm iron and hemoglobin with clinical symptoms ofpreeclampsia. MATERIALS AND METHODS: A prospective randomized controlled investigation of 62 women in the gestation of 30 to 39 weeks. Women were divided into 2 main groups. The first group included 38 nulliparous women with preeclampsia moderate degree (Io group) gestational age from 30 to 39 weeks, at the age of 26,8±2,7 years. The second main group included 24 nulliparous women with preeclampsia severe degree (II group) in gestational age from 30 to 39 weeks of similar age. The conditionfor inclusion in the main groups was iron supplementation in the period of total hemoglobin reducing < 115 g/l. The first control group (I) included 26 nulliparous women average 26,2±1,6 years, which admitted to a maternity hospital for planned Cesarean section. The second group (IQ included 22 healthy non-pregnant women at the age of 25,8±4,4 years. During hospitalization, before delivery and at 2 hours after delivery was investigated the concentration of total hemoglobin, serum iron, total bilirubin, creatinine, urea, endothelin-1 (immediately before delivery and after delivery). The total analyses of urine examined the number of red blood cells and white blood cells and protein concentration. RESULTS: It''s revealed that the serum iron level has a direct correlation with the level of blood preasure (r = 0,5412 and r = 0,6229) and concentration of endothelin- with total hemoglobin (r = 0,6446 in p < 0,03) and with serum iron concentration (r = 0,7841 in p < 0,02). Conclusuion. The analysis of conducted investigation allows to approve about the pathogenetic importance of iron in the development ofpreeclampsia and post-partum complications, that require new approaches of iron during gestation.

Renal functional and structural integrity in infants with iron deficiency anemia: relation to oxidative stress and response to iron therapy.

BACKGROUND: Iron deficiency anemia (IDA) is the most common nutritional deficiency in the world. The aim of our study was to evaluate and compare renal functional and structural integrity in 50 infants with IDA and 50 healthy controls and to assess the relation between IDA and oxidative stress and response to iron therapy. METHODS: This was a prospective study in which peripheral blood samples were collected from all study subjects and the following laboratory investigations performed: serum iron profile, urinary microalbumin, urinary leucine aminopeptidase (LAP), fractional excretion of sodium (FeNa), serum total antioxidant capacity (TAC), serum malondialdehyde (MDA), serum and urinary trace elements (iron, copper, zinc, calcium and magnesium). All patients received oral iron therapy and were followed-up for 3 months. RESULTS: The levels of baseline urinary markers were higher among the patients with IDA than among the controls (p < 0.05). Patients had a lower pre-therapy TAC and lower serum zinc and magnesium levels than controls as well as higher MDA and serum copper levels (p < 0.05). MDA level was positively correlated to microalbumin and LAP level (p < 0.05). Urinary LAP concentration was positively correlated to urinary trace element concentrations (p < 0.05). A significant decrease in microalbumin, LAP, FeNa, and urinary trace elements was observed post-iron therapy while hemoglobin and ferritin levels were increased (p < 0.05). CONCLUSION: Among the study subjects, IDA had an adverse influence on renal functional and structural integrity which could be reversed with iron therapy. Oxidative stress played an important role in the pathogenesis of renal injury in IDA.

Heme iron polypeptide for the management of anaemia of chronic kidney disease.

WHAT IS KNOWN AND OBJECTIVE: Anaemia is a common clinical finding among patients with chronic kidney disease (CKD) and is associated with significant morbidity and healthcare costs. Iron deficiency is an important contributing factor, and adequate iron supplementation is essential to optimize the management of anaemia of CKD. Oral iron is convenient and inexpensive but is poorly absorbed and associated with gastrointestinal distress. Intravenous iron overcomes these limitations but is more expensive, requires additional clinical visits for administration and is associated with serious adverse events. Oral heme iron polypeptide (HIP) is a newer dosage form that has been reported to have higher bioavailability and fewer side effects when compared with non-heme iron in healthy subjects, but data in patients with CKD are limited. The purpose of this review is to evaluate the safety and effectiveness of HIP for the management of CKD. METHODS: Searches for PubMed (1947-2015) and International Pharmaceutical Abstracts (1970-2015) were conducted using the following terms: heme iron, heme iron polypeptide, oral iron, anaemia and chronic kidney disease. The bibliography of each relevant article was evaluated for additional studies. Articles were selected for review if they were published in the English language and were randomized controlled trials evaluating the bioavailability, tolerability or efficacy of oral HIP in human subjects with CKD. RESULTS AND DISCUSSION: This search yielded three clinical studies. The safety and efficacy of HIP was evaluated in a total of 161 subjects with anaemia and various stages of CKD. HIP was consistently associated with lower ferritin values when compared with traditional iron supplementation. With few exceptions, the effect of HIP on haemoglobin, haematocrit, transferrin saturation and recombinant human erythropoietin dose, and adverse effects appeared similar to intravenous and oral non-heme iron supplementation. The cost of HIP is substantially more than non-heme iron and comparable to intravenous iron. WHAT IS NEW AND CONCLUSION: Heme iron polypeptide does not appear to confer benefit over traditional iron supplementation among patients with anaemia of CKD and is more expensive.