Paper-Based Analytical Devices for Accurate Assessment of Transferrin Saturation in Diagnosed Clinical Samples from Ischemic Stroke Patients.

For the first time, a paper-based analytical device (PAD) was developed for the assessment of transferrin saturation (TSAT), which is defined as the ratio between iron bound to transferrin (Tf) and the total iron-binding capacity (TIBC) of Tf. Both parameters were simultaneously measured on the same PAD using ferrozine as a chromophore and a smartphone as the color reader. To this end, Tf was first isolated from serum using anti-Tf immunomagnetic beads to ensure that only the Tf-bound iron was measured, improving the selectivity and accuracy of TSAT assessment. To demonstrate the practical utility of the device, it was validated by analyzing a certified reference material, showing excellent accuracy (Er < 4%) and good precision (RSD ≤ 6%). Finally, 18 diagnosed serum samples from ischemic stroke patients were analyzed by this approach, and the results were compared with those obtained by urea-PAGE, showing not only an excellent correlation (r = 0.93, p < 0.05) but that the PAD approach has become statistically identical to the free-interference urea-PAGE. In comparison with the slow, tedious, and non-miniaturized-PAGE, this PAD approach exhibited attractive characteristics such as low cost, disposability, and connectivity, showing great potential for future point-of-care testing, especially in developing countries and/or remote areas, where access to medical or clinical facilities is limited.

Assessment of serum iron stores in regular plateletpheresis donors.

BACKGROUND: Iron deficiency anaemia is the most common nutritional deficiency disorder in the world. Iron deficiency is a potential complication in repeated apheresis donation. The present study was aimed to evaluate serum iron stores in regular plateletpheresis donors. MATERIALS AND METHODS: A total of 60 donors were included in this study, which included 30 regular plateletpheresis donors as cases and controls were 30 first time donors. The donor samples were collected before donation for complete hemogram, transfusion transmissible infections screening and serum iron, total iron binding capacity, percentage saturation of transferrin and serum ferritin. RESULTS: Out of 60 donors, more than half of the donors (56.6 %) had serum ferritin less than 30 ng/mL. Out of these 34 donors, 25 were from the case group and 9 donors in the control group. The median serum ferritin level in cases and controls was 11.86 ng/mL (Interquartile range 4.18-17.34 ng/mL) and 37.92 ng/mL (Interquartile range 27.87-86.20 ng/mL) respectively (p < 0.001). The mean serum iron in cases and controls was 71.23 ± 31.32 µg/dL and 93.53 ± 33.53 µg/dL respectively (p = 0.016). The mean percentage saturation in cases and controls was 20.09 ± 9.31 % and 26.26 ± 9.03 % respectively (p = 0.012). A significant decline in mean serum ferritin with increase in number of annual donations and decrease in donation interval was observed. DISCUSSION: Regular plateletpheresis donation may lead to depletion of iron stores and subclinical iron deficiency. Donors with high platelet count are more likely to exhibit iron deficiency. Periodic serum ferritin estimation in donors participating in regular plateletpheresis donation is warranted.

Iron Deficiency in Celiac Disease: Prevalence, Health Impact, and Clinical Management.

Iron is an essential nutrient to life and is required for erythropoiesis, oxidative, metabolism, and enzymatic activities. It is a cofactor for mitochondrial respiratory chain enzymes, the citric acid cycle, and DNA synthesis, and it promotes the growth of immune system cells. Thus, iron deficiency (ID) leads to deleterious effects on the overall health of individuals, causing significant morbidity. Iron deficiency anemia (IDA) is the most recognized type of anemia in patients with celiac disease (CD) and may be present in over half of patients at the time of diagnosis. Folate and vitamin B12 malabsorption, nutritional deficiencies, inflammation, blood loss, development of refractory CD, and concomitant Heliobacter pylori infection are other causes of anemia in such patients. The decision to replenish iron stores and the route of administration (oral or intravenous) are controversial due, in part, to questions surrounding the optimal formulation and route of administration. This paper provides an algorithm based on the severity of symptoms; its impact on the health-related quality of life (HRQL); the tolerance and efficiency of oral iron; and other factors that predict a poor response to oral iron, such as the severity of histological damage, poor adherence to GFD, and blood loss due to mucosal lesions.

Assessment of Micronutrient Situation among Reproductive-Age Women (15-49) and Under-Five Children in Sudan.

BACKGROUND: Micronutrient malnutrition is a form of undernutrition that causes diseases, and this is mainly due to insufficient intake of nutrients in daily foods. The status of micronutrients for people in Sudan remains scarce, and information is limited. The aim of this study is to highlight the status of micronutrients among women of reproductive age (15-49 years of age) and their children in Sudan. METHODS: This manuscript is a quantitative descriptive study, based on the data from Sudan Micronutrient Survey (SMS); it is part of the second round of the Simple Spatial Survey Method (S3M II) in Sudan (a total of 93,882 households). RESULTS: The level of consumption of vitamin A-rich foods was found to be moderate at 67.36% for reproductive-age women and low at 23.44% for under-five children. Similarly, consumption rate of vitamin B-rich foods among reproductive-age women was 62.13%, and low for children at 11.02%. The consumption of iron-, calcium-, and zinc-rich foods was moderate among women (66.75%, 47.69%, 69.72%, respectively) and very low in children (12.28%, 17.62%, 14.99%, respectively). The iron deficiency prevalence was 47% in non-pregnant women, 58% in pregnant women, and 54% in children. The prevalence of anemia was 30% in non-pregnant women, 37% in pregnant women, and 48% in children. Generally, urinary iodine concentration was inadequate in lactating and non-pregnant women as well as in pregnant women. Most indicators of micronutrients in Sudan for children and women of reproductive age were highly significant. Sudan needs more efforts to create an enabling environment through legislation, policies, and strategies to strengthen the nutrition-sensitive and specific interventions and improving status of micronutrients among women and children, focusing on food fortification, food supplements, and counseling on micronutrients intake for mothers during antenatal and postnatal services as well as raising community awareness.

Adiposity and pathogen exposure: An investigation of response to iron supplementation and hypothesized predictors in anemic pre-school-aged children living in a dual burden environment.

OBJECTIVES: Peruvians are experiencing rapid dietary and lifestyle changes, resulting in a phenomenon known as the "dual burden of disease." A common manifestation of the dual burden in individuals is the co-occurrence of overweight and anemia. Despite recent initiatives introduced to address these concerns, rates continue to be public health concerns. This study investigates the relationship between immune activation and lack of response to iron supplementation after 1 month of treatment and explores variation in body fat stores as a potential moderator between immune function and response to treatment. METHODS: Data come from children, aged 2-5 years (n = 50) from a peri-urban community in Lima, Peru. Multivariate logistic regression models were used to explore the associations between response to treatment (Hb > =11.0 g/dl) after 1 month of treatment), markers of immune activation (C-reactive protein [CRP] and reported morbidity symptoms), and measures of body fat (waist-to-height ratio, triceps skinfold thickness, and body mass index [BMI]). RESULTS: We found that high CRP is associated with a lack of response to iron supplementation after 1 month of treatment and that BMI z-score may moderate this association. Generally, larger body size is associated with response to iron supplementation whether or not the children in this sample have high immune activation. However, the probability of anemic children responding to iron supplementation treatment differed across adiposity measures. CONCLUSIONS: Our finding suggesting that adiposity and CRP influence response to iron supplementation, furthers our understanding of the relationship between inflammation and anemia treatment in children and has both theoretical and public health implications.

Assessment of positive iron balance in end-stage renal disease: Could hepcidin-25 be useful?

INTRODUCTION: The aim of our study was to examine the relationship of hepcidin-25 with red blood cell and reticulocyte indices and to evaluate the diagnostic properties of hepcidin-25 in the assessment of positive iron balance in end-stage renal disease (ESRD) patients. METHODS: Eighty anemic ESRD patients (hemoglobin < 110 g/L) were classified as having iron deficiency (ID, N = 20), iron sufficiency (IS, N = 29), and positive iron balance (PB, N = 31) using the conventional biomarkers for iron status evaluation. Hepcidin-25 was determined by a chemiluminescent direct ELISA. RESULTS: Hepcidin-25 was significantly negatively correlated with the proportion of hypochromic erythrocytes (%HYPO) (P = .034) and immature reticulocyte fraction (P = .010) in ID and with the absolute reticulocyte concentration in ID (P = .048) and PB (P = .040). In multivariate models, hepcidin-25 was independently negatively associated with the mean reticulocyte hemoglobin content (CHr; ß = -0.493, P = .004) and red blood cell size factor (RSf) (ß = -0.334, P = .036) only in the PB group. The best hepcidin-25 value to exclude PB was 66.13 µg/L, showing a sensitivity of 61.3%, a specificity of 75.5%, and an AUC of 0.808. CONCLUSION: Our results suggest that hepcidin-25 levels are independently negatively associated with the iron demand for the most recent erythropoiesis only in PB. Hepcidin-25 performed acceptable in discriminating anemic ESRD patients with positive iron balance and may prove to be a useful additional tool in the evaluation of iron status.

Ferric carboxymaltose vs. ferrous sulfate for the treatment of anemia in advanced chronic kidney disease: an observational retrospective study and cost analysis.

In non-dialysis-dependent chronic kidney disease (NDD-CKD), erythropoiesis-stimulating agents (ESAs) and iron supplementation are essential for anemia management. Ferric carboxymaltose (FCM) is a relatively novel intravenous iron formulation used in different clinical settings, although scarce data exist in NDD-CKD patients. Primary objective of this study was to retrospectively evaluate the efficacy of FCM compared with oral ferrous sulfate for the treatment of iron-deficiency anemia in a cohort of NDD-CKD patients, considering also the treatment costs. This was a monocentric, retrospective observational study reviewing 349 NDD-CKD patients attending an outpatient clinic between June 2013 and December 2016. Patients were treated by either FCM intravenous infusion or oral ferrous sulfate. We collected serum values of hemoglobin, ferritin and transferrin saturation (TSAT) and ESAs doses at 12 and 18 months. The costs related to both treatments were also analysed. 239 patients were treated with FCM intravenous infusion and 110 patients with oral ferrous sulfate. The two groups were not statistically different for age, BMI and eGFR values. At 18 months, hemoglobin, serum ferritin and TSAT values increased significantly from baseline in the FCM group, compared with the ferrous sulfate group. ESAs dose and rate of infusion decreased only in the FCM group. At 18 months, the treatment costs, analysed per week, was higher in the ferrous sulfate group, compared with the FCM group, and this was mostly due to a reduction in ESAs prescription in the FCM group. Routine intravenous FCM treatment in an outpatient clinic of NDD-CKD patients results in better correction of iron-deficiency anemia when compared to ferrous sulfate. In addition to this, treating NDD-CKD patients with FCM leads to a significant reduction of the treatment costs by reducing ESAs use.

Direct assessment of body iron balance in women with and without iron supplementation using a long-term isotope dilution method in Benin and Switzerland.

BACKGROUND: Long-term isotopic dilution measurements of body iron may allow quantification of basal body iron balance and iron gains during an iron intervention with higher precision and accuracy than conventional iron indices. OBJECTIVES: We compared body iron balance before, during, and after oral iron supplementation in women in Benin and in Switzerland. METHODS: In prospective studies, Beninese (n = 11) and Swiss (n = 10) women previously labeled with stable iron isotopes were followed preintervention for 90-120 d, then received 50-mg iron daily for 90-120 d and were followed postintervention for 90-120 d. We used changes in blood isotopic composition to calculate iron absorption (Feabs), iron loss (Feloss), and net iron balance (Fegain). RESULTS: Compliance with supplementation was >90%. In Benin, during the preintervention, intervention, and postintervention periods, Fe means ± SDs were as follows: 1) Feabs: 0.92 ± 1.05, 3.75 ± 2.07, and 0.90 ± 0.93 mg/d; 2) Feloss: 1.46 ± 1.95, 1.58 ± 1.57, and 1.84 ± 1.61 mg/d; and 3) Fegain: -0.55 ± 1.56 mg/d, 2.17 ± 1.81 mg/d, and -0.94 ± 1.13 mg/d. In Switzerland, the corresponding values were: 1) 1.51 ± 0.37, 4.09 ± 1.52, and 0.97 ± 0.41 mg/d; 2) 0.76 ± 1.37, 2.54 ± 1.43, and 2.08 ± 1.05 mg/d; and 3) 0.75 ± 1.37, 1.55 ± 1.75, and -1.11 ± 1.06 mg/d. Inflammation was low in both settings, and isotopically calculated iron balance was comparable to that calculated from changes in conventional iron indices. CONCLUSION: Without iron supplementation, Beninese women had lower long-term dietary iron absorption and higher iron losses in the preintervention period than Swiss women. During iron supplementation, both groups had high iron absorption and similar iron gains. However, there was a 3-fold increase in iron losses in the Swiss women during the supplementation and postintervention period compared with the preintervention period. Body iron isotope dilution is a promising new method for quantifying long-term body iron balance and for assessing the impact of iron interventions. The studies were registered at clinicaltrials.gov as NCT02979080 and NCT02979132, respectively.

Effects of a multifaceted intervention to promote the use of intravenous iron sucrose complex instead of ferric carboxymaltose in patients admitted for more than 24 h.

PURPOSE: Although more practical for use, the impact of ferric carboxymaltose (FCM) on the hospital budget is considerable, and intravenous iron sucrose complex (ISC) represents a cost-saving alternative for the management of iron deficiency anemia in patients during hospitalization. The Drug Committee decided to reserve FCM for day hospitalizations and contraindications to ISC, especially allergy. ISC was available for prescription for all other situations. METHODS: The impact of a multifaceted intervention promoting a switch from FCM to ISC was evaluated using an interrupted time series model with segmented regression analysis. The standardized rate of the dispensing of FCM, ISC, and oral iron by the hospital pharmacy, as well as the rate of the dispensing of packed red blood cells and the number of biological iron status measurements, was analyzed before and after the intervention. RESULTS: There was an immediate decrease in FCM consumption following the intervention, with a reduction of 88% (RR: 0.12 [CI95% 0.10 to 0.15]). Conversely, there was a large increase in ISC use (RR: 5.1 [CI95% 4.4 to 5.9]). We did not observe a prescription shift to packed red blood cells or oral iron after the intervention. The time series analysis showed the frequency of iron status testing to remain stable before and after. The direct savings for intravenous iron for 8 months were 187,417.54 €. CONCLUSION: Our intervention to lower the impact of intravenous iron therapy on the hospital budget was effective.

Screening and treating pre-operative anaemia and suboptimal iron stores in elective colorectal surgery: a cost effectiveness analysis.

Our study investigated whether pre-operative screening and treatment for anaemia and suboptimal iron stores in a patient blood management clinic is cost effective. We used outcome data from a retrospective cohort study comparing colorectal surgery patients admitted pre- and post-implementation of a pre-operative screening programme. We applied propensity score weighting techniques with multivariable regression models to adjust for differences in baseline characteristics between groups. Episode-level hospitalisation costs were sourced from the health service clinical costing data system; the economic evaluation was conducted from a Western Australia Health System perspective. The primary outcome measure was the incremental cost per unit of red cell transfusion avoided. We compared 441 patients screened in the pre-operative anaemia programme with 239 patients not screened; of the patients screened, 180 (40.8%) received intravenous iron for anaemia and suboptimal iron stores. The estimated mean cost of screening and treating pre-operative anaemia was AU$332 (£183; US$231; €204) per screened patient. In the propensity score weighted analysis, screened patients were transfused 52% less red cell units when compared with those not screened (rate ratio = 0.48, 95%CI 0.36-0.63, p < 0.001). The mean difference in total screening, treatment and hospitalisation cost between groups was AU$3776 lower in the group screened (£2080; US$2629; €2325) (95%CI AU$1604-5947, p < 0.001). Screening elective patients pre-operatively for anaemia and suboptimal iron stores reduced the number of red cell units transfused. It also resulted in lower total costs than not screening patients, thus demonstrating cost effectiveness.

Parity-based assessment of anemia and iron deficiency in pregnant women.

OBJECTIVE: This study aimed to separately evaluate the prevalence of anemia and iron deficiency in nulliparous and multiparous women. MATERIALS AND METHODS: We retrospectively examined data of women who delivered in our clinic from January 2016 to December 2018. Inclusion criteria were delivery occurring at ≥36 weeks and singleton pregnancy. Pregnant women with severe medical disorders were excluded. We estimated complete blood count (CBC) and serum ferritin (SF) in the first trimester and only CBC in the late second trimester. Data of nulliparas and multiparas were analyzed separately. Statistically significance was set at p < 0.05. RESULTS: Totally, 481 nulliparas and 603 and multiparas were enrolled. Mean hemoglobin values in the first trimester were 12.6 ± 1.0 and 12.4 ± 1.0 g/dl (p < 0.001), while median SF values were 42.7 (12.2, 108.2) and 27.7 (8.0, 72.6) ng/ml (p < 0.001) in nulliparas and multiparas, respectively. Hemoglobin in the late second trimester was 11.2 ± 0.9 and 10.7 ± 1.0 g/dl (p < 0.001) in nulliparas and multiparas, respectively. Low ferritin levels (SF < 12 ng/ml) were more frequently found in multiparas than in nulliparas (111/603 vs. 46/481, p < 0.001, Odds ratio [OR] = 2.13). Anemia in the first trimester (hemoglobin<11.0 g/dl) was found in 3.5% (17/481) and 8.8% (53/603) (p < 0.001; OR, 2.63), while that in late second trimester (hemoglobin<10.5) was observed in 21.0% (101/481) and 36.3% (219/603) (p < 0.001, OR = 2.15) nulliparas and multiparas, respectively. Non-anemic women (hemoglobin level ≥11.0) with low ferritin levels (SF < 12 ng/ml) in the first trimester showed higher rate of anemia development in the second trimester than those with both normal hemoglobin and ferritin levels, irrespective of parity (51.3% [19/37] vs. 16.2% [69/427], p < 0.001 in nulliparas and 76.9% [60/78] vs. 26.5% [125/472], p < 0.001 in multiparas]. CONCLUSION: Anemia and low SF levels occurred more commonly in multiparous than in nulliparas. Further, low SF was a risk factor for anemia development in later pregnancy.

In vitro assessment of the anti-sickling properties of Buchholzia coriacea and Mucuna pruriens seed extracts.

Sickle cell disease is a group of diseases inherited through the gene and it affects the haemoglobin in the red blood cell. This study investigated the methanol seed extract of Buchholzia coriacea for possible in vitro anti-sickling effects and also determined the effect of Mucuna pruriens seed extract on the solubility and oxygen-binding rate of sickle cell haemoglobin. Sickle cell blood was collected from sickle cell disease patients with subsequent addition of 2% sodium metabisulphite to cause more sickling. Varying concentrations of the seed extracts (50%, 25%, 12.5% and 6.25%) were added to the pre-treated blood for these in vitro assays. The results showed that the extract of Buchholzia coriacea significantly (P < 0.05) inhibited sickling at all concentrations with the highest percentage inhibition of 73.3 ± 5.8, reversed sickled erythrocytes at all concentrations with the highest percentage reversal of 83.3 ± 5.8 and significantly (P < 0.05) inhibited polymerisation at all concentrations used in comparison to the parallel control. The extract of Mucuna pruriens seed significantly (P < 0.05) increased the solubility of sickle haemoglobin at 50%, 25%, 12.5% and 6.25% concentrations, increased Fe2+/Fe3+ ratio from 1.7 (control) to 12.2 (50% concentration) and reduced osmotic fragility (at 12.5% and 6.25% concentrations) when compared with parallel control. The results indicate the feasibility of the seed extracts as promising agents in the management of sickle cell disease.

Clinical thresholds for diagnosing iron deficiency: comparison of functional assessment of serum ferritin to population based centiles.

Low serum ferritin is diagnostic of iron deficiency, yet its published lower cut-off values are highly variable, particularly for pediatric populations. Lower cut-off values are commonly reported as 2.5th percentiles, and is based on the variation of ferritin values in the population. Our objective was to determine whether a functional approach based on iron deficient erythropoiesis could provide a better alternative. Utilizing 64,443 ferritin test results from pediatric electronic health records, we conducted various statistical techniques to derive 2.5th percentiles, and also derived functional reference limits through the association between ferritin and erythrocyte parameters: hemoglobin, mean corpuscular volume, mean cell hemoglobin concentration, and red cell distribution width. We find that lower limits of reference intervals derived as centiles are too low for clinical interpretation. Functional limits indicate iron deficiency anemia starts to occur when ferritin levels reach 10 µg/L, and are largely similar between genders and age groups. In comparison, centiles (2.5%) presented with lower limits overall, with varying levels depending on age and gender. Functionally-derived limits better reflects the underlying physiology of a patient, and may provide a basis for deriving a threshold related to treatment of iron deficiency and any other biomarker with functional outcomes.

Preliminary assessment of the new Sysmex XN parameter Iron-Def for identifying iron deficiency.

BACKGROUND: Although the clinical assessment of iron status is usually based on iron stores, a rapid and accurate diagnosis of iron deficiency is challenging since ferritin is often unavailable as an urgent test and its value is frequently increased in acute phase conditions. This study was therefore aimed at evaluating the diagnostic performance of the new Sysmex XN "Iron Deficiency?" (Iron-Def) parameter for identifying patients with iron deficiency. MATERIALS AND METHODS: The study population consisted of 688 consecutive patients (median age: 71 years; 341 women and 347 men), referred for routine diagnostics to the Laboratory of Clinical Pathology of Lecco Hospital, Italy. A complete clinical chemistry profile and haematological testing were performed for identifying iron deficiency anaemia. RESULTS: A significant negative correlation was found between Sysmex XN Iron-Def and ferritin, serum iron, mean cell haemoglobin concentration, mean cell haemoglobin, mean corpuscular volume and age, while a positive correlation was noted with transferrin, percentage of microcytic red cell, red blood cell count and red blood cell distribution width. The diagnostic accuracy of Iron-Def for identifying patients with a percentage of saturation of transferrin <15% (n=104) was 84%, with a sensitivity of 0.952 and specificity of 0.538. A sub-analysis of 71 patients with ferritin <20 ng/dL yielded an even better diagnostic performance (86%, with a sensitivity of 0.935 and specificity of 0.620). DISCUSSION: Although additional confirmatory investigations would be needed, the preliminary findings of our study attest that Iron-Def may be an easy, inexpensive, rapid and reliable parameter for screening iron deficiency anaemia.

Association of Family Income and Risk of Food Insecurity With Iron Status in Young Children.

Importance: Iron deficiency (ID) has the greatest prevalence in early childhood and has been associated with poor developmental outcomes. Previous research examining associations of income and food insecurity (FI) with ID is inconsistent. Objective: To examine the association of family income and family risk of FI with iron status in healthy young children attending primary care. Design, Setting, and Participants: This cross-sectional study included 1245 children aged 12 to 29 months who attended scheduled primary care supervision visits from 2008 to 2018 in Toronto, Canada, and the surrounding area. Exposures: Family income and risk of FI were collected from parent-reported questionnaires. Children whose parents provided an affirmative response to the 1-item FI screen on the Nutrition Screening Tool for Every Toddler or at least 1 item on the 2-item Hunger Vital Sign FI screening tool were categorized as having family risk of FI. Main Outcomes and Measures: Iron deficiency (serum ferritin level <12 ng/mL) and ID anemia (IDA; serum ferritin level <12 ng/mL and hemoglobin level <11.0 g/dL). All models were adjusted for age, sex, birth weight, body mass index z score, C-reactive protein level, maternal education, breastfeeding duration, bottle use, cow's milk intake, and formula feeding in the first year. Results: Of 1245 children (595 [47.8%] girls; median [interquartile range] age, 18.1 [13.3-24.0] months), 131 (10.5%) were from households with a family income of less than CAD $40 000 ($29 534), 77 (6.2%) were from families at risk of FI, 185 (14.9%) had ID, and 58 (5.3%) had IDA. The odds of children with a family income of less than CAD $40 000 having ID and IDA were 3 times higher than those of children in the highest family income group (ID: odds ratio [OR], 3.08; 95% CI, 1.66-5.72; P < .001; IDA: OR, 3.28; 95% CI, 1.22-8.87; P = .02). Being in a family at risk of FI, compared with all other children, was not associated with ID or IDA (ID: OR, 0.43; 95% CI, 0.18-1.02; P = .06; IDA: OR, 0.16; 95% CI, 0.02-1.23; P = .08). Conclusions and Relevance: In this study, low family income was associated with increased risk of ID and IDA in young children. Risk of FI was not a risk factor for ID or IDA. These findings suggest that targeting income security may be more effective than targeting access to food to reduce health inequities in the prevention of iron deficiency.

Mean blood glucose-independent HbA1c racial disparity and iron status in youth with Type 1 DM.

INTRODUCTION: Black patients have higher HbA1c than Whites even after adjustment for mean blood glucose (MBG). Decreased iron status has been associated with increased HbA1c independently of glucose. We hypothesized that decreased iron status might account for higher HbA1c in Black patients. METHODS: Pediatric patients with T1D in the Diabetes Center at Children's Hospital of New Orleans who self-identified as either Black or White were recruited for the study. At the time of their clinic visit labs were obtained for ferritin (Fer), soluble transferrin receptor (sTfR), HbA1c, and CBC. MBG was derived from patient's home glucose meter records over the last 30 days. Total body iron (TBI) and sTfr/log10 Fer (R/lFer) were calculated. RESULTS: A total of 80 (35 Blacks/45 Whites; 41 female/39 male) patients were recruited. Unadjusted levels of HbA1c, MBG, sTfR, Fer, RDW-CV, and RDW-SD were all higher in Blacks than Whites. TBI and R/lFer were not different between groups. Fer was correlated with Hb, MBG but not HbA1c. sTfR was correlated with HbA1c, MCV, MCH, and RDW-SD. In multiple variable analysis with HbA1c as the dependent variable, race and MBG were statistically significant in the model. However, measures of iron status: Fer, sTfR, R/lFer and TBI were not statistically influential. CONCLUSION: After adjustment for race, MBG and RDW-CV, iron indices were not statistically significant independent predictors of HbA1c levels. These observations indicate that factors besides iron status and CBC indices contribute to MBG-independent racial disparity in HbA1c.

Iron deficiency in 78 805 people admitted with heart failure across England: a retrospective cohort study.

Objectives: Iron deficiency (ID), with or without anaemia (IDA), is an important comorbidity in people with chronic heart failure (HF), but the prevalence and significance in those admitted with HF is uncertain. We assessed the prevalence of ID or IDA in adults (age ≥21 years) hospitalised with a primary diagnosis of HF, and examined key metrics associated with these secondary diagnoses. Methods: A retrospective cohort study of Hospital Episode Statistics describing all adults admitted to National Health Service (NHS) hospitals across England from April 2015 through March 2016 with primary diagnostic discharge coding as HF, with or without subsidiary coding for ID/IDA. Results: 78 805 adults were admitted to 177 NHS hospitals with primary coding as HF: 26 530 (33.7%) with secondary coding for ID/IDA, and 52 275 (66.3%) without. Proportionately more patients coded ID/IDA were admitted as emergencies (94.8% vs 87.6%; p<0.0001). Tending to be older and female, they required a longer length of stay (15.8 vs 12.2 days; p<0.0001), with higher per capita costs (£3623 vs £2918; p<0.0001), the cumulative excess expenditure being £21.5 million. HF-related (8.2% vs 5.2%; p<0.0001) and all-cause readmission rates (25.8% vs 17.7%; p<0.05) at ≤30 days were greater in those with ID/IDA against those without, and they manifested a small but statistically significant increased inpatient mortality (13.5% v 12.9%; p=0.009). Conclusions: For adults admitted to hospitals in England, principally with acute HF, ID/IDA are significant comorbidities and associated with adverse outcomes, both for affected individuals, and the health economy.

Intravenous ferric carboxymaltose for iron deficiency anemia in dialysis patients: Effect of a new protocol adopted for a hemodialysis limited assistance center.

Iron and erythropoietin deficiencies are determinants of anemia in chronic kidney disease. In hemodialysis (HD) patients, intravenous (IV) iron is associated with a greater hemoglobin (Hb) production and better erythropoietin response but may be associated to hypersensitivity reaction. After the 2013 European Medicines Agency report regarding early detection/management of iron allergic reactions, IV iron administration dramatically reduced in Italian Hemodialysis-Limited-Assistance-Centre (HD-CAL) where a physician is present only once a week. Objective of the study was providing an effective and secure IV iron administration protocol for HD-CAL patients. IV ferric carboxymaltose (FCM) administration was more effective and better tolerated than sodium ferric gluconate for iron deficiency correction and resolution of anemia in 24 patients undergoing HD in our HD-CAL. Six months of FCM IV treatment once a week increased ferritin and Hb compared to sodium ferric gluconate once a week leading to decreased erythropoietin consumption from 24 000 to 15 000 U/patient/week with an erythropoietin annual expense reduction. No blood transfusions, gastrointestinal intolerance or other adverse effects were reported. The FCM IV administration protocol for our HD-CAL patients was safe and no adverse events were reported, resulting in significantly increased ferritin, transferrin saturation, and Hb levels, reduction of erythropoietin requirements, and consequently reduction of erythropoietin expenses.

Validity of plasma collection cards for ferritin assessment-A proof-of-concept study.

OBJECTIVES: Iron depletion is common around the world and among certain risk groups in developed countries. The overall purpose was to test the suitability of a novel plasma collection card for minimally invasive iron status assessment. METHODS: Twenty participants (10 f/10 m) participated in this cross-sectional study. Ferritin and hemoglobin were measured from blood collected from a forearm vein, serving as reference method. Blood was also collected from the fingertip using the NoviplexTM Plasma Prep Card as well as capillary collection tubes. RESULTS: There was substantial concordance between ferritin measured from samples collected via NoviplexTM and venous ferritin (concordance correlation coefficient (CCC) = 0.96) with a mean bias of -0.8 ng/mL. Storing NoviplexTM cards at room temperature for 2 weeks resulted in slightly lower but good concordance when compared to venous ferritin (CCC = 0.95). Capillary hemoglobin (CCC = 0.42) and hematocrit (CCC = 0.25) were in poor agreement with venous data. CONCLUSIONS: NoviplexTM cards offer a suitable alternative for a minimally invasive ferritin screening in the field when compared to capillary collection tubes. Despite overall substantial concordance with the reference method, findings indicative of iron status abnormalities should be confirmed in venous samples.

Analytical and biological assessment of circulating human erythroferrone.

BACKGROUND: Erythroferrone (ERFE) is an erythroid hormone putatively involved in stress erythropoiesis. Its regional clearance and circulating form in humans, as well as levels in normal health and coronary disease remain unclear. METHODS: To establish a reference interval, ERFE was measured in 155 healthy volunteers using the Intrinsic LifeSciences ELISA. To identify trans-organ gradients in ERFE, regional blood sampling was undertaken in patients (n = 13) undergoing clinically indicated cardiac catheterisation. The Intrinsic ELISA was assessed for reproducibility, stability, linearity and possible cross-reactivity, interference and anticoagulant effects. Circulating forms of ERFE were evaluated by HPLC. RESULTS: In healthy individuals, the median concentration of ERFE was 0.51 ng/mL (IQR: 0.12-1.25), with men (n = 78) having higher levels than women (n = 77) (0.67 vs 0.32 ng/mL, p = 0.0001). ERFE concentrations in trans-organ sampling revealed no clear organ of clearance or production. Samples with high endogenous ERFE levels were suppressed by haemoglobin (≥2 g/L), bilirubin (≥200 µmol/L), lipaemia (>1 g/L), and freeze thawing (≥2 cycles), but this was not observed with low ERFE concentrations. Endogenous ERFE immunoreactivity was 46% higher in EDTA plasma compared with serum and lithium heparin plasma. On SE-HPLC, ERFE eluted as intact and cleaved forms. CONCLUSION: We provide a useful reference range for ERFE in EDTA plasma. We found no specific site of secretion or clearance. The Intrinsic ELISA performed adequately but is limited by interference and stability when endogenous levels are high. Circulating forms are multiple and complex.