Iron serum levels and iron homeostasis parameters in patients with nosocomial pneumonia treated with cefiderocol: post hoc analysis of the APEKS-NP study

Critically ill patients often present with low serum iron levels or anemia. We evaluated the impact of iron levels and iron homeostasis on the efficacy and safety of cefiderocol, an iron-chelator siderophore cephalosporin, in patients with nosocomial pneumonia in a post hoc analysis of the randomized, double-blind, Phase 3 APEKS-NP study (NCT03032380). Patients with Gram-negative nosocomial pneumonia received cefiderocol 2 g, 3-h infusion, q8h, or high-dose, extended-infusion meropenem 2 g, 3-h infusion, q8h, for 7–14 days. Efficacy and safety parameters, including specific iron homeostasis parameters (i.e., hepcidin, iron, total iron binding capacity, transferrin saturation), were analyzed according to baseline iron levels. In the cefiderocol and meropenem arms, 79.1% (117/148) and 83.3% (125/150) randomized patients, respectively, had low baseline serum iron levels. Rates of 14-day (12.3% [14/114] vs 11.6% [14/121]) and 28-day all-cause mortality (20.5% [23/112] vs 19.0% [23/121]), clinical cure (63.2% [72/114] vs 67.2% [82/122]), and microbiological eradication (43.6% [41/94] vs 48.1% [51/106]) at test of cure were similar in cefiderocol vs meropenem arms, respectively. In the overall safety population, rates of anemia-related adverse events were similar (cefiderocol arm 18.2% [27/148], meropenem arm 18.7% [28/150]). Changes from baseline to test of cure in hepcidin, iron, total iron binding capacity, and transferrin saturation were similar between treatment arms. Cefiderocol treatment did not affect iron homeostasis, and its efficacy and safety were not influenced by baseline serum iron levels. Clinicaltrials.gov registration: NCT03032380. Date of registration: 26 January 2017.

Prevalence and associated risk factors of iron deficiency without anemia among school adolescents in Mbouda, Western Cameroon

Background: Adolescents are a particularly vulnerable age group to iron deficiency without anemia (IDWA). This study aimed at determining the prevalence and associated risks factors of IDWA among apparently healthy school teenagers in Mbouda, West-Cameroon.Methods: The 778 blood samples were randomly collected from adolescents aged 10-19 years of four schools in Mbouda. Appropriate indicators including haemoglobin and haematocrit, serum iron, ferritin, transferrin, and total iron binding capacity, transferrin saturation were determined using standard methods.Results: The overall prevalence of IDWA was 40.4%. High significant difference in the mean values of serum iron (p≤0.001), serum ferritin (p≤0.001), TIBC (p=0.007), CST (p≤0.001) were observed in participants with IDWA compared to those without IDWA. The sociodemographic risk factors of IDWA in school adolescents were school site (p=0.022; 0.14 (0.90-1.43) and period of menstruation (p=0.015; 1.48 (1.083-2.03). Consumption of roots-tubers [OR: 0.92 (0.48-1.77)] legumes [OR: 2.65 (1.91-3.67)], cereals [OR: 0.90 (0.67-1.22)], increased the risk of IDWA while consumption of vegetables [OR: 0.29 (0.22-0.39)], eggs [OR: 0.66 (0.49-0.90)], and fish-shrimp [OR: 0.172 (0.10-0.295)] decreased the risk of IDWA. Meal consumption frequency had a statistically significant association with IDWA (p≤0.001).Conclusions: This study identified that IDWA was a major public health in adolescents. This study will help in planning and implementation of the policy for prevention of IDWA in adolescents.

Role of Hepcidin in Pediatric Chronic Kidney Disease with Anemia

Introduction: Anemia is a frequent complication of chronic kidney disease (CKD) in children and it causes an increase in morbidity, mortality and accelerates the rate of progression of CKD. Inflammation and impaired kidney clearance increase plasma hepcidin, inhibiting duodenal iron absorption and sequestering iron in macrophages. However, the role of hepcidin in increasing the risk of anemia in children with CKD is still uncertain. This study aimed to investigate the association between hepcidin levels and anemia in children with pre-dialysis CKD. Methods: A cross-sectional study was conducted at Dr. Soetomo Academic Hospital from December 2018 to February 2019. Children with pre-dialysis CKD were enrolled in this study. The subject had no history of erythropoietin administration and blood transfusion 3 months before the blood sample were withdrawn. A complete blood count, ferritin serum, transferrin saturation (TSAT) and hepcidin serum were performed. The correlations between Hepcidin and ferritin level, between ferritin level and anemia, and between TSAT and anemia were analyzed using Spearman correlation and the Mann-Whitney test. Results: A total of 47 children, 27 boys and 20 girls, ranged in age from 3 months to 18 years old. There was a significant correlation between hepcidin and ferritin levels (p=0.006) and the value of the Spearman correlation was r=0.392. While the correlation between ferritin level and anemia showed a significant result, p=0.001. However, TSAT did not show any significant correlation with anemia (p=0.230). Conclusion: There was an indirect association between hepcidin level and anemia by increasing ferritin level that induces anemia in pre-dialysis CKD children.

The Paediatric Iron Deficiency Assessment with Reticulocyte Haemoglobin Equivalent (Ret-He) in Comparison with Biochemical Markers of Serum Ferritin and Transferrin Saturation

Diagnosis of iron deficiency anaemia (IDA) is a challenge as the conventional methods often diagnose the disease at the later stage. Haemoglobin content of reticulocytes is useful to identify IDA at earlier stage. The objective of this study was to evaluate reticulocyte-haemoglobin equivalent (Ret-He) in diagnosing IDA in children and to compare it with other conventional methods. This prospective study was conducted on 120 paediatric patients aged 12 years and below, who attended Hospital Sultanah Aminah Johor Bahru, Malaysia with haemoglobin <12 g/dL. Ret-He and serum iron, ferritin and transferrin saturation were measured. Using a cut-off point of 20% for transferrin saturation, 81 out of 120 subjects (67.5%) were found as iron deficient. Based on the diagnosis of IDA, cut-off value for Ret-He using the Receiver Operating Characteristics (ROC) curve analysis was found as 22.65 pg. Ret-He showed a good sensitivity and specificity of 77.8% and 66.7%, respectively. As compared with Ret-He, serum ferritin showed a sensitivity of only 18.9%. However, a good specificity of 100% suggest it is useful for ruling in the disease but not suitable for screening. Transferrin saturation showed a good sensitivity and specificity, but it is biologically variable and not cost effective as a screening tool. Correlation study showed serum iron and transferrin saturation have significant positive correlation with Ret-He (r=0.415 to 0.518). However, there was no correlation between Ret-He and serum ferritin (r=0.051, p=0.578). This study shows that Ret-He at a cut-off point of 22.65 pg has a better sensitivity and potentially be useful as a screening tool in the paediatric population.

Hepatitis B-Associated Symptomatic Iron Overload, with Complete Resolution after Nucleoside Analogue Treatment

Symptomatic iron overload and hyperferritinemia are rarely mentioned as complications of chronic hepatitis B infection. We report a case of a 70-year-old woman who presented with symptoms of iron overload including aches in the calves, fatigue, poor appetite, and low mood. Laboratory results showed a serum ferritin of 2449 μg/L and transferrin saturation of 74%. Her symptoms completely resolved with hepatitis B antiviral treatment. Serum ferritin and transferrin saturation also normalized. Symptomatic iron overload is a rare yet clinically important complication that can result from chronic hepatitis B infection.

Magnesium supplementation and iron status among female students: the intervention study

Background: Literature data indicate the benefit of magnesium (Mg) supplementation. The aim of this study was to examine the effect of short-term Mg supplementation on iron status in healthy female participants. Methods: One hundred healthy female students of the University of Belgrade - Faculty of Pharmacy participated in the study during eleven intervention days. Students ingested Mg preparations with the same dose of the active substance. The analysis included the measurement of serum iron, unsaturated iron binding capacity (UIBC), total iron binding capacity (TIBC), total Mg (tMg), ionized Mg (iMg), complete blood count, met-, carboxy- and oxy-haemoglobin (metHgb, COHgb, O2Hgb). Transferrin concentrations and the percentage of transferrin saturation (SAT) were calculated manually. The association among the analyzed biochemical parameters was examined using polynomial regression. A principal component analysis (PCA) was used for the evaluation of interdependence between the analyzed parameters. Results: A statistically significant trend for change in O2Hgb (%) by tertiles of iMg concentrations was found (P = 0.029). Serum tMg reached a significant positive correlation with the SAT at concentration levels greater than 0.9 mmol/L, after 11 days of intervention (R2=0.116). Ionized Mg in a concentration higher than 0.6 mmol/L is positively correlated with SAT and serum Fe (R2=0.214; 0.199, respectively). PCA revealed variability of 64.7% for two axes after 11 days. Conclusions: Mg supplementation leads to an improvement in certain iron status parameters even in individuals with optimal levels of these indices. However, caution should be exercised when supplementing Mg, and laboratory monitoring of the interaction is required.

Abdominal pain and cirrhosis at diagnosis of hemochromatosis: Analysis of 219 referred probands with HFE p.C282Y homozygosity and a literature review

Background In hemochromatosis, causes of abdominal pain and its associations with cirrhosis are poorly understood. Methods We retrospectively compared characteristics of referred hemochromatosis probands with HFE p.C282Y homozygosity with/without biopsy-proven cirrhosis: sex, age, diabetes, heavy alcohol consumption, abdominal pain/tenderness, hepatomegaly, splenomegaly, non-alcoholic fatty liver disease, chronic viral hepatitis, ascites, transferrin saturation (TS), serum ferritin (SF), and iron removed by phlebotomy (QFe). We performed logistic regression on cirrhosis using characteristics identified in univariate comparisons. We performed computerized and manual searches to identify hemochromatosis case series and compiled prevalence data on cirrhosis and abdominal pain and causes of abdominal pain. Results Of 219 probands, 57.1% were men. Mean age was 48±13 y. In 22 probands with cirrhosis, proportions of men, mean age, prevalences of heavy alcohol consumption, abdominal pain, abdominal tenderness, hepatomegaly, splenomegaly, and chronic viral hepatitis, and median TS, SF, and QFe were significantly greater than in probands without cirrhosis. Regression analysis revealed three associations with cirrhosis: abdominal pain (p = 0.0292; odds ratio 9.8 (95% CI: 1.2, 76.9)); chronic viral hepatitis (p = 0.0153; 11.5 (95% CI: 1.6, 83.3)); and QFe (p = 0.0009; 1.2 (95% CI: 1.1, 1.3)). Of eight probands with abdominal pain, five had cirrhosis and four had diabetes. One proband each with abdominal pain had heavy alcohol consumption, chronic viral hepatitis B, hepatic sarcoidosis, hepatocellular carcinoma, and chronic cholecystitis, cholelithiasis, and sigmoid diverticulitis. Abdominal pain was alleviated after phlebotomy alone in four probands. In 12 previous reports (1935–2011), there was a negative correlation of cirrhosis prevalence and publication year (p = 0.0033). In 11 previous reports (1935–1996), a positive association of abdominal pain prevalence and publication year was not significant (p = 0.0802). Conclusions Abdominal pain, chronic viral hepatitis, and QFe are significantly associated with cirrhosis in referred hemochromatosis probands with HFE p.C282Y homozygosity. Iron-related and non-iron-related factors contribute to the occurrence of abdominal pain.

HeGRI: A Novel Index of Serum Hepcidin Suppression in Relation to the Degree of Renal Dysfunction among β-Thalassemia Major Patients

Background: The progressive renal function inadequacy results in altered hepcidin metabolism due to a shifting of its renal elimination, which consequently affects enteric iron absorption and iron stores’ availability. This study aimed to investigate and correlate renal function, iron status, and hepcidin in patients with β-thalassemia major through a novel index. Methods: In this 1:1 case–control study, serum hepcidin, serum ferritin, iron study, hematological and renal function parameters were compared between 60 β-thalassemia major patients with iron overload and 61 healthy individuals (2–30 years old). Results: The concentrations of serum hepcidin (21.898 vs. 9.941 ng/mL; p < 0.001) and eGFR (179.71 vs. 132.95; p < 0.001) were significantly higher in β-thalassemia major patients compared to the controls. The serum hepcidin levels decreased with increasing levels of total iron-binding capacity (TIBC; β = −0.442; p = 0.024), transferrin saturation (β = −0.343; p = 0.023), serum creatinine (β = −0.625; p = 0.0030), and eGFR (β = −0.496; p = 0.011). The mean hepcidin/ferritin ratio was significantly lower in the β-thalassemia major cases (0.0069 vs. 0.3970; p < 0.001). The novel hepcidin/eGFR ratio index (HeGRI) was significantly higher in the patient group compared to controls (0.12 vs. 0.09; p = 0.031), respectively. Conclusions: These results suggest that HeGRI could be a potential index of the appropriateness of serum hepcidin suppression associated with the degree of renal dysfunction among β-thalassemia major patients.

115 Prognostic significance of iron deficiency status in chronic inflammatory cardiomyopathy

Aims Iron deficiency (ID) and associated anaemia (IDA) represent major comorbidities in chronic diseases. However, their prevalence and prognostic significance have never been investigated in chronic inflammatory cardiomyopathy (CIC). Methods and results This is a single-centre, prospective study, on consecutive adult patients with CIC (symptom onset &gt; 3 months, endomyocardial biopsy-proven chronic myocarditis) undergoing iron status assessment (enrollment: January 2014–January 2019). ID was defined as either serum ferritin &lt; 100 µg/l or transferrin saturation &lt; 20%. IDA was defined as haemoglobin &lt; 12 g/dl in women, &lt; 13 g/dl in men. The primary endpoint was the occurrence of heart failure events (HFE) and/or arrhythmic events (AE). The study cohort is composed by 219 CIC patients (mean age 46 ± 15 y, 71% males, mean LVEF 50 ± 14%). Diagnosis was furtherly supported by cardiac magnetic resonance in 194 cases (89%). Baseline characteristics of patients with IDA (n = 48), ID (n = 70), and non-ID controls (n = 101) were largely comparable. We found that median in-hospital stay length was 13 days (IQR: 6–20) in IDA patients vs. 8 (IQR: 5–11) in the remaining groups (P = 0.002), and was inversely correlated with haemoglobin values on admission. By 3.9 ± 1.8 year prospective follow-up, events occurred in 86 patients (39%). For the composite endpoint, the only factors associated with events were ID status (HR: 6.3, 95% CI: 2.1–19.5, P = 0.001) and male gender (HR: 5.4, 95% CI: 1.2–24.9, P = 0.030). In detail, HFE occurred in 48 patients (40/118 IDA or ID vs. 8/101 controls, P &lt; 0.001), and AE in 51 (34/118 IDA or ID vs. 17/101 controls, P = 0.039). All cardiac deaths (n = 7) occurred in ID or IDA patients (P = 0.016; n = 1 and 6, respectively). Conclusions ID and IDA are common among CIC patients, and may bare a negative prognostic value. Our findings suggest a careful evaluation of haemoglobin levels and iron status, and call for further investigation on both pathophysiological and prognostic implications of ID and IDA among CIC patients.