Do Parenteral Iron Therapies Preserve or Deteriorate Kidney Functions? "Iron Carboxy Maltose or Iron Sucrose?"

BACKGROUND: Treatment of end stage renal disease (ESRD) is based on preserving renal functions. Since renal anemia is frequently detected, we use parenteral iron treatments in patients with chronic kidney disease (CKD). However, there need to be more precise and sufficient studies on the effect of these treatments on the rate of decrease in the glomerular filtration rate (GFR). Therefore, we conducted a study comparing the rates of change in renal function in patients who had used parenteral iron for at least five years. METHODS: Our study is a retrospective cohort study, and 180 patients with CKD (86 women, 94 men, mean age: 63.5 ± 11.4 years) who had been followed and treated in nephrology outpatient clinics for at least five years and met the study criteria were included in the study. Patients were divided into three groups for iron therapy: not receiving iron therapy, iron carboxy maltose (ICM), and iron sucrose (IS) parenterally. Each group consisted of 60 people. The first and last creatinine and GFR values were compared for a 5-year follow-up in each group. RESULTS: There was no significant difference between the two groups, those using and those not using iron, regarding creatinine increase and GFR decrease rate. Additionally, no significant difference was detected in the GFR decline rates of patients using ICM and IS. CONCLUSIONS: This study reduces the concerns that correcting anemia through parenteral iron therapy in patients with CKD may harm renal function.

Evaluation of left ventricular systolic function in patients with iron deficiency anemia based on non-invasive left ventricular pressure-strain loops.

BACKGROUND: Iron deficiency anemia (IDA) is a common health problem worldwide. The objective of this study was to noninvasively and quantitatively evaluate early changes in left ventricular systolic function in patients with IDA using the left ventricular press-strain loop (LV-PSL). METHODS: Sixty-two patients with IDA were selected and divided into two groups based on hemoglobin (Hb) concentration: Group B with Hb > 9 g/dL and group C with 6 g/dL < Hb < 9 g/dL. Thirty-three healthy individuals were used as the control (Group A). The global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global waste work (GWW), global work efficiency (GWE) were derived using LV-PSL analysis. Receiver operating characteristic (ROC) curves were constructed for MW parameters to detect abnormal left ventricular systolic function in IDA patients. RESULTS: Compared to group A, GWI and GCW were reduced in group B (both P < 0.01). Compared with groups B and A, GLS, GWI, GCW and GWE, and E/A were all diminished, and GWW, LVEDV, LVESV, and E/mean e' were all increased in group C (all P < 0.01). GLS was positively correlated with GWI, GCW, and GWE (r = 0.679, 0.681, and 0.447, all P < 0.01), and negatively associated with GWW (r = - 0.411, all P < 0.01). For GWI, area under the ROC curve (AUROC) was 0.783. The optimal GWI threshold for detecting abnormal LV systolic function in IDA was1763 mmHg%, with sensitivity of 0.71 and specificity of 0.78. CONCLUSIONS: LV-PSL allows noninvasive quantitative assessment of early impaired LV systolic function in IDA patients with preserved LV ejection fraction, and GWI has high sensitivity and specificity compared with other parameters.

Iron deficiency in patients with a Fontan circulation and its impact on exercise capacity.

BACKGROUND: Iron deficiency (ID) has been reported in patients with congenital heart disease. There is, however, a scarcity of data on its prevalence in patients with a Fontan circulation. The aim of this study is to investigate the prevalence of ID in Fontan patients and to investigate the association between ID and exercise capacity in this population. METHODS AND RESULTS: Blood count and haematological parameters were determined in plasma of 61 Fontan patients (51% female, mean age 29±9 years). ID was defined as transferrin saturation (TSAT) ≤19.8%. The prevalence of ID was 36% (22/61 patients). Especially among women, the diagnosis of ID was highly prevalent (52%) despite normal haemoglobin levels (153.7±18.4 g/L). Mean ferritin levels were 98±80 µg/L and mean TSAT levels were 22%±12%. Cardiopulmonary exercise testing was performed in 46 patients (75%). Patients with ID had a lower peak oxygen uptake (V̇O2peak) (1397±477 vs 1692±530 mL/min; p=0.039), although this relationship was confounded by sex. The presence of ID increased the likelihood of not achieving a respiratory exchange ratio (RER) ≥1.1 by 5-fold (p=0.035). CONCLUSION: ID is highly prevalent among patients with a Fontan circulation. V̇O2peak is lower in patients with ID. Fontan patients with ID are less likely to achieve an RER≥1.1 during cardiopulmonary exercise testing.

Iron homeostasis, recycling and vulnerability in the stressed kidney: A neglected dimension of iron-deficient heart failure.

The available evidence suggests that the kidney may contribute importantly to the development of an iron deficiency state in patients with heart failure and may be injured by therapeutic efforts to achieve iron repletion. The exceptional workload of the proximal renal tubule requires substantial quantities of iron for ATP synthesis, which it derives from Fe3+ bound to transferrin in the bloodstream. Following ferrireduction, Fe2+ is conveyed by divalent transporters (e.g. DMT1) out of the endosome of the proximal renal tubule, and highly reactive Fe2+ can be directed to the mitochondria, sequestered safely in a ferritin nanocage or exported through the actions of hepcidin-inhibitable ferroportin. The actions of ferroportin, together with transferrin endocytosis and DMT1-mediated transport, play a key role in the recycling of iron from the tubular fluid into the bloodstream and preventing the loss of filtered iron in the urine. Activation of endogenous neurohormonal systems and proinflammatory signalling in heart failure decrease megalin-mediated uptake and DMT1 expression, and increase hepcidin-mediated suppression of ferroportin, promoting the loss of iron in the urine and contributing to the development of an iron deficiency state. Furthermore, the failure of ferroportin-mediated efflux at the basolateral membrane heightens the susceptibility of the renal tubules to cytosolic excesses of Fe2+, causing lipid peroxidation and synchronized cell death (ferroptosis) through the iron-dependent free radical theft of electrons from lipids in the cell membrane. Ferroptosis is a central mechanism to most disorders that can cause acute and chronic kidney disease. Short-term bolus administration of intravenous iron can cause oxidative stress and is accompanied by markers of renal injury. Experimentally, long-term maintenance of an iron-replete state is accompanied by accelerated loss of nephrons, oxidative stress, inflammation and fibrosis. Intravenous iron therapy increases glomerular filtration rate rapidly in patients with heart failure (perhaps because of a haemodynamic effect) but not in patients with chronic kidney disease, and the effects of intravenous iron on the progression of renal dysfunction in the long-term trials - AFFIRM-AHF, IRONMAN and HEART-FID - have not yet been reported. Given the potential role of dysregulated renal iron homeostasis in the pathogenesis of iron deficiency and the known vulnerability of the kidney to intravenous iron, the appropriate level of iron repletion with respect to the risk of acute and chronic kidney injury in patients with heart failure requires further study.

Effect of anaemia and iron deficiency in heart failure with mildly reduced ejection fraction.

OBJECTIVE: The present study aims to clarify the prevalence and prognostic impact of anaemia and iron deficiency in patients with heart failure with mildly reduced ejection fraction (HFmrEF). BACKGROUND: The prognostic impact of anaemia and iron deficiency in HFmrEF has not yet been clarified. METHODS: Consecutive patients with HFmrEF were retrospectively included at one institution from 2016 to 2022. Patients with anaemia (i.e. haemoglobin <13 g/dL in males and < 12 g/dL in females) were compared to patients without, respectively patients with or without iron deficiency. The primary endpoint was all-cause mortality at 30 months (median follow-up), secondary endpoints comprised HF-related rehospitalisation. RESULTS: Two thousand one hundred and fifty four patients with HFmrEF with a median haemoglobin level of 12.2 g/dL were included. Anaemia was present in 52% of patients with HFmrEF and associated with a higher risk of all-cause mortality (44% vs. 18%; HR = 3.021; 95% CI 2.552-3.576; p =.001) and HF-related rehospitalisation (18% vs. 8%; HR = 2.351; 95% CI 1.819-3.040; p =.001) at 30 months, which was confirmed after multivariable adjustment. Although iron status was infrequently assessed in anaemics with HFmrEF (27%), the presence of iron deficiency was associated with higher risk of rehospitalisation for worsening HF (25% vs. 15%; HR = 1.746; 95% CI 1.024-2.976; p =.038), but not all-cause mortality (p =.279) at 30 months. CONCLUSION: Anaemia and iron deficiency are very common in atleast half of patients with HFmrEF and independently associated with adverse long-term prognosis.

Assessment of fetal cardiac function in pregnant women with anemia: prospective case-control study.

OBJECTIVE: To compare fetal cardiac function in pregnant women with iron deficiency anemia (IDA) vs healthy pregnant controls. METHODS: This was a single-center, prospective, case-control study conducted in a tertiary hospital between November 2022 and September 2023. Women diagnosed with IDA who attended as outpatients at the pregnancy follow-up clinic at 30-34 weeks' gestation or who were hospitalized for intravenous iron treatment owing to profound anemia were included. The control group consisted of randomly selected gestational-age-matched pregnant women with no obstetric complications or comorbidities and who did not have anemia. Patients underwent two-dimensional imaging, followed by pulsed-wave Doppler and M-mode and tissue Doppler imaging (TDI) to evaluate fetal cardiac function. A fetal cardiac score was calculated using systolic, diastolic and global hemodynamic function parameters, and was compared between patients with IDA and those without. The fetal cardiac score was also assessed according to the severity of anemia in the IDA group. RESULTS: A total of 150 patients, comprising 50 patients with IDA and 100 healthy pregnant women at 30-34 weeks' gestation, were included in the study. Of the patients with IDA, 20 had mild, 18 had moderate and 12 had severe anemia. The fetal myocardial performance index and isovolumetric relaxation time were significantly higher in the IDA group compared with the control group (P < 0.0001 for both), while isovolumetric contraction time was similar. Among the fetal tricuspid and mitral valve diastolic parameters, the E, A and E/A values were significantly lower in the IDA group (P < 0.05 for all). Mitral (MAPSE) and tricuspid (TAPSE) annular plane systolic excursions were significantly lower in the IDA group (P < 0.05 for both). The IDA group also had significantly lower values for the TDI parameters mitral and tricuspid E', A', S' and E'/A' ratio and a significantly higher E/E' ratio (P < 0.05 for all). Among the IDA subgroups, a significant decrease was observed in the tricuspid and mitral A, E and E/A ratio in fetuses whose mothers had severe anemia (P = 0.001). M-mode Doppler analysis revealed significantly lower fetal TAPSE and MAPSE in the patient group with severe maternal anemia (P = 0.001 for both). According to the subgroup comparison of TDI findings, the fetuses of mothers with severe anemia had significantly lower tricuspid and mitral E', A', S' and E'/A' ratio values and a significantly higher E/E' ratio (P < 0.05 for all). The fetal cardiac score was significantly higher in the maternal IDA group compared with the control group (P < 0.001). A significant negative correlation was found between maternal hemoglobin level and fetal cardiac score (P < 0.001). CONCLUSIONS: We observed differences in fetal systolic and diastolic cardiac function in pregnancies with maternal IDA. Fetal cardiac function was affected more among patients with severe anemia. This study found an increased E/E' ratio in the fetuses of pregnant women with IDA, suggesting decreased fetal heart maturation. Prenatal fetal cardiac evaluation, especially in women with severe anemia, can facilitate a more seamless transition to the postnatal period for these newborns. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Oral Iron Absorption Test: A Simple Test with Relevance in the Clinical Setting.

BACKGROUND: Iron deficiency anemia is a widespread problem. Although oral and intravenous therapy are available, iron malabsorption is a distinct possibility. OBJECTIVES: To evaluate the applicability of the oral iron absorption test (OIAT) as a simple and effective means of determining the degree of oral iron absorption. METHODS: The study comprised 81 patients diagnosed with iron deficiency anemia who were referred to a hematology outpatient clinic. Participants were given two ferrous sulphate tablets. Iron levels in the blood were evaluated at intervals from 30 to 180 minutes after iron administration. RESULTS: We divided patients into three distinct groups. The first group consisted of patients with little iron absorption with a maximum iron increment (Cmax) in the blood of 0-49 ug/dl. The second group had a moderate maximum absorption of 50-100 ug/dl, while a third group had considerable absorption of with maximum iron increase of over 100 ug/dl. CONCLUSIONS: The oral iron absorption test, although not clearly standardized, is easy to conduct in any outpatient clinic. This test can readily and clearly determine absorption or nonabsorption of iron. This test can have major implications on the need of oral or intravenous iron therapy and can also determine the need for further gastrointestinal evaluation of the small intestine, where iron absorption takes place and the success of therapy on subsequent iron absorption.

Clinical investigation of fertility after uterine artery embolization.

BACKGROUND: Uterine artery embolization is an effective and safe technique for the treatment of uterine fibroids, but its use remains controversial for women who wish to procreate. OBJECTIVE: This study aimed to study the clinical, anatomic, and obstetrical results of uterine artery embolization in patients of childbearing age not eligible for myomectomy. STUDY DESIGN: This was a retrospective cohort study of 398 female patients under the age of 43 years who were treated by uterine artery embolization between 2003 and 2017 for symptomatic fibroids and/or adenomyosis. Uterine artery embolization was performed according to a standardized procedure (fertility-sparing uterine artery embolization technique), with ovarian protection in the event of dangerous utero-ovarian anastomosis. Magnetic resonance imaging and pelvic ultrasounds were performed before and after uterine artery embolization. RESULTS: The overall clinical success rate (ie, resolution of preembolization symptoms such as heavy menstrual bleeding, iron-deficiency anemia, pelvic pressure) was 91.2%, and there were no major complications. One year after uterine artery embolization, we observed a mean 73% reduction in myoma volume. A total of 108 patients (49.3%) presented with dangerous utero-ovarian anastomosis and 33 (14.5%) benefited from ovarian protection. In our group, there were 148 pregnancies and 109 live births; 74 children were born at term; 23 were born preterm, on average at 35.12±2.78 weeks. Including preterm births, the mean birthweight and birth length of the children were within normal limits. Restoration of uterine anatomy and ovarian protection were identified as the main predictive factors for obstetrical success. Restoration was also a major predictive factor for clinical success and was associated with a lower rate of miscarriage. CONCLUSION: This study provided detailed clinical and obstetrical outcomes for 398 female patients who underwent uterine artery embolization for fibroid treatment; it contributes to the identification of anatomic and technical factors that could have an impact on fertility after uterine artery embolization. Further controlled clinical trials are needed to confirm our findings and reevaluate this procedure's indications and limitations for women with a desire to procreate.

Rationale and design of the intravenous iron for treatment of anemia before cardiac surgery trial.

Background Approximately 20% to 30% of patients awaiting cardiac surgery are anemic. Anemia increases the likelihood of requiring a red cell transfusion and is associated with increased complications, intensive care, and hospital stay following surgery. Iron deficiency is the commonest cause of anemia and preoperative intravenous (IV) iron therapy thus may improve anemia and therefore patient outcome following cardiac surgery. We have initiated the intravenous iron for treatment of anemia before cardiac surgery (ITACS) Trial to test the hypothesis that in patients with anemia awaiting elective cardiac surgery, IV iron will reduce complications, and facilitate recovery after surgery. Methods ITACS is a 1,000 patient, international randomized trial in patients with anemia undergoing elective cardiac surgery. The patients, health care providers, data collectors, and statistician are blinded to whether patients receive IV iron 1,000 mg, or placebo, at 1-26 weeks before their planned date of surgery. The primary endpoint is the number of days alive and at home up to 90 days after surgery. Results To date, ITACS has enrolled 615 patients in 30 hospitals in 9 countries. Patient mean (SD) age is 66 (12) years, 63% are male, with a mean (SD) hemoglobin at baseline of 118 (12) g/L; 40% have evidence (ferritin <100 ng/mL and/or transferrin saturation <25%) suggestive of iron deficiency. Most (59%) patients have undergone coronary artery surgery with or without valve surgery. Conclusions The ITACS Trial will be the largest study yet conducted to ascertain the benefits and risks of IV iron administration in anemic patients awaiting cardiac surgery.

Laboratory Testing in Telogen Effluvium.

Telogen effluvium (TE) – a common cause of non- scarring hair loss – is managed with varying clinical protocols given the paucity of evidence-based practices.

Physiological and pathophysiological mechanisms of hepcidin regulation: clinical implications for iron disorders.

The discovery of hepcidin has provided a solid foundation for understanding the mechanisms of systemic iron homeostasis and the aetiologies of iron disorders. Hepcidin assures the balance of circulating and stored iron levels for multiple physiological processes including oxygen transport and erythropoiesis, while limiting the toxicity of excess iron. The liver is the major site where regulatory signals from iron, erythropoietic drive and inflammation are integrated to control hepcidin production. Pathologically, hepcidin dysregulation by genetic inactivation, ineffective erythropoiesis, or inflammation leads to diseases of iron deficiency or overload such as iron-refractory iron-deficiency anaemia, anaemia of inflammation, iron-loading anaemias and hereditary haemochromatosis. In the present review, we discuss recent insights into the molecular mechanisms governing hepcidin regulation, how these pathways are disrupted in iron disorders, and how this knowledge is being used to develop novel diagnostic and therapeutic strategies.

NIMO-CKD-UK: a real-world, observational study of iron isomaltoside in patients with iron deficiency anaemia and chronic kidney disease.

BACKGROUND: Intravenous iron is often used to treat iron deficiency anaemia in non-dialysis chronic kidney disease (ND-CKD), but the optimal dosing regimen remains unclear. We evaluated the impact of high- versus low-dose intravenous iron isomaltoside on the probability of retreatment with intravenous iron in iron-deficient ND-CKD patients. METHODS: This real-world, prospective, observational study collected data from 256 ND-CKD patients treated for anaemia in the UK. Following an initial course of iron isomaltoside, patients were followed for ≥12 months. Iron dose and the need for retreatment were determined at the investigators' discretion. The primary study outcome was the need for retreatment at 52 weeks compared between patients who received >1000 mg of iron during Course 1 and those who received ≤1000 mg. Safety was evaluated through adverse drug reactions. RESULTS: The probability of retreatment at Week 52 was significantly lower in the >1000 mg iron group (n = 58) versus the ≤1000 mg group (n = 198); hazard ratio (95% confidence interval [CI]): 0.46 (0.20, 0.91); p = 0.012. Mean (95% CI) haemoglobin increased by 6.58 (4.94, 8.21) g/L in the ≤1000 mg group and by 10.59 (7.52, 13.66) g/L in the >1000 mg group (p = 0.024). Changes in other blood and iron parameters were not significantly different between the two groups. Administering >1000 mg of iron isomaltoside saved 8.6 appointments per 100 patients compared to ≤1000 mg. No serious adverse drug reactions were reported. Of the patients who received ≤1000 mg of iron in this study, 82.3% were eligible for a dose >1000 mg. CONCLUSIONS: The >1000 mg iron isomaltoside regimen reduced the probability of retreatment, achieved a greater haemoglobin response irrespective of erythropoiesis-stimulating agent treatment, and reduced the total number of appointments required, compared to the ≤1000 mg regimen. Many of the patients who received ≤1000 mg of iron were eligible for >1000 mg, indicating that there was considerable underdosing in this study. TRIAL REGISTRATION: ClinicalTrials.gov NCT02546154 , 10 September 2015.

Anemia grave no puerpério / Severe anemia in the puerperium

A anemia no puerpério é bastante prevalente, estando principalmente relacionada à ocorrência de anemia não corrigida durante a gestação e às hemorragias agudas durante o parto. Essas situações aumentam significativamente a probabilidade de anemia grave no período pós-parto, gerando manifestações orgânicas e psicológicas que trazem prejuízo ao binômio materno-fetal. A forma grave da doença é caracterizada laboratorialmente por hemoglobina < 7 g/dL e suas manifestações clínicas variam na dependência de diversos fatores. O objetivo do tratamento é corrigir a hipóxia tecidual, revertendo as alterações adaptativas relacionadas à carência de oxigênio. Enquanto o tratamento agressivo de perdas volêmicas agudas diminui a morbimortalidade por esses eventos, políticas restritivas de transfusão sanguínea em pacientes hemodinamicamente estáveis mostram-se benéficas. Se não houver indicação de transfusão, a reposição de ferro atuará na correção das principais etiologias, pelas vias endovenosa ou oral, na dependência de disponibilidade, custo e tolerância individual aos medicamentos disponíveis.(AU)

Anemia is quite prevalent in puerperium; in this population, the disease is mainly related to the occurrence of uncorrected anemia during pregnancy and to acute bleeding during childbirth. These situations significantly increase the likelihood of severe anemia in the postpartum period, generating organic and psychological manifestations that cause damage to the maternal-fetal binomial. The severe form of anemia is characterized by hemoglobin < 7 g/dL and its clinical manifestations vary depending on several factors. The goal of treatment is to correct tissue hypoxia, reversing adaptive changes related to oxygen deficiency. While the aggressive treatment of acute blood losses decreases the morbidity and mortality of these events, restrictive blood transfusion policies in hemodynamically stable patients are beneficial. If there is no indication for transfusion, iron replacement will act to correct the main etiologies, through the intravenous or oral routes, depending on availability, cost and individual tolerance to the available drugs.(AU)

Iron deficiency is a possible risk factor causing right heart failure in Tibetan children living in high altitude area.

The aim of the study is to discuss the risk factor of right heart failure (RHF) especially the association of iron deficiency with RHF in Tibetan children who live in high altitude area. In this retrospective study, we collected the data of Tibetan children from January 2011 to December 2018 in our hospital. The patients included in the study had the following data: age, gender, ferritin, echocardiography, hemoglobin, C-reaction protein, and altitude of residence. According to whether RHF was diagnosed, the patients were divided into RHF group and non-RHF group. Totally 133 patients were included with 59 in RHF group and 74 in non-RHF group. In single factor analysis, age (P = .008), altitude of residence (P < .001), ferritin (P < .001), and pulmonary arterial systolic pressure (P < .001) showed significant difference between the 2 groups. Binary logistic regression was performed to further identify the association of the clinical factors with RHF. Higher pulmonary arterial systolic pressure (odds ratio: 29.303, 95% confidence interval: 5.249-163.589, P < .001) and lower ferritin level (odds ratio: 5.849, 95% confidence interval: 1.585-21.593, P = .008) were independent risk factors associated with RHF. In receiver-operating characteristic curve, the optimal cutoff value of ferritin level was 14.6 µg/L with the sensitivity of 81.4% and specificity of 89.2%. As continuous variable, the correlation between ferritin and RHF was not certain (P = .281). Due to the possibility that iron deficiency be a risk factor of RHF in Tibetan children, prevention and treatment of iron deficiency might be a potential way in reducing the incidence of RHF in this high altitude area.

Iron Deficiency and Its Role in Sleep Disruption in Patients With Angelman Syndrome.

OBJECTIVE: To determine if Angelman syndrome patients with sleep complaints have an increased risk of iron deficiency, and if iron therapy improves their sleep difficulties. BACKGROUND: About two-thirds of Angelman syndrome patients experience sleep difficulties, which are likely multifactorial. Because iron deficiency can contribute toward restlessness in sleep, we investigated whether it might be a contributing factor in this special population. METHODS: This retrospective study involved medical record review of Angelman syndrome patients <18 years old who had attended our multidisciplinary Angelman syndrome clinic and had sleep complaints. Serum ferritin levels were compared to age- and sex-matched controls. Sleep history and nocturnal polysomnogram findings of the Angelman syndrome patients were also characterized. RESULTS: Nineteen Angelman syndrome patients (9 female, mean age 6.2±4.4 years) were identified. All 19 reported sleep difficulties. The mean serum ferritin level was 19.9±8.5 µg/L, while that in controls was 27.8±17.8 µg/L (P value .13). The odds ratio of iron deficiency in Angelman syndrome compared to controls was 4.17 (95% confidence interval 1.23-14.10), using normal serum ferritin level of 24 µg/L based on literature. Fifteen Angelman syndrome patients underwent nocturnal polysomnogram with 9/15 showing an elevated periodic limb movement index (overall mean 9.8±10.4). Seventeen of 19 received iron therapy. Twelve had follow-up after iron therapy, with parents reporting improved sleep quality. Eight had serum ferritin levels rechecked after iron therapy, showing a mean increase of 24±5.1 µg/L. CONCLUSIONS: Sleep difficulties in Angelman syndrome, though multifactorial, may in part be related to iron deficiency. Treatment with iron improved sleep to a modest degree in this population.

Appetite and ghrelin levels in iron deficiency anemia and the effect of parenteral iron therapy: A longitudinal study.

BACKGROUND: Iron deficiency anemia (IDA) is associated with decreased appetite. The ghrelin hormone is one of the major regulators of appetite. OBJECTIVES: To evaluate appetite and ghrelin levels in patients with IDA, and to investigate the change in appetite and ghrelin following intravenous iron therapy. METHODS: A total of 56 IDA patients and 51 controls were included in the study. Both appetite and ghrelin were assessed at baseline and following intravenous iron therapy. These were assessed at corresponding time intervals in the control group. Appetite was assessed by the SNAQ score (Simplified Nutritional Appetite Questionnaire) and fasting ghrelin levels were assessed by acylated ghrelin (AG), unacylated ghrelin (UAG) and their respective ratio AG/UAG. RESULTS: IDA patients had significantly lower SNAQ scores, yet higher AG levels and higher AG/UAG ratios compared to healthy controls; the mean SNAQ scores were 12.56 ± 3.45 and 16.1 ± 2, respectively (P<0.01); the median AG levels were 57.5 pg/ml and 43 pg/ml respectively (P = 0.007); and the median AG/UAG ratios were 0.48 and 0.25 respectively (P = 0.04). On multivariate linear regression analysis, IDA remained independently associated with decreased SNAQ score (ß = -0.524, P<0.001) and increased acylated ghrelin (ß = 0.289, P = 0.013). After IDA was treated, SNAQ scores increased significantly by a mean of 2 points. AG and AG/UAG ratios decreased significantly by a mean of -18.44 pg/ml and -0.2 respectively. The control group showed no significant change in SNAQ scores or ghrelin at corresponding time intervals. CONCLUSIONS: IDA patients have a reduced appetite and paradoxically elevated ghrelin hormone activity compared to healthy controls. Treating IDA enhances appetite and lowers ghrelin levels. Future studies are needed to explore the mechanism of this paradoxical ghrelin activity.

Delayed iron does not alter cognition or behavior among children with severe malaria and iron deficiency.

BACKGROUND: Malaria and iron deficiency (ID) in childhood are both associated with cognitive and behavioral dysfunction. The current standard of care for children with malaria and ID is concurrent antimalarial and iron therapy. Delaying iron therapy until inflammation subsides could increase iron absorption but also impair cognition. METHODS: In this study, Ugandan children 18 months to 5 years old with cerebral malaria (CM, n = 79), severe malarial anemia (SMA, n = 77), or community children (CC, n = 83) were enrolled and tested for ID. Children with ID were randomized to immediate vs. 28-day delayed iron therapy. Cognitive and neurobehavioral outcomes were assessed at baseline and 6 and 12 months (primary endpoint) after enrollment. RESULTS: All children with CM or SMA and 35 CC had ID (zinc protoporphyrin concentration ≥80 µmol/mol heme). No significant differences were seen at 12-month follow-up in overall cognitive ability, attention, associative memory, or behavioral outcomes between immediate and delayed iron treatment (mean difference (standard error of mean) ranged from -0.2 (0.39) to 0.98 (0.5), all P ≥ 0.06). CONCLUSIONS: Children with CM or SMA and ID who received immediate vs. delayed iron therapy had similar cognitive and neurobehavioral outcomes at 12-month follow-up. IMPACT: The optimal time to provide iron therapy in children with severe malaria is not known. The present study shows that delay of iron treatment to 28 days after the malaria episode, does not lead to worse cognitive or behavioral outcomes at 12-month follow-up. The study contributes new data to the ongoing discussion of how best to treat ID in children with severe malaria.

Anaemia, iron homeostasis and pulmonary hypertension: a review.

Anaemia is a highly prevalent condition, which negatively impacts on patients' cardiovascular performance and quality of life. Anaemia is mainly caused by disturbances of iron homeostasis. While absolute iron deficiency mostly as a consequence of chronic blood loss or insufficient dietary iron absorption results in the emergence of iron deficiency anaemia, inflammation-driven iron retention in innate immune cells and blockade of iron absorption leads to the development of anaemia of chronic disease. Both, iron deficiency and anaemia have been linked to the clinical course of pulmonary hypertension. Various mechanistic links between iron homeostasis, anaemia, and pulmonary hypertension have been described and current treatment guidelines suggest regular iron status assessment and the implementation of iron supplementation strategies in these patients. The pathophysiology, diagnostic assessment as well as current and future treatment options concerning iron deficiency with or without anaemia in individuals suffering from pulmonary hypertension are discussed within this review.

Iron deficiency in non-anemic chronic obstructive pulmonary disease in a predominantly male population: an ignored entity.

Non-anemic iron deficiency has been studied in heart failure, but studies are lacking in chronic obstructive pulmonary disease (COPD). The potential clinical implications of association of iron deficiency with the severity of COPD warrant research in this direction. This was an observational, cross-sectional study on patients with COPD to compare disease severity, functional status and quality of life in non-anemic patients with COPD between two groups - iron deficient and non-iron deficient. Stable non-anemic COPD with no cause of bleeding were evaluated for serum iron levels, ferritin levels, TIBC, 6MWD, SGRQ, spirometry, and CAT questionnaire. The study patients were divided into iron replete (IR) and iron deficient (ID) groups. A total of 79 patients were studied, out of which 72 were men and seven were women. The mean age was 61.5±8.42 years. Of these, 36 (45.5%; 95% CI, 34.3-56.8%) had iron deficiency. Mean 6-minute-walk distance was significantly shorter in ID (354.28±82.4 meters vs 432.5±47.21 meters; p=0.001). A number of exacerbations in a year were more in ID group (p=0.003), and more patients in ID had at least two exacerbations of COPD within a year (p=0.001). However, the resting pO2, SaO2, and SpO2 levels did not differ significantly between the two groups (p=0.15 and p=0.52, respectively). Also, there was no significant difference in the distribution of patients of a different class of airflow limitations between the two groups. Non-anemic iron deficiency (NAID) is an ignored, yet easily correctable comorbidity in COPD. Patients with iron deficiency have a more severe grade of COPD, had lesser exercise capacity and more exacerbations in a year as compared to non-iron deficient patients. So, foraying into the avenue of iron supplementation, which has shown promising results in improving functional capacity in heart failure and pulmonary hypertension, may well lead to revolutionary changes in the treatment of COPD.

Diagnosis and management of iron deficiency in children with or without anemia: consensus recommendations of the SPOG Pediatric Hematology Working Group.

Iron deficiency is the most prevalent nutritional deficiency affecting children and adolescents worldwide. A consistent body of epidemiological data demonstrates an increased incidence of iron deficiency at three timepoints: in the neonatal period, in preschool children, and in adolescents, where it particularly affects females.Conclusion: This narrative review focuses on the most suggestive symptoms of iron deficiency in childhood, describes the diagnostic procedures in situations with or without anemia, and provides Swiss expert-based management recommendations for the pediatric context.What is Known:• Iron deficiency (ID) is one of the most common challenges faced by pediatricians.• Significant progress in the diagnosis and therapy of ID has been made over the last decade.What is New:• Our expert panel provides ID management recommendations based on the best available evidence.• They include strategies for ID diagnosis and therapy, both oral and intravenous.