A meta-analysis of ferric carboxymaltose versus other intravenous iron preparations for the management of iron deficiency anemia during pregnancy.

Objective: We conducted a meta-analysis of randomized clinical trials evaluating the clinical effects of ferric carboxymaltose therapy compared to other intravenous iron in improving hemoglobin and serum ferritin in pregnant women. We also assessed the safety of ferric carboxymaltose vs. other intravenous iron. Data source: EMBASE, PubMed, and Web of Science were searched for trials related to ferric carboxymaltose in pregnant women, published between 2005 and 2021. We also reviewed articles from google scholar. The keywords "ferric carboxymaltose," "FCM," "intravenous," "randomized," "pregnancy," "quality of life," and "neonatal outcomes" were used to search the literature. The search was limited to pregnant women. Selection of studies: Studies related to ferric carboxymaltose in pregnancy were scanned. Observational studies, review articles, and case reports were excluded. Randomized studies in pregnant women involving ferric carboxymaltose and other intravenous iron formulations were shortlisted. Of 256 studies, nine randomized control trials were selected. Data collection: Two reviewers independently extracted data from nine selected trials. Data synthesis: The final effect size for increase in hemoglobin after treatment was significant for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 0.89g/dl [95% confidence interval 0.27,1.51]). The final effect size for the increase in ferritin after treatment was more for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 22.53µg/L [-7.26, 52.33]). No serious adverse events were reported with ferric carboxymaltose or other intravenous iron. Conclusion: Ferric carboxymaltose demonstrated better efficacy than other intravenous iron in increasing hemoglobin and ferritin levels in treating iron deficiency anemia in pregnant women.

Efficacy of ferric carboxymaltose on haemoglobin response among older patients with gastrointestinal bleeding: a randomised clinical trial.

BACKGROUND: Acute gastrointestinal bleeding (AGIB) is common in older patients but the use of iron in this context remains understudied. AIMS: This study aimed to evaluate prospectively the efficacy of ferric carboxymaltose to treat anaemia in older patients after AGIB. METHODS: This randomised double-blinded placebo-controlled clinical trial was conducted in 10 French centres. Eligible patients were 65 years or more, had controlled upper or lower gastrointestinal bleeding and a haemoglobin level of 9-11 g/dl. Patients were randomly assigned, in a 1:1 ratio, to receive either one intravenous iron injection of ferric carboxymaltose or one injection of saline solution. The primary endpoint was the difference in haemoglobin level between day 0 and day 42. Secondary endpoints were treatment-emergent adverse events, serious adverse events, rehospitalisation and improvement of quality of life (QOL) at day 180. RESULTS: From January 2013 to January 2017, 59 patients were included. The median age of patients was 81.9 [75.8, 87.3] years. At day 42, a significant difference in haemoglobin level increase was observed (2.49 g/dl in the ferric carboxymaltose group vs. 1.56 g/dl in the placebo group, P = 0.02). At day 180, QOL, measured on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, improved by 10.5 points in the ferric carboxymaltose group and by 8.2 points in the placebo group (P = 0.56). Rates of adverse events and rehospitalisation were similar in the two groups. CONCLUSIONS: Intravenous iron seems safe and effective to treat anaemia in older patients after AGIB and should be considered as a standard-of-care treatment. ClinicalTrials.gov (NCT01690585).

Clinical efficacy and safety of intravenous ferric carboxymaltose for treatment of restless legs syndrome: a multicenter, randomized, placebo-controlled clinical trial.

STUDY OBJECTIVES: Iron therapy is associated with improvements in restless legs syndrome (RLS). This multicenter, randomized, double-blind study evaluated the effect of intravenous ferric carboxymaltose (FCM) on RLS. METHODS: A total of 209 adult patients with a baseline International RLS (IRLS) score ≥ 15 were randomized (1:1) to FCM (750 mg/15 mL) or placebo on study days 0 and 5. Ongoing RLS medication was tapered starting on Day 5, with the goal of discontinuing treatment or achieving the lowest effective dose. Co-primary efficacy endpoints were changed from baseline in IRLS total score and the proportion of patients rated as much/very much improved on the Clinical Global Impression (CGI)-investigator (CGI-I) scale at day 42 in the "As-Treated" population. RESULTS: The "As-Treated" population comprised 107 FCM and 101 placebo recipients; 88 (82.2%) and 68 (67.3%), respectively, completed the day 42 assessment. The IRLS score reduction was significantly greater with FCM versus placebo: least-squares mean (95% confidence interval [CI]) -8.0 (-9.5, -6.4) versus -4.8 (-6.4, -3.1); p = .0036. No significant difference was observed in the proportion of FCM (35.5%) and placebo (28.7%) recipients with a CGI-I response (odds ratio 1.37 [95% CI: 0.76, 2.47]; p = .2987). Fewer patients treated with FCM (32.7%) than placebo (59.4%) received RLS interventions between day 5 and study end (p = .0002). FCM was well tolerated. CONCLUSIONS: The IRLS score improved with intravenous FCM versus placebo, although the combination of both co-primary endpoints was not met. Potential methodological problems in the study design are discussed.

Cellular signaling in the hypoxic cancer microenvironment: Implications for drug resistance and therapeutic targeting.

The rewiring of cellular metabolism is a defining characteristic of cancer, as tumor cells adapt to acquire essential nutrients from a nutrient-poor environment to sustain their viability and biomass. While hypoxia has been identified as a major factor depriving cancer cells of nutrients, recent studies have revealed that cancer cells distant from supporting blood vessels also face nutrient limitations. To overcome this challenge, hypoxic cancer cells, which heavily rely on glucose as an energy source, employ alternative pathways such as glycogen metabolism and reductive carboxylation of glutamine to meet their energy requirements for survival. Our preliminary studies, alongside others in the field, have shown that under glucose-deficient conditions, hypoxic cells can utilize mannose and maltose as alternative energy sources. This review aims to comprehensively examine the hypoxic cancer microenvironment, its association with drug resistance, and potential therapeutic strategies for targeting this unique niche. Furthermore, we will critically evaluate the current literature on hypoxic cancer microenvironments and explore state-of-the-art techniques used to analyze alternate carbohydrates, specifically mannose and maltose, in complex biological fluids. We will also propose the most effective analytical methods for quantifying mannose and maltose in such biological samples. By gaining a deeper understanding of the hypoxic cancer cell microenvironment and its role in drug resistance, novel therapeutic approaches can be developed to exploit this knowledge.

Patient reported outcome measures and cardiovascular outcomes following high dose modern intravenous iron in non-dialysis dependent chronic kidney disease: secondary analysis of ExplorIRON-CKD.

Intravenous iron is commonly used to treat iron deficiency anemia in non-dialysis chronic kidney disease (ND-CKD). There is a paucity of information on the potential impact of intravenous iron on patient reported outcome measures, functional status and markers of cardiovascular health. As part of the secondary analysis of this double-blind exploratory randomized controlled trial focusing on patients with iron deficiency (+ /- anemia) and ND-CKD (serum ferritin < 200 µg/L or transferrin saturation ≤ 20% and serum ferritin 200-299 µg/L; CKD stages: 3a-5), 26 patients were randomized in a 1:1 ratio to receive ferric derisomaltose or ferric carboxymaltose. Participants received 1000 mg at baseline and 500-1000 mg at one month to achieve iron repletion. Quality of life and fatigue status were assessed using the Short-Form (36) questionnaire and the fatigue severity scale. Functional status was evaluated using the Duke Activity Status Index and the 1-min-sit-to-stand test. Cardiac markers such as NT-proBNP, Troponin T and pulse wave velocity were monitored. Intravenous iron was associated with similar improvements in most domains of the Short-Form (36) questionnaire, fatigue status, and 1-min-sit-to-stand ability increased significantly by the end of the trial in both groups (p < 0.001). Markers of cardiac function remained stable, with no arterial stiffness impact. Longer term studies are required to further evaluate the impact of intravenous iron on quality of life and cardiac safety in patients with ND-CKD.

Intravenous iron administration before cardiac surgery reduces red blood cell transfusion in patients without anaemia.

BACKGROUND: Reducing the need for blood transfusion among patients undergoing cardiac surgery FLA reduce postoperative complications and mortality. Our study aimed to assess the effects of administering preoperative i.v. ferric carboxymaltose on postoperative red cell transfusion requirements in patients without anaemia undergoing on-pump cardiac surgery. METHODS: This double-blind, randomised, placebo-controlled trial was conducted between October 2016 and November 2019, with a follow-up period of up to 6 weeks after surgery. Patients without anaemia who underwent on-pump cardiac surgery were included as participants and administered i.v. iron in the form of ferric carboxymaltose or placebo once, 24-72 h before surgery. The primary outcome was the number of red cell units transfused during the first four postoperative days, and the secondary outcome measures were blood haemoglobin concentrations at 4 days and 6 weeks after surgery. RESULTS: The 200 patients included were randomly assigned to the ferric carboxymaltose (n=102) and placebo (n=98) groups. By postoperative Day 4, a significantly lower mean number of red cell units were transfused in the ferric carboxymaltose than in the placebo group, 0.3 (0.8) vs 1.6 (4.4), respectively; P=0.007. The mean haemoglobin concentrations on postoperative Day 4 were 9.7 (1) g dl-1 and 9.3 (1) g dl-1, respectively (P=0.03). Corresponding values at 6 weeks after surgery were 12.6 (1.4) g dl-1 and 11.8 (1.5) g dl-1, respectively (P=0.012). CONCLUSIONS: In patients without anaemia undergoing on-pump cardiac surgery, treatment with a single dose of 1000 mg ferric carboxymaltose i.v. 1-3 days before surgery significantly reduced the need for red cell transfusions and increased the postoperative haemoglobin concentration. CLINICAL TRIAL REGISTRATION: NCT02939794.

In HF with iron deficiency, IV ferric derisomaltose was associated with lower rates of HF hospitalization or CV death.

SOURCE CITATION: Kalra PR, Cleland JG, Petrie MC, et al. Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial. Lancet. 2022;400:2199-209. 36347265.

Impact of ferric carboxymaltose for iron deficiency at discharge after heart failure hospitalization: a European multinational economic evaluation.

AIMS: Iron deficiency (ID) is comorbid in up to 50% patients with heart failure (HF) and exacerbates disease burden. Ferric carboxymaltose (FCM) reduced HF hospitalizations and improved quality of life when used to treat ID at discharge in patients hospitalized for acute HF with left ventricular ejection fraction <50% in the AFFIRM-AHF trial. We quantified the effect of FCM on burden of disease and the wider pharmacoeconomic implications in France, Germany, Poland, Spain and Sweden. METHODS AND RESULTS: The per country eligible population was calculated, aligning with the 2021 European Society of Cardiology (ESC) HF guidelines and the AFFIRM-AHF trial. Changes in burden of disease with FCM versus standard of care (SoC) were represented by disability-adjusted life years (DALYs), hospitalization episodes and bed days, using AFFIRM-AHF data. A Markov model was adapted to each country to estimate cost-effectiveness and combined with epidemiology data to calculate the impact on healthcare budgets. Between 335 (Sweden) and 13 237 (Germany) DALYs were predicted to be avoided with FCM use annually. Fewer hospitalizations and shorter lengths of stay associated with FCM compared to SoC were projected to result in substantial annual savings in bed days, from 5215 in Sweden to 205 630 in Germany. In all countries, FCM was predicted to be dominant (cost saving with gains in quality-adjusted life years), resulting in net savings to healthcare budgets within 1 year. CONCLUSIONS: This comprehensive evaluation of FCM therapy highlights the potential benefits that could be realized through implementation of the ESC HF guideline recommendations regarding ID treatment.

Clinical and economic impact of ferric carboxymaltose treatment for iron deficiency in patients stabilized following acute heart failure: a multinational study.

OBJECTIVE: To estimate clinical events and evaluate the financial implications of introducing ferric carboxymaltose (FCM) to treat iron deficiency (ID) at discharge in patients hospitalized for acute heart failure (AHF) with left ventricular ejection fraction (LVEF) <50% in the UK, Switzerland and Italy. METHODS: A decision analytic cost-offset model was developed to evaluate the costs associated with introducing FCM for all eligible patients in three countries compared to a world without FCM, over a five-year time horizon. Data from AFFIRM-AHF clinical trial were used to model clinical outcomes, using an established cohort state-transition Markov model. Country-specific prevalence estimates were derived using data from real-world studies to extrapolate number of events and consequent cost totals to the population at risk on a national scale. RESULTS: The cost-offset modeling demonstrated that FCM is projected to be a cost-saving intervention in all three country settings over a five-year time horizon. Savings were driven primarily by reduced hospitalizations and avoided cardiovascular deaths, with net cost savings of -£14,008,238, -CHF25,456,455 and -€105,295,146 incurred to the UK, Switzerland and Italy, respectively. LIMITATIONS: Although AFFIRM-AHF was a multinational trial, efficacy data per country was not sufficiently large to enable country-specific analysis, therefore overall clinical parameters have been assumed to apply to all countries. CONCLUSIONS: This study provides further evidence of the potential cost savings achievable by treating ID with FCM at discharge in patients hospitalized for AHF with LVEF <50%. The value of FCM treatment within the healthcare systems of the UK, Switzerland and Italy was demonstrated even within a limited time frame of one year, with consistent cost savings indicated over a longer term.

Ferric Carboxymaltose Versus Ferrous Fumarate in Anemic Children with Inflammatory Bowel Disease: The POPEYE Randomized Controlled Clinical Trial.

OBJECTIVE: To determine whether intravenous (IV) or oral iron suppletion is superior in improving physical fitness in anemic children with inflammatory bowel disease (IBD). STUDY DESIGN: We conducted a clinical trial at 11 centers. Children aged 8-18 with IBD and anemia (defined as hemoglobin [Hb] z-score < -2) were randomly assigned to a single IV dose of ferric carboxymaltose or 12 weeks of oral ferrous fumarate. Primary end point was the change in 6-minute walking distance (6MWD) from baseline, expressed as z-score. Secondary outcome was a change in Hb z-score from baseline. RESULTS: We randomized 64 patients (33 IV iron and 31 oral iron) and followed them for 6 months. One month after the start of iron therapy, the 6MWD z-score of patients in the IV group had increased by 0.71 compared with -0.11 in the oral group (P = .01). At 3- and 6-month follow-ups, no significant differences in 6MWD z-scores were observed. Hb z-scores gradually increased in both groups and the rate of increase was not different between groups at 1, 3, and 6 months after initiation of iron therapy (overall P = .97). CONCLUSION: In this trial involving anemic children with IBD, a single dose of IV ferric carboxymaltose was superior to oral ferrous fumarate with respect to quick improvement of physical fitness. At 3 and 6 months after initiation of therapy, no differences were discovered between oral and IV therapies. The increase of Hb over time was comparable in both treatment groups. TRIAL REGISTRATION: NTR4487 [Netherlands Trial Registry].

Effect of intravenous ferric carboxymaltose on exercise capacity and quality of life in patients with COPD : A pilot study.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is associated with reduced exercise capacity. In COPD iron deficiency is found in up to 50% of patients and may impair exercise capacity, the potential therapeutic effect is yet unknown. We aimed to estimate the beneficial effect of intravenous ferric carboxymaltose on exercise capacity and quality of life in patients with COPD. METHODS: In this non-randomized, interrupted time series pilot trial we enrolled outpatients with stable COPD (GOLD II and III) and nonanemic iron deficiency (i.e., ferritin level < 100 µg/l or ferritin level 100-300 µg/l if transferrin saturation < 20%). Patients with cardiovascular-or inflammatory diseases were excluded. Participants performed 6­minute walking test (6-MWT) and cardiopulmonary exercise testing (CPET) and completed the St. George's Respiratory Questionnaire (SGRQ). RESULTS: From 35 screened patients, 11 (72% male, 63 ± 8 years, FEV1%predicted 44 ± 14) were included. Mean ferritin and hemoglobin were 70 ± 41 µg/l and 13.8 ± 1.7 g/dl, respectively. Four weeks after iron administration the 6­MWT distance increased by 34.7 ± 34.4 m (95% CI, 10.0-59.3); p = 0.011. The VO2max increased by 1.87 ± 1.2 ml/kg/min (95% CI, 0.76-3); p = 0.006. Mean score of SGRQ was reduced by 7.56 ± 6.12 units (95% CI, 3 to 11); p = 0.004. The insignificant alteration in hemoglobin did not correlate with increase in exercise capacity. CONCLUSION: Administration of intravenous iron was associated with improved exercise capacity and quality of life in stable COPD patients independent of hemoglobin. Our data provide a basis to calculate a statistically sufficient sample size for a randomized controlled follow-up study.

Testing equivalence of two doses of intravenous iron to treat iron deficiency in pregnancy: A randomised controlled trial.

OBJECTIVE: To test the equivalence of two doses of intravenous iron (ferric carboxymaltose) in pregnancy. DESIGN: Parallel, two-arm equivalence randomised controlled trial with an equivalence margin of 5%. SETTING: Single centre in Australia. POPULATION: 278 pregnant women with iron deficiency. METHODS: Participants received either 500 mg (n = 152) or 1000 mg (n = 126) of intravenous ferric carboxymaltose in the second or third trimester. MAIN OUTCOME MEASURES: The proportion of participants requiring additional intravenous iron (500 mg) to achieve and maintain ferritin >30 microg/L (diagnostic threshold for iron deficiency) at 4 weeks post-infusion, and at 6 weeks, and 3-, 6- and 12-months postpartum. Secondary endpoints included repeat infusion rate, iron status, birth and safety outcomes. RESULTS: The two doses were not equivalent within a 5% margin at any time point. At 4 weeks post infusion, 26/73 (36%) participants required a repeat infusion in the 500-mg group compared with 5/67 (8%) in the 1000-mg group: difference in proportions, 0.283 (95% confidence interval [CI] 0.177-0.389). Overall, participants in the 500-mg arm received twice the repeat infusion rate (0.81 [SD = 0.824] versus 0.40 [SD = 0.69], rate ratio 2.05, 95% CI 1.45-2.91). CONCLUSIONS: Administration of 1000 mg ferric carboxymaltose in pregnancy maintains iron stores and reduces the need for repeat infusions. A 500- mg dose requires ongoing monitoring to ensure adequate iron stores are reached and sustained.

The effect of immediate postoperative intravenous administration of ferric carboxymaltose after autologous free-flap breast reconstruction.

Intravenous ferric carboxymaltose (IV-FCM) can effectively correct perioperative anemia in patients undergoing major surgeries. However, its efficacy and side effects in patients undergoing free flap-based breast reconstruction are yet to be investigated. At our institution, from year 2020, patients with breast cancer undergoing abdominal free flap-based breast reconstruction were injected 500 mg of IV-FCM immediately post-operation. Propensity-matched 82 IV-FCM injected (study group) and 164 historical control group patients were retrospectively analyzed for transfusion rates, changes in hematological parameters, and flap or donor-site related complications. The major and minor complication rates related to the operation site were similar between the two groups. There was no significant difference in the transfusion rate between the two groups (control 29.9% vs. study 32.9%, p = 0.71). However, the total amount of transfusion required was significantly higher in the historical control group (control-53.2% 1 pack, 42.6% 2 packs, 4.3% 3 packs of RBC vs. Study-66.7% 1 pack, 33.3% 2 packs, p = 0.02) than in the study group. Additionally, the historical control group showed a significantly higher drop in red blood cell count, hemoglobin, and hematocrit levels from postoperative days 1-2 and 2-3 compared to the study group. Immediate postoperative use of IV-FCM in free flap-based breast reconstruction was well tolerated by patients and reduced overall transfusion volume.

Real-world experience of intravenous ferric derisomaltose evaluated through safety and efficacy reporting in the UK.

Ferric derisomaltose (FDI; Monofer) is used in clinical practice to treat iron deficiency, but the safety and efficacy of FDI has not been robustly evaluated in a large real-world study. This retrospective, multicentre, audit-based, observational study provides pragmatic information about safety and clinical responses with FDI across therapy areas and patient populations, helping to facilitate treatment decisions. Participating sites provided data from the medical records of adults who had received ≥ 1 FDI infusion. The primary outcome was the incidence of adverse reactions within 24 hours of the FDI infusion. Secondary outcomes included the change from baseline in haemoglobin and ferritin up to 12 months post infusion. In total, 19 sites provided data for a total of 7354 FDI-treated patients; 64.3% of patients were female, and 42.2% were aged ≥ 70 years. Surgery was the main hospital specialty (34.5%). The incidence of any recorded adverse reactions, hypersensitivity reactions, and anaphylaxis were 1.7%, 0.4%, and < 0.1%, respectively, regardless of baseline anaemia status. Statistically significant increases in haemoglobin and ferritin were observed between baseline and Month 4 following FDI treatment (p < 0.0001). Improvements in haemoglobin were more pronounced for hospital specialties where operative blood loss is expected (surgery/obstetrics) compared with those where blood loss is not expected. This study provides real-world clinical evidence for the low risk of adverse reactions with FDI across diverse patient populations, providing reassurance that intravenous iron is not associated with serious toxicity. These findings may inform changes in intravenous iron delivery to provide effective therapy to more patients in need.

Clinical, economical and safety impact of ferric carboxymaltose use in Patient Blood Management programme in Portuguese National Health Service hospitals.

Ferric carboxymaltose (FCM) can be used in Patient Blood Management (PBM) to promote the optimization of preoperative haemoglobin (Hb), which aims to minimise the use of allogeneic blood components and improve clinical outcomes, with better cost-effectiveness. This was an observational study conducted in a retrospective and multicentre cohort with adults from elective orthopaedic, cardiac and colorectal surgeries, treated according to local standards of PBM with allogeneic blood product transfusions (ABTs) on demand and with FCM to correct iron deficiency with or without anaemia. In this work, only the first pillar of the PBM model issue by Directorate-General for Health (DGS) was evaluated, which involves optimising Hb in the preoperative period with iron treatment if it's necessary/indicated. Before the implementation of PBM in Portugal, most patients did not undergo preoperative laboratory evaluation with blood count and iron kinetics. Therefore, the existence of Iron Deficiency Anaemia (IDA) or Iron Deficiency (ID) without anaemia was not early detected, and there was no possibility of treating these patients with iron in order to optimise their Hb and/or iron stores. Those patients ended up being treated with ABTs on demand. A total of 405 patients from seven hospitals were included; 108 (26.7%) underwent FCM preoperatively and 197 (48.6%) were transfused with ABTs on demand. In the FCM preoperative cohort, there was an increase in patients with normal preoperative Hb, from 14.4 to 45.7%, before and after FCM, respectively, a decrease from 31.7 to 9.6% in moderate anaemia and no cases of severe anaemia after FCM administration, while 7.7% of patients were severely anaemic before FCM treatment. There were significant differences (p < 0.001) before and after correction of preoperative anaemia and/or iron deficiency with FCM in Hb, serum ferritin and transferrin saturation rate (TS). In the ABT group, there were significant differences between pre- and postoperative Hb levels (p < 0.001). Hb values tended to decrease, with 44.1% of patients moving from mild anaemia before transfusion to moderate anaemia in the postoperative period. Concerning the length of hospital stay, the group administered with ABTs had a longer hospital stay (p < 0.001). Regarding the clinical outcomes of nosocomial infection and mortality, there was no evidence that the rate of infection or mortality differed in each group (p = 0.075 and p = 0.243, respectively). However, there were fewer nosocomial infections in the FCM group (11.9% versus 21.2%) and mortality was higher in the transfusion group (21.2% versus 4.2%). Economic analysis showed that FCM could reduce allogenic blood products consumption and the associated costs. The economic impact of using FCM was around 19%. The preoperative Hb value improved when FMC was used. Patients who received ABTs appeared to have a longer hospital stay. The FCM group reported fewer infections during hospitalisation. The economic results showed savings of around €1000 for each patient with FCM administration. The use of FCM as part of the PBM program had a positive impact on patients' outcomes and on economic results. However, it will be essential to perform studies with a larger sample to obtain more robust and specific results.

Fine-tuned cholesterol solubilizer, mono-6-O-α-D-maltosyl-γ-cyclodextrin, ameliorates experimental Niemann-Pick disease type C without hearing loss.

Niemann-Pick disease type C (NPC) is a fatal disorder with abnormal intracellular cholesterol trafficking resulting in neurodegeneration and hepatosplenomegaly. A cyclic heptasaccharide with different degrees of substitution of 2-hydroxypropyl groups, 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD), acts as a strong cholesterol solubilizer and is under investigation for treating this disease in clinical trials, but its physicochemical properties and ototoxicity remain a concern. Here, we evaluated the potential of mono-6-O-α-maltosyl-γ-CD (G2-γ-CD), a single-maltose-branched cyclic octasaccharide with a larger cavity than HP-ß-CD, for treating NPC. We identified that G2-γ-CD ameliorated NPC manifestations in model mice and showed lower ototoxicity in mice than HP-ß-CD. To investigate the molecular mechanisms of action behind the differential ototoxicity of these CDs, we performed cholesterol solubility analysis, proton nuclear magnetic resonance spectroscopy, and molecular modeling, and estimated that the cholesterol inclusion mode of G2-γ-CD maintained solely the 1:1 inclusion complex, whereas that of HP-ß-CD shifted to the highly-soluble 2:1 complex at higher concentrations. We predicted the associations of these differential complexations of CDs with cholesterol with the profile of disease attenuation and of the auditory cell toxicity using specific cell models. We proposed that G2-γ-CD can serve as a fine-tuned cholesterol solubilizer for treating NPC, being highly biocompatible and physicochemically suitable for clinical application.

Efficacy of high-dose intravenous iron in middle-aged to elderly iron-deficient patients.

Iron deficiency (ID) impacts about fifty percent of elderly patients with many symptoms present before iron deficiency anaemia . If left untreated, ID may increase morbidity and mortality. Oral iron is often not tolerated or the absorption is suboptimal. We describe our initial experiences of using high-dose intravenous ferric derisomaltose (Monofer®) infusions of 500 and 1000mg for iron deficiency and iron deficiency anaemia respectively in the outpatient setting. Rapid correction of laboratory parameters and improvement in common symptoms (such as fatigue) were observed. Intravenous iron may be an option for symptomatic iron deficient patients unsuitable for oral iron.

Comparative efficacy of intravenous and oral iron supplements for the treatment of iron deficiency in patients with heart failure: A network meta-analysis of randomized controlled trials.

OBJECTIVE: We aimed at comparing the efficacy of intravenous and oral iron supplementations for the treatment of iron deficiency (ID) in patients with heart failure (HF). METHODS: We searched the PubMed, Cochrane, and Embase databases from inception to January 15, 2022. We included randomized controlled trials enrolling patients with HF who were treated for ID with intravenous iron supplements, oral iron supplements, or placebo. The primary outcomes were all-cause death, cardiovascular mortality, and hospitalization for heart failure. The secondary outcomes were evaluated through the six-minute walking test (6MWT) and the Kansas City Cardiomyopathy Questionnaire (KCCQ). RESULTS: The network meta-analysis included sixteen studies. Compared to placebo/control groups, intravenous iron supplements did not decrease all-cause death (0.69, 0.39-1.23) or cardiovascular mortality (0.89, 0.66-1.20). After 12 weeks, a reduced hospitalization for heart failure was associated with the administration of intravenous iron supplementations (0.58, 0.34-0.97). The most significant improvements regarding 6MWT (44.44, 6.10-82.79) and KCCQ (5.96, 3.19-8.73) were observed with intravenous iron supplements. Oral iron supplements reduced hospitalization for heart failure (0.36, 0.14-0.96) and all-cause death (0.34, 0.12-0.95), but did not influence the 6MWT (29.74, -47.36 to 106.83) and KCCQ (0.10, -10.95 to 11.15). CONCLUSIONS: Administering intravenous iron supplements for ID in patients with HF improves their exercise capacity and quality of life. In order to reduce hospitalizations for heart failure, the supplementation should be administered for more than 12 weeks. Although oral iron supplements did not improve exercise capacity and quality of life, they could reduce all-cause death and hospitalizations for heart failure.