Ferritin Cutoffs and Diagnosis of Iron Deficiency in Primary Care.

Importance: Ferritin is often measured by general practitioners, but the association of different cutoffs with the rates of iron deficiency diagnoses, particularly nonanemic iron deficiency, is unknown. Objective: To investigate the association of the ferritin cutoff choice with the incidence of nonanemic and anemic iron deficiency diagnoses in primary care. Design, Setting, and Participants: In this retrospective cohort study, patients 18 years or older with at least 1 consultation with a general practitioner participating in the Family Medicine Research Using Electronic Medical Records (FIRE) project, an electronic medical records database of Swiss primary care, from January 1, 2021, to November 30, 2023, were evaluated. Exposures: Sex, age, clinical patient characteristics, and professional general practitioner characteristics. Main Outcomes and Measures: Incidence of iron deficiency diagnoses (nonanemic and anemic) at ferritin cutoffs of 15, 30, and 45 ng/mL and ferritin testing itself. Time-dependent Cox proportional hazards regression was used to examine associations of patient and general practitioner characteristics with ferritin testing as adjusted hazard ratios (AHRs). Results: The study included 255 351 patients (median [IQR] age, 52 [36-66] years; 52.1% female). Per 1000 patient-years and at ferritin cutoffs of 15, 30, and 45 ng/mL, iron deficiency diagnoses had incidences of 10.9 (95% CI, 10.6-11.2), 29.9 (95% CI, 29.4-30.4), and 48.3 (95% CI, 47.7-48.9) cases, respectively; nonanemic iron deficiency diagnoses had incidences of 4.1 (95% CI, 3.9-4.2), 14.6 (95% CI, 14.3-15.0), and 25.8 (95% CI, 25.3-26.2) cases, respectively; and anemic iron deficiency diagnoses had incidences of 3.5 (95% CI, 3.3-3.7), 6.0 (95% CI, 5.8-6.2), and 7.5 (95% CI, 7.3-7.7) cases, respectively. Ferritin testing showed notable associations with fatigue (AHR, 2.03; 95% CI, 1.95-2.12), anemia (AHR, 1.75; 95% CI, 1.70-1.79), and iron therapy (AHR, 1.50; 95% CI, 1.46-1.54). Ferritin testing was associated with female sex in all age groups, including postmenopausal. Of the patients who received ferritin testing, 72.1% received concomitant hemoglobin testing, and 49.6% received concomitant C-reactive protein testing. Conclusions and Relevance: In this retrospective cohort study of primary care patients, ferritin cutoffs of 30 and 45 ng/mL were associated with a substantially higher incidence of iron deficiency compared with 15 ng/mL. These results provide a basis for health system-level evaluation and benchmarking of ferritin testing in high-resource settings and call for a harmonization of diagnostic criteria for iron deficiency in primary care.

Iron-dependent KDM4D activity controls the quiescence-activity balance of MSCs via the PI3K-Akt-Foxo1 pathway.

Iron deficiency is a prevalent nutritional deficit associated with organ damage and dysfunction. Recent research increasingly associates iron deficiency with bone metabolism dysfunction, although the precise underlying mechanisms remain unclear. Some studies have proposed that iron-dependent methylation-erasing enzyme activity regulates cell proliferation and differentiation under physiological or pathological conditions. However, it remains uncertain whether iron deficiency inhibits the activation of quiescent mesenchymal stem cells (MSCs) by affecting histone demethylase activity. In our study, we identified KDM4D as a key player in the activation of quiescent MSCs. Under conditions of iron deficiency, the H3K9me3 demethylase activity of KDM4D significantly decreased. This alteration resulted in increased heterochromatin with H3K9me3 near the PIK3R3 promoter, suppressing PIK3R3 expression and subsequently inhibiting the activation of quiescent MSCs via the PI3K-Akt-Foxo1 pathway. Iron-deficient mice displayed significantly impaired bone marrow MSCs activation and decreased bone mass compared to normal mice. Modulating the PI3K-Akt-Foxo1 pathway could reverse iron deficiency-induced bone loss.

The Effects of Prenatal Iron Supplementation on Offspring Neurodevelopment in Upper Middle- or High-Income Countries: A Systematic Review.

Iron supplementation is commonly recommended for the prevention and treatment of maternal iron deficiency (ID) or iron deficiency anemia (IDA). However, the impacts of prophylactic of therapeutic prenatal iron supplementation on child neurodevelopment in upper middle-income (UMI) and high-income countries (HICs), where broad nutritional deficiencies are less common, are unclear. To investigate this, we conducted a systematic review, searching four databases (Medline, CINAHL, EMBASE, Cochrane Library) through 1 May 2023. Randomized controlled trials (RCTs) assessing oral or intravenous iron supplementation in pregnant women reporting on child neurodevelopment (primary outcome: age-standardized cognitive scores) were eligible. We included three RCTs (five publications) from two HICs (Spain and Australia) (N = 935 children; N = 1397 mothers). Due to clinical heterogeneity of the RCTs, meta-analyses were not appropriate; findings were narratively synthesized. In non-anemic pregnant women, prenatal iron for prevention of IDA resulted in little to no difference in cognition at 40 days post-partum (1 RCT, 503 infants; very low certainty evidence). Similarly, the effect on the intelligence quotient at four years was very uncertain (2 RCTs, 509 children, very low certainty evidence). No RCTs for treatment of ID assessed offspring cognition. The effects on secondary outcomes related to language and motor development, or other measures of cognitive function, were unclear, except for one prevention-focused RCT (302 children), which reported possible harm for children's behavioral and emotional functioning at four years. There is no evidence from UMI countries and insufficient evidence from HICs to support or refute benefits or harms of prophylactic or therapeutic prenatal iron supplementation on child neurodevelopment.

Iron Deficiency and Sleep/Wake Behaviors: A Scoping Review of Clinical Practice Guidelines-How to Overcome the Current Conundrum?

Current evidence suggests that iron deficiency (ID) plays a key role in the pathogenesis of conditions presenting with restlessness such as attention deficit hyperactivity disorder (ADHD) and restless legs syndrome (RLS). In clinical practice, ID and iron supplementation are not routinely considered in the diagnostic work-up and/or as a treatment option in such conditions. Therefore, we conducted a scoping literature review of ID guidelines. Of the 58 guidelines included, only 9 included RLS, and 3 included ADHD. Ferritin was the most frequently cited biomarker, though cutoff values varied between guidelines and depending on additional factors such as age, sex, and comorbidities. Recommendations surrounding measurable iron biomarkers and cutoff values varied between guidelines; moreover, despite capturing the role of inflammation as a concept, most guidelines often did not include recommendations for how to assess this. This lack of harmonization on the interpretation of iron and inflammation biomarkers raises questions about the applicability of current guidelines in clinical practice. Further, the majority of ID guidelines in this review did not include the ID-associated disorders, ADHD and RLS. As ID can be associated with altered movement patterns, a novel consensus is needed for investigating and interpreting iron status in the context of different clinical phenotypes.

Impact of Iron Intake and Reserves on Cognitive Function in Young University Students.

Iron is a key nutrient for cognitive function. During periods of high academic demand, brain and cognitive activity increase, potentially affecting iron intake and reserves. The present study aimed to investigate the impact of iron levels on cognitive function in a university sample, considering the influence of gender. A cross-sectional study was conducted with 132 university students (18-29 years) from the University of Castilla-La Mancha (Spain). A dietary record was formed through a questionnaire to analyze iron consumption, and blood and anthropometric parameters were measured. The Wechsler Adult Intelligence Scale-IV was used to determine the Intelligence Quotient (IQ), as well as the Verbal Comprehension Index (VCI), Working Memory Index (WMI), Processing Speed Index (PSI), and Perceptual Reasoning Index (PRI), to assess cognitive abilities. Among women, the prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) was 21% and 4.2%, respectively. No ID or IDA was found in men. The impact of iron intake on IQ and cognitive abilities was mainly associated with the female population, where a positive association between iron intake, serum ferritin, and total IQ was revealed. In conclusion, low iron intake is related to poorer intellectual ability, suggesting that an iron-rich diet is necessary to maintain the academic level of university students.

Comprehensive perioperative blood management in patients undergoing elective bypass cardiac surgery: Benefit effect of health care education and systematic correction of iron deficiency and anemia on red blood cell transfusion.

STUDY OBJECTIVE: The aim of this study was to investigate the efficacy of a two-step patient blood management (PBM) program in red blood cell (RBC) transfusion requirements among patients undergoing elective cardiopulmonary bypass (CPB) surgery. DESIGN: Prospective, non-randomized, two-step protocol design. SETTING: Cardiac surgery department of Clinique Pasteur, Toulouse, France. PATIENTS: 897 patients undergoing for elective CPB surgery. INTERVENTIONS: We conducted a two-steps protocol: PBMe and PBMc. PBMe involved a short quality improvement program for health care workers, while PBMc introduced a systematic approach to pre- and postoperative correction of deficiencies, incorporating iron injections, oral vitamins, and erythropoiesis-stimulating agents. MEASUREMENTS: The PBM program's effectiveness was evaluated through comparison with a pre-PBM retrospective cohort after propensity score matching. The primary objective was the proportion of patients requiring RBC transfusions during their hospital stay. Secondary objectives were also analyzed. MAIN RESULTS: After matching, 343 patients were included in each group. Primary outcomes were observed in 35.7% (pre-PBM), 26.7% (PBMe), and 21.1% (PBMc) of patients, resulting in a significant reduction (40.6%) in the overall RBC transfusion rate. Both the PBMe and PBMc groups exhibited significantly lower risks of RBC transfusion compared to the pre-PBM group, with adjusted odds ratios of 0.59 [95% CI 0.44-0.79] and 0.44 [95% CI 0.32-0.60], respectively. Secondary endpoints included reductions in transfusions exceeding 2 units, total RBC units transfused, administration of allogeneic blood products, and total bleeding volume recorded on Day 1. There were no significant differences noted in mortality rates or the duration of hospital stays. CONCLUSIONS: This study suggests that health care education and systematic deficiency correction are associated with reduced RBC transfusion rates in elective CPB surgery. However, further randomized, controlled studies are needed to validate these findings and refine their clinical application.

Screening and Supplementation for Iron Deficiency and Iron Deficiency Anemia During Pregnancy: US Preventive Services Task Force Recommendation Statement.

Importance: Iron deficiency is the leading cause of anemia during pregnancy. According to survey data from 1999 to 2006, overall estimated prevalence of iron deficiency during pregnancy is near 18% and increases across the 3 trimesters of pregnancy (from 6.9% to 14.3% to 28.4%). An estimated 5% of pregnant persons have iron deficiency anemia. Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the evidence on the benefits and harms of screening and supplementation for iron deficiency with and without anemia on maternal and infant health outcomes in asymptomatic pregnant persons. Population: Asymptomatic pregnant adolescents and adults. Evidence Assessment: The USPSTF concludes that the current evidence is insufficient, and the balance of benefits and harms of screening for iron deficiency and iron deficiency anemia in asymptomatic pregnant persons on maternal and infant health outcomes cannot be determined. The USPSTF also concludes that the current evidence is insufficient, and the balance of benefits and harms of iron supplementation in asymptomatic pregnant persons on maternal and infant health outcomes cannot be determined. Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for iron deficiency and iron deficiency anemia in pregnant persons to prevent adverse maternal and infant health outcomes. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of routine supplementation for iron deficiency and iron deficiency anemia in pregnant persons to prevent adverse maternal and infant health outcomes. (I statement).

Screening for Iron Deficiency and Iron Deficiency Anemia During Pregnancy.

This JAMA Patient Page discusses the pros and cons of screening for iron deficiency and iron deficiency anemia during pregnancy.

Screening and Supplementation for Iron Deficiency and Iron Deficiency Anemia During Pregnancy: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: In 2015 the US Preventive Services Task Force (USPSTF) found insufficient evidence to assess the balance of benefits and harms of routine screening and supplementation for iron deficiency anemia during pregnancy. Objective: To update the 2015 review on screening for iron deficiency anemia, in addition to iron deficiency during pregnancy, to inform the USPSTF. Data Sources: Ovid MEDLINE and Cochrane databases through May 24, 2023; surveillance through May 24, 2024. Study Selection: Randomized clinical trials of iron supplementation, screening effectiveness, treatment, and harms; observational studies of screening. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, study quality, and data abstraction. Data were pooled using a random-effects model. Main Outcomes and Measures: Maternal and infant clinical outcomes, hematologic indices, and harms. Results: Seventeen trials (N = 24 023) on maternal iron supplementation were included. Iron supplementation was associated with decreased risk of maternal iron deficiency anemia at term (4 trials, n = 2230; 8.6% vs 19.8%; relative risk, 0.40 [95% CI, 0.26-0.61]; I2 = 20.5%) and maternal iron deficiency at term (6 trials, n = 2361; 46% vs 70%; relative risk, 0.47 [95% CI, 0.33-0.67]; I2 = 81.9%) compared with placebo or no iron supplement. There were no statistically significant differences in maternal quality of life, rates of gestational diabetes, maternal hemorrhage, hypertensive disorders of pregnancy, cesarean delivery, preterm birth, infant low birth weight, or infants small for gestational age for maternal iron supplementation compared with placebo or no supplementation. Harms of iron supplementation included transient gastrointestinal adverse effects. No studies evaluated the benefits or harms of screening for iron deficiency or iron deficiency anemia during pregnancy. Data on the association between iron status and health outcomes, such as hypertensive disorders of pregnancy and preterm birth, were very limited. Conclusions and Relevance: Routine prenatal iron supplementation reduces the incidence of iron deficiency and iron deficiency anemia during pregnancy, but evidence on health outcomes is limited or indicates no benefit. No studies addressed screening for iron deficiency or iron deficiency anemia during pregnancy. Research is needed to understand the association between changes in maternal iron status measures and health outcomes.

The role of reticulocyte hemoglobin equivalent on the evaluation of iron deficiency and iron deficiency anemia in pediatric cyanotic heart disease: a diagnostic study in Indonesia.

BACKGROUND: In light of prolonged hypoxia, children with cyanotic heart disase (CHD) are at a high risk of developing iron deficiency iron deficiency (ID) and iron deficiency anemia (IDA). Reticulocyte hemoglobin equivalent (Ret-He) is a novel and dependable indicator for assessing iron status. However, there has been no previous study regarding cut-off value in pediatric CHD group. The purpose of this study is to assess the role of Ret-He and to establish cut-off points in the diagnosis of iron deficiency and IDA in pediatric cyanotic heart disease. METHOD: This study was conducted in two tertiary hospitals in Jakarta, Indonesia. 59 children with CHD, aged 3 months to 18 years, were enrolled consecutively. To determine iron status, hematological parameters (hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin) and biochemical parameters for iron status (serum ferritin, transferrin saturation) were analysed and compared to Ret-He levels. The receiver operating characteristic (ROC) analysis was performed for the Ret-He cut-off points for ID and IDA. Sensitivity, specificity, positive and negative predictive value were calculated for each cut-off point. RESULT: Normal iron status was identified in 27 (45.8%) subjects, ID in 8 (13.5%) subjects, and IDA 24 (40.7%) subjects. The ID cut-off value for Ret-He is 28.8 pg (sensitivity 75%, specificity 85.2%, PPV 60%, NPV 92%, and AUC 0.828) and the Ret-He cut-off point for IDA is 28.15 pg (sensitivity 75%, specificity 88.9%, PPV 85.7%, NPV 80%, and AUC 0.824). Hemoglobin should be used in conjunction with Ret-He. ID might be detected in this cohort with Ret-He 28.8 pg and hemoglobin > 16,5 g/dL. While Ret-He 28.15 pg or Ret-He 28.15-28.8 pg with hemoglobin 16.5 g/dL could be used to diagnose IDA. CONCLUSION: The reticulocyte hemolgobin equivalent could be utilised as an iron status parameter in pediatric CHD, with a cut-off value of 28.8 pg for ID and 28.15 pg for IDA.

Signaling function of NH4+ in the activation of Fe-deficiency response in cucumber (Cucumis sativus L.).

MAIN CONCLUSION: NH4+ is necessary for full functionality of reduction-based Fe deficiency response in plants. Nitrogen (N) is present in soil mainly as nitrate (NO3-) or ammonium (NH4+). Although the significance of a balanced supply of NO3- and NH4+ for optimal growth has been generally accepted, its importance for iron (Fe) acquisition has not been sufficiently investigated. In this work, hydroponically grown cucumber (Cucumis sativus L. cv. Maximus) plants were supplied with NO3- as the sole N source under -Fe conditions. Upon the appearance of chlorosis, plants were supplemented with 2 mM NH4Cl by roots or leaves. The NH4+ treatment increased leaf SPAD and the HCl-extractable Fe concentration while decreased root apoplastic Fe. A concomitant increase in the root concentration of nitric oxide and activity of FRO and its abolishment by an ethylene action inhibitor, indicated activation of the components of Strategy I in NH4+-treated plants. Ammonium-pretreated plants showed higher utilization capacity of sparingly soluble Fe(OH)3 and higher root release of H+, phenolics, and organic acids. The expression of the master regulator of Fe deficiency response (FIT) and its downstream genes (AHA1, FRO2, and IRT1) along with EIN3 and STOP1 was increased by NH4+ application. Temporal analyses and the employment of a split-root system enabled us to suggest that a permanent presence of NH4+ at concentrations lower than 2 mM is adequate to produce an unknown signal and causes a sustained upregulation of Fe deficiency-related genes, thus augmenting the Fe-acquisition machinery. The results indicate that NH4+ appears to be a widespread and previously underappreciated component of plant reduction-based Fe deficiency response.

Transcriptomics Provide Insights into Early Responses to Sucrose Signaling in Lupinus albus, a Model Plant for Adaptations to Phosphorus and Iron Deficiency.

Phosphorus (P) and iron (Fe) deficiency are major limiting factors for plant productivity worldwide. White lupin (Lupinus albus L.) has become a model plant for understanding plant adaptations to P and Fe deficiency, because of its ability to form cluster roots, bottle-brush-like root structures play an important role in the uptake of P and Fe from soil. However, little is known about the signaling pathways involved in sensing and responding to P and Fe deficiency. Sucrose, sent in increased concentrations from the shoot to the root, has been identified as a long-distance signal of both P and Fe deficiency. To unravel the responses to sucrose as a signal, we performed Oxford Nanopore cDNA sequencing of white lupin roots treated with sucrose for 10, 15, or 20 min compared to untreated controls. We identified a set of 17 genes, including 2 bHLH transcription factors, that were up-regulated at all three time points of sucrose treatment. GO (gene ontology) analysis revealed enrichment of auxin and gibberellin responses as early as 10 min after sucrose addition, as well as the emerging of ethylene responses at 20 min of sucrose treatment, indicating a sequential involvement of these hormones in plant responses to sucrose.

Efficacy of iron supplementation on physical capacity in non-anaemic iron-deficient individuals: protocol for an individual patient data meta-analysis.

BACKGROUND: A deficiency in iron stores is associated with various adverse health complications, which, if left untreated, can progress to states of anaemia, whereby there is significant detriment to an individual's work capacity and quality of life due to compromised erythropoiesis. The most common methods employed to treat an iron deficiency include oral iron supplementation and, in persistent and/or unresponsive cases, intravenous iron therapy. The efficacy of these treatments, particularly in states of iron deficiency without anaemia, is equivocal. Indeed, both randomised control trials and aggregate data meta-analyses have produced conflicting evidence. Therefore, this study aims to assess the efficacy of both oral and intravenous iron supplementation on physical capacity, quality of life, and fatigue scores in iron-deficient non-anaemic individuals using individual patient data (IPD) meta-analysis techniques. METHODS: All potential studies, irrespective of design, will be sourced through systematic searches on the following databases: Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase Ovid, Web of Science: Science Citation Index Expanded, Web of Science: Conference Proceedings Citation Index-Science, ClinicalTrials.gov, and World Health Organization (WHO) International Clinical Trials Registry Platform. Individual patient data from all available trials will be included and subsequently analysed in a two-stage approach. Predetermined subgroup and sensitivity analyses will be employed to further explain results. DISCUSSION: The significance of this IPD meta-analysis is one of consolidating a clear consensus to better inform iron-deficient individuals of the physiological response associated with iron supplementation. The IPD approach, to the best of our knowledge, is novel for this research topic. As such, the findings will significantly contribute to the current body of evidence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020191739.

Iron Metabolism in the Recovery Phase of Critical Illness with a Focus on Sepsis.

Iron is an essential nutrient for humans and microbes, such as bacteria. Iron deficiency commonly occurs in critically ill patients, but supplementary iron therapy is not considered during the acute phase of critical illness since it increases iron availability for invading microbes and oxidative stress. However, persistent iron deficiency in the recovery phase is harmful and has potential adverse outcomes such as cognitive dysfunction, fatigue, and cardiopulmonary dysfunction. Therefore, it is important to treat iron deficiency quickly and efficiently. This article reviews current knowledge about iron-related biomarkers in critical illness with a focus on patients with sepsis, and provides possible criteria to guide decision-making for iron supplementation in the recovery phase of those patients.

Faecal immunochemical tests can improve colonoscopy triage in patients with iron deficiency: A systematic review and meta-analysis.

BACKGROUND: Use of the faecal immunochemical test (FIT) to triage patients with iron deficiency (ID) for colonoscopy due to suspected colorectal cancer (CRC) may improve distribution of colonoscopic resources. We reviewed the diagnostic performance of FIT for detecting advanced colorectal neoplasia, including CRC and advanced pre-cancerous neoplasia (APCN), in patients with ID, with or without anaemia. METHODS: We performed a systematic review of three databases for studies comprising of patients with ID, with or without anaemia, completing a quantitative FIT within six months prior to colonoscopy, where test performance was compared against the reference standard colonoscopy. Random effects meta-analyses determined the diagnostic performance of FIT for advanced colorectal neoplasia. RESULTS: Nine studies were included on a total of n=1761 patients with ID, reporting FIT positivity thresholds between 4-150 µg haemoglobin/g faeces. Only one study included a non-anaemic ID (NAID) cohort. FIT detected CRC and APCN in ID patients with 90.7 % and 49.3 % sensitivity, and 81.0 % and 82.4 % specificity, respectively. FIT was 88.0 % sensitive and 83.4 % specific for CRC in patients with ID anaemia at a FIT positivity threshold of 10 µg haemoglobin/g faeces. CONCLUSIONS: FIT shows high sensitivity for advanced colorectal neoplasia and may be used to triage those with ID anaemia where colonoscopic resources are limited, enabling those at higher risk of CRC to be prioritised for colonoscopy. There is a need for further research investigating the diagnostic performance of FIT in NAID patients.

A rapid review of strategies to manage low iron levels in adults donating whole-blood: A focus on donor behaviour.

In recognition of the impact of whole-blood donation on body iron stores, there has been an increased focus assessing the efficacy of strategies to minimise the risk of iron deficiency (ID). Whilst donor behaviour is an important determinant of success, this literature is yet to be fully synthesised to help guide blood collection agencies when implementing these strategies into routine practice. This rapid review identifies strategies for management of low iron, how they have been communicated to donors, donor compliance with advice, donor use of external health services and their effect on donor retention. Web of Science, Medline, CINAHL and Wiley online library databases were searched from 2012 to November 2023, with 29 studies meeting inclusion criteria. Five iron management strategies were identified: oral iron supplementation (IS), education, dietary advice, lengthening inter-donation interval and switching donation type. Most studies (n = 16) focused on IS, with only four reporting how they communicated this to donors. Donor use of IS was high in controlled research environments but has not been evaluated when implemented into routine practice. None of the four studies on dietary advice included findings on donor acceptability. The proportion of donors consulting their doctor about a low iron result or their risk of ID was found to be suboptimal. However, in general, the identified strategies and communications had a positive effect on donor retention. More evidence is needed on how to increase donor knowledge and awareness of donation-related risk of ID as well as to identify how to effectively communicate strategies to donors to ensure optimal acceptability and use.

Iron Deficiency in Pulmonary Hypertension.

Pulmonary hypertension (PH) is a complex cardiovascular condition that is characterized by elevated pulmonary arterial pressure, which leads to significant morbidity and mortality. Among the various factors that influence the pathophysiology and progression of PH, iron deficiency has become a critical, yet often overlooked, element. In this review, the prevalence, implications, and therapeutic potential of addressing iron deficiency in patients with PH are elucidated.Iron deficiency, which is prevalent in a significant proportion of patients with PH, has been associated with worsened clinical outcomes, including diminished exercise capacity, impaired oxygen transport and utilization, and compromised right ventricular function. The pathophysiological linkages between iron deficiency and PH are multifaceted and involve alterations in oxygen sensing, endothelial function, and metabolic disturbances.In this review, the evidence from recent clinical trials and studies that assess the impact of iron supplementation, both oral and intravenous, on PH outcomes is critically analyzed. Although some studies suggest improvements in exercise capacity and hemodynamic parameters following iron repletion, the responses appear variable and are not universally beneficial. This review highlights the complexities of iron metabolism in PH and the challenges in effectively diagnosing and treating iron deficiency in this patient population.Furthermore, the potential mechanisms through which iron supplementation might influence pulmonary vascular and right ventricular function, emphasizing the need for personalized treatment approaches are discussed. In this review, the importance of recognizing iron deficiency in the management of patients with PH is highlighted, and further research is warranted to establish comprehensive, evidence-based guidelines for iron supplementation in this unique patient cohort. The ultimate goal of this review is to improve clinical outcomes and quality of life for patients suffering from this debilitating condition.

Iron deficiency in athletes: Prevalence and impact on VO2 peak.

BACKGROUND: Iron is an important micronutrient in pathways of energy production, adequate nutrient intake and its balance is essential for optimal athletic performance. However, large studies elucidating the impact of iron deficiency on athletes' performance are sparse. METHODS: Competitive athletes of any age who presented for preparticipation screening 04/2020-10/2021 were included in this study and stratified for iron deficiency (defined as ferritin level <20 µg/l with and without mild anemia [hemoglobin levels ≥11 g/dl]). Athletes with and without iron deficiency were compared and the impact of iron deficiency on athletic performance was investigated. RESULTS: Overall, 1190 athletes (mean age 21.9 ± 11.6 years; 34.2% females) were included in this study. Among these, 19.7% had iron deficiency. Patients with iron deficiency were younger (18.1 ± 8.4 vs. 22.8 ± 12.1 years, P < 0.001), more often females (64.5% vs. 26.8%, P < 0.001), had lower VO2 peak value (43.4 [38.5/47.5] vs. 45.6 [39.1/50.6]ml/min/kg, P = 0.022) and lower proportion of athletes reaching VO2 peak of >50 ml/min/kg (8.5% vs. 16.1%, P = 0.003). Female sex (OR 4.35 [95% CI 3.13-5.88], P > 0.001) was independently associated with increased risk for iron deficiency. In contrast, the risk for iron deficiency decreased by every life year (OR 0.97 [95% CI 0.95-0.99], P = 0.003). Iron deficiency was independently associated with reduced VO2 peak (OR 0.94 [0.91-0.97], P < 0.001) and lower probability to reach VO2 peak >50 ml/min/kg (OR 0.42 [95% CI 0.25-0.69], P = 0.001). CONCLUSIONS: Iron deficiency is common in athletes (predominantly in female and in young athletes). Iron deficiency was independently associated with reduced VO2 peak during exercise testing and lower probability to reach a VO2 peak >50 ml/min/kg.

The impact of iron deficiency on patients under evaluation for colorectal cancer, a prospective cross-sectional study.

BACKGROUND AND OBJECTIVE: Iron deficiency affects more than 60% of colorectal cancer patients at the time of diagnosis. Iron deficiency ultimately leads to anemia, but additionally, iron deficiency might impact other domains of colorectal cancer patients' health and well-being. The aim of this study was to evaluate the impact of iron deficiency on fatigue, quality of life, cognition, and physical ability in patients undergoing evaluation for colorectal cancer. METHODS: Multicenter, prospective, observational cross-sectional study (2021-2023). Fatigue was the primary outcome, measured using the Focused Assessment of Cancer Treatment-Anemia questionnaire (FACT-An). Quality of Life, Cognition, Aerobe capacity, mobility, and peripheral muscle strength were tested as secondary outcomes. Multivariate analysis was performed to estimate the impact of iron deficiency on all outcomes. RESULTS: Two hundred and one patients were analyzed, 57% being iron deficient. In multivariate regression analysis, iron deficiency was not associated with fatigue: FACT-An (r = -1.17, p = 0.57, 25% CI: -5.27 to 2.92). Results on quality of life, cognition, and mobility were non-significant and with small regression coefficients. Iron deficiency showed a nearly significant association with reduced hand-grip-strength (r = -3.47 kg, p = 0.06, 25%CI -7.03 to 0.08) and reduced 6 min walking distance (r = -40.36 m, p = 0.07, 25%CI: -84.73 to 4.00). CONCLUSION: Iron deficiency in patients undergoing evaluation for colorectal cancer was not associated with fatigue, quality of life, or cognition, but might affect aerobic endurance and peripheral muscle strength to a degree that is clinically relevant.