Impact of Magnesium and Ferritin Deficiency on Depression Among Adolescent Students.

BACKGROUND: Depression is considered the fourth-leading cause of health problems. It is the fourth-leading cause of health problems and disability, which causes 16% of the worldwide burden of disease and injury among adolescents. OBJECTIVE: The aim of the present study was to evaluate the possible association of magnesium (Mg) and ferritin deficiency with depression in adolescent students. PATIENTS AND METHODS: This case control study in secondary schools at Al-Ghanayem discrete. The total number included was 358 students. All were screened for depression by the Arabic version of the Beck questionnaire. The students who had positive score was selected as cases 86 and a matched same number of students with negative score was selected as controls. Serum level of ferritin and magnesium was measured in the 2 groups. RESULTS: There was statistically significant difference between the studied groups when comparing depression grade with each of ferritin and Mg Depressed group cases had lower mean values of ferritin and Mg. The ferritin cut-off level for the prediction of depression was (35.5 µg/dL, which had a sensitivity of 74.4% and a specificity of 75.6%. The magnesium cut-off levels for the prediction of depression were1.95 mg/dL and 104.5 ng/dL which had a sensitivity of 70% and 64%, respectively. CONCLUSION: There was a statistically significant negative correlation between depression severity and each of socio-economic status ferritin and Mg. Each of ferritin and Mg were predictors for depression.

Characteristics of Virology and Immune Inflammation of Epstein-Barr Virus Infection Related Non-Neoplastic Diseases in Children.

BACKGROUND: The goal was to study the difference of virological, immunologic, and inflammatory indicators between Epstein-Barr associated infectious mononucleosis (EBV-IM) and EBV associated hemophagocytic lymphohistiocytosis (EBV-HLH) and to explore the evaluation indicators for monitoring the therapeutic efficacy of EBV-HLH. METHODS: Twenty children with EBV-IM (IM group) and 10 children with EBV-HLH (HLH group) were selected. Virology indicators were detected; the absolute count of lymphocyte, and lymphocyte subsets were detected; the levels of immunoglobulin and ferritin were assayed. RESULTS: Compared to the IM group, the HLH group showed a decrease in EBV-specific VCA-IgM antibody levels (U = 29.0, p = 0.006) and an increase in EBV-specific NA-IgG antibody levels (U = 17.0, p = 0.001), while there was no significant difference in EB-DNA loads (t = 0.417, p = 0.680). The counts of lymphocytes, and various lymphocyte subsets in the HLH group were lower than those in the IM group. Inflammatory markers in the HLH group were significantly higher than those in IM group. Dynamic monitoring of virological, immunological, and inflammatory indicators in HLH patients during treatment showed that EBV DNA gradually decreased in patients with good prognosis. Inflammatory indicators significantly decreased and returned to normal, lymphocyte count significantly increased and returned to normal during treatment. However, patients with poor prognosis showed rebound increase in EBV DNA and inflammatory indicators in the later stage of treatment, while lymphocyte count further decreased with the recurrence of the disease. CONCLUSIONS: Exhausted and damaged immune function in host by persistent stimulation of EB viral antigen is one of the main pathogeneses of EB-HLH. Lymphocyte count and serum ferritin level are effective indicators to monitor the therapeutic efficacy during the treatment to HLH.

Cross-sectional and longitudinal associations of Iron biomarkers and cardiovascular risk factors in pre- and postmenopausal women: leveraging repeated measurements to address natural variability.

BACKGROUND: The association between iron biomarkers and cardiovascular disease risk factors (CVD-RFs) remains unclear. We aimed to (1) evaluate the cross-sectional and longitudinal associations between iron biomarkers (serum ferritin, transferrin saturation (TSAT), transferrin) and CVD-RFs among women, and (2) explore if these associations were modified by menopausal status. METHOD: Cross-sectional and longitudinal analyses including 2542 and 1482 women from CoLaus cohort, respectively. Multiple linear regression and multilevel mixed models were used to analyse the associations between Iron biomarkers and CVD-RFs. Variability of outcomes and iron markers between surveys was accessed using intraclass correlation (ICC). RESULTS: After multivariable adjustment, elevated serum ferritin levels were associated with increased insulin and glucose levels, while higher transferrin levels were linked to elevated glucose, insulin and total cholesterol, and systolic and diastolic blood pressure (p < 0.05). No association was observed between CVD-RFs and TSAT (p > 0.05). Iron biomarkers demonstrated low reliability across reproductive stages but exhibited stronger associations in the perimenopausal group. In longitudinal analysis, we found association only for transferrin with lower glucose levels [ß = - 0.59, 95% CI (- 1.10, - 0.08), p = 0.02] and lower diastolic blood pressure [ß = - 7.81, 95% CI (- 15.9, - 0.56), p = 0.04]. CONCLUSION: In cross-sectional analysis, transferrin was associated with several CVD-RFs, and the associations did not change according to menopausal status. Conversely, in the longitudinal analyses, changes in transferrin were associated only with lower glucose and diastolic blood pressure levels. These differences might stem from the substantial longitudinal variation of iron biomarkers, underscoring the need for multiple iron measurements in longitudinal analyses.

Dynamic indicators of acute respiratory diseases treatment in children after correction.

OBJECTIVE: Aim: To study the Respiratory pathology of the upper respiratory tract, markers of the inflammatory response of the organism, Oxidative stress, Metabolic adaptation and possibilities of correction. PATIENTS AND METHODS: Materials and Methods: The study group (n=111) included school-aged children (10-14 years old). The general group of inflammatory diseases of the respiratory tract (J000-J06) was considered, with a diagnosis of acute respiratory infection (ARI) of viral and bacterial origin and included local inflammationof the upper respiratory tract with presentation of acute pharyngitis (68.0%), acute bronchitis (22,0%), acute tonsillitis (10,0%). RESULTS: Results: Dynamic observation of groups of children who received optimized (group 1, n=60) and basic (group 2, n=51) treatment was carried out. The level of the erythrocyte pool correlated with IL-1 (r=-0,29, p=0,03), IL-4 (r=0,32, p=0,01), TNF-α (r=-0,35 , p=0,006). Creatinine value correlated with IL-10 (r=0,3, p=0,005), γ-IFN (r=0,42, p=0,001), TNF-α (r=0,25, p=0,05). Correlations of ferritin presented positive correlation values with the level of total protein (r=0,26, p=0,04) and TNF-α (r=0,41, p=0,001). CONCLUSION: Conclusions: After the optimized treatment, there was a significant decrease in the reliable levels of CRP and γ-IFN by 7 and 4,4 times (by groups) and 5,8 and 3,2 times (by groups), respectively. Correlation relationships of urea levels with IL-2,4 were detected. The level of the erythrocyte pool correlated with IL-1,4, TNF-α, Ferritin presented positive correlation values with the level of total protein,TNF-α .

Efficacy and Safety of Oral Supplementation with Liposomal Iron in Non-Dialysis Chronic Kidney Disease Patients with Iron Deficiency.

INTRODUCTION: Iron deficiency is common in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). Oral iron supplementation is recommended in these patients, but it is associated with a higher incidence of gastrointestinal adverse reactions. Liposomal iron therapy has been proposed as a new iron formulation, improving iron bioavailability with less side effects; however, few data are available in patients with NDD-CKD. METHODS: We designed a single-arm pilot study to evaluate the efficacy of liposomal iron administered for six months in correcting iron deficiency (defined as serum ferritin < 100 ng/mL and/or transferrin saturation < 20%) in patients with NDD-CKD stages 1-5. The primary endpoints were the achievement of serum ferritin ≥ 100 ng/mL and transferrin saturation ≥ 20%. Secondary outcomes were hemoglobin (Hb) changes and the safety of liposomal iron. RESULTS: The efficacy population included 34/38 patients, who completed at least one visit after baseline. Liposomal iron increased the achievement of transferrin saturation targets from 11.8% at baseline to 50.0% at month 6 (p = 0.002), while no significant correction of serum ferritin (p = 0.214) and Hb was found (p = 0.465). When patients were stratified by anemia (Hb < 12 g/dL in women and Hb < 13 g/dL in men), a significant improvement of transferrin saturation was observed only in anemic patients (from 13.3 ± 5.8% to 20.2 ± 8.1%, p = 0.012). Hb values slightly increased at month 6 only in anemic patients (+0.60 g/dL, 95%CI -0.27 to +1.48), but not in those without anemia (+0.08 g/dL, 95%CI -0.73 to +0.88). In patients taking at least one dose of liposomal iron (safety population, n = 38), the study drug was discontinued in eight patients due to death (n = 2), a switch to intravenous iron (n = 2), and the occurrence of side effects (n = 4). CONCLUSIONS: The use of liposomal iron in patients with NDD-CKD is associated with a partial correction of transferrin saturation, with no significant effect on iron storage and Hb levels.

Diagnosing aceruloplasminemia: navigating through red herrings.

A 58-year-old female was found to have hyperferritinemia (Serum ferritin:1683 ng/mL) during work-up for mild normocytic anemia. Transferrin saturation(TSAT) was low-normal. Magnetic resonance imaging (MRI) abdomen showed evidence of hepatic iron deposition. Liver biopsy showed 4 + hepatic iron deposition without any evidence of steatosis or fibrosis. Quantitative liver iron was elevated at 348.3 µmol/g dry liver weight [Reference range(RR): 3-33 µmol/g dry liver weight]. She was presumptively diagnosed with tissue iron overload, cause uncertain. A diagnosis of ferroportin disease (FD) was considered, but the pattern of iron distribution in the liver, mainly within the hepatic parenchyma (rather than in the hepatic Kupffer cells seen in FD), and the presence of anemia (uncommon in FD) made this less likely. She was treated with intermittent phlebotomy for over a decade with poor tolerance due to worsening normocytic to microcytic anemia. A trial of deferasirox was done but it was discontinued after a month due to significant side effects. During the course of treatment, her ferritin level decreased. Over the past 1.5 years, she developed progressively worsening neurocognitive decline. MRI brain showed areas of susceptibility involving basal ganglia, midbrain and cerebellum raising suspicion for metabolic deposition disease. Neuroimaging findings led to testing for serum copper and ceruloplasmin levels which were both found to be severely low. Low serum copper, ceruloplasmin levels and neuroimaging findings led us to consider Wilson disease however prior liver biopsy showing elevated hepatic iron rather than hepatic copper excluded the diagnosis of Wilson disease. After shared decision making, ceruloplasmin gene analysis was not pursued due to patient's preference and prohibitive cost of testing. The diagnosis of aceruloplasminemia was ultimately made. The biochemical triad of hyperferritinemia, low-normal TSAT and microcytic anemia should raise the possibility of aceruloplasminemia. Since neurological manifestations are rare in most inherited iron overload syndromes, neurological symptoms in a patient with tissue iron overload should prompt consideration of aceruloplasminemia as a differential diagnosis.

Imbalance of Iron Availability and Demand in Patients With Acute and Chronic Heart Failure.

BACKGROUND: Iron deficiency (ID) is a frequent comorbidity in patients with acute (AHF) and chronic heart failure (CHF) associated with morbidity and death. We aimed to better characterize iron homeostasis in patients with heart failure applying different biomarkers and to evaluate the accuracy of current ID definition by the European Society of Cardiology/American College of Cardiology/American Heart Association to indicate tissue iron availability and demand. METHODS AND RESULTS: We performed a retrospective cohort study investigating 277 patients with AHF and 476 patients with CHF between February 2021 and May 2022. Patients with AHF had more advanced ID than patients with CHF, reflected by increased soluble transferrin receptor and soluble transferrin receptor-ferritin index, and lower ferritin, serum iron, transferrin saturation, hepcidin, and reticulocyte hemoglobin. Decreased iron availability or increased tissue iron demand, reflected by increased soluble transferrin receptor-ferritin index and decreased reticulocyte hemoglobin, was found in 84.1% (AHF) and 28.0% (CHF) with absolute ID and in 50.0% (AHF) and 10.5% (CHF) with combined ID according to the current European Society of Cardiology/American College of Cardiology/American Heart Association-based ID definition. Low hepcidin expression as an indicator of systemic ID was found in 91.1% (AHF) and 80.4% (CHF) of patients with absolute ID and in 32.3% (AHF) and 18.8% (CHF) of patients with combined ID. ID definitions with higher specificity reduce the need for iron supplementation by 25.5% in patients with AHF and by 65.6% in patients with CHF. CONCLUSIONS: Our results suggest that the current European Society of Cardiology/American College of Cardiology/American Heart Association-based ID definition might overestimate true ID, particularly in CHF. More stringent thresholds for ID could more accurately identify patients with heart failure with reduced tissue iron availability who benefit from intravenous iron supplementation.

[Epidemiological investigation of iron deficiency among preschool children in 10 provinces, autonomous regions, or municipalities in China].

Objective: To understand the current status of anemia, iron deficiency, and iron-deficiency anemia among preschool children in China. Methods: A cross-sectional study was conducted with a multi-stage stratified sampling method to select 150 streets or townships from 10 Chinese provinces, autonomous regions, or municipalities (East: Jiangsu, Zhejiang, Shandong, and Hainan; Central: Henan; West: Chongqing, Shaanxi, Guizhou, and Xinjiang; Northeast: Liaoning). From May 2022 to April 2023, a total of 21 470 children, including community-based children aged 0.5 to<3.0 years receiving child health care and kindergarten-based children aged 3.0 to<7.0 years, were surveyed. They were divided into 3 age groups: infants (0.5 to<1.0 year), toddlers (1.0 to<3.0 years), and preschoolers (3.0 to<7.0 years). Basic information such as sex and date of birth of the children was collected, and peripheral blood samples were obtained for routine blood tests and serum ferritin measurement. The prevalence rates of anemia, iron deficiency, and iron-deficiency anemia were analyzed, and the prevalence rate differences were compared among different ages, sex, urban and rural areas, and regions using the chi-square test. Results: A total of 21 460 valid responses were collected, including 10 780 boys (50.2%). The number of infants, toddlers, and preschoolers were 2 645 (12.3%), 6 244 (29.1%), and 12 571 (58.6%), respectively. The hemoglobin level was (126.7±14.8) g/L, and the serum ferritin level was 32.3 (18.5, 50.1) µg/L. The overall rates of anemia, iron deficiency, and iron-deficiency anemia were 10.4% (2 230/21 460), 28.3% (6 070/21 460), and 3.9% (845/21 460), respectively. The prevalence rate of anemia was higher for boys than for girls (10.9% (1 173/10 780) vs. 9.9% (1 057/10 680), χ2=5.58, P=0.018), with statistically significant differences in the rates for infants, toddlers and preschoolers (18.0% (475/2 645), 10.6% (662/6 244), and 8.7% (1 093/12 571), respectively, χ2=201.81, P<0.01), and the rate was significantly higher for children in rural than that in urban area (11.8% (1 516/12 883) vs. 8.3% (714/8 577), χ2=65.54, P<0.01), with statistically significant differences in the rates by region (χ2=126.60, P<0.01), with the highest rate of 15.8% (343/2 173) for children in Central region, and the lowest rate of 5.3% (108/2 053) in Northeastern region. The prevalence rates of iron deficiency were 33.8% (895/2 645), 32.2% (2 011/6 244), and 25.2% (3 164/12 571) in infants, toddlers, and preschoolers, respectively, and 30.0% (3 229/10 780) in boys vs. 26.6% (2 841/10 680) in girls, 21.7% (1 913/8 821), 40.0% (870/2 173), 27.1% (2 283/8 413), 48.9% (1 004/2 053) in Eastern, Central, Western, and Northeastern regions, respectively, and each between-group showed a significant statistical difference (χ2=147.71, 29.73, 773.02, all P<0.01). The prevalence rate of iron-deficiency anemia showed a significant statistical difference between urban and rural areas, 2.9% (251/8 577) vs. 4.6% (594/12 883) (χ2=38.62, P<0.01), while the difference in iron deficiency prevalence was not significant (χ2=0.51, P=0.476). Conclusions: There has been a notable improvement in iron deficiency and iron-deficiency anemia among preschool children in China, but the situation remains concerning. Particular attention should be paid to the prevention and control of iron deficiency and iron-deficiency anemia, especially among infants and children in the Central, Western, and Northeastern regions of China.

Overview of Trends in Anemia and Iron Deficiency in the Mexican Population From 1999 to 2018-19.

BACKGROUND: Despite the emergence of diverse programs in Mexico to address anemia and micronutrient deficiencies in disadvantaged groups, progress on reducing their prevalence has stagnated. In Mexico, anemia surveillance at the population level is conducted through the National Health and Nutrition Survey ENSANUT (for its acronym in Spanish). OBJECTIVE: To overview the trends in anemia and iron deficiency (ID) from 1999 to 2018-19 in the Mexican population before COVID-19 pandemic. METHODS: Data from five nationwide surveys in Mexico were used. Where available, data on anemia, ID, and ID anemia (IDA) were extracted from ENSANUTs 1999, 2006, 2012, 2016, and 2018-19 in participants from 1 to 99 years old. Blood sample collection methods were similar across surveys (1999-2018) where capillary drop blood was used to estimate Hb using a HemoCue and serum blood samples to measure ferritin and C-reactive protein concentration. RESULTS: The trend in anemia prevalence shows a U-shape from 1999 to 2018-19 in <60 years old. In older adults (≥60 years), an increasing trend was observed. Anemia declined progressively from 1999 to 2012 but increased from 2016 to 2018-19 in comparison with 2012. In contrast, ID declined from 2006 to 2018-19, mainly in children, while IDA did not change over this period. In older adults, ID prevalence remained constant over time. CONCLUSIONS: The shifting trend in anemia prevalence across ENSANUTs 1999 through 2018-19 did not mimic the decreasing trend of ID over the same period of time. Other noncausal factors seem to play an important role in the variability of hemoglobin measurements.

Plain language titleOverview of Trends in the Prevalence of Anemia and Iron Deficiency in the Mexican Population From 1999 to 2018-19Plain language summaryIn Mexico, anemia surveillance has been monitored through the National Health and Nutrition Survey since 1999. Nonetheless, progress on reducing their prevalence seems to be stagnated despite the emergence of diverse social programs in Mexico to tackle micronutrient deficiencies in children and women. The main cause of anemia in children and women is iron deficiency (ID). Any progress in tackling ID should be reflected in anemia prevalence. To investigate the prevalence trend, we used information about anemia (based on hemoglobin concentration) and ID (based on serum ferritin levels) where available, from 5 nationwide surveys in Mexico among participants from 1 to 99 years old, to discuss some of the potential factors behind anemia and ID trends. From 1999 to 2018-19, we observed an ¨U" shape in the prevalence of anemia in all age groups <60 years old, contrasting with the prevalence of ID, which trend is in decline. No major changes in terms of social programs can explain the trend in anemia. In fact, other nutritional indicators seem to have improved in Mexican children. A major difference in the measurement of anemia and ID is that hemoglobin was measured in situ using drop of capillary blood in HemoCue, a portable photometer, while ferritin was measured in venous blood in the central laboratory. While many external factors might influence the hemoglobin measurement in the field setting, it seems that the technique of finger prick capillary introduces more errors to the measurement of hemoglobin than other techniques (e.g., pool capillary or venous blood using HemoCue). This difference, in turn, affects anemia diagnosis. Since the drop of capillary blood has been widely acceptable, we did not perform any validation of hemoglobin measurement in those past surveys, so we cannot role out the contribution of other factors that affected hemoglobin measurement. Future studies should use venous blood to improve anemia classification; otherwise, validation studies should be carried out to improve hemoglobin measurement when using capillary blood.

Iron status and sarcopenia-related traits: a bi-directional Mendelian randomization study.

Although serum iron status and sarcopenia are closely linked, the presence of comprehensive evidence to establish a causal relationship between them remains insufficient. The objective of this study is to employ Mendelian randomization techniques to clarify the association between serum iron status and sarcopenia. We conducted a bi-directional Mendelian randomization (MR) analysis to investigate the potential causal relationship between iron status and sarcopenia. MR analyses were performed using inverse variance weighted (IVW), MR-Egger, and weighted median methods. Additionally, sensitivity analyses were conducted to verify the reliability of the causal association results. Then, we harvested a combination of SNPs as an integrated proxy for iron status to perform a MVMR analysis based on IVW MVMR model. UVMR analyses based on IVW method identified causal effect of ferritin on appendicular lean mass (ALM, ß = - 0.051, 95% CI - 0.072, - 0.031, p = 7.325 × 10-07). Sensitivity analyses did not detect pleiotropic effects or result fluctuation by outlying SNPs in the effect estimates of four iron status on sarcopenia-related traits. After adjusting for PA, the analysis still revealed that each standard deviation higher genetically predicted ferritin was associated with lower ALM (ß = - 0.054, 95% CI - 0.092, - 0.015, p = 0.006). Further, MVMR analyses determined a predominant role of ferritin (ß = - 0.068, 95% CI - 0.12, - 0.017, p = 9.658 × 10-03) in the associations of iron status with ALM. Our study revealed a causal association between serum iron status and sarcopenia, with ferritin playing a key role in this relationship. These findings contribute to our understanding of the complex interplay between iron metabolism and muscle health.

Serum ferritin and the risk of myocardial infarction: A Mendelian randomization study.

The potential role of serum ferritin as a risk factor for myocardial infarction (MI) is controversial, necessitating a systematic exploration of the causal relationship between ferritin and MI through Mendelian randomization (MR) methods. Genetic data were derived from a genome-wide association study (GWAS), employing the inverse variance-weighted (IVW) method as the primary approach. Comprehensive sensitivity analyses were conducted to validate the robustness of the results. Evaluation of instrumental variables was performed using the F-statistic, and a meta-analysis was employed to assess the average gene-predicted effect between ferritin and MI. The MR study revealed a negative correlation between ferritin and MI. The odds ratios (ORs) in the IVW method were 0.83 [95% confidence interval (CI) = 0.72-0.97; P = .017] and 0.86 (95% CI = 0.72-1.02; P = .080). Additionally, meta-analysis consistently indicated a negative causal relationship between ferritin and MI, with no heterogeneity or horizontal pleiotropy, thereby indicating a negative correlation between ferritin levels and the risk of MI. The genetic evidence sheds light on the causal relationship between ferritin levels and MI risk, providing new perspectives for future interventions in acute myocardial infarction (AMI).

Correlation Between the 8-hydroxy-2'-deoxyguanosine Level in the Peritoneal Solution of Patients Undergoing Peritoneal Dialysis and the Peritoneal Equilibration Test, Kt/V, Ferritin, and Albumin Levels.

INTRODUCTION: Peritoneal dialysis (PD) is an effective treatment  modality for advanced kidney failure, offering patients a significant  degree of independence. However, the long-term use of PD is  limited due to the degeneration of the peritoneal membrane,  resulting in reduced dialysis adequacy. Evaluating the peritoneal  membrane condition in patients with advanced kidney failure  who are undergoing PD is challenging with existing methods.  Therefore, this study aimed to investigate the correlation between  8-hydroxy-2'-deoxyguanosine (8OHDG) levels in the peritoneal  solution of patients undergoing PD and various factors, such  as peritoneal equilibration test (PET), dialysis adequacy (Kt/V),  underlying diseases, serum ferritin, and albumin levels. 8OHDG  is a sensitive marker of oxidative stress caused by DNA damage. METHODS: A total of 56 patients were included in this cross-sectional  study. Five milliliters of PD fluid were collected from the patients,  and 8-OHdG levels were measured using ELISA method. Then, they  were compared with PET, Kt/V, albumin, and ferritin markers in  the patients' files, and the results were analyzed by statistical tests. RESULTS: The study examined the correlation between 8OHDG  and other markers. It was found that this index had significant  associations with PET and underlying HTN (P < .05), whereas no  significant associations were identified with the other markers. CONCLUSION: The results of the present study demonstrate that  the level of 8OHDG, as one of the oxidative stress markers, could  be used to evaluate the function of the peritoneum in patients  undergoing PD. DOI: 10.52547/ijkd.7654.

Multivariate logistic regression analysis of poor prognosis of dermatomyositis and clinical value of ferritin/Kl-6 in predicting prognosis.

BACKGROUND: Dermatomyositis (DM) is a rare inflammatory disease. Our research focuses on predicting poor prognosis in DM patients and evaluating the prognostic significance of ferritin and Salivary Sugar Chain Antigen-6 (KL-6) through multivariate logistic regression analysis. METHODS: Between February 2018 and April 2020, 80 DM patients at our hospital were categorized into MDA5 positive (n = 20) and negative (n = 60) groups. We conducted multivariate logistic regression to determine DM's poor prognosis risk factors and evaluate ferritin/KL-6's predictive value for prognosis. RESULTS: Analysis showed no gender, age, body mass index (BMI), or lifestyle (smoking, drinking) differences, nor in dyspnea, muscle weakness, skin ulcers, and acetylcysteine treatment effects (p > 0.05). Significant differences emerged in arrhythmias, interstitial pneumonia, C-reactive protein, albumin, and lactate dehydrogenase levels (p < 0.05). Before treatment, differences were negligible (p > 0.05), but post-treatment, serum KL-6 and ferritin levels dropped. MDA5 positive patients had elevated serum KL-6 and ferritin levels than survivors (p < 0.05), with a strong correlation to DM. Combined diagnosis using serum KL-6 and ferritin for DM prognosis showed area under curves of 0.716 and 0.634, significantly outperforming single-index diagnoses with an area under curve (AUC) of 0.926 (p < 0.05). CONCLUSION: Serum KL-6 and ferritin show marked abnormalities in DM, useful as indicators for evaluating polymyositis and DM conditions. However, the study's small sample size is a drawback. Expanding the sample size is essential to monitor serum KL-6 and ferritin changes in DM patients under treatment more closely, aiming to improve clinical assessment and facilitate detailed research.

Clinical characteristics of HFE C282Y/H63D compound heterozygotes identified in a specialty practice: key differences from HFE C282Y homozygotes.

BACKGROUND: Patients with p.C282Y homozygous (p.C282Y) HFE mutations are more likely to develop hemochromatosis (HC) than p.C282Y/p.H63D compound heterozygotes (p.C282Y/H63D). RESEARCH DESIGN AND METHODS: We conducted a retrospective chart review of 90 p.C282Y and 31 p.C282Y/H63D patients at a referral practice to illustrate the differences in the natural history of the disease in these two HC cohorts. RESULTS: Over a median follow-up of 17 years, p.C282Y had higher mean serum ferritin (1105 mg/dL vs. 534 mg/dL, p = 0.001) and transferrin saturations (75.3% vs. 49.5%, p = 0.001) at diagnosis. p.C282Y underwent more therapeutic phlebotomies (TP) till de-ironing (mean 24 vs. 10), had higher mean mobilized iron stores (4759 mg vs. 1932 mg), and required more annual maintenance TP (1.9/year vs. 1.1/year, p = 0.039). p.C282Y/H63D were more likely to have obesity (45.2% vs. 20.2%, p = 0.007) at diagnosis, with a non-significant trend toward consuming more alcohol. There was no significant difference in the development of HC-related complications between the two cohorts. CONCLUSIONS: p.C282Y have a higher mobilizable iron and require more TP. p.C282Y/H63D likely require additional insults such as obesity or alcohol use to develop elevated ferritin. De-ironing may mitigate the risk of developing HC-related complications.

Factors affecting responsiveness of vadadustat in patients with anemia associated with chronic kidney disease: a post-hoc subgroup analysis of Japanese phase 3 randomized studies.

BACKGROUND: Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor developed for treating anemia in chronic kidney disease (CKD). The purpose of this post-hoc analysis was to investigate the factors affecting the responsiveness to vadadustat in anemia patients with nondialysis-dependent (NDD) or hemodialysis-dependent (HDD) CKD in two Japanese phase 3 studies. METHODS: Of 151 and 162 patients enrolled in NDD-CKD and HDD-CKD studies, 136 and 140 patients, respectively, were included and divided into subgroups for the analysis. To assess vadadustat responsiveness, the resistance index was defined as the mean body weight-adjusted dose of vadadustat (mg/kg) at weeks 20-24 divided by the mean hemoglobin (g/dL) at weeks 20-24. Multivariate analysis was performed to identify the variables affecting the resistance index. RESULTS: Independent factors identified as determinants for better response to vadadustat were as follows: high baseline hemoglobin, low baseline eGFR, high week-20-24 ferritin, and CKD not caused by autoimmune disease/glomerulonephritis/vasculitis in NDD-CKD; and male sex, high baseline C-reactive protein, and low baseline erythropoiesis-stimulating agent resistance index (ERI) in HDD-CKD. CONCLUSIONS: In this post-hoc analysis, several factors were identified as affecting the response to vadadustat. These results may provide useful information leading to an appropriate dose modification for vadadustat. CLINICAL TRIAL REGISTRATION: NCT03329196 (MT-6548-J01) and NCT03439137 (MT-6548-J03).

Hemodynamic, ventilatory and gas exchange responses to exercise using a cycle ergometer and the incremental shuttle walk test in pregnant women.

BACKGROUND: Cardiovascular disease, including hypertension, in pregnant women is a leading cause of morbidity and mortality globally. The development of reference intervals for cardiovascular responses using exercising testing to measure oxygen utilisation (V̇O2) with cardiopulmonary exercise testing (CPET), and distances walked using the incremental shuttle walk test (ISWT), may be promising methods to assess and stratify pregnant women regarding their risk of adverse pregnancy outcomes, to encourage exercise during pregnancy, and to improve exercise prescriptions during pregnancy. We aimed to determine the reference intervals for V̇O2 at rest, anaerobic threshold (AT), and submaximal exercise using CPET, and the reference interval for the ISWT, to develop a correlation equitation that predicts submaximal V̇O2 from the distance walked in the ISWT, and to explore the relationship between hemoglobin (Hb) and ferritin concentration and V̇O2 at AT in women in second trimester. METHODS: After prospective IRB approval (HREC 15/23) and clinical trials registration (ANZCTR ACTRN12615000964516), and informed written consent, we conducted CPET and the ISWT according to international guidelines in a university associated tertiary referral obstetric and adult medicine hospital, in healthy pregnant women in second trimester (14 to 27 gestational weeks). Hemoglobin and ferritin concentrations were recorded from pathology results in the participants' medical records at the time of exercise testing. Adverse events were recorded. RESULTS: About 90 participants undertook CPET, 28 of which also completed the ISWT. The mean ± SD age and body mass index (BMI) were 32 ± 3.2 years, and 25 ± 2.7 kg/m2. Median (IQR) gestation was 23 (22-24) weeks. One in 4 women were 24 weeks or greater gestation. The reference intervals for V̇O2 at rest, AT, and submaximal exercise were 2.9 to 5.3, 8.1 to 20.7, and 14.1 to 30.5 mL/kg/min respectively. The reference interval for the ISWT was 218 to 1058 meters. The correlation equation to predict submaximal V̇O2 from the distance walked in the ISWT was submaximal V̇O2 (mL/kg/min) = 0.012*distance walked in ISWT (m) + 14.7 (95%CI slope 0.005-0.070, Pearson r = 0.5426 95%CI 0.2126-0.7615, P = .0029). Hemoglobin concentration was positively correlated with V̇O2 at AT (AT V̇O2 (mL/kg/min) = 0.08*Hb (g/L) + 4.9 (95%CI slope 0.0791-0.143, Pearson r = 0.2538 95%CI 0.049-0.438, P = .016). There was no linear association between ferritin and submaximal V̇O2 (Pearson r = 0.431 P = .697). There were no maternal or fetal complications. CONCLUSIONS: CPET and ISWT are safe and feasible in women in second trimester including those at or beyond 24 weeks gestation. We have established the reference interval for V̇O2 at rest, AT, and submaximal exercise by CPET, the reference interval for the distance walked for the ISWT, and a correlation equation to predict submaximal V̇O2 for use in clinical practice and research. Hemoglobin rather than ferritin is likely correlated with exercise capacity in pregnancy suggesting vigilance to correct lower hemoglobin levels may positively impact maternal health. CLINICAL TRIALS REGISTRY: The study was prospectively registered with the Australian and New Zealand Clinical Date of registration - 15/9/2015; Date of initial participant enrolment - 4/11/2015; Clinical trial identification number; ACTRN12615000964516; URL of the registration site - https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369216.

Transferrin Saturation, Serum Ferritin, and C-Reactive Protein vs. Serum Ferritin for an optimal Iron Deficiency Diagnosis in Candidates for Bariatric Surgery.

INTRODUCTION: Iron has different physiological processes and is regulated by hepcidin that is also an acute phase reactant, which increases with inflammation. Obesity produces a pro-inflammatory state, affecting directly the normal regulation of iron, causing ferritin (FER) deficiency. FER is used as the only indicator of the status of iron in patients with obesity, so the majority of them would be underdiagnosed, leading to a high prevalence of iron deficiency (ID) and anemia. The aim of this study is to evaluate the diagnostic tests: transferrin saturation (TS), FER, and C-reactive protein (CRP) vs. FER with the objective of analyzing the most accurate variable for the diagnosis of ID. MATERIALS AND METHODS: We present a cross-sectional, analytical, and retrospective study, evaluating the diagnostic tests in 96 patients, to whom two methods were applied for the diagnosis of ID: method 1 (FER < 30 ng/mL) and method 2 divided into 2A (FER < 30 ng/mL), 2B (FER 30-100 ng/mL + CRP ≥ 5 mg/L), 2C (FER 100-300 ng/mL + CRP ≥ 5 mg/L + TS < 20%), and 2D (TS < 20%). RESULTS: The prevalence of ID obtained using method 1 was 30.2% while 69.8% presented ID using total method 2, confirming an underdiagnosis of 39.6%. CONCLUSION: The inflammatory state in patients with obesity must be considered in the diagnosis of ID. The use of TS, FER, and CRP has greater validity than the use of serum FER for the diagnosis of ID in patients with obesity.

Lower serum ferritin levels are associated with worse cognitive performance in aging.

OBJECTIVES: Iron is important for neurogenesis, synaptic development, and neurotransmitter synthesis. Serum ferritin (SF) is a reliable marker for assessing iron stores. Therefore, we evaluated the cognitive function associated with SF levels. We also assessed brain iron content using R2* Magnetic Resonance Imaging (MRI) and its association with SF levels. DESIGN: Data from three cross-sectional observational studies were used. Aging Imageomics (n = 1030) was conducted on aged subjects. Health Imageomics (n = 971) and IR0NMET (n = 175) were conducted in middle-aged subjects. SETTING AND PARTICIPANTS: Participants were enrolled at Dr. Josep Trueta University Hospital facilities. The three cohorts included a total of 2176 subjects (mean age, 52 years; 48% men). MEASUREMENTS: SF levels were measured by standard laboratory methods. Total Digits Span (TDS), and Phonemic Verbal Fluency (PVF) were used to assess executive function. Language function was assessed by semantic verbal fluency (SVF), attention by the Symbol Digit Modalities Test, and memory by the Memory Binding Tests - Total Free Recall and Total Delayed Free Recall. MRI was used to assess the iron content of the brain by R2*. RESULTS: In subjects aged 65 years or older, SF levels were associated with increased TDS (ß = 0.003, p = 0.02), PVF (ß = 0.004, p = 0.01), and SVF (ß = 0.004, p = 0.002) scores. After stratification by sex, these findings were significant only in men, where SF was associated with increased TDS (ß = 0.003, p = 0.01), PVF (ß = 0.004, p = 0.03), and SVF (ß = 0.004, p = 0.009) scores. In middle-aged subjects, SF was also associated with increased SVF scores (ß = 0.005, p = 0.011). Lastly, in men, SF levels were negatively associated with R2*, a surrogate marker of brain iron content, in both the left frontal inferior opercular area (r = -0.41, p = 0.005) and the right frontal inferior opercular area (r = -0.44, p = 0.002). CONCLUSIONS: SF is significantly and positively associated with cognition. In older people with low SF levels, iron supplementation may be a promising therapy to improve cognition.

Serum ferritin level is associated with liver fibrosis and incident liver-related outcomes independent of HFE genotype in the general population.

BACKGROUND & AIMS: Hyperferritinemia reflects iron accumulation in the body and has been associated with metabolic disturbances and alcohol use, and is also a common finding in individuals diagnosed with liver disease. The major genetic regulator of iron metabolism is the HFE gene. METHODS: The aim of this this study was to investigate the association between serum ferritin and liver fibrosis using the enhanced liver fibrosis (ELF) test, and the association between ferritin and liver-related outcomes in a Finnish population-based cohort of 6194 individuals (45% male, mean [± standard deviation] age, 52.9 ± 14.9 years; body mass index 26.9 ± 4.7 kg/m2). The effects of HFE variants on these associations were also evaluated. RESULTS: Serum ferritin levels were significantly associated with liver fibrosis, as estimated by enhanced liver fibrosis (ELF) test in weighted linear regression analysis. Serum ferritin was significantly associated with both all liver-related outcomes (n = 92) and severe liver-related outcomes (n = 54) in weighted Cox regression analysis (hazard ratio [HR] per 1 SD, 1.11 [95% confidence interval (CI) 1.02-1.21]; p = 0.012 and HR 1.11 [95% CI 1.02-1.21]; p = 0.013, respectively). However, there was association neither between HFE risk variants and ELF test nor between HFE risk variants and liver-related outcomes. CONCLUSION: Serum ferritin levels were associated with liver fibrosis and incident liver disease, independent of HFE genotype in the general population. Furthermore, data demonstrated that metabolic disturbances and alcohol use were major risk factors for hyperferritinemia.

Serum iron concentration and leptin inversely relate, partially mediated by body mass index in American adults.

Iron metabolism and leptin are interconnected, and both link with obesity. In this cross-sectional study, we hypothesized that serum iron markers associate with leptin, with body mass index (BMI) acting as a mediator, confounder, and effect modifier in this relationship. We analyzed data from the National Health and Nutrition Examination Survey III, with a focus on serum iron markers and leptin. The relationship between serum iron markers and leptin was determined by multiple linear regression. The bootstrap method was used to investigate the mediating effect of BMI on this association. Among 3888 American adults, serum iron and transferrin saturation showed a negative association with leptin (log2-transformed) (ß: -0.010, 95% confidence interval [CI], -0.013 to -0.006, P < .001; ß: -0.006, 95% CI, -0.008 to -0.004, P < .001). Total iron-binding capacity was positively associated with the serum concentration of leptin (log2-transformed) (ß: 0.002, 95% CI, 0-0.004, P = .0292). Sex, BMI, and body fat percentage significantly influenced these associations. Notably, the association between the iron markers and leptin diminished in individuals with a BMI ≥30 kg/m2. There was no observable relationship between leptin and serum ferritin concentrations. BMI mediated 4.81% of the serum iron-leptin association, with no mediation of body fat percentage. Our study identified a link between serum iron and leptin, with BMI as a mediating factor. In clinical settings, it is vital to understand how treatments targeting iron metabolism can directly impact serum leptin concentration and the subsequent physiological changes.