Prevalence of Iron Deficiency Using 3 Definitions Among Women in the US and Canada.

Importance: The prevalence of iron deficiency varies widely according to how it is defined. Objective: To compare the prevalence of iron deficiency among women using 3 different definitions. Design, Setting, and Participants: The cross-sectional Hemochromatosis and Iron Overload Screening Study (HEIRS; 2000-2006) evaluated the prevalence, determinants, and outcomes of hemochromatosis and other iron-related disorders. Multiethnic, primary care-based screening (2001-2003) was performed at 5 field centers (4 in the US and 1 in Canada). Volunteer women aged 25 years and older were recruited at primary care venues associated with the field centers. Data were analyzed from June to December 2023. Main Outcomes and Measures: Measures included transferrin saturation, serum ferritin level, and self-reported age, pregnancy, and race and ethnicity. Three iron deficiency definitions were studied: (1) combined transferrin saturation less than 10% and serum ferritin less than 15 ng/mL (HEIRS), (2) serum ferritin less than 15 ng/mL (World Health Organization [WHO]), and (3) serum ferritin less than 25 ng/mL (a threshold for iron-deficient erythropoiesis [IDE]). Results: Among 62 685 women (mean [SD] age, 49.58 [14.27] years), 1957 women (3.12%) had iron deficiency according to the HEIRS definition, 4659 women (7.43%) had iron deficiency according to the WHO definition, and 9611 women (15.33%) had iron deficiency according to the IDE definition. Among 40 381 women aged 25 to 54 years, 1801 women (4.46%) had iron deficiency according to HEIRS, 4267 women (10.57%) had iron deficiency according to WHO, and 8573 women (21.23%) had iron deficiency according to IDE. Prevalence rates of iron deficiency among 2039 women aged 25 to 44 years who reported pregnancy were 5.44% (111 women) according to HEIRS, 18.05% (368 women) according to WHO, and 36.10% (736 women) according to IDE. Iron deficiency prevalence by the 3 respective definitions increased significantly in each racial and ethnic group and was significantly higher among Black and Hispanic participants than Asian and White participants. The relative iron deficiency prevalence among the 62 685 women increased 2.4-fold (95% CI, 2.3-2.5; P < .001) using the WHO definition and increased 4.9-fold (95% CI, 4.7-5.2; P < .001) using the IDE definition. Conclusions and Relevance: Three definitions of iron deficiency were associated with significantly different prevalence of iron deficiency in women, regardless of self-reported age, pregnancy, or race and ethnicity. Using higher serum ferritin thresholds to define iron deficiency could lead to diagnosis and treatment of more women with iron deficiency and greater reduction of related morbidity.

Development and Validation of a Nomogram for Predicting Survival Based on Ferritin and Transferrin Ratio in Breast Cancer Patients.

BACKGROUND: Our objective is to develop a predictive model utilizing the ferritin and transferrin ratio (FTR) and clinical factors to forecast overall survival (OS) in breast cancer (BC) patients. METHODS: We conducted a retrospective analysis of clinical data from 2858 BC patients diagnosed between 2013 and 2021. Subsequently, the cohort of 2858 BC patients underwent random assignment into distinct subsets: a training cohort comprising 2002 patients and a validation cohort comprising 856 patients, maintaining a proportional ratio of 7:3. Employing multivariable Cox regression analysis within the training cohort, we derived a prognostic nomogram. The predictive performance was assessed using calibration curves, C-index, and decision curve analysis. RESULTS: The final prognostic model included the TNM stage, subtype, hemoglobin levels, and the ferritin-transferrin ratio. The nomogram achieved a C-index of .794 (95% CI: .777-.810). The nomogram demonstrated superior predictive accuracy for OS at 3, 5, and 7 years for BC, with area under the time-dependent curves of .812, .782, and .773, respectively. These values notably outperformed those of the conventional TNM stage. Decision curve analysis reaffirmed the greater net benefit of our nomogram compared to the TNM stage. These findings were subsequently validated in the independent validation cohort. CONCLUSION: The FTR-based prognostic model may predict a patient's OS better than the TNM stage in a clinical setting. The nomogram can provide an early, affordable, and reliable tool for survival prediction, as well as aid clinicians in treatment option-making and prognosis evaluation. However, further multi-center prospective trials are required to confirm the reliability of the existing nomogram.

BackgroundOur objective is to develop a predictive model utilizing the ferritin and transferrin ratio (FTR) and clinical factors to forecast overall survival (OS) in breast cancer (BC) patients.MethodsWe conducted a retrospective analysis of clinical data from 2858 BC patients diagnosed between 2013 and 2021. Subsequently, the cohort of 2858 BC patients underwent random assignment into distinct subsets: a training cohort comprising 2002 patients and a validation cohort comprising 856 patients, maintaining a proportional ratio of 7:3. Employing multivariable Cox regression analysis within the training cohort, we derived a prognostic nomogram. The predictive performance was assessed using calibration curves, C-index, and decision curve analysis.ResultsThe final prognostic model included the TNM stage, subtype, hemoglobin levels, and the ferritin-transferrin ratio. The nomogram achieved a C-index of .794 (95% CI: .777-.810). The nomogram demonstrated superior predictive accuracy for OS at 3, 5, and 7 years for BC, with area under the time-dependent curves of .812, .782, and .773, respectively. These values notably outperformed those of the conventional TNM stage. Decision curve analysis reaffirmed the greater net benefit of our nomogram compared to the TNM stage. These findings were subsequently validated in the independent validation cohort.ConclusionThe FTR-based prognostic model may predict a patient's OS better than the TNM stage in a clinical setting. The nomogram can provide an early, affordable, and reliable tool for survival prediction, as well as aid clinicians in treatment option-making and prognosis evaluation. However, further multi-center prospective trials are required to confirm the reliability of the existing nomogram.

Serum iron level is independently associated with sarcopenia: a retrospective study.

Sarcopenia greatly reduces the quality of life of the elderly, and iron metabolism plays an important role in muscle loss. This study aimed to investigate the association between iron status and sarcopenia. A total of 286 adult patients hospitalized between 2019 and 2021 were included in this study, of which 117 were diagnosed with sarcopenia. Serum iron, total iron binding capacity (TIBC), transferrin, and transferrin saturation levels were compared between groups with and without sarcopenia and were included in the logistic analyses, with significant variables further included in the logistic regression model for the prediction of sarcopenia. Serum iron, TIBC, and transferrin levels decreased significantly in the sarcopenia group (p < 0.05), and were negatively associated with handgrip strength, relative skeletal muscle index, and multiple test performances (p < 0.05). Multivariate logistic analysis showed that sex, age, body mass index (BMI), and serum iron level were independent risk factors for sarcopenia. In the final logistic regression model, male sex (odds ratio [OR] 3.65, 95% confidence interval [CI] 1.67-7.98), age > 65 years (OR 5.40, 95% CI 2.25-12.95), BMI < 24 kg/m2 (OR 0.17, 95% CI 0.08-0.36), and serum iron < 10.95 µmol/L (OR 0.39, 95% CI 0.16-0.93) were included. Our study supported the impact of iron metabolism on muscle strength and performance.

Iron parameters analysis in dogs with myxomatous mitral valve disease.

BACKGROUND: Myxomatous mitral valve disease (MMVD) is the most common acquired cardiovascular disease in small breed dogs. In contrast to human patients with heart failure (HF), iron deficiency (ID) prevalence in dogs with MMVD is weakly known. The study aimed to assess the usability of ID markers in serum and reticulocyte parameters from whole blood of dogs with MMVD to evaluate early ID symptoms. RESULTS: Sixty-eight dogs (43 male and 25 female) were included in the study. MMVD dogs were assigned according to the 2019 ACVIM guidelines for groups B1 (n = 9), B2 (n = 10), C (n = 27) and D (n = 10). Groups were also combined into B1 and B2 as non-symptomatic HF and C with D as symptomatic HF. Healthy controls were 12 dogs. Serum iron concentration below the reference range in dogs with MMVD was 12.5%. Other ID indices, such as %SAT, UIBC, and TIBC were similar in the MMVD groups and healthy controls (p > 0.05 for all parameters). Statistical comparison between control group and 4 groups of different stages of MMVD showed that significant differences occur only in serum transferrin. The assessment of ferritin and soluble transferrin receptors using Western Blotting did not show differences between control (n = 7) and MMVD (n = 33) dogs. Study has shown positive correlation between ID parameters and echocardiographic indices such as LA/Ao and LVIDdN, and some biochemical parameters. A significant increase in reticulocytes percentage, assessed manually, was observed in the HF group of animals (p = 0.027) compared to the control group. CONCLUSIONS: Studies have shown that ID parameters in serum are not significantly different in dogs with MMVD compared to healthy dogs. However, there is a clear correlation between atrial size and normalised left ventricular size to body size and some biochemical parameters, including ID parameters and therefore the severity of MMVD.

Molecularly imprinted polymer-based SERS sensing of transferrin in human serum.

Specific detection of glycoproteins such as transferrin (TRF) related to neurological diseases, hepatoma and other diseases always plays an important role in the field of disease diagnosis. We designed an antibody-free immunoassay sensing method based on molecularly imprinted polymers (MIPs) formed by the polymerization of multiple functional monomers for the sensitive and selective detection of TRF in human serum. In the sandwich surface-enhanced Raman spectroscopy (SERS) sensor, the TRF-oriented magnetic MIP nanoparticles (Fe3O4@SiO2-MIPs) served as capture units to specifically recognize TRF and 4-mercaptophenylboronic acid-functionalized gold nanorods (MPBA-Au NRs) served as SERS probes to label the targets. In order to achieve stronger interaction between the recognition cavities of the prepared MIPs and the different amino acid fragments that make up TRF, Fe3O4@SiO2-MIPs were obtained through polycondensation reactions between more silylating reagents, enhancing the specific recognition of the entire TRF protein and achieving high IF. This sensing method exhibited a good linear response to TRF within the TRF concentration range of 0.01 ng mL-1 to 1 mg mL-1 (R2 = 0.9974), and the LOD was 0.00407 ng mL-1 (S/N = 3). The good stability, reproducibility and specificity of the resulting MIP based SERS sensor were demonstrated. The determination of TRF in human serum confirmed the feasibility of the method in practical applications.

Iron Management and Anemia in Patients on the Active Kidney Transplant List.

INTRODUCTION: Iron metabolism disorders and anemia are one of the main complications of end-stage renal disease that may affect the evaluation process for kidney transplantation. The study aimed to assess the iron metabolism in hemodialysis patients in relation to waiting list status. STUDY METHOD: The study included 5068 hemodialysis patients, including those on the active waiting list (N = 449) and those who were not eligible for the waitlist (N = 4619). Demographic and biochemical data, Charlson's comorbidity index, duration of hemodialysis therapy and, respectively, hemoglobin, ferritin, and transferrin saturation levels were compared in both groups of patients. RESULTS: Patients on the active waiting list were significantly younger -53.2 vs 67.2 years (P < .001), with a lower Charlson comorbidity index score: 3.33 vs 4.42 (P < .001). The duration of hemodialysis therapy was similar: 66.0 vs 63.2 months (P = .416), the incidence of anemia according to World Health Organization (90.6%, vs 91.2%) and KDIGO (72.4% vs 70.4%). The degree of anemia correction in terms of hemoglobin concentration and transferrin saturation was comparable in both groups and amounted to an average of 10.9 g/dL (P = .349) for hemoglobin concentration and 32.7% vs 33.4% (P = .513) for transferrin saturation. However, there was a statistically significant difference in ferritin concentration: 554 ug/L vs 733 ug/L (P = .001). CONCLUSIONS: Patients on the active list have significantly lower ferritin levels despite similar duration of hemodialysis treatment and comparable hemoglobin values. This may be due to lower inflammation, and less frequent blood transfusions, and lead to a lower risk of immunization and an increased chance of potential kidney transplantation.

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.

Absolute iron deficiency, coronary artery calcification and cardiovascular mortality in maintenance haemodialysis patients.

AIM: The effects of iron on vascular calcification in rats and vascular smooth muscle cells were recently reported, but clinical studies on iron and vascular calcification are scant. We studied the associations of absolute iron deficiency, coronary artery calcification and mortality in patients with maintenance haemodialysis (MHD). METHODS: Transferrin saturation (TSAT), ferritin, mean corpuscular haemoglobin (MCH) and Agatston coronary artery calcium score (CACS) were studied at baseline in MHD patients and followed up for 3 years. Cox proportional hazard analyses for mortality and linear regression analyses for CACS were performed. RESULTS: In 306 patients, the median age was 67 (56-81) years, dialysis duration was 76 (38-142) months, and diabetes prevalence was 42.5%. Fifty-two patients had died by 3 years. Patients with absolute iron deficiency (TSAT <20% and ferritin <100 ng/mL) (n = 102) showed significantly higher CACS (p = .0266) and C-reactive protein (p = .0011), but a lower frequency of iron formulation administration compared with patients without absolute iron deficiency at baseline (n = 204). Absolute iron deficiency was a significant predictor for 3-year cardiovascular (CV) mortality (hazard ratio: 2.08; p = .0466), but not for 3-year all-cause mortality. CACS was significant predictor for both 3-year CV and all-cause mortality (p <.05). Absolute iron deficiency and MCH were significant determinants of CACS (p < .05). CONCLUSION: MHD patients with absolute iron deficiency showed significantly higher CACS than others, and absolute iron deficiency was a significant risk factor for coronary artery calcification and 3-year CV mortality in MHD patients, but was not a significant predictor for 3-year all-cause mortality.

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.

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.

Using Ipratropium Bromide Nasal Spray Response as a Screening Tool in the Diagnostic Workup of Cerebrospinal Fluid Rhinorrhea.

OBJECTIVES: Unilateral clear thin rhinorrhea (UCTR) can be concerning for a nasal cerebrospinal fluid (CSF) leak. Beta-2 transferrin electrophoresis has been the gold standard for initial non-invasive confirmatory testing for CSF rhinorrhea, but there can be issues with fluid collection and testing errors. Ipratropium bromide nasal spray (IBNS) is highly effective at reducing rhinitis-related rhinorrhea, and should presumably not resolve CSF rhinorrhea. This study assessed whether different clinical features and IBNS response helped predict presence or absence of CSF rhinorrhea. METHODS: A prospective cohort study was conducted where all patients with UCTR had nasal fluid tested for beta-2 transferrin, and were prescribed 0.06% IBNS. Patients were diagnosed with CSF rhinorrhea or other rhinologic conditions. Clinical variables like IBNS response (rhinorrhea reduction), positional worsening, salty taste, postoperative state, female gender, and body-mass index were assessed for their ability to predict CSF rhinorrhea. Sensitivity, specificity, and predictive values and odds ratios were calculated for all clinical variables. RESULTS: Twenty patients had CSF rhinorrhea, and 53 had non-CSF etiologies. Amongst clinical variables assessed for predicting CSF absence or presence, significant associations were shown for IBNS response (OR = 844.66, p = 0.001), positional rhinorrhea worsening (OR = 8.22, p = 0.049), and body-mass index ≥30 (OR = 2.92, p = 0.048). IBNS response demonstrated 96% sensitivity and 100% specificity, and 100% positive and 91% negative predictive values for predicting CSF rhinorrhea. CONCLUSIONS: In patients with UCTR, 0.06% IBNS response is an excellent screening tool for excluding CSF rhinorrhea, and should be considered in the diagnostic workup of CSF rhinorrhea. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:56-61, 2024.

Associations Between Serum Iron Biomarkers and Breast Cancer Tumor Size.

Excess iron has been shown to promote tumor growth in animals whereas iron deficiency has been associated with reduced or slowed tumor growth. The objective of this analysis was to estimate the associations between serum iron biomarkers and tumor size at diagnosis and metastatic status in a sample of breast cancer cases from the Sister Study.The analytic sample included 2,494 incident breast cancer cases with information on tumor size and iron biomarkers, including serum iron (mcg/dL), ferritin (mcg/dL), and percent transferrin saturation, measured in serum collected at baseline. We used Spearman rank correlation and linear regression models to assess the associations between one SD changes in serum iron biomarker levels and natural log of tumor size (cm) adjusting for body mass index and age at study entry.We did not find strong associations between any of the three serum iron biomarkers and tumor size. Adjusted regression slopes (95% confidence interval) were -0.016 (-0.048 to 0.016) for serum iron, -0.032 (-0.064 to <0.001) for ferritin, and -0.010 (-0.043 to 0.023) for transferrin saturation.This study did not provide evidence supporting the hypothesis of a positive association between breast cancer tumor size at diagnosis and prediagnostic serum iron levels. Conflicting evidence between this study and previous research in animal models suggests that iron in the human tumor microenvironment may operate independently of circulating iron or body iron stores.Iron has shown protumorigenic activity in animal models, but our data do not support a positive relationship between breast tumor growth and iron status. SIGNIFICANCE: Using a large sample of women from a U.S. prospective cohort, we assessed associations between several serum iron measures at baseline and breast cancer tumor size and metastatic status. All estimated associations were close to zero with no evidence to support our hypothesis of higher body iron levels associated with larger tumor size. These results suggest the human tumor microenvironment operates independently of circulating serum iron levels.

Defining trimester-specific reference intervals for carbohydrate deficient transferrin in pregnant women.

OBJECTIVES: Extensive consumption of alcohol during pregnancy can lead to severe complications for the unborn child. Carbohydrate-deficient transferrin (CDT) levels in serum have become a common biomarker for excessive alcohol intake. However, during pregnancy CDT levels can rise to levels above commonly used cut-off values, for reasons unrelated to alcohol intake. The aim of this study is to investigate the changes in CDT values during pregnancy and to determine accurate, trimester dependent reference intervals. METHODS: 439 serum samples of 147 healthy pregnant women were obtained for trimester 1, 2, 3, and post-partum and were analysed by high-performance liquid chromatography (HPLC) and an N-Latex immunonephelometric assay. New trimester-specific reference intervals were established. RESULTS: This study demonstrates there is a trimester-dependent increase of %CDT, as up to 39.4% of the population exceeded the previously established upper reference limit of 1.7%. In our study the estimated upper reference limit for %DST/%CDT were 1.55%, 1.96%, 2.05% and 1.35% for trimester 1, 2, 3 and post-partum for the HPLC-method and 2.02%, 2.19%, 2.19% and 1.96% for the N-Latex immunoassay. CONCLUSIONS: We demonstrate that CDT levels rise during pregnancy. The magnitude of the increase is method-dependent and needs to be taken into account. We have established method- and trimester-specific reference intervals to prevent false-positive results in alcohol abuse screening tests during pregnancy.

Utility of iron biomarkers in differentiating menopausal status: Findings from CoLaus and PREVEND.

AIM: To examine the association of iron biomarkers with menopausal status and assess whether these biomarkers can help differentiate menopausal status beyond age. METHODS: In this cross-sectional study we included 1679 women from the CoLaus and 2133 from the PREVEND cohorts, with CoLaus used as primary cohort and PREVEND for replication. Ferritin, transferrin, iron, and transferrin saturation (TSAT) were used to assess iron status. Hepcidin and soluble transferrin receptor were assessed only in PREVEND. Menopausal status was self-reported and defined as menopausal or non-menopausal. Logistic regressions were used to explore the association of these iron biomarkers with menopause status. Sensitivity, specificity, area under the receiver operating characteristic curves (AUC), positive and negative predictive values as well as cut-off points for the iron biomarkers were calculated. The model with the highest AUC was defined as the best. RESULTS: In the CoLaus and PREVEND cohorts, respectively, 513 (30.6 %) and 988 (46.3 %) women were postmenopausal. Ferritin (OR, 2.20; 95 % CI 1.72-2.90), transferrin (OR, 0.03; 95 % CI 0.01-0.10), and TSAT (OR, 1.28; 95 % CI 1.06-1.54) were significantly associated with menopausal status in CoLaus, with the findings replicated in PREVEND. AUC of age alone was 0.971. The best model resulted from combining age, ferritin, and transferrin, with an AUC of 0.976, and sensitivity and specificity of 87.1 % and 96.5 %, respectively. Adding transferrin and ferritin to a model with age improved menopause classification by up to 7.5 %. In PREVEND, a model with age and hepcidin outperformed a model with age, ferritin, and transferrin. CONCLUSION: Iron biomarkers were consistently associated with menopausal status in both cohorts, and modestly improved a model with age alone for differentiating menopause status. Our findings on hepcidin need replication.

Association of Estimated Total Body Iron with All-Cause Mortality in Japanese Hemodialysis Patients: The Miyazaki Dialysis Cohort Study.

Iron deficiency/excess may be associated with worse prognosis in patients undergoing hemodialysis. This study ascertained the association of the estimated total body iron (TBI) with mortality in patients receiving hemodialysis. Multicenter clinical data collected in the Miyazaki Dialysis Cohort Study from 943 patients receiving hemodialysis were analyzed after stratification into tertile categories by baseline TBI-estimated as the heme iron plus iron storage from ferritin levels. The primary outcome was a 5-year all-cause mortality; hazard ratios of the TBI-all-cause mortality association were estimated using Cox models adjusted for potential confounders, including clinical characteristics, laboratory, and drug data, wherein patients with high TBI were the reference category. The receiver operating characteristic (ROC) curve analyses of TBI, serum ferritin levels, and transferrin saturation were performed to predict all-cause mortality; a total of 232 patients died during the follow-up. The low TBI group (<1.6 g) had significantly higher hazard ratios of mortality than the high TBI group (≥2.0 g). As ROC curve analyses showed, TBI predicted mortality more accurately than either levels of serum ferritin or transferrin saturation. Lower TBI increases the mortality risk of Japanese hemodialysis patients, and further studies should examine whether iron supplementation therapy that avoids low TBI improves prognosis.

Predictive risk markers in alcoholism.

The medical disorders of alcoholism rank among the leading public health problems worldwide and the need for predictive and prognostic risk markers for assessing alcohol use disorders (AUD) has been widely acknowledged. Early-phase detection of problem drinking and associated tissue toxicity are important prerequisites for timely initiations of appropriate treatments and improving patient's committing to the objective of reducing drinking. Recent advances in clinical chemistry have provided novel approaches for a specific detection of heavy drinking through assays of unique ethanol metabolites, phosphatidylethanol (PEth) or ethyl glucuronide (EtG). Carbohydrate-deficient transferrin (CDT) measurements can be used to indicate severe alcohol problems. Hazardous drinking frequently manifests as heavy episodic drinking or in combinations with other unfavorable lifestyle factors, such as smoking, physical inactivity, poor diet or adiposity, which aggravate the metabolic consequences of alcohol intake in a supra-additive manner. Such interactions are also reflected in multiple disease outcomes and distinct abnormalities in biomarkers of liver function, inflammation and oxidative stress. Use of predictive biomarkers either alone or as part of specifically designed biological algorithms helps to predict both hepatic and extrahepatic morbidity in individuals with such risk factors. Novel approaches for assessing progression of fibrosis, a major determinant of prognosis in AUD, have also been made available. Predictive algorithms based on the combined use of biomarkers and clinical observations may prove to have a major impact on clinical decisions to detect AUD in early pre-symptomatic stages, stratify patients according to their substantially different disease risks and predict individual responses to treatment.

Correlation of iron and related factors with disease severity and outcomes and mortality of patients with Coronavirus disease 2019.

BACKGROUND: Iron is a trace element that possesses immunomodulatory properties and modulates the proneness to the course and outcome of a diverse viral diseases. This study intended to investigate the correlation of different iron-related factors with disease severity and outcomes as well as the mortality of coronavirus disease 2019 (COVID-19) patients. METHODS: Blood serum samples were obtained from 80 COVID-19 cases and 100 healthy controls. Concentrations of ferritin, transferrin, total iron binding capacity (TIBC) was measured by Enzyme-linked immunosorbent assay (ELISA) and iron level was measured by immunoturbidometric method. RESULTS: Concentrations of iron, transferrin, and TIBC were low, while ferritin level was high in the COVID-19 cases in comparison to controls. In non-survivor (deceased) patients as well as severe subjects, the levels of iron, ferritin, transferrin, and TIBC were significantly different than survivors (discharged) and mild cases. Significant correlations were found between iron and related factors and the clinicopathological features of the patients. Based on ROC curve analysis, iron, ferritin, transferrin, and TIBC had potential to estimate disease severity in COVID-19 subjects. CONCLUSION: Iron metabolism is involved in the pathogenesis of COVID-19. Iron and related factors correlate with disease outcomes and might serve as biomarker in diagnosis of the disease severity and estimation of mortality in the COVID-19 subjects.

Evaluation of Albumin, Transferrin and Transthyretin in Inflammatory Bowel Disease Patients as Disease Activity and Nutritional Status Biomarkers.

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is often accompanied by malnutrition that manifests itself as nutrient deficiencies and body mass loss or deficit. The purpose of this study is to evaluate the utility of albumin, transferrin and transthyretin levels in the assessment of nutritional status and IBD activity. The case-control study included 82 IBD patients. The serum concentrations of albumin, transferrin and transthyretine were determined by a quantitative sandwich enzyme-linked immunosorbent assay (ELISA). Significantly lower median concentrations of albumin were found in the IBD patients vs. controls and in CD patients compared to the UC patients. Significantly higher median transthyretin concentrations were found in the IBD patients compared to the healthy subjects. There were no significant differences in median transferrin concentrations between the IBD patients and the healthy subjects. Significantly higher albumin levels were found in IBD patients in remission compared to patients with moderate and severe exacerbation of IBD symptoms. There were no significant differences in the median transferrin or transthyretin levels in patients with IBD depending on disease activity. No differences were identified in the median transferrin or transthyretin levels in the IBD patients according to nutritional status. The median albumin concentrations in the IBD subjects were significantly higher in patients with normal body fat, normal BMI and normal waist circumferences compared to those with an abnormal nutritional status. The albumin levels reflect both nutritional status and disease activity and therefore cannot be considered a prognostic marker of malnutrition in IBD. As regards the utility of transferrin and transthyretin as markers of activity and nutritional status in IBD patients, further studies are required.

Compositional variations in metal nanoparticle components of welding fumes impact lung epithelial cell toxicity.

Welding fumes contain harmful metals and gas by-products associated with development of lung dysfunction, asthma, bronchitis, and lung cancer. Two prominent welding fume particulate metal components are nanosized iron (Fe) and manganese (Mn) which might induce oxidative stress and inflammation resulting in pulmonary injury. Welding fume toxicity may be dependent upon metal nanoparticle (NP) components. To examine toxicity of welding fume NP components, a system was constructed for controlled and continuous NP generation from commercial welding and customized electrodes with varying proportions of Fe and Mn. Aerosols generated consisted of nanosized particles and were compositionally consistent with each electrode. Human alveolar lung A459 epithelial cells were exposed to freshly generated metal NP mixtures at a target concentration of 100 µg/m3 for 6 hr and then harvested for assessment of cytotoxicity, generation of reactive oxygen species (ROS), and alterations in the expression of genes and proteins involved in metal regulation, inflammatory responses, and oxidative stress. Aerosol exposures decreased cell viability and induced increased ROS production. Assessment of gene expression demonstrated variable up-regulation in cellular mechanisms related to metal transport and storage, inflammation, and oxidative stress based upon aerosol composition. Specifically, interleukin-8 (IL-8) demonstrated the most robust changes in both transcriptional and protein levels after exposure. Interleukin-8 has been determined to serve as a primary cytokine mediating inflammatory responses induced by welding fume exposures in alveolar epithelial cells. Overall, this study demonstrated variations in cellular responses to metal NP mixtures suggesting compositional variations in NP content within welding fumes may influence inhalation toxicity.