Search Results (1,616)

Heart failure (HF) is frequently associated with iron deficiency and anemia, negatively impacting patient outcomes. This study aimed to investigate the contribution of genetic variation in iron metabolism-related genes to biochemical and hematological phenotypes in HF. An HF population of 182 patients with functional iron deficiency (ID) and anemia was stratified by sex and heart failure subtype, including HF with reduced ejection fraction (HFrEF) and HF with non-reduced ejection fraction (HFnrEF). Genetic variants in HFE (rs1799945), SLC40A1 (rs1439816, rs2304704), and TMPRSS6 (rs855791) were evaluated. Variants in HFE and SLC40A1 were associated with differences in serum iron, ferritin, transferrin saturation, hemoglobin, and RDW. The phenotypic impact of these variants was modulated by sex and heart failure subtype, highlighting the influence of iron availability, inflammatory burden, and erythropoietic demand. In contrast, no significant associations were observed for the TMPRSS6 variant. In conclusion, genetic variation in key regulators of iron metabolism contributes to the heterogeneity of iron-related biochemical and hematological phenotypes in HF. These findings emphasize the interplay between genetic background, sex, and heart failure physiology and support the relevance of personalized approaches to iron assessment and management in heart failure. Full article

Background: Brucellosis is a globally distributed zoonotic disease characterized by highly variable clinical manifestations that may mimic systemic autoimmune and inflammatory disorders. In Europe, where the incidence of brucellosis is relatively low, limited clinical awareness may contribute to delayed diagnosis and inappropriate management. In addition to zoonotic transmission, Brucella species are a well-recognized cause of laboratory-acquired infections (LAIs) among microbiology laboratory personnel. Methods: We report a case of laboratory-acquired Brucella abortus infection in a young woman presenting with undulant fever, arthralgia, systemic inflammation, elevated ferritin levels, and antinuclear antibody (ANA) positivity. Microbiological confirmation was achieved through serological testing (ELISA), repeat blood cultures, species-specific quantitative PCR, and whole-genome sequencing (WGS) followed by core genome multilocus sequence typing (cgMLST). Results: Initial laboratory evaluation revealed elevated C-reactive protein, mildly increased ferritin levels (146 ng/mL), abnormal liver enzyme levels, and rising ANA titers (from 1:160 to 1:320), raising suspicion of a systemic autoimmune disorder and prompting consideration of corticosteroid therapy. Although the initial blood culture was negative, subsequent molecular diagnostics and repeat cultures confirmed B. abortus infection. Epidemiological investigation suggested a possible occupational exposure in a diagnostic microbiology laboratory, consistent with a laboratory-acquired infection. Genomic analysis classified the isolate as sequence type 1 (ST1) and demonstrated zero allelic differences compared with the ST1 reference strain. Targeted antimicrobial therapy resulted in complete clinical recovery, supporting an infection-triggered immune response rather than primary autoimmunity. Conclusions: Acute brucellosis should be considered in the differential diagnosis of febrile syndromes accompanied by autoimmune-like laboratory abnormalities, even in low-incidence regions. This case highlights the diagnostic challenges posed by laboratory-acquired brucellosis and underscores the importance of early microbiological investigation and strict biosafety awareness in laboratory settings. Full article

We evaluated the interplay between systemic total antioxidant capacity (TAC), oxidative stress (OS) (lipid hydroperoxides), inflammation, iron status, and oral contraception (OC) use in 182 healthy 23-year-old women (76 OC-users, and 106 non-OC-users). In all women, blood TAC (FORD units) values were significantly inversely associated with OS (FORT units), high-sensitivity C-reactive protein (hsCRP), and transferrin; and positively associated with transferrin saturation (TfS%). No significant associations were observed for hemoglobin, hematocrit, red blood cells, serum iron, soluble transferrin receptor (sTfR), sTfR/log(ferritin) ratio (sTfR-F index), ferritin, folate, uric acid, or creatinine. OS hydroperoxides were positively associated with hsCRP and transferrin, and inversely associated with TfS%. sTfR was positively correlated with hydroperoxides in non-OC-users and with folate in all women and non-OC-users, but was not associated with hsCRP in any group. The combined abnormal condition of low TAC and elevated OS (n = 71) was significantly more frequent among OC-users (OR = 39.0), women with hsCRP ≥ 3 mg L⁻¹ (OR = 10.1), transferrin ≥ 330 mg dL⁻¹ (OR = 6.58), and smokers (OR = 3.76). OC use modulated the TAC/OS balance and inflammation. Low TAC and elevated OS may impact health status. Enhanced TAC/OS knowledge may increase awareness of effects of OC use among fertile-age women. Ferritin was independent of TAC/OS status and OC use, supporting its reliability as an iron biomarker. Full article

Background/Objectives: This study aimed to investigate the impact of allergic diseases (AD) or obstructive sleep apnea (OSA) risk, as a host factor, on the development of severe Mycoplasma pneumoniae Pneumonia (SMPP) in children by analyzing the clinical data of pediatric patients with Mycoplasma pneumoniae Pneumonia (MPP). Methods: This retrospective study enrolled children hospitalized with Mycoplasma pneumoniae pneumonia (MPP) at Shanghai Ninth People’s Hospital from November 2024 to November 2025. Patients were classified into severe (SMPP) and mild (MMPP) groups. Demographic, clinical, laboratory, and questionnaire data were collected and compared between groups. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of SMPP and construct a nomogram. The model was validated for discrimination, calibration, and clinical utility using ROC curves, calibration plots, and decision curve analysis, with internal validation by bootstrap resampling. Results: Among the 150 enrolled children with MPP, 35 (23.3%) were classified as severe (SMPP) and 115 (76.7%) as mild (MMPP). Patients with SMPP exhibited significantly higher frequencies of allergic diseases, prolonged fever and steroid use, elevated inflammatory markers (CRP, LDH, D-dimer, ferritin, ALT), and higher PSQ and RQLQ scores (all p < 0.05). Disease severity was positively correlated with these clinical, laboratory, and questionnaire-based parameters. Multivariate logistic regression identified allergic diseases, PSQ score, LDH, and ferritin as independent predictors of SMPP. A nomogram incorporating these four factors demonstrated good predictive performance, with an internally validated C-index of 0.827, satisfactory calibration (Hosmer–Lemeshow p = 0.116), and clinical utility within a 0–25% threshold probability range on decision curve analysis. Conclusions: Children with MPP and comorbid AD or OSA risk are more likely to develop SMPP. Among children aged 6–12 years, RQLQ score is positively correlated with the severity of MPP. AD, PSQ score, LDH, and ferritin are independent risk factors for SMPP. Clinicians should be alert to the development of SMPP when children with MPP present with a history of AD, PSQ score >3.5, LDH >327.50 U/L, or ferritin >120.05 ng/mL. The visual nomogram model constructed by combining these risk factors demonstrates improved predictive performance for SMPP, with high predictive efficacy and accuracy. It has great clinical value and can be used for individualized risk assessment and early intervention. However, our proposed nomogram requires external validation prior to broader implementation. Full article

Background: Test descriptions from major diagnostic manufacturers do not include ferritin reference intervals (RIs) for individuals aged 60 and older. The absence of older adults-specific RIs contrasts with the widespread use of serum ferritin testing in older adults. We aimed to establish and verify RIs using two common analytical methods. Methods: For this study, 1467 older adults were prospectively enrolled and monitored for morbidity and mortality, and exclusion criteria were applied. Ferritin was measured using chemiluminescent microparticle immunoassay (CMIA) and transferred to an electrochemiluminescence immunoassay (ECLIA) using method comparison. RIs were evaluated using a direct method with a prospective observational study based on healthy individuals according to the Clinical and Laboratory Standards Institute (CLSI) 28-A3c guideline and compared with RIs obtained using an indirect approach based on data obtained in clinical routine outpatients, where normal and abnormal values are supposed to be statistically differentiated to determine RIs. When applied within a countrywide population-based setting in Liechtenstein, the impact of novel RIs on the frequency of abnormal values was analyzed. Results: A total of 386 men and 532 women were included in the direct RI determination. Women (W) had significantly lower ferritin levels than men (M), while age over the age of 60 years had no significant association with ferritin in men and women. RIs were 23–241 ng/mL (W) and 19–396 ng/mL (M) for CMIA and 27–293 ng/mL (W) and 23–480 ng/mL (M) for ECLIA. These RIs are higher than those mentioned in the test descriptions in both tests. In comparison, the indirect method for both assays showed comparably lower reference limits, whereas upper reference limits were only approximately similar. The prevalence of high abnormal ferritin levels was considerably lower with this study’s RIs compared with manufacturer RIs. Conclusions: Employing older adults-specific RIs in clinical routine seems to be advisable. This reduces the frequency of abnormal high values in comparison with the widely applied practice of extrapolating RIs obtained from younger age groups to older adults and therefore leads to fewer follow-up investigations. Full article

Fish oil (FO) has been shown to confer beneficial effects on hepatic diseases in both humans and animals. This study aimed to investigate whether dietary fish oil (FO) supplementation alleviates deoxynivalenol (DON)-induced liver injury by modulating the ferroptosis signaling pathway in weaned piglets. Twenty-four weaned piglets were allocated to a 2 × 2 factorial design, with the main factors consisting of dietary treatment (5% corn oil or 5% FO supplementation) and DON exposure (basal diet or diet contaminated with 4 mg/kg DON). After 21 days of dietary treatment, piglets were euthanized for collection of blood and liver samples. Dietary FO significantly attenuated DON-induced hepatic structural damage and inflammatory infiltration. Specifically, FO supplementation reduced the activities of aspartate transaminase (AST) and alkaline phosphatase (ALP), as well as the AST/alanine aminotransferase (ALT) ratio following DON exposure. Dietary FO also decreased malondialdehyde (MDA) concentrations in both the liver and serum, lowered hepatic 4-hydroxynonenal (4-HNE) level and Fe²⁺ content, and increased hepatic glutathione (GSH) content. Moreover, dietary FO ameliorated ultrastructural liver damage induced by DON. Furthermore, DON significantly downregulated the mRNA levels of multiple genes associated with iron metabolism and ferroptosis, including heat shock protein beta-1 (HSPB1), acyl-CoA synthetase long chain family member 4 (ACSL4), and arachidonate 15-lipoxygenase (ALOX15), and upregulated the mRNA levels of transferrin (TF), ferritin heavy chain (FTH), solute carrier family 7 member 11 (SLC7A11), and transferrin receptor 1 (TFR1). Dietary FO counteracted these alterations by decreasing the mRNA of SLC7A11, TFR1, FTH, and TF after DON exposure. Finally, FO significantly decreased the protein expression of SLC7A11, iron-responsive element-binding protein 2 (IREB2), and FHT1 and increased the GPX4 protein expression following DON exposure. These findings suggest that FO may ameliorate DON-induced liver injury in weaned piglets, possibly through suppressing the ferroptosis signaling pathway. Full article

Background and aim: Celiac disease (CD) is a systemic autoimmune disorder triggered by gluten ingestion, and the only effective treatment is strict adherence to a gluten-free diet (GFD). Many factors, including limited dietary diversity and poor adherence, are associated with an increased risk of specific micronutrient deficiencies and malnutrition. This study aims to evaluate the relationship between adherence to GFD, celiac antibody levels, micronutrient levels, and nutritional status in children with CD. Methods: This retrospective study was conducted on 402 children aged 2–18 years with a diagnosis of CD confirmed positive by anti-tTG IgA and duodenal biopsy, all of whom had been on GFD for at least six months. Demographic, anthropometric, clinical, serological, and biochemical data (including hemogram, serum iron, ferritin, vitamin D, folate, and B12 levels), and GFD adherence were collected from medical records. Results: Most individuals are girls (64.9%), with a mean age of 10.6 ± 4.20 years. Chronic malnutrition was observed in 29.4% of patients. Acute malnutrition was identified in 27.8% of children, and wasting was observed in 6.7%. Iron deficiency anemia was the most frequently encountered micronutrient deficiency among the patients (23.9%). The prevalence of stunting was significantly higher among individuals with positive tTG-IgA levels and poor adherence to the GFD. Conclusions: Poor adherence to the GFD and positive tTG-IgA levels were associated with higher rates of stunting, underlining the need for individualized dietary follow-up and regular monitoring of both nutritional status and serological response in children with CD. Full article

Background: Iron overload and its associated complications are major concerns in patients with transfusion-dependent β-thalassaemia (TDT). Iron chelation is an important part of TDT therapy with monotherapy or dual iron chelation being the most commonly used strategies. Evidence regarding the efficacy and safety of triple iron chelation therapy remains limited. Case presentation: We present the case of a 21-year-old immigrant from the Middle East with TDT and a history of irregular transfusion management without chelation therapy, leading to clinically significant iron overload. She was successfully treated with the combination of deferoxamine, deferasirox and deferiprone over a course of 8 years. Triple chelation therapy led to sustained reductions in serum ferritin levels and improvement in hepatic and cardiac iron burden on follow-up MRI, with good tolerability. Conclusions: This case highlights the potential role of triple iron chelation therapy as a therapeutic strategy in TDT patients with severe iron overload. Further studies are needed to establish optimal dosing, eligible patients and long-term safety. Full article

The responsiveness of the stress axis is fundamental for maintaining health and sustaining productive performance; however, the effect of modulating this stress axis with bovine appeasing substance and its effects on biochemical, immunological, oxidative parameters and uterine involution have not been determined, which are the objectives of this experiment. To elucidate these questions, Holstein cows, from the prepartum to lactation period in a cross-ventilation system, received an application of a bovine appeasing substance (treated group) and a 0.9% saline solution (control group) at the time of calving, and blood samples were collected on calving day and on days 3, 7, 14 and 21 postpartum for analysis. Modulation of the stress axis by bovine appeasing substance increased magnesium levels on days 7 and 14 postpartum, with a reduction in fructosamine levels on days 3, 7, 14, and 21 postpartum. A reduction in ferritin levels, an acute-phase protein, and a reduction in interleukin 1 beta and interleukin 6 were also observed, demonstrating an anti-inflammatory effect in cows of the treated group. Creatine kinase activity decreased on day 21 postpartum in cows treated with bovine appeasing substances. An increase in cholinesterase activity on day 7 and a marked decrease on day 21 postpartum in treated cows were observed compared to the control. This was accompanied by a reduction in beta-hydroxybutyrate levels on day 7 and a reduction in reactive oxygen species levels on day 14 in animals of the treated group, indicating modulation of ketogenesis and reduced oxidation through an anti-inflammatory effect. Mean uterine thickness was also affected by the bovine appeasing substance, with a lower mean thickness on day 21 postpartum in treated cows. Modulation of the stress axis by the bovine appeasing substance reduces inflammation, improving energy dynamics and reducing oxidation, thus facilitating tissue repair associated with postpartum uterine involution in dairy cows. Full article

Vitamin D insufficiency is highly prevalent in athletic populations residing at northern latitudes, particularly among young athletes training predominantly indoors. The impact of vitamin D on musculoskeletal health is well-established, while its influence on physical performance is not entirely clear. The aim of this study was to determine the prevalence of vitamin D insufficiency in Estonian female adolescent athletes and to examine associations of serum 25-hydroxyvitamin D [25(OH)D] with body composition, energy intake, physical performance and ferritin. Seventy-three female athletes aged 14–18 years participated. Body composition was assessed by dual-energy X-ray absorptiometry; physical performance by peak oxygen consumption (VO₂peak/kg) and countermovement jumps; dietary intake was estimated using repeated 24 h recalls; and fasting blood samples were analyzed for 25(OH)D and ferritin. The mean serum 25(OH)D concentration was 67.6 ± 21.4 nmol.L⁻¹ and ranged from 27.4 to 118.0 nmol.L⁻¹. Vitamin D insufficiency (25(OH)D < 75 nmol.L⁻¹) was present in 67% of participants, leaving only one-third with sufficient levels. Serum 25(OH)D concentration was positively associated with VO₂peak/kg (r = 0.26; p = 0.043) independent of confounding variables. In conclusion, these findings suggest that vitamin D insufficiency is highly prevalent among Estonian female adolescent athletes, and 25(OH)D concentration is associated with aerobic performance. Full article

Background/Objectives: Iron deficiency (ID) is a critical comorbidity in chronic heart failure (CHF) that impairs myocardial energy metabolism and clinical outcomes. Despite its significance, data regarding ID prevalence in Southeast Asian CHF populations remain insufficient. This study aimed to determine the prevalence of ID and identify its independent clinical correlates among CHF patients at a leading tertiary hospital in Vietnam using high-precision automated diagnostic platforms. Methods: A descriptive cross-sectional study was conducted on 138 adult CHF patients. Serum iron and ferritin were quantified using photometric and electrochemiluminescence immunoassay (ECLIA) methods on cobas c702 and e602 systems. ID was defined according to 2021 ESC guidelines (ferritin < 100 ng/mL or ferritin 100–299 ng/mL with TSAT < 20%). Multivariable logistic regression identified independent factors associated with ID. Results: The overall ID prevalence was 75.4%, consisting of functional (39.9%) and absolute ID (35.5%). A significant gender disparity was observed (p = 0.0326): absolute ID was more prevalent in females (44.4%), while functional ID predominated in males (47.4%). Multivariable analysis revealed that NT-proBNP (aOR = 2.29; 95% CI: 1.13–4.66; p = 0.021) and C-reactive protein (aOR = 2.17; 95% CI: 1.07–4.43; p = 0.031) were independent correlates of ID status. The association with anemia was borderline non-significant (p = 0.055). Conclusions: ID is nearly ubiquitous among Vietnamese CHF patients in this tertiary setting, driven by hemodynamic severity and systemic inflammation. These findings advocate for integrating routine iron status screening into the standard diagnostic workup for all CHF patients, regardless of hemoglobin levels. Full article

Renal involvement in β-thalassemia minor (β-TMin) has been described mainly in case reports and small observational studies, and its clinical significance remains incompletely characterized. Using real-world data from routinely collected electronic medical records, we performed a retrospective cohort study including 1516 adult patients with β-TMin insured by Clalit Healthcare Services to explore renal abnormalities identified during routine clinical care. Urine testing for hematuria, microalbuminuria, and proteinuria was not performed systematically but was ordered at clinicians’ discretion, resulting in evaluation of a clinically selected subset of patients. Among those tested, hematuria, microalbuminuria, and proteinuria were commonly documented, often in the absence of hypertension, diabetes mellitus, congestive heart failure, or impaired kidney function, consistent with largely subclinical renal involvement. Patients who underwent urine testing were older and had more comorbidities than untested patients, indicating potential selection bias. Correlation analyses showed weak associations between hematological and renal parameters, while ferritin levels correlated modestly with selected proteinuria measures. Due to the retrospective design and non-systematic urine assessment, population-level prevalence and clinical impact cannot be determined. Therefore, prospective studies with standardized renal evaluations are needed to better characterize the frequency, mechanisms, and clinical relevance of renal abnormalities in β-TMin. Full article

Background: Screening patients admitted to internal medicine for hyperferritinemia might reveal a dichotomy between normoferritinemic inflammation and hyperferritinemic inflammation phenotypes, opening new research into innate immunity activation during acute inflammation. Methods: We identified 4514 consecutive patients screened for CRP and ferritin on admission. Patients with CRP ≤ 150 mg/L were excluded. We selected 100 patients with the lowest (normoferritinemic inflammation) and 100 with the highest (hyperferritinemic inflammation) ferritin concentrations. Sub-analysis of 39 CRP-matched pairs (±15 mg/L) and multivariable logistic regression—adjusting for age, sex, sepsis, malignancy, CRP, and comorbidities—were performed. Results: Groups did not differ significantly by age (p = 0.068) or sex (p = 0.319). Mortality was significantly higher in the hyperferritinemic inflammation group (41% vs. 7%, p < 0.001), a trend maintained in non-malignant (31.1% vs. 6.5%, p < 0.001) and CRP-matched (25.6% vs. 2.6%, p = 0.012) subgroups. Multivariable regression confirmed hyperferritinemic inflammation as a significant independent predictor of mortality (OR 3.726; 95% CI 1.304–10.647; p = 0.014), even after adjusting for the Charlson Comorbidity Index. Conclusions: Significant inflammation accompanied by hyperferritinemic inflammation is associated with elevated mortality compared to normoferritinemic inflammation, suggesting a dichotomous divergence of the inflammatory response. Full article

Background: Iron deficiency remains a major nutritional challenge, partly due to the limited stability and bioavailability of conventional iron formulations in foods and during digestion. In this study, iron–protein microparticles (IP-MPs) based on bovine serum albumin (IA-MPs) and hemp protein (IH-MPs) were developed via coprecipitation and evaluated as food-compatible iron delivery systems. Methods: Iron–protein microparticles (IP-MPs) were fabricated by a coprecipitation technique. The stability of IP-MPs was investigated in a three-phase digestion model. The uptake of IP-MPs by Caco-2 cells as well as the Ferritin concentration in Caco-2 cells were investigated. Results: Particle morphology and size distribution were strongly dependent on the protein matrix, with hemp protein microparticles exhibiting greater size uniformity and higher stability under simulated gastric conditions. In a standardized in vitro gastrointestinal digestion model, both IP-MP formulations preserved iron predominantly in the bioactive Fe(II) state and remained sufficiently intact to reach the intestinal phase. Biocompatibility and iron uptake were assessed using Caco-2 cell monolayers. Neither formulation induced cytotoxic effects, while iron delivered via IP-MPs showed enhanced cellular uptake compared to a commercial iron supplement and ferrous sulfate. The amount of Fe(II) detected in the basolateral compartment of IH-MP and IA-MP samples (1.4 µg and 1.3 µg, respectively) was higher than that observed for Floradix^® samples (approximately 0.7 µg) and corresponded to about 25% of the total iron applied. Functional iron bioavailability, assessed by ferritin formation, was significantly higher for IP-MPs, with hemp protein microparticles yielding the strongest ferritin response. Conclusions: These results demonstrate that iron–protein microparticles, particularly those based on hemp protein, effectively improve iron stability during digestion and enhance cellular iron bioavailability, highlighting their potential for application in iron fortification and functional food systems. Full article

Background: Children with β-thalassemia major (β-TM) survive longer due to advances in transfusion and chelation therapy; however, cardiovascular complications have emerged as a leading cause of long-term morbidity. Chronic hemolysis, oxidative stress, and iron overload may promote early endothelial dysfunction and premature vascular aging, yet their impact on myocardial deformation in pediatric patients remains incompletely characterized. Objectives: To evaluate subclinical myocardial dysfunction and arterial stiffness in children with β-TM and to investigate hemolysis-related changes in asymmetric dimethylarginine (ADMA) and L-arginine as biomarkers of endothelial dysfunction in relation to cardiovascular involvement. Methods: Twenty-four children with β-TM and 20 age-matched healthy controls were included. Cardiac structure and myocardial deformation were assessed by conventional echocardiography, tissue Doppler imaging, and speckle-tracking strain analysis. Arterial stiffness was evaluated using oscillometric pulse wave analysis and bilateral carotid intima–media thickness (CIMT). Serum ADMA and L-arginine levels were measured, and hemoglobin, reticulocyte count, and ferritin levels were recorded. Results: Children with β-thalassemia major demonstrated significantly increased arterial stiffness compared with controls, including higher PWV (4.61 ± 0.37 vs. 4.38 ± 0.31), AIx@75 (augmentation index at 75 bpm) (28.5 ± 8.34 vs. 22.8 ± 6.51), left CIMT [0.45 (0.39–0.51) vs. 0.41 (0.38–0.46)], and right CIMT [0.43 (0.39–0.54) vs. 0.40 (0.34–0.46)]. In addition, patients exhibited reduced global longitudinal strain (−19.3 ± 2.91 vs. −21.84 ± 1.91), prolonged isovolumetric relaxation time [53 (37–71) vs. 45 (37–55)], and elevated E/Em (8.44 ± 2.19 vs. 6.92 ± 1.10). ADMA levels were significantly higher in patients (0.54 ± 0.19 vs. 0.39 ± 0.22) and were positively associated with reticulocyte counts and inversely correlated with hemoglobin levels. In addition, both ADMA and ferritin levels were positively correlated with arterial stiffness indices and left ventricular filling pressures. Conclusions: Children with β-thalassemia major exhibit features suggestive of early cardiovascular aging, including impaired myocardial deformation, diastolic involvement, and increased arterial stiffness. The observed association between ADMA levels and markers of hemolysis, vascular stiffness, and myocardial deformation highlights the potential involvement of endothelial dysfunction in premature myocardial–vascular remodeling. These findings suggest that ADMA may serve as a promising biomarker for early cardiovascular risk in pediatric β-thalassemia major; however, further longitudinal and multi-center studies are needed to confirm its clinical utility for risk stratification. Full article