Transferrin Saturation Research Articles

Accuracy of Mentzer index for predicting iron deficiency anemia in adults

Background: It is of great clinical significance to differentiate between causes of microcytic, hypo chromatic anemias, iron deficiency anemia being one of them as it will improve with iron supplements. Complete blood picture is unable to differentiate. Iron studies and Hemoglobin electrophoresis are expensive tests. This necessitates the need of a cost-effective test and therefore we tried to determine the effectiveness of mentzer index in predicting iron deficiency anemia. Methods: It was an Observational, Cross-sectional study, conducted in Department of General Medicine, Federal government polyclinic hospital, Islamabad. Patients with microcytic hypochromic anemia, both from indoor and outdoor were included in study. Iron deficiency Anemia was diagnosed by iron studies (serum ferritin, Serum Iron, TIBC and transferrin saturation) and then mentzer index was calculated to check accuracy. Patient with normocytic or macrocytic anemia or other cell lines deficiency, patients with infectious diseases or inflammatory process were excluded from study. Results: A total of 155 patients were included in the study. Out of all the patients 145(93.5%) had mentzer index of > 13 while 10(6.5%) had mentzer index of <13. All of 150 patients (100%) had transferrin saturation lessthan 20 % indicating iron deficiency anemia against 93.5% picked up by Mentzer index. The receiver operator curves (ROC) showed that the MCV was the most important predictor of anemia while calculating mentzer index. The AUC value for MCV was 0.886(CI: 95%, 0.806-0.966, p value <0.000). MCV value between 52.6 to 63.5 fl predicted that the Mentzer index would be above 13, thus suggesting iron deficiency anemia with a sensitivity of more than 86%. Conclusion: Study findings support the use of Mentzer index, particularly MCV, as a valuable tool for predicting iron deficiency anemia.

Iron Deficiency Anemia: Etiology, Pathophysiology, Diagnosis, and Treatment Approaches

Iron deficiency anemia (IDA) is a common health problem that affects about 1.24 billion people around the world, mostly children and women of childbearing age. IDA happens when the body doesn't get enough iron, loses too much iron, or can't absorb it properly. This makes erythropoiesis, cellular metabolism, and immune function worse. The World Health Organization says that 40% of women who are pregnant and 32.5% of women who are not pregnant have anemia. People with IDA often feel tired, weak, pale, and have trouble thinking clearly. Lab tests, such as hemoglobin, blood ferritin, and transferrin saturation, are used to make the diagnosis. You can treat the condition in two ways: by taking iron supplements by mouth, such as ferrous sulfate, ferrous gluconate, and ferrous fumarate; or, for serious cases, by giving iron through an IV. Strategies for prevention depend on increasing the amount of iron you get from food, making it more bioavailable, and keeping infections under control. Food addition and fortification programs have been shown to help lower the number of people with IDA. However, problems still exist, especially in areas with poor economies. Recent advance in acknowledging how iron is used and controlled has implications for creating targeted therapeutic approaches. A key regulator of iron balance, hepcidin, is a key player in the pathophysiology of IDA. This review shows how complicated IDA is and how important it is to have treatment plans that consider underlying causes, dietary factors, and socioeconomic factors. Keywords: Iron Deficiency Anemia (IDA), Erythropoiesis, Hemoglobin, Nutritional Deficiencies, Neurological Disorders, Iron Supplements.

Pharmacokinetics and Pharmacodynamics of Rusfertide, a Hepcidin Mimetic, Following Subcutaneous Administration of a Lyophilized Powder Formulation in Healthy Volunteers.

Hepcidin, an endogenous peptide hormone, binds to ferroportin and is the master regulator of iron trafficking. Rusfertide, a synthetic peptide, is a potent hepcidin mimetic. Clinical studies suggest rusfertide may be effective in the treatment of polycythemia vera. This study investigated the dose-ranging pharmacokinetics, pharmacodynamics, and safety of a lyophilized formulation of rusfertide. A randomized open-label crossover study was conducted in two groups of healthy adult subjects to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of subcutaneous rusfertide doses that ranged from 10 to 60 mg of a lyophilized formulation and 20 mg of an aqueous prefilled syringe formulation that were used in clinical trials. Rusfertide showed a rapid initial absorption. Median time to peak plasma concentrations for the lyophilized formulation was 24h for doses of 10-30 mg and 2-4 h for doses of 45 and 60 mg. Mean terminal half-life ranged from 19.6 to 57.1 h. Rusfertide peak concentration and area under the concentration-time curve increased with an increasing dose, but in a less than dose-proportional manner. Metabolites M4 and M9 were identified as major metabolites. At the rusfertide 20-mg dose, the lyophilized formulation had an area under the concentration-time curve from time zero to infinity approximately 1.5-fold higher than the aqueous formulation. The elimination half-life was comparable for the two formulations. Dose-related decreases in serum iron and transferrin-iron saturation were seen following rusfertide treatment. The majority of treatment-emergent adverse events were mild; treatment-related treatment-emergent adverse events seen in ≥10% of subjects were injection-site erythema and injection-site pruritus. Rusfertide was well tolerated; the pharmacokinetic and pharmacodynamic results indicate that lyophilized rusfertide is suitable for once-weekly or twice-weekly administration.

The causal relationships between iron status and sarcopenia in Europeans: a bidirectional two-sample Mendelian randomization study.

Previous studies have indicated potential associations between metals, lifestyle factors, and sarcopenia. However, the specific causal relationships between iron status, lifestyle factors, and sarcopenia remain unclear. Therefore, we conducted a bidirectional two-sample Mendelian Randomization (MR) approach to investigate these relationships. The exposure variables included iron status, living alone, coffee intake, alcohol taken with meals, and moderate physical activity, while the outcome variable was sarcopenia, assessed by grip strength in both hands and usual walking pace. We employed the Weighted Median (WM), the Inverse Variance-Weighted (IVW), and other MR methods to explore these problems for analysis. Simultaneously, we conducted a bidirectional MR analysis to assess whether sarcopenia has a reverse causal relationship with internal iron status. In our present research, we found serum iron (P = 0.033), ferritin (P = 0.001), transferrin saturation (P = 0.029) and coffee intake (P = 0.002) revealed a negative trend for sarcopenia, living alone (P = 0.022) and alcohol taken with meal (P = 0.006) showed a opposite trend for sarcopenia. Whereas sarcopenia showed negative trend for ferritin (P = 0.041) and transferrin saturation (P = 0.043), showed the opposite trend for transferrin (P = 0.021). Our study suggested that higher serum iron levels might reduce the risk of sarcopenia. Moreover, living alone and alcohol consumption might increase the sarcopenia risk, while coffee intake and moderate physical activity could reduce the sarcopenia risk.

Could Hepcidin Be a New Biomarker in Patients with Idiopathic Pulmonary Fibrosis (IPF)?

Objectives: Hepcidin is a biomarker produced by hepatocytes in chronic disease anemia and is known to increase during chronic inflammation. This study compares the hepcidin levels in idiopathic pulmonary fibrosis (IPF) patients and controls, evaluating its relationship with anemia and systemic inflammation in IPF patients. Methods: This study included 82 IPF patients and 31 controls. Hepcidin levels were compared between the two groups. In the IPF group, the hepcidin and anemia parameters were compared between anemic and non-anemic patients. The significance between the hepcidin and systemic inflammation parameters such as Erythrocyte Sedimentation Rate, CRP (C-reactive protein) levels, ferritin levels, and the Systemic Immune–Inflammation Index (SII) was investigated. Erythrocyte Sedimentation Rate, C-reactive protein (CRP) levels, and ferritin levels were measured using automated analyzers. Hepcidin and erythropoietin (EPO) levels were determined using ELISA kits. Results: A significant difference in hepcidin levels was found between the IPF and control groups (37.13 ± 14.92 vs. 25.77 ± 11.25, p < 0.001). No significant difference in hepcidin levels was found between anemic and non-anemic IPF patients (38.25 ± 16.2 vs. 36.7 ± 14.6, p = 0.719). No significant correlation was found between hepcidin levels and anemia parameters (serum iron, ferritin, vitamin B12, serum transferrin, transferrin saturation, total iron-binding capacity, hemoglobin, folate, and erythropoietin) in IPF patients. Despite significant differences in the systemic inflammation parameters (ferritin and CRP) between patients and controls, no significant correlation was found between their hepcidin and systemic inflammation parameters. Conclusions: Our study demonstrates that the hepcidin levels in IPF patients are elevated independently of anemia and systemic inflammation. We propose that hepcidin could be a potential biomarker to be investigated in IPF patients.

BS O05 - Prevalence and Patterns of Iron Deficiency in Patients Living with Obesity: Insights from Bariatric Surgery Candidates

Abstract Background Iron deficiency anaemia (IDA) is a recognised complication of obesity, and its associated co-morbidities. Iron deficiency has been implicated in immunologic dysfunction in obesity. However, the patterns of iron deficiency in people with obesity, independent of IDA, and its implications for patients with obesity remain unclear. This study aimed to investigate potential causes of iron deficiency, including relationship with glycaemic control and relationship with systemic inflammation. Relationship between iron deficiency and body mass index (BMI) was also considered. Method A retrospective review of a prospectively maintained database of consecutive patients undergoing bariatric surgery was performed. Pre-operative haematologic assessments were reviewed, and linear regression models were used to identify the associations of iron deficiency in patients with obesity. Statistical analysis was performed using SPSS. 384 consecutive patients over a 2-year time period were included in the analysis. 72.1% of patients were female and the mean age was 49.44±10.2. The mean weight of included patients was 144.1±31.02 kg, and the mean BMI was 50.66±9.61 kg/m2 Results ​2.45% of patients met the criteria for iron deficiency anaemia. However, 15.49 % had low serum iron(<9 mmol/L), 12.1% had low ferritin(<30mg/L), 1.38% had low transferrin(<2g/L), 15.17% had high Total Iron Binding Capacity(>71.6mmol/L), 37.93% had low transferrin saturation(<20%). High BMI was a significant predictor of low serum iron(β=-0.206, p=0.031). Dysregulated glycaemic metabolism(HbA1c and glucose) was not a significant predictor of iron deficiency. Baseline inflammation (elevated CRP) was associated with low serum iron(β=-0.320, p=<0.001) and low transferrin(β=-0.205, p=0.028). Conclusion Iron deficiency in patients with obesity is common, but not iron deficiency anaemia dependent. It does not appear to be linked to patients’ glycaemic regulation, as previously thought. Our findings suggest it may instead be attributable to the systemic inflammation caused by obesity.

Complexes of Iron(II), Cobalt(II), and Nickel(II) with DOTA-Tetraglycinate for pH and Temperature Imaging Using Hyperfine Shifts of an Amide Moiety.

Paramagnetic complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA4-) derivatives have shown potential for molecular imaging with magnetic resonance. DOTA-tetraglycinate (DOTA-4AmC4-) coordinated with lanthanide metal ions (Ln3+) demonstrates pH/temperature sensing with Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) and Chemical Exchange Saturation Transfer (CEST), respectively, detecting nonexchangeable (e.g., -CHy, where 3 ≥ y ≥ 1) and exchangeable (e.g., -OH or -NHx, where 2 ≥ x ≥ 1) protons. Herein, we report paramagnetic complexes of divalent transition-metal ions (M2+ = Fe2+, Co2+, Ni2+) with DOTA-4AmC4- that endow a unique amide proton (-NH) moiety for pH/temperature sensing. Crystallographic data reveal that DOTA-4AmC4- coordinates with M2+ through oxygen and nitrogen donor atoms, ranging in coordination numbers from 8-coordinate in Fe(II)DOTA-4AmC2-, 7-coordinate in Co(II)DOTA-4AmC2-, and 6-coordinate in Ni(II)DOTA-4AmC2-. The -CHy protons in M(II)DOTA-4AmC2- displayed modest pH/temperature sensitivities, but -NH protons exhibited higher intensity, suggesting prominent BIRDS properties. The pH sensitivity was the highest for Ni(II)DOTA-4AmC2- (1.42 ppm/pH), followed by Co(II)DOTA-4AmC2- (0.21 ppm/pH) and Fe(II)DOTA-4AmC2- (0.16 ppm/pH), whereas temperature sensitivities were comparable (i.e., 0.22, 0.13, and 0.17 ppm/°C, respectively). The CEST image contrast for -NH in M(II)DOTA-4AmC2- was much weaker compared to that of Ln(III)DOTA-4AmC-. Given its high pH sensitivity and low cytotoxicity, Ni(II)DOTA-4AmC2- shows promise for use in preclinical BIRDS-based pH imaging.

Formulation and Release of Active Pharmaceutical Ingredients Using a Supramolecular Self-Healing Two-Component Gel.

A two-component low-molecular-weight gelator (LMWG) formed from a modified amino acid and an aldehyde was formulated with active pharmaceutical ingredients (APIs). Basic APIs (propranolol, atropine) can be mixed with the LMWG prior to gel assembly while acidic APIs (naproxen, rosuvastatin) inhibit assembly by disrupting the LMWG imine bond and were loaded by diffusion after gel assembly. For diffusion-loaded gels, the API in the liquid-like phase was rapidly released, with the remainder, interacting with gel fibres, retained in the gel. Rosuvastatin release was particularly low with Saturation Transfer Difference (STD) NMR indicating interactions between the aromatic ring and the self-assembled gel network. Propranolol also interacted with the gel via its aromatic unit, and its release led to gel erosion. Using agarose as a polymer gelator additive reinforced the gel, restricting erosion. In contrast, atropine was readily released over a period of hours - it is primarily in the liquid-like phase with STD NMR indicating no interactions with the gel network. The atropine-loaded gel retained its thixotropic properties. Overall, APIs must be carefully chosen to optimise formulation/release. Of the APIs investigated, atropine has most potential for further development. Atropine has applications in treating myopia, and our results suggest potential ophthalmic applications of supramolecular gels.

Motion and magnetic field inhomogeneity correction techniques for chemical exchange saturation transfer (CEST) MRI: A contemporary review.

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) has emerged as a powerful imaging technique sensitive to tissue molecular composition, pH, and metabolic processes in situ. CEST MRI uniquely probes the physical exchange of protons between water and specific molecules within tissues, providing a window into physiological phenomena that remain invisible to standard MRI. However, given the very low concentration (millimolar range) of CEST compounds, the effects measured are generally only on the order of a few percent of the water signal. Consequently, a few critical challenges, including correction of motion artifacts and magnetic field (B0 and B1 +) inhomogeneities, have to be addressed in order to unlock the full potential of CEST MRI. Motion, whether from patient movement or inherent physiological pulsations, can distort the CEST signal, hindering accurate quantification. B0 and B1 + inhomogeneities, arising from scanner hardware imperfections, further complicate data interpretation by introducing spurious variations in the signal intensity. Without proper correction of these confounding factors, reliable analysis and clinical translation of CEST MRI remain challenging. Motion correction methods aim to compensate for patient movement during (prospective) or after (retrospective) image acquisition, reducing artifacts and preserving data quality. Similarly, B0 and B1 + inhomogeneity correction techniques enhance the spatial and spectral accuracy of CEST MRI. This paper aims to provide a comprehensive review of the current landscape of motion and magnetic field inhomogeneity correction methods in CEST MRI. The methods discussed apply to saturation transfer (ST) MRI in general, including semisolid magnetization transfer contrast (MTC) and relayed nuclear Overhauser enhancement (rNOE) studies.

Effects of Iron Saturations on the Physicochemical Properties and Potential Physiological Functions of Ovotransferrin: Based on Structure-Activity Relationship.

Ovotransferrin (OVT) is a multifunctional protein related to lactoferrin (LF), sharing similar characteristics and considered a cost-effective alternative. Researchers were intrigued by the differences in iron saturation between native-LF and native-OVT, but whether iron saturation affected the cost-effectiveness of the ligand of OVT compared to LF was still uncertain. This study investigated the structure, physicochemical properties, and potential functions of an OVT with varying iron saturation levels, aiming to clarify the impact of iron saturation on an OVT. The findings showed that increased iron saturation altered the structure of an OVT, leading to changes in its physicochemical properties, such as larger particle size and better thermal stability. The findings from peptidomics indicated that iron saturation affects the resistance of OVT to digestion, resulting in the generation of peptides with distinct molecular weights and diverse potential functionalities. Overall, this study provided evidence to support that iron saturation was a limiting factor for the functional performance of the OVT.

Associations between iron status and psychosocial wellbeing among pregnant women in Cape Coast, Ghana: a longitudinal study.

To determine the associations among iron status, depressive/anxiety symptoms, and quality of life (QoL) throughout pregnancy. This longitudinal study recruited participants in their 1st trimester (< 13 weeks; n=116) and followed in their 2nd (n=71) and 3rd (n=71) trimesters. Sociodemographic, food security, anxiety, depressive symptoms, and QoL questions were collected. Hemoglobin (Hb), ferritin (Ft), and transferrin saturation (TSAT) were determined. Women were categorized as iron improvers or non-improvers based on changes in iron status. Associations were assessed using difference-in-difference analyses. Cape Coast, Ghana between October 2017 to September 2018. Pregnant women, 18-38 years. Improvement in Ft levels from the 1st to 2nd trimester were associated with reduced depressive symptoms (-2.96 vs -0.58, p=0.028), and higher overall QoL (13.99 vs 1.92, p=0.006) particularly role physical (23.32 vs -2.55, p=0.025) and role emotional (27.50 vs 10.06, p=0.025) subscales. Improvement in Hb levels during the same period were linked to less anxiety, particularly fear factor (-2.62 vs -0.51, p=0.020); and worsened physical health aspect of QoL (-21.80 vs -3.75, p=0.005). Improvement in TSAT levels from 2nd to 3rd trimester were associated with increased total anxiety (1.56 vs -0.64, p=0.030) and panic factor (0.45 vs -0.26, p=0.004) and decreased total QoL (-1.08 vs 7.94, p=0.017), specifically role physical (-10.98 vs 11.93, p=0.018). Increases in iron status from first to second trimester were related to improvements in psychosocial wellbeing, implying potential benefit of iron supplementation on affect in early pregnancy. Larger studies are needed to confirm these findings.

Simultaneous monitoring of glycogen, creatine, and phosphocreatine in type II glycogen storage disease using saturation transfer MRI.

There is a need for non-invasive approaches to assess the progression of glycogen storage diseases (GSD). Here, we use saturation transfer (ST) MRI via relayed nuclear Overhauser effects (glycoNOE) to detect abnormal changes in muscle glycogen of a GSD II mouse model. In addition to glycogen, the energy metabolites phosphocreatine (PCr) and creatine (Cr) were studied to assess the muscle disease. Water saturation (Z-spectra) and 1H MRS were acquired at 9.4 T on the skeletal muscle of healthy control mice and homozygous acid -glucosidase (GAA) knock-out mice (ages of 2-48 weeks). The glycoNOE (-1 ppm), total creatine (tCr)* (+2 ppm, = a × [Cr] + b × [PCr]), and PCr (+2.5 ppm) from Z-spectra and the ratio between tCr and taurine signals (tCr/Tau) from 1H MRS spectra were quantified by using multi-pool Lorentzian fitting methods. The concentrations of the metabolites were also measured via tissue assays. The postnatal GSD II mice (age <12 weeks) showed a continued accumulation of muscle glycoNOE signal. GlycoNOE in adult GSD II mice (age ≥12 weeks) reached a plateau, at a level above 400% of that in normal mice. PCr, tCr*, and tCr/Tau gradually decreased in GSD II mice during the postnatal stage, then stabilized at levels comparable to adult control, yet PCr in adult GSD II mice was lower than that in controls. This study demonstrates that ST MRI of glycogen can provide in situ non-invasive biomarkers for GSD II disease progression, with the potential to study the progression and treatment response of GSDs.

Glucose chemical exchange saturation transfer MRI for predicting the histological grade of rectal cancer: a comparative study with amide proton transfer-weighted and diffusion-weighted imaging.

To evaluate the utility of glucose chemical exchange saturation transfer (glucoCEST) MRI with non-contrast injection in predicting the histological grade of rectal cancer. This prospective analysis included 60 patients with preoperative rectal cancer who underwent pelvic glucoCEST, amide proton transfer-weighted imaging (APTWI), and diffusion-weighted imaging (DWI). In total, 21 low-grade and 39 high-grade cases were confirmed by postoperative pathology. The MTRasym (1.2 ppm), MTRasym (3.5 ppm), and apparent diffusion coefficient (ADC) values of lesions between the low-grade and high-grade groups were compared. The area under the receiver operating characteristic curve (AUC) was generated to evaluate the diagnostic performance of each technique. Logistic regression (LR) analysis was applied to determine independent predictors and for multi-parameter combined diagnosis. Elevated MTRasym (1.2 ppm), MTRasym (3.5 ppm) values and lower ADC values were observed in the high-grade group compared with low-grade cases (all p < 0.01). The AUCs of MTRasym (1.2 ppm), MTRasym (3.5 ppm), and ADC for differentiating between low- and high-grade rectal cancer cases were 0.792, 0.839, and 0.855, respectively. The diagnostic performance of the combination of the three indexes was improved (AUC, 0.969; sensitivity, 95.24%; specificity, 87.18%). The good consistency and reliability of the combination of independent predictors were demonstrated by calibration curve analysis and DCA. The glucoCEST MRI without contrast injection, APTWI, and DWI all facilitate the assessment of histological grade in rectal cancer, and the combination of the three can effectively discriminate between high- and low-grade rectal cancer, which is expected to be a promising imaging marker. The glucose chemical exchange saturation transfer MRI method facilitates the assessment of histological grade in rectal cancer and offers additional information to improve the diagnostic performance of amide proton transfer-weighted imaging, and diffusion-weighted imaging. Glucose chemical exchange saturation transfer imaging could differentiate histological grade. Amide proton transfer-weighted and diffusion-weighted were associated with histological grade. The combination of different parameters showed the best diagnostic performance.

BIOM-25. MOLECULAR PROFILING PREDICTS EARLY AND LATE PROGRESSION IN GLIOBLASTOMA

Abstract Patients with glioblastoma experience a wide variation in response to standard treatment, with nearly 30% experiencing tumour progression during treatment, and nearly 6% surviving more than 5 years. To date, there are few non-invasive clinical biomarkers to predict response to first – line treatment. Chemical exchange saturation transfer (CEST) MRI may have the potential to fill this gap. CEST MRI is sensitive to treatment-induced changes and changes in tumor metabolism. Our team has obtained CEST data for patients before, during and after the end of standard chemoradiation treatment, and found that CEST provides markers of early response and can identify early, standard and late progressors before treatment initiation. In this study, we aimed to establish molecular profiles of early, standard and late progressors with IDH wild-type glioblastoma. Patients (n=180) with primary, IDH wild-type glioblastoma were imaged with CEST-MRI at multiple time points throughout standard chemoradiation treatment. DNA and RNA were co-extracted from matched normal and tumour pairs and processed for whole genome sequencing, enzymatic methyl-seq and gene expression analysis using Nanostring. Clinical variables such as age, extent of resection, sex, ECOG status and MGMT promoter methylated were also collected. A survival analysis was conducted using the Kaplan-Meier method with log-rank tests. Univariate and multi-variate hazard ratios for clinical variables were calculated by fitting Cox Proportional Hazards Models. Early progressors reported a median progression-free survival (PFS) of 142 days compared to 832 days in late progressors (p&amp;lt;0.0001). Early progressors also harbored distinct and statistically significant differences in gene expression and genomic alterations, namely in DNA damage repair, glucose transport and arginine metabolism pathways. A gene signature was prognostic of PFS and overall survival. Collectively, this data has the potential to serve as a radiogenomic biomarker to assess treatment response before or within early phases of treatment and allow for individual tailoring of the treatment plan.

Magnetic resonance imaging techniques for monitoring glioma response to chemoradiotherapy.

Treatment response assessment for gliomas currently uses changes in tumour size as measured with T1- and T2-weighted MRI. However, changes in tumour size may occur many weeks after therapy completion and are confounded by radiation treatment effects. Advanced MRI techniques sensitive to tumour physiology may provide complementary information to evaluate tumour response at early timepoints during therapy. The objective of this review is to provide a summary of the history and current knowledge regarding advanced MRI techniques for early treatment response evaluation in glioma. The literature survey included perfusion MRI, diffusion-weighted imaging, quantitative magnetization transfer imaging, and chemical exchange transfer MRI. Select articles spanning the history of each technique as applied to treatment response evaluation in glioma were chosen. This report is a narrative review, not formally systematic. Chemical exchange saturation transfer imaging potentially offers the earliest method to detect tumour response due to changes in metabolism. Diffusion-weighted imaging is sensitive to changes in tumour cellularity later during radiotherapy and is prognostic for progression-free and overall survival. Substantial evidence suggests that perfusion MRI can differentiate between tumour recurrence and treatment effect, but consensus regarding acquisition, processing, and interpretation is still lacking. Magnetization transfer imaging shows promise for detecting subtle white matter damage which could indicate tumour invasion, but more research in this area is needed. Advanced MRI techniques show potential for early treatment response assessment, but each technique alone lacks specificity. Multiparametric imaging may be necessary to aid biological interpretation and enable treatment guidance.

Alterations of Hepcidin and Iron Markers Associated with Obesity and Obesity-related Diabetes in Gambian Women

Aims Obesity, type 2 diabetes (T2D), and chronic inflammation are associated with disturbances in iron metabolism. Hepcidin is hypothesized to play a role in these alterations owing to its strong association with inflammation via the JAK-STAT3 pathway. The current study investigated the differences between inflammatory markers and iron indices and their association with hepcidin in lean women, women with obesity, and women with obesity and T2D (obesity-T2D) in The Gambia. Materials and methods In a cross-sectional study design, fasted blood samples were collected from three groups of women: lean women (n=42, body mass index (BMI)=20.9 kg/m2), women with obesity (n=48, BMI=33.1 kg/m2) and women with obesity-T2D (n=30, BMI=34.5 kg/m2). Markers of inflammation (IL-6 and CRP) and iron metabolism [hepcidin, iron, ferritin, soluble transferrin receptor (sTfR), transferrin, transferrin saturation, and unsaturated iron-binding capacity (UIBC)] were compared using linear regression models. Simple regression analyses were performed to assess the association between hepcidin levels and respective markers. Results Women with obesity and obesity-T2D showed elevated levels of inflammatory markers. There was no evidence that markers of iron metabolism differed between lean women and obese women, but women with obesity-T2D had higher transferrin saturation, higher serum iron concentration, and lower UIBC. Serum hepcidin concentrations were similar in all the groups. Hepcidin was not associated with markers of inflammation but was strongly associated with all other iron indices (all P&lt;0.002). Conclusion Contrary to our original hypothesis, hepcidin was not associated with markers of inflammation in the three groups of Gambian women, despite the presence of chronic inflammation in women with obesity and obesity-T2D.

Quality of life as a reflection of metabolic indicators in patients undergoing programmed hemodialysis

Metabolic disorders associated with chronic kidney disease (CKD) can lead to a decrease in the quality of life of patients on hemodialysis. The aim of this study is to analyze the correlation between quality of life (QOL) in patients receiving treatment with PHD and clinical and laboratory indicators. Material and methods. 251 patients with stage 5 CKD were included in the study. There were 108 men and 143 women. The mean age was 54.4 ± 9.9 years. All participants completed a specific quality of life questionnaire KDQOL-SF. Results. The interviewed patients reported more concern about symptoms such as weakness, dizziness, and muscle pain (U = 765, p &lt; 0.001), which was correlated with albumin levels (R = 0.5, p &lt; 0.01) and calcium-phosphorus product levels (R = –0.48, p &lt; 0.05). They also expressed concern about the inability to travel or follow a special diet (U = 553, p &lt; 0.005), which correlated with heart rate levels (R = –0.51, P &lt; 0.1) and serum potassium levels (R = –0.6, P &lt; 0.1). Additionally, the burden of CKD correlated with triglycerides (R = 0.36, p = 0,01).Work capacity is associated with age (R = –0.54; p &lt; 0.001), eKT/V (R = 0.47; p &lt; 0.01). Indicators of cognitive function correlate with blood pressure (BP) (R = –0.51, p &lt; 0,001) and pulse pressure (P = –0,55, p &lt; 0,01). Sexual functions are associated with BP (R = –0,64, p &lt; 0,05), calcium levels (R = 0,76, p &gt; 0.80), iron (0,42, p = 0,90), transferrin saturation coefficient (0.5, p = 0.91). Sleep quality correlates with calcium-phosphate production (0.3, p &gt; 0.15). The feeling of social support correlates with magnesium (0,3, P &gt; 0,8), calcium (0.2, P &gt; 0,1). Conclusions. Correlations between quality of life, blood pressure, albumin, and calcium phosphate metabolism, iron, were found.

Influence of TMPRSS6 genotype on iron status parameters in stable COPD patients

Background: The SNP rs855791 has been linked to increased hepcidin levels, variations in serum iron, transferrin saturation and red blood cell indices. Our goal was to determine the prevalence of this polymorphism among COPD patients and to assess its impact on iron status parameters including hepcidin in patients with stable COPD. Methods: We analysed iron status parameters and genetic data form 94 COPD patient: 29 patients with wild-type genotype (WT group) and 65 patients with either homozygous or heterozygous genotype (HH group). Additionally, the prevalence of SNP rs855791 was assessed in 192 volunteers. Results: The frequency distribution of SNP rs855791 was comparable between the COPD patients and control subjects (p=0.791). Iron status parameters were within their respective reference values and did not show neither statistically nor clinically significant difference between the WT and HH group of COPD patients. However, after excluding patients with (sub)clinical vitamin B12 deficiency and/or hypoxemia, WT group of patients exhibited significantly lower erythropoietin levels (p=0.015). The area under the curve for EPO was 0.688 (95% CI: 0.545-0.830, p=0.015), with an optimal cut-off of 9.74, sensitivity of 61.2% (95% CI: 58.1-64.3) and specificity of 65.0% (95% CI: 61.8-68.3). Conclusion: In patients with stable COPD, iron status parameters do not differ between WT and HH group of patients. After excluding those with (sub)clinical vitamin B12 deficiency and/or hypoxia, only statistical and not clinical difference in EPO levels was observed suggesting that EPO may regulate hepcidin levels and thus influence the development of iron deficiency and/or anaemia.

Prognostic impact of iron deficiency in new-onset chronic heart failure: Danish Heart Failure Registry insights.

Iron deficiency (ID) is prevalent in chronic heart failure (HF) but lacks a consensus definition. This study evaluates the prevalence and the prognostic impact of ID using different criteria on all-cause and cardiovascular mortality, as well as first hospitalization for HF in patients with new-onset chronic HF. In this nationwide registry-based cohort, we explored four definitions of ID: the current European Society of Cardiology (ESC) guidelines [ferritin <100ng/mL or ferritin 100-299ng/mL and transferrin saturation (TSAT) <20%], ferritin level <100ng/mL, TSAT<20% and serum iron ≤13μmol/L. Patients were identified through the Danish Heart Failure Registry. Of 9477 new-onset chronic HF patients registered in the Danish Heart Failure Registry from April 2003 to December 2019, we observed ID prevalence rates ranging from 35.8% to 64.3% depending on the ID definition used. Among patients with ID defined by iron ≤13μmol/L or TSAT<20%, 26% and 15.5%, respectively, did not meet the ESC guidelines definitionfor ID. Conversely, 11% of patients meeting the ESC criteria exhibited serum iron >13μmol/L and TSAT>20%. Regardless of anaemia status, ID defined by TSAT<20% or serum iron ≤13μmol/L was associated with all-cause mortality [non-anaemic, hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.30-1.89 and HR: 1.47, 95% CI: 1.24-1.73; anaemic, HR: 1.22, 95% CI: 1.07-1.38 and HR: 1.25, 95% CI: 1.09-1.44, respectively] and cardiovascular mortality (non-anaemic, HR: 2.21, 95% CI: 1.59-3.06 and HR: 1.47, 95% CI: 1.12-1.95; anaemic, HR: 1.37, 95% CI: 1.11-1.69 and HR: 1.28, 95% CI: 1.02-1.61, respectively), as well as increased risk of first hospitalization for HF (non-anaemic, HR: 1.28, 95% CI: 1.09-1.1.50 and HR: 1.27, 95% CI: 1.10-1.46; anaemic, HR: 1.25, 95% CI: 1.08-1.44 and HR: 1.22, 95% CI: 1.05-1.42, respectively). ID defined by ESC guidelines was associated with all-cause and cardiovascular mortality only in non-anaemic patients (HR: 1.41, 95% CI: 1.18-1.1.70 and HR: 1.58, 95% CI: 1.18-2.12.). Furthermore, the ESC guideline definition was associated with increased risk of first hospitalization for HF, regardless of anaemia status (non-anaemic, HR: 1.26, 95% CI: 1.08-1.1.47; anaemic, HR: 1.34, 95% CI: 1.17-1.53). ID, when defined by TSAT<20% or serum iron ≤13μmol/L, is associated with increased risk of all-cause and cardiovascular mortality, as well as first hospitalization for HF in patients with new-onset chronic HF, regardless of anaemia status. Conversely, ID defined as ESC guidelines is associated with all-cause and cardiovascular mortality only in non-anaemic patients.

Association of Clinical and Paraclinical Factors with Pain Crisis Severity in Sickle-Thalassemia Patients in Iran

Objectives: This study aimed to evaluate the effects of several factors, including hospitalization frequency, inflammatory and hemolytic markers, and the numbers of blood transfusions and crises, on the severity of pain crises in sickle-thalassemia patients. Methods: Of all patients visiting hematologists in university-affiliated hospitals and clinics, only 75 sickle cell disease (SCD) and sickle-thalassemia patients met the inclusion criteria for this study. Disease severity was measured based on pain crises per year and laboratory markers, including hemolytic and inflammatory indicators, outpatient or inpatient status, the number of hospital admissions, and the number of blood units transfused over one year. Results: In sickle cell patients, a significant correlation was observed between hospital admission and WBC (0.01), ALP (0.001), MCHC (0.001), ferritin (0.021), and ESR (0.006). Additionally, pain crises were positively correlated with transferrin saturation (TS) (+0.28) and the number of transfused blood units (+0.49) and negatively correlated with Hb (-0.30) and total iron binding capacity (TIBC) (-0.23). Blood unit transfusions showed a positive correlation with serum iron (+0.44), RDW (+0.36), ferritin (+0.39), pain crises (+0.49), and TS (+0.49), along with a negative correlation with Hb (-0.75) and MCHC (-0.33). When categorizing pain crises into two groups, patients experiencing more frequent crises generally exhibited lower hemoglobin levels and a higher number of blood units transfused. Hemoglobin also showed a significant negative correlation with lactate dehydrogenase (LDH) level in both groups: -0.604 (P = 0.005) in patients with ≥ 3 crises per year and -0.368 (P = 0.006) in patients with &lt; 3 crises per year. Patients with hemoglobin levels of 7.5 or higher tended to maintain an LDH level below 1000. Among patients referred with pain crises, hemoglobin was negatively correlated with hemolytic markers such as LDH (-0.41) and retic (-0.29). Conclusions: Hemoglobin and LDH can serve as follow-up markers, as they are routinely measured in all sickle cell patients and, in this study, hemoglobin levels of 7.5 or higher and LDH levels below 1000 were associated with fewer and less severe pain crises. Regular monitoring of hemolytic markers may help in pain crisis prevention, as this study found that hemolytic crises frequently coincided with pain crises. Further research is needed to provide conclusive evidence in this area.