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1.
J Frailty Aging ; 13(2): 172-178, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38616374

RESUMO

BACKGROUND: Older patients in hemodialysis have high prevalence of malnutrition that is often associated with rapid weight loss till cachexia. OBJECTIVES: We aimed to investigate whether in older patients undergoing hemodialysis the association between poor nutritional status and mortality may be independent of comorbidities and other risk factors. DESIGN: Retrospective longitudinal study. SETTING: Unit of Nephrology, Dialysis and Kidney Transplantation of the Policlinic Hospital of Milan, Milan, Italy. PARTICIPANTS: A total of 107 prevalent patients undergoing hemodialysis for at least three months. MEASUREMENTS: Sociodemographic, clinical, and biological data were recorded. Unintentional weight loss (UWL) was defined as loss of body weight > 5% in 3 months or > 10% in 6 months. We computed a 21-item Frailty Index that included clinical conditions associated with malnutrition and mortality in this population. Unadjusted and adjusted Cox proportional hazard models were performed to test the association of UWL, albumin and transferrin levels with death. Survival analyses based on Kaplan-Meier estimates were performed. RESULTS: Patients' age was 79 (±7.7) years; 38 (35%) were women. Thirty-one patients (29%) died during follow-up. Eighteen (16.8%) patients experienced UWL during the follow-up period. UWL was positively associated with death in the unadjusted model and even after the progressive inclusion of potential confounders. Low albumin levels were positively associated with death only in the unadjusted and partially adjusted models while low transferrin levels were not associated with death in none of the models. Mortality was significantly higher in those patients experiencing both UWL and albumin levels below 3.5 mg/dL. CONCLUSIONS: In older patients undergoing chronic hemodialysis UWL is associated with mortality independently of comorbidities and other risk factors. Patients presenting both UWL and low albumin levels were those experiencing the worst outcomes in terms of mortality.


Assuntos
Desnutrição , Estado Nutricional , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Estudos Longitudinais , Estudos Retrospectivos , Desnutrição/epidemiologia , Redução de Peso , Albuminas , Transferrinas
2.
J Nepal Health Res Counc ; 21(4): 550-556, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38616582

RESUMO

BACKGROUND: Sickle cell anemia is the most common hemoglobinopathy in the world. The study aimed to evaluate the iron profile and its association with socio-demographic characteristics in patients with sickle cell disease. METHODS: A hospital-based descriptive cross-sectional study was conducted to know the iron profile and its socio-demographic association in patients with sickle cell disease. RESULTS: The average serum iron, TIBC, and transferrin saturation were 16.75 ± 6.40 mcgMole/L, 69.46 ± 16.94 mcg/dl and 25.15 ± 12.51% respectively. The serum ferritin ranged from 10.00 to 3000.00 ng/ml. The proportion of participants with normal serum iron, TIBC, serum ferritin, and transferrin saturation were 86.10%, 0.00%, 33.90% and 36.40% respectively. All of the participants of this study had low TIBC (1005), and more than half of the participants had elevated serum ferritin (56.40%). CONCLUSIONS: Iron overload is a common complication of sickle cell disease. There was no association of age and sex with iron profile. The TIBC variation between the Chaudhary ethnic group compared to other ethnic groups signifies the ethnic role in the iron profile.


Assuntos
Anemia Falciforme , Humanos , Estudos Transversais , Nepal , Etnicidade , Ferro , Transferrinas , Ferritinas
3.
Front Immunol ; 15: 1376838, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590521

RESUMO

Background: Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system. Currently, the pathological mechanisms of MS are not fully understood, but research has suggested that iron metabolism disorder may be associated with the onset and clinical manifestations of MS. Methods and materials: The study utilized publicly available databases and bioinformatics techniques for gene expression data analysis, including differential expression analysis, weighted correlation network analysis, gene enrichment analysis, and construction of logistic regression models. Subsequently, Mendelian randomization was used to assess the causal relationship between different iron metabolism markers and MS. Results: This study identified IREB2, LAMP2, ISCU, ATP6V1G1, ATP13A2, and SKP1 as genes associated with multiple sclerosis (MS) and iron metabolism, establishing their multi-gene diagnostic value for MS with an AUC of 0.83. Additionally, Mendelian randomization analysis revealed a potential causal relationship between transferrin saturation and MS (p=2.22E-02; OR 95%CI=0.86 (0.75, 0.98)), as well as serum transferrin and MS (p=2.18E-04; OR 95%CI=1.22 (1.10, 1.36)). Conclusion: This study comprehensively explored the relationship between iron metabolism and MS through integrated bioinformatics analysis and Mendelian randomization methods. The findings provide important insights for further research into the role of iron metabolism disorder in the pathogenesis of MS and offer crucial theoretical support for the treatment of MS.


Assuntos
Distúrbios do Metabolismo do Ferro , Esclerose Múltipla , Humanos , Esclerose Múltipla/genética , Genes Reguladores , Transferrinas , Ferro
5.
J Physiol Pharmacol ; 75(1)2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38583437

RESUMO

The dysregulation of iron metabolism is closely linked to the onset and progression of lung cancer. This study aimed to explore the association between iron metabolism indicators (serum iron, transferrin, ferritin) and the expression level of programmed death factor ligand 1 in primary lesions of advanced non-small cell lung cancer. A cohort of 62 patients, including 42 men and 20 women, was recruited from October 2022 to July 2023, all diagnosed with advanced non-small cell lung cancer, confirmed through radiographic imaging and histopathological analysis. Comprehensive clinical data (such as gender, age, familial lung cancer history, smoking history, pathological classification, clinical stage, etc.) and concentrations of fasting serum iron, transferrin, and ferritin were collected. Patients were categorized into PD-L1 negative (<1% expression) and programmed death ligand 1 (PD-L1) positive (≥1% expression) groups based on PD-L1 expression levels in tumor tissues. Subsequently, the correlation between levels of serum iron, transferrin, ferritin, and PD-L1 expression in advanced non-small cell lung cancer were examined. Patients in the PD-L1 positive group exhibited lower levels of peripheral serum iron and transferrin compared to those in the PD-L1 negative group (P<0.05). For patients exhibiting positive PD-L1 expression, a negative correlation was observed between PD-L1 expression and both serum iron and transferrin levels (r = -0.465, P=0.003; r = -0.447, P=0.005), and a positive correlation was noted between PD-L1 expression and ferritin levels (r=0.393, P=0.015). We conclude that in In patients with advanced non-small cell lung cancer, serum iron and transferrin levels can serve as partial predictors of PD-L1 expression; among those positive for PD-L1, a significant association exists between indicators of iron metabolism and PD-L1 expression.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Feminino , Humanos , Masculino , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Ferritinas , Ferro/metabolismo , Neoplasias Pulmonares/patologia , Transferrinas
6.
Acta Med Indones ; 56(1): 20-25, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38561882

RESUMO

BACKGROUND: Osteoporosis is a major problem in transfusion-dependent thalassemia patients (TDT) patients. Osteoprotegerin (OPG) is one of several bone markers that are closely associated with osteoporosis in TDT patients. OPG is a glycoprotein that functions as a feedback receptor for the Receptor Activator of Nuclear Factor kappa B Ligand (RANKL), which is an alpha tumor necrosis factor receptor. One of the causes of decreased bone mass density is iron toxicity, which can be identified by showing elevated transferrin saturation. Bone mass dual X-ray absorptiometry (DEXA) is a gold standard for the diagnosis of osteoporosis, these procedures are not commonly available in Indonesia. This study was conducted to analyze the correlation between serum levels of OPG and transferrin saturation in TDT patients. METHODS: A correlational study with a cross-sectional approach analyzed data from TDT patients at Hemato-Oncology Medic Outpatient Clinic, Hasan Sadikin General Hospital, Bandung, Indonesia. Primary data were obtained through blood sampling and anthropometry measurement while secondary data were obtained from the patient's medical records. OPG and transferrin saturation levels were assessed using the ELISA method. Research data were analyzed using the rank Spearman correlation test. RESULTS: Data were collected from 51 research subjects (30 women dan 21 men). The median OPG level was 380 (170-1230) pg/mL and the median transferrin saturation level was 89.4 (66.7 - 96.2)%. Analysis of correlation showed a significant correlation between and transferrin saturation level with a coefficient value of r -0.539 and p-value <0.001. CONCLUSION: There was a significant inverse correlation between OPG with transferrin saturation in TDT patients.


Assuntos
Osteoporose , Talassemia , Masculino , Humanos , Feminino , Osteoprotegerina , Densidade Óssea , Osteoporose/etiologia , Osteoporose/patologia , Talassemia/terapia , Talassemia/complicações , Transferrinas , Ligante RANK
7.
Anticancer Drugs ; 35(5): 397-411, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38527419

RESUMO

This study aimed to investigate the role and molecular mechanism of heme oxygenase-1 (HMOX1) in chemotherapy resistance in small-cell lung cancer (SCLC). Employed bioinformatics, qPCR, and Western Blot to assess HMOX1 levels in SCLC versus normal tissues and its prognostic relevance. CCK-8, flow cytometry, and thiobarbituric acid assays determined HMOX1's impact on SCLC chemosensitivity, ferroptosis markers, lipid peroxidation, and mic14's role in chemoresistance. In the GSE40275 and GSE60052 cohorts, HMOX1 expression was downregulated in SCLC tissues compared to normal tissues. Higher HMOX1 expression was associated with improved prognosis in the Sun Yat-sen University Cancer Hospital cohort and GSE60052 cohort. The RNA and protein levels of HMOX1 were reduced in drug-resistant SCLC cell lines compared to chemosensitive cell lines. Upregulation of HMOX1 increased chemosensitivity and reduced drug resistance in SCLC, while downregulation of HMOX1 decreased chemosensitivity and increased drug resistance. Upregulation of HMOX1 elevated the expression of ferroptosis-related proteins ACSL4, CD71, Transferrin, Ferritin Heavy Chain, and Ferritin Light Chain, while decreasing the expression of GPX4 and xCT. Conversely, downregulation of HMOX1 decreased the expression of ACSL4, CD71, Transferrin, Ferritin Heavy Chain, and Ferritin Light Chain, while increasing the expression of GPX4 and xCT. Upregulation of HMOX1 promoted cellular lipid peroxidation, whereas downregulation of HMOX1 inhibited cellular lipid peroxidation. Upregulation of HMOX1 reduced the RNA level of mic14, while downregulation of HMOX1 increased the RNA level of mic14. mic14 exhibited inhibitory effects on cellular lipid peroxidation in SCLC cells and contributed to reduced chemosensitivity and increased drug resistance in chemoresistant SCLC cell lines. HMOX1 plays a role in ferroptosis by regulating mic14 expression, thereby reversing chemoresistance in SCLC.


Assuntos
Ferroptose , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Apoferritinas/genética , Apoferritinas/farmacologia , Apoferritinas/uso terapêutico , Heme Oxigenase-1/genética , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular Tumoral , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/metabolismo , RNA/farmacologia , RNA/uso terapêutico , Transferrinas/farmacologia
8.
BMC Cancer ; 24(1): 293, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438901

RESUMO

BACKGROUND: Hepatic proteins, including albumin, prealbumin, and transferrin have been confirmed to be prognostic predictors in various cancers. This study aimed to comprehensively assess the prognostic value of these three serum markers in patients with cancer cachexia. METHODS: This multicenter prospective cohort study included 1303 cancer cachexia patients, among whom 592 deaths occurred during a median follow-up of 20.23 months. The definition of cachexia was based on the 2011 international consensus. Concordance index (C-index) and receiver operating characteristic (ROC) curves were applied to compare the prognostic performance. The primary outcome was overall survival, which was calculated using the Kaplan-Meier method generated by log-rank test. A Cox proportional hazard regression model was used to identify independent predictors associated with survival. The secondary outcomes included 90-days mortality and quality of life (QoL). RESULTS: C-index and ROC curves showed that albumin had the most accurate predictive capacity for survival, followed by transferrin and prealbumin. Multivariate Cox analysis confirmed that low albumin (hazard ratio [HR] = 1.51, 95% confidence interval [95%CI] = 1.28-1.80, P < 0.001), prealbumin (HR = 1.42, 95%CI = 1.19-1.69, P < 0.001), and transferrin (HR = 1.50, 95%CI = 1.25-1.80, P < 0.001) were independent risk factors for long-term survival in cancer patients with cachexia. In subgroup analysis, the prognostic value of low albumin was significant in patients with upper gastrointestinal, hepatobiliary and pancreatic, and colorectal cancers; low prealbumin was significant in colorectal cancer; and low transferrin was significant in patients with upper gastrointestinal and colorectal cancer. All three hepatic proteins were valuable as prognostic predictors for patients with advanced (Stage III and IV) cancer with cachexia. The risks of 90-days mortality and impaired QoL were higher in cachexia patients with low albumin, prealbumin, and transferrin levels. CONCLUSION: Low albumin, prealbumin, and transferrin levels were all independent prognostic factors affecting patients with cancer cachexia, especially in patients in the advanced stages. These results highlight the value of routinely checking serum hepatic proteins in clinical practice to predict the prognosis of patients with cancer cachexia.


Assuntos
Neoplasias Colorretais , Pré-Albumina , Humanos , Qualidade de Vida , Caquexia/diagnóstico , Caquexia/etiologia , Estudos Prospectivos , Prognóstico , Albuminas , Proteínas Sanguíneas , Estudos de Coortes , Transferrinas
9.
Ital J Pediatr ; 50(1): 39, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38439018

RESUMO

BACKGROUND: Previous studies of maternal iron and birth outcomes have been limited to single indicators that do not reflect the comprehensive relationship with birth outcomes. We aimed to investigate the relationship between maternal iron metabolism and neonatal anthropometric indicators using comprehensive iron-related indicators. METHODS: A total of 914 Chinese mother-child dyads were enrolled in this prospective study. Subjects' blood samples were collected at ≤ 14 weeks of gestation. Serum concentrations of iron-related indicators were measured by enzyme-linked immunosorbent assay (ELISA). Femur length was measured by B-ultrasound nearest delivery. Neonatal anthropometric indicators were collected from medical records. RESULTS: After adjustment for potential covariates, higher iron (per one standard deviation, SD increase) was detrimentally associated with - 0.22 mm lower femur length, whereas higher transferrin (per one SD increase) was associated with 0.20 mm higher femur length. Compared with normal subjects (10th-90th percentiles), subjects with extremely high (> 90th percentile) iron concentration were detrimentally associated with lower femur length, birth weight, and chest circumference, and a higher risk of low birth weight, LBW (HR: 3.92, 95%CI: 1.28, 12.0). Subjects with high concentration of soluble transferrin receptor, sTFR and transferrin (> 90th percentile) were associated with higher femur length. Subjects with low concentration of iron and ferritin concentrations (< 10th percentile) were associated with a higher risk of LBW (HR: 4.10, 95%CI: 1.17, 14.3) and macrosomia (HR: 2.79, 95%CI: 1.06, 7.35), respectively. CONCLUSIONS: Maternal iron overload in early pregnancy may be detrimentally associated with neonatal anthropometric indicators and adverse birth outcomes.


Assuntos
Povo Asiático , Ferro , Recém-Nascido , Feminino , Gravidez , Humanos , Estudos Prospectivos , Transferrinas , China/epidemiologia
10.
Eur J Pharm Biopharm ; 198: 114242, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38442794

RESUMO

Asthma impacts over 300 million patients globally, with significant health implications, especially in cases of its allergic subtype. The disease is characterized by a complex interplay of airway inflammation and immune responses, often mediated by Th2 cell-related cytokines. In this study, we engineered lipid nanoparticles (LNPs) to specifically deliver therapeutic siRNA via the transferrin receptor to T cells. Strain-promoted azide-alkyne cycloaddition (SPAAC) was employed for the conjugation of transferrin ligands to PEGylated lipids in the LNPs, with the goal of enhancing cellular uptake and gene knockdown. The obtained LNPs exhibited characteristics that make them suitable for pulmonary delivery. Using methods such as nanoparticle tracking analysis (NTA) and enzyme-linked immunosorbent assay (ELISA), we determined the average number of transferrin molecules bound to individual LNPs. Additionally, we found that cellular uptake was ligand-dependent, achieving a GATA3 knockdown of more than 50% in relevant in vitro and ex vivo models. Notably, our findings highlight the limitations inherent to modifying the surface of LNPs, particularly with regard to their targeting capabilities. This work paves the way for future research aimed at optimizing targeted LNPs for the treatment of immunologic diseases such as allergic asthma.


Assuntos
Asma , Lipossomos , Nanopartículas , Humanos , Linfócitos T , Asma/metabolismo , RNA Interferente Pequeno/metabolismo , Transferrinas/metabolismo
11.
Exp Oncol ; 45(4): 483-492, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38328841

RESUMO

BACKGROUND: The current studies demonstrate that SARS-CoV-2 infection results in increasing complications incidence and the total risk of death in cancer patients. SARS-CoV-2 infection triggers oxidative stress representing one of the major factors of the inflammation contributing to the complicated course of the diseases including cancer. AIM: To assess the effect of hypoxia caused by SARS-CoV-2 infection on the redox status of blood in patients with metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: 10 patients with SARS-CoV-2, 11 mCRC patients with metachronous liver disease, and 14 mCRC patients with preceding SARS-CoV-2 infection were included in the study. The data on blood biochemistry (C-reactive protein, ferritin, transferrin, and free iron) were analyzed. The levels of superoxide radicals (ROS) in blood cells were determined by electron paramagnetic resonance (EPR) using the spin trap technique. The metalloproteinase activity was measured by polyacrylamide gel zymography with the addition of gelatin as a substrate. RESULTS: In mCRC patients with prior SARS-CoV-2 infection, a 1.26-fold increase in ROS-generating activity of blood neutrophils was observed compared to mCRC patients with no history of SARS-CoV-2 infection. The blood content of C-reactive protein, transferrin, and free iron in mCRC patients with prior SARS-CoV-2 infection increased by 2, 6, and 1.4 times, respectively. The total activity of gelatinases in platelets and neutrophils in the blood of mCRC patients with prior SARS-CoV-2 infection was 1.4 and 1.2 times higher compared to mCRC patients with no history of SARS-CoV-2 infection. CONCLUSION: mCRC patients with prior COVID-19 have a higher risk of exacerbation of inflammatory reactions. SARS-CoV-2 infection results in redox dіsbalance, which may contribute to the unfavorable course of the disease.


Assuntos
COVID-19 , Neoplasias do Colo , Humanos , SARS-CoV-2 , Projetos Piloto , COVID-19/complicações , Espécies Reativas de Oxigênio/metabolismo , Proteína C-Reativa/metabolismo , Ferro/metabolismo , Oxirredução , Transferrinas/metabolismo
12.
ACS Nano ; 18(10): 7455-7472, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38417159

RESUMO

The epithelial mucosa is a key biological barrier faced by gastrointestinal, intraoral, intranasal, ocular, and vaginal drug delivery. Ligand-modified nanoparticles demonstrate excellent ability on this process, but their efficacy is diminished by the formation of protein coronas (PCs) when they interact with biological matrices. PCs are broadly implicated in affecting the fate of NPs in vivo and in vitro, yet few studies have investigated PCs formed during interactions of NPs with the epithelial mucosa, especially mucus. In this study, we constructed transferrin modified NPs (Tf-NPs) as a model and explored the mechanisms and effects that epithelial mucosa had on PCs formation and the subsequent impact on the transcellular transport of Tf-NPs. In mucus-secreting cells, Tf-NPs adsorbed more proteins from the mucus layers, which masked, displaced, and dampened the active targeting effects of Tf-NPs, thereby weakening endocytosis and transcellular transport efficiencies. In mucus-free cells, Tf-NPs adsorbed more proteins during intracellular trafficking, which enhanced transcytosis related functions. Inspired by soft coronas and artificial biomimetic membranes, we used mucin as an "active PC" to precoat Tf-NPs (M@Tf-NPs), which limited the negative impacts of "passive PCs" formed during interface with the epithelial mucosa and improved favorable routes of endocytosis. M@Tf-NPs adsorbed more proteins associated with endoplasmic reticulum-Golgi functions, prompting enhanced intracellular transport and exocytosis. In summary, mucus shielded against the absorption of Tf-NPs, but also could be employed as a spear to break through the epithelial mucosa barrier. These findings offer a theoretical foundation and design platform to enhance the efficiency of oral-administered nanomedicines.


Assuntos
Nanopartículas , Coroa de Proteína , Feminino , Humanos , Enterócitos/metabolismo , Coroa de Proteína/metabolismo , Transcitose , Muco/metabolismo , Transferrinas/metabolismo , Transferrinas/farmacologia , Transferrina/metabolismo
13.
Adv Ther ; 41(4): 1526-1552, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38363463

RESUMO

INTRODUCTION: Thromboembolic events have occurred in clinical trials of roxadustat. This post hoc analysis explored potential factors related to thromboembolic events in dialysis-dependent patients treated with roxadustat in four phase 3 clinical trials in Japan. METHODS: Thromboembolic events with onset before and after week 12 were evaluated. Baseline risk factors for thromboembolic events were investigated by Cox regression analyses. Nested case-control analyses using conditional logistic models with matched pairs of case-control data explored relationships between thromboembolic events and laboratory parameters. RESULTS: Of the 444 patients, 56 thromboembolic events were observed in 44 patients during ≤ 52 weeks of treatment. The proportion of venous and arterial thromboembolic events gradually increased after week 12. Baseline risk factors included hemodialysis (vs peritoneal dialysis), advanced age (≥ 65 years), shorter dialysis vintage (< 4 months), and history of thromboembolism. The absence of concomitant intravenous or oral iron therapy (including ferric citrate) was associated with thromboembolic events before week 12 (hazard ratio 11.25; 95% confidence interval [CI] 3.36-37.71; vs presence). Case-control analysis revealed that low average transferrin saturation (< 10%; unadjusted odds ratio [OR] 6.25; 95% CI 1.52-25.62; vs ≥ 20%), high average transferrin level (≥ 2.5 g/L; unadjusted OR 4.36; 95% CI 1.23-15.39; vs < 2.0 g/L), and high average roxadustat dose (≥ 150 mg; unadjusted OR 5.95; 95% CI 1.07-33.16; vs < 50 mg) over the previous 8 weeks before the event onset were associated with thromboembolic events after week 12. However, adjustment for iron status extinguished the significant relationship between roxadustat dose and events. Multivariate case-control analysis showed that increased transferrin from baseline (≥ 1.0 g/L; adjusted OR 7.85; 95% CI 1.82-33.90; vs < 0.5 g/dL) and decreased mean corpuscular volume (< - 2 fL; adjusted OR 5.55; 95% CI 1.73-17.83; vs ≥ 0 fL) were associated with increased risk of thromboembolic events. CONCLUSION: In addition to established risk factors, iron deficiency may be related to thromboembolic events. Graphical Abstract available for this article. TRIAL REGISTRATION: NCT02780726, NCT02952092, NCT02780141, NCT02779764.


Roxadustat is an oral medicine that treats anemia in patients with chronic kidney disease (CKD). Thromboembolic events, or blood vessels blocked by a blood clot, have occurred in clinical trials of roxadustat. This study explored potential factors that may be related to thromboembolic events in roxadustat-treated patients with anemia of CKD on dialysis before and after week 12. This study found that hemodialysis (vs peritoneal dialysis), advanced age (older than 65 years), short amount of time on dialysis (less than 4 months), previous history of thromboembolic events, and not receiving iron therapy were risk factors for thromboembolic events before week 12. Iron deficiency and high roxadustat dose were risk factors for thromboembolic events after week 12. When iron status was also considered, we did not find that roxadustat dose was related to thromboembolic events. A different model found that increased levels of transferrin, a protein that transports iron, from baseline and decreased mean corpuscular volume, or smaller red blood cells, increased the risk of thromboembolic events. Patients with anemia of CKD on dialysis may benefit from more intentional monitoring and management of iron while receiving roxadustat.


Assuntos
Anemia , Insuficiência Renal Crônica , Humanos , Idoso , Anemia/tratamento farmacológico , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Japão/epidemiologia , Prolina Dioxigenases do Fator Induzível por Hipóxia/uso terapêutico , Glicina/efeitos adversos , Isoquinolinas/efeitos adversos , Ferro/análise , Ferro/uso terapêutico , Transferrinas , Hemoglobinas/análise
14.
Obes Surg ; 34(4): 1174-1184, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38367125

RESUMO

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.


Assuntos
Anemia Ferropriva , Cirurgia Bariátrica , Deficiências de Ferro , Obesidade Mórbida , Humanos , Proteína C-Reativa/metabolismo , Estudos Transversais , Estudos Retrospectivos , Obesidade Mórbida/cirurgia , Ferro , Ferritinas , Cirurgia Bariátrica/efeitos adversos , Obesidade/complicações , Transferrinas , Anemia Ferropriva/etiologia , Transferrina/metabolismo , Biomarcadores
15.
J Equine Vet Sci ; 134: 105010, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38286193

RESUMO

The aim of the study was to compare and correlate levels of ferritin, transferrin, iron and APPs in healthy horses and those surgically treated for strangulating colic. On admission, measurements of inflammatory markers related to iron and total protein, fibrinogen, albumin, haptoglobin and ceruloplasmin were made. The study comprised 22 horses, divided into a control group (CG) of healthy horses (n = 10) and horses with surgically treated acute abdomen (n = 12), obstruction group (OG). The OG was subdivided according to the affected intestinal segment (small vs. large) and according to outcome (survivors vs. non survivors). The OG had higher haptoglobin (34.8±14.2 mg/dL vs 20.8±7.21 mg/dL) and transferrin (487±161 mg/dL vs 369±71.4 mg/dL) values and lower iron (96.9±65 µg/dL vs 218±105 µg/dL) values than the CG. The OG horses with large intestine obstruction had lower values of transferrin (374.6±130 mg/dL) than horses with small intestinal obstruction (598.6±98.9 mg/dL). There was no difference in outcome between horses with large and small intestinal obstruction. Ferritin levels were moderately correlated with total protein (r = 0.594; P = 0.042) and albumin (r = 0.584; P = 0.046) in OG. In the multivariate exploratory analysis, fibrinogen levels were higher in animals that did not survive. In conclusion, haptoglobin, transferrin and iron were useful inflammatory markers for colic in horses. The correlation of ferritin with other APPs shows a possible role of ferritin as an APP in horses. Fibrinogen levels are higher in horses with greater risk of death from strangulating obstructions.


Assuntos
Cólica , Doenças dos Cavalos , Obstrução Intestinal , Animais , Cavalos , Haptoglobinas/metabolismo , Ferro/metabolismo , Cólica/veterinária , Fibrinogênio/metabolismo , Inflamação/veterinária , Obstrução Intestinal/veterinária , Ferritinas , Albuminas/metabolismo , Transferrinas , Doenças dos Cavalos/metabolismo
16.
Eur Rev Med Pharmacol Sci ; 28(1): 303-309, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38235900

RESUMO

OBJECTIVE: The aim of this study was to investigate the hemoglobin variability in patients undergoing maintenance hemodialysis during the application of erythropoietin (EPO) and roxadustat. PATIENTS AND METHODS: For this retrospective study, we analyzed the clinical records of 80 patients with renal anemia on maintenance hemodialysis (MHD) admitted to our hospital between January 2017 and December 2022. We adopted a self-control design comparing the hemoglobin variability of the values before and after roxadustat administration in each patient. The patients received EPO from January 2017 to December 2019 and roxadustat from January 2020 to December 2022. We compared the levels of serum ferritin, transferrin saturation, and hemoglobin and calculated the hemoglobin variabilities by comparing values before and after roxadustat treatments. RESULTS: We found higher transferrin saturation levels at different time points after the roxadustat treatments (p<0.01); meanwhile, the serum ferritin and hemoglobin levels were significantly higher after the roxadustat treatment (p<0.001). During the treatments with EPO and roxadustat, the transferrin saturation, serum ferritin, and hemoglobin levels differed significantly at different time points for each patient (p<0.05). After roxadustat administration, the hemoglobin levels were significantly higher than after EPO administration (p<0.001) and changed more rapidly after roxadustat administration than after EPO administration (p<0.05). The hemoglobin variability after roxadustat administration was significantly lower than that after EPO administration (p<0.05). CONCLUSIONS: Treatment with roxadustat led to higher hemoglobin levels and less hemoglobin variability than the treatment with EPO, with high transferrin saturation and higher ferritin levels in patients with renal anemia on MHD.


Assuntos
Anemia , Eritropoetina , Humanos , Estudos Retrospectivos , Diálise Renal , Hemoglobinas/análise , Eritropoetina/uso terapêutico , Anemia/tratamento farmacológico , Ferritinas , Transferrinas
17.
PLoS One ; 19(1): e0296965, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38271442

RESUMO

BACKGROUND: High-sensitive cardiac troponin T (h-cTnT), which serves as a marker for myocardial damage, has also been linked to adverse outcomes in asymptomatic hemodialysis patients. This study aims to explore the correlation between interleukin-6 (IL-6) and h-cTnT in asymptomatic hemodialysis patients to unravel the relationship between inflammation and cardiovascular risk. METHODS: A cross-sectional study involving 81 patients was conducted from November 2022 to March 2023 at An-Najah National University Hospital in Palestine. We gathered clinical data, including comorbidities, and obtained blood samples for measuring IL-6 and h-cTnT levels. We performed statistical analyses, including correlation tests and linear regression, to assess the associations between these variables. RESULTS: The study revealed a notable increase in both h-cTnT and IL-6 levels, and a significant correlation between the two (rho = 0.463, P<0.001) in asymptomatic hemodialysis patients. Likewise, h-cTnT levels displayed positive correlations with age (rho = 0.519, P<0.001) and negative correlations with albumin (rho = -0.297, p = 0.007) and transferrin saturation (rho = -0.227, P = 0.042). IL-6 levels exhibited correlations with age (rho = 0.422, P<0.001), albumin (rho = -0.389, P<0.001), iron (rho = -0.382, P<0.001), and transferrin saturation (rho = -0.362, P = 0.001). Notably, higher h-cTnT levels were associated with diabetes, hypertension, a history of coronary artery disease, cerebrovascular accidents, older age, and male gender. CONCLUSION: This study underscores the significant association between the inflammatory marker IL-6 and h-cTnT in asymptomatic hemodialysis patients, suggesting that inflammation may play an essential role in the elevation of h-cTnT levels. This association may have implications for predicting cardiovascular events and guiding interventions to reduce cardiovascular disease morbidity and mortality in hemodialysis patients.


Assuntos
Interleucina-6 , Falência Renal Crônica , Humanos , Masculino , Falência Renal Crônica/complicações , Troponina T , Estudos Transversais , Biomarcadores , Diálise Renal/efeitos adversos , Progressão da Doença , Albuminas , Inflamação/complicações , Transferrinas
18.
Sci Rep ; 14(1): 1682, 2024 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-38242893

RESUMO

Iron status is often assessed in epidemiologic studies, and toenails offer a convenient alternative to serum because of ease of collection, transport, and storage, and the potential to reflect a longer exposure window. Very few studies have examined the correlation between serum and toenail levels for trace metals. Our aim was to compare iron measures using serum and toenails on both a cross-sectional and longitudinal basis. Using a subset of the US-wide prospective Sister Study cohort, we compared toenail iron measures to serum concentrations for iron, ferritin and percent transferrin saturation. Among 146 women who donated both blood and toenails at baseline, a subsample (59%, n = 86) provided specimens about 8 years later. Cross-sectional analyses included nonparametric Spearman's rank correlations between toenail and serum biomarker levels. We assessed within-woman maintenance of rank across time for the toenail and serum measures and fit mixed effects models to measure change across time in relation to change in menopause status. Spearman correlations at baseline (follow-up) were 0.08 (0.09) for serum iron, 0.08 (0.07) for transferrin saturation, and - 0.09 (- 0.17) for ferritin. The within-woman Spearman correlation for toenail iron between the two time points was higher (0.47, 95% CI 0.30, 0.64) than for serum iron (0.30, 95% CI 0.09, 0.51) and transferrin saturation (0.34, 95% CI 0.15, 0.54), but lower than that for ferritin (0.58, 95% CI 0.43, 0.73). Serum ferritin increased over time while nail iron decreased over time for women who experienced menopause during the 8-years interval. Based on cross-sectional and repeated assessments, our evidence does not support an association between serum biomarkers and toenail iron levels. Toenail iron concentrations did appear to be moderately stable over time but cannot be taken as a proxy for serum iron biomarkers and they may reflect physiologically distinct fates for iron.


Assuntos
Ferro , Unhas , Humanos , Feminino , Ferro/metabolismo , Unhas/metabolismo , Seguimentos , Estudos Prospectivos , Pós-Menopausa , Estudos Transversais , Ferritinas , Biomarcadores , Transferrinas , Transferrina
19.
Eur J Clin Nutr ; 78(4): 328-334, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38243059

RESUMO

INTRODUCTION: Nutrition plays an important role in management of acute pancreatitis (AP) and decreases its severity and infectious complications. Various formulations of enteral nutrition (EN) are available and are costly. For developing countries, cost and availability is a major issue and kitchen-based diet should be explored in patients with AP. AIM: Comparison of kitchen-based diet with a commercially available polymeric formulation in terms of various outcomes in patients with AP within 14 days after the onset of pain. METHODS: Sixty patients (39 male, mean age 36.1 ± 12.7 years) of moderately severe and severe AP of any etiology were randomized (30 in each group) to either kitchen-based diet or commercial polymeric formulation group. Outcome measures were refeeding pain, tolerability, infectious complications, mortality, total hospital/intensive care unit stay; and change in serum C-reactive protein (CRP), transferrin and pre albumin. RESULTS: There was no significant difference in baseline demographic and biochemical parameters in both groups. No difference was observed in refeeding pain (7.1% vs 8%, p = 0.99), tolerability (28.6% vs 12%, p = 0.17), infectious complications (57.14% vs 36%, p = 0.12), mortality (31.7% vs 20%, p = 0.69), hospital stay (19.5 vs 23.5 days, p = 0.86), CRP (74.4 vs 59 mg/L, p = 0.97), transferrin levels (23.6 vs 25.6 mg/dL, p = 0.75) and pre albumin (9.45 vs 13.09 mg/dL, p = 0.68) in both groups. CONCLUSION: Kitchen-based diet is comparable to commercial polymeric formulation for the early initiation of enteral nutrition in patients with severe or moderately severe acute pancreatitis. CLINICAL TRIAL REGISTRATION: Trial registered with the Clinical Trials registry-India (CTRI/2018/01/011188).


Assuntos
Pancreatite , Humanos , Masculino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Pancreatite/terapia , Doença Aguda , Projetos Piloto , Dieta , Proteína C-Reativa , Dor , Transferrinas
20.
J Cachexia Sarcopenia Muscle ; 15(2): 681-689, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38225218

RESUMO

BACKGROUND: Iron deficiency (ID) is associated with impaired functional capacity in patients with heart failure (HF), even in those with preserved ejection fraction (HFpEF). This study aimed to evaluate the effect of baseline ferrokinetics on peak oxygen consumption (peakVO2) improvement after a 12-week physical therapy programme in patients with stable HFpEF. METHODS: This study is a post-hoc sub-analysis of a randomized clinical trial in which 59 stable patients with HFpEF were randomized to receive a 12-week programme of inspiratory muscle training (IMT), functional electrical stimulation (FES), IMT + FES or usual care (UC) to evaluate change in peakVO2 (NCT02638961). Serum ferritin and transferrin saturation (TSAT) determinations were assessed at baseline. ID was defined as ferritin <100 ng/mL and/or TSAT <20% if ferritin was within 100-299 ng/mL. We used a linear mixed regression model to analyse between-treatment changes in peakVO2 across ferrokinetics status at 12 and 24 weeks. RESULTS: The mean age was 74 ± 9 years, and 36 (61%) had ID. The mean of peakVO2 was 9.9 ± 2.5 mL/kg/min. The median of ferritin and transferrin saturation (TSAT) was 91 (50-181) ng/mL and 23% (16-30), respectively. A total of 52 patients completed the trial (13 patients per arm). Compared with those patients on UC, patients allocated to any of the active arms showed less improvement in peak VO2 when they showed ID (P-value for interaction <0.001), lower values of ferritin (P-value for interaction <0.001), or TSAT (P-value for interaction <0.001). CONCLUSIONS: Ferrokinetics status plays an essential role in modifying the aerobic capacity response to physical therapies in patients with HFpEF. Further studies are required to confirm these findings.


Assuntos
Insuficiência Cardíaca , Deficiências de Ferro , Humanos , Idoso , Idoso de 80 Anos ou mais , Volume Sistólico/fisiologia , Insuficiência Cardíaca/terapia , Ferritinas , Exercício Físico , Transferrinas
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