Elevated Serum Ferritin Research Articles

Strength in Numbers - Identifying a Significant Association Between High Serum Ferritin Levels and Newly diagnosed Malignancy in a Large Health Organization Cohort.

Ferritin, an iron storage protein and acute phase reactant, has been implicated in various aspects of human health and disease, including cancer. Previous studies have identified elevated serum ferritin (SF) levels in several cancer types, but a comprehensive examination across different malignancies remains lacking. This study aims to fill this gap by utilizing anonymized data from Maccabi Health Services (MHS), one of Israel's largest health organizations, to explore the association between elevated SF levels and the diagnosis of different malignancies. An extensive dataset from MHS, comprising 2.7 million members, including 1.3 million individuals who underwent SF level testing, was analyzed. Odds Ratios (OR) and 95% confidence intervals (CI) were calculated to assess the association between high SF levels and cancer diagnosis. Subgroup analysis was conducted to investigate variations across different malignancies. The analysis revealed a significant association between elevated SF levels and cancer diagnosis among MHS members, with an OR of 1.9 (95% CI 1.71-2.15). Sub- group analysis unveiled differences in the association across malignancy types, with hematological, hepatobiliary and respiratory malignancies more strongly associated with high SF levels. This study provides further support for the link between elevated SF levels and malignancy, leveraging a vast dataset from MHS, underscoring potential utilities of elevated SF levels as a potential indicator for cancer with a variable role among different malignancy types. The identification of elevated SF levels as a potential indicator for underlying malignancy for seemingly-healthy individuals.

A Case of Tick-borne Disease with Yezo Virus and Borrelia miyamotoi Coinfection.

Yezo virus is a novel virus transmitted by tick bites that causes fever with thrombocytopenia. To date, two reports have been published on patients with Yezo virus infection. However, the clinical characteristics of Yezo virus infection remain unclear. A patient who presented with fever, fatigue, headaches, and muscle pain and was admitted to our hospital. The patient had thrombocytopenia, leukopenia, and elevated liver enzyme and serum ferritin levels. The patient was diagnosed with Yezo virus and Borrelia miyamotoi coinfection based on the detection of Yezo virus in a blood sample by PCR and the detection of elevated serum antibody titers to Yezo virus and Borrelia miyamotoi.

Dose-response relationship of serum ferritin and dietary iron intake with metabolic syndrome and non-alcoholic fatty liver disease incidence: a systematic review and meta-analysis.

This study aims to assess the dose-response impact of iron load on systemic and hepatic metabolic disorders including metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD). Serum ferritin (SF) and dietary iron intake were selected to represent the indicators of iron load in the general population. PubMed, EMBASE and Web of Science databases were searched for epidemiological studies assessing the impact of SF/dietary iron intake on MetS/NAFLD occurrence. All literature was published before September 1st, 2023 with no language restrictions. Fifteen and 11 papers were collected with a focus on connections between SF and MetS/NAFLD, respectively. Eight papers focusing on dietary iron and MetS were included in the following meta-analysis. For the impact of SF on MetS, the pooled odds ratio (OR) of MetS was 1.88 (95% CI: 1.58-2.24) for the highest versus lowest SF categories. In males, the OR was 1.15 (95% CI: 1.10-1.21) per incremental increase in SF of 50 μg/L, while for females, each 50 μg/L increase in SF was associated with a 1.50-fold higher risk of MetS (95% CI: 1.15-1.94). For connections between SF and NAFLD, we found higher SF levels were observed in NAFLD patients compared to the control group [standardized mean difference (SMD) 0.71; 95% CI: 0.27-1.15], NASH patients against control group (SMD1.05; 95% CI:0.44-1.66), NASH patients against the NAFLD group (SMD 0.6; 95% CI: 0.31-1.00), each 50 μg/L increase in SF was associated with a 1.08-fold higher risk of NAFLD (95% CI: 1.07-1.10). For the impact of dietary iron on MetS, Pooled OR of MetS was 1.34 (95% CI: 1.10-1.63) for the highest versus lowest dietary iron categories. Elevated SF levels is a linear relation between the incidence of MetS/NAFLD. In addition, there is a positive association between dietary iron intake and metabolic syndrome. The association between serum ferritin and metabolic syndrome may be confounded by body mass index and C-reactive protein levels.

Chinese guidelines for the diagnosis and treatment of hereditary hemochromatosis

Hereditary hemochromatosis is an iron overload disease caused by mutations in iron-regulating genes, resulting in excessive iron deposition in organs such as the liver, heart, skin, pancreas, and gonads, leading to corresponding multi-system damage. This condition is relatively common in European and American populations, primarily caused by mutations in the HFE gene; however, it is rare in China and other Asian countries, almost exclusively due to mutations in non-HFE genes. Clinical features include unexplained chronic hepatitis or cirrhosis, accompanied by elevated serum ferritin and/or increased transferrin saturation. MRI shows iron deposition in the liver, liver biopsy reveals iron accumulation in hepatocytes, and genetic testing facilitate the diagnosis of this disease. Repeated phlebotomy is the first-line therapy for this condition. For those who cannot tolerate phlebotomy, iron chelation therapy may be used, and patients who progress to end-stage liver disease will require liver transplantation. To assist clinicians in making informed decisions on the diagnosis and treatment of hereditary hemochromatosis, the Chinese Society of Hepatology, Chinese Medical Association has invited experts from clinical medicine, molecular genetics, pathology, imaging, and methodology to systematically summarize the advancement in this field and collaboratively develop the current guidelines.

Serum ferritin is a risk factor for pulmonary dysfunction in young patients with transfusion-dependent thalassemia

Research into the pulmonary function of patients with transfusion-dependent thalassemia (TDT) is limited, with existing studies presenting conflicting results. We carried out a retrospective study involving 140 patients with TDT. The mean patient age was 8.7 ± 3.2 years, with a median serum ferritin (SF) level of 3791.4 ng/ml (IQR: 2424.1–5733.3 ng/ml). Pulmonary function abnormalities were detected in 46.43 % (65 out of 140) of patients, primarily manifesting as diffusion dysfunction (26.43 %), followed by ventilatory dysfunction (5.0 %), and mixed pulmonary dysfunction (15.0 %). A serum ferritin level above 2500 ng/ml significantly correlated with the occurrence of these abnormalities(OR = 3.187, 95%CI:1.312–7.741, P = 0.010), while higher hemoglobin concentrations demonstrated a protective effect (OR = 0.966, 95%CI: 0.943–0.989, P = 0.004). Our study highlights diffusion dysfunction as the most prevalent type of pulmonary function abnormalities in TDT patients. Furthermore, it establishes a correlation between elevated serum ferritin levels and pulmonary dysfunction.

Crosstalk between FTH1 and PYCR1 dysregulates proline metabolism and mediates cell growth in KRAS-mutant pancreatic cancer cells.

Ferritin, comprising heavy (FTH1) and light (FTL) chains, is the main iron storage protein, and pancreatic cancer patients exhibit elevated serum ferritin levels. Specifically, higher ferritin levels are correlated with poorer pancreatic ductal adenocarcinoma (PDAC) prognosis; however, the underlying mechanism and metabolic programming of ferritin involved in KRAS-mutant PDAC progression remain unclear. Here, we observed a direct correlation between FTH1 expression and cell viability and clonogenicity in KRAS-mutant PDAC cell lines as well as with in vivo tumor growth through the control of proline metabolism. Our investigation highlights the intricate relationship between FTH1 and pyrroline-5-carboxylate reductase 1 (PYCR1), a crucial mitochondrial enzyme facilitating the glutamate-to-proline conversion, underscoring its impact on proline metabolic imbalance in KRAS-mutant PDAC. This regulation is further reversed by miR-5000-3p, whose dysregulation results in the disruption of proline metabolism, thereby accentuating the progression of KRAS-mutant PDAC. Additionally, our study demonstrated that deferasirox, an oral iron chelator, significantly diminishes cell viability and tumor growth in KRAS-mutant PDAC by targeting FTH1-mediated pathways and altering the PYCR1/PRODH expression ratio. These findings underscore the novel role of FTH1 in proline metabolism and its potential as a target for PDAC therapy development.

Musculoskeletal ultrasound findings in adult-onset Still's disease: A case series

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology characterized by high spiking fever, salmon-like skin rash, arthritis, and elevated serum ferritin levels. Early detection of AOSD is remarkably difficult because of the lack of serologic biomarkers, nonspecific presentation, and rarity of the disease. Although arthralgia and arthritis are the most frequent symptoms and are correlated with health-related quality of life in patients with AOSD, the inflammatory changes associated with these symptoms have not been elucidated. We performed musculoskeletal ultrasound (MSKUS) in 11 patients between January 1, 2008 and July 31, 2023, seven of whom had abnormalities. MSKUS findings of those cases suggested that some patients with AOSD could present with tenosynovitis, tendonitis/peritendonitis, bursitis, and enthesitis along with synovitis. This case series demonstrate the diversity of inflammatory articular manifestations of AOSD identified by MSKUS.

Study of platelet activation, hypercoagulable state, and pulmonary hypertension in patients with transfusion-dependent beta-thalassemia

Abstract: BACKGROUND: Thalassemic patients require lifelong blood transfusions, which can lead to complications such as pulmonary arterial hypertension. The pathogenesis involves hypercoagulability, in which researches on coagulation abnormalities in this regard are limited. OBJECTIVES: The aims of the study was to investigate the mechanism of hypercoagulability and pulmonary hypertension in transfusion-dependent thalassemic patients and compare it with healthy controls. PATIENTS MATERIALS AND METHODS: This case–control analysis enrolled 50 transfusion-dependent thalassemia patients and 50 healthy controls. Complete blood counts, liver function tests, coagulation markers (P-selectin, protein C, antithrombin III, and fibrinogen), serum ferritin, and transthoracic echocardiography were performed, and blood transfusion/chelation history and splenectomy status were recorded. RESULTS: Thalassemia patients revealed severe anemia, leukocytosis, thrombocytosis, significantly elevated serum ferritin (1957.50 ± 2455.05 g/L), elevated liver enzymes serum glutamic oxaloacetic transaminase (22.01 ± 9.89 U/L), serum glutamic pyruvic transaminase (22.70 ± 9.78 U/L) in comparison to controls, and mean serum P-selectin was significantly higher in thalassemic patients (100.48 ± 53.29 ng/mL). Mean serum antithrombin-III and protein C were significantly lower in thalassemic patients (89.27 ± 16.08 units/h, 86.04 ± 25.21 μg/mL) in comparison to controls. CONCLUSIONS: Transfusion-dependent thalassemia is characterized by severe anemia and splenomegaly, leading to complex hemodynamic changes with evidence of platelet activation, hypercoagulable state, liver injury, and increased atherosclerosis. It induces pulmonary artery thrombosis contributing to the development of pulmonary artery hypertension.

Iron Overload Induces Hepatic Ferroptosis and Insulin Resistance by Inhibiting the Jak2/stat3/slc7a11 Signaling Pathway.

Recent studies showed that patients with iron overload had increased risk of insulin resistance or diabetes. Ferroptosis is a new type of cell death mainly caused by iron-dependent oxidative damage. In the present study, we investigated potential mechanisms of iron overload induced hepatic ferroptosis and insulin resistance through in vivo and in vitro experiments. In vivo, the mice models of iron overload were established by intraperitoneal injection of iron dextran. The changes of body weight, serum ferritin and blood glucose were measured. Hematoxylin-eosin (HE) and Perl's stainings were used to observe the pathological changes and iron deposition in the liver of mice. In vitro, HepG2 cells were treated with ferric ammonium citrate (FAC, 9 mmol/L, 24 h) to establish the cell models of iron overload. The labile iron pool, cell viability, glucose consumption and glycogen contents were measured. The ultrastructure of mitochondria was observed by transmission electron microscope (TEM). The malondialdehyde (MDA) and glutathione (GSH) kits were used to detect lipid peroxidation in liver tissues of mice and HepG2 cells. RT-PCR and Western blot were used to detect the mRNA and protein expression levels of ferroptosis factors and JAK2/STAT3 signaling pathway. In this study, we used the iron chelator deferasirox in mice and HepG2 cells. Iron overload caused weight loss, elevated serum ferritin, fasting blood glucose, fasting insulin, HOMA-IR, impaired glucose tolerance, and decreased insulin sensitivity in mice. HE staining and Perls staining showed clumps of iron deposition in the liver of iron overload mice. Iron overload could reduce the glucose consumption, increase MDA contents of HepG2 cells, while reduce glycogen and GSH contents in liver tissues of mice and HepG2 cells. TEM showed deletion of mitochondrial ridge and rupture of outer membrane in HepG2 cells with iron overload. Iron chelator deferasirox could significantly improve the above indicators, which might be related to the activation of JAK2/STAT3/SLC7A11 signaling pathway and hepatic ferroptosis. Iron overload could induce hepatic ferroptosis and insulin resistance by inhibiting the JAK2/STAT3/SLC7A11 signaling pathway, and the iron chelator deferasirox might improve hepatic insulin resistance induced by iron overload.

Iron Homeostasis-Related Parameters and Hepcidin/Ferritin Ratio: Emerging Sex-Specific Predictive Markers for Metabolic Syndrome.

Metabolic syndrome (MetS) is a worldwide public health challenge. Accumulating evidence implicates elevated serum ferritin and disruptions in iron metabolism as potential elements linked to an increased risk of MetS. This study investigates the relationship between iron homeostasis-including hepcidin levels, serum iron concentration, unsaturated iron-binding capacity (UIBC), and the hepcidin/ferritin (H/F) ratio-and MetS. In this descriptive cross-sectional study, 209 participants aged 24-70 were categorized into two groups: 103 with MetS and 106 without MetS. All participants underwent medical assessment, including anthropometric measures, indices of glycemic control, lipid profiles, and iron-related parameters. Participants were further stratified by the Homeostasis Model Assessment-Insulin Resistance index into three subgroups: insulin-sensitive (IS) (<1.9), early insulin resistance (EIR) (>1.9 to <2.9), and significant insulin resistance (SIR) (>2.9). Notable increments in serum ferritin and hepcidin were observed in the SIR group relative to the IS and EIR groups, with a significant association between metabolic parameters. The UIBC and serum ferritin emerged as significant predictors of MetS, particularly in men, with an area under the curve (AUC) of 0.753 and 0.792, respectively (p ≤ 0.001). In contrast, hepcidin was notably correlated with MetS in women, with an AUC of 0.655 (p = 0.007). The H/F ratio showed superior predictive capability for MetS across both sexes (at cutoff level = 0.67). Among women, this ratio had an AUC of 0.639 (p = 0.015), and for men, it had an AUC of 0.792 (p < 0.001). Hypertension proved an independent risk factor for MetS, affirming its role in metabolic dysregulation. The findings highlight a significant interconnection between iron homeostasis parameters and MetS, with sex-specific variations underscoring the importance of personalized diagnostic criteria. The crucial role of the H/F ratio and the UIBC as emerging predictive markers for MetS indicates their potential utility in identifying at-risk individuals. Further longitudinal research is essential to establish causality and explore the interplay between these biomarkers and MetS.

Correlation of Liver Enzymes and Serum Ferritin in Patients With β-Thalassaemia Major

Background: β-Thalassemia major is a hereditary hematological disorder that necessitates regular blood transfusions, leading to iron overload and subsequent liver injury. Elevated serum liver enzymes and ferritin are commonly used to monitor liver function in these patients; however, their reliability in predicting true hepatic dysfunction remains unclear. Objective: To determine the sensitivity, specificity, and diagnostic accuracy of serum liver enzymes and ferritin in predicting liver dysfunction, with hypoalbuminemia as the gold standard, in pediatric patients with β-thalassemia major. Methods: This cross-sectional validation study was conducted at the Department of Paediatrics, Combined Military Hospital, Rawalpindi, from July 2022 to February 2024. A total of 75 pediatric patients with β-thalassemia major were included using consecutive non-probability sampling. Patients with concurrent liver diseases, metabolic disorders, or conditions that could alter liver enzyme levels were excluded. Blood samples were collected to measure serum Alanine Transaminase (ALT), Aspartate Transaminase (AST), γ-Glutamyltransferase (γ-GT), ferritin, and albumin levels. Hypoalbuminemia was defined as a serum albumin level &lt;3.5 g/L. The diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ALT, AST, γ-GT, and ferritin in predicting hypoalbuminemia were calculated using 2×2 contingency tables. Data were analyzed using SPSS version 25. Results: Among the 75 patients, 18 (24.0%) exhibited hypoalbuminemia. The sensitivity, specificity, and diagnostic accuracy of ALT in detecting hypoalbuminemia were 83.33%, 31.58%, and 44.00%, respectively. For AST, these values were 50.00%, 29.82%, and 34.67%, respectively. γ-GT showed a sensitivity of 83.33%, specificity of 14.04%, and diagnostic accuracy of 30.67%. Ferritin had a sensitivity of 83.33%, specificity of 19.30%, and diagnostic accuracy of 34.67%. None of the markers showed satisfactory predictive value for hypoalbuminemia. There was a partial correlation between hyperferritinemia and elevated liver enzymes, with γ-GT showing the highest sensitivity (91.80%) and diagnostic accuracy (82.67%). Conclusion: Serum liver enzymes and ferritin are not reliable markers for predicting liver dysfunction as indicated by hypoalbuminemia in pediatric patients with β-thalassemia major. These findings suggest that additional clinical assessments and more specific biomarkers are necessary for accurate evaluation of liver health in this population.

The Association of Serum Ferritin with Disease Severity in Non-alcoholic Fatty Liver Disease

Abstract Background NONALCOHOLIC FATTY LIVER DISEASE is emerging as the most common chronic liver condition in the Western world. It is associated with insulin resistance and frequently occurs with features of the metabolic syndrome. Disease presentation ranges from asymptomatic elevated liver enzyme levels to cirrhosis with complications of liver failure and hepatocellular carcinoma. Current treatment recommendations are limited to weight loss and exercise, although several promising medications are on the horizon. Aim of the Work The aim of this study is to evaluate the association of serum ferritin with non- alcoholic fatty liver disease. Patients and Methods The study was cross sectional study which conducted at Ain Shams University Hospital. This study was conducted on 80 patients both sexes, with age (18years old - 60 years), duration of study will be 6 months. All study patients approved to participate in this study. Patients were divided in to 2 groups as following: Results Our study reveals that patients with non alcoholic steatohepatitis (NASH) have significantly higher median serum ferritin levels, compared to those with non alcohoholic fatty liver disease (NAFLD). Also ROC curve shows that the best cutoff point of serum ferritin to differentiate between normal lipid profile group and elevated lipid profile group was found &amp;gt; 80 with sensitivity of 82.5%, specificity of 60.0% and AUC of 69.5% while the best cutoff point of fatty liver index to differentiate between normal lipid profile group and elevated lipid profile group was found &amp;gt; 89 with sensitivity of 67.5%, specificity of 80.0% and AUC of 76.8%. Conclusion Elevated serum ferritin may reflect increased disease severity in NAFLD either because of increased ongoing hepatic or systemic inflammation or increased body iron stores or a combination of these factors. Our study also reveals that patients with non alcoholic steatohepatitis (NASH) have significantly higher median serum ferritin levels, compared to those with non alcohoholic fatty liver disease (NAFLD).

Biomarkers of hemorrhagic transformation of acute ischemic stroke – A cross-sectional study

Background. Hemorrhagic transformation (HT) is a serious complication that can arise in individuals experiencing acute ischemic stroke (AIS), whether it occurs spontaneously or following thrombolytic therapy, resulting in considerable morbidity and mortality. Hemorrhagic changes are associated with several risk factors, including excessive blood sugar levels, hypertension, the severity of a stroke, and reperfusion. Aim. To assess the commonly available blood parameters such as lipid profile, serum magnesium, and serum ferritin as tools to identify patients who are at risk of hemorrhagic transformation after an acute ischemic stroke. Materials and methods. The study was conducted at the Saveetha Medical College, Chennai, Tamil Nadu, in India, as a cross-sectional study, and a total of 142 patients diagnosed with acute ischemic stroke were enrolled for this study from January 2023 to January 2024. Results. Among the 32 patients who had a hemorrhagic transformation, all 32 (100%) patients had elevated serum ferritin levels and the remaining 110 patients who had no hemorrhagic transformation were found to have normal serum ferritin levels and the difference was statically significant (p&lt;0.001). Total cholesterol, serum LDL, serum HDL, and serum triglycerides had no statistically significant association with hemorrhagic transformation among the patients. Conclusion. The present study concludes that people with lower serum magnesium on admission and higher serum ferritin were found to be at risk. Serum lipid profile had no statistically significant association with hemorrhagic transformation among the patients.

Analysis of how Serum Ferritin and the Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) are correlated to Hepatic MRI T2* Findings in Children with Beta-Thalassemia Major

Background: Iron overload is a major complication in patients with beta-thalassemia major. Excessive iron accumulation leads to organ dysfunction. The regular assessment of iron is crucial to effectively manage iron overload in these patients. This study evaluated the correlation between serum ferritin levels, the Aspartate Aminotransferase-to-Platelet Ratio Index (APRI), and hepatic MRI T2* findings in children with beta-thalassemia major. Materials and Methods: This retrospective analytical study was conducted at Shahid Sadoughi Hospital in Yazd in 2023. The research population comprised all the children under the age of 15 with beta-thalassemia major who had undergone multiple blood transfusions (at least ten units of blood). Results: The participants in this study were 70 children with beta-thalassemia major, including 35 males and 35 females. Their mean age was 3.52 ± 10.76 years. The mean relaxation time of liver MRI T2* was 4.42 ± 4.91 ms. The participants also had the APRI score of 0.55 ± 1.90, the aspartate aminotransferase (AST) level of 23.82 ± 36.29, and the serum ferritin level of 285.01 ± 3244.04 (ng/mL). Based on MRI T2* results, 30% of the patients had a severe liver iron overload, 27.1% had a moderate overload, 21.4% had a severe overload, 18.6% had a mild overload, and 2.9% had near-normal iron levels.The AST level demonstrated a significant association with the type of chelation treatment (P = 0.003). The duration of blood transfusion (in years) showed a strong positive correlation with the patients' age (Pearson's coefficient = 0.996). Conclusion: This study indicates the elevated serum ferritin levels and APRI scores in patients with beta-thalassemia major, most of whom have abnormal MRI T2* findings. However, no significant correlation was observed between the APRI score, serum ferritin level, and MRI T2* results.

Serum Ferritin Level as a Predictor for Intra Uterine Growth Restriction

Background: Maternal serum ferritin is being explored as a potential predictor for Intrauterine Growth Restriction (IUGR). Early detection of IUGR is crucial for improving perinatal outcomes and reducing associated mortality and morbidity. Objective: To evaluate the role of elevated maternal serum ferritin in predicting the risk of developing IUGR. Patients and Methods: A prospective case-control study was conducted at Al-Batool Teaching Hospital, Diyala, involving 51 pregnant women divided into two groups based on pregnancy status. Demographic data, obstetric history, and risk factors for IUGR were collected through a questionnaire, and blood samples were taken to measure hemoglobin and serum ferritin levels. Results: The study found that the mean serum ferritin level was significantly higher in the patient group (209.89±50.95 ng/ml) compared to the control group (66.91±37.49 ng/ml), with a p-value of &lt;0.001. The mean birth weight was significantly lower in the patient group (1873.81±425.62 g) compared to the control group (3078.67±415.56 g), also with a p-value of &lt;0.001. There were no significant differences in age and hemoglobin levels between the two groups. Conclusion: Elevated maternal serum ferritin levels may suggest an increased risk of IUGR, emphasizing the need for further research to validate its role as a predictive marker.

Serum Ferritin Level as a Predictor for Intra Uterine Growth Restriction

Background: Maternal serum ferritin is being explored as a potential predictor for Intrauterine Growth Restriction (IUGR). Early detection of IUGR is crucial for improving perinatal outcomes and reducing associated mortality and morbidity. Objective: To evaluate the role of elevated maternal serum ferritin in predicting the risk of developing IUGR. Patients and Methods: A prospective case-control study was conducted at Al-Batool Teaching Hospital, Diyala, involving 51 pregnant women divided into two groups based on pregnancy status. Demographic data, obstetric history, and risk factors for IUGR were collected through a questionnaire, and blood samples were taken to measure hemoglobin and serum ferritin levels. Results: The study found that the mean serum ferritin level was significantly higher in the patient group (209.89±50.95 ng/ml) compared to the control group (66.91±37.49 ng/ml), with a p-value of &lt;0.001. The mean birth weight was significantly lower in the patient group (1873.81±425.62 g) compared to the control group (3078.67±415.56 g), also with a p-value of &lt;0.001. There were no significant differences in age and hemoglobin levels between the two groups. Conclusion: Elevated maternal serum ferritin levels may suggest an increased risk of IUGR, emphasizing the need for further research to validate its role as a predictive marker. Keywords: Intrauterine Growth Restriction (IUGR), Serum Ferritin, Pregnancy, Predictive Marker, Perinatal Outcomes.

SLC40A1-related hemochromatosis associated with a p.Y333H mutation in mainland China: a pedigree report and literature review

BackgroundHaemochromatosis is a genetic disease characterized by the excessive deposition of iron in various tissues and organs, eventually results in organ damage including cirrhosis, diabetes, cardiomyopathy, etc. SLC40A1-related haemochromatosis is associated with gain-of-function mutations in the SLC40A1 gene, which encodes ferroportin. While sporadic reports of this condition exist in mainland China, the understanding of the phenotype and genetic pattern associated with the SLC40A1 p.Y333H mutation remains incomplete.Case presentationWe report a pedigree with heterozygous p.Y333H mutation in Chinese Han population. The proband is a 64-year-old man complaining of persistent abnormality of liver enzyme levels for 1 year, with a history of knee joint pain, diabetes and skin pigmentation. He displayed markedly elevated serum ferritin level and transferrin saturation. Magnetic resonance imaging showed iron deposition in the liver, spleen, and pancreas, along with cirrhosis and splenomegaly. Whole exome sequencing identified a heterozygous allelic variant c.997T > C (p.Y333H). Genetic screening of family members identified four first-degree relatives and three second-degree relatives having the same mutation. Additional cases with this mutation from two published studies were included. Among the probands and screened relatives, all eight males aged over 30 y had ferritin level > 1000 µg/L, transferrin saturation > 90%. Four patients with organ damage in the present study received therapeutic phlebotomy, alleviating clinical symptoms and improving in transferrin saturation and serum ferritin.ConclusionsThis study reports the largest pedigree with heterozygous SLC40A1 p.Y333H mutation in the Chinese population to date. In Chinese families, males over 30 years old with hemochromatosis due to SLC40A1 p.Y333H mutation exhibit severe iron overload phenotypes.

Early prediction of severe ICANS after standard-of-care CD19 CAR T-cell therapy using gradient-boosted classification trees.

7034 Background: Severe immune effector cell-associated neurotoxicity syndrome (ICANS) has arisen as a major complication leading to morbidity, mortality, and increased resource utilization. There is an urgent need to accurately predict the development of severe ICANS after CAR T-cell therapy. Here, we demonstrate the high performance of the XGBoost (“eXtreme Gradient Boosting”) machine learning algorithm in predicting the development of severe ICANS using commonly available laboratory and vital sign data from patients with B-cell lymphomas undergoing standard-of-care CD19 CAR T-cell therapy. Methods: We included patients who received axicabtagene ciloleucel (axi-cel) or brexucabtagene autoleucel (brexu-cel) per standard of care. ICANS was graded by CTCAE 4.03 criteria (pre-12/2018) or ASTCT Consensus Grading System (post-1/2019). Predictions were generated using XGBoost, a widely used supervised machine learning algorithm that trains ensembles of decision trees to learn iteratively from prior trees and allows for very flexible modeling (e.g. non-linear effects, complex high-order interaction effects). K-fold cross-validation was used to assess calibration and overfitting. Variables assessed included age, ferritin, CRP, LDH, IL-6, fibrinogen, platelet count, and temperature at pre-infusion, day 0, and day +3 post-infusion timepoints. Results: A total of 175 patients were included with 39 receiving brexu-cel (22%) and 136 receiving axi-cel (78%). Grade ≥3 ICANS occurred in 40 patients (23.3%). XGBoost modeling of factors demonstrated that serum ferritin level on day +3 was the most important variable predictive of grade ≥3 ICANS (accuracy gain: 0.28). Other influential factors included day 0 and +3 platelet count, patient age, day +3 IL-6 level, day 0 fibrinogen level, and day 0 and +3 CRP level, in descending order of importance. The XGBoost model maintained high discrimination (ability to distinguish high-risk from low-risk patients; mean AUROC 0.74, sensitivity 0.95, specificity 0.90). Longitudinal LOESS smoothing confirmed associations between severe ICANS and elevation in serum ferritin at day 0 (OR 3.01, 95% CI 1.41 – 6.73, p = 0.005) and day +3 (OR 5.50, 95% CI 2.31-14.5, p &lt;0.001). Conclusions: A supervised machine learning model using XGBoost incorporating age, temperature and commonly accessible laboratory data including ferritin, CRP, LDH, IL-6, fibrinogen, and platelet count predicted severe ICANS prior to the development of symptoms with high discrimination (AUROC 0.74) in patients undergoing standard of care CAR T-cell therapy. This allows for the early identification of patients at highest risk for developing severe ICANS who may benefit from prophylactic interventions. Once externally validated, we plan to develop a user-friendly web application to generate individualized predictions from our model.

Predictive indicators and risk model construction for coronary artery lesions in Kawasaki disease children over 5 years old

To study predictive indicators for coronary artery lesions (CAL) and construct a risk prediction model for CAL in Kawasaki disease (KD) children over 5 years old. A retrospective analysis of KD children over 5 years old at Wuhan Children's Hospital of Tongji Medical College of Huazhong University of Science and Technology from January 2018 to January 2023 was conducted. Among them, 47 cases were complicated with CAL, and 178 cases were not. Multivariate logistic regression analysis was used to explore predictive indicators for CAL in KD children over 5 years old and construct a risk prediction model. The receiver operating characteristic curve was used to evaluate the effectiveness of the prediction model. Finally, the Framingham risk scoring method was used to quantify the predictive indicators, calculate the contribution of each indicator to the prediction of CAL in KD children over 5 years old, and construct a risk prediction scoring model. The multivariate logistic regression analysis showed that the duration of fever before the initial intravenous immunoglobulin (IVIG) treatment (OR=1.374, 95%CI: 1.117-1.689), levels of hypersensitive C-reactive protein (hs-CRP; OR=1.008, 95%CI: 1.001-1.015), and serum ferritin levels (OR=1.002, 95%CI: 1.001-1.003) were predictive indicators for CAL in KD children over 5 years old. The optimal cutoff values for predicting CAL were: duration of fever before initial IVIG treatment of 6.5 days (AUC=0.654, 95%CI: 0.565-0.744), hs-CRP of 110.50 mg/L (AUC=0.686, 95%CI: 0.597-0.774), and ferritin of 313.62 mg/L (AUC=0.724, 95%CI: 0.642-0.805). According to the Framingham risk scoring method, the low, medium, and high-risk states of CAL occurrence were defined as probabilities of <10%, 10%-20%, and >20%, respectively, with corresponding scores of 0-4 points, 5-6 points, and ≥7 points. In KD children over 5 years old, those with a longer duration of fever before initial IVIG treatment, higher levels of hs-CRP, or elevated serum ferritin levels are more likely to develop CAL.

Association between Serum Ferritin Levels and Metabolic-associated Fatty Liver Disease in Adults: a Cross-sectional Study Based on the NHANES.

Ferritin, initially acting as an iron-storage protein, was found to be associated with metabolic diseases. Our study was designed to investigate the association between serum ferritin and metabolic-associated fatty liver disease (MAFLD) using data from the National Health and Nutrition Examination Survey (NHANES) of the United State of America. A cross-sectional study was conducted, enrolling a total of 2145 participants from the NHANES in the 2017-2018 cycles. Hepatic steatosis and liver fibrosis were assessed by ultrasound images and several non-invasive indexes. Multiple regression analysis was conducted to determine the associations between serum ferritin concentration and MAFLD and liver fibrosis. The analysis revealed that participants with higher serum ferritin levels (Q3 and Q4 groups) had a higher prevalence of MAFLD than those with the lowest serum ferritin levels [Q3 vs. Q1: OR=2.17 (1.33, 3.53), P<0.05 in fatty liver index (FLI); Q4 vs. Q1: OR=3.13 (1.91, 5.13), P<0.05 in FLI]. Additionally, participants with the highest serum ferritin levels (Q4 group) displayed a higher prevalence of liver fibrosis [Q4 vs. Q1: OR=2.59 (1.19, 5.62), P<0.05 in liver stiffness measurement; OR=5.06 (1.12, 22.94), P<0.05 in fibrosis-4 index], with significantly increased risk observed in participants with concomitant diabetes [OR=7.45 (1.55, 35.72), P=0.012]. Our study revealed that elevated serum ferritin levels are associated with a higher prevalence of MAFLD and advanced liver fibrosis in patients. Elevated serum ferritin levels combined with diabetes are important risk factors for liver fibrosis.