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SARS-CoV-2 often causes viral pneumonitis, hyperferritinemia, elevations in D-dimer, lactate dehydrogenase (LDH), transaminases, troponin, CRP, and other inflammatory markers. Lung ultrasound is increasingly used to diagnose and stratify viral pneumonitis severity. We retrospectively reviewed 427 visits in patients aged 14 days to 21 years who had had a point-of-care lung ultrasound in our pediatric emergency department from 30/November/2019 to 14/August/2021. Lung ultrasounds were categorized using a 6-point ordinal scale. Lung ultrasound abnormalities predicted increased hospitalization with a threshold effect. Increasingly abnormal laboratory values were associated with decreased discharge from the ED and increased admission to the ward and ICU. Among patients SARS-CoV-2 positive patients ferritin, LDH, and transaminases, but not CRP or troponin were significantly associated with abnormalities on lung ultrasound and also with threshold effects. This effect was not demonstrated in SARS-CoV-2 negative patients. D-Dimer, CRP, and troponin were sometimes elevated even when the lung ultrasound was normal.

Aim Methods Results Conclusion Recent evidence suggests that acute liver failure (ALF) in some patients may reflect a dysregulated immune response, and that corticosteroids improve survival of the native liver in ALF patients with high serum alanine aminotransferase levels, which are an indication of liver inflammation. However, it is unclear whether steroids are effective for pediatric acute liver failure (PALF). The aim of this retrospective case–control study is to examine whether steroid therapy for PALF accompanied by immune activation improves the survival of native liver and to identify factors that predict responses to steroid treatment.Of 38 patients with PALF treated at Kyoto University Hospital from February 2006 to August 2022, 19 receiving steroids who met the specific criteria for identifying the pathophysiology of immune activity in the liver (the “Steroid group”), and seven steroid‐free patients who also met the criteria (“Nonsteroid group”) were enrolled. Patients in the “Steroid group” were categorized as “responders” or “nonresponders” according to treatment outcome. Clinical and histological data were analyzed.Survival of the native liver in the Steroid group was significantly higher than that in the Nonsteroid group (68% vs. 0%, respectively; p = 0.0052). Nonresponders were significantly younger, with higher Model for End‐stage Liver Disease and pediatric end‐stage liver disease scores, higher prothrombin time – international normalized ratio, and higher serum ferritin levels than responders. Massive hepatic necrosis was more common in nonresponders.Steroid therapy is effective for PALF patients with liver inflammation; however, liver transplantation should be prioritized for young children with ALF accompanied by severe coagulopathy or massive hepatic necrosis. [ABSTRACT FROM AUTHOR]

Background: Iron (Fe) supplementation is a critical component of anemia therapy for patients with chronic kidney disease (CKD). However, serum Fe, ferritin, and transferrin saturation, used to guide Fe replacement, are far from optimal, as they can be influenced by malnutrition and inflammation. Currently, there is a trend of increasing Fe supplementation to target high ferritin levels, although the long-term risk has been overlooked. Methods: We prospectively enrolled 28 patients with CKD on hemodialysis with high serum ferritin (> 1000 ng/ml) and tested the effects of 1-year deferoxamine treatment, accompanied by withdrawal of Fe administration, on laboratory parameters (Fe status, inflammatory and CKD-MBD markers), heart, liver, and iliac crest Fe deposition (quantitative magnetic resonance imaging [MRI]), and bone biopsy (histomorphometry and counting of the number of Fe positive cells in the bone marrow). Results: MRI parameters showed that none of the patients had heart iron overload, but they all presented iron overload in the liver and bone marrow, which was confirmed by bone histology. After therapy, ferritin levels decreased, although neither hemoglobin levels nor erythropoietin dose was changed. A significant decrease in hepcidin and FGF-23 levels was observed. Fe accumulation was improved in the liver and bone marrow, reaching normal values only in the bone marrow. No significant changes in turnover, mineralization or volume were observed. Conclusions: Our data suggest that treatment with deferoxamine was safe and could improve Fe accumulation, as measured by MRI and histomorphometry. Whether MRI is considered a standard tool for investigating bone marrow Fe accumulation requires further investigation. Registry and the registration number of clinical trial: ReBEC (Registro Brasileiro de Ensaios Clinicos) under the identification RBR-3rnskcj available at: https://ensaiosclinicos.gov.br/pesquisador. [ABSTRACT FROM AUTHOR]

Background: Diabetes Mellitus is a prevalent metabolic disorder influenced by genetic and environmental factors, with India facing a substantial rise in its diabetic population. Recent research has highlighted the association between elevated body iron levels and the onset of diabetes and its complications. This study aimed to explore the relationship between Serum Ferritin, HbA1c%, and Blood Glucose in patients with Type 2 Diabetes Mellitus. To evaluate the association between Serum Ferritin, HbA1c%, and Blood Glucose in patients with Type 2 Diabetes Mellitus. Material & Method: This cross-sectional study was conducted among patients with Type 2 Diabetes Mellitus attending the outpatient and inpatient departments of MNR Medical College & Hospital from June 2023 to January 2024. Patients meeting the inclusion criteria were enrolled, while those with specific exclusions were excluded. Detailed demographic and medical history data were collected, and blood samples were obtained for various biochemical analyses. Statistical analysis was performed using SPSS version 20. Results: The study included 100 patients, with no significant demographic differences between groups. Participants with diabetes exhibited significantly higher fasting and postprandial blood glucose levels, glycemic control, and LDL cholesterol compared to controls (p<0.05). Serum ferritin showed significant correlations with blood glucose (FBS=0.59, PPBS=0.69) and HbA1c (r=0.62). Conclusion: Elevated Serum Ferritin levels correlated significantly with higher Blood Glucose and HbA1c levels in patients with Type 2 Diabetes Mellitus, suggesting a potential role of iron metabolism in glycemic control. These findings underscore the importance of further investigation into the link between iron status and diabetes management. [ABSTRACT FROM AUTHOR]

This article discusses a rare case of a 49-year-old woman who developed a specific type of dermatomyositis (DM) after using a medication for rheumatoid arthritis (RA). The article suggests a possible association between the medication and the development of DM. It emphasizes the importance of considering this diagnosis in RA patients who develop interstitial lung disease. The article includes a detailed case presentation with images and laboratory findings. It also mentions that the patient did not receive a COVID-19 vaccine, although there have been reports of similar cases occurring after vaccination. The article was edited by Editage and did not receive any funding. [Extracted from the article]

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 betathalassemia 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 betathalassemia 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. [ABSTRACT FROM AUTHOR]

Introduction: Adult hemophagocytic lymphohistiocytosis (HLH) is a rare disease with a dismal prognosis. Early diagnosis and prompt management are necessary for improved outcomes. Methods: This multicenter retrospective study investigated the etiologies, survival, and prognostic factors of HLH, including the utility of HLH-2004 criteria and HScore in real-life clinical practice. Results: A total of 147 HLH patients were identified by using a combination of hemophagocytosis identification in bone marrow and the HLH-related international classification disease-10. A total of 116 (78.9%) patients fulfilled the HLH diagnosis by HScore, while 91 (61.9%) patients fulfilled 5 of 8 HLH-2004 criteria. In Thailand, the clinical application of HLH-2004 criteria needed to be reduced from 8 to 6 due to a lack of sCD25 and natural killer cell activity tests. Using the adapted HLH-2004 with a cutoff value of 4 resulted in 132 (89.9%) cases meeting the diagnostic criteria. Among these 132 confirmed HLH patients by using adapted HLH-2004, HLH was triggered by infection (29.5%), autoimmune disease (12.9%), malignancy (40.9%), and unknown cause (16.7%). Median overall survival of HLH patients was extremely short (67 days). Ferritin >6,000 μg/L, HLH from infection, malignancy, and unknown etiology were demonstrated as independent prognostic factors for inferior survival (hazard ratio [HR] 2.47; 95% confidence interval [CI] 1.39–4.37, HR 4.69; 95% CI 1.38–15.92, HR 6.09; 95% CI 1.84–20.14, and HR 6.02; 95% CI 1.64–22.05, respectively). Conclusion: Ferritin is a helpful biomarker for HLH diagnosis and prognostic prediction. Autoimmune disease-triggered HLH has favorable outcomes. Future prospective study is required to verify the use of the adapted HLH-2004 criteria. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a common comorbidity in COVID-19 subjects. Hyperglycemia at hospital admission identified as a major risk factor and is responsible for poor prognosis. Hematological and inflammatory parameters have been recognized as predictive markers of severity in COVID-19. In this clinical study, we aimed to assess the impact of hyperglycemia at hospital admission on hematological and several inflammatory parameters in COVID-19 patients. A total of 550 COVID-19 subjects were primarily categorized into two major groups (normoglycemic and hyperglycemic) based on random blood sugar levels. On the first day of hospitalization, subjects' oxygen saturation, random blood sugar, hematological variables, and inflammatory parameters were recorded. The hyperglycemic group exhibited higher levels of serum ferritin, total leukocyte count (TLC), lactate dehydrogenase (LDH), neutrophil count, and neutrophil-to-lymphocyte ratio (NLR). In contrast, oxygen saturation and lymphocyte count were lower compared to the normoglycemic group. Significantly elevated levels of hematological variables (TLC, neutrophil count, NLR) and inflammatory parameters (serum ferritin) were observed in the hyperglycemic group. Among inflammatory parameters, only serum ferritin levels showed statistical significance. This study supports the clinical association between hyperglycemia and an increased severity of COVID-19. Consequently, the identification of these parameters is a crucial and valuable prognostic indicator for assessing disease severity in hyperglycemic subjects. [ABSTRACT FROM AUTHOR]

Macrophage activation syndrome (MAS) is potentially fatal; so, early diagnosis and timely treatment are essential. However, detecting MAS is sometimes challenging because its principal features can be observed in other pediatric diseases that cause severe inflammation. Cytokine storm due to immune dysregulation represents the clinical and laboratory features of MAS that are included in the diagnostic criteria. Most cases of MAS occur as an underlying condition worsens and progresses. Therefore, a patient with autoimmune or autoinflammatory disease who shows unexplained clinical deterioration despite appropriate management should be considered at high risk for MAS (i.e., occult MAS). The basic principles of treatment are control of triggering factors, supportive care, and relief of hyperinflammation. Systemic steroids and cyclosporine A are frequently used as a first-line treatment. For the treatment of refractory MAS, cytokine-specific biologic agents such as anakinra have recently become preferred over traditional immunosuppressive agents such as etoposide. MAS might be underrecognized in pediatric patients with infectious and inflammatory diseases due to its diverse clinical presentations. Clinical suspicion of MAS is of the utmost importance for early recognition of the disease. [ABSTRACT FROM AUTHOR]

Diabetes significantly impacts the immune system; however, its role in worsening sepsis prognosis remains poorly understood. This study investigated the effect of hyperferritinemia on immune modulation in septic diabetic patients. A cohort study at Kyungpook National University Hospital stratified sepsis patients by diabetes status and followed them for 28 days. Additionally, CD4+ T cells from mice were analyzed for proliferation, apoptosis, and metabolic changes under ferritin treatment. Results from the clinical study showed higher ferritin levels in diabetic patients, and those with lower lymphocyte counts had increased mortality. In the mice study, ferritin inhibited T cell activation and proliferation by shifting metabolism from glycolysis to oxidative phosphorylation without increasing cell death. These findings suggest that the suppression of T cell proliferation due to elevated ferritin levels contributes to an immunosuppressive environment, leading to worse outcomes. In conclusion, hyperferritinemia is a biomarker for sepsis severity, particularly in diabetic patients, highlighting potential therapeutic strategies targeting ferritin levels or glycolytic pathways.

Abstract Pre-treatment host and viral factors may affect serum ferritin levels in patients with hepatitis C virus (HCV) infection. We delineated pre-treatment factors associated with hyperferritinemia in these patients. 1682 eligible patients underwent pre-treatment assessment for serum ferritin and various host/viral factors. Univariate and multivariate logistic regression analyses were conducted to evaluate factors associated with hyperferritinemia. Multivariate logistic regression analyses revealed that age > 50 years (adjusted odds ratio [OR]: 1.38 (95% confidence interval [CI] 1.09–1.74), p = 0.008), fibrosis stage ≥ F3 (adjusted OR: 1.36 (95% CI 1.04–1.77), p = 0.02), fibrosis index based on four parameters (FIB-4) > 3.25 (adjusted OR: 1.46 (95% CI 1.11–1.92), p = 0.01), presence of metabolic dysfunction-associated steatotic liver disease (MASLD) (adjusted OR: 1.43 (95% CI 1.21–1.76), p = 0.001), and alanine transaminase (ALT) > 2 folds upper limit of normal (ULN) (adjusted OR: 2.87 (95% CI 2.20–3.75), p

Adult-onset Still’s disease (AOSD) is a remarkably rare illness. One well-known pathogenic process that results in systemic manifestations is auto-inflammatory disease. We report on a young man who complained of joint pain, sore throat, and a high spiking fever. After a thorough assessment using the Yamaguchi criteria, the patient’s clinical examination, elevated serum ferritin and C-reactive protein (CRP), absence of serologic markers (RA factor, Antinuclear antibody levels), and lymphadenopathy all contributed to the diagnosis of AOSD. He was treated with analgesics, steroids, and disease-modifying anti-rheumatic drugs (DMARDs). Three weeks later, at the follow-up, his symptoms and lab parameters had improved.

Background: Thalassemia is the most prevalent hereditary anaemia worldwide. Severe forms of thalassemia can lead to reduced life expectancy due to disease-related complications. Objectives: To investigate the survival of thalassemia patients across varying disease severity, causes of death and related clinical factors. Patients and methods: We conducted a retrospective review of thalassemia patients who received medical care at Chiang Mai University Hospital. The analysis focused on survival outcomes, and potential associations between clinical factors and patient survival. Results: A total of 789 patients were included in our study cohort. Among them, 38.1% had Hb H disease, 35.4% had Hb E/beta-thalassemia and 26.5% had beta-thalassemia major. Half of the patients (50.1%) required regular transfusions. Sixty-five patients (8.2%) had deceased. The predominant causes of mortality were infection-related (36.9%) and cardiac complications (27.7%). Transfusion-dependent thalassemia (TDT) (adjusted HR 3.68, 95% CI 1.39-9.72, p = 0.008) and a mean serum ferritin level ≥3000 ng/mL (adjusted HR 4.18, 95% CI 2.20-7.92, p < 0.001) were independently associated with poorer survival. Conclusions: Our study highlights the primary contributors to mortality in patients with thalassemia as infection-related issues and cardiac complications. It also underscores the significant impact of TDT and elevated serum ferritin levels on the survival of thalassemia patients. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion To investigate characteristics and outcomes of critically ill cancer patients with marked hyperferritinemia.A single‐center retrospective analysis comprising cancer patients with a ferritin level >10.000 μg/L treated in the intensive care unit (ICU) between 2012 and 2022 was conducted.A total of 117 patients were included in the analysis. The median age was 59 years (range: 15–86 years). Females accounted for 48% of cases. 90% of patients had a hematologic malignancy. The median maximum ferritin level was 27.349 μg/L (range: 10.300–426.073 μg/L). The diagnostic criteria of septic shock were fulfilled in 51% of cases; 31% of patients had hemophagocytic lymphohistiocytosis (HLH) according to the HLH‐2004 criteria. Mechanical ventilation, renal replacement therapy and the use of vasopressors were necessary in 59%, 35% and 70% of cases, respectively. The ICU, hospital, 90‐day and 1‐year survival rates were 33.3%, 23.1%, 23.7% and 11.7%. Patients with septic shock had a worse survival than those without septic shock (p = .001); the survival of patients who fulfilled the HLH‐2004 criteria did not differ from those who did not (p = .88).Critically ill cancer patients with marked hyperferritinemia have poor outcomes. The present data may help to make informed decisions for this patient group. [ABSTRACT FROM AUTHOR]

Background: Haemochromatosis 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 presentation: We 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. Conclusions: This 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. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with increasing prevalence worldwide. NAFLD could develop from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), NASH-related fibrosis, cirrhosis, and even hepatocellular carcinoma. However, the mechanism of NAFLD development has not yet been fully defined. Recently, emerging evidence shows that the dysregulated iron metabolism marked by elevated serum ferritin, and ferroptosis are involved in the NAFLD. Understanding iron metabolism and ferroptosis can shed light on the mechanisms of NAFLD development. Here, we summarized studies on iron metabolism and the ferroptosis process involved in NAFLD development to highlight potential medications and therapies for treating NAFLD. [ABSTRACT FROM AUTHOR]

Background and Objectives: Oral contraceptive pills are widely used for family planning worldwide. However, their effects on physiological processes including inflammation and iron homeostasis are not fully elucidated. The present study aimed to comprehensively evaluate the impact of oral contraceptives on serum ferritin as an indicator of iron stores, and C-reactive protein as a marker of inflammation, in women of reproductive age. Methods: The study enrolled 100 women aged 21-45 years, comprising 50 oral contraceptive users and 50 nonusers. Demographic and clinical data were gathered through questionnaires. Blood samples were collected for measurement of ferritin and C-reactive protein levels. Results: The findings revealed significantly elevated serum ferritin and C-reactive protein in oral contraceptive users compared to non-users. Moreover, increasing body weight was positively correlated with higher ferritin and C-reactive protein concentrations among contraceptive users. Menstrual irregularities and increased abortion rates were also observed in oral contraceptive users relative to non-users. Conclusion: The results highlight that long-term use of oral contraceptives may perturb iron homeostasis and provoke low-grade chronic inflammation in women of childbearing age. Additionally, overweight oral contraceptive users represent a particularly high-risk group warranting close monitoring of iron and inflammation markers. Further research into the intricate biomolecular mechanisms and downstream health impacts of altered ferritin and C-reactive protein levels with oral contraceptive use is recommended. [ABSTRACT FROM AUTHOR]

A 58-year-old female was found to have hyperferritinemia (Serum ferritin:1683 ng/mL) during work-up for mild normocytic anemia. Transferrin saturation(TSAT) was low-normal. Magnetic resonance imaging (MRI) abdomen showed evidence of hepatic iron deposition. Liver biopsy showed 4 + hepatic iron deposition without any evidence of steatosis or fibrosis. Quantitative liver iron was elevated at 348.3 µmol/g dry liver weight [Reference range(RR): 3–33 µmol/g dry liver weight]. She was presumptively diagnosed with tissue iron overload, cause uncertain. A diagnosis of ferroportin disease (FD) was considered, but the pattern of iron distribution in the liver, mainly within the hepatic parenchyma (rather than in the hepatic Kupffer cells seen in FD), and the presence of anemia (uncommon in FD) made this less likely. She was treated with intermittent phlebotomy for over a decade with poor tolerance due to worsening normocytic to microcytic anemia. A trial of deferasirox was done but it was discontinued after a month due to significant side effects. During the course of treatment, her ferritin level decreased. Over the past 1.5 years, she developed progressively worsening neurocognitive decline. MRI brain showed areas of susceptibility involving basal ganglia, midbrain and cerebellum raising suspicion for metabolic deposition disease. Neuroimaging findings led to testing for serum copper and ceruloplasmin levels which were both found to be severely low. Low serum copper, ceruloplasmin levels and neuroimaging findings led us to consider Wilson disease however prior liver biopsy showing elevated hepatic iron rather than hepatic copper excluded the diagnosis of Wilson disease. After shared decision making, ceruloplasmin gene analysis was not pursued due to patient's preference and prohibitive cost of testing. The diagnosis of aceruloplasminemia was ultimately made. The biochemical triad of hyperferritinemia, low-normal TSAT and microcytic anemia should raise the possibility of aceruloplasminemia. Since neurological manifestations are rare in most inherited iron overload syndromes, neurological symptoms in a patient with tissue iron overload should prompt consideration of aceruloplasminemia as a differential diagnosis. [ABSTRACT FROM AUTHOR]

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 <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 <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. [ABSTRACT FROM AUTHOR]

Context There is limited data on the clinical significance of metabolic hyperferritinemia (MHF) based on the most recent consensus. Objective We aimed to validate the clinical outcomes of MHF in the general population and patients with biopsy-proven metabolic dysfunction–associated fatty liver disease (MAFLD). Methods The NHANES database and PERSONS cohort were included. MHF was defined as elevated serum ferritin with metabolic dysfunction (MD) and stratified into different grades according to ferritin (grade 1: 200 [females]/300 [males]—550 ng/mL; grade 2: 550-1000 ng/mL; grade 3: >1000 ng/mL). The clinical outcomes, including all-cause death, comorbidities, and liver histology, were compared between non-MHF and MHF in adjusted models. Results In NHANES, compared with non-MHF with MD, MHF was related to higher risks of advanced fibrosis (P =.036), elevated albumin–creatinine ratio (UACR, P =.001), and sarcopenia (P =.013). Although the association between all grades of MHF and mortality was insignificant (P =.122), grades 2/3 was associated with increased mortality (P =.029). When comparing with non-MHF without MD, the harmful effects of MHF were more significant in mortality (P <.001), elevated UACR (P <.001), cardiovascular disease (P =.028), and sarcopenia (P <.001). In the PERSONS cohort, MHF was associated with more advanced grades of steatosis (P <.001), lobular inflammation (P <.001), advanced fibrosis (P =.017), and more severe hepatocellular iron deposition (P <.001). Conclusion Both in the general population and in at-risk individuals with MAFLD, MHF was related with poorer clinical outcomes. [ABSTRACT FROM AUTHOR]

Dengue fever is the most common arboviral disease transmitted globally. It was estimated about 400,000 cases of severe dengue occur in Asian countries. Patients with severe dengue are at risk of developing secondary Haemophagocytic Lymphohistiocytosis (HLH) which contribute to high morbidity and mortality. Thus, a high index of suspicion should be considered in critical dengue patient. We presented a case of young girl, who initially had classical symptoms and sign of dengue fever and was in compensated shock at presentation. The condition further deteriorated as she developed Acute respiratory distress syndrome (ARDS) and secondary HLH due to severe infection. She developed unremitting fever despite already out of defervenscence window period. With some positive laboratory findings; highly elevated serum ferritin of more than 10,000 mcg/L, low natural killer (NK) cells, bicytopenias and hypertriglyceridemia in which directed towards diagnosis of secondary HLH. However, due to ill condition, the bone marrow aspiration was not able to be performed to confirm the presence of haemophagocytosis. HLH is a hyper inflammatory condition which is characterized by macrophage activation with phagocytosis of blood cells in the bone marrow and cytokine storm, leading to organ dysfunction and death. [ABSTRACT FROM AUTHOR]

Introduction: It is well known that preterm birth (PTB) contributes to perinatal mortality and long-term morbidity. Elevated serum ferritin levels have been frequently reported in PTB compared to term births; however, most studies had blood samples taken during the peripartum period. We aim to evaluate the relationship between antenatal serum ferritin levels and PTB. Methods: A retrospective study of pregnant women delivered at our hospital between January 2013 and December 2020 was conducted. Demographic data, medical history, gestation, and blood ferritin results were retrieved from the hospital and laboratory information system. Patients with maternal serum ferritin measured antenatally who were not documented to have chronic diseases, infection, iron disorders, multiple gestations, and uterine or cervical anomalies were included in the analysis. We compared the preterm and term groups' ferritin levels and other risk factors. Results: Among 202 recruited women, 27 (14.4%) had spontaneous PTB. Most ferritin measurements (80%) were taken during the third trimester. There was no significant difference in the median ferritin levels between PTBs (15.81µg/L, IQR 10.09 - 32.41 µg/L) and term births (16.11µg/L, IQR 9.09 - 34.38 µg/L), P=0.801. However, ferritin levels in the second trimester nearly doubled that in the first trimester in the PTB group. PTB was associated with more cases of preeclampsia (P=0.003), a history of antepartum haemorrhage (p=0.040) and premature rupture of membrane status (P<0.001). Conclusion: Despite the elevation of ferritin levels in the second trimester, there is no significant association between maternal antenatal ferritin levels and PTB. [ABSTRACT FROM AUTHOR]

Objectives: Iron metabolism and insulin resistance (IR) are closely related to non‐alcoholic fatty liver disease (NAFLD). However, the interplay between them on the occurrence and progression of NAFLD is not fully understood. We aimed to disentangle the crosstalk between iron metabolism and IR and explore its impact on NAFLD. Methods: We analyzed data from the National Health and Nutritional Examination Survey (NHANES) 2017–2018 to evaluate the association between serum iron metabolism indicators (ferritin, serum iron, unsaturated iron‐binding capacity [UIBC], total iron‐binding capacity [TIBC], transferrin saturation, and transferrin receptor) and NAFLD/non‐alcoholic steatohepatitis (NASH). Mediation analysis was conducted to explore the role of IR played in these relationship. Results: A total of 4812 participants were included, among whom 43.7% were diagnosed with NAFLD and 13.2% were further diagnosed with NASH. After adjusting the covariates, the risk of NAFLD increases with increasing serum ferritin (adjusted odds ratio [aOR] 1.71, 95% confidence interval [CI] 1.37–2.14), UIBC (aOR 1.45, 95% CI 1.17–1.79), and TIBC (aOR 1.36, 95% CI 1.11–1.68). Higher levels of serum ferritin (aOR 3.70, 95% CI 2.25–6.19) and TIBC (aOR 1.69, 95% CI 1.13–2.56) were also positively associated with NASH. Participants with IR were more likely to have NAFLD/NASH. Moreover, IR‐mediated efficacy accounted for 85.85% and 64.51% between ferritin and NAFLD and NASH, respectively. Conclusion: Higher levels of serum ferritin and TIBC are closely associated with the occurrence of NAFLD and NASH. IR may be considered a possible link between NAFLD or NASH and increased serum ferritin levels. [ABSTRACT FROM AUTHOR]

Hyperferritinemia reflects iron accumulation in the body and has been associated with metabolic disturbances and alcohol use, and is also a common finding in individuals diagnosed with liver disease. The major genetic regulator of iron metabolism is the HFE gene. The aim of this this study was to investigate the association between serum ferritin and liver fibrosis using the enhanced liver fibrosis (ELF) test, and the association between ferritin and liver-related outcomes in a Finnish population-based cohort of 6194 individuals (45% male, mean [± standard deviation] age, 52.9 ± 14.9 years; body mass index 26.9 ± 4.7 kg/m2). The effects of HFE variants on these associations were also evaluated. Serum ferritin levels were significantly associated with liver fibrosis, as estimated by enhanced liver fibrosis (ELF) test in weighted linear regression analysis. Serum ferritin was significantly associated with both all liver-related outcomes (n = 92) and severe liver-related outcomes (n = 54) in weighted Cox regression analysis (hazard ratio [HR] per 1 SD, 1.11 [95% confidence interval (CI) 1.02–1.21]; p = 0.012 and HR 1.11 [95% CI 1.02–1.21]; p = 0.013, respectively). However, there was association neither between HFE risk variants and ELF test nor between HFE risk variants and liver-related outcomes. Serum ferritin levels were associated with liver fibrosis and incident liver disease, independent of HFE genotype in the general population. Furthermore, data demonstrated that metabolic disturbances and alcohol use were major risk factors for hyperferritinemia. [ABSTRACT FROM AUTHOR]

To investigate the prevalence, risk factors and prognosis of invasive pulmonary aspergillosis (IPA) in patients with anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+ DM). Methods: A retrospective analysis was conducted in anti-MDA5+ DM patients diagnosed between January 2016 and March 2023. Patients with lower respiratory tract specimens were categorized into IPA+ and IPA- groups based on the presence of IPA and their clinical characteristics and prognoses then compared. Results: Of the 415 patients diagnosed with anti-MDA5+ DM, 28 cases had IPA (prevalence rate of 6.7%) with Aspergillus fumigatus being the most common species. The patients were categorized into IPA+ (n=28) and IPA- (n=98) groups, with no significant age or gender-related differences (P 0.05). The IPA+ group had a lower lymphocyte count, particularly the CD4+ T-cell count, and reduced serum albumin and higher serum ferritin levels (P all< 0.05). An elevated bronchoalveolar lavage fluid (BALF) galactomannan level was found to be the sole independent risk factor for the occurrence of IPA (adjusted OR=2.191, P=0.029) with a cut-off value of 0.585 and area under the curve of 0.779. The mortality rate in the IPA+ group was 25%. Compared to survivors, non-survivors in this group exhibited a higher incidence of rapidly progressive interstitial lung disease, lower lymphocyte counts, and increased co-infection with Pneumocystis jirovecii (P all< 0.05). Conclusion: IPA was not rare in patients with anti-MDA5+ DM, with elevated BALF galactomannan levels being an independent risk factor for IPA occurrence. Clinicians must exercise vigilance to identify patients exhibiting the aforementioned risk factors. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 attributed to severe acute respiratory syndrome has been implicated with life threatening opportunistic infections like mucormycosis. COVID-19 is a hyperferritinemic syndrome and emerging data project the role of iron in the susceptibility and pathogenesis of mucormycosis but whether high ferritin is an indicator of severity of mucormycosis is debated. The study aimed to determine the relationship between serum ferritin levels and the extent of involvement of COVID-19 associated mucormycosis. A hospital based observational study was conducted with a sample size of 70. All biopsy confirmed cases of COVID-19 associated mucormycosis were included. Retrospective data from hospital records prepared at the time of patient admission were retrieved. The imaging data was used to determine the extent of disease involvement and serum ferritin values were analysed. During the study period 40 patients had mild extent mucormycosis and 30 had severe extent. A statistically significant difference was seen in levels of serum ferritin between mild extent mucormycosis and severe extent involvement (p < 0.01). COVID-19 associated Mucormycosis patients tend to have higher serum ferritin values especially in severe extent disease and with active COVID-19 infection along with diabetes mellitus as a potent aggravating factor. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) is a common metabolic disorder affecting insulin secretion, insulin sensitivity, or both, resulting in hyperglycemia. As it progresses, almost all systems including cardiovascular, nervous, renal, etc. are involved eventually manifesting as several health-related complications. As all the systems of the human body work in harmony with each other, development of insulin resistance, dyslipidemia, and setting in of chronic inflammatory states evidenced by the rise in inflammatory markers are interrelated. Aims and Objectives: The aim of this study was to establish the correlation of the inflammatory markers, serum ferritin and high sensitivity C-reactive protein (hs-CRP), with glycated hemoglobin (HbA1c) and dyslipidemia in patients of type 2 DM. Materials and Methods: The present cross-sectional study was carried out in the Department of Biochemistry, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand. A total of 80 male patients of type 2 DM aged between 40 and 60 years with blood HbA1c level of more than 6.5% were included in the study. Results: The inflammatory markers hs-CRP and ferritin were found to be positively correlated with HbA1c, triglycerides, total cholesterol, and low-density lipoprotein-cholesterol but negatively correlated with high-density lipoprotein-cholesterol. Conclusion: Estimation of serum ferritin and hs-CRP can detect the ongoing inflammatory and free radical-mediated damages in diabetic patients at an early period before the development of diabetic-related complications such as atherosclerosis and myocardial infarction. [ABSTRACT FROM AUTHOR]

Very preterm infants often need red blood cell transfusions (RBCT) during intensive care and are at risk of iron overload. This study reviewed the records of 65 very preterm neonates who required at least one RBCT to ascertain the iron status using serum ferritin levels at 4–6 weeks age before oral iron was commenced. High serum ferritin level was found in 52.3% (n = 34) neonates. Need for > 1RBCT was significantly and independently associated with iron excess (P < 0.001). Increased ferritin noted following transfusions in neonatal period can have implications for determining the appropriate time for starting iron supplementation in this subgroup of neonates. [ABSTRACT FROM AUTHOR]

Background and aims: This study evaluated whether stored iron determines the adaptive response induced by Nordic walking (NW) training combined with 10 hours' time-restricted eating (TRE) in older adults. Trial design and methods: Twenty-four participants underwent 12-week NW training supported by 10 h of TRE. The group was divided due to baseline ferritin concentration low < 75 ng/ml (LF) and high level ≥ 75 ng/ml (HF). Body composition, physical fitness and blood collection were assessed at baseline and post-intervention. Results: NW + TRE induced a statistically significant decrease in ferritin levels in all participants (p = 0.01). Additionally, statistically significant intergroup differences in the LF vs. HF in the reduction of serum ferritin levels (p = 0.04) were observed. The procedure NW + TRE diminished HbA1c levels (p < 0.01) and glucose in all participants (p = 0.05). The range of HbA1c drop was more pronounced among those participants who experienced a greater decrease in the stored iron (p = 0.04, =0.17, F=4.59). Greater changes in body weight and percent of body fat were recorded in the HF group (for both p<0.01). Conclusion: Body iron stores determine the effects of a 12-week NW + TRE intervention on serum ferritin. The changes in HbA1c are more pronounced in subjects with a higher decrease in serum ferritin. Trial registration: All experimental protocols were approved by the Bioethical Committee of the Regional Medical Society in Gdansk, Poland (NKBBN/330/2021) according to the Declaration of Helsinki. We confirm that all methods were carried out in accordance with relevant guidelines and regulations. The trial was registered as a clinical trial (NCT05229835, date of first registration: 14/01/2022, direct link: https://classic.clinicaltrials.gov/ct2/show/NCT05229835). Informed consent was obtained from all subjects. [ABSTRACT FROM AUTHOR]

Introduction: Beta thalassaemia is the most prevalent hereditary autosomal disorder, significantly impacting endocrine function during pubertal development. The pathology is rooted in the excessive deposition of iron in vital organs. If left untreated, this condition leads to serious morbidity and mortality. Hypogonadism stands as the most common endocrine complication. Aim: To observe pubertal development in girls with thalassaemia and evaluate the adequacy of chelation therapy in such patients by measuring levels of Follicle Stimulating Hormone (FSH), Luteinising Hormone (LH), oestrogen, and serum ferritin. Materials and Methods: A quasi-experimental study was conducted at the Thalassaemia Clinic at the Department of Obstetrics and Gynaecology, Burdwan Medical College, Purba Bardhaman, West Bengal, India involving 300 diagnosed Beta Thalassaemia Major (BTM) (case) patients aged 13 to 17 years over a period of one and a half years (January 2020 to June 2021). The girls in the study groups were sequentially enrolled from the Outpatient Department of the Thalassaemia Clinic after meeting inclusion and exclusion criteria. Demographic data, anthropometric measurements, and Sexual Maturity Rating (SMR) were recorded. Hormonal assays of serum FSH, LH, oestrogen, and serum ferritin levels were conducted. Thalassaemic girls with serum ferritin levels exceeding 500 ng/mL received chelation therapy. Serum ferritin levels were measured at two-month intervals for up to six months, with reassessment of serum FSH, LH, oestrogen, and ferritin levels at the end of the six-month period. Statistical analysis was conducted using Statistical Package for Social Sciences (SPSS) version 27.0, Microsoft excel spreadsheet, and Epi Info 7. Results: A total of 190 (63.3%) of the thalassaemic girls were aged 13 to 15 years, with a mean Body Mass Index (BMI) of 22.5000±2.6100 kg/m², and 74 of them (38.94%) experienced menarche in this age group. Out of 300 cases, 269 thalassaemic girls (89.6%) received chelation therapy, and 89 cases (33.09%) reached menarche after chelation therapy. A significant (p<0.0001) increase in mean LH and FSH levels was observed after chelation therapy. The mean ferritin level decreased from 3168.85 ng/mL to 2227.24 ng/mL following chelation therapy. Conclusion: Pubertal development failure is common in beta thalassaemic girls. Intervention in the form of adequate chelation therapy in girls with high serum ferritin levels yielded favourable outcomes, as evident from serum gonadotropin and oestrogen levels. [ABSTRACT FROM AUTHOR]

Introduction: Improvement in the standard of care of Thalassaemia by regular blood transfusion increases life expectancy. Multiple transfusions with concurrent iron overload and chronic anaemia, leading to tissue-level hypoxemia, cause significant renal dysfunction. Microalbuminuria is a sensitive marker of glomerular damage, and studies in thalassemic children have demonstrated variable prevalence rates of microalbuminuria. Aim: To study the prevalence of microalbuminuria and its association with clinical and laboratory parameters in children with Beta Thalassaemia Major (BTM). Materials and Methods: A cross-sectional study was conducted from January 2018 to June 2019 at Indira Gandhi Institute of Child Health, Bangaluru, Karnataka, India. A total of 155 children with Beta Thalassaemia Major (BTM) aged 2-18 years, attending the Thalassaemia Day Care Centre, were included in the study. Their demographic details such as age, gender, clinical parameters like frequency of transfusions, type of chelation therapy, height, weight, Body Mass Index (BMI), organomegaly, and laboratory parameters like serum creatinine, ferritin, pretransfusion Hb%, and Urinary Microalbumin Creatinine Ratio (UMCR) were studied as per a predesigned proforma. The association between microalbuminuria with clinical and laboratory parameters was evaluated using the independent sample T-test or Mann-Whitney U test and Chi-square/Fischer's-exact test. Results: A total of 155 children with BTM were studied. In the present study, out of a total of 155 patients, microalbuminuria was found in 66 (42.6%). A significant increase in the prevalence of microalbuminuria was observed as the age advanced, as the frequency of blood transfusions increased, with low pretranfusion haemoglobin (g%), and with elevated serum ferritin. Conclusion: In the present study, the prevalence of microalbuminuria was found to be 42.6%. Screening for microalbuminuria is recommended in all children with beta thalassaemia major for the early detection of renal dysfunction, prevention of disease progression, and improvement in the quality of their lives. [ABSTRACT FROM AUTHOR]

Elevated serum ferritin (SF) levels have been associated with poor prognosis in various cancer types, but its impact on nasopharyngeal carcinoma (NPC) remains unclear. This retrospective study analyzed clinical data from 252 non-metastatic NPC patients admitted to Hainan General Hospital between January 2014 and May 2016. SF levels were measured using the chemiluminescence method. Patients were categorized into low, medium, and high-level SF groups based on tertile median SF levels. Survival outcomes were assessed using Kaplan–Meier analysis and Cox regression models. The overall survival rates of the entire patient cohort at 1, 3, 5, and 8 years were 95.2%, 85.7%, 76.2%, and 68.9% respectively. The high-level SF group (SF > 164.00 ng/mL) had significantly worse overall survival (83.1 vs 96.3 months, P = 0.023) and progression-free survival (77.8 vs 93.3 months, P = 0.019) compared to the low-level SF group. Univariate and multivariate analyses confirmed that high SF levels, along with T3/T4 staging and N3 staging, were independent risk factors for poor prognosis. In conclusion, high SF levels are associated with shorter overall survival and progression-free survival in NPC patients. [ABSTRACT FROM AUTHOR]

This document discusses the prognostic value of ferritin in patients with multiple myeloma (MM) who have undergone autologous stem cell transplantation (ASCT). The authors collected data from 3446 MM patients who received ASCT therapy and had serum ferritin testing. They found that high serum ferritin levels were associated with a poorer prognosis in MM patients, regardless of gender, race, or age. Additionally, they observed that ferritin had a significant impact on the prognosis of patients in different MM staging systems, such as the International Staging System (ISS) and the Revised International Staging System (R-ISS). The authors conclude that ferritin is an independent risk factor for MM patients' overall survival and progression-free survival. [Extracted from the article]

Objective: To investigate the relationship between transfusion frequency, serum ferritin levels, and hepatomegaly in beta-thalassemia major patients. Study Design: Cross-sectional study. Setting: Thalassemia Center, Liaquat University Hospital, Hyderabad. Period: January 2023 to June 2023. Material & Methods: Among 158 patients, age until 19 years, and ß-thalassemia type major was considered as inclusion criteria. Data regarding hematological parameters and hepatomegaly was collected after informed consent. Data was analyzed using SPSS (version 22). Chi-square test was used to investigate the association between ferritin levels and hepatomegaly while Pearson's correlation was used assess the correlation between ferritin levels and transfusion frequency. P-Value = 0.05 was considered as statistically significant. Results: Majority of the participants were males (58.22%) as compared to females (41.77%). The mean age of the study participants was 9.31±4.47 years, and the mean age at first transfusion was 8.98±0.93 years. Majority of the participants were underweight 107(67.72%). Monthly transfusion rate was 1.95±0.31. The mean serum ferritin levels among the study participants were 2033.06±1309.36 ng/mL. Hepatomegaly was found to be present in 99 (62.65%) of the study participants. Statistically significant positive correlation between the frequency of transfusion and serum ferritin levels (r = 0.71, p<0.05) was observed. The difference of hepatomegaly in low-ferritin vs high-ferritin was also found to be statistically significant (p<0.05). Conclusion: It was concluded that higher transfusion rates were associated with elevated ferritin levels, and there was a significant association between higher serum ferritin levels and the presence of hepatomegaly. [ABSTRACT FROM AUTHOR]

Objective: To determine the influence of serum ferritin levels on glycemic control in patients with type 2 diabetes mellitus (T2DM) patients. Study Design: Cross-sectional study. Setting: Department of Medicine, Liaquat University Hospital, Hyderabad, Pakistan. Period: July 2021 to December 2021. Material & Methods: A total of 180 patients of 30-60 years of age and either gender, and known cases of diabetes mellitus for =3 year duration were included. Demographic, clinical and laboratory data was recorded. HbA1c below 7% was labeled as good glycemic control while HbA1c above or equal to 7% was designated as poor glycemic control. The serum ferritin =307 µg/L was considered as raised. Association of glycemic control with respect to serum ferritin levels was noted. Results: In a total of 180 patients of T2DM, the mean age, duration of diabetes, and HbA1c were 53.62 ± 5.82 years, 11.91±4.92 years, and 12.41 ± 5.73% respectively. The mean serum ferritin was 512±22.53 ug/L, whereas serum ferritin was raised in 109 (60.5%). The serum ferritin levels were significantly higher in patients with poor glycemic control than those having good glycemic control (56.0% versus 44.0%, p=0.044). Conclusion: In contrast to individuals with good glycemic control, patients with poor glycemic control more frequently had elevated serum ferritin levels, according to the current study. In order to properly manage diabetes patients and prevent the negative effects of elevated serum ferritin levels, serum ferritin should be included in the usual screening protocol of diabetic patients while monitoring their glycemic status. [ABSTRACT FROM AUTHOR]

PURPOSE: It is widely accepted that there is a strong relationship between iron levels and cancer. This study aimed to investigate the relationship between serum ferritin levels and the severity and prognosis of gynecological malignant tumors. METHODS: This retrospective study included patients with gynecological malignant tumors at Sir Run Run Shaw Hospital in the Department of Obstetrics and Gynecology from January 2013 to June 2019. Patients were grouped according to their serum ferritin level: low (< 13 μ g/L), normal (13–150 μ g/L), and high (> 150 μ g/L). Correlation analyses were performed between serum ferritin level and other factors. Cox univariable and multivariable analysis and Kaplan-Meier survival curves were used to assess the impact of ferritin on survival in patients with gynecologic tumors. RESULTS: The 402 total patients were divided into a low (n = 37), normal (n = 182), and high (n = 183) ferritin level group. Correlation analyses were performed that WBC, MCV, CRP, CA125, and CA153 were significantly positively correlated with serum ferritin level. The Kaplan-Meier survival curves revealed that of the three groups analyzed, the high serum ferritin level group had a significantly shorter survival time versus the normal and low serum ferritin level groups (log-rank P = 0.003). Univariable Cox regression analysis identified that patients with high serum ferritin levels had a significant correlation with risk of death compared to the patients with lower and normal serum ferritin levels. Serum ferritin was not found to be significant (HR = 0.792, 95% CI: 0.351–1.787, P = 0.574) in the multivariable Cox analysis. CONCLUSION: Although this study did not find serum ferritin to be a significant independent prognosis indicator in gynecological malignant tumors, this study did identify that gynecological malignant tumor patients with high serum ferritin levels have significantly less survival time than patients with low or normal serum ferritin levels. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a severe systemic inflammatory disorder manifested by a dysregulated immune response to infection and multi-organ failure. Numerous studies have shown that elevated ferritin levels exist as an essential feature during sepsis and are able to suggest patients' prognoses. At the same time, the specific mechanism of ferritin-induced inflammatory injury remains unclear. Methods: Hyper-ferritin state during inflammation was performed by injecting ferritin into a mouse model and demonstrated that injection of ferritin could induce a systemic inflammatory response and increase neutrophil extracellular trap (NET) formation.Padi4−/−, Elane−/− and Cybb−/− mice were used for the NETs formation experiment. Western blot, immunofluorescence, ELISA, and flow cytometry examined the changes in NETs, inflammation, and related signaling pathways. Results: Ferritin induces NET formation in a peptidylarginine deiminase 4 (PAD4), neutrophil elastase (NE), and reactive oxygen species (ROS)-dependent manner, thereby exacerbating the inflammatory response. Mechanistically, ferritin induces the expression of neutrophil macrophage scavenger receptor (MSR), which promotes the formation of NETs. Clinically, high levels of ferritin in patients with severe sepsis correlate with NETs-mediated cytokines storm and are proportional to the severity of sepsis-induced lung injury. Conclusions: In conclusion, we demonstrated that hyper-ferritin can induce systemic inflammation and increase NET formation in an MSR-dependent manner. This process relies on PAD4, NE, and ROS, further aggravating acute lung injury. In the clinic, high serum ferritin levels are associated with elevated NETs and worse lung injury, which suggests a poor prognosis for patients with sepsis. Our study indicated that targeting NETs or MSR could be a potential treatment to alleviate lung damage and systemic inflammation during sepsis. CG19NQAB-3s1ZkbgUbzmoX Video Abstract [ABSTRACT FROM AUTHOR]

Background & Aims: Ferritin has been investigated as a biomarker for liver fibrosis and iron in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, whether metabolic hyperferritinaemia predicts progression of liver disease remains unknown. In this study, we sought to understand associations between hyperferritinaemia and (1) adverse clinical outcomes and (2) common genetic variants related to iron metabolism and liver fibrosis. Methods: This was a retrospective analysis of adults with MASLD seen at the University of Michigan Health System, where MASLD was defined by hepatic steatosis on imaging, biopsy or vibration-controlled transient elastography, plus metabolic risk factors in the absence of chronic liver diseases other than hemochromatosis. The primary predictor was serum ferritin level, which was dichotomized based on a cut-off of 300 or 450 mcg/L for women or men. Primary outcomes included (1) incident cirrhosis, liver-related events, congestive heart failure (CHF), and mortality and (2) distribution of common genetic variants associated with hepatic fibrosis and hereditary hemochromatosis. Results: Of 7333 patients with MASLD, 1468 (20%) had elevated ferritin. In multivariate analysis, ferritinaemia was associated with increased mortality (HR 1.68 [1.35--2.09], p < .001) and incident liver-related events (HR 1.92 [1.11--3.32], p = .019). Furthermore, elevated ferritin was associated with carriage of cirrhosis-promoting alleles including PNPLA3-rs738409-G allele (p = .0068) and TM6SF2-rs58542926-T allele (p = 0.0083) but not with common HFE mutations. Conclusions: In MASLD patients, metabolic hyperferritinaemia was associated with increased mortality and higher incidence of liver-related events, and cirrhosis-promoting alleles but not with iron overload-promoting HFE mutations. [ABSTRACT FROM AUTHOR]

The study aimed to determine efficacy and safety of generic deferasirox monotherapy. Deferasirox was administered in transfusion-induced iron overloaded thalassemia. Efficacy was defined as responders and nonresponders by ≤ 15 reduced serum ferritin from baseline. Adverse events were also monitored. Fifty-two patients with mainly Hb E/β-thalassemia at the mean (SD) age of 8.7 (4.1) years, were enrolled. The mean (SD) daily transfusion iron load was 0.47 (0.1) mg/kg and maximum daily deferasirox was 35.0 (6.2) mg/kg. Altogether, 52, 40 and 18 patients completed the first, second and third years of study, respectively. The median baseline serum ferritin 2,383 ng/mL decreased to 1,478, 1,038 and 1,268 ng/mL at the end of first, second and third years, respectively, with overall response rate at 73.1% (38/52). Patients with baseline serum ferritin >2,500 ng/mL showed a change in serum ferritin higher than those ≤2,500 ng/mL starting from the 9th month of chelation. Adverse events were found in 5 of 52 patients (9.6%) including transaminitis (n = 2), one each of proteinuria, rash and proximal tubular dysfunction which resolved after transient stopping or decreasing the chelation dose. Generic deferasirox was effective and safe among pediatric patients with transfusion-induced iron overloaded thalassemia. [ABSTRACT FROM AUTHOR]

Anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is a subtype of dermatomyositis. Although the aetiology and pathology remain unclear, increasing evidence suggests that viral infection is a potential trigger of MDA5-DM. Multiple factors, including T cells, B cells, neutrophils and macrophages, are implicated in the pathophysiology of MDA5-DM. Distinctive skin rashes, rapidly progressive interstitial lung disease, peripheral lymphopenia and elevated serum ferritin levels are the most prominent clinical and laboratory features of MDA5-DM. Concomitant infection is a common complication of MDA5-DM. The proper evaluation of patients with MDA5-DM requires knowledge of the disease heterogeneity and clinical course variability. Several biomarkers, including serum levels of anti-MDA5 antibodies and biomarkers related to macrophage activation, have been identified as useful tools for monitoring disease activity and prognosis. MDA5-DM shows a poor response to conventional glucocorticoid and immunosuppressant therapy and has a poor overall prognosis. Therefore, there is an urgent need to explore the key pathogenic mechanisms of MDA5-DM and develop novel therapeutic options for patients. This Review discusses recent clinical progress and pathogenic findings of MDA5-DM. In this Review, the authors provide an overview of what is known of the clinical features, pathogenesis and treatment of anti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis, including emerging biomarkers and clinical subtypes. Key points: Anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is a subtype of dermatomyositis with a poor prognosis that typically presents as skin manifestations and rapidly progressive interstitial lung disease. Although the aetiology of MDA5-DM is unknown, emerging epidemiological evidence of the seasonal and geographical distributions of MDA5-DM implicate viral infection as a potential trigger. The pathomechanism of MDA5-DM is complex, with a potential contributing role for T cells, B cells, neutrophils, macrophages and natural killer cells. Proper evaluation of patients with MDA5-DM requires knowledge of the diversity in clinical features, with several studies showing that MDA5-DM can be grouped into different clinical subtypes. Various biomarkers that predict disease activity and severity have been identified and used in clinical practice, including anti-MDA5 antibodies, ferritin and KL-6. Given the absence of randomized controlled trials in MDA5-DM, current therapeutic approaches rely on empirical evidence; therefore, novel treatments are needed to improve the prognosis of patients with MDA5-DM. [ABSTRACT FROM AUTHOR]

Background: Hemophagocytic syndrome or hemophagocytic lymphohistiocytosis (HL) is an immune hyperactivation of multifactorial etiology, characterized by excessive activation of lymphocytes and macrophages, as well as numerous pro-inflammatory cytokines. It has a non-specific and highly variable clinical presentation, with splenomegaly being one of the clinical manifestations. Due to its nature, it can manifest during childhood or adult life, which is why it is a disease of diagnostic and therapeutic complexity. Clinical case: 38-year-old male patient without comorbidities, who presented with abdominal pain, choluria, fever > 38 °C and diaphoresis of more than 10 days of evolution. A bone marrow aspirate was performed as part of the diagnostic approach with data compatible with hemophagocytosis and cytopenias. The immunosuppressive management did not show the expected response, which is why an open splenectomy was performed as the last therapeutic option with adequate hematological control. A documentary review of the disease was carried out, and of the therapeutic options, emphasizing surgical management in case of refractoriness to medical treatment. Conclusions: Splenectomy increases the overall survival rate and the time free of HL progression, even though there are still no studies to determine with certainty the ideal time to perform a splenectomy in patients with pancytopenia without splenomegaly who suffer from hemophagocytic syndrome. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we aimed to analyze patients with ferritin levels of = 1000 ng/mL based on diagnoses and the wards they received both before the COVID pandemic and during the pandemic periods. Materials and Methods: This retrospective study evaluated the patients who applied to a tertiary hospital and had ferritin onset of the pandemic. The patients' demographic and clinical characteristics and ferritin levels were obtained from the hospital's medical records. Results: There were 2022 patients, 635 (31.4%) female and 1387 (68.6%) male, with a median age of 62 (49-71) years. 554 patients (27.4%) before the pandemic, and 1468 patients (72.6%) during the pandemic had ferritin levels of = 1000 ng/mL. Hyperferritinemia was detected more frequently in males during the pandemic (p<0.001). Before the pandemic, the most prevalent cause of hyperferritinemia was hematologic malignancies, while COVID-19 was the most common cause of hyperferritinemia during the pandemic. Hyperferritinemia was commonly detected in the hematology department before the pandemic, while it was frequently performed in COVID-19 clinics and intensive care units after the onset of the pandemic. Conclusion: In the current study, the most prevalent cause of hyperferritinemia was hematological malignancies before the pandemic, and COVID-19 infection during the pandemic. Therefore, it is important to consider the most common conditions that match the patient's clinical condition when detecting extremely high ferritin values. Nevertheless, many other important clinical situations should also be kept in mind. [ABSTRACT FROM AUTHOR]

To investigate the role of parameters of iron metabolism in systemic lupus erythematosus (SLE) patients with pulmonary arterial hypertension (PAH). This was a prospective observational study recruiting patients diagnosed with systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH). Patients with other factors that might lead to PAH were excluded from the study. All patients were assessed for PAH every 1–3 months and were followed up for 6 months. The primary outcome was considered improved if the grade of risk stratification declined at the endpoint; otherwise, it was considered unimproved. In total, 29 patients with SLE-PAH were included in this study. The mean of serum ferritin was higher than normal, and total iron binding capacity (TIBC) decreased in 48% of patients. Correlation analyses showed that serum iron (SI) was negatively correlated with World Health Organization functional class (WHO-FC) (r = −0.409, p = 0.028), and positively correlated with Six-Minute Walk Test distance (6MWD) (r = 0.427, p = 0.021) and tricuspid annular plane systolic excursion (TAPSE) (r = 0.388, p = 0.037). Primary outcomes improved in 12 patients at the endpoint, and univariate logistic regression analyses indicated that TIBC was associated with improved primary outcomes in patients with SLE-PAH (odds ratio 12.00, 95% confidence interval 1.90–75.72). SI was negatively correlated with WHO-FC, and positively correlated with 6MWD and TAPSE. Furthermore, TIBC was associated with improved outcomes of patients with SLE-PAH, which could be an independent predictor of prognosis. Further research is needed to verify the findings. [ABSTRACT FROM AUTHOR]

L'hépatopathie stéatosique métabolique (Non-alcoholic fatty liver disease – NAFLD, ou plus récemment Metabolic Dysfunction Associated Steatotic Liver Disease – MASLD) est la première cause de perturbation du bilan hépatique. Sa prévalence mondiale est estimée à 25 %. La MASLD est suspectée, dans un contexte métabolique, devant la présence d'une stéatose hépatique, d'une cytolyse hépatique modérée ou d'une hyperferritinémie. La sévérité de la maladie dépend du stade de fibrose hépatique qui peut être suspectée en pratique clinique par des tests sanguins simples tels que le FIB-4 ou le NAFLD fibrosis Score, accessibles à tous. Le traitement repose sur des mesures hygiénodiététiques associant une perte pondérale avec une augmentation de l'activité physique et un régime de type méditerranéen. Seule une petite minorité de patients atteints de MASLD développera une maladie hépatique avancée nécessitant un suivi spécialisé en hépato-gastroentérologie. Compte tenu de la prévalence élevée de la MASLD, l'identification de ces patients ne pourra pas s'envisager sans la participation de l'ensemble des médecins (généralistes et spécialistes). Non-alcoholic fatty liver disease (NAFLD) or recently called Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD), is the leading cause of liver disease, with an estimated worldwide prevalence of 25%. MASLD is suspected, in a metabolic condition, in the presence of hepatic steatosis, moderate hepatic cytolysis or hyperferritinemia. The severity of the disease depends on the stage of liver fibrosis, which can be suspected in clinical practice by simple blood tests such as the FIB-4 or NAFLD fibrosis Score. The treatment is based on lifestyle intervention combining weight loss, increased physical activity and a Mediterranean-style diet. Only a small minority of patients with MASLD will develop advanced liver disease and require liver specialist. Given the high prevalence of MASLD, the identification of these patients cannot be envisaged without the taking part in the screening of all physicians (general practitioners and specialists). [ABSTRACT FROM AUTHOR]