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OBJECTIVE: The aim of this study was to assess the role of elevated serum ferritin levels in the onset, pathological progression and prognosis of nonalcoholic fatty liver disease. Nonalcoholic fatty liver disease has been rapidly increasing worldwide. Despite extensive research on the pathogenesis of nonalcoholic fatty liver disease, a lack of sufficient clinical research on the relationship between nonalcoholic fatty liver disease and serum ferritin levels remains. METHODS: We analysed 968 patients with type 2 diabetes mellitus who underwent liver ultrasound examination and had their serum ferritin levels measured. The presence of nonalcoholic fatty liver disease and advanced liver fibrosis was determined through abdominal ultrasound examination and the nonalcoholic fatty liver disease fibrosis score. RESULTS: Compared to that in the non-nonalcoholic fatty liver disease group, the presence of hyperferritinemia was significantly more common in the nonalcoholic fatty liver disease group (83.3 vs. 56.3%, p=0.005). When patients with nonalcoholic fatty liver disease were stratified by the nonalcoholic fatty liver disease fibrosis score, those with advanced liver fibrosis exhibited a higher prevalence of hyperferritinemia (56.3, 78.9, and 88.9% for none, simple steatosis, and advanced fibrosis, respectively; p for trend=0.002). In multivariate logistic regression, liver fibrosis was independently associated with hyperferritinemia (odds ratio [OR] 1.45; 95% confidence interval [CI] 1.18-2.02; p=0.014), and this association remained significant in male patients after adjusting for other risk factors (OR 2.66; 95% CI 1.43-5.48; p=0.026). CONCLUSION: Identifying nonalcoholic fatty liver disease patients at a risk of developing nonalcoholic steatohepatitis and advanced fibrosis is crucial for implementing timely interventions and improving patient outcomes. This study highlights the potential utility of serum ferritin levels as a serum biomarker for identifying nonalcoholic steatohepatitis patients and those at a risk of late-stage fibrosis, particularly in male patients with nonalcoholic fatty liver disease.
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Diabetes Mellitus Tipo 2 , Ferritinas , Cirrosis Hepática , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Masculino , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Ferritinas/sangre , Persona de Mediana Edad , Femenino , Cirrosis Hepática/sangre , Cirrosis Hepática/complicaciones , Factores de Riesgo , Anciano , Hiperferritinemia/sangre , Adulto , Biomarcadores/sangre , UltrasonografíaAsunto(s)
Fiebre , Hiperferritinemia , Humanos , Recién Nacido , Hiperferritinemia/diagnóstico , Hiperferritinemia/sangre , Fiebre/etiología , Fiebre/diagnóstico , Masculino , FemeninoRESUMEN
BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Ferritinas , Genotipo , Proteína de la Hemocromatosis , Cirrosis Hepática , Humanos , Masculino , Cirrosis Hepática/sangre , Cirrosis Hepática/genética , Persona de Mediana Edad , Ferritinas/sangre , Proteína de la Hemocromatosis/genética , Femenino , Adulto , Finlandia/epidemiología , Anciano , Modelos de Riesgos Proporcionales , Modelos Lineales , Hiperferritinemia/sangre , Hiperferritinemia/genética , Factores de RiesgoRESUMEN
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]-550â ng/mL; grade 2: 550-1000â ng/mL; grade 3: >1000â 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.
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Ferritinas , Hiperferritinemia , Humanos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Estudios de Cohortes , Hiperferritinemia/sangre , Hiperferritinemia/diagnóstico , Ferritinas/sangre , Consenso , Encuestas Nutricionales , Anciano , PronósticoRESUMEN
INTRODUCTION: The distribution of causes of hyperferritinemia in international series is heterogeneous. Also, the association between ferritin and prognosis is controversial. This study aims to describe the diagnosis associated with hyperferritinemia in a retrospective cohort at an academic healthcare network in Chile. METHODS: A retrospective review of adult patients admitted to our academic medical center from June 2014 to February 2017 with ferritin ≥3,000 ng/mL. All patients were classified into nine diagnostic categories. Then, the association between ferritin level and disease category, as well as mortality, was evaluated. RESULTS: Ninety-nine patients were identified. The mean age was 50.8 ± 19.9 years, 54.5% were men. The most frequent categories were "inflammatory and autoimmune diseases" (21.2%) and "hematological malignancies" (19.2%). The average ferritin was 10,539 ± 13,016.9 ng/mL, while the higher mean was 16,707 ng/mL in the "inflammatory and autoimmune diseases" category. There was a statistically significant association between the ferritin value and age but not between ferritin and diagnostic categories. In the group over 50, hematologic neoplasms (19%) and infections (19%) were more frequent. In those under 50, inflammatory and autoimmune diseases were more frequent (26.8%). There was no association between the ferritin level and mortality at 1, 3, and 12 months. CONCLUSIONS: The most frequent categories were "inflammatory and autoimmune diseases" and "hematological malignancies", but ferritin level was similar in both. Further research could validate a prognostic role.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Ferritinas/sangre , Hiperferritinemia/sangre , Pronóstico , Enfermedades Autoinmunes/sangre , Chile/epidemiología , Estudios Retrospectivos , Centros Médicos Académicos/estadística & datos numéricosRESUMEN
INTRODUCTION: The distribution of causes of hyperferritinemia in international series is heterogeneous. Also, the association between ferritin and prognosis is controversial. This study aims to describe the diagnosis associated with hyperferritinemia in a retrospective cohort at an academic healthcare network in Chile. METHODS: A retrospective review of adult patients admitted to our academic medical center from June 2014 to February 2017 with ferritin ≥3,000 ng/mL. All patients were classified into nine diagnostic categories. Then, the association between ferritin level and disease category, as well as mortality, was evaluated. RESULTS: Ninety-nine patients were identified. The mean age was 50.8 ± 19.9 years, 54.5% were men. The most frequent categories were "inflammatory and autoimmune diseases" (21.2%) and "hematological malignancies" (19.2%). The average ferritin was 10,539 ± 13,016.9 ng/mL, while the higher mean was 16,707 ng/mL in the "inflammatory and autoimmune diseases" category. There was a statistically significant association between the ferritin value and age but not between ferritin and diagnostic categories. In the group over 50, hematologic neoplasms (19%) and infections (19%) were more frequent. In those under 50, inflammatory and autoimmune diseases were more frequent (26.8%). There was no association between the ferritin level and mortality at 1, 3, and 12 months. CONCLUSIONS: The most frequent categories were "inflammatory and autoimmune diseases" and "hematological malignancies", but ferritin level was similar in both. Further research could validate a prognostic role.
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Ferritinas , Hiperferritinemia , Humanos , Estudios Retrospectivos , Masculino , Chile/epidemiología , Persona de Mediana Edad , Femenino , Adulto , Ferritinas/sangre , Anciano , Hiperferritinemia/sangre , Pronóstico , Centros Médicos Académicos/estadística & datos numéricos , Enfermedades Autoinmunes/sangre , Adulto JovenRESUMEN
Hyperferritinemia comes to light frequently in general practice. However, the characteristics of COVID-19-associated hyperferritinemia and the relationship with the prognosis were not well described. The retrospective study included 268 documented COVID-19 patients. They were divided into the hyperferritinemia group (≥ 500 µg/L) and the non-hyperferritinemia group (< 500 µg/L). The prevalence of fever and thrombocytopenia and the proportion of patients with mechanical ventilator support and in-hospital death were much higher in the hyperferritinemia group (P < 0.001). The hyperferritinemia patients showed higher median IL-6, D-dimer, and hsCRP (P < 0.001) and lowered FIB level (P = 0.036). The hyperferritinemia group had a higher proportion of patients with AKI, ARDS, and CSAC (P < 0.001). According to the multivariate analysis, age, chronic pulmonary disease, and hyperferritinemia were found to be significant independent predictors for in-hospital mortality [HR 1.041 (95% CI 1.015-1.068), P = 0.002; HR 0.427 (95% CI 0.206-0.882), P = 0.022; HR 6.176 (95% CI 2.447-15.587), P < 0.001, respectively]. The AUROC curve was 0.88, with a cut-off value of ≥ 971 µg/L. COVID-19 patients with hyperferritinemia had a high proportion of organ dysfunction, were more likely to show hyper-inflammation, progressed to hemophagocytic lymphohistiocytosis, and indicated a higher proportion of death.
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COVID-19/sangre , Hiperferritinemia/sangre , Fagocitosis , SARS-CoV-2/metabolismo , Anciano , Proteína C-Reactiva/inmunología , Proteína C-Reactiva/metabolismo , COVID-19/complicaciones , COVID-19/mortalidad , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/inmunología , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Mortalidad Hospitalaria , Humanos , Hiperferritinemia/etiología , Hiperferritinemia/inmunología , Hiperferritinemia/mortalidad , Inflamación/sangre , Inflamación/inmunología , Inflamación/mortalidad , Interleucina-6/sangre , Interleucina-6/inmunología , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , SARS-CoV-2/inmunologíaRESUMEN
AIM: Anti-ribosomal P protein antibodies (anti-ribo P) have been reported as one of the specific autoantibodies in patients with systemic lupus erythematosus (SLE) and has been demonstrated to bind and activate macrophages in vitro. Clinically, hyperferritinemia has been known to be a biomarker for macrophage activation. The aim of this study is to clarify the relationship of anti-ribo P and clinical characteristics and biomarkers including serum ferritin in patients with SLE. METHODS: Clinical parameters and laboratory data were measured in patients with active SLE (N = 127) in our university hospital. The risk factors affected by anti-ribo P were retrospectively calculated by logistic regression analysis, and the correlation of anti-ribo P and clinical factors was demonstrated. RESULTS: Anti-ribo P was significantly elevated in active SLE compared to non-SLE diseases (P < .0001). Sensitivity and the specificity of anti-ribo P in patients with SLE were 32.0% and 99.3%, respectively. Patients positive for anti-ribo P had the highest risk for elevated serum ferritin (odds ratio: 8.432). Accordingly, anti-ribo P positive patients had significantly elevated serum ferritin compared to negative patients (P = .024). A significant positive correlation was observed between the anti-ribo P titer and the serum ferritin level (r2 = .07, t = 5.22, P = .0081), but not serum interleukin (IL)-6 in SLE patients. CONCLUSION: The presence of anti-ribo P is a risk factor for higher ferritin levels that is independent of systemic inflammation regulated by IL-6. We speculate that anti-ribo P could be directly associated with macrophage activation leading to hyperferritinemia in patients with SLE.
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Anticuerpos Antinucleares/sangre , Hiperferritinemia/diagnóstico , Lupus Eritematoso Sistémico/sangre , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Femenino , Ferritinas/sangre , Humanos , Hiperferritinemia/sangre , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Factores de RiesgoAsunto(s)
Hiperferritinemia/sangre , Hiperferritinemia/diagnóstico , Consumo de Bebidas Alcohólicas/epidemiología , Femenino , Ferritinas/sangre , Humanos , Hiperferritinemia/epidemiología , Hiperferritinemia/etiología , Linfohistiocitosis Hemofagocítica/epidemiología , Masculino , Insuficiencia Renal Crónica/epidemiología , Factores de Riesgo , Enfermedad de Still del Adulto/epidemiología , Transferrina/análisis , Ultrasonografía/métodosRESUMEN
BACKGROUND: Ferritin is the major iron storage protein and an acute phase reactant. Hyperferritinemia is frequently seen in the critically ill where it has been hypothesized that not only underlying conditions but also factors such as transfusions, hemodialysis and extracorporeal life support (ECLS) lead to hyperferritinemia. This study aims to investigate the influence of transfusions, hemodialysis, and ECLS on hyperferritinemia in a multidisciplinary ICU cohort. METHODS: This is a post-hoc analysis of a retrospective observational study including patients aged ≥ 18 years who were admitted to at least one adult ICU between January 2006 and August 2018 with hyperferritinemia ≥ 500 µg/L and of ≥ 14 days between two ICU ferritin measurements. Patients with hemophagocytic lymphohistiocytosis (HLH) were excluded. To identify the influence of transfusions, hemodialysis, and ECLS on ferritin change, multivariable linear regression analysis with ferritin change between two measurements as dependent variable was performed. RESULTS: A total of 268 patients was analyzed. Median duration between measurements was 36 days (22-57). Over all patients, ferritin significantly increased between the first and last measurement (p = 0.006). Multivariable linear regression analysis showed no effect of transfusions, hemodialysis, or ECLS on ferritin change. Changes in aspartate aminotransferase (ASAT) and sequential organ failure assessment (SOFA) score were identified as influencing factors on ferritin change [unstandardized regression coefficient (B) = 2.6; (95% confidence interval (CI) 1.9, 3.3); p < 0.001 and B = 376.5; (95% CI 113.8, 639.1); p = 0.005, respectively]. Using the same model for subgroups of SOFA score, we found SOFA platelet count to be associated with ferritin change [B = 1729.3; (95% CI 466.8, 2991.9); p = 0.007]. No association of ferritin change and in-hospital mortality was seen in multivariable analysis. CONCLUSIONS: The present study demonstrates that transfusions, hemodialysis, and ECLS had no influence on ferritin increases in critically ill patients. Hyperferritinemia appears to be less the result of iatrogenic influences in the ICU thereby underscoring its unskewed diagnostic value. TRIAL REGISTRATION: The study was registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016.
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Transfusión Sanguínea , Enfermedad Crítica/terapia , Oxigenación por Membrana Extracorpórea , Hiperferritinemia/terapia , Diálisis Renal , Adulto , Anciano , Femenino , Ferritinas/sangre , Mortalidad Hospitalaria , Humanos , Hiperferritinemia/sangre , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis MultivarianteRESUMEN
Fever of unknown origin (FUO) is defined as persistent fevers without an identifiable cause despite extensive medical workup. Emergency physicians caring for patients reporting a persistent, nonspecific, febrile illness should carefully consider potentially serious non-infectious causes of FUO. We present a case of a 35-year-old man who presented to the emergency department (ED) three times over a 10-day period for persistent febrile illness and was ultimately diagnosed with Adult-Onset Still's Disease (AOSD) after a serum ferritin level was found to be over 42,000 µg/L. AOSD, along with macrophage activation syndrome, catastrophic antiphospholipid syndrome, and septic shock comprise the four hyperferritinemic syndromes. These are potentially life-threatening febrile illnesses that characteristically present with elevated ferritin levels. In this article, we highlight the value of a serum ferritin level in the workup of a patient with prolonged febrile illness and its utility in facilitating early diagnosis and prompt treatment of hyperferritinemic syndromes in the ED.
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Fiebre de Origen Desconocido/fisiopatología , Hiperferritinemia/sangre , Enfermedad de Still del Adulto/diagnóstico , Adulto , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/complicaciones , Servicio de Urgencia en Hospital , Fiebre de Origen Desconocido/etiología , Humanos , Hiperferritinemia/etiología , Síndrome de Activación Macrofágica/sangre , Síndrome de Activación Macrofágica/complicaciones , Masculino , Choque Séptico/sangre , Choque Séptico/complicaciones , Enfermedad de Still del Adulto/sangre , Enfermedad de Still del Adulto/complicaciones , Enfermedad de Still del Adulto/fisiopatologíaRESUMEN
In this study, laboratorial parameters of hospitalized novel coronavirus (COVID-19) patients, who were complicated with severe pneumonia, were compared with the findings of cytokine storm developing in macrophage activation syndrome (MAS)/secondary hemophagocytic lymphohistiocytosis (sHLH). Severe pneumonia occurred as a result of cytokine storm in some patients who needed intensive care unit (ICU), and it is aimed to determine the precursive parameters in this situation. Also in this study, the aim is to identify laboratory criteria that predict worsening disease and ICU intensification, as well as the development of cytokine storm. This article comprises a retrospective cohort study of patients admitted to a single institution with COVID-19 pneumonia. This study includes 150 confirmed COVID-19 patients with severe pneumonia. When they were considered as severe pneumonia patients, the clinic and laboratory parameters of this group are compared with H-score criteria. Patients are divided into two subgroups; patients with worsened symptoms who were transferred into tertiary ICU, and patients with stable symptoms followed in the clinic. For the patients with confirmed COVID-19 infection, after they become complicated with severe pneumonia, lymphocytopenia (55.3%), anemia (12.0%), thrombocytopenia (19.3%), hyperferritinemia (72.5%), hyperfibrinogenemia (63.7%) and elevated lactate dehydrogenase (LDH) (90.8%), aspartate aminotransaminase (AST) (31.3%), alanine aminotransaminase (ALT) (20.7%) are detected. There were no significant changes in other parameters. Blood parameters between the pre-ICU period and the ICU period (in which their situation had been worsened and acute respiratory distress syndrome [ARDS] was developed) were also compared. In the latter group lymphocyte levels were found significantly reduced (p = 0.01), and LDH, highly sensitive troponin (hs-troponin), procalcitonin, and triglyceride levels were significantly increased (p < 0.05). In addition, there was no change in hemoglobin, leukocyte, platelet, ferritin, and liver function test levels, including patients who developed ARDS, similar to the cytokine storm developed in MAS/sHLH. COVID-19 pneumonia has similar findings as hyperinflammatory syndromes but does not seem to have typical features as in cytokine storm developed in MAS/sHLH. In the severe patient group who has started to develop ARDS signs, a decrease in lymphocyte level in addition to the elevated LDH, hs-troponin, procalcitonin, and triglyceride levels can be a predictor in progression to ICU admission and could help in the planning of anti-cytokine therapy.
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COVID-19/patología , Síndrome de Liberación de Citoquinas/patología , Linfohistiocitosis Hemofagocítica/patología , Síndrome de Activación Macrofágica/patología , SARS-CoV-2/patogenicidad , Anciano , Alanina Transaminasa/sangre , Anemia/sangre , Anemia/diagnóstico , Anemia/inmunología , Anemia/patología , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , COVID-19/sangre , COVID-19/diagnóstico , COVID-19/inmunología , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/diagnóstico , Síndrome de Liberación de Citoquinas/inmunología , Diagnóstico Diferencial , Progresión de la Enfermedad , Femenino , Fibrinógeno/metabolismo , Humanos , Hiperferritinemia/sangre , Hiperferritinemia/diagnóstico , Hiperferritinemia/inmunología , Hiperferritinemia/patología , Unidades de Cuidados Intensivos , L-Lactato Deshidrogenasa/sangre , Linfohistiocitosis Hemofagocítica/sangre , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/inmunología , Linfopenia/sangre , Linfopenia/diagnóstico , Linfopenia/inmunología , Linfopenia/patología , Síndrome de Activación Macrofágica/sangre , Síndrome de Activación Macrofágica/diagnóstico , Síndrome de Activación Macrofágica/inmunología , Masculino , Persona de Mediana Edad , Polipéptido alfa Relacionado con Calcitonina/sangre , Estudios Retrospectivos , Trombocitopenia/sangre , Trombocitopenia/diagnóstico , Trombocitopenia/inmunología , Trombocitopenia/patología , Triglicéridos/sangre , Troponina/sangreRESUMEN
Hyperferritinemia is associated with poor outcomes in critically ill patients with sepsis, hemophagocytic lymphohistiocytosis (HLH), macrophage activation syndromes (MAS) and coronavirus disease 19 (COVID-19). Autopsies of hyperferritinemic patients that succumbed to either sepsis, HLH, MAS or COVID-19 have revealed disseminated microvascular thromboses with von Willebrand factor (VWF)-, platelets-, and/or fibrin-rich microthrombi. It is unknown whether high plasma ferritin concentration actively promotes microvascular thrombosis, or merely serves as a prognostic biomarker in these patients. Here, we show that secretion of VWF from human umbilical vein endothelial cells (HUVEC) is significantly enhanced by 100,000 ng/ml of recombinant ferritin heavy chain protein (FHC). Ferritin fraction that was isolated by size exclusion chromatography from the plasma of critically ill HLH patients promoted VWF secretion from HUVEC, compared to similar fraction from non-critically ill control plasma. Furthermore, recombinant FHC moderately suppressed the activity of VWF cleaving metalloprotease ADAMTS-13. These observations suggest that a state of marked hyperferritinemia could promote thrombosis and organ injury by inducing endothelial VWF secretion and reducing the ADAMTS-13 activity.
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Proteína ADAMTS13/metabolismo , COVID-19/sangre , COVID-19/complicaciones , Ferritinas/metabolismo , Hiperferritinemia/sangre , Hiperferritinemia/complicaciones , Factor de von Willebrand/metabolismo , Proteína ADAMTS13/antagonistas & inhibidores , COVID-19/inmunología , Enfermedad Crítica , Ferritinas/sangre , Células Endoteliales de la Vena Umbilical Humana , Humanos , Linfohistiocitosis Hemofagocítica/sangre , Linfohistiocitosis Hemofagocítica/complicaciones , Oxidorreductasas/sangre , Oxidorreductasas/metabolismo , Proteínas Recombinantes/sangre , Proteínas Recombinantes/metabolismo , SARS-CoV-2 , Trombosis/sangre , Trombosis/etiologíaRESUMEN
The authors present the case of a 58-year-old man with the unique combination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and, later on, haemophagocytic lymphohistiocytosis admitted to the intensive care unit. During his ICU stay the patient developed a variety of complications including acute respiratory distress syndrome, pulmonary embolism, right heart failure and suspected HLH leading to multiorgan failure and death. Despite the proven diagnosis of haemophagocytic lymphohistiocytosis, the excessively high ferritin levels of the patient did not seem fully explained by this diagnosis. Therefore, the authors want to highlight different causes of hyperferritinaemia in critically ill patients and underline the importance of differential diagnoses when interpreting continuously rising ferritin levels.
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Lesión Renal Aguda/fisiopatología , COVID-19/fisiopatología , Insuficiencia Cardíaca/fisiopatología , Hiperferritinemia/sangre , Fallo Hepático/fisiopatología , Linfohistiocitosis Hemofagocítica/fisiopatología , Embolia Pulmonar/fisiopatología , Lesión Renal Aguda/sangre , Lesión Renal Aguda/etiología , Alanina Transaminasa/sangre , COVID-19/sangre , COVID-19/complicaciones , COVID-19/terapia , Creatinina/sangre , Progresión de la Enfermedad , Resultado Fatal , Insuficiencia Cardíaca/etiología , Humanos , Hiperferritinemia/etiología , Fallo Hepático/sangre , Fallo Hepático/etiología , Linfohistiocitosis Hemofagocítica/etiología , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/fisiopatología , Embolia Pulmonar/etiología , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/fisiopatología , Síndrome de Dificultad Respiratoria/terapia , SARS-CoV-2Asunto(s)
COVID-19/virología , Ferritinas/sangre , Paro Cardíaco/virología , Hiperferritinemia/virología , SARS-CoV-2/patogenicidad , Animales , Biomarcadores/sangre , COVID-19/complicaciones , Paro Cardíaco/tratamiento farmacológico , Paro Cardíaco/fisiopatología , Humanos , Hiperferritinemia/sangre , Hiperferritinemia/tratamiento farmacológico , Hiperferritinemia/fisiopatología , Quelantes del Hierro/uso terapéutico , Pronóstico , Tratamiento Farmacológico de COVID-19RESUMEN
BACKGROUND: The aim of this study was to evaluate hyperferritinemia could be a predicting factor of mortality in hospitalized patients with coronavirus disease-2019 (COVID-19). METHODS: A total of 100 hospitalized patients with COVID-19 in intensive care unit (ICU) were enrolled and classified into moderate (n=17), severe (n=40) and critical groups (n=43). Clinical information and laboratory results were collected and the concentrations of ferritin were compared among different groups. The association between ferritin and mortality was evaluated by logistic regression analysis. Moreover, the efficiency of the predicting value was assessed using receiver operating characteristic (ROC) curve. RESULTS: The amount of ferritin was significantly higher in critical group compared with moderate and severe groups. The median of ferritin concentration was about three times higher in death group than survival group (1722.25µg/L vs. 501.90µg/L, p<0.01). The concentration of ferritin was positively correlated with other inflammatory cytokines, such as interleukin (IL)-8, IL-10, C-reactive protein (CRP) and tumor necrosis factor (TNF)-α. Logistic regression analysis demonstrated that ferritin was an independent predictor of in-hospital mortality. Especially, high-ferritin group was associated with higher incidence of mortality, with adjusted odds ratio of 104.97 [95% confidence interval (CI) 2.63-4185.89; p=0.013]. Moreover, ferritin had an advantage of discriminative capacity with the area under ROC (AUC) of 0.822 (95% CI 0.737-0.907) higher than procalcitonin and CRP. CONCLUSION: The ferritin measured at admission may serve as an independent factor for predicting in-hospital mortality in patients with COVID-19 in ICU.
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COVID-19/mortalidad , Reglas de Decisión Clínica , Ferritinas/sangre , Hiperferritinemia/diagnóstico , Hiperferritinemia/virología , Unidades de Cuidados Intensivos , Índice de Severidad de la Enfermedad , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , COVID-19/complicaciones , COVID-19/diagnóstico , COVID-19/terapia , China/epidemiología , Femenino , Mortalidad Hospitalaria , Humanos , Hiperferritinemia/sangre , Modelos Logísticos , Masculino , Persona de Mediana Edad , Admisión del Paciente , Pronóstico , Curva ROC , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Ferritin, the cellular protein storage for iron, has emerged as a key molecule in the immune system, orchestrating the cellular defense against inflammation. At the end of 2019, the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rapidly spread throughout China and other countries around the world, resulting in a viral pandemic. OBJECTIVES: To evaluate the correlation between ferritin and disease severity in coronavirus disease-2019 (COVID-19). METHODS: In this cross-sectional study, we obtained clinical and laboratory data regarding 39 hospitalized patients with confirmed COVID-19 from two hospitals in Israel. RESULTS: A significant increase in ferritin levels was demonstrated in patients with moderate and severe disease, compared to patients with mild disease (P = 0.006 and 0.005, respectively). Severe patients had significantly higher levels of ferritin (2817.6 ng/ml) than non-severe patients (708.6 ng/ml) P = 0.02. CONCLUSIONS: In this preliminary cross-sectional study, elevated ferritin levels were shown to correlate with disease severity in 39 patients from Israel with confirmed COVID-19 infection. Our results further strengthen the hypothesis that severe COVID-19 disease might be due to an underlying dysregulated hyperimmune response. In order to identify these patients early and prioritized resources, we believe that all patients with COVID-19 should be screened for hyperferritinemia.
Asunto(s)
COVID-19/sangre , Ferritinas/sangre , Hiperferritinemia/sangre , Gravedad del Paciente , Adulto , Anciano , Biomarcadores/sangre , COVID-19/complicaciones , Estudios Transversales , Femenino , Humanos , Hiperferritinemia/virología , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Adulto JovenRESUMEN
BACKGROUND: A virally-induced cytokine storm syndrome, associated with a massive and overwhelming systemic inflammation, burdens a subgroup of patients with severe coronavirus disease-2019 (COVID-19), which leads to pulmonary inflammation and extensive lung damage. These severe COVID-19 patients are characterized by high ferritin levels. These findings mirror what was previously reported about the prognostic role of this iron storage protein in other inflammatory diseases included in the hyperferritinemic syndrome. The latter suggests that ferritin could be a further pathogenic mediator in enhancing the inflammatory process, stimulating inflammatory pathways, and thus perpetuating a vicious pathogenic loop. Considering its activity as an immune activator, a therapeutic approach targeting ferritin may be also postulated in these diseases. Considering these observations, high ferritin levels characterize severe COVID-19 and other diseases included in the hyperferritinemic syndrome. Because ferritin could enhance the inflammatory process, it could be tested as a possible new therapeutic target to improve the outcome of these patients.
Asunto(s)
COVID-19/sangre , COVID-19/complicaciones , Ferritinas/sangre , Hiperferritinemia/sangre , Hiperferritinemia/terapia , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/virología , Humanos , Hiperferritinemia/virología , Gravedad del Paciente , SARS-CoV-2RESUMEN
OBJECTIVE: To develop a composite disease activity score for systemic JIA (sJIA) and to provide preliminary evidence of its validity. METHODS: The systemic Juvenile Arthritis Disease Activity Score (sJADAS) was constructed by adding to the four items of the original JADAS a fifth item that aimed to quantify the activity of systemic features. Validation analyses were conducted on patients with definite or probable/possible sJIA enrolled at first visit or at the time of a flare, who had active systemic manifestations, which should include fever. Patients were reassessed 2 weeks to 3 months after baseline. Three versions were examined, including ESR, CRP or no acute-phase reactant. RESULTS: A total of 163 patients were included at 30 centres in 10 countries. The sJADAS was found to be feasible and to possess face and content validity, good construct validity, satisfactory internal consistency (Cronbach's alpha 0.64-0.65), fair ability to discriminate between patients with different disease activity states and between those whose parents were satisfied or not satisfied with illness outcome (P < 0.0001 for both), and strong responsiveness to change over time (standardized response mean 2.04-2.58). Overall, these properties were found to be better than those of the original JADAS and of DAS for RA and of Puchot score for adult-onset Still's disease. CONCLUSION: The sJADAS showed good measurement properties and is therefore a valid instrument for the assessment of disease activity in children with sJIA. The performance of the new tool should be further examined in other patient cohorts that are evaluated prospectively.
Asunto(s)
Artralgia/fisiopatología , Artritis Juvenil/sangre , Artritis Juvenil/fisiopatología , Calidad de Vida , Anemia/sangre , Niño , Preescolar , Exantema/fisiopatología , Femenino , Fiebre/fisiopatología , Hepatomegalia/fisiopatología , Humanos , Hiperferritinemia/sangre , Linfadenopatía/fisiopatología , Masculino , Dimensión del Dolor , Rango del Movimiento Articular , Reproducibilidad de los Resultados , Serositis/fisiopatología , Índice de Severidad de la Enfermedad , Esplenomegalia/fisiopatología , Trombocitosis/sangreRESUMEN
BACKGROUND: Hyperferritinemic syndromes are systemic inflammatory disorders characterized by a dysfunctional immune response, which leads to excessive activation of the monocyte-macrophage system with hypercytokinemia and may pursue a rapidly fatal course. CASE PRESENTATION: We describe two patients of 11 and 9 years of age with hyperferritinemic syndromes, one with impending macrophage activation syndrome (MAS) and one with overt MAS, who were refractory or intolerant to conventional therapies, but improved dramatically with canakinumab. CONCLUSIONS: Our report indicates that canakinumab may be efficacious in the management of hyperferritinemic syndromes, including MAS.