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Purpose: Recent years have seen a clear link established between elevated ferritin levels and COVID-19 prognosis. However, the impact of heightened ferritin levels on the prognosis of individuals with severe ischemic heart disease remains uncertain. Methods: We utilized the MIMIC IV database to identify a cohort of ischemic heart disease patients who underwent serum ferritin testing. We conducted regression analyses, employed the overlap propensity score weighting model, and utilized the restricted cubic splines model to comprehensively investigate the associations between serum ferritin levels and clinical outcomes. Results: Our cohort included 1173 patients with diagnosed ischemic heart disease, categorized into high and low serum ferritin groups. After meticulous adjustment for confounding factors in a fully adjusted model, the hazard ratios (HRs) for 90-day and 1-year mortality were 1.63 (95% CI: 1.27–2.09) and 1.49 (95% CI: 1.19–1.86), respectively, in the high-ferritin group compared to the low-ferritin group. Subsequent analyses with propensity score weighting confirmed these results. Remarkably, restricted cubic spline analysis revealed an almost linear relationship between log-transformed serum ferritin levels and the risk of both 90-day and 1-year all-cause mortality. Moreover, incorporating ferritin into conventional severity of illness scores significantly improved the area under the curve for both 90-day and 1-year mortality. Conclusions: This study provides compelling evidence regarding the prognostic significance of serum ferritin in predicting 90-day and one-year mortality rates among patients diagnosed with ischemic heart disease. [ABSTRACT FROM AUTHOR]

Objective: The most common symptom of post-acute coronavirus disease 2019 (COVID-19) is fatigue, and it potentially leads to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, a specific prognosticator is lacking. We aimed to elucidate the clinical characteristics of patients who developed ME/CFS after COVID-19. Methods: In this retrospective observational study, patients who visited Okayama University Hospital for long COVID between February 2021 and March 2022 were investigated. Results: Of the 234 patients, 139 (59.4%) had fatigue symptoms. Fifty patients with fatigue symptoms (21.4%) met the criteria for ME/CFS (ME/CFS group), while the other 89 patients did not (non-ME/CFS group); 95 patients had no fatigue complaints (no-fatigue group). Although the patients' backgrounds were not significantly different between the three groups, the ME/CFS group presented the highest scores on the self-rating symptom scales, including the Fatigue Assessment Scale (FAS), EuroQol, and the Self-Rating Depression Scale (SDS). Furthermore, serum ferritin levels, which were correlated with FAS and SDS scores, were significantly higher in the ME/CFS group (193.0 μg/L, interquartile range (IQR): 58.8–353.8) than in the non-ME/CFS group (98.2 μg/L, 40.4–251.5) and no-fatigue group (86.7 μg/L, 37.5–209.0), and a high serum ferritin level was prominent in female patients. Endocrine workup further showed that the ME/CFS group had higher thyrotropin levels but lower growth hormone levels in serum and that insulin-like growth factor-I levels were inversely correlated with ferritin levels (R = −0.328, p < 0.05). Conclusions: Serum ferritin level is a possible predictor of the development of ME/CFS related to long COVID, especially in female patients. [ABSTRACT FROM AUTHOR]

Background: Elevated serum ferritin is a common condition in critically ill patients. It is well known that hyperferritinemia constitutes a good biomarker for hemophagocytic lymphohistiocytosis (HLH) in critically ill patients. However, further differential diagnoses of hyperferritinemia in adult critically ill patients remain poorly investigated. We sought to systematically investigate hyperferritinemia in adult critically ill patients without HLH. Methods: In this secondary analysis of a retrospective observational study, patients ≥18 years admitted to at least one adult intensive care unit at Charité–Universitätsmedizin Berlin between January 2006 and August 2018, and with hyperferritinemia of ≥500 μg/L were included. Patients with HLH were excluded. All patients were categorized into non-sepsis, sepsis, and septic shock. They were also classified into 17 disease groups, based on their ICD-10 codes, and pre-existing immunosuppression was determined. Uni- and multivariable linear regression analyses were performed in all patients. Results: A total of 2583 patients were analyzed. Multivariable linear regression analysis revealed positive associations of maximum SOFA score, sepsis or septic shock, liver disease (except hepatitis), and hematological malignancy with maximum ferritin. T/NK cell lymphoma, acute myeloblastic leukemia, Kaposi's sarcoma, acute or subacute liver failure, and hepatic veno-occlusive disease were positively associated with maximum ferritin in post-hoc multivariable linear regression analysis. Conclusions: Sepsis or septic shock, liver disease (except hepatitis) and hematological malignancy are important differential diagnoses in hyperferritinemic adult critically ill patients without HLH. Together with HLH, they complete the quartet of important differential diagnoses of hyperferritinemia in adult critically ill patients. As these conditions are also related to HLH, it is important to apply HLH-2004 criteria for exclusion of HLH in hyperferritinemic patients. Hyperferritinemic critically ill patients without HLH require quick investigation of differential diagnoses. [ABSTRACT FROM AUTHOR]

The significance of extreme hyperferritinemia and its association with certain diagnoses and prognoses are not well characterized. We performed a retrospective analysis of adult patients with at least one total serum ferritin (TSF) measurement ≥ 5000 µg/L over 2 years, in three university hospitals. Conditions associated with hyperferritinemia were collected, and patients were classified into 10 etiological groups. Intensive care unit (ICU) transfer and mortality rates were recorded. A total of 495 patients were identified, of which 56% had a TSF level between 5000 and 10,000 µg/L. There were multiple underlying causes in 81% of the patients. The most common causes were infections (38%), hemophagocytic lymphohistiocytosis (HLH, 18%), and acute hepatitis (14%). For TSF levels > 10,000 µg/L, there were no solid cancer or hematological malignancy without another cause of hyperferritinemia. Isolated iron-overload syndromes never exceeded TSF levels > 15,000 µg/L. Extreme hyperferritinemia (TSF levels > 25,000 µg/L) was associated with only four causes: HLH, infections, acute hepatitis and cytokine release syndromes. A total of 32% of patients were transferred to an ICU, and 28% died. Both ICU transfer rate and mortality were statistically associated with ferritin levels. An optimized threshold of 13,405 μg/L was the best predictor for the diagnosis of HLH, with a sensitivity of 76.4% and a specificity of 79.3%. Hyperferritinemia reflects a variety of conditions, but only four causes are associated with extreme hyperferritinemia, in which HLH and acute hepatitis are the most common. Extreme hyperferritinemia has a poor prognosis with increased mortality. [ABSTRACT FROM AUTHOR]

Background: Ferric carboxymaltose (FCM) is an intravenous (IV) high-dose iron that is effective in the treatment of iron deficiency anemia. This study was performed to determine whether postoperative FCM infusion is effective at improving hemoglobin (Hb) responders, Hb and iron profiles, and the patient's quality of life (QOL). Methods: A total of 110 patients with postoperative anemia, defined by a Hb < 10 g/dL within 3 days of unilateral primary TKA, between June 2018 and February 2020 were randomized into either the FCM or Control group. On postoperative day 3, the FCM group (55 patients) received IV FCM while the Control group (55 patients) did not. The Hb responders (Hb increase ≥ 2 g/dL compared to baseline), Hb level, iron profiles (ferritin, total iron-binding capacity (TIBC), transferrin saturation (TSAT)), and EQ-5D scores were compared at weeks 2, 4, and 8. Results: The FCM group demonstrated a significantly greater number of Hb responders (p < 0.001) and a higher Hb level (p = 0.008) at 2 weeks postoperative than did the Control group. The FCM group recovered its preoperative Hb level between 4 and 8 weeks. In contrast, the Control group did not recover its preoperative level until 8 weeks. The FCM infusion group also had higher serum ferritin, iron and TSAT, and lower TIBC levels than those of the Control group between 2 and 8 weeks (all p < 0.001). However, there was no significant difference in the postoperative transfusion rate (p = 0.741) or EQ-5D score between the two groups (all p > 0.05). Discussion: In postoperative anemia following TKA, IV FCM increases the Hb response and improves Hb and iron metabolism variables, however, it does not affect the transfusion rate or QOL. [ABSTRACT FROM AUTHOR]

The aim of this study is the evaluation of the safety and the efficacy of long-term combination therapy deferasirox plus desferrioxamine and deferasirox plus deferiprone in a large group of transfusion-dependent thalassemia patients with high values of serum ferritin and/or magnetic resonance, indicative of severe liver and cardiac iron accumulation. Sixteen adults with transfusion-dependent thalassemia were treated simultaneously with deferasirox plus desferrioxamine, while another 42 patients (seven children) were treated with deferasirox plus deferiprone. The hepatic and cardiac iron overload was assessed prior to treatment and then annually with magnetic resonance imaging, and the serum ferritin was measured monthly. Adverse events were checked at each transfusion visit. The safety of both the combinations was consistent with established monotherapies. Both treatments were able to decrease the serum ferritin and liver iron concentration over time, depending on the level of compliance with therapy. Cardiac iron measured as R2* did not significantly change in patients treated with deferasirox plus desferrioxamine. Most patients with MRI indicative of myocardial siderosis at the beginning of treatment reached normal values of cardiac iron at the last determination if treated with deferasirox plus desferrioxamine. The greatest limitation of these therapies was low patient adherence to the two drugs, which is not surprising considering that the need for an intensive chelation is generally linked to previous issues of compliance. [ABSTRACT FROM AUTHOR]

By contrast, in the article by Origa et al., the effects of new combined therapies were retrospectively evaluated in TDT patients with high serum ferritin values and severe or moderate liver IO, refractory, intolerant or not adherent to previous chelation regimens [[2]]. The first article by Ricchi et al. reported a cross-sectional study and focuses on the feasibility of achieving serum ferritin < 500 ng/mL for several TDT patients under different chelation regimens [[1]]. This Special Issue on "Emerging Therapies and Strategies in Thalassemia: Toward a New Era in management" aims to update researchers and clinicians regarding the field of thalassemia syndromes. [Extracted from the article]

Anemia is the most common form of cytopenia in patients with myelodysplastic syndromes (MDS), who require chronic red blood cell transfusions and may present high serum ferritin (SF) levels as a result of iron overload. To better understand the potential effects of high SF levels, we conducted a systematic literature review (SLR) to identify evidence on the relationship between SF levels and clinical, economic, or humanistic outcomes in adult patients with MDS. Of 267 references identified, 21 were included. No studies assessing SF levels and their relationship with humanistic or economic outcomes were identified. Increased SF levels were an indicator of worse overall survival and other worsened outcomes; however, the association was not consistently significant. SF levels were a significant prognostic factor for relapse incidence of MDS and showed a significant positive correlation with number of blood units transfused but were not associated with progression to acute myeloid leukemia or the time to transformation. Higher SF levels were also an indicator of a lower likelihood of leukemia-free survival, relapse-free survival, and event-free survival. The SLR suggests that SF levels are associated with clinical outcomes in MDS, with higher levels correlated with number of blood units transfused, frequently indicating worse outcomes. [ABSTRACT FROM AUTHOR]

Background: The incidence of AKI in coronavirus disease 2019 (COVID-19) patients is variable and has been associated with worse prognosis. A significant number of patients develop persistent kidney damage defined as Acute Kidney Disease (AKD). There is a lack of evidence on the real impact of AKD on COVID-19 patients. We aim to identify risk factors for the development of AKD and its impact on mortality in COVID-19 patients. Methods: Retrospective analysis of COVID-19 patients with AKI admitted at the Centro Hospitalar Universitário Lisboa Norte between March and August of 2020. The Kidney Disease Improving Global Outcomes (KDIGO) classification was used to define AKI. AKD was defined by presenting at least KDIGO Stage 1 criteria for >7 days after an AKI initiating event. Results: In 339 COVID-19 patients with AKI, 25.7% patients developed AKD (n = 87). The mean age was 71.7 ± 17.0 years, baseline SCr was 1.03 ± 0.44 mg/dL, and the majority of patients were classified as KDIGO stage 3 AKI (54.3%). The in-hospital mortality was 18.0% (n = 61). Presence of hypertension (p = 0.006), CKD (p < 0.001), lower hemoglobin (p = 0.034) and lower CRP (p = 0.004) at the hospital admission and nephrotoxin exposure (p < 0.001) were independent risk factors for the development of AKD. Older age (p = 0.003), higher serum ferritin at admission (p = 0.008) and development of AKD (p = 0.029) were independent predictors of in-hospital mortality in COVID-19-AKI patients. Conclusions: AKD was significantly associated with in-hospital mortality in this population of COVID-19-AKI patients. Considering the significant risk of mortality in AKI patients, it is of paramount importance to identify the subset of higher risk patients. [ABSTRACT FROM AUTHOR]

Corona Virus Disease-19 (COVID-19) recently emerged as a global pandemic. Advanced age is the most important risk factor for increased virus susceptibility and worse outcomes. Many older adults are currently treated with renin–angiotensin–aldosterone system (RAAS) inhibitors and there is concern that these medications might increase the risk of mortality by COVID-19. This is a retrospective cohort of 346 patients older than 65 years with COVID-19, at the Department of Medicine of the Centro Hospitalar Universitário Lisboa Norte, in Portugal, hospitalized between March 2020 and August 2020. Mean age was 80.9 ± 8.7 years old. Most patients had arterial hypertension (n = 279, 80.6%), almost half (n = 161, 46.5%) had cardiovascular disease and approximately one-third of patients had heart failure (n = 127, 36.7%) or diabetes Mellitus (n = 113, 32.7%). Ninety-eight patients (28.3%) had chronic kidney disease and almost half of the patients (49.4%) were chronically under renin–angiotensin–aldosterone system (RAAS) inhibitors. Twenty percent of patients died during hospitalization. In a multivariate analysis, older age (OR 1.11, 95% CI 1.04, 1.18, p = 0.002), absence of baseline medication with RAAS inhibitors (OR 0.27, 95% CI 0.10, 0.75, p = 0.011), higher serum ferritin (OR 1.00, 95% CI 1.00, 1.00, p = 0.003) and higher lactate levels (OR 1.08, 95% CI 1.02, 1.14, p = 0.006) were independent predictors of mortality. Older age, higher serum ferritin and lactate levels at admission were found to be independent predictors of mortality and might act as early predictors of worsening disease in clinical practice. Chronic treatment with RAAS inhibitors appeared to be protective, supporting guidelines in not discontinuing such drugs. [ABSTRACT FROM AUTHOR]

Ferritin is one of the most frequently requested laboratory tests in primary and secondary care, and levels often deviate from reference ranges. Serving as an indirect marker for total body iron stores, low ferritin is highly specific for iron deficiency. Hyperferritinemia is, however, a non-specific finding, which is frequently overlooked in general practice. In routine medical practice, only 10% of cases are related to an iron overload, whilst the rest is seen as a result of acute phase reactions and reactive increases in ferritin due to underlying conditions. Differentiation of the presence or absence of an associated iron overload upon hyperferritinemia is essential, although often proves to be complex. In this review, we have performed a review of a selection of the literature based on the authors' own experiences and assessments in accordance with international recommendations and guidelines. We address the biology, etiology, and epidemiology of hyperferritinemia. Finally, an algorithm for the diagnostic workup and management of hyperferritinemia is proposed, and general principles regarding the treatment of iron overload are discussed. [ABSTRACT FROM AUTHOR]