RESUMEN
BACKGROUND AND AIMS: What is the relationship between blood tests for iron deficiency, including anaemia, and the response to intravenous iron in patients with heart failure? METHODS: In the IRONMAN trial, 1137 patients with heart failure, ejection fraction ≤ 45%, and either serum ferritin < 100â µg/L or transferrin saturation (TSAT) < 20% were randomized to intravenous ferric derisomaltose (FDI) or usual care. Relationships were investigated between baseline anaemia severity, ferritin and TSAT, to changes in haemoglobin from baseline to 4 months, Minnesota Living with Heart Failure (MLwHF) score and 6-minute walk distance achieved at 4 months, and clinical events, including heart failure hospitalization (recurrent) or cardiovascular death. RESULTS: The rise in haemoglobin after administering FDI, adjusted for usual care, was greater for lower baseline TSAT (Pinteraction < .0001) and ferritin (Pinteraction = .028) and more severe anaemia (Pinteraction = .014). MLwHF scores at 4 months were somewhat lower (better) with FDI for more anaemic patients (overall Pinteraction = .14; physical Pinteraction = .085; emotional Pinteraction = .043) but were not related to baseline TSAT or ferritin. Blood tests did not predict difference in achieved walking distance for those randomized to FDI compared to control. The absence of anaemia or a TSAT ≥ 20% was associated with lower event rates and little evidence of benefit from FDI. More severe anaemia or TSAT < 20%, especially when ferritin was ≥100â µg/L, was associated with higher event rates and greater absolute reductions in events with FDI, albeit not statistically significant. CONCLUSIONS: This hypothesis-generating analysis suggests that anaemia or TSAT < 20% with ferritin > 100â µg/L might identify patients with heart failure who obtain greater benefit from intravenous iron. This interpretation requires confirmation.
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Anemia Ferropénica , Anemia , Insuficiencia Cardíaca , Deficiencias de Hierro , Humanos , Hierro/uso terapéutico , Anemia Ferropénica/tratamiento farmacológico , Ferritinas/uso terapéutico , Compuestos Férricos/uso terapéutico , Hemoglobinas , Insuficiencia Cardíaca/tratamiento farmacológicoRESUMEN
BACKGROUND: Intravenous iron (IV-iron) is used as an alternative to, or alongside, red blood cell transfusion (RBC-T) to treat more severe postpartum anemia (PPA), although optimal treatment options remain unclear. No previous systematic reviews have examined IV-iron and RBC-T, including patient-reported outcomes and hematological responses. METHODS: A systematic review and meta-analysis of randomized trials comparing IV-iron and RBC-T with each other, oral iron, no treatment, and placebo for the treatment of PPA. Key inclusion criteria were PPA (hemoglobin < 12 g/dL) and IV-iron or RBC-T as interventions. Key exclusion criteria were antenatal IV-iron or RBC-T. Fatigue was the primary outcome. Secondary outcomes included hemoglobin and ferritin concentrations, and adverse events. From 27th August 2020 to 26th September 2022, databases, registries, and hand searches identified studies. A fixed-effect meta-analysis was undertaken using RevMan (5.4) software. The quality of the studies and the evidence was assessed using the Cochrane Risk of Bias table, and Grading of Recommendations, Assessment, Development, and Evaluation. This review is registered with the Prospective Register of Systematic Reviews (CRD42020201115). RESULTS: Twenty studies and 4196 participants were included: 1834 assigned IV-iron, 1771 assigned oral iron, 330 assigned RBC-T, and 261 assigned non-intervention. Six studies reported the primary outcome of fatigue (1251 participants). Only studies of IV-iron vs. oral iron (15 studies) were available for meta-analysis. Of these, three reported on fatigue using different scales; two were available for meta-analysis. There was a significant reduction in fatigue with IV-iron compared to oral iron (standardized mean difference - 0.40, 95% confidence interval (CI) - 0.62, - 0.18, I2 = 0%). The direction of effect also favored IV-iron for hemoglobin (mean difference (MD) 0.54 g/dL, 95% confidence interval (CI) 0.47, 0.61, I2 = 91%), ferritin, (MD 58.07 mcg/L, 95% CI 55.74, 60.41, I2 = 99%), and total adverse events (risk-ratio 0.63, 95% CI 0.52, 0.77, I2 = 84%). The overall quality of the evidence was low-moderate. DISCUSSION: For all outcomes, the evidence for RBC-T, compared to IV-iron, non-intervention, or dose effects of RBC-T is very limited. Further research is needed to determine whether RBC-T or IV-iron for the treatment of PPA is superior for fatigue and hematological outcomes.
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Anemia , Hierro , Femenino , Humanos , Embarazo , Hierro/uso terapéutico , Anemia/tratamiento farmacológico , Transfusión Sanguínea , Hemoglobinas/metabolismo , Ferritinas/uso terapéutico , Periodo Posparto , Fatiga/tratamiento farmacológicoRESUMEN
BACKGROUND: The association between different phenotypes and genotypes of circulating tumor cells (CTCs) and efficacy of neoadjuvant chemotherapy (NAC) remains uncertain. This study was conducted to evaluate the relationship of FTH1 gene-associated CTCs (F-CTC) with/without epithelial-mesenchymal transition (EMT) markers, or their dynamic changes with the efficacy of NAC in patients with non-metastatic breast cancer. PATIENTS AND METHODS: This study enrolled 120 patients with non-metastatic breast cancer who planned to undergo NAC. The FTH1 gene and EMT markers in CTCs were detected before NAC (T0), after 2 cycles of chemotherapy (T1), and before surgery (T2). The associations of these different types of CTCs with rates of pathological complete response (pCR) and breast-conserving surgery (BCS) were evaluated using the binary logistic regression analysis. RESULTS: F-CTC in peripheral blood ≥1 at T0 was an independent factor for pCR rate in patients with HER2-positive (odds ratio [OR]=0.08, 95% confidence interval [CI], 0.01-0.98, P = .048). The reduction in the number of F-CTC at T2 was an independent factor for BCS rate (OR = 4.54, 95% CI, 1.14-18.08, P = .03). CONCLUSIONS: The number of F-CTC prior to NAC was related to poor response to NAC. Monitoring of F-CTC may help clinicians formulate personalized NAC regimens and implement BCS for patients with non-metastatic breast cancer.
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Neoplasias de la Mama , Células Neoplásicas Circulantes , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/cirugía , Células Neoplásicas Circulantes/patología , Estudios Prospectivos , Terapia Neoadyuvante , Mastectomía Segmentaria , Ferritinas/uso terapéutico , Oxidorreductasas/uso terapéuticoRESUMEN
Antihypertensive medications have been associated with a reduction in hemoglobin (Hb) levels, leading to clinically significant anemia. We aimed to provide valuable insights into the impact of angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs) on hematological parameters by measuring the levels of erythropoietin (EPO), ferritin, and complete blood count (CBC) in individuals with type 2 diabetes mellitus (T2DM), particularly considering the duration of the antihypertensives use. In addition to comparing their effects on blood pressure, glycemic status, and renal function, a retrospective cohort study was conducted at the consultation unit of Alsalam Teaching Hospital, Mosul, Nineveh Province, between October 2022 and February 2023. A total of 160 participants were enrolled after being fully examined by the consultants to detect their eligibility for inclusion in the study and to rule out any abnormality. They consisted of 40 healthy controls, 30 T2DM patients (T2DM group), 30 T2DM patients with newly diagnosed hypertension (HT) (T2DM+HT group), 30 type 2 diabetic-hypertensives on ARBs (T2DM+HT+ARBs group), and 30 type 2 diabetic-hypertensives on CCBs (T2DM+HT+CCBs group). Five milliliters of blood was drawn from a vein and divided into two parts. Two milliliters was transferred into an anticoagulant tube for the measurement of HbA1c and complete blood picture. Serum was obtained from the remaining blood and used for assessment of ferritin, EPO, FSG, creatinine, urea, and uric acid. Significantly reduced FSG and HbA1c levels were observed in T2DM+HT+CCBs and T2DM+HT+ARBs groups vs T2DM+HT group (p < 0.05). The T2DM+HT+CCBs group had statistically higher urea levels than the T2DM group (p < 0.05). Both CCBs and ARBs use resulted in reduced creatinine clearance (CrCl). T2DM+HT+CCBs group exhibited slightly higher uric acid levels compared to controls (p < 0.05). Prolonged use of CCBs and ARBs led to disturbances in hematological parameters, with CCBs users showing the lowest levels of hemoglobin (Hb), RBCs, and hematocrit (Hct) among the groups. ARBs users displayed the lowest values of EPO and ferritin compared to other patient groups, along with reduced levels of Hb, RBCs, and Hct, albeit slightly higher than CCBs users. Our study highlights the importance of a balanced approach in prescribing ARBs and CCBs to patients with T2DM, given their potential to induce blood abnormalities, particularly with prolonged usage.
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Diabetes Mellitus Tipo 2 , Hipertensión , Humanos , Bloqueadores de los Canales de Calcio/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Antagonistas de Receptores de Angiotensina/uso terapéutico , Hemoglobina Glucada , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Creatinina , Estudios Retrospectivos , Ácido Úrico , Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Hemoglobinas , Urea , Ferritinas/uso terapéuticoRESUMEN
BACKGROUND: Hyperphosphataemia is a common complication of kidney disease. Current dialysis techniques do not provide enough phosphorus clearance, hence the need to use phosphorus binders. Treatment options include calcium carbonate, calcium acetate, lanthanum carbonate, sevelamer hydrochloride and iron-based binders. Patients receiving peritoneal dialysis (PD) with sustained elevated ferritin levels exceeding 800 ng/mL are at a higher risk of death. We identify PD patients treated with iron-based binders and compare ferritin and risk of iron accumulation to patients treated with non-iron-based binders. METHODS: All records of patients receiving PD at Emory dialysis centres until 30 October 2021 were reviewed for phosphorus binders. Basic demographics and laboratory data were time-referenced to the days on treatment with a particular binder. Patients were followed until discontinuation of the phosphorus binder, death, transplant, transfer to another dialysis provider or censoring at 36 months after medication was started. RESULTS: Compared to calcium acetate and sevelamer, ferric citrate utilisation in PD patients resulted in a sustained increase in ferritin. The proportion of patients with a ferritin equal to or greater than 800 ng/dL and transferrin saturation greater than 40% increased over time in patients treated with ferric citrate and was higher during the second and third year of follow-up compared to baseline values and to patients treated with calcium acetate or sevelamer. Two patients (7%) treated with ferric citrate developed clinically significant haemosiderosis. CONCLUSIONS: Use of ferric citrated in PD resulted in significant iron accumulation as judged by ferritin levels.
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Acetatos , Compuestos Férricos , Hiperfosfatemia , Diálisis Peritoneal , Humanos , Hierro/metabolismo , Sevelamer/uso terapéutico , Diálisis Peritoneal/efectos adversos , Diálisis Renal , Fósforo/metabolismo , Fósforo/uso terapéutico , Hiperfosfatemia/tratamiento farmacológico , Hiperfosfatemia/etiología , Ferritinas/uso terapéutico , Biomarcadores , Fosfatos , Quelantes/efectos adversos , Compuestos de CalcioRESUMEN
BACKGROUND: Ferroptosis, a newly form of regulated cell death (RCD), is characterized by iron dyshomeostasis and unrestricted lipid peroxidation. Emerging evidence depicts a pivotal role for ferroptosis in driving some pathological processes, especially in cancer. Triggering ferroptosis can suppress tumor growth and induce an anti-tumor immune response, denoting the therapeutic promises for targeting ferroptosis in the management of cancer. As an autophagic phenomenon, ferritinophagy is critical to induce ferroptosis by degradation of ferritin to release intracellular free iron. Recently, a great deal of effort has gone into designing and developing anti-cancer strategies based on targeting ferritinophagy to induce ferroptosis. CONCLUSION: This review delineates the regulatory mechanism of ferritinophagy firstly and summarizes the role of ferritinophagy-induced ferroptosis in cancer. Moreover, the strategies targeting ferritinophagy to induce ferroptosis are highlighted to unveil the therapeutic value of ferritinophagy as a target to manage cancer. Finally, the future research directions on how to cope with the challenges in developing ferritinophagy promoters into clinical therapeutics are discussed.
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Ferroptosis , Neoplasias , Humanos , Hierro/metabolismo , Hierro/farmacología , Hierro/uso terapéutico , Ferritinas/metabolismo , Ferritinas/uso terapéutico , Neoplasias/metabolismo , AutofagiaRESUMEN
Glioblastoma (GBM) is the deadliest tumor of the central nervous system, with a median survival of less than 15 months. Despite many trials, immune checkpoint-blocking (ICB) therapies using monoclonal antibodies against the PD-1/PD-L1 axis have demonstrated only limited benefits for GBM patients. Currently, the main hurdles in brain tumor therapy include limited drug delivery across the blood-brain barrier (BBB) and the profoundly immune-suppressive microenvironment of GBM. Thus, there is an urgent need for new therapeutics that can cross the BBB and target brain tumors to modulate the immune microenvironment. To this end, we developed an ICB strategy based on the BBB-permeable, 24-subunit human ferritin heavy chain, modifying the ferritin surface with 24 copies of PD-L1-blocking peptides to create ferritin-based ICB nanocages. The PD-L1pep ferritin nanocages first demonstrated their tumor-targeting and antitumor activities in an allograft colon cancer model. Next, we found that these PD-L1pep ferritin nanocages efficiently penetrated the BBB and targeted brain tumors through specific interactions with PD-L1, significantly inhibiting tumor growth in an orthotopic intracranial tumor model. The addition of PD-L1pep ferritin nanocages to triple in vitro cocultures of T cells, GBM cells, and glial cells significantly inhibited PD-1/PD-L1 interactions and restored T-cell activity. Collectively, these findings indicate that ferritin nanocages displaying PD-L1-blocking peptides can overcome the primary hurdle of brain tumor therapy and are, therefore, promising candidates for treating GBM.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/patología , Antígeno B7-H1/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Ferritinas/uso terapéutico , Péptidos/uso terapéutico , Microambiente TumoralRESUMEN
Systemic lupus erythematosus (SLE) associated macrophage activation syndrome (MAS) is clinically severe, with a high mortality rate and rare neuropsychiatric symptoms. In the course of diagnosis and treatment, it is necessary to actively determine whether the neuropsychiatric symptoms in patients are caused by neuropsychiatric systemic lupus erythematosus (NPSLE) or macrophage activation syndrome. This paper retrospectively analyzed the clinical data of 2 cases of SLE associated MAS with neuropsychiatric lesions, Case 1: A 30-year-old female had obvious alopecia in 2019, accompanied by emaciation, fatigue and dry mouth. In March 2021, she felt weak legs and fell down, followed by fever and chills without obvious causes. After completing relevant examinations, she was diagnosed with SLE and given symptomatic treatments such as hormones and anti-infection, but the patient still had fever. The relevant examinations showed moderate anemia, elevated ferritin, elevated triglycerides, decreased NK cell activity, and a perforin positivity rate of 4.27%, which led to the diagnosis of "pre-hemophagocytic syndrome (HPS)". In May 2021, the patient showed mental trance and babble, and was diagnosed with "SLE-associated MAS"after completing relevant examinations. After treatment with methylprednisolone, anti-infection and psychotropic drugs, the patient's temperature was normal and mental symptoms improved. Case 2: A 30-year-old female patient developed butterfly erythema on both sides of the nose on her face and several erythema on her neck in June 2019, accompanied by alopecia, oral ulcers, and fever. She was diagnosed with "SLE" after completing relevant examinations, and her condition was relieved after treatment with methylprednisolone and human immunoglobulin. In October 2019, the patient showed apathy, no lethargy, and fever again, accompanied by dizziness and vomiting. The relevant examination indicated moderate anemia, decreased NK cell activity, elevated triglycerides, and elevated ferritin. The patient was considered to be diagnosed with "SLE, NPSLE, and SLE-associated MAS". After treatment with hormones, human immunoglobulin, anti-infection, rituximab (Mabthera), the patient's condition improved and was discharged from the hospital. After discharge, the patient regularly took methylprednisolone tablets (Medrol), and her psychiatric symptoms were still intermittent. In November 2019, she developed symptoms of fever, mania, and delirium, and later turned to an apathetic state, and was given methylprednisolone intravenous drip and olanzapine tablets (Zyprexa) orally. After the mental symptoms improved, she was treated with rituximab (Mabthera). Later, due to repeated infections, she was replaced with Belizumab (Benlysta), and she was recovered from her psychiatric anomalies in March 2021. Through the analysis of clinical symptoms, imaging examination, laboratory examination, treatment course and effect, it is speculated that the neuropsychiatric symptoms of case 1 are more likely to be caused by MAS, and that of case 2 is more likely to be caused by SLE. At present, there is no direct laboratory basis for the identification of the two neuropsychiatric symptoms. The etiology of neuropsychiatric symptoms can be determined by clinical manifestations, imaging manifestations, cerebrospinal fluid detection, and the patient's response to treatment. Early diagnosis is of great significance for guiding clinical treatment, monitoring the condition and judging the prognosis. The good prognosis of the two cases in this paper is closely related to the early diagnosis, treatment and intervention of the disease.
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Anemia , Lupus Eritematoso Sistémico , Vasculitis por Lupus del Sistema Nervioso Central , Síndrome de Activación Macrofágica , Humanos , Femenino , Adulto , Rituximab/uso terapéutico , Síndrome de Activación Macrofágica/diagnóstico , Síndrome de Activación Macrofágica/tratamiento farmacológico , Síndrome de Activación Macrofágica/etiología , Estudios Retrospectivos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Metilprednisolona/uso terapéutico , Fiebre/tratamiento farmacológico , Eritema/complicaciones , Eritema/tratamiento farmacológico , Hormonas/uso terapéutico , Alopecia/complicaciones , Alopecia/tratamiento farmacológico , Triglicéridos/uso terapéutico , Ferritinas/uso terapéuticoRESUMEN
PURPOSE: Iron deficiency (ID) is a complication of gastrointestinal (GI) cancers that may manifest as iron deficiency anemia (IDA). Serum ferritin monitoring and oral iron supplementation have the limitations of being falsely elevated and poorly absorbed, respectively. This study aims to assess the discordance in surveillance, treatment practices, and awareness of ID/IDA in GI cancer patients by Canadian physicians treating these patients. METHODS: From February 2020 to September 2021, a 22-question electronic survey was sent to medical oncologists (MOs), surgical oncologists (SOs), and gastroenterologists (GEs). The survey collected information about four domains: physician demographics, surveillance practices, treatment practices, and awareness of ID/IDA in GI cancer patients and ASCO/ASH guidelines. RESULTS: A total of 108 (34 MOs, 19 SOs, and 55 GEs) of the 872 (12.4%) invited physicians completed the survey. Of these, 26.5% of MOs, 36.8% of SOs, and 70.9% of GEs measured baseline iron parameters, with few continuing surveillance throughout treatment. Ferritin was widely measured by MOs (88.9%), SOs (100%), and GEs (91.4%). Iron was supplemented if ID/IDA was identified pre-treatment by 66.7% of MOs, 85.7% of SOs, and 94.2% of GEs. Parenteral iron was prescribed by SOs (100%), while oral iron was prescribed by MOs (83.3%) and GEs (87.9%). Only 18.6% of physicians were aware of the ASCO/ASH guidelines regarding erythropoiesis-stimulating agents with parenteral iron for treating chemotherapy-induced anemia. CONCLUSION: Results illustrate variations in practice patterns for IDA management across the different physician specialties. Moreover, there appeared to be gaps in the knowledge and care surrounding evidence-based IDA management principles which may contribute to poor clinical outcomes.
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Anemia Ferropénica , Neoplasias Gastrointestinales , Médicos , Humanos , Hierro/uso terapéutico , Canadá , Anemia Ferropénica/tratamiento farmacológico , Anemia Ferropénica/etiología , Ferritinas/uso terapéuticoRESUMEN
Immunotherapy of lung cancer has achieved promising clinical results. However, it is urgent to develop predictive biomarkers for effective immunotherapy. While ferroptosis plays a critical role in immunotherapy efficacy, ferritin is an important regulatory factor. We, therefore, hypothesize that basal serum ferritin levels before immunotherapy and their corresponding changes during immunotherapy can be useful predictors of immunotherapy response in patients with lung cancer. We measured serum ferritin levels in 107 patients with lung cancer before and during immune checkpoint blockade treatments and studied the correlation between ferritin levels, response rate, and survival. Moreover, the correlation between basal ferritin and PD-L1 expression, tumor stages and pathological types was also analyzed. Patients with lower basal serum ferritin levels before immunotherapy had longer progression-free survival (PFS) (median 7 vs 4 months, P = .023) and higher disease control rate (DCR) (X2 = 4.837, P = .028), those with downregulated serum ferritin levels during immunotherapy correlated with longer PFS (median 9.5 vs 4 months, P < .001) and higher DCR (X2 = 6.475, P = .011). However, the "integrated factor", which was calculated as the combination of lower basal serum ferritin levels before immunotherapy and downregulated serum ferritin levels during immunotherapy, correlated with prolonged PFS (P < .001). Multivariate analyses revealed that the basal serum ferritin levels before immunotherapy and the corresponding changes during immunotherapy were both strong independent prognostic factors (hazard ratio (HR) = 1.60, P = .041; HR = 2.65, P = .001). These findings suggest that serum ferritin levels can be used as a prognostic biomarker for lung cancer in predicting immunotherapy efficacy.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Pronóstico , Biomarcadores de Tumor/metabolismo , Inmunoterapia/métodos , Antígeno B7-H1/metabolismo , Ferritinas/uso terapéuticoRESUMEN
Iron deficiency (ID) is the world's most common disorder and one of the top five causes of years lived with disability. Whereas low serum ferritin is diagnostic of ID, ferritin-an acute phase reactant-may be elevated in inflammatory states and the first trimester of pregnancy even if ID exists. Consequently, in early pregnancy or chronic inflammation, percent transferrin saturation (TSAT) measurement is the best indicator of iron status. Unfortunately, current guidelines do not recommend routine screening for ID in either pregnant or nonpregnant women in the absence of anemia. This circumstance should be urgently reviewed based on available data. While oral formulations have long been the standard for iron replacement therapy and are widely available and inexpensive, oral iron is frequently associated with adverse gastrointestinal effects for the majority-a major reason for poor adherence, inadequate repletion, and persisting ID symptoms and sequellae. Although safe intravenous iron administration was introduced in the mid-1950s, formulations with cores binding the elemental iron more tightly became available in the 2000s, allowing complete and safe replacement, even in a single setting. Prospectively acquired neonatology evidence reports oral iron's failure to reach the developing fetus when the mother is iron deficient. Consequently, while oral iron remains frontline in the first trimester because of insufficient safety data for intravenous iron, the author recommends that the intravenous route should be the gold standard for second-trimester ID when hemoglobin concentrations are less than 10.5 g/dL and for all iron-deficient women in their third trimester.
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Anemia Ferropénica , Anemia , Deficiencias de Hierro , Embarazo , Femenino , Humanos , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/tratamiento farmacológico , Hierro/uso terapéutico , Ferritinas/uso terapéutico , Hemoglobinas/análisisRESUMEN
BACKGROUND: Little is known about the laboratory variable risks with bone mineral density (BMD) in patients with schizophrenia. This study was designed to fully investigate the related risk factors for decreased BMD in schizophrenia, as well as evaluate the gender difference of BMD. METHOD: The BMD of the forearm of 211 patients (males/females = 140/71) who met the diagnostic criteria for DSM-5 schizophrenia was measured by dual-energy X-ray absorptiometry. Basic demographic information, clinical assessments, and laboratory variables (regarding nutrition, hormones, metabolism, and inflammatory markers) were comprehensively collected. RESULTS: Among 211 subjects, seventy-four (35%) patients had low BMD. Males had a significantly lower BMD T-score than females (P = 0.002). Multiple regression analyses showed that the independent risks with low BMD were lower folate, glycosylated hemoglobin levels, higher age, serum ferritin, and follicle-stimulating hormone (FSH) levels. In female patients, the BMD was mainly associated with age and serum hormones (FSH and testosterone), while the BMD of male patients was primarily related to age, microelements (serum ferritin and 25-OH-VD), and parathyroid hormone. CONCLUSION: Our study found several meaningful correlations between osteoporosis and schizophrenia, especially regarding laboratory measures, which may provide new clues to identifying or preventing osteoporosis in clinical patients.
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Antipsicóticos , Osteoporosis , Esquizofrenia , Humanos , Femenino , Masculino , Antipsicóticos/efectos adversos , Estudios Transversales , Esquizofrenia/complicaciones , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/inducido químicamente , Osteoporosis/complicaciones , Densidad Ósea , Factores de Riesgo , Hormona Folículo Estimulante/farmacología , Hormona Folículo Estimulante/uso terapéutico , Ferritinas/farmacología , Ferritinas/uso terapéuticoRESUMEN
BACKGROUND: Iron-deficiency anemia in pregnancy is highly prevalent and presents significant risk to patients. Initial treatment is often with oral medication. We hypothesized that intravenous ferumoxytol would result in superior treatment of anemia as compared to oral ferrous sulfate. OBJECTIVE: This study aimed to investigate whether 2 infusions of intravenous ferumoxytol are superior to the use of twice-daily oral ferrous sulfate for the treatment of iron-deficiency anemia in pregnancy. STUDY DESIGN: A randomized controlled trial was performed in which participants with anemic (hemoglobin <11 g/dL and hematocrit <33%) were allocated to receive either 2 infusions of 510 mg of intravenous ferumoxytol approximately 7 days apart, or 325 mg oral ferrous sulfate twice daily from enrollment to the end of their pregnancy. Participants were randomized in a 1:1 ratio to each treatment. Our primary outcome was the change in maternal hemoglobin. Secondary outcomes included maternal iron indices, maternal safety, and maternal tolerability. RESULTS: There were 124 participants (N=62 per group). In the intravenous iron group, the mean change in hemoglobin was 1.86 g/dL (95% confidence interval, 1.57 g/dL-2.14 g/dL) and in the oral group was 0.79 g/dL (95% confidence interval, 0.42 g/dL-1.17 g/dL) (P<.0001). The median change in ferritin between groups was 64.5 (range, 31-364) vs 8 (range, -436 to +167) (P=.0001). The median change in iron between groups was also statistically significant with 47.5 ug/dL (range, -133 ug/dL to +664 ug/dL) in the intravenous group vs 8.5 ug/dL (range, -313 ug/dL to +437 ug/dL) in the oral iron group (P=.001). CONCLUSION: Intravenous ferumoxytol was well tolerated, and it was associated with statistically significant increases in maternal hemoglobin, hematocrit, iron, and ferritin compared to oral ferrous sulfate.
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Anemia Ferropénica , Óxido Ferrosoférrico , Embarazo , Femenino , Humanos , Óxido Ferrosoférrico/efectos adversos , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/tratamiento farmacológico , Anemia Ferropénica/epidemiología , Infusiones Intravenosas , Resultado del Tratamiento , Hierro/uso terapéutico , Ferritinas/uso terapéutico , Hemoglobinas/análisis , Hemoglobinas/metabolismo , Hemoglobinas/uso terapéuticoRESUMEN
PURPOSE: Lymphoma-associated haemophagocytic syndrome (LAHS) is a group of malignant diseases with rapid progression and a high mortality rate. Our study aimed to discover the significance of serum sCD25/ferritin ratio as well as cytokines in assisting the diagnosis of LAHS. METHODS: We retrospectively analyzed the clinical data of 82 patients with LAHS with hemophagocytic lymphohistiocytosis (HLH) as the first manifestation and divided them into B-LAHS group and T/NK-LAHS group according to lymphoma pathological diagnosis for comparison. And patients with LAHS were divided into responding group, non-responding group according to the assessment of efficacy after receiving DEP/L-DEP induction therapy for 2 weeks to compare possible valuable indicators. RESULTS: Serum sCD25/ferritin ratio and MCP-1 levels were significantly different between B-LAHS and T/NK-LAHS groups (P = 0.001, P = 0.022). An sCD25/ferritin ratio > 7.8 tended to suggest a diagnosis of B-LAHS (AUC = 0.71, 95% CI: 0.596-0.823), and the sCD25/ferritin ratio had better predictive value when combined with MCP-1 (AUC = 0.81, 95% CI: 0.699-0.922). The sCD25/ferritin ratio was also significantly different between the two groups responding or not responding to induction therapy (P = 0.002), yielding an optimal cutoff value of 11.48. An sCD25/ferritin ratio > 11.48 tended to suggest that the patient's LAHS was responsive to induction therapy. CONCLUSION: Our study reveals that serum sCD25/ferritin ratio combined with MCP-1 is a valid predictor for identifying LAHS with HLH as the first manifestation and may assist in predicting whether the lymphoma is of B-cell or T/NK-cell origin. The sCD25/ferritin ratio can also be used to predict the early response of LAHS after induction therapy.
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Linfohistiocitosis Hemofagocítica , Linfoma , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Estudios Retrospectivos , Linfoma/diagnóstico , Pronóstico , Ferritinas/uso terapéuticoRESUMEN
Objective: To investigate the effect of information management of intravenous drugs on anemia in maintenance hemodialysis patients. Methods: The information management of intravenous drugs was a management system developed by the Hemodialysis Center of Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital in April 2020. The parameters six months before and after the use of the information management system were retrospectively collected and compared, including the rate of reaching the standard of hemoglobin, ferritin, transferrin saturation rate and the incidence of cardiovascular events. Specifically, the control stage was from October 2019 to March 2020, which was before the use of information management, and the study stage was from April to September 2020, which was after the use of information management. Results: There were 285 patients (190 males and 95 females) included in the control stage, with an average age of (62.4±13.2) years, while 278 patients (193 males and 85 females) were included in the study stage, with an average age of (62.8±13.2) years. Compared with the control stage, the rate of reaching the standard of hemoglobin [47.8% (797/1 668) vs 40.2% (687/1 710), P<0.001], ferritin [39.0% (217/556) vs 31.2% (178/570), P=0.006], and transferrin saturation [64.7% (360/556) vs 58.6% (334/570), P=0.034] increased in the study stage. The incidence of cardiovascular events in the study stage was 11.2% (31/278), which was significantly lower than that in the control stage [16.5% (47/285)] (P=0.043). Conclusion: The information management of intravenous drugs in the hemodialysis center may help improve the anemia status in maintenance hemodialysis patients.
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Anemia , Enfermedades Cardiovasculares , Fallo Renal Crónico , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Fallo Renal Crónico/complicaciones , China , Diálisis Renal/efectos adversos , Ferritinas/uso terapéutico , Hemoglobinas/análisis , Hemoglobinas/metabolismo , Hemoglobinas/uso terapéutico , Gestión de la Información , Enfermedades Cardiovasculares/complicaciones , TransferrinasRESUMEN
INTRODUCTION: Hemosiderosis of chronic dialysis has always been a frequent phenomenon in dialysis; formerly related to blood transfusions before the advent of Erythropoiesis Stimulating Agents (ESA), it is currently in connection with the use of massive doses of injectable iron, to ensure the full therapeutic efficacy of ESA. Few studies have looked at the therapeutic aspect of iron chelators in the dialysis population. METHODS: We followed 31 dialysis patients treated for secondary hemosiderosis with deferasirox (DFX) at the dose 10 mg/kg/day, by hepatic MRI from September 2017 to September 2021, in order to evaluate the efficacy of iron chelators on the reduction of liver iron concentration (LIC). The diagnosis of hemosiderosis was carried for a value of the LIC > 50 µmol/g of dry liver. RESULTS: Chelation resulted in a significant reduction in liver iron burden as measured by liver MRI: (201.4 ± 179.9 vs. 122.6 ± 154.3 µmol/g liver) (p = 0.000) and in mean ferritin level: (2058.8 ± 2004.9 vs. 644.2 ± 456.6 ng/mL) (p = 0.002). A gain of 1.1 g/dL in mean hemoglobin level: (10.5 ± 1.6 vs. 11.6 ± 2.0 g/dL) (p = 0.006). A significant increase in mean albumin level: (43 ± 5.5 to 46.2 ± 6.1 g/L) (p = 0.04). The therapeutic response was clearly influenced by the cause of overload, longer in polytransfused patients (p = 0.023) and the degree of overload assessed by MRI (p = 0.003) and ferritin level (p = 0.04). CONCLUSION: DFX, prescribed at a dose of 10 mg/kg/day, resulted in a significant reduction in hepatic iron burden as measured by liver MRI and ferritin. The therapeutic response was clearly influenced by blood transfusions and the degree of iron overload.
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Hemosiderosis , Sobrecarga de Hierro , Humanos , Deferasirox/uso terapéutico , Ferritinas/uso terapéutico , Hemosiderosis/etiología , Hemosiderosis/complicaciones , Hierro/uso terapéutico , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/tratamiento farmacológico , Sobrecarga de Hierro/etiología , Hígado/diagnóstico por imagen , Hígado/metabolismo , Hígado/patología , Imagen por Resonancia Magnética , Diálisis Renal/efectos adversosRESUMEN
AIM: Single-arm, open-label, phase 3 study to evaluate the efficacy and safety of ferric derisomaltose (FDI) for iron deficiency anemia (IDA) in Japanese women with postpartum hemorrhage (PPH). METHODS: Postpartum women aged 20-39 years with serum ferritin <25.0 ng/ml, hemoglobin (Hb) <10.0 g/dl, and blood loss ≥500 ml within 24 h post-delivery were eligible to receive high-dose intravenous FDI. The primary endpoint was the maximum change in Hb concentration by Week 8. Key secondary endpoints included change in iron parameters and percentage of patients with a total Edinburgh Postnatal Depression Score (EPDS) ≥9. Safety assessments included treatment-emergent adverse events (TEAEs) and iron concentrations in maternal milk. RESULTS: All (n = 21 [100.0%]) patients received the predetermined total iron dose by Day 8. Hb concentrations increased rapidly and significantly (p < 0.001) following FDI. Serum ferritin levels also increased rapidly and were maintained near or above the upper limit of normal reference value (250 ng/ml). Following FDI, two (9.5%) patients had a total EPDS score of ≥9. TEAEs occurred in 23 of 42 (54.8%) patients and neonates overall, including 18 of 21 (85.7%) patients and 5 of 21 (23.8%) neonates. TEAEs were mild in all adult patients and four neonates, and moderate in one neonate. Iron concentrations in maternal milk remained within normal reference values. Appropriate patient selection and patient-adjusted dosage selection facilitated safe and effective administration of high-dose (≥1000 mg) FDI. CONCLUSIONS: Rapid and sustained improvements in Hb and iron stores occurred following FDI for IDA with PPH, with no new safety signals identified. CLINICAL TRIAL IDENTIFIER: JapicCTI-194888.
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Anemia Ferropénica , Depresión Posparto , Hemorragia Posparto , Adulto , Embarazo , Recién Nacido , Humanos , Femenino , Anemia Ferropénica/tratamiento farmacológico , Maltosa , Japón , Compuestos Férricos , Hierro , Hemoglobinas/análisis , Hemoglobinas/uso terapéutico , Ferritinas/uso terapéuticoRESUMEN
OBJECTIVES: Anti-melanoma differentiation-associated protein-5 (MDA5) autoantibodies (Abs) are associated with rapidly progressive interstitial lung disease (RP-ILD) in dermatomyositis (DM). Because the addition of plasma exchange (PE) and rituximab (RTX) to triple therapy is inadequate in severe cases, we treat such cases with intensive induction therapy (IIT) combining all these options with tofacitinib (TOF). In this study, we investigated the poor prognostic factors and the efficacy and safety of IIT. METHODS: Thirty-three patients diagnosed with anti-MDA5 Ab-positive DM in our institution between 2014 and 2021 were included. The clinical characteristics of poor prognosis were retrospectively analysed using principal component analysis (PCA), and the outcomes of IIT were analysed in terms of survival, assessed using the Kaplan-Meier test, and adverse events. RESULTS: Although triple therapy with RTX, PE, or intravenous immunoglobulin was administered before the introduction of IIT, eight of 12 RP-ILD cases with a ferritin level >400 ng/mL (mean, 2,342) died within a median of 2.5 months. PCA revealed distinct clusters for prognosis, and age and serum ferritin were leading predictors of the prognosis. IIT, consisting of combinations of triple therapy with higher doses of methylprednisolone, PE, RTX, and TOF, was applied to eight patients (mean ferritin, 3,558). Although two patients died even with these regimens, a significant improvement in survival was documented. Several IIT-related adverse events were observed, including viral and fungal infections and cytopenia. CONCLUSIONS: IIT significantly improved the survival of patients with severe anti-MDA5 Ab-positive RP-ILD. Although infections are noted, their benefits outweigh the risks in younger patients with high serum ferritin levels.
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Dermatomiositis , Enfermedades Pulmonares Intersticiales , Humanos , Autoanticuerpos , Dermatomiositis/complicaciones , Progresión de la Enfermedad , Ferritinas/uso terapéutico , Quimioterapia de Inducción/efectos adversos , Helicasa Inducida por Interferón IFIH1 , Enfermedades Pulmonares Intersticiales/diagnóstico , Intercambio Plasmático/efectos adversos , Estudios Retrospectivos , Rituximab/uso terapéuticoRESUMEN
In the intravenous iron therapy to treat iron deficiency anaemia in patients undergoing major abdominal surgery (PREVENTT) trial, the use of intravenous iron did not reduce the need for blood transfusion or reduce patient complications or length of hospital stay. As part of the trial protocol, serum was collected at randomisation and on the day of surgery. These samples were analysed in a central laboratory for markers of iron deficiency. We performed a secondary analysis to explore the potential interactions between pre-operative markers of iron deficiency and intervention status on the trial outcome measures. Absolute iron deficiency was defined as ferritin <30 µg.l-1 ; functional iron deficiency as ferritin 30-100 µg.l-1 or transferrin saturation < 20%; and the remainder as non-iron deficient. Interactions were estimated using generalised linear models that included different subgroup indicators of baseline iron status. Co-primary endpoints were blood transfusion or death and number of blood transfusions, from randomisation to 30 days postoperatively. Secondary endpoints included peri-operative change in haemoglobin, postoperative complications and length of hospital stay. Most patients had iron deficiency (369/452 [82%]) at randomisation; one-third had absolute iron deficiency (144/452 [32%]) and half had functional iron deficiency (225/452 [50%]). The change in pre-operative haemoglobin with intravenous iron compared with placebo was greatest in patients with absolute iron deficiency, mean difference 8.9 g.l-1 , 95%CI 5.3-12.5; moderate in functional iron deficiency, mean difference 2.8 g.l-1 , 95%CI -0.1 to 5.7; and with little change seen in those patients who were non-iron deficient. Subgroup analyses did not suggest that intravenous iron compared with placebo reduced the likelihood of death or blood transfusion at 30 days differentially across subgroups according to baseline ferritin (p = 0.33 for interaction), transferrin saturation (p = 0.13) or in combination (p = 0.45), or for the number of blood transfusions (p = 0.06, 0.29, and 0.39, respectively). There was no beneficial effect of the use of intravenous iron compared with placebo, regardless of the metrics to diagnose iron deficiency, on postoperative complications or length of hospital stay.
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Anemia Ferropénica , Deficiencias de Hierro , Humanos , Anemia Ferropénica/tratamiento farmacológico , Anemia Ferropénica/prevención & control , Anemia Ferropénica/complicaciones , Cuidados Preoperatorios/métodos , Hemoglobinas/análisis , Complicaciones Posoperatorias/prevención & control , Ferritinas/uso terapéutico , TransferrinasRESUMEN
Although immunotherapy of hepatocellular carcinoma using immune checkpoint inhibitors has achieved certain success, only a subset of patients benefits from this therapeutic strategy. The combination of immunostimulatory chemotherapeutics represents a promising strategy to enhance the effectiveness of immunotherapy. However, it is hampered by the poor delivery of conventional chemotherapeutics. Here, it is shown that H-ferritin nanocages loaded with doxorubicin (DOX@HFn) show potent chemo-immunotherapy in hepatocellular carcinoma tumor models. DOX@HFn is constructed with uniform size, high stability, favorable drug loading, and intracellular acidity-driven drug release. The receptor-mediated targeting of DOX@HFn to liver cancer cells promote cellular uptake and tumor penetration in vitro and in vivo. DOX@HFn triggers immunogenic cell death to tumor cells and promotes the subsequent activation and maturation of dendritic cells. In vivo studies in H22 subcutaneous hepatoma demonstrate that DOX@HFn significantly inhibits the tumor growth with >30% tumors completely eliminated, while alleviating the systemic toxicity of free DOX. DOX@HFn also exhibits robust antitumor immune response and tumoricidal effect in a more aggressive Hepa1-6 orthotopic liver tumor model, which is confirmed by the in situ magnetic resonance imaging and transcriptome sequencing. This study provides a facile and robust strategy to improve therapeutic efficacy of liver cancer.