Progression of a corticotroph tumour during durable medical therapy with osilodrostat in a patient with persistent Cushing's disease.

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Current Status of Renal Anemia Pharmacotherapy-What Can We Offer Today.

Chronic kidney disease (CKD) is one of the fastest-growing major causes of death internationally. Better treatment of CKD and its complications is crucial to reverse this negative trend. Anemia is a frequent complication of CKD and is associated with unfavorable clinical outcomes. It is a devastating complication of progressive kidney disease, that negatively affects also the quality of life. The prevalence of anemia increases in parallel with CKD progression. The aim of this review is to summarize the current knowledge on therapy of renal anemia. Iron therapy, blood transfusions, and erythropoietin stimulating agents are still the mainstay of renal anemia treatment. There are several novel agents on the horizon that might provide therapeutic opportunities in CKD. The potential therapeutic options target the hepcidin-ferroportin axis, which is the master regulator of iron homeostasis, and the BMP-SMAD pathway, which regulates hepcidin expression in the liver. An inhibition of prolyl hydroxylase is a new therapeutic option becoming available for the treatment of anemia in CKD patients. This new class of drugs stimulates the synthesis of endogenous erythropoietin and increases iron availability. We also summarized the effects of prolyl hydroxylase inhibitors on iron parameters, including hepcidin, as their action on the hematological parameters. They could be of particular interest in the out-patient population with CKD and patients with ESA hyporesponsiveness. However, current knowledge is limited and still awaits clinical validation. One should be aware of the potential risks and benefits of novel, sophisticated therapies.

Cerebrospinal Fluid and Blood CX3CL1 as a Potential Biomarker in Early Diagnosis and Prognosis of Dementia.

BACKGROUND: A growing body of evidence highlights the crucial role of neuroinflammation and chemokine involvement in cognitive impairment pathophysiology. Fractalkine (CX3CL1) appears to be a relevant causative factor in the development of dementia, particularly at the early stages of the disease. However, limited data are available on the levels of CX3CL1 in the cerebrospinal fluid (CSF) and blood. Additionally, to date, its utility as a biomarker for MCI or AD has not been studied. OBJECTIVE: The aim of the present study was to evaluate the clinical utility of CX3CL1 in the early diagnosis of cognitive impairment. We also compared the diagnostic usefulness of CX3CL1 with other biomarkers associated with neuroinflammation. METHODS: A total of 60 patients with cognitive impairment, including 42 patients with AD and 18 subjects with MCI, as well as 20 cognitively healthy controls were enrolled in the study. CSF and blood concentrations of CX3CL1, CCL-2, and YKL-40 were measured by ELISA. RESULTS: Significantly higher CSF and blood concentrations of CX3CL1 were observed in MCI and AD patients compared to older individuals without cognitive impairment. The increase in the levels of CX3CL1 and YKL-40 in non-demented subjects was associated with MCI. The area under the ROC curve for CX3CL1 in MCI subjects was larger in comparison to classical AD markers. CONCLUSION: Presented results indicate a crucial role of CX3CL1 in the pathology of cognitive impairment and the potential usefulness of this protein in the early diagnosis of MCI and AD.

Iron, ferroptosis, and new insights for prevention in acute kidney injury.

Acute kidney injury (AKI) is a very common condition with high morbidity and mortality, which can be seen in 5-7% of all hospitalized patients and in up to 57% of all intensive care unit admissions. Despite recent advances in clinical care, the prevalence of AKI has been shown to increase with virtually no change in mortality. AKI is a complex syndrome occurring in a variety of clinical settings. Early detection is crucial to prevent irreversible loss of renal function. The pathogenesis of AKI is highly multifactorial and complex, including vasoconstriction, reactive oxygen species formation, cell death, abnormal immune modulators and growth factors. Emerging evidence from both human and animal studies suggests that dysregulation of iron metabolism may play a potentially important role in AKI. Therefore, targeting the iron homeostasis may provide a new therapeutic intervention for AKI. New therapeutic strategies including iron chelation therapy, targeting iron metabolism related proteins and direct inhibitors of ferroptosis are imperative to improve the outcomes of patients. Taking into consideration the complexity of AKI, one intervention may not be enough for therapeutic success. Future preclinical studies in animal disease models followed by well-designed clinical trials should be conducted to extend findings from animal AKI models to humans.