Heart failure (HF) prognosis, particularly readmission and mortality, remains poor irrespective of advances in its management. Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor-beta (TGF-β) superfamily that arises as a promising biomarker to improve HF management, still despite two decades of extensive investigation some issues remain controversial. We performed a search in PubMed using the following Medical Subject Headings (MeSH) to identify relevant studies published in the last five years (after the latest updates of the guidelines by major Scientific Societies): “Growth differentiation factor-15 (GDF-15)”, “heart failure”, “prognosis” and “diagnosis”. The search was supplemented by data previous to this period, considered of utmost importance. A total of 115 articles written in English were retrieved. Extensive evidence supports GDF-15 as an independent predictor of adverse outcomes across the heterogeneous HF spectrum and its addition to risk scores based on traditional biomarkers improves prognostic power. However, limited tissue specificity restricts its diagnostic value. Tailored treatment strategies and its role as a therapeutic target remain speculative, as the effect of HF therapies on GDF-15 levels is unclear and clinical trials have been unsuccessful. Large prospective studies are needed to validate its reliability for routine clinical use.

Heart failure (HF) prognosis, particularly readmission and mortality, remains poor irrespective of advances in its management. Growth differentiation factor 15 (GDF-15) is a member of the transforming growth fac-tor-beta (TGF-β) superfamily that arises as a promising biomarker to improve HF management, still despite two decades of extensive investigation some issues remain controversial. We performed a search in PubMed using the following Medical Subject Headings (MeSH) to identify relevant studies published in the last five years (after the latest updates of the guidelines by major Scientific Societies): “Growth Differentiation Fac-tor 15 (GDF-15)”, “heart failure”, “prognosis” and “diagnosis”. The search was supplemented by data pre-vious to this period, considered of utmost importance. A total of 105 articles written in English were re-trieved. Extensive evidence supports GDF-15 as an independent predictor of adverse outcomes across the heterogeneous HF spectrum and its addition to risk scores based on traditional biomarkers improves prog-nostic power. However, limited tissue specificity restricts its diagnostic value. Tailored treatment strategies and its role as a therapeutic target remain speculative, as the effect of HF therapies on GDF-15 levels are unclear and clinical trials have been unsuccessful. Large prospective studies are needed to validate its relia-bility for routine clinical use.

Background: Drug-induced liver injury is an uncommon, idiosyncratic adverse reaction with heterogeneous clinical presentations, ranging from asymptomatic transaminase elevations to acute liver failure. Sodium-glucose cotransporter 2 inhibitors, widely prescribed for type 2 diabetes due to their glycaemic, cardiovascular, and renal benefits, are generally considered safe to the liver. Nonetheless, rare cases of cholestatic and hepatocellular drug-induced liver injury have been reported, highlighting the need for vigilance and systematic evaluation when liver dysfunction occurs in patients receiving these agents. Case report: We describe a 56-year-old man with type 2 diabetes and chronic schizophrenia who developed cholestatic liver injury 36 days after initiating empagliflozin 10 mg od. The patient presented with jaundice, dark urine, and pale stools, with laboratory findings revealing elevated bilirubin, gamma-glutamyl transferase, and alkaline phosphatase disproportionate to alanine aminotransferase. Comprehensive work-up excluded viral, autoimmune, metabolic, and obstructive causes. Imaging confirmed intrahepatic cholestasis without biliary obstruction. Causality assessment using the Roussel Uclaf Causality Assessment Method, Maria and Victorino and Naranjo scores indicated probable adverse drug reaction. Liver biopsy demonstrated acute cholestatic injury with portal inflammatory infiltrates and ductular reaction, consistent with drug-related pathology. Empagliflozin withdrawal led to gradual clinical and biochemical recovery. Conclusion: Empagliflozin can, in rare cases, trigger idiosyncratic cholestatic drug-induced liver injury, even in patients with cirrhosis. Early recognition, prompt drug withdrawal, and systematic evaluation are essential. This case adds to the limited literature on sodium-glucose cotransporter 2 inhibitor-associated hepatotoxicity.

Background: Spontaneous intracranial hypotension (SIH) is a rare, underdiagnosed cause of secondary headache due to cerebrospinal fluid (CSF) leakage. While typically presenting with orthostatic headache, atypical manifestations may mimic infectious or inflammatory diseases. Case description: A 45-year-old man presented with acute alteration of consciousness, expressive aphasia, and nuchal rigidity after 1 month of orthostatic occipital headache. Brain magnetic resonance imaging (MRI) showed diffuse pachy- and leptomeningeal enhancement initially interpreted as infectious meningoencephalitis. Lumbar puncture revealed turbid, blood-stained CSF with elevated protein and neutrophilic pleocytosis, but microbiological and autoimmune studies were negative. Neurological symptoms improved with conservative management (bed rest, hydration, analgesia), and follow-up imaging confirmed full resolution. Retrospective neuroradiological review reclassified findings as SIH. Conclusion: SIH can mimic infectious meningoencephalitis both clinically and in CSF appearance. Recognition of preceding orthostatic headache and characteristic MRI features is essential to avoid unnecessary antimicrobial therapy and invasive diagnostic procedures.

Background: Systemic mastocytosis is a rare clonal disorder characterised by the proliferation and accumulation of mast cells in one or more extracutaneous organs. Its clinical presentation is highly heterogeneous and aggressive variants may mimic metastatic malignancy, leading to significant diagnostic delay. Case description: We report the case of an 83-year-old woman presenting with fatigue, weight loss, low-grade evening fever and night sweats over two months. Laboratory evaluation showed pancytopenia, mild inflammatory response, and normal hepatic and renal function. Imaging studies revealed diffuse osteoblastic lesions throughout the axial skeleton, initially interpreted as bone metastases from an unknown primary tumour. Further imaging demonstrated hepatosplenomegaly and prominent periportal lymph nodes. Bone biopsy of an iliac lesion revealed replacement of marrow by sheets of epithelioid mast cells (CD117+, tryptase, CD68+). Serum tryptase was elevated (56.3 ng/ml), fulfilling World Health Organization (WHO) diagnostic criteria for systemic mastocytosis. The patient was diagnosed with aggressive systemic mastocytosis and started cladribine therapy with antimicrobial prophylaxis, with progressive improvement of constitutional symptoms and she remains under follow-up in the haematology department. Discussion: Aggressive systemic mastocytosis presenting with diffuse osteoblastic bone lesions is extremely uncommon and may closely mimic metastatic carcinoma, particularly of breast or prostate origin. Diagnosis requires a high index of suspicion and confirmation through histopathology, immunophenotyping and serum tryptase measurement. KIT mutations, especially D816V, are frequent but were absent in this case. Conclusion: This case highlights the importance of considering systemic mastocytosis in the differential diagnosis of osteoblastic bone disease, particularly in elderly patients with constitutional symptoms and unexplained cytopenias. Early recognition allows timely initiation of appropriate therapy and avoids unnecessary oncology investigations.

Heart failure (HF) is frequently associated with iron deficiency and anemia, negatively impacting patient outcomes. This study aimed to investigate the contribution of genetic variation in iron metabolism-related genes to biochemical and hematological phenotypes in HF. An HF population of 182 patients with functional iron deficiency (ID) and anemia was stratified by sex and heart failure subtype, including HF with reduced ejection fraction (HFrEF) and HF with non-reduced ejection fraction (HFnrEF). Genetic variants in HFE (rs1799945), SLC40A1 (rs1439816, rs2304704), and TMPRSS6 (rs855791) were evaluated. Variants in HFE and SLC40A1 were associated with differences in serum iron, ferritin, transferrin saturation, hemoglobin, and RDW. The phenotypic impact of these variants was modulated by sex and heart failure subtype, highlighting the influence of iron availability, inflammatory burden, and erythropoietic demand. In contrast, no significant associations were observed for the TMPRSS6 variant. In conclusion, genetic variation in key regulators of iron metabolism contributes to the heterogeneity of iron-related biochemical and hematological phenotypes in HF. These findings emphasize the interplay between genetic background, sex, and heart failure physiology and support the relevance of personalized approaches to iron assessment and management in heart failure.