INTRODUCTION:Tumor-induced osteomalacia is a rare paraneoplastic disorder caused by excess fibroblast growth factor 23 (FGF23), most often produced by phosphaturic mesenchymal tumors. Delayed diagnosis may result in severe metabolic and skeletal complications. CASE PRESENTATION:We report the case of a 32-year-old woman with a three-year history of progressive weakness and a rapidly enlarging thoracic mass. Imaging revealed an 18 × 13 cm highly vascularized thoracic lesion with multiple lytic bone metastases. Laboratory evaluation showed severe hypophosphatemia (0.9 mg/dL), renal phosphate wasting (fractional excretion of phosphate 24.5%), elevated intact parathyroid hormone, low vitamin D levels, and markedly increased serum FGF23 (7926 kRU/L). Histopathological examination and immunohistochemistry demonstrated a malignant phosphaturic mesenchymal tumor with positivity for CD56, SATB2, and SSTR2A. DISCUSSION:This case highlights the aggressive clinical behavior that malignant phosphaturic mesenchymal tumors may exhibit, including extensive local invasion, metastatic disease, and profound metabolic derangements. The diagnosis of tumor-induced osteomalacia requires a high index of suspicion and an integrated approach combining biochemical evaluation, functional imaging, and detailed pathological assessment. CONCLUSIONS:Tumor-induced osteomalacia should be considered in patients with persistent hypophosphatemia and phosphate wasting. Early recognition is essential, as complete surgical resection remains the only curative option. In advanced or unresectable disease, management is challenging and may be limited by tumor burden and access to targeted therapies, including anti-FGF23 agents, which offer biochemical and symptomatic benefit in selected cases.
Abstract Introduction Pulmonary vein isolation (PVI) has been demonstrated to reduce mortality in patients with heart failure (HF) and atrial fibrillation (AF). However, the safety of PVI in patients with acute HF decompensation has not been extensively studied. Purpose To determine the efficacy and safety of PVI during hospitalizations for acute HF decompensation (AHFD). Methods Patients with HF undergoing PVI between January 2022 and May 2025 were included. All patients underwent PVI using point-by-point radiofrequency ablation under general anesthesia using high-frequency low-tidal volume ventilation, performing wide antral catheter ablation using 40W and an irrigation flow rate of 15 mL/min. All ablations were performed guided by lesion indexes (lesion severity index 5 or ablation index of 550 for the anterior wall and lesion severity index of 4 or ablation index of 400 for the posterior wall), with a targeted interlesion distance of 3mm. Results A total of 134 patients (female n=36, age 65±9 years, AHFD n=39) were included (Table 1). Patients with AHFD less frequently had paroxysmal AF (15% vs. 48%, p =0.005), were more frequently diagnosed with new onset HF (31% vs. 8%, p 0.002), had a lower left ventricular ejection fraction (30% vs. 37%, p<0.001), and larger left atrial volumes (56 vs. 47ml/m2, p 0.018). Procedural time was significantly longer (143 vs. 140 min, p 0.03) in patients with acute decompensation; however, there were no cases of pulmonary edema or volume overload. There were 6 procedure-related complications, without significant differences between groups (7% vs. 13% p=0.257): 5 were related to vascular access, with one patient in the no AHFD group presenting with pericardial effusion requiring drainage 1 week after the procedure. After a median follow-up of 441[272-624] days, there were no significant differences in the risk of all atrial arrhythmia recurrence in the AHFD vs the no AHFD groups (HR 0.95, 95% CI 0.31-2.93; Log rank P 0.93)(Figure 1). Significant improvements in LVEF were observed in both groups. Conclusions Pulmonary vein isolation can be performed safely in patients hospitalized for acute HF hospitalization, even though patients with AHFD tend to have more severe structural cardiac compromise. During follow-up, there are no significant differences in the risk of all-atrial arrhythmia recurrence between groups, with significant improvements in LVEF in both groups. Given the benefits of PVI in patients with HF, AHFD should not be considered a contraindication to perform PVI.Table 1Figure 1
Alzheimer's disease is characterized by amyloid-β and tau protein accumulation. Growing evidence suggests that white matter degeneration contributes to disease progression. Despite Alzheimer's disease being more prevalent in women, understanding of sex differences in white matter microstructure across the Alzheimer's disease continuum remains limited. This study investigated sex-specific patterns of white matter integrity in individuals genetically predisposed to autosomal dominant Alzheimer's disease. We analysed data from 63 individuals (30 presenilin-1 glutamic acid to Alanine at codon 280 (PSEN1 E280A) mutation carriers, 33 non-carriers) from a Colombian kindred with early-onset autosomal dominant Alzheimer's disease. Participants underwent diffusion-weighted imaging, amyloid and tau positron emission tomography and cognitive assessment. Using fixel-based analysis, we examined fibre density, fibre-bundle cross-section and combined fibre density and cross-section across major white matter tracts. Linear regression models assessed sex differences in white matter microstructure and examined how sex moderated relations between pathological burden, white matter integrity and cognitive performance. Females showed trends towards higher fibre cross-section than males in the anterior thalamic radiation (β = 0.057, P = 0.004), forceps minor of the corpus callosum (β = 0.047, P = 0.012) and inferior fronto-occipital fasciculus (β = 0.030, P = 0.015), but lower values in the cingulum (cingulate gyrus portion) (β = -0.07, P = 0.031). Sex appeared to moderate the association between pathology and white matter in multiple tracts. However, these findings did not survive correction for multiple comparisons and should be interpreted as exploratory. In the right temporal superior longitudinal fasciculus, females showed relatively preserved integrity compared to males as tau burden increased (β = 0.23, P = 0.016), while males exhibited greater amyloid-β-associated disruption than females in the uncinate fasciculus (β = -0.14, P = 0.05). Sex also moderated relations between white matter integrity and cognition, with males showing stronger structure-function coupling than females in tracts such as the cingulum (hippocampus portion), forceps major and corticospinal tract. Our findings revealed significant sex-specific patterns of white matter microstructural alterations in autosomal dominant Alzheimer's disease, with females showing preserved fibre cross-section in key tracts and slower rates of white matter deterioration with increasing tau pathology in memory-related circuits, whereas males demonstrated advantages in structure-function coupling. These data highlight the importance of considering sex differences in understanding white matter alterations in Alzheimer's disease and suggest the potential utility of considering sex differences in the development of personalized interventions and clinical trials for persons with Alzheimer's disease.
Introduction and Objectives Metabolic dysfunction-associated steatotic liver disease (MASLD) has a well-established hereditary component, yet the risk of hepatic fibrosis in extended family networks remains unexplored. This study aimed to explore the prevalence of significant hepatic fibrosis in biological relatives of patients with MASLD-related cirrhosis and to identify associated risk factors. Materials and Methods This exploratory, multicenter, cross-sectional study enrolled 165 biological relatives of 58 index cases with MASLD-related cirrhosis across three hepatology centers. Relatives were classified by coefficient of genetic relationship into first-degree -parents, children, siblings- (n=114) and second/third-degree relatives -grandparents, grandchildren, aunts, uncles, nephews, or nieces - (n=51). Significant hepatic fibrosis was defined as liver stiffness measurement 8.0 kPa by transient elastography. Univariate logistic regression identified associated variables. Results Significant hepatic fibrosis was detected in 8.5% (14/165) of biological relatives, a rate exceeding general population estimates. Abdominal obesity by ATP III criteria was the only independent predictor of significant fibrosis (OR 3.3; 95% CI 1.008–11.19; p=0.049). No significant associations were observed for diabetes mellitus, dyslipidemia, or other cardiometabolic risk factors. Prevalence was comparable between first-degree and second/third-degree relatives (8.8% vs. 7.8%; p=0.84). Conclusions This exploratory study provides preliminary evidence that hepatic fibrosis affects extended family networks of MASLD-related cirrhosis patients at rates exceeding general population estimates, with central adiposity as the primary associated factor. These findings justify adequately powered confirmatory studies incorporating genetic characterization to refine family screening strategies in high-risk population
