Treatment Outcomes in Patients with Advanced Fibrolamellar Hepatocellular Carcinoma Under Systemic Treatment: Analysis of Clinical Characteristics, Management, and Radiomics.

Purpose: Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare primary liver malignancy often diagnosed at advanced stages. While there are limited data on the efficacy of specific agents, we aim to report outcomes of patients treated with systemic therapies and explore prognostic factors. Patients and Methods: Medical records of patients treated between 2010 and 2022 were reviewed. Treatments were defined after multidisciplinary assessment. Descriptive statistics were used for baseline demographics. Time-to-event outcomes were estimated using the Kaplan-Meier method, compared by log-rank and adjusted by a regression model. Radiomic features (including size, shape, and texture) of the primary lesion were extracted and dimensionality reduced. An unsupervised Gaussian Mixture Model (GMM) clustering was performed, and survival was compared between clusters. Results: We identified 23 patients: 12 males, with a median age of 23.6 years. At diagnosis, 82.6% had metastases, most frequently to the lungs (39.1%), lymph nodes (39.1%), and peritoneum (21.7%). Patients received a median of three lines (1-8) of treatment, including different regimens. Sorafenib (39.1%), capecitabine (30.4%), and capecitabine/interferon (13%) were the most used first-line regimens. The median time-to-failure was 3.8 months (95% CI: 3.2-8.7). Capecitabine + interferon (42.1%) and platinum combinations (39.1%) were the most used second-line regimens, with a time-to-failure of 3.5 months (95% CI: 1.5-11.6). Median overall survival was 26.7 months (95% CI: 15.1-40.4). A high baseline neutrophil-to-lymphocyte ratio (NLR) was associated with worse survival (p=0.02). Radiomic features identified three clusters, with one cluster (n=6) having better survival (40.4 vs 22.6 months, p=0.039). Tumor sphericity in the arterial phase was the most relevant characteristic associated with a better prognosis (accuracy=0.93). Conclusion: FLHCC has unique features compared to conventional HCC, including young onset, gender balance, and absence of hepatopathy. Systemic therapies can provide encouraging survival, but lack of uniformity precludes defining a preferable regimen. Radiomics and NLR were suggested to correlate with prognosis and warrant further validation.

Association study in Alzheimer’s disease of single nucleotide polymorphisms implicated with coffee consumption

There is evidence from animal and in vitro models of the protective effects of caffeine in Alzheimer’s disease. The suggested mechanisms through which caffeine may protect neurons against Alzheimer’s disease pathology include the facilitation of beta-amyloid clearance, upregulation of cholinergic transmission, and increased neuronal plasticity and survival. Epidemiological studies support that Alzheimer’s disease patients consume smaller amounts of coffee beverages throughout their lives as compared to age-matched cognitively healthy individuals. Objective: The aim of the present study was to determine whether the negative association between Alzheimer’s disease and coffee consumption may be influenced by a common genetic predisposition, given the fact that the pattern of coffee consumption is determined by both environmental and genetic factors. Method: We conducted an in silico search addressing the association between genetic polymorphisms related to coffee consumption and the diagnosis of Alzheimer’s disease. We further investigated the interactions between genes located in regions bearing these polymorphisms. Results: Our analysis revealed no evidence for a genetic association (nor interaction between related proteins) involving coffee consumption and Alzheimer’s disease. Discussion: The negative association between Alzheimer’s disease and coffee consumption suggested by epidemiological studies is most likely due to environmental factors that are not necessarily regulated by genetic background...