Instituto de Investigación Sanitaria La Fe

Pancreatic adenocarcinoma (PDAC) is characterized by its poor prognosis. Cytology is essential for diagnostic confirmation and ancillary studies. The endoscopic ultrasound (EUS) set a precedent, facilitating cytological sampling through fine-needle aspiration (FNA), with a sensitivity of 93% and a specificity of 95%. In this work, we analyzed all EUS-guided pancreatic FNAs performed at our center over 2014-2025 and compared the cytological findings with the corresponding surgical specimen results. Observational, descriptive, and retrospective study of all EUS-guided pancreatic FNAs performed at our center (2014-January 2025) in patients ≥ 18 years and their corresponding surgical specimens. Samples were obtained using a linear echoendoscope and 25G needles, processed with Romanowsky and Papanicolaou stains, and cell blocks prepared for immunohistochemistry. Cytological diagnoses followed WHO criteria; histology from surgical specimens served as the reference standard. Statistical analysis was performed using SPSS v.22 with p < 0.05 considered significant. One hundred and sixty-three EUS-guided pancreatic FNAs were performed and 34 patients underwent surgical treatment (20.8%), 31 of them (91.2%) with a cytological diagnosis of malignancy. Thirty-three patients had malignant lesions (97%) in the surgical specimen. Cytology showed a sensitivity of 96.9%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 50%. Cyto-histological correlation was 91.2% with a κ = 0.654 (p < 0.001). Cytopathologists' expertise was statistically significant (p < 0.001). Cytology is highly reliable for confirming malignancy. Final management will be multidisciplinary.

The incidence of cancer-associated venous thromboembolism (CAT) has risen in recent decades, underscoring the need for novel risk biomarkers and mechanistic insights. MicroRNAs (miRNAs) have emerged as promising biomarkers for various diseases, with elevated miRNA-145-5p (miR-145-5p) levels linked to reduced venous thromboembolism (VTE) risk. We aimed to investigate the association between plasma miR-145-5p levels and risk of future VTE related to (CAT) and unrelated to cancer (non-CAT). Plasma miR-145-5p levels were measured in a case cohort derived from the Trøndelag Health Study (HUNT3; N = 50 807). The study included 455 VTEs (95 CATs), occurring during 9 years of follow-up, and 1740 randomly sampled age-weighted subcohort participants. VTEs were classified as CAT if they occurred within 1 year before or 2 years after a cancer diagnosis. Multivariable adjusted hazard ratios (HRs) for CAT and non-CAT were estimated using weighted Cox regression, with cancer modeled as a time-varying covariate. Increasing miR-145-5p levels were associated with lower risk of CAT (HR per 1 SD, 0.70; 95% CI, 0.52-0.96) and non-CAT (HR, 0.81; 95% CI, 0.72-0.91). Individuals in the highest miR-145-5p quartile had lower risk of both CAT (HR, 0.55; 95% CI, 0.25-1.20) and non-CAT (HR, 0.48; 95% CI, 0.33-0.69) than those in the lowest quartile. High plasma miR-145-5p levels were associated with lower risk of CAT and non-CAT, suggesting that miR-145-5p has the potential to serve as a risk biomarker for CAT.

Abstract Cardiorespiratory fitness (CRF) is a strong indicator of overall physical health, but its relevance for mental and neurocognitive health across the life course remains unclear. Here we synthesize evidence from cohort studies examining the associations between CRF and the risk of mental and neurocognitive disorders across all age groups in the general population. Twenty-seven studies comprising 4,007,638 individuals were included. Compared with low CRF, high CRF was associated with a reduced risk of depression (hazard ratio (HR) = 0.64; 95% confidence interval (CI), 0.56–0.74), all-cause dementia (HR = 0.61; 95% CI: 0.55–0.68) and psychotic disorders (HR = 0.71; 95% CI: 0.65–0.77) in adults. A one metabolic equivalent of task (1 MET; 3.5 ml kg −1 min −1 ) higher level of CRF was associated with lower risks of depression (HR = 0.95; 95% CI: 0.92–0.98) and all-cause dementia (HR = 0.81; 95% CI: 0.67–0.98). Overall certainty of evidence ranged from very low to moderate. These findings suggest that CRF may be a useful marker for identifying adults at increased risk of depression, dementia and psychotic disorders, highlighting the need for further large-scale longitudinal studies.

Nusinersen was the first disease modifying treatment approved for 5q spinal muscular atrophy (SMA). Long-term results of broad populations, particularly for adolescents and adults, remain limited. We conducted a population-based, ambispective observational study of all SMA patients living in the Valencian Community (Spain) between September 2017 and December 2022 and follow-up until December 2025. Demographic, clinical and motor outcomes using revised SMA Functional Composite Score (SMA-FCR) were collected. Patients were classified as responders or non-responders. The risk for nusinersen discontinuation was assessed with a Bayesian model, and SMA-FCR trajectories with mixed linear regression. Of 72 patients included, 18 were &lt;12 years old (all treated with nusinersen) and 54 were ≥12 years (28 treated; 26 untreated) at the baseline visit. After a median of 7 years, all patients &lt;12 years were classified as responders versus 68% of patients ≥12 years. Discontinuation rates were 11% in children compared to75% in the older cohort. In patients ≥12 years, reasons for discontinuation included: treatment burden (71%), and loss(53%) or lack of benefit (43 %). Lower baseline SMA-FCR (expEstimate= 0.84 [0.718,0.93], prob:1) and older age (expEstimate=1.028 [1.011,1.055], prob:1) independently predicted higher discontinuation risk. Sustained nusinersen treatment was independently associated with SMA-FCR increase, while untreated and discontinued patients showed slight deterioration over time. In this long-term population-based study, nusinersen use and persistence was high in children but declined significantly after age 12 due to treatment burden and limited efficacy. However, a proportion of adolescents and adults (those younger and with higher baseline function) experienced sustained benefit.

Background/Objectives: Senescence has been recently described in brain cells following ischemic stroke. The potential of targeting senescence as an effective therapeutic approach in the treatment of ischemic stroke requires further investigation. This study evaluated the effects of the senolytic drug navitoclax after experimental ischemic stroke. Methods: Navitoclax was injected into male young Wistar rats at doses of 10 and 30 mg/kg (i.p.). to evaluate its pharmacokinetics, cerebral levels and potential to cause thrombocytopenia. Subsequently, a second group of rats underwent 60 min of transient middle cerebral artery occlusion (tMCAO). Navitoclax (10 mg/kg, i.p.) or vehicle was injected every other day between days 3 and 13 after tMCAO. Neurofunctional performance, infarct size, and senescence markers were assessed on day 14. Results: Navitoclax (10 mg/kg) administration resulted in a maximum plasma concentration of 0.702 mg/L and half-life of 11.33 h. Additionally, a brain concentration of 0.04 ± 0.02 µg/g was detected. Moderate thrombocytopenia was induced by 10 mg/kg, and to a greater extent by 30 mg/kg. Navitoclax (6 × 10 mg/kg) improved neurofunctional impairment, as indicated by significant decrease by 66% in the total time for the tape removal test, and significantly reduced infarct area by 52% when compared to vehicle. Moreover, navitoclax significantly reduced levels of SA-β-gal (by 80%), lipofuscin (by 91%), and Checkpoint kinase 2 (Chk2; by 69%) in the ischemic hemisphere. Conclusions: Navitoclax protects the brain after ischemic stroke by improving neurofunctional outcome and reducing infarct size, which is associated with reducing senescence markers. Although moderate thrombocytopenia warrants caution, targeting senescence emerges as a promising therapeutic strategy for ischemic stroke.