BACKGROUND:Pain in knee osteoarthritis (KOA) often shows a limited correlation with radiographic severity, complicating clinical assessment and highlighting the relevance of central pain mechanisms. Functional magnetic resonance imaging (fMRI) enables the investigation of brain regions such as the amygdala and nucleus accumbens, which are increasingly recognized as key components of the affective-motivational dimension of chronic pain and may show differential activation across clinical treatment contexts. This study is part of the HOLOA Project (Clinical and virtual examination of patients for holistic and objective description of the osteoarthritis progression mechanisms). METHODS:We conducted a cross-sectional observational study nested within the HOLOA cohort. Thirty-one patients with KOA (20 managed conservatively [CM] and 11 observed in the surgical treatment context) with Kellgren Lawrence (KL) grades 2-3 were included. Participants underwent two fMRI paradigms involving pressure stimulation (Knee Interline and Tibial Surface tests). Clinical assessment included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS), and Numeric Rating Scale (NRS). Group comparisons and correlation analyses were performed to examine associations between clinical measures and brain activation patterns. RESULTS:Groups were broadly comparable with no statistically significant differences in demographic or radiographic severity measures. These patients showed higher WOMAC and PCS scores, indicating greater functional impairment and pain catastrophizing. Across the whole cohort, painful stimulation elicited robust activation of classical pain-processing regions, while no significant amygdala or nucleus accumbens activation was observed at the group level. However, nucleus accumbens activity was positively associated with PCS scores. In between-group analyses, patients observed in the surgical treatment context exhibited significant bilateral amygdala activation during Tibial Surface stimulation, which was absent in the conservatively managed group, and reported higher post-test NRS scores. CONCLUSION:Limbic system activation and pain catastrophizing were associated with the surgical treatment context in patients with knee osteoarthritis within a similar range of radiographic severity. The observed involvement of the amygdala and nucleus accumbens underscores the relevance of affective-motivational and cognitive processes in chronic KOA pain. These findings support the value of integrating clinical, psychological, and neurobiological perspectives when interpreting symptom burden and treatment context in knee osteoarthritis.
Epidemiological data from Sapin are lacking, especially in a publication relating Spanish data and prevalence of programmed cell death ligand-1 (PD-L1) expression. This study aimed to evaluate the prevalence of PD-L1 expression by Combined Positive Score (CPS) ≥ 5 in patients with advanced esophagogastric adenocarcinoma (aEGAC) in Spain. This observational, retrospective, and multicenter study collected sociodemographic and clinical data from adult patients with locally advanced unresectable, recurrent, or metastatic EGAC across 21 centers in the AGAMENON-SEOM registry. CPS PD-L1 expression was centrally analyzed using the IHC 28–8 pharmDx. A total of 166 patients were included, with 144 valid and evaluable samples. The primary tumor locations were stomach (70.1
To describe the genetic mutation and its action mechanism in patients with compatible diagnosis of fundus albipunctatus (FAP). We describe the clinical evolution and genetic findings of two female Spanish children of 14 and 16 years old who have been followed at the children’s hospital Sant Joan de Déu (Barcelona, Spain). Nyctalopia without detectable field constriction was the initial symptom. Retinal fundus was compatible with FAP or retinitis punctata albescens (RPA). We have registered ophthalmological examination from each visit, including visual acuity, visual field assessment, wide-field fundoscopy imaging, fundus autofluorescence and optical coherence tomography. Full-field electroretinogram (ERG) was also performed. DNA sampling was analysed by next-generation sequency (NGS). Compound heterozygous pathogenic variants in the LRAT gene were identified in both children. Interestingly, these were the same two pathogenic variants, despite the families being unrelated. No additional genetic alterations were found that could explain the disease in our patients. To the best of our knowledge, up to the present time, only a single clinical case involving a genetic variant in the LRAT gene leading to an FAP phenotype has been reported in the literature. LRAT genetic variants, despite their low frequency in clinical practice, seem to lead to a FAP-like phenotype, in addition to their established association with Leber congenital amaurosis (LCA) and Early Onset Severe Retinal Dystrophy (EOSRD).
BACKGROUND:Patients with muscle-invasive bladder cancer who are ineligible for cisplatin-based chemotherapy proceed directly to radical cystectomy with pelvic lymph-node dissection. Perioperative therapy may improve outcomes in this population. METHODS:In this phase 3, open-label trial, participants with muscle-invasive bladder cancer who were ineligible for or declined cisplatin-based chemotherapy were randomly assigned to perioperative (neoadjuvant and adjuvant) enfortumab vedotin, an antibody-drug conjugate directed at nectin-4, plus pembrolizumab and surgery (9 total cycles of enfortumab vedotin [1.25 mg per kilogram of body weight on days 1 and 8] plus 17 total cycles of pembrolizumab [200 mg on day 1 every 3 weeks], with surgery after 3 cycles) or surgery alone (control). The primary end point was event-free survival. Key secondary end points were overall survival and pathological complete response (absence of viable tumor after surgical resection). Other secondary end points included safety. RESULTS:A total of 344 participants underwent randomization (170 in the enfortumab vedotin-pembrolizumab group and 174 in the control group). At data cutoff, median follow-up was 25.6 months (range, 11.8 to 53.7). Surgery was performed in 87.6% of participants in the enfortumab vedotin-pembrolizumab group and in 89.7% in the control group. At 2 years, estimated event-free survival was 74.7% in the enfortumab vedotin-pembrolizumab group and 39.4% in the control group (hazard ratio for an event or death, 0.40; 95% confidence interval [CI], 0.28 to 0.57; two-sided P<0.001); estimated overall survival was 79.7% and 63.1% (hazard ratio for death, 0.50; 95% CI, 0.33 to 0.74; two-sided P<0.001). A pathological complete response had occurred in 57.1% and 8.6% of the participants (estimated difference, 48.3 percentage points; 95% CI, 39.5 to 56.5; two-sided P<0.001). Adverse events occurred in all participants in the enfortumab vedotin-pembrolizumab group (grade ≥3, 71.3%; grade ≥3 drug-related, 45.5%) and in 64.8% in the control group (grade ≥3, 45.9%). CONCLUSIONS:Perioperative enfortumab vedotin plus pembrolizumab and surgery led to significantly better event-free and overall survival outcomes and a greater percentage of participants with pathological complete response than surgery alone in a predominantly cisplatin-ineligible population with muscle-invasive bladder cancer. Safety was also assessed. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; KEYNOTE-905 ClinicalTrials.gov number, NCT03924895.).
Since the publication of the previous consensus document on point-of-care lung ultrasound (PoCLUS) in 2012, new evidence has emerged. This consensus aims to update current recommendations by focusing on the clinical applications of PoCLUS as a standalone tool, while acknowledging that this focused approach represents a necessary preliminary step toward its effective integration with other organ-specific ultrasound examinations and complementary diagnostic modalities. A Delphi-based consensus process was conducted under the supervision of a Steering Committee (five voting members) and a Delphi Committee (two non-voting members). Experts were selected according to strict predefined criteria based on highly impactful scientific output and were assigned to specific domains. A structured literature review covering publications from 2012 to 2025 was performed. Statements were drafted, discussed through multiple online rounds, and iteratively refined. Anonymous voting was conducted for each statement using a predefined agreement threshold (80
