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<title>RESUMEN</title> <p>A pesar de que la Práctica Basada en la Evidencia (PBE) ha estandarizado los tratamientos psicológicos, la realidad clínica sigue enfrentándose a una barrera persistente: la dificultad de traducir los resultados de ensayos clínicos grupales a la singularidad de cada paciente en contextos reales. Como respuesta, la Salud Mental de Precisión (SMP) propone una evolución del modelo actual, integrando el cuidado basado en la medición y la toma de decisiones basada en datos para ajustar la intervención a las necesidades específicas de cada persona, gracias en gran medida a desarrollos tecnológicos recientes como la Inteligencia Artificial (IA). En este contexto, el presente artículo persigue dos objetivos fundamentales. En primer lugar, sintetiza los pilares operativos de la SMP, analizando cómo la medición rutinaria y las predicciones algorítmicas pueden potenciar el juicio clínico del profesional. En segundo lugar, se introduce el proyecto NOVA (Navigating Outcomes via Analytics), un proyecto traslacional diseñado para superar las barreras actitudinales, tecnológicas, estadísticas y contextuales de la implementación de herramientas de SMP en España. Se discute sobre los pasos necesarios para cerrar la brecha entre la innovación tecnológica y la práctica asistencial en psicología, acelerando la adopción sostenible de una psicología de precisión en el mundo real.</p>

SUMMARY Aging is accompanied by profound changes in bladder function, leading to increased urinary frequency and incontinence that impair quality of life in humans and are recapitulated in mouse models. Bladder filling and emptying rely on precise mechanosensory feedback, yet how aging alters this sensory control remains unclear. PIEZO ion channels convert mechanical forces into cellular signals essential for bladder fullness sensation. Using inducible smooth-muscle specific Piezo1 deletion, we find that loss of Piezo1 attenuates aging-related bladder dysfunction. Dietary enrichment with margaric acid, a membrane-active fatty acid previously shown to inhibit PIEZO channels, reduced urinary dysfunction in aged mice. In humans, genotype–phenotype analyses reveal an association between a PIEZO1 gain-of-function variant and early-onset neuromuscular bladder dysfunction. Together, these findings define a smooth-muscle, PIEZO1-mediated mechanosensory basis for aging-related bladder dysfunction and introduce a non-invasive strategy for targeting PIEZO channels in vivo .

Purpose Mycobacterium avium complex lung disease (MAC-LD) represents the most common form of nontuberculous mycobacterial lung infection, particularly affecting women and older adults. Clinical management remains challenging, including prediction and differentiation between progressive and non-progressive disease. Overexpression of PD-1 pathways have been reported in progressive disease, and we hypothesize that PD-1 inhibition can restore antigen-specific immune responses detectable by FluoroSpot assay. Methods Peripheral blood mononuclear cells from 22 participants, including progressive and non-progressive MAC-LD patients, healthy controls, and individuals with latent tuberculosis infection (LTBI) were stimulated with nontuberculous mycobacteria and Mycobacterium tuberculosis antigens. Cytokine secretion of interferon-gamma (IFN-γ) and interleukin-2 (IL-2) were quantified using dual FluoroSpot assay, with and without PD-1 blockade. Results Progressive MAC-LD cases demonstrated significant increases in glycopeptidolipid (GPL)- and PPD-stimulated IFN-γ responses following PD-1 blockade, which was not seen in healthy controls, LTBI, or non-progressive MAC-LD patients. After GPL stimulation and in the presence of anti-PD-1, the number of IFN-γ responses increased from 25% to 75% in samples from progressive MAC-LD patients. This supports an association between PD-1–mediated T-cell dysfunction and disease progression. Mycobacterial MTB300 peptide pool antigen failed to discriminate MAC-LD from healthy controls, underscoring antigen specificity. Conclusions Our pilot study demonstrates that IFN-γ FluoroSpot assays, particularly when combining GPL or PPD stimulation and PD-1 inhibition, may help identify progressive MAC-LD. These findings also support other studies reporting that immune checkpoint dysregulation can be present in some patients with progressive and severe MAC-LD patients. Additional studies are warranted to determine its pathogenic role.

Abstract Inflammatory bowel diseases (IBD), principally Crohn’s disease (CD) and ulcerative colitis (UC), are common chronic disorders involving inflammation and often progressive tissue damage. Genome-wide association studies have mapped many risk signals, but the causal variants, effector genes and relevant cellular contexts remain difficult to resolve, limiting mechanistic interpretation and therapeutic translation. Here we performed a multi-ancestry GWAS meta-analysis of 125,992 individuals with IBD and more than 1.2 million controls, identifying 619 independent association signals (374 novel) at 420 IBD regions that account for 77–80% of SNP-based heritability. Fine-mapping resolved 81 high-confidence variants, 41 not previously reported. Although most signals were shared between CD and UC, 39% showed IBD subtype specificity, with UC signals showing stronger enrichment in functional annotations from intestinal epithelial, secretory and enteroendocrine cells, and CD showing stronger genetic correlations with circulating inflammatory biomarkers, including C-reactive protein and glycoprotein acetylation. Latent causal modelling supported a causal effect of decreased high-density lipoprotein on CD risk. By integrating bulk and single-cell eQTL and pQTL resources using colocalisation and Mendelian randomisation, together with coding-variant evidence from exome sequencing, we prioritised 664 candidate effector genes across 341 signals, including 390 newly implicated IBD genes, revealing new biological mechanisms and candidate therapeutic targets supported by human genetics.

Abstract Oligodendroglioma is a primary central nervous system tumor classified by the presence of isocitrate dehydrogenase (IDH) mutations and codeletion of 1p/19q. Here we describe the generation of an IDH-mutant 1p/19q-codeleted oligodendroglioma mouse model using in utero electroporation. We identified IDH1 R132H , PIK3CA E545K , Cic KO , Fubp1 KO and Cdkn2a KO as the optimal combination (termed Oligo Cdkn2a ) to drive fully penetrant tumors that histologically resemble human grade II/III IDH-mutant, 1p/19q-codeleted oligodendroglioma. Replacing Cdkn2a with Trp53 loss in this mouse model shifted tumor histology towards high grade astrocytoma. Oligo Cdkn2a tumors displayed metabolic and transcriptional changes associated with IDH and CIC mutations, and single cell sequencing identified a bias towards oligodendrocyte differentiation compared to an IDH wild-type glioblastoma mouse model. Oligo Cdkn2a tumors represent the first mouse model system to recapitulate the genetic, histological and transcriptional features of human IDH-mutant 1p/19q-codeleted oligodendrogliomas, offering a platform to further dissect tumor biology and test new therapeutic strategies.

PURPOSE We tested the hypothesis that adding metastasis-directed therapy (MDT) to standard-of-care (SOC) systemic therapy improves progression-free survival (PFS) among patients with oligometastatic disease. METHODS EXTEND was a multicenter randomized phase II trial. Patients with 1-5 metastases were randomly assigned to MDT + SOC versus SOC in one of the six baskets (breast, pancreas, kidney, two prostate baskets, and an other basket) with basket-specific stratification and powering. PFS, the primary end point, was prespecified in the per-protocol set within each basket, across all baskets, and across all baskets excluding the prostate baskets. Exploratory end points included circulating tumor DNA (ctDNA) and immune profiling. RESULTS From 2018 through 2023, 521 patients were screened, 350 were randomly assigned, and 334 were analyzed per protocol (MDT + SOC, n = 166; SOC, n = 168). Radiotherapy was used as MDT for 98% of metastases (370/379). Overall, after a median follow-up of 53 months, PFS was improved with MDT + SOC (hazard ratio [HR], 0.54 [95% CI, 0.41 to 0.72], P < .001). Similarly, PFS was improved when excluding the prostate baskets (HR, 0.60 [95% CI, 0.40 to 0.89]). Within each basket, PFS superiority was identified for the pancreas, prostate, and other baskets, whereas the breast and kidney baskets were inconclusive. At enrollment, detectable ctDNA correlated with shorter PFS and survival; by contrast, ctDNA clearance 3 months postenrollment correlated with improved survival. MDT + SOC-induced systemic immune activation was most pronounced among baskets demonstrating PFS superiority. CONCLUSION The phase II EXTEND trial supports the addition of MDT to SOC for oligometastatic disease. Histology-specific efficacy signals were identified for phase III testing. Translational insights suggest the potential for optimizing the definition of oligometastasis using ctDNA and point to systemic immune responses as a possible mechanism of benefit from MDT.

ABSTRACT Disease Overview Plasmablastic lymphoma (PBL) is a rare CD20‐negative aggressive lymphoma with poor prognosis when treated with standard treatment options. Although PBL is associated with HIV infection and other immunosuppressed states, it can also affect immunocompetent individuals. Diagnosis The diagnosis of PBL requires a high clinical suspicion and pathological confirmation. EBV‐encoded RNA (EBER) expression and MYC gene rearrangements are frequently detected in the malignant cells. The differential diagnosis includes EBV+ diffuse large B‐cell lymphoma (DLBCL), extracavitary primary effusion lymphoma, ALK+ DLBCL, and HHV8+ large B‐cell lymphoma, among others. Risk Stratification Age ≥ 60 years, advanced clinical stage, and high International Prognostic Index scores are associated with worse survival. Management Combination chemotherapy regimens, such as infusional EPOCH, are recommended. The addition of bortezomib or daratumumab might improve outcomes. B‐cell maturation antigen‐targeted therapies have shown early efficacy. The participation of patients with PBL in prospective clinical trials is warranted.

Background The middle meningeal artery (MMA) has emerged as an endovascular route for treating chronic subdural hematoma (CSDH), meningioma, and refractory headaches. The third ARISE roundtable convened experts from neurology, neurosurgery, neuroradiology, industry, and regulatory agencies to develop consensus guidance on current evidence for MMA-based therapies Methods Over 50 experts participated in a multi-stakeholder discussion. Evidence from randomized and observational studies, early-phase interventional series, and preclinical work was reviewed. Breakout groups focused on four domains: (1) MMA embolization (MMAE) for CSDH, (2) preoperative embolization of meningiomas, (3) MMA-targeted therapies for headache, and (4) transvascular access for endovascular drainage of subdural hematomas. Consensus recommendations were developed by a writing committee Results Randomized trials support MMAE as an adjunct to surgery or medical management for selected patients with non-acute, symptomatic CSDH to reduce recurrence, progression, and reoperation. Evidence remains insufficient to support MMAE for acute or asymptomatic subdural hematomas. For meningioma, observational data suggest that preoperative embolization in experienced centers can reduce blood loss and operative time and may delay recurrence in large, hypervascular tumors with predominant dural or external carotid supply; primary embolization and intra-arterial oncologic therapies remain investigational. Early series of MMA-directed lidocaine infusion for refractory migraine, status migrainosus, and post-subarachnoid hemorrhage headache show short-term benefit, highlighting the need for controlled trials. Preclinical and first-in-human studies of combined MMAE and transvascular drainage for CSDH demonstrate high technical success, rapid radiographic and clinical improvement, and no early recurrences Conclusion The MMA represents a vascular pathway for an expanding spectrum of neurointerventional therapies.