Hospital Universitario Virgen de las Nieves

Computational fluid dynamics (CFD) has been widely used to study cerebrospinal fluid (CSF) flow in Chiari Malformation Type I (CM-I). However, most approaches rely on limited patient-specific detail, and it remains unclear whether such minimal input is sufficient to yield physiologically realistic flow predictions. In this study, we construct a series of MRI-based models of the craniocervical CSF space in a CM-I patient, complemented with representations of microanatomical features derived from ex vivo measurements and patient MRI data, to assess how CFD predictions are influenced by the choice of boundary conditions in the numerical integrations and the inclusion or omission of nerve roots and denticulate ligaments in the anatomical model. Our results reveal that while increasing patient-specific detail in boundary conditions improves agreement with velocity fields measured via phase-contrast MRI, key flow features—most notably anterior–posterior compartmentalization and bidirectional patterns during flow reversal—only emerge when denticulate ligaments are included in the model. In contrast, inclusion of nerve roots has a more localized effect on the velocity field and a modest impact on pressure drops. Our findings not only clarify how more detailed boundary conditions and improved anatomical fidelity affect velocity and pressure predictions, but also provide a mechanistic explanation for flow patterns commonly observed in CM-I that have remained unexplained, highlighting the critical role of denticulate ligaments.

<h3>Background and Importance</h3> The combination of encorafenib and binimetinib is a standard option for BRAF-mutated metastatic melanoma. However, its clinical management is complex due to the risk of class-related toxicities. Pharmaceutical care may play a key role in early identification of adverse effects, supporting treatment adjustments and improving patient safety. <h3>Aim and Objectives</h3> To describe pharmaceutical interventions made during treatment with encorafenib/binimetinib and analyse their association with the occurrence of toxicities, treatment duration and therapeutic outcomes. <h3>Material and Methods</h3> Multicentre, retrospective study that included all patients with unresectable or metastatic melanoma treated with encorafenib/binimetinib since their introduction in hospital guidelines. Data collected: sex, age, treatment duration and outcomes (partial/complete response, stable disease, or tumour progression), reported toxicities (hepatic, muscular, renal, cutaneous) and pharmaceutical interventions. Data were collected from medical electronic record system and analysed using R commander. <h3>Results</h3> A total of 38 patients were included (84% male) with a median age of 63 years (IQR 47–73). BRAF V600E mutation was present in 89.4% of cases. Prior treatment had been received by 64.8% of patients: nivolumab in 92.1% and dabrafenib/trametinib in 7.9%. The most frequent metastatic sites were lung (36.8%), lymph nodes (31.5%), peritoneum (21.1%), and brain (21.1%). Median treatment duration with encorafenib/binimetinib was 22.5 months (IQR 12–37). Clinical outcomes included complete response in 42.1%, partial response in 36.8%, and stable disease in 10.5%. The most common toxicities were muscular (57.8%), cutaneous (31.5%), renal (26.3%), hepatic (26.3%), and ophthalmologic (26.3%). Overall, 73.6% of patients required a pharmacist intervention, most frequently for monitoring adverse effects (63.1%), providing additional patient information (31.5%), dose adjustment recommendations (26.3%), drug–drug interaction management (21.1%), medication error prevention (21.1%), and medication reconciliation (10.5%). The acceptance rate of interventions was 89.4%. Following these interventions, 36.8% of patients experienced improved adverse effects, optimised dosing (21%), enhanced patient understanding and adherence and improved coordination of care (26.3%). 31.5% of patients required a dose adjustment of binimetinib, and 21% discontinued treatment, with only one discontinuation due to toxicity. <h3>Conclusion and Relevance</h3> Pharmaceutical interventions were frequent and essential in patients treated with encorafenib/binimetinib. Their role in monitoring toxicities and supporting treatment adjustments highlights the value of integrating pharmacists into multidisciplinary care teams for melanoma management. <h3>Conflict of Interest</h3> No conflict of interest

Precision psychiatry aims to overcome clinical heterogeneity by means of biomarkers that allow predicting the clinical evolution and therapeutic response in psychiatric disorders. This literature review addresses its prognostic role and its potential integration into healthcare practice. The main objective was to compile and synthesize current evidence on prognostic biomarkers in psychiatry, evaluating their usefulness in anticipating clinical evolution, therapeutic response, and risk of relapse. A strategic search was carried out on PubMed, selecting original studies that evaluated blood, genetic, epigenetic, neuroimaging, or electrophysiological biomarkers with prognostic value. We included 30 final studies that met the established inclusion and exclusion criteria and were evaluated according to standardized scales (RoB 2, NOS, AXIS). Inflammatory biomarkers showed potential as clinical modulators. Metabolomic, neuroendocrine, and neurotrophic factors reflected specific biological profiles associated with response to treatment or risk of relapse. Functional connectivity and brain morphometry were useful in the therapeutic prediction and stratification of patients. Finally, genetics and epigenetics are consolidated as tools of sensitivity and pharmacological response. Taken together, the findings reveal specific prognostic utility based on the type of biomarker and the patient's clinical context. Despite the current methodological limitations and scarce replication of studies, prognostic biomarkers represent a step towards a more personalized psychiatry based on biological mechanisms. The future integration of multimodal models will improve clinical decision-making.

Management of pancreatic neuroendocrine tumors (pNETs) < 20 mm remains controversial. Endoscopic ultrasound-guided tissue acquisition is crucial for diagnosis and grading, but data on small pNETs and Ki-67 sample adequacy are limited. This systematic review and meta-analysis evaluated sample adequacy, diagnostic yield, and histologic concordance with surgical specimens. A systematic search of MEDLINE, EMBASE, and SCOPUS was conducted. Studies reporting diagnostic yield or concordance between EUS-guided fine-needle aspiration (FNA) or biopsy (FNB) and surgical histology in pNETs < 20 mm were included. The primary outcomes were diagnostic yield, concordance with surgical histology, and adequacy of samples for Ki-67-based tumor grading. Pooled estimates were calculated using random-effects models. 27 studies were included: 17 reported sample adequacy, 9 diagnostic yield, 13 grade concordance, and 5 both yield and grading. Pooled diagnostic yield was 84.4% (95% CI: 0.80-0.87) and pooled concordance rate was 84.2% (95% CI: 0.803-0.882). For sample adequacy to establish tumor grade, the pooled rate was 71.6%. Notably, EUS-FNB demonstrated significantly higher adequacy (79.8%) compared to FNA (52.5%). EUS-guided tissue acquisition offers high diagnostic accuracy and reliable tumor grading in pNETs < 20 mm. FNB outperforms FNA in obtaining adequate tissue for grading, underscoring its importance in clinical decision-making.