BACKGROUND:Immunotherapy based on anti-PD1 inhibitors has significantly improved survival in advanced melanoma. However, a significant proportion of patients do not benefit, and predicting response to immunotherapy remains an area of unmet need. Our group previously defined an immune signature able to predict response to anti-PD1 inhibitors in this scenario. METHODS:In this study, we analyzed two cohorts of patients with advanced melanoma treated with anti-PD1 inhibitors: the GEM cohort, previously used to validate our immune signature, and Campbell's cohort, which contains data about different immunotherapy schemes. Using the 107 genes that compose our immune signature and consensus clustering, samples were classified as immune-low or immune-high. Then, CIBERSORTx and Ecotyper were used to estimate the proportion of each immune cell type and carcinoma ecotypes in both cohorts. RESULTS:We confirmed that the immune-low group includes mostly patients who do not response to anti-PD1 inhibitors. We also studied the distribution of carcinoma ecotypes in the immune-high and immune-low groups defined by our immune classification. Ecotypes CE9 and CE10 clustered in the immune-high group, with good response to treatment. The use of combination immunotherapy improved response rate both in immune-low and immune-high tumors. The immune-high group contained a higher number of CD8 T cells, B memory cells and T follicular helper cells. CONCLUSIONS:Our immune-based classification defines an immune-low group of tumors with poor response to anti-PD1 inhibitors. This immune classification is related to carcinoma ecotypes. Finally, a use of a combo scheme improves the rates of response both in immune-high and low groups but in the case of immune-low tumors, our results suggests that a combo treatment approach could be an adequate strategy and should be further explored in these patients. Altogether, our results support the utility of our immune signature in the prediction of response to anti-PD1 inhibitors in advanced melanoma.
INTRODUCTION:The occiput-posterior (OP) fetal position is the most frequent form of labor dystocia. This position has been associated with delaying the second stage of labor and adverse outcomes. OBJECTIVES:This project aimed to improve the quality of intrapartum care provided by midwives for OP fetal positions during the second stage of labor. METHODS:This best practice implementation project was conducted at the Río Hortega University Hospital in Valladolid, Spain. The project followed the JBI Evidence Implementation Framework, which is based on an audit, feedback, and re-audit process. Current practices were compared against best practices in a baseline audit using 13 audit criteria. Barriers to compliance with best practices were identified and improvement strategies were implemented. An initial follow-up audit was carried out after 4 months to avoid secondary bias. After another 4 months, a second follow-up audit was conducted. Data were collected and compared using the JBI Practical Application of Clinical Evidence System (JBI PACES). RESULTS:The results revealed an improvement in all structure criteria (1-3), five of the process criteria (4-6, 8, 10), and all results criteria (11-13). One process criterion (8) reached maximum compliance in all audits. A key finding was the inadequate recording of upright positions (criterion 7) and the interpretation of cardiotocography (criterion 9). CONCLUSIONS:Evidence-based interventions for managing OP labor improved the quality of care and underlined the importance of ongoing training for midwives. Additional studies are required on positions and fetal monitoring during labor. SPANISH ABSTRACT:http://links.lww.com/IJEBH/A279.
OBJECTIVES:To analyze the current situation of Healthcare Ethics Committees (HECs) in Spain, their composition and functions, as well as the implementation of Clinical Ethics Consultancy (CEC). Finally, to assess the involvement of internists in HECs. MATERIALS AND METHODS:A cross-sectional descriptive study conducted through a self-administered online survey distributed between February and May 2025 to all identified HECs in the country. RESULTS:A total of 112 HECs (47.66%) out of the 235 accredited nationwide participated. The average number of members per committee was 16 (range: 6-29). The most represented professional profiles were nursing and medicine. In 99.1% of the committees, at least one member had postgraduate training in Bioethics. The most frequent range of meetings per year was between 7 and 12 (46.8%). Most HECs (91.1%) were involved in educational activities, and 58% had produced ethical documents. The majority reviewed between 1 and 5 cases annually (69.6%). The CEC role was established in 40.2% of HECs and in the process of implementation in 18.8%. Internists were present in 54% of HECs. In 65% of cases, the internist is part of the CEC. CONCLUSIONS:HECs in Spain demonstrate significant involvement in educational activities and the development of ethical documents; however, they receive a relatively low number of annual consultations. Clinical Ethics Consultancy is gradually being integrated into the structure of HECs, which may enhance the management of ethical inquiries. Internists are members of more than half of the HECs and play a very active role in their operations.
Immune checkpoints critically regulate T-cell activation and tolerance, yet their role in mucosal immune dysregulation in ulcerative colitis (UC) remains poorly defined. While expansion of regulatory T cells (Treg) in active UC is well-documented, how checkpoints and activation markers shape local T-cell phenotypes remains unclear. Indeed, the paradoxical co-expression of activation and exhaustion markers suggests a complex immune state that may underlie ineffective regulation or persistent inflammation. Characterizing these tissue-specific signatures could reveal biomarkers of disease activity and novel therapeutic targets. Paired blood and intestinal samples were collected from patients with endoscopically active UC (aUC, n = 8), quiescent UC (qUC, n = 5), and non-IBD controls (n = 6). Peripheral blood mononuclear cells (PBMCs) were isolated by ficoll gradient, and lamina propria mononuclear cells (LPMCs) by enzymatic digestion. High-dimensional spectral flow cytometry profiled T-cell subsets and assessed expression of activation (HLA-DR, CD25, CD69) and checkpoint markers (PD-1, CTLA-4, TIGIT, LAG-3, VISTA). Statistical comparisons used Kruskal–Wallis tests with p < 0.05 considered significant. We uncovered a compartmentalized immune response unique to aUC. In blood, patients showed depletion of memory T cells, Th17, and Treg subsets that were expanded in the inflamed mucosa, consistent with active migration. The mucosal compartment also exhibited a striking enrichment of a PD-1+TIGIT+HLA-DR+CD25+ T-cell subset, completely absent in their circulating precursors or in the blood or mucosa from controls or qUC patients. These cells represented activated/exhausted phenotypes across tissue-resident memory CD8+, effector memory, and pathogenic Th17 subsets. Their expression of both activation markers (HLA-DR, CD25) and inhibitory checkpoints (PD-1, TIGIT) suggest sustained antigenic stimulation and functional exhaustion. The restriction of this population to inflamed tissue indicates local induction by the inflammatory microenvironment and its disappearance during remission highlights a reversible, inflammation-dependent process. Whether these cells represent a failed regulatory mechanism or active drivers of pathology remains to be determined. We hereby have identified a unique PD-1+TIGIT+HLA-DR+CD25+ T-cell subset enriched in the inflamed mucosa from aUC but largely absent in remission and controls. This subset may serve as a biomarker of active disease, reflect local immune induction, and illustrate the coexistence of activation and exhaustion that characterizes chronic intestinal inflammation. Conflict of interest: Dr. Romero Castillo, Laura: No conflict of interest Esteva Fernández, Andrea: No conflict of interest López Pascual, Francisco Javier: I declare that I have no conflicts of interest De Prado Santos, Ángel: No conflict of interest. Arribas Rodríguez, Elisa: I have no conflict of interest Garcia Alonso, Francisco Javier: I have acted as a speaker for Abbvie, Lilly and Johnson and Johnson De Andrés-Asenjo, Beatriz: I have no conflict of interest Godoy Martínez, Lucía: I do not have conflict of interest. Velayos, Benito: No Izquierdo, Sandra: None. Romero, Alejandro: No conflicts Alcaide Suárez, Noelia: No conflicts Cuesta-Sancho, Sara: I have no conflicts of interest to declare Escudero-Hernández, Celia: Grant: ECCO grant, ECCO fellowship Other: ECCO young researcher award 2025, UEG J junior editor Barrio Andres, Jesus: Jesús Barrio has served as a speaker, as consultant or has received research or education funding Abbvie, Takeda,Kern Pharma and Ferring. Fernández-Salazar, Luis: My institution has been granted by Johnosn & Johnson for investigation. I have been financed to attend IBD meetings by Ferring, Lilly and Sandoz. Bernardo, David: David Bernardo has received funding from Pfizer (to develop research projects) as well as from Janssen and Takeda (consulting)
Introduction:ICHD-3 integrates neuralgias affecting trigeminal terminal branches within broader trigeminal pain categories rather than defining them as distinct entities. In this context, their frequency and clinical characteristics remain poorly characterized. We aimed to describe their frequency and clinical characteristics in a headache unit registry. Methods:We conducted a retrospective, descriptive cohort study based on a prospective registry initiated in January 2008 at a headache unit. Patients diagnosed between January 2008 and January 2023 who fulfilled ICHD-2 criteria for nasociliary (code 13.5), supraorbital (13.6), or other terminal branch neuralgias (13.7) were included. Demographic and clinical data were collected and analyzed. Results:Among 8728 patients evaluated during the study period, 108 (1.2%) met inclusion criteria; 71 (65.7%) were women. Mean age at symptom onset was 47.4 ± 18.7 years (range 6-89), and mean time from onset to diagnosis was 34.4 ± 68.5 months (range 1-420). The most frequent neuralgias were supraorbital (39.8%) and auriculotemporal (25.9%), followed by supratrochlear (8.3%), infraorbital (7.4%), lacrimal (7.4%), mental (5.6%), nasociliary (4.6%), and infratrochlear (0.9%). Conclusion:Trigeminal terminal branch neuralgias represent a small but consistent clinical presentation defined by topographic distribution and sensory features. Recognition of these features supports anatomically guided evaluation and peripheral interventions.
