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Introduction Major depressive disorder (MDD) is a mental health disorder characterised by persistently low mood; anhedonia; feelings of worthlessness and guilt; altered appetite, weight and sleep and suicidal ideation. About one-third of patients do not respond to available antidepressants (AD). Treatment-resistant depression (TRD) is a clinical term used to define a lack of response to two or more AD in patients with MDD that do not respond to other lines of treatment either. TRD is associated with an increased risk of relapse, hospitalisation and suicide. Esketamine is a non-competitive NMDAR antagonist that acts as an antidepressant by modulating glutamatergic neurotransmission, disturbed in MDD patients. It has recently been approved by the European Commission as a fast-acting nasal spray therapy for depression and suicidal ideation after showing effectiveness in TRD patients (Papakostas et al. JCP 2020; 81 4). Objectives The aim of this study is to determine the effectiveness, safety and tolerability of intranasal esketamine in two TRD-diagnosed patients and to assess their clinical evolution. Methods A prospective study was conducted describing the evolution of two TRD patients treated with intranasal esketamine. We used The Hamilton Depression Rating Scale (HDRS) to quantify the severity of their symptoms and assess their recovery over time, analyzing the score change from baseline to endpoint as a primary outcome of the study. We also applied the Addensbrooke Cognitive Examination (ACE-III) as a tool to establish their cognitive condition before therapy and its evolution. Changes in dosage during treatment, adverse effects, time required for onset of action, clinical outcomes and other variables were also measured. Results Intranasal esketamine was administered twice a week during the first 4-week induction phase and weekly during the following 6-month maintenance phase. Dosage of antidepressant was determined depending on each patient’s age and clinical evolution, being 56 mg the initial dose for case 1 (57 years old) and 28 mg for case 2 (71 years old). This antidepressant was effective in both patients in a fast-acting way, with the onset of action occuring within the first two weeks. During the course of treatment, the HDRS score significantly decreased, associated with improvement and remission of depressive symptoms. Cognitive performance got better in both cases. None of the patients discontinued treatment due to adverse effects or lack of efficacy. Conclusions Our data suggest that intranasal esketamine therapy is a good alternative in TRD patients, being effective, fast-acting and well-tolerated, with a manageable safety profile. Clinical stability was also observed in the medium-term follow-up after the end of treatment. This presents esketamine as a promising therapeutic and effective strategy in MDD patients who are either treatment-resistant or acutely suicidal. Disclosure of Interest None Declared

Abstract Little is known about the pathophysiological mechanisms of relapse in first-episode schizophrenia, which limits the study of potential biomarkers. To explore relapse mechanisms and identify potential biomarkers for relapse prediction, we analyzed gene expression in peripheral blood in a cohort of first-episode schizophrenia patients with less than 5 years of evolution who had been evaluated over a 3-year follow-up period. A total of 91 participants of the 2EPs project formed the sample for baseline gene expression analysis. Of these, 67 provided biological samples at follow-up (36 after 3 years and 31 at relapse). Gene expression was assessed using the Clariom S Human Array. Weighted gene co-expression network analysis was applied to identify modules of co-expressed genes and to analyze their preservation after 3 years of follow-up or at relapse. Among the 25 modules identified, one module was semi-conserved at relapse (DarkTurquoise) and was enriched with risk genes for schizophrenia, showing a dysregulation of the TCF4 gene network in the module. Two modules were semi-conserved both at relapse and after 3 years of follow-up (DarkRed and DarkGrey) and were found to be biologically associated with protein modification and protein location processes. Higher expression of DarkRed genes was associated with higher risk of suffering a relapse and early appearance of relapse (p = 0.045). Our findings suggest that a dysregulation of the TCF4 network could be an important step in the biological process that leads to relapse and suggest that genes related to the ubiquitin proteosome system could be potential biomarkers of relapse.

Abstract Background The role of dietary patterns in the prevention of unipolar depression has been analyzed in several epidemiological studies. The primary aims of this study are to determine the effectiveness of an extra-olive oil-enriched Mediterranean diet in reducing the recurrence of depression and improving the symptoms of this condition. Methods Multicenter, two-arm, parallel-group clinical trial. Arm 1, extra-virgin olive oil Mediterranean diet; Arm 2, control group without nutritional intervention. Dieticians are in charge of the nutritional intervention and regular contact with the participants. Contacts are made through our web platform (https://predidep.es/participantes/) or by phone. Recurrence of depression is assessed by psychiatrists and clinical psychologists through clinical evaluations (semi-structured clinical interviews: Spanish SCID-I). Depressive symptoms are assessed with the Beck Depression Inventory. Information on quality of life, level of physical activity, dietary habits, and blood, urine and stool samples are collected after the subject has agreed to participate in the study and once a year. Discussion To the best of our knowledge, the PREDI-DEP trial is the first ongoing randomized clinical trial designed to assess the role of the Mediterranean diet in the prevention of recurrent depression. It could be a cost-effective approach to avoid recurrence and improve the quality of life of these patients. Trial registration The study has been prospectively registered in the U.S. National Library of Medicine (https://clinicaltrials.gov) with NCT number: NCT03081065.

Introduction Social cognition has been associated with functional outcome in patients with first episode psychosis (FEP). Social cognition has also been associated with neurocognition and cognitive reserve. Although cognitive reserve, neurocognitive functioning, social cognition, and functional outcome are related, the direction of their associations is not clear. Objectives The aim of the study was to analyze the influence of social cognition as a mediator between cognitive reserve and cognitive domains on functioning in FEP both at baseline and at 2 years. Methods The sample of the study was composed of 282 FEP patients followed up for 2 years. To analyze whether social cognition mediates the influence of cognitive reserve and cognitive domains on functioning, a path analysis was performed. The statistical significance of any mediation effects was evaluated by bootstrap analysis. Results At baseline, as neither cognitive reserve nor the cognitive domains studied were related to functioning, the conditions for mediation were not satisfied. Nevertheless, at 2 years of follow-up, social cognition acted as a mediator between cognitive reserve and functioning. Likewise, social cognition was a mediator between verbal memory and functional outcome. The results of the bootstrap analysis confirmed these significant mediations (95% bootstrapped CI (−10.215 to −0.337) and (−4.731 to −0.605) respectively). Conclusions Cognitive reserve and neurocognition are related to functioning, and social cognition mediates in this relationship. Disclosure This work was supported by the Carlos III Institute of Health and European Fund for Regional Development (PI08/1213, PI11/ 01977, PI14/01900, PI08/01026, PI11/02831, PI14/01621, PI08/1161, PI16/ 00359, PI16/01164, PI18/00805), the Basque Foundation for He

Introduction Suicidal behaviour and cognition: A systematic review with special focus on prefrontal deficits Introduction: Suicide is a major health concern worldwide, thus, identifying risk factors would enable a more comprehensive understanding and prevention of this behaviour. Neuropsychological alterations could lead to difficulties in interpreting and managing life events resulting in a higher risk of suicide. Objectives Objective: Bibliographic review about the influence of neuropsychological deficits on suicidal behaviour. Methods Method: A systematic literature search from 2000 to 2020 was performed in Medline (Pubmed), Web of Science, SciELO Citation Index, PsycInfo, PsycArticles and Cochrane Library databases regarding studies comparing cognition of attempters versus non-attempters that share same psychiatric diagnosis. Results: 1.885 patients diagnosed with an Affective Disorder (n = 1512) and Schizophrenia/ Schizoaffective Disorder (n = 373) were included. Results In general comparison, attention was found to be clearly dysfunctional. Regarding diagnosis, patients with Schizophrenia and previous history of suicidal behaviour showed a poorer performance in executive function. Patients with current symptoms of an Affective Disorder and a previous history of suicidal attempt had poorer performance in attention and executive function. Similarly, euthymic affective patients with history of suicidal behaviour had worse decision-making, attention and executive function performance compared to euthymic non-attempters. Conclusions Patients who have attempted suicide have a poorer neuropsychological functioning than non-attempters with a similar psychiatric disorder in attention and executive function. These alterations increase vulnerability for suicide. Conflict of interest Jessica Fernández-Sevillano is beneficiary of the Pre-PhD Training Programme of the Basque Government. Dr. Gonzalez-Pinto has received grants and served as consultant, advisor or CME speaker for the following entities: Almirall, AstraZeneca, Bristol-Myers

Introduction: Recent studies have shown that symptoms of psychiatric illness, functionality, and cognitive function improve with exercise. The aim of this study will be to investigate whether the implementation of an individualized exercise program will improve the functional status of patients with bipolar disorder (BD).Methods: This longitudinal, interventional, randomized, controlled, simple-blind clinical trial will include 80 patients aged 18–65 years, all of them with BD diagnosis. Patients will be randomly assigned to a physical exercise intervention + Treatment-As-Usual (TAU) group and a non-intervention + TAU group. Patients will be assessed by an extensive battery of clinical tests, physical parameters (e.g., brain structure changes measured by optical coherence tomography, cardiorespiratory fitness) and biological parameters (inflammation, oxidative stress and neurotrophic factors) at baseline, after a 4-month intervention period, and 6-month follow-up.Discussion: This is an innovative study aimed at gaining a deeper understanding of the physiopathology of BD and determining whether the prognosis and evolution of the disease can be improved through modifiable areas of the patient's lifestyle.Clinical Trial Registration: NCT04400630. NCT clinicaltrials.gov. Date of registration in primary registry 22 May 2020. clinicaltrials.gov.

Introducción: Revisiones sistemáticas previas han apoyado la eficacia del consejo médico, como intervención breve, en el abordaje de bebedores excesivos detectados en la asistencia primaria. Sin embargo, estos resultados no pueden extrapolarse directamente a poblaciones que, como las mediterráneas, no están representadas en dichas revisiones. El objetivo de este estudio fue actualizar la evidencia sobre la eficacia de la intervención breve en consumidores excesivos de alcohol según estudios españoles. Métodos: Búsqueda de estudios en bases bibliográficas y consultas a expertos para localizar estudios no publicados. Se calcularon las estimaciones combinadas para dos variables de resultado, la reducción del consumo de alcohol y la disminución de la frecuencia de bebedores excesivos. Resultados: Dos de los 5 estudios localizados no estaban incluidos en una revisión previa. La eficacia de la intervención breve fue moderada para la disminución del consumo de alcohol (d = - 0,46; intervalo de confianza (IC) del 95%, - 0,29 a - 0,63; p < 0,0005; el grupo tratado mejoró un 22% más que el control) y pequeña para la disminución de la frecuencia de bebedores excesivos (OR = 1,55; IC del 95%, 1,06 a 2,26; p = 0,02; el grupo tratado mejoró un 11% más que el control). El análisis basado en el cumplimiento del protocolo sobrestimó 1,5 veces el tamaño del efecto respecto del análisis basado en la intención de tratamiento. Conclusiones: Los resultados del estudio señalan que, en nuestro país, la intervención breve en atención primaria sobre bebedores a riesgo es eficaz, aunque su efecto sea sólo moderado.Introduction: Former systematic reviews have backed the efficacy of medical counselling, a form of brief intervention, on the treatment of excessive drinkers detected in primary care settings. Nevertheless, these results cannot be applied without criticism to Mediterranean populations which, so far, have not been represented in the aforementioned studies. The aim of the present study was to update the results on the efficacy of brief interventions in primary care by pooling Spanish studies. Methods: Studies were searched for by using appropriate databases and also by consulting to experts in the field to retrieve grey literature. Pooled estimations of effect sizes were calculated for two outcomes, the reduction in the amount of alcohol consumption and the decrease in the number of excessive drinkers. Results: Two over the 5 retrieved studies were not included in a former review. The effect size regarding the decrease of alcohol consumption was medium (d = - 0.46; 95% CI, - 0.29 to - 0.63; p < 0.0005; the intervention group outperformed the control by a 22%) and small for the decrease in the frequency of excessive drinkers (OR = 1.55; 95% CI, 1.06 to 2.26; p = 0.02; the intervention group outperformed the control by a 11%). The analysis by complimented protocols at the end of the study showed an effect size 1.5 times larger than the analysis performed on intention-to-treat basis. Conclusions: The results of this meta-analysis support the efficacy of brief intervention for excessive drinkers in primary care settings in Spain.

Heart transplantation (HT) poses high bleeding risks, especially for patients on anticoagulation. This study evaluates the use of idarucizumab for dabigatran (DBG) reversal compared to vitamin K antagonist (VKA) strategies in HT. A retrospective analysis of HT patients from January 2018 to December 2022, excluding those requiring ECMO immediately before or after surgery, was conducted. Outcomes included transfusion needs, re-surgery due to bleeding, ICU stay lengths, and 30-day survival. A cost analysis compared the direct expenses of each strategy. Among 34 patients, 20 were on DBG and 14 on VKAs or not anticoagulated. Idarucizumab significantly reduced the number of patients requiring transfusion (p = 0.034) and ICU stay lengths (p = 0.014), with no significant impact on re-surgery rates (p = 0.259) or survival (p = 0.955). Despite higher initial costs, overall expenses for idarucizumab were comparable to VKA reversal due to reduced transfusion needs and shorter ICU stays. Idarucizumab offers a viable and potentially cost-neutral anticoagulation reversal option for HT patients on DBG, presenting an alternative to VKA strategies. However, due to the retrospective nature of the study and the small sample size, further prospective studies are needed to confirm these findings.

En la actualidad existe controversia acerca del tipo adecuado de canulación para los dispositivos de asistencia circulatoria izquierda. Algunos autores defienden la superioridad de la canulación apical, en cuanto a la optimización de flujos medios del dispositivo y sangrado perioperatorio1,2. En los últimos 2 años se han implantado en nuestro centro un total de 22 dispositivos Abiomed BVS 5000, 18 de ellos fueron canulados por el ápex del ventrículo izquierdo (grupo I), mientras que 4 fueron canulados por la aurícula izquierda (grupo II). Del total de enfermos, el 59,09% llegaron al trasplante cardíaco, falleciendo el 30% de los trasplantados; la mortalidad global fue del 54,55%. Analizando comparativamente las cifras de sangrado medio en 24 h y el flujo medio del dispositivo en nuestra serie, el grupo I presentó unas cifras de flujo medio significativamente mayores (4,8 1/min en el grupo I frente a 4,1 1/min en el grupo II), así como menos sangrado 24 h. La mortalidad del grupo I fue del 50% (9 de 18), frente al 75% del grupo II (1 de 4). A pesar del reducido número de enfermos, los datos obtenidos en nuestro centro insinúan mejores parámetros hemodinámicos usando la canulación apical. Sería necesario realizar estudios posteriores con un mayor tamaño muestral para obtener conclusiones definitivas.

El vídeo muestra la cirugía de una enferma de 42 años que acude a nuestro centro diagnosticada de hidatidosis miocárdica. Bajo anestesia general, hipotermia moderada y circulación extracorpórea se realiza una pericistectomía completa, con instilación de suero hipertónico dentro del quiste y con reconstrucción posterior de la pared ventricular. La película incluye clips de ecocardiograma pre y postoperatorio, así como la cardiorresonancia.

The co-creation of educational services that promote youth resilience and mental health is still scarce. UPRIGHT (Universal Preventive Resilience Intervention Globally implemented in schools to improve and promote mental Health for Teenagers) is a research and intervention program in the Basque Country (Spain), Trentino (Italy), Low Silesia (Poland), Denmark and Reykjavik (Iceland). UPRIGHT implemented a co-creation research process whose results, outcomes and policy implications are presented here. The co-creation had a mixed-methods participatory research design with nine specific objectives linked to paired strategies of inquiry for adolescents, families, teachers and school staff. The overarching objective was to generate a valid and feasible regional adaptation strategy for UPRIGHT intervention model. Participants answered surveys (n = 794) or attended 16 group sessions (n = 217). The results integrate quantitative and qualitative information to propose a regional adaptation strategy that prioritizes resilience skills, adolescents' concerns, and preferred methods for implementation across countries and in each school community. In conclusion, a whole-school resilience program must innovate, include and connect different actors, services and communities, and must incorporate new technologies and activities outside the classroom. A participatory co-creation process is an indispensable step to co-design locally relevant resilience interventions with the involvement of the whole-school community.