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PURPOSE: CAR therapy targeting BCMA is under investigation as treatment for multiple myeloma. However, given the lack of plateau in most studies, pursuing more effective alternatives is imperative. We present the preclinical and clinical validation of a new optimized anti-BCMA CAR (CARTemis-1). In addition, we explored how the manufacturing process could impact CAR-T cell product quality and fitness. METHODS: CARTemis-1 optimizations were evaluated at the preclinical level both, in vitro and in vivo. CARTemis-1 generation was validated under GMP conditions, studying the dynamics of the immunophenotype from leukapheresis to final product. Here, we studied the impact of the manufacturing process on CAR-T cells to define optimal cell culture protocol and expansion time to increase product fitness. RESULTS: Two different versions of CARTemis-1 with different spacers were compared. The longer version showed increased cytotoxicity. The incorporation of the safety-gene EGFRt into the CARTemis-1 structure can be used as a monitoring marker. CARTemis-1 showed no inhibition by soluble BCMA and presents potent antitumor effects both in vitro and in vivo. Expansion with IL-2 or IL-7/IL-15 was compared, revealing greater proliferation, less differentiation, and less exhaustion with IL-7/IL-15. Three consecutive batches of CARTemis-1 were produced under GMP guidelines meeting all the required specifications. CARTemis-1 cells manufactured under GMP conditions showed increased memory subpopulations, reduced exhaustion markers and selective antitumor efficacy against MM cell lines and primary myeloma cells. The optimal release time points for obtaining the best fit product were > 6 and < 10 days (days 8-10). CONCLUSIONS: CARTemis-1 has been rationally designed to increase antitumor efficacy, overcome sBCMA inhibition, and incorporate the expression of a safety-gene. The generation of CARTemis-1 was successfully validated under GMP standards. A phase I/II clinical trial for patients with multiple myeloma will be conducted (EuCT number 2022-503063-15-00).

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OBJECTIVES: Sexually transmitted infections (STIs) have markedly increased over the last decade in Spain, calling for prevention and control innovative approaches. While there is evidence indicating the effectiveness of self-sampling for STI diagnosis, no kits for this purpose have been authorised in Spain. METHODS: A prospective single-blind cross-sectional study carried out between November and December 2022 in an STI clinic in Madrid, Spain, to determine the validity, feasibility and acceptability of self-sampling kits used by non-healthcare professionals from vagina, pharynx, rectum and urethra to diagnose Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). Self-samples were compared with samples collected by healthcare professional (HC samples) and analysed by PCR. Frequency of CT and NG diagnosis by sample type was compared using McNemar's test for paired data. Sensitivity and specificity of self-samples for CT and NG diagnosis were also calculated. RESULTS: 306 self-samples from 51 participants were analysed. 80% were men with median age of 33 (IQR: 28-38) years. Self-samples and HC samples showed no significant statistical differences in CT and NG diagnosis. Self-samples had a sensitivity of 81% for CT and 93% for NG, with a specificity of 97% for CT and 95% for NG. More than 90% of participants had no difficulty understanding the kit instructions and 71% expressed high levels of satisfaction with the self-sampling kit. CONCLUSION: Self-sampling kits for CT and NG diagnosis can be safely and effectively used by non-healthcare professionals in Spain. National strategies for STI prevention and control should prioritise self-sampling strategies.

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P60, a Foxp3 inhibitory peptide, can hinder the regulatory T cell (Treg) activity and impair tumor proliferation. However, low systemic stability and poor specificity have led to daily dosing to achieve therapeutic effect. Therefore, this study aims to improve P60 stability and specific delivery through its encapsulation in liposomes targeting CD25, constitutively expressed in Tregs. P60 liposomes formulated with DSPE-PEG750 or DSPE-PEG2000 were incubated with DSPE-PEG2000-Maleimide micelles conjugated to Fab' fragments of anti-CD25 to develop two targeted formulations or immunoliposomes (IL): IL-P602000 (DSPE-PEG2000 only) and IL-P60750 (combining DSPE-PEG750 and DSPE-PEG2000). P60 encapsulation efficiency was 50%-60% irrespective of PEG chain length. Treg uptake was 2.5 and 14 times higher for IL-PEG750 compared with IL-PEG2000 and non-targeted liposomes, respectively, in in-vitro assays. In fact, IL-P60750 allowed CD8+  T cells ex-vivo proliferation in presence of Treg at doses 10-20 times lower than for free P60. Antitumor response of P60 and IL-P60750 in monotherapy and combined with anti-PD-1 was evaluated in MC38 and LLCOVA tumor bearing mice. In MC38 model, IL-P60750 monotherapy induced total tumor regression in 40% of mice reaching 100% for anti-PD-1 combination. This effect was associated with a significant increase in activated CD8+ T cells in tumors. Notably, IL-P60750 also inhibited human Treg in ex-vivo assay, showing the translational capability of this formulation. In conclusion, IL-P60750 formulated with different PEG chain lengths, has demonstrated antitumor efficacy by selective inhibition of Treg activity and enhances the effect of anti-PD1. Altogether, this novel IL represents a promising nanoplatform for cancer immunotherapies.

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Immunotherapy has become an important part of the oncotherapy arsenal. Its applicability in various cancer types is impressive, as well as its use of endogenous mechanisms to achieve desired ends. However, off-target or on-target-off-tumor toxicity, limited activity, lack of control in combination treatments and, especially for solid tumors, low local accumulation, have collectively limited clinical use thereof. These limitations are partially alleviated by delivery systems. Lipid-based nanoparticles (NPs) have emerged as revolutionary carriers due to favorable physicochemical characteristics, with specific applications and strengths particularly useful in immunotherapeutic agent delivery. The aim of this review is to highlight the challenges faced by immunotherapy and how lipid-based NPs have been, and may be further utilized to address such challenges. We discuss recent fundamental and clinical applications of NPs in a range of areas and provide a detailed discussion of the main obstacles in immune checkpoint inhibition therapies, adoptive cellular therapies, and cytokine therapies. We highlight how lipid-based nanosystems could address these through either delivery, direct modulation of the immune system, or targeting of the immunosuppressive tumor microenvironment. We explore advanced and emerging liposomal and lipid nanoparticle (LNP) systems for nucleic acid delivery, intrinsic and extrinsic stimulus-responsive formulations, and biomimetic lipid-based nanosystems in immunotherapy. Finally, we discuss the key challenges relating to the clinical use of lipid-based NP immunotherapies, suggesting future research directions for the near term to realize the potential of these innovative lipid-based nanosystems, as they become the crucial steppingstone towards the necessary enhancement of the efficacy of immunotherapy.

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Introduction: Introduction: malnutrition is a very frequent problem in oncology patients and may have serious repercussions. Adequate nutritional management is cost-effective in terms of health and survival in this population, but it requires multidisciplinary coordination, specific training, and continuous follow-up. Objective: to validate the applicability and efficacy of a multidisciplinary nutritional support protocol in oncology patients. Methods: a multidisciplinary nutritional protocol was developed for oncology patients, with guidelines for screening and assessment of malnutrition, treatment, re-evaluation, and management of side effects, as well as guidance on supplementation and eating patterns. The protocol would be implemented in various clinical centers, collecting data through a structured questionnaire, registering variables before and after implementation. Results: the protocol and its impact were implemented and evaluated in 39 centers. An improvement in nutritional care was observed, evidenced by an earlier initiation of nutritional assessment and an increase in the number of patients receiving adequate care following the protocol implementation. Problems related to inadequate malnutrition coding in the centers, limited resources, and the need for greater interdepartmental collaboration were identified. Conclusions: the conduct of this study provides insights into how the implementation of a multidisciplinary nutritional support protocol can improve the nutritional care received by patients and informs about the main obstacles to adequate implementation.

Introducción: Introducción: la desnutrición es un problema muy frecuente en el paciente oncológico y puede tener graves repercusiones. Un manejo nutricional adecuado es coste-efectivo en términos de salud y supervivencia en esta población, pero requiere de coordinación multidisciplinar, formación específica y seguimiento continuo. Objetivo: validar la aplicabilidad y eficacia de un protocolo multidisciplinar de soporte nutricional en pacientes oncológicos. Métodos: se desarrolló un protocolo nutricional multidisciplinar para pacientes oncológicos, con pautas para el cribado y valoración de la desnutrición, el tratamiento, la reevaluación y la gestión de los efectos secundarios, además de orientaciones sobre suplementación y patrones de alimentación. Se implementaría el protocolo en diversos centros clínicos, recogiendo datos a través de un cuestionario estructurado, registrando variables antes y después de la implementación. Resultados: se implementó y se valoraron el protocolo y su impacto en 39 centros. Se observó una mejoría en la atención nutricional, evidenciada por un inicio más precoz de la valoración nutricional y un aumento en el número de pacientes que recibían atención adecuada tras la implementación del protocolo. Se identificaron problemas relacionados con una inadecuada codificación de la desnutrición en los centros, recursos limitados y la necesidad de mayor colaboración interdepartamental. Conclusiones: la realización de este estudio ofrece información de cómo la implementación de un protocolo multidisciplinar de soporte nutricional puede contribuir a mejorar la atención nutricional que reciben los pacientes e informa de cuáles son los principales obstáculos para una implementación adecuada.

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Este es el segundo artículo de una serie de dos publicados en esta revista, en los que examinamos las características histopatológicas, así como el diagnóstico diferencial, de las principales entidades que se presentan en forma de estructuras quísticas y pseudoquísticas en la biopsia cutánea. En este segundo artículo, abordamos los quistes cutáneo ciliado, branquial, de Bartholino, onfalomesentérico, tímico, del conducto tirogloso, sinovial, y del rafe medio, así como el mucocele, el ganglión y los pseudoquistes auricular y mixoide digital. (AU)

This is the second article in a two-part series published in this journal, in which we examine the histopathological characteristics, as well as the differential diagnosis, of the main entities that present as cystic and pseudocystic structures in cutaneous biopsy. In this second article, we address ciliated cutaneous cysts, branchial cysts, Bartholin's cysts, omphalomesenteric cysts, thymic cysts, thyroglossal duct cysts, synovial cysts, and median raphe cysts, as well as mucocele, ganglion, and auricular and digital myxoid pseudocysts. (AU)

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Resumen Introducción: La experiencia de vivir con una enfermedad crónica no es una tarea sencilla, se requiere de herramientas que permitan aumentar el grado de conciencia para enfrentar las necesidades y superar desafíos sobre el estado de salud y enfermedad. En los últimos años, se ha instaurado el apoyo al automanejo, con la finalidad de potenciar las habilidades en personas con este tipo de afecciones. Resulta trascendental considerar como desde enfermería se puede contribuir al logro de aquello. El objetivo del presente ensayo es reflexionar acerca de la teoría de las transiciones de Meléis como paradigma de apoyo al automanejo en personas con condiciones crónicas. Desarrollo: La teoría de las transiciones de Meléis establece que las personas están en constante cambio, tal como ocurre en el proceso de transición de salud-enfermedad. Recibir el diagnóstico de una enfermedad crónica, conlleva una serie de procesos complejos para la persona, debido a la multiplicidad de variables que ello implica. La teoría de Meléis entrega lineamientos para orientar a la persona profesional de enfermería sobre elementos claves e interrelacionados, como la concepción previa de la naturaleza de la transición y sus condiciones, lo que servirá para la planificación de modalidades de intervención congruentes con las experiencias de la persona y su evaluación en el transcurso del proceso de salud y enfermedad. Conclusión: El paradigma ofrecido por Meléis puede ser considerado un enfoque clave para emprender el proceso de cuidado de enfermería tendiente a apoyar a las personas con enfermedad crónica en el logro del automanejo.

Abstract Introduction: The experience of living with a chronic disease is not a simple task, since it requires tools that allow increasing the degree of awareness to face the needs and overcome challenges about the state of health and disease. In recent years, support for self-management has been established, with the aim of enhancing the skills of people with this type of condition. It is important to consider how the nursing discipline can contribute to achieve this. The aim of this paper is to reflect on Meléis' theory of transitions as a paradigm to support self-management in people with chronic conditions. Development: Meléis' theory of transitions establishes that people are in constant change, as occurs in the health-illness transition process. Receiving the diagnosis of a chronic disease involves a series of complex processes for the person, due to the multiplicity of variables involved. Meléis' theory provides guidelines to orient the nursing professional on key and interrelated elements, such as the previous conception of the nature of the transition and its conditions, which will serve for the planning of intervention modalities congruent with the person's experiences and their evaluation in the course of the health and disease process. Conclusion: The paradigm offered by Meléis can be considered a key approach to undertake the nursing care process aimed at supporting people with chronic illness in achieving self-management.

Resumo Introdução: A experiênca de viver com uma doença crônica não é uma tarefa simple, pois requer ferramentas que permitam aumentar o nível de consciência para enfrentar as necessidades e superar desafios relativos ao estado de saúde e doença. Nos últimos anos, foi estabelecido o apoio à autogestão, com o objetivo de melhorar as habilidades das pessoas com este tipo de condições. É transcendental considerar como a disciplina de Enfermagem pode contribuir para isso. O objetivo deste ensaio é refletir sobre a teoria das transições de Meleis como paradigma de apoio à autogestão em pessoas com condições crônicas. Desenvolvimento: A teoria das transições de Meléis estabelece que as pessoas estão em constante mudança, como acontece no processo de transição saúde-doença. Receber o diagnóstico de uma doença crónica implica uma série de processos complexos para a pessoa, devido à multiplicidade de variáveis envolvidas. A teoria de Meléis fornece directrizes para orientar o profissional de enfermagem sobre elementos-chave e inter-relacionados, como a conceção prévia da natureza da transição e das suas condições, que servirão para o planeamento de modalidades de intervenção congruentes com as experiências da pessoa e a sua avaliação no decurso do processo saúde-doença. Conclusão: O paradigma oferecido por Meleis pode ser considerado uma abordagem chave para empreender o processo de cuidado de enfermagem que visa apoiar as pessoas com doenças crônicas no alcance do autogerenciamento.

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BACKGROUND/AIM: The appropriate sonographic protocol for assessing urate crystal deposits in asymptomatic hyperuricemia (AH) is undefined, as well as how the choice would impact on deposit rates and accompanying sonographic, clinical and laboratory features. METHODS: Patients with AH (serum urate ≥7 mg/dL) underwent musculoskeletal ultrasound of 10 locations for OMERACT elementary gout lesions (double contour [DC] signs, tophi, aggregates). Different definitions for AH with deposits were applied, varying according to deposits (any deposits; only DC and/or tophi); gradation (any grade; only grade 2-3 deposits), location (10 locations; 4-joint scheme including knees and 1MTPs; >1 location with deposits), or pre-defined definitions (DC sign in femoral condyles/1MTP and/or tophi in 1MTP). We evaluated crystal deposits rates and compared between other sonographic features, clinical and laboratory variables. RESULTS: Seventy-seven participants with AH showed a median 1 location (IQR 0-2) with tophi, 1 (IQR 1-2) with aggregates, and 0 locations (IQR 0-1) with DC sign. The deposition rate ranged from 23.4% (in >1 location with grade 2-3 DC or tophi) to 87.0% (in any deposit in all 10 locations). Accompanying inflammation - assessed by a positive power-Doppler (PD) signal - and erosions were found in 19.5% and 28.4% of participants, respectively. Positive PD signal was better discriminated by criteria requiring grade 2-3 or >1 location with lesions. Erosions and the different clinical and laboratory variables were similar among protocols. CONCLUSION: Rates of sonographic deposition in AH varied dramatically among studied protocols, while some could discriminate accompanying inflammation, all highlighting the need for a validated, consensus-based definition.

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BACKGROUND: Limited data are available regarding the real-world effectiveness and safety of Cyclin Dependent Kinase 4/6 inhibitor (CDK4/6i) (palbociclib/ribociclib) just as a first-line treatment for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2‒) metastatic breast cancer (MBC). OBJECTIVE: To assess whether clinical or demographic characteristics limit access to first-line CDK4/6i treatment in clinical practice in the Autonomous Community of Andalusia (Spain) between November 2017 and April 2020. In addition, effectiveness will be described in an exploratory analysis. METHODS: Physicians from 12 centers participated in selecting demographic and clinical characteristics, treatment, and outcome data from women with HR + /HER2- MBC treated with or without CDK4/6i in addition to hormonal in the first-line setting, in a 3:1 proportion. Kaplan-Meier analysis estimated progression-free rates (PFRs) and survival rates (SRs). RESULTS: A total of 212 patients were included, of whom 175 (82.5%) were in the CDK4/6i treatment group and 37 (17.5%) were in the non-CDK4/6i treatment group (control group). Patients in the CDK 4/6i treatment group were younger (p = 0.0011), the biopsies of the metastatic site at the moment of the relapse were most commonly performed (p = 0.0454), and had multiple metastatic sites (p = 0.0025). The clinical benefit rate (CBR) was 82.3% in the CDK4/6i group and 67.8% in the control group. Median time to a progression event or death (PFS) was 20.4 months (95%CI 15.6-28) in the CDK4/6i group and 12.1 months (95%CI 7.9-not reached) in the control group. CONCLUSIONS: Younger patients, biopsies of metastatic disease and with multiple metastatic sites were more frequently treated with CDK4/6i in our daily clinical practice.

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This is the second article in a two-part series published in this journal, in which we examine the histopathological characteristics, as well as the differential diagnosis, of the main entities that present as cystic and pseudocystic structures in cutaneous biopsy. In this second article, we address ciliated cutaneous cysts, branchial cysts, Bartholin's cysts, omphalomesenteric cysts, thymic cysts, thyroglossal duct cysts, synovial cysts, and median raphe cysts, as well as mucocele, ganglion, and auricular and digital myxoid pseudocysts.

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INTRODUCTION: The rise of new technologies in the field of health is yielding promising results. In certain chronic conditions such as type 2 diabetes mellitus, which ranks among the top five causes of global mortality, it could be useful in supporting patient management. MATERIALS AND METHODS: A systematic review will be conducted on scientific publications from the last 5 years (January 2019 to October 2023) to describe the effect of mobile app usage on glycated hemoglobin for the management of adult patients with type 2 diabetes mellitus who participated in randomized controlled clinical trials. The search will be carried out in the databases of MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), CENTRAL, WoS, Scopus, Epistemonikos, and LILACS. The search strategy will be constructed using both controlled and natural language. Additionally, the Cochrane filter will be applied to identify randomized controlled trials. The review will include scientific articles reporting studies that present results from randomized controlled trials, with texts in Spanish, English, or French, utilizing mobile applications for the management of adult individuals (over 18 years) with type 2 diabetes mellitus, and whose outcomes report the effects on glycated hemoglobin. The Cochrane Risk of Bias Tool will be used to assess the quality of the studies, and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology will be implemented to evaluate the certainty of the evidence. RESULTS: The analysis will be conducted by observing the value of the glycated hemoglobin levels of the participants. Given that this data is a quantitative and continuous value, it facilitates the identification of the effects of the mobile applications used for the management of type 2 diabetes mellitus (T2DM) in adults. Furthermore, if sufficient data are available, a meta-analysis will be conducted using IBM-SPSS. The effect of the intervention will be estimated by the mean difference. All point estimates will be accompanied by 95% confidence intervals. A random effects model will be used. The heterogeneity of the results will be assessed using Cochrane's Q and I2 statistics. DISCUSSION: Considering that the quality of content and functionality of certain applications in the healthcare field is highly variable, it is necessary to evaluate the scientific evidence reported on the effect of the use of this type of technology in people with T2DM.

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AIMS: Ventral pathway circuits are constituted by the interconnected brain areas that are distributed throughout the brain. These brain circuits are primarily involved in processing of object related information in brain. However, their role in object recognition memory (ORM) enhancement remains unknown. Here, we have studied on the implication of these circuits in ORM enhancement and in reversal of ORM deficit in aging. METHODS: The brain areas interconnected to ventral pathway circuits in rat brain were activated by an expression of a protein called regulator of G-protein signaling 14 of 414 amino acids (RGS14414). RGS14414 is an ORM enhancer and therefore used here as a gain-in-function tool. ORM test and immunohistochemistry, lesions, neuronal arborization, and knockdown studies were performed to uncover the novel function of ventral pathway circuits. RESULTS: An activation of each of the brain areas interconnected to ventral pathway circuits individually induced enhancement in ORM; however, same treatment in brain areas not interconnected to ventral pathway circuits produced no effect. Further study in perirhinal cortex (PRh), area V2 of visual cortex and frontal cortex (FrC), which are brain areas that have been shown to be involved in ORM and are interconnected to ventral pathway circuits, revealed that ORM enhancement seen after the activation of any one of the three brain areas was unaffected by the lesions in other two brain areas either individually in each area or even concurrently in both areas. This ORM enhancement in all three brain areas was associated to increase in structural plasticity of pyramidal neurons where more than 2-fold higher dendritic spines were observed. Additionally, we found that an activation of either PRh, area V2, or FrC not only was adequate but also was sufficient for the reversal of ORM deficit in aging rats, and the blockade of RGS14414 activity led to loss in increase in dendritic spine density and failure in reversal of ORM deficit. CONCLUSIONS: These results suggest that brain areas interconnected to ventral pathway circuits facilitate ORM enhancement by an increase in synaptic connectivity between the local brain area circuits and the passing by ventral pathway circuits and an upregulation in activity of ventral pathway circuits. In addition, the finding of the reversal of ORM deficit through activation of an interconnected brain area might serve as a platform for developing not only therapy against memory deficits but also strategies for other brain diseases in which neuronal circuits are compromised.

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La malformación de Arnold Chiari es una enfermedad rara que consiste en una alteración anatómica de la base del cráneo, en la que se produce herniación del cerebelo y del tronco del encéfalo a través del foramen magnum hasta el canal cervical. Muchos niños afectados nunca llegan a tener síntomas. En el caso de que cause síntomas, estos no suelen aparecer hasta la infancia tardía o adolescencia. Presentamos el caso clínico de un paciente de 2 años con malformación de Arnold Chiari tipo I. (AU)

Arnold Chiari malformation is a rare disease that consists of an anatomical alteration of the base of the skull, in which herniation of the cerebellum and brainstem occurs through the foramen magnum to the cervical canal. Many affected children never develop symptoms. If it does cause symptoms, they usually don’t appear until late childhood or adolescence. We present the clinical case of a 2-year-old patient with Arnold Chiari malformation type I. (AU)

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Las estructuras quísticas son uno de los hallazgos más frecuentes en dermatopatología. Se trata de tumores quísticos y de pseudoquistes por acumulación de ciertas sustancias, por ejemplo, mucina. En una serie de dos artículos (de los cuales este es el primero) hemos revisado los principales tipos de quistes y pseudoquistes que pueden verse en la biopsia cutánea, examinando sus aspectos histopatológicos y los principales diagnósticos diferenciales. En esta primera parte, se abordan los quistes infundibulares, dermoides, vellosos eruptivos, foliculares pigmentados, pilonidales, tricolemales, de milium, híbridos y broncogénicos, así como el esteatocistoma, el hidrocistoma y los comedones. (AU)

Cystic structures represent one of the most common findings in dermatopathology. These encompass both cystic tumors and pseudocysts resulting from the accumulation of certain substances, such as mucin. In a two-part series (of which this is the first part), we have reviewed the principal types of cysts and pseudocysts that may be observed in cutaneous biopsies, examining their histopathological features and primary differential diagnoses. This first part encompasses infundibular cysts, eruptive dermoid cysts, pigmented follicular cysts, pilonidal cysts, tricholemmal cysts, milium cysts, hybrid cysts, bronchogenic cysts, as well as steatocystoma, hydrocystoma, and comedones. (AU)

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Las estructuras quísticas son uno de los hallazgos más frecuentes en dermatopatología. Se trata de tumores quísticos y de pseudoquistes por acumulación de ciertas sustancias, por ejemplo, mucina. En una serie de dos artículos (de los cuales este es el primero) hemos revisado los principales tipos de quistes y pseudoquistes que pueden verse en la biopsia cutánea, examinando sus aspectos histopatológicos y los principales diagnósticos diferenciales. En esta primera parte, se abordan los quistes infundibulares, dermoides, vellosos eruptivos, foliculares pigmentados, pilonidales, tricolemales, de milium, híbridos y broncogénicos, así como el esteatocistoma, el hidrocistoma y los comedones. (AU)

Cystic structures represent one of the most common findings in dermatopathology. These encompass both cystic tumors and pseudocysts resulting from the accumulation of certain substances, such as mucin. In a two-part series (of which this is the first part), we have reviewed the principal types of cysts and pseudocysts that may be observed in cutaneous biopsies, examining their histopathological features and primary differential diagnoses. This first part encompasses infundibular cysts, eruptive dermoid cysts, pigmented follicular cysts, pilonidal cysts, tricholemmal cysts, milium cysts, hybrid cysts, bronchogenic cysts, as well as steatocystoma, hydrocystoma, and comedones. (AU)

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Purpose: Basal cell carcinoma (BCC) is the most frequent malignant periocular tumor. It is associated with exposure to ultraviolet radiation, and its incidence is gradually increasing. It may occasionally display more aggressive behavior and result in orbital or intracranial invasion. Mortality from periocular BBC with orbital invasion is very low, but the associated morbidity can be significant, from disfigurement to blindness. Traditionally, these cases have been treated with orbital exenteration or with radiotherapy (RT), but in recent years, hedgehog pathway inhibitors (HPIs) have emerged, are effective in more serious cases, and are used primarily or combined with surgery, changing our perspective on the management of these patients. Methods: We studied 24 cases of periocular BCC with orbital invasion, some primary and others recurrent, which were treated between 2011 and 2021 in the same hospital. All patients had clinical or radiological evidence of orbital invasion. Orbital exenteration was performed on 9/24 of the patients (1 received vismodegib after surgery), and 12/24 were treated, surgically preserving the eyeball, with 3 of them receiving adjuvant vismodegib. Three of the twenty-four patients were treated exclusively with vismodegib (Erivedge®, Genentech). Results: One patient died due to poor tumor evolution, but the rest evolved favorably and they have had no recurrences. Vismodegib was generally well tolerated, except for in one patient who discontinued treatment due to the side effects. Conclusions: In advanced BBC with orbital invasion, mutilating surgical treatments such as exenteration or potentially vision-threatening treatments such as RT remain as options. In recent years, however, very promising new medical therapies have emerged, such as HPI, which can be used effectively instead of surgery or in combination with it, preserving the eye and vision, which implies a new approach to treatment.

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Right ventricular (RV) failure remains the strongest determinant of survival in pulmonary hypertension (PH). We aimed to identify relevant mechanisms, beyond pressure overload, associated with maladaptive RV hypertrophy in PH. To separate the effect of pressure overload from other potential mechanisms, we developed in pigs two experimental models of PH (M1, by pulmonary vein banding and M2, by aorto-pulmonary shunting) and compared them with a model of pure pressure overload (M3, pulmonary artery banding) and a sham-operated group. Animals were assessed at 1 and 8 months by right heart catheterization, cardiac magnetic resonance and blood sampling, and myocardial tissue was analyzed. Plasma unbiased proteomic and metabolomic data were compared among groups and integrated by an interaction network analysis. A total of 33 pigs completed follow-up (M1, n = 8; M2, n = 6; M3, n = 10; and M0, n = 9). M1 and M2 animals developed PH and reduced RV systolic function, whereas animals in M3 showed increased RV systolic pressure but maintained normal function. Significant plasma arginine and histidine deficiency and complement system activation were observed in both PH models (M1&M2), with additional alterations to taurine and purine pathways in M2. Changes in lipid metabolism were very remarkable, particularly the elevation of free fatty acids in M2. In the integrative analysis, arginine-histidine-purines deficiency, complement activation, and fatty acid accumulation were significantly associated with maladaptive RV hypertrophy. Our study integrating imaging and omics in large-animal experimental models demonstrates that, beyond pressure overload, metabolic alterations play a relevant role in RV dysfunction in PH.

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INTRODUCTION: The European Environment Agency estimates that 75% of the European population lives in cities. Despite the many advantages of city life, the risks and challenges to health arising from urbanisation need to be addressed in order to tackle the growing burden of disease and health inequalities in cities. This study, Urban environment and health: a cross-sectional multiregional project based on population health surveys in Spain (DAS-EP project), aims to investigate the complex association between the urban environmental exposures (UrbEEs) and health. METHODS AND ANALYSIS: DAS-EP is a Spanish multiregional cross-sectional project that combines population health surveys (PHS) and geographical information systems (GIS) allowing to collect rich individual-level data from 17 000 adult citizens participating in the PHS conducted in the autonomous regions of the Basque Country, Andalusia, and the Valencian Community, and the city of Barcelona in the years 2021-2023. This study focuses on the population living in cities or metropolitan areas with more than 100 000 inhabitants. UrbEEs are described by objective estimates at participants' home addresses by GIS, and subjective indicators present in PHS. The health outcomes included in the PHS and selected for this study are self-perceived health (general and mental), prevalence of chronic mental disorders, health-related quality of life, consumption of medication for common mental disorders and sleep quality. We aim to further understand the direct and indirect effects between UrbEEs and health, as well as to estimate the impact at the population level, taking respondents' sociodemographic and socioeconomic characteristics, and lifestyle into consideration. ETHICS AND DISSEMINATION: The study was approved by the regional Research Ethics Committee of the Basque Country (Ethics Committee for Research Involving Medicinal Products in the Basque Country; PI2022138), Andalusia (Biomedical Research Ethics Committee of the Province of Granada; 2078-N-22), Barcelona (CEIC-PSMar; 2022/10667) and the Valencian Community (Ethics Committee for Clinical Research of the Directorate General of Public Health and Center for Advanced Research in Public Health; 20221125/04). The results will be communicated to the general population, health professionals, and institutions through conferences, reports and scientific articles.

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Colorectal cancer (CRC) is one of the most common tumours worldwide, and 70% of CRC patients are over 65 years of age. However, the scientific evidence available for these patients is poor, as they are underrepresented in clinical trials. Therefore, a group of experts from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (SEOM), the Spanish Cooperative Group for the Treatment of Digestive Tumours, (TTD) and the Multidisciplinary Spanish Group of Digestive Cancer (GEMCAD) have reviewed the scientific evidence available in older patients with CRC. This group of experts recommends a multidisciplinary approach and geriatric assessment (GA) before making a therapeutic decision because GA predicts the risk of toxicity and survival and helps to individualize treatment. In addition, elderly patients with localized CRC should undergo standard cancer resection, preferably laparoscopically. The indication for adjuvant chemotherapy (CT) should be considered based on the potential benefit, the risk of recurrence, the life expectancy and patient comorbidities. When the disease is metastatic, the possibility of radical treatment with surgery, radiofrequency (RF) or stereotactic body radiation therapy (SBRT) should be considered. The efficacy of palliative CT is similar to that seen in younger patients, but elderly patients are at increased risk of toxicity. Clinical trials should be conducted with the elderly population and include GAs and specific treatment plans (AU)

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