CD155/PVR determines acute myeloid leukemia targeting by Delta One T cells.

ABSTRACT: Relapsed or refractory acute myeloid leukemia (AML) remains a major therapeutic challenge. We have recently developed a Vδ1+ γδ T cell-based product for adoptive immunotherapy, named Delta One T (DOT) cells, and demonstrated their cytolytic capacity to eliminate AML cell lines and primary blasts in vitro and in vivo. However, the molecular mechanisms responsible for the broad DOT-cell recognition of AML cells remain poorly understood. Here, we dissected the role of natural killer (NK) cell receptor ligands in AML cell recognition by DOT cells. Screening of multiple AML cell lines highlighted a strong upregulation of the DNAM-1 ligands, CD155/pulmonary vascular resistance (PVR), CD112/nectin-2, as well as the NKp30 ligand, B7-H6, in contrast with NKG2D ligands. CRISPR-mediated ablation revealed key nonredundant and synergistic contributions of PVR and B7-H6 but not nectin-2 to DOT-cell targeting of AML cells. We further demonstrate that PVR and B7-H6 are critical for the formation of robust immunological synapses between AML and DOT cells. Importantly, PVR but not B7-H6 expression in primary AML samples predicted their elimination by DOT cells. These data provide new mechanistic insight into tumor targeting by DOT cells and suggest that assessing PVR expression levels may be highly relevant to DOT cell-based clinical trials.

In-depth analysis of the interplay between oncogenic mutations and NK cell-mediated cancer surveillance in solid tumors.

Natural killer (NK) cells play a crucial role in antitumoral and antiviral responses. Yet, cancer cells can alter themselves or the microenvironment through the secretion of cytokines or other factors, hindering NK cell activation and promoting a less cytotoxic phenotype. These resistance mechanisms, often referred to as the "hallmarks of cancer" are significantly influenced by the activation of oncogenes, impacting most, if not all, of the described hallmarks. Along with oncogenes, other types of genes, the tumor suppressor genes are frequently mutated or modified during cancer. Traditionally, these genes have been associated with uncontrollable tumor growth and apoptosis resistance. Recent evidence suggests oncogenic mutations extend beyond modulating cell death/proliferation programs, influencing cancer immunosurveillance. While T cells have been more studied, the results obtained highlight NK cells as emerging key protagonists for enhancing tumor cell elimination by modulating oncogenic activity. A few recent studies highlight the crucial role of oncogenic mutations in NK cell-mediated cancer recognition, impacting angiogenesis, stress ligands, and signaling balance within the tumor microenvironment. This review will critically examine recent discoveries correlating oncogenic mutations to NK cell-mediated cancer immunosurveillance, a relatively underexplored area, particularly in the era dominated by immune checkpoint inhibitors and CAR-T cells. Building on these insights, we will explore opportunities to improve NK cell-based immunotherapies, which are increasingly recognized as promising alternatives for treating low-antigenic tumors, offering significant advantages in terms of safety and manufacturing suitability.

[Pilot programme for screening perimenopausal women for cardiovascular risk from community pharmacy: MENOVASC Project]. / Programa piloto de cribado de riesgo cardiovascular en la mujer perimenopáusica desde la farmacia comunitaria: proyecto 'MENOVASC'.

Introduction: Cardiovascular diseases have been the leading cause of death in the world for more than 20 years. They are generally unusual in premenopausal women due to the cardiovascular protection of endogenous estrogens, so the cardiovascular risk in these has traditionally been underestimated. Objectives: Establish a protocol for vascular risk screening in perimenopausal women from the community pharmacy. Material and methods: Descriptive study from an opportunistic sample in a community pharmacy of women between 45 and 55 years old. Participants were cited at the pharmacy and their cholesterol and blood pressure levels, weight, and height were taken. Information was collected on women's general and specific cardiovascular risk factors, medication they were taking and smoking. These data were used to estimate cardiovascular risk using SCORE tables. Results: 18 forms were collected, with the average age of the applicants being 49 (SD 3) years old. 38.9% (CI95%: 17.3 a 64.3) had high blood pressure and 44.4% (CI95%: 21.5 a 69.2) had cholesterol levels equal to or higher than 190 mg/ml. 100% had some traditional or specific risk factor for women. Conclusions: The usefulness of vascular risk screening in perimenopausal women is confirmed. All this places value on the intervention of the community pharmacist in the detection and management of cardiovascular risk factors.

Utilización de antidepresivos y prescripción fuera de ficha técnica en atención primaria en España (2013-2018) / Antidepressant use and off-label prescribing in primary care in Spain (2013–2018)

Introducción: Estudios recientes muestran un aumento del uso de antidepresivos en menores de 18 años, aunque pocos de ellos cuentan con indicación en este grupo de edad. El objetivo de este estudio es calcular la prevalencia anual del uso de antidepresivos en niños y adolescentes y revisar la adecuación de la prescripción a las indicaciones actuales. Métodos: Estudio de prevalencia de la utilización de antidepresivos en menores de 18 años a partir de los registros de la Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) durante el periodo 2013-2018, considerando al menos una prescripción por año para un mismo paciente. Resultados: La prevalencia de prescripción de antidepresivos entre los pacientes de la cohorte BIFAP ha aumentado de 2013 (7,97 prescripciones/1.000 pacientes) a 2018 (8,87 prescripciones/1.000 pacientes) en la mayoría de los grupos y en ambos sexos. El sexo femenino suma la mayoría de las prescripciones, superando al masculino en hasta 2,5 puntos en las tasas generales. En menores de 13 años la tendencia se invierte y los antidepresivos predominan en los chicos. La prevalencia de las prescripciones aumenta con la edad de los pacientes, igual que la proporción de tratamientos fuera de ficha técnica. El empleo de fármacos sin indicación disminuye con el transcurso del tiempo. Conclusiones: Observamos un aumento gradual en la prevalencia de prescripción de antidepresivos en menores de 18 años, preponderante en el sexo femenino. La elevada proporción de uso de estos fármacos sin indicación autorizada exige profundizar en el balance beneficio-riesgo y en alternativas de tratamiento más seguras. (AU)

Introduction: Recent studies show an increase in the use of antidepressants in minors (younger than 18 years), although few antidepressants are indicated for this age group. The aim of our study was to calculate the annual prevalence of antidepressant use in children and adolescents and to review the adherence of prescription to current indications. Methods: Study of the prevalence of antidepressant use in minors based on the records of the Electronic Database for Pharmacoepidemiologic Studies in Primary Care (BIFAP) of Spain for the 2013–2018 period, considering at least one prescription per year for each patient. Results: The prevalence of antidepressant prescription in patients from the BIFAP cohort increased between 2013 (7.97 prescriptions per 1000 patients) and 2018 (8.87 prescriptions per 1000 patients), in most groups and in both sexes. In this period, female patients received the most prescriptions, surpassing prescriptions in male patients by up to 2.5 points in the overall rates. In patients younger than 13 years, this trend was inverted and antidepressant use was higher in male patients. The prevalence of prescription rose with increasing patient age, as did the proportion of off-label prescriptions. The use of off-label medication decreased over time. Conclusions: There was a gradual increase in the prevalence of antidepressant prescription in minors younger than 18 years, with a predominance of the female sex. The high proportion of unapproved medication use in this age group calls for more thorough investigation of the risk–benefit balance of these treatments and of safer treatment alternatives. (AU)

Nefrolitiasis en la paciente gestante: revisión de la literatura / Renal lithiasis in pregnant patient: a literary review

Resumen La litiasis renal en la paciente gestante es una condición relativamente infrecuente; sin embargo, es la causa más común de dolor no obstétrico durante el embarazo. En el periodo de gestación se producen diversos cambios anatomofisiológicos en el tracto urinario, como la dilatación de los cálices renales, la pelvis renal y los uréteres por causa del efecto que ejerce la progesterona sobre el músculo liso uretral, y la compresión de los uréteres por el útero grávido. Estas modificaciones conducen a un aumento del flujo plasmático renal y de la tasa de filtrado glomerular, ocasionando hiperuricosuria e hipercalciuria. Del mismo modo, durante el embarazo también se produce un aumento de la secreción de inhibidores de cálculos, por lo cual la prevalencia de la formación de cálculos durante el embarazo es similar a la de las mujeres no embarazadas. El bajo índice de sospecha por parte del médico tratante puede entorpecer el diagnóstico y el tratamiento de esta patología, que también son limitados en la gestación debido a los potenciales riesgos teratogénicos. Se realiza una revisión narrativa de la literatura partiendo de la evidencia científica disponible en las diferentes bases de datos y de esta manera se pretende instruir al médico en los aspectos clave de dicho tema.

Abstract Renal lithiasis in pregnant women is a relatively rare condition. However, it is the most common cause of non-obstetric pain during pregnancy. During the gestation period, various anatomical-physiological changes occur in the urinary tract. These changes include dilation of the renal calyces, renal pelvis, and ureters due to the effect of progesterone on urethral smooth muscle and compression of the ureters by the gravid uterus. These modifications lead to an increase in renal plasma flow and glomerular filtration rate, thus causing hyperuricosuria and hypercalciuria. Similarly, during pregnancy there is also an increase in the secretion of stone inhibitors, therefore, the prevalence of stone formation during pregnancy is similar to non-pregnant women. The low index of suspicion on the part of the treating physician can hinder the diagnosis and treatment of this pathology, which is also limited in pregnancy due to teratogenic risks. A narrative review of the literature is carried out based on the scientific evidence available in the different databases and in this way it is intended to instruct the doctor in the key aspects of said topic.

Amiloidosis asociada a hemodiálisis: revisión de sus aspectos etiopatogénicos / Hemodialysis-Associated Amyloidosis: Review of its ethiopathogenic aspects

Resumen La amiloidosis constituye una complicación importante en los pacientes con enfermedad renal crónica que son sometidos a hemodiálisis durante extensos períodos de tiempo. Al igual que en otras amiloidosis sistémicas, en la amiloidosis asociada a hemodiálisis intervienen diferentes sustancias, algunas de ellas de carácter fibrilar, como la βeta-2-microglobulina, la cual representa una de las proteínas de mayor relevancia dada su implicación etiopatogénica. A pesar de que las técnicas de hemodiálisis han sido mejoradas con el paso de los años, dicha entidad continúa siendo una complicación relativamente frecuente; tal es que se puede presentar hasta en el 80 % de los pacientes con hemodiálisis prolongadas. Por lo tanto, se hizo imprescindible realizar una revisión narrativa partiendo de la literatura científica disponible en las diferentes bases de datos, con el objetivo de contribuir a mejorar y actualizar el conocimiento del médico en dicho tópico; al abarcar desde los aspectos generales y su fisiopatología, hasta su presentación clínica, diagnóstico y tratamiento.

Abstract Amyloidosis is a major complication in patients with chronic kidney disease who undergo hemodialysis for long periods of time. As in other systemic amyloidosis, different substances are involved in amyloidosis associated with different substances, some of them fibrillar in nature, such as βeta-2-microglobulin, which represents one of the most relevant proteins given its etiopathogenic involvement. Despite the fact that hemodialysis techniques have been improved over the years, this entity continues to be a frequent complication; such is that it can occur in up to 80% of patients with prolonged hemodialysis. Therefore, it was essential to carry out a narrative review based on the scientific literature available in the different databases with the aim of contributing to improve and update the doctor's knowledge on this topic; ranging from the general aspects and its pathophysiology, to its clinical presentation, diagnosis, and treatment.

Edulcorantes artificiales y su papel en la enfermedad renal crónica: una revisión

Los edulcorantes no calóricos surgieron como una opción segura y saludable en el marco de la alimentación y, por lo tanto, han sido de gran interés en la cultura dietética adquirida en la actualidad; es importante mencionar que en esta cultura adquirida el consumo de comida rápida y con altos niveles de azúcar ha tomado especial fuerza, lo que repercute negativamente en la incidencia de enfermedades metabólicas. En este orden de ideas, los edulcorantes no calóricos se convierten en una mejor opción para la salud en la que no es necesario hacer un cambio drástico en el estilo de vida. No obstante, los beneficios de los edulcorantes artificiales no calóricos no han sido estudiados a profundidad y no se ha evidenciado que una dieta a base de estos sustitutivos provoque un cambio significativo en el desarrollo de enfermedades metabólicas asociadas al consumo de azúcar, por el contrario, se han relacionado con enfermedades como obesidad, diabetes mellitus tipo 2 y síndrome metabólico. Asimismo, estos pueden provocar una serie de cambios metabólicos a través de distintos mecanismos que terminan en proteinuria progresiva y descenso de la tasa de filtrado glomerular. A partir de lo anterior, se hace necesario un análisis del riesgo que se corre al elegir esta opción alimenticia, para así no dejarse llevar por los procesos mediáticos que los promocionan, sino más bien, regirse por los hallazgos científicos.

Non-caloric artificial sweeteners have emerged to offer a safe and healthy option in the framework of food. They have received special attention in recent decades, precisely because of the current food culture, where fast food and high sugar consumption have taken on special strength, which has a negative impact on the incidence of metabolic diseases. In that order of ideas, non-caloric artificial sweeteners propose better health without the need for a drastic change in lifestyle. However, its benefits have not been studied in depth, in addition to the fact that there has been no significant change in the development of metabolic diseases associated with sugar consumption, on the contrary, they have been related to diseases such as obesity, type 2 diabetes mellitus and metabolic syndrome. Likewise, they cause a series of metabolic changes by different mechanisms that end in progressive proteinuria and a decrease in the glomerular filtration rate. In order with the above, an analysis of the risk to which one is subjected when choosing this food option is necessary, and not be deafened, much less dazzled by the media processes, if not rather, be governed by scientific findings.

Epidemiología del tratamiento farmacológico del trastorno por déficit de atención e hiperactividad (TDAH) en la Región de Murcia: diferencias por sexo, edad y lugar de residencia / The epidemiology of pharmacologically treated attention deficit hyperactivity disorder (ADHD) in the Region of Murcia, Spain: Differences by gender, age and location of residence

INTRODUCCIÓN: El trastorno por déficit de atención e hiperactividad (TDAH) es la alteración del comportamiento más frecuente en la infancia y la adolescencia, representando un problema de salud pública. El tratamiento recomendado incluye tratamiento farmacológico y psicosocial. El objetivo de este estudio es analizar la evolución del consumo de los fármacos utilizados para el TDAH en la Región de Murcia y su variabilidad sociodemográfica. MÉTODO: Estudio observacional retrospectivo referido a la dispensación de medicamentos para el tratamiento del TDAH mediante receta en la Región de Murcia entre los años 2010 y 2014. Se calcularon las tasas de consumo expresadas en dosis diarias definidas (DDD) por 1.000 habitantes/día (DHD), estratificadas por sexo y edad y las razones de prevalencia de tratamiento por sexo comparando las tasas de consumo de hombres y de mujeres. RESULTADOS: Durante el periodo estudiado prácticamente se ha duplicado el consumo de medicamentos para el tratamiento del TDAH, pasando de tasas de 5,58 DHD y 3,39 DHD en 2010 a 9,34 DHD y 6,71 DHD en 2014, para las franjas de edad de 10 a 14 años y de 15 a 19 años, respectivamente. Los varones de entre 10 y 14 años presentan las tasas de consumo más elevadas, observándose variabilidad geográfica con menores consumos relativos en las zonas rurales. CONCLUSIÓN: Se ha producido un importante aumento del uso de los medicamentos para el TDAH en la Región de Murcia, si bien las tasas de consumo siguen siendo inferiores a los datos de otras comunidades autónomas o países de nuestro entorno. Se observa una gran variabilidad geográfica con un mayor consumo en adolescentes de zonas urbanas

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is the most frequent disorder in childhood and adolescence, and is seen as a public health problem. The recommended treatment includes pharmacological and psychosocial treatment. The aim of this work was to study the changes in the prescribing of the medicines used in ADHD treatment in the Region of Murcia, as well as their socio-demographic variability. METHOD: A retrospective observational study was conducted using the dispensing of medicines for ADHD treatment by means of prescription in the Region of Murcia from 2010 to 2014. The consumption rates were determined as defined daily doses (DDD) per thousand inhabitants/day (DHD), stratified by gender and age. The reasons for prevalence of treatment by gender were also determined by comparing male and female consumption rates. RESULTS: The consumption of medicines for ADHD treatment had almost doubled in the period studied, from 5.58 DHD and 3.39 DHD in 2010 to 9.34 DHD and 6.71 DHD in 2014, for the age range of 10-14 and 15-19, respectively. Boys from 10-14 showed the highest consumption rates, showing a high geographical variability with less consumption in rural areas. CONCLUSION: The results showed a large increase in the use of medicines for ADHD treatment in the Region of Murcia, although the consumption rates are still lower than in other Autonomous Communities or neighbouring countries. A wide geographical variability was found, with a higher consumption in adolescents from urban areas

Variabilidad del consumo de antibióticos en una región sanitaria según áreas de salud y modelo de cobertura: sistema nacional de salud vs. mutualidad de funcionarios / Variability in antibiotic consumption within a regional health service, according to health area and model of healthcare coverage: national health system vs. civil servants’ mutual insurance society

Introducción. El objetivo de este estudio es analizar el consumo de antibióticos en la Región de Murcia en el contexto nacional y europeo en el año 2011 y su patrón de consumo en las distintas áreas de salud, y entre los usuarios del servicio regional de salud y los de la mutualidad de funcionarios civiles del estado (MUFACE). Métodos. Estudio observacional retrospectivo referido a la dispensación de antibióticos mediante receta en la Región de Murcia durante el año 2011. Se calcularon las tasas de consumo expresada en dosis diarias definidas (DDD) por mil habitantes/día (DHD) y las razones de utilización estandarizadas (RUE). Resultados. La tasa de consumo de antibióticos en 2011 en la Región de Murcia fue de 30,05 DHD, muy superior a la media nacional (20,9 DHD) y a la de la Unión Europea (21,57 DHD). Las áreas de salud con mayor y menor tasa de consumo son, respectivamente Vega Alta (RUE: 124,44; IC95% 124,26 a 124,61) y Cartagena (RUE: 84,16; IC95% 84,10 a 84,22). Los usuarios mutualistas de la Región de Murcia tienen tasas de consumo superiores a las de los beneficiarios del servicio regional de salud (RUE: 105,01; IC95% 104,86 a 105,17). Conclusiones. Existe una elevada prescripción de antibióticos en la Región de Murcia, observándose además una notable variabilidad entre las distintas áreas de salud, principalmente en el caso de cefalosporinas y macrólidos, que podría estar en parte asociada al nivel de frecuentación (AU)

Introduction. The aim of this study is to describe antibiotic consumption in the Region of Murcia in 2011, within the Spanish and European context, as well as to analyze the differences within the Region, both between health areas, and between users of the regional health service and those protected by the civil servants’ mutual insurance society (MUFACE). Methods. Retrospective observational study of prescriptions dispensed by the pharmacies in the Region of Murcia during 2011. Consumption rates were expressed as defined daily doses (DDD) per 1,000 inhabitants/day and standardized consumption ratios (SCR). Results. Overall antibiotics consumption rate in the Region of Murcia in 2011 was 30.05 DDD/1000/ day (DID), which is much above the average rate for Spain (20.9 DID) and for the European Union (21.57 DID). Health areas within the Region with the highest and lowest consumption rate are, respectively, Vega Alta (SCR: 124.44; CI95% 124.26 to 124.61) and Cartagena (SCR:84.16; CI95% 84.10 to 84.22). Civil servants covered by the mutual society have higher consumption rates than users of the regional health service (SCR: 105.01; CI95% 104.86 to 105.17). Conclusions. There is a high level of antibiotic prescription in the Region of Murcia Region in relative terms. A great variability in antibiotics consumption was observed between the different health areas, which might be related to the higher rate of the frequency of visits. The highest amount of variability in antibiotics prescription was found in cephalosporins and macrolides (AU)