Triple Therapy and Clinical Control in B+ COPD Patients: A Pragmatic, Prospective, Randomized Trial.

INTRODUCTION: Treatment with LABA/LAMA is recommended in GOLD B patients. We hypothesized that triple therapy (LABA/LAMA/ICS) will be superior to LABA/LAMA in achieving and maintaining clinical control (CC), a composite outcome that considers both impact and disease stability in a subgroup of GOLD B patients (here termed GOLD B+ patients) characterized by: (1) remaining symptomatic (CAT≥10) despite regular LABA/LAMA therapy; (2) having suffered one moderate exacerbation in the previous year; and (3) having blood eosinophil counts (BEC) ≥150cells/µL. METHODS: The ANTES B+ study is a prospective, multicenter, open label, randomized, pragmatic, controlled trial designed to test this hypothesis. It will randomize 1028 B+ patients to continue with their usual LABA/LAMA combination prescribed by their attending physician or to begin fluticasone furoate (FF) 92µg/umeclidinium (UMEC) 55µg/vilanterol (VI) 22µg in a single inhaler q.d. for 12 months. The primary efficacy outcome will be the level of CC achieved. Secondary outcomes include the clinical important deterioration index (CID), annual rate of exacerbations, and FEV1. Exploratory objectives include the interaction of BEC and smoking status, all-cause mortality and proportion of patients on LABA/LAMA arm that switch therapy arms. Safety analysis include adverse events and incidence of pneumonia. RESULTS: The first patient was recruited on February 29, 2024; results are expected in the first quarter of 2026. CONCLUSIONS: The ANTES B+ study is the first to: (1) explore the efficacy and safety of triple therapy in a population of B+ COPD patients and (2) use a composite index (CC) as the primary result of a COPD trial.

Metronomic and single high-dose paclitaxel treatments produce distinct heterogenous chemoresistant cancer cell populations.

More than 75% of epithelial ovarian cancer (EOC) patients experience disease recurrence after initial treatment, highlighting our incomplete understanding of how chemoresistant populations evolve over the course of EOC progression post chemotherapy treatment. Here, we show how two paclitaxel (PTX) treatment methods- a single high dose and a weekly metronomic dose for four weeks, generate unique chemoresistant populations. Using mechanically relevant alginate microspheres and a combination of transcript profiling and heterogeneity analyses, we found that these PTX-treatment regimens produce distinct and resilient subpopulations that differ in metabolic reprogramming signatures, acquisition of resistance to PTX and anoikis, and the enrichment for cancer stem cells (CSCs) and polyploid giant cancer cells (PGCCs) with the ability to replenish bulk populations. We investigated the longevity of these metabolic reprogramming events using untargeted metabolomics and found that metabolites associated with stemness and therapy-induced senescence were uniquely abundant in populations enriched for CSCs and PGCCs. Predictive network analysis revealed that antioxidative mechanisms were likely to be differentially active dependent on both time and exposure to PTX. Our results illustrate how current standard chemotherapies contribute to the development of chemoresistant EOC subpopulations by either selecting for intrinsically resistant subpopulations or promoting the evolution of resistance mechanisms. Additionally, our work describes the unique phenotypic signatures in each of these distinct resistant subpopulations and thus highlights potential vulnerabilities that can be exploited for more effective treatment.

Spatial Heterogeneity in Cytoskeletal Mechanics Response to TGF-ß1 and Hypoxia Mediates Partial Epithelial-to-Meshenchymal Transition in Epithelial Ovarian Cancer Cells.

Metastatic progression of epithelial ovarian cancer (EOC) involves the partial epithelial-to-mesenchymal transition (EMT) of cancer cells in the primary tumor and dissemination into peritoneal fluid. In part to the high degree of heterogeneity in EOC cells, the identification of EMT in highly epithelial cells in response to differences in matrix mechanics, growth factor signaling, and tissue hypoxia is very difficult. We analyzed different degrees of EMT by tracking changes in cell and nuclear morphology, along with the organization of cytoskeletal proteins. In our analysis, we see a small percentage of individual cells that show dramatic response to TGF-ß1 and hypoxia treatment. We demonstrate that EOC cells are spatially aware of their surroundings, with a subpopulation of EOC cells at the periphery of a cell cluster in 2D environments exhibited a greater degree of EMT. These peripheral cancer cells underwent partial EMT, displaying a hybrid of mesenchymal and epithelial characteristics, which often included less cortical actin and more perinuclear cytokeratin expression. Collectively, these data show that tumor-promoting microenvironment conditions can mediate invasive cell behavior in a spatially regulated context in a small subpopulation of highly epithelial clustered cancer cells that maintain epithelial characteristics while also acquiring some mesenchymal traits through partial EMT.

Vaporizadores en adolescentes: factores asociados, prevalencia, y perspectiva comunitaria de la promoción de la salud / Vaporizers in Adolescents: Associated Factors, Prevalence, and Community Perspective on Health Promotion

Resumen Objetivo: En el tercero de los Objetivos del Desarrollo Sostenible: Salud y Bienestar, se encuentra la meta destinada a fortalecer la prevención y el tratamiento del abuso de sustancias. Se proponen tres objetivos: (1) identificar bibliografía referente al uso de vaporizadores en adolescentes y jóvenes para constatar variables importantes como factores asociados, (2) realizar una recopilación comunitaria mediante entrevistas y foros para reconocer la percepción social del uso de vaporizadores, y (3) determinar, en la población de jóvenes y adolescentes puertorriqueños, la prevalencia del uso de vaporizadores. Materiales y Métodos: Un estudio mixto: cualitativo observacional y transversal analítico fue realizado basado en el modelo conceptual de la Promoción de la Salud (comunitario, individual y científico) con una recopilación de datos consistente en: revisión de 13 artículos, entrevistas a informantes claves que trabajan con la salud y seguridad de jóvenes puertorriqueños, y análisis, utilizando el programado SPSS, de prevalencias del cuestionario puertorriqueño autoadministrado Consulta Juvenil (n=8,603), base de datos secundaria. Resultados: La literatura establece factores asociados como: mercadeo, relación familiar y socialización. Se encontró que las organizaciones visualizan a la promoción de la salud comunitaria como un método preventivo. El 21.9% de estudiantes de escuela superior hacen uso de vaporizadores. 22.1% no saben la sustancia que contiene su vaporizador. Conclusión: La promoción de la salud se basa en políticas públicas favorables, educación en salud, movilización social-comunitaria y trabajo multidisciplinario. Recomendamos que, se practiquen evaluaciones y prevenciones del uso de vaporizadores basados en una salud pública promotora de la salud. De esta manera, se trabajará el Objetivo del Desarrollo Sostenible: Salud y Bienestar, para la protección de generaciones jóvenes y disminuir las prevalencias del uso de sustancias.

Abstract Objective: In the third of the Sustainable Development Goals: Health and Well-being, there is a goal aimed at strengthening the prevention and treatment of substance abuse. Three objectives are proposed: (1) identify a bibliography regarding the use of vaporizers in adolescents and young people to verify important variables as associated factors, and (2) carry out a community compilation through interviews and forums to recognize the social perception of the use of vaporizers, and (3) determine, in the population of Puerto Rican youth and adolescents, the prevalence of the use of vaporizers. Materials and methods: A mixed study: qualitative observational and cross-sectional analytical was carried out with data collection consisting of a review of 13 articles, interviews with key informants who work with the health and safety of young Puerto Ricans, and analysis, using the SPSS program, of the prevalence of the Puerto Rican self-administered questionnaire Consulta Juvenil as a secondary database (n=8,603). Results: The literature establishes associated factors such as marketing, family relationship, and socialization. It was found that organizations view community health promotion as a preventive method. 21.9% of high school students use vaporizers. 22.1% do not know the substance contained in their vaporizer. Conclusion: Health promotion is based on favorable public policies, health education, social- community mobilization, and multidisciplinary work. We recommend that evaluations and prevention of the use of vaporizers be practiced based on health-promoting public health. In this way, the Sustainable Development Goal will be worked on: Health and Well-being for the protection of young generations and to reduce the prevalence of substance use.

Real-world Data of Paclitaxel and Cetuximab in Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck.

BACKGROUND/AIM: Prior immune-checkpoint inhibitors, weekly paclitaxel-cetuximab was one of the few options for platinum-ineligible patients with recurrent/ metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN). This real-world study analyzed the long-term outcomes of this regimen. PATIENTS AND METHODS: A multicenter, retrospective, observational, cross-sectional, chart review study was realized in nine hospitals of the Galician Group of Head and Neck Cancer. Eligible population was adult platinum-ineligible patients with R/M SCCHN (unfit to, or after progressing following EXTREME or other platinum-based regimens) that received weekly paclitaxel plus cetuximab regimen as first- or second-line (1L or 2L) between January 2009 and December 2014. The efficacy was evaluated (1L-2L) in regards to overall survival (OS) and progression-free survival (PFS), and safety was assessed as the incidence of adverse events (AEs). RESULTS: Seventy-five R/M-SCCHN patients received the scheme (1L, n=50; 2L: n=25). The mean age of the patients was 59 years (1L, 59.5 years; 2L, 59.2 years), 90% were male (1L, 96%; 2L, 79%), 55% were smokers (1L, 60.4%; 2L, 45.8%), and 61% presented ECOG performance status (PS) 1 (1L, 54%; 2L, 62.5%). Median OS [interquartile range (IQR)] was 8.85 (4.22-40.96) months. Median PFS (IQR) was 8.5 (3.93-12.55) (1L) and 8.8 (5.62-16.91) (2L) months. Disease control rate was 60% (1L) and 85% (2L). Weekly paclitaxel-cetuximab was well tolerated in 1L/2L (cutaneous-toxicity, mucositis, neuropathy; mainly Grade 1-2). No grade 4 AEs were notified in 2L. CONCLUSION: Weekly paclitaxel-cetuximab is an active and well tolerated therapeutical option in platinum-ineligible or after platinum regimens in R/M-SCCHN patients.

Orientaciones de las maestrías para profesionales de la salud / Orientations of the Master's Degree courses for health professionals

Introducción: El Reglamento de Educación de Posgrado de la República de Cuba de 2019 abre nuevas respuestas a las necesidades de formación académica de maestría para profesionales de la salud, cuestión pendiente en las áreas asistencial, administrativa y especializada. Esto tributa a la continuidad, pertinencia e interdisciplinariedad de la formación profesional, y a los diseños curriculares de maestría en este sector. Objetivo: Fundamentar las orientaciones que pueden asumir los programas de maestría para profesionales de la salud. Posicionamiento del autor: Se parte de posiciones teórico-metodológicas del proceso pedagógico de posgrado en el área de la salud, de su relación con la actividad laboral que desempeñan sus trabajadores y de la legislación vigente en materia de posgrado en el país, para considerar el sistema de actividades profesionales fundamentales que aseguran el cumplimiento de las misiones de la institución. Esto requiere de una generalización esencial y de abstracción sucesiva, a partir del análisis de las funciones que se desempeñan en los puestos de trabajo y que tributan al cumplimiento de esas misiones. La maestría aporta una amplia y avanzada cultura científica en determinada área del saber, así como mayor capacidad y desarrollo para llevar a cabo las actividades. Esto se reinvierte de forma potenciada en sus desempeños en el puesto de trabajo, y en el desarrollo y cumplimiento de la misión social de la institución. Conclusiones: Las orientaciones de las maestrías para profesionales de la salud son asistencia, investigación, docencia y administración. Independientemente de la orientación que asuma el programa, la investigación continúa siendo esencial(AU)

Introduction: The 2019 regulations on postgraduate education of the Republic of Cuba open new responses to the needs of academic master's degree courses for training health professionals, a pending issue in the healthcare, management and specialization areas. This contributes to the continuity, pertinence and interdisciplinarity of professional training, as well as to the master's degree curricular designs in this sector. Objective: To substantiate the orientations that master's degree programs for health professionals can assume. Author position: The foundations are made up of theoretical-methodological positions corresponding to the postgraduate pedagogical process in the health area, its relation with the occupational activity carried out by health workers, and the currently valid legislation on postgraduate education in the country, in order to consider the system of fundamental professional activities that ensure the fulfillment of institutional missions. This requires an essential generalization and subsequent abstraction, based on the analysis of the occupational functions performed and contributing to the fulfillment of these missions. The master's degree courses provide a broad and advanced scientific culture in a certain field of knowledge, as well as greater capacity and development to carry out activities. This is retrieved in an enhanced way in terms of occupational performance, as well as in the development and fulfillment of the social mission of the institution. Conclusions: The master's degree courses for health professionals are oriented to the healthcare, research, teaching and management scenarios. Regardless of the orientation of the program, research continues to be essential(AU)

Comparing the Secretomes of Chemorefractory and Chemoresistant Ovarian Cancer Cell Populations.

High-grade serous ovarian cancer (HGSOC) constitutes the majority of all ovarian cancer cases and has staggering rates of both refractory and recurrent disease. While most patients respond to the initial treatment with paclitaxel and platinum-based drugs, up to 25% do not, and of the remaining that do, 75% experience disease recurrence within the subsequent two years. Intrinsic resistance in refractory cases is driven by environmental stressors like tumor hypoxia which alter the tumor microenvironment to promote cancer progression and resistance to anticancer drugs. Recurrent disease describes the acquisition of chemoresistance whereby cancer cells survive the initial exposure to chemotherapy and develop adaptations to enhance their chances of surviving subsequent treatments. Of the environmental stressors cancer cells endure, exposure to hypoxia has been identified as a potent trigger and priming agent for the development of chemoresistance. Both in the presence of the stress of hypoxia or the therapeutic stress of chemotherapy, cancer cells manage to cope and develop adaptations which prime populations to survive in future stress. One adaptation is the modification in the secretome. Chemoresistance is associated with translational reprogramming for increased protein synthesis, ribosome biogenesis, and vesicle trafficking. This leads to increased production of soluble proteins and extracellular vesicles (EVs) involved in autocrine and paracrine signaling processes. Numerous studies have demonstrated that these factors are largely altered between the secretomes of chemosensitive and chemoresistant patients. Such factors include cytokines, growth factors, EVs, and EV-encapsulated microRNAs (miRNAs), which serve to induce invasive molecular, biophysical, and chemoresistant phenotypes in neighboring normal and cancer cells. This review examines the modifications in the secretome of distinct chemoresistant ovarian cancer cell populations and specific secreted factors, which may serve as candidate biomarkers for aggressive and chemoresistant cancers.

Senescent mesenchymal stem cells remodel extracellular matrix driving breast cancer cells to a more-invasive phenotype.

Mesenchymal stem cells (MSCs) are essential for the regenerative process; however, biological aging and environmental stress can induce senescence - an irreversible state of growth arrest - that not only affects the behavior of cells but also disrupts their ability to restore tissue integrity. While abnormal tissue properties, including increased extracellular matrix stiffness, are linked with the risk of developing breast cancer, the role and contribution of senescent MSCs to the disease progression to malignancy are not well understood. Here, we investigated senescence-associated biophysical changes in MSCs and how this influences cancer cell behavior in a 3D matrix interface model. Although senescent MSCs were far less motile than pre-senescent MSCs, they induced an invasive breast cancer phenotype, characterized by increased spheroid growth and cell invasion in collagen gels. Further analysis of collagen gels using second-harmonic generation showed increased collagen density when senescent MSCs were present, suggesting that senescent MSCs actively remodel the surrounding matrix. This study provides direct evidence of the pro-malignant effects of senescent MSCs in tumors.

Un modelo Ecológico para la Salud mental Infanto Juvenil / Children and Adolescents Mental Health Ecological Model

Desarrollar un programa de salud mental Infanto-juvenil es complejo, por la multiplicidad de variables implicadas y la dificultad para integrarlas. Son muchos los sectores de la sociedad que juegan un rol determinante en el desarrollo infantil, lo que complejiza la generación de un diálogo integrador y efectivo entre ellos hacia un fin común, la salud mental. En el artículo se analiza la aplicación del modelo ecológico de Bronfenbrenner en la organización de salud mental de nuestro país. Planteamos que a través de él es posible ampliar la mirada y la comprensión de la complejidad del fenómeno de salud mental Infanto juvenil, facilitando el desarrollo de propuestas de intervención que incorporen la mayoría de las variables e intersectores intervinientes, como, salud, educación, Servicio nacional de menores (Sename), justicia, entre otros, y por supuesto la comunidad en general, como actores relevantes y determinantes sociales en el proceso salud­ cuidados­enfermedad.

Developing a mental health program for children and adolescents is very complex, due to the multiplicity of variables involved and the difficulty in integrating them. There are many sectors of our society that play a decisive role in child development, which complicate the generation of an inclusive and effective dialogue between them towards a common goal, mental health. The article analyzes the application of the ecological model of Urie Bronfenbrenner in the organization of public health and mental health in our country. We propose that through it, it is possible to broaden the view and understanding of the complexity of the mental health phenomenon for children and young people, facilitating the development proposals that incorporate most of the intervening variables and intervention target areas, such as health, education, Sename, justice, among others, and of course the community in general, as relevant actors and social determinants in the health- care-disease process.

Pseudohipoparatiroidismo de presentación tardía: reporte de dos casos / Pseudohypoparathyroidism: report of two cases of late presentation

Pseudohypoparathyroidism (PHP) is a group of rare genetic disorders that share organ targeted resistance to the action of parathyroid hormone (PTH) as a common feature. Biochemically, they may present with hypocalcemia, hyperphosphatemia and elevated PTH. Some forms present with a specific phenotype: short stature, round facies, short neck, obesity, brachydactyly and subcutaneous calcifications, called Albrigth's Hereditary Osteodystrophy (AHO). This spectrum of disorders are caused by several alterations in the gene coding for the alpha subunit of the G protein (GNAS): an ubiquitous signaling protein that mediates the action of numerous hormones such as PTH, TSH, gonadotropins, and ACTH, among others. According to their inheritance with maternal or paternal imprinting, they may manifest in a diversity of clinical forms. Although most commonly diagnosed during childhood, PHP may manifest clinically during adolescence or early adulthood. We report two late presenting cases of pseudohypoparathyroidism. A 21-year-old female with biochemical abnormalities characteristic of pseudohypoparathyroidism who was misdiagnosed as epilepsy and a 13-year-old boy with the classic AHO phenotype but without alterations in phospho-calcium metabolism, compatible with pseudopseudohypoparathyrodism.

Caracterización de los pacientes diabéticos y prediabéticos portadores de VIH en hospital terciario de Concepción / Characterization of diabetic and prediabetic patients carriying of HIV in a tertiary hospital in Concepcion

The increased survival of patients with Human Immunodeficiency Virus (HIV), due in great part to antiretroviral therapy, has led to the disease becoming a chronic condition. The result of this new picture, is the development of several chronic metabolic diseases, including diabetes mellitus. The aim of this retrospective study is to evaluate the prevalence of diabetes mellitus and prediabetes in HIV people that is controlled in a tertiary Chilean hospital and other epidemiological aspects of this condition. The results show a prevalence of 2.95 percent of diabetes and 13.0 percent of prediabetes in HIV patients, similar results to the international literature. The vast majority of these patients acquire diabetes or prediabetes after the HIV debut. It is important to know our local prevalence of metabolic comorbidities in these patients, in this case diabetes and prediabetes, to improve our research and adequate treatment in this population.

EGFR testing and clinical management of advanced NSCLC: a Galician Lung Cancer Group study (GGCP 048-10).

PURPOSE: This study aimed to assess the incidence of mutations in the epidermal growth factor receptor (EGFR) gene in non-small-cell lung cancer (NSCLC) patients in the Galician region of Spain and the clinical management and outcome of patients carrying EGFR mutations. PATIENTS AND METHODS: All newly diagnosed advanced or metastatic NSCLC patients were screened for EGFR mutations in matched tumor samples (tissue or cytology specimens) and serum samples. RESULTS: Of 198 patients screened for EGFR mutations in tumor samples, 184 had evaluable data and, of these, 25 (13.6%) had EGFR mutations (84% sensitizing mutations). EGFR mutation was found in serum in 14 (8.1%) patients (of 174 evaluable). Compared to matched tumor tissue, serum EGFR mutation testing specificity and sensitivity were 99% and 52%, respectively. All but two patients received gefitinib. Median progression-free survival and overall survival were 10 (95% confidence interval: 4.8-15.3) months and 17.8 (95% confidence interval: 13.9-21.6) months, respectively, in patients carrying sensitizing mutations. CONCLUSION: The incidence of EGFR mutations in Galicia is consistent with previous data in Spain. Our results also support the feasibility of EGFR testing to guide treatment decision making using tumor tissue or cytology samples, or serum samples if tumor specimens are unavailable. These findings also confirm that first-line gefitinib is an active treatment option in Caucasians with EGFR mutation-positive NSCLC.

Small cell lung cancer in never-smokers.

Our aim was to describe the characteristics of a case-series of never-smoker small cell lung cancer (SCLC) cases.Cases of SCLC were selected from a prospective, multicenter, hospital-based case-control study performed in Spain. Participants were never-smokers older than 30 years with an anatomo-pathological confirmation of primary lung cancer. We collected clinical and epidemiological variables according to the study's protocol.We included 19 SCLC cases, 18 females (94.7%), median age 75 years (interquartile range (IQR) 70-80 years). Median residential radon concentration was 195 Bq·m(-3) (IQR 130-229 Bq·m(-3)). 10 patients had limited disease and nine had extended disease. Median survival was 242 days (IQR 94-496 days); 1- and 2-year survival were 36.8% and 17.6%, respectively. Survival was much higher for individuals with limited disease than for those with extended disease (median 336 versus 235 days; 1-year survival 50% versus 22.2% and 2-year survival 27% versus 0%, respectively). Performance status at diagnosis was closely related to survival.SCLC is an infrequent, highly aggressive disease in never-smokers. Survival is poor, even for limited disease. Age at diagnosis in SCLC is higher than that observed for never-smokers with adenocarcinoma. Residential radon exposure is higher than the action levels recommended by the World Health Organization.

Alpha-1 Antitrypsin Deficiency and Lung Cancer Risk: A Case-Control Study in Never-Smokers.

BACKGROUND: Never-smokers comprise up to 25% of all lung cancer cases. They could have different molecular pathways for lung cancer induction compared with smokers. Alpha-1 antitrypsin (AAT) deficiency is a hereditary trait whose main characteristic is early onset of lung emphysema. Our aim is to know if AAT-deficient carriers have a higher risk of lung cancer in a study performed exclusively in never-smokers. METHODS: We designed a multicentre hospital-based case-control study, which included incident never-smoking lung cancer cases. Controls were never-smokers attending nonmajor surgery at the participating hospitals. Controls were frequency matched on age and gender with cases. We determined AAT variants (alleles S and Z) through polymerase chain reaction. RESULTS: Two hundred and twelve cases and 318 controls were included. PiSS individuals showed a lung cancer risk of 4.64 (95% confidence interval: 1.08-19.92) compared with those with normal genotype (PiMM). When the analysis was restricted to women, the risk for PiSS increased to 7.58 (95% confidence interval: 1.40-40.87). This risk for homozygous SS was even higher for individuals exposed to environmental tobacco smoke (greater than 20 years). The presence of other alleles did not show any effect on lung cancer risk. CONCLUSIONS: Never smoking SS homozygous individuals pose an increased risk of lung cancer. The risk is higher for individuals exposed to environmental tobacco smoke.

Exposure to residential radon and lung cancer in never-smokers: the preliminary results of the LCRINS study.

INTRODUCTION AND OBJECTIVE: Residential radon is the second most important risk factor for lung cancer and the first among never-smokers. The objective of this study is to report the concentrations of residential radon in a series of never-smoker cases recruited in a multicenter study of cases and controls in northwestern Spain. In this study, all the hospitals in the Spanish province of Galicia and one from Asturias participated. PATIENTS AND METHODS: The present article includes a series of cases with residential radon measurements. All the subjects were personally interviewed, 3 ml of blood were taken from each, and they were each given instructions about how to place a residential radon detector in their homes. RESULTS: Sixty-nine case subjects were recruited, 84% of whom were women with a mean age of 71, and 81% of whom had adenocarcinoma. The average concentration of residential radon in the cases was 237 Bq/m(3), while the average concentration in the Galician population is 79 Bq/m(3). No relationship was observed between the concentration of residential radon and either sex or age at the time of diagnosis of the cases, but there was a tendency towards having a greater concentration in those diagnosed with small-cell and large-cell carcinoma. CONCLUSIONS: The concentrations of residential radon in the cases included are very high at about three times the average concentration of residential radon to which the general population of Galicia is exposed.