Nivolumab plus ipilimumab in metastatic melanoma: a critical appraisal focused on specific subpopulations

The development of immune checkpoint inhibitors has revolutionized the landscape of treatment of advanced melanoma in recent years. Based on the efficacy results of the phase III CheckMate 067 trial, nivolumab in combination with ipilimumab is one of the first-line standard options for advanced melanoma along with pembrolizumab, nivolumab, and, recently, nivolumab plus relatlimab. Counterbalancing its efficacy, nivolumab plus ipilimumab is associated with severe immune-related toxicity. This article will review the efficacy and safety of the nivolumab plus ipilimumab combination in advanced melanoma across phase I, II, and III clinical trials that evaluated this approach. We also explore the benefit of the combination schedule across different subgroups of patients and possible predictive biomarkers for efficacy outcomes in order to elucidate which patients could be the best candidates for combination or single-agent therapy. Patients with BRAF-mutant tumours, asymptomatic brain metastases, or PD-L1-negative status appear to reach better survival outcomes with the combination relative to single-agent immunotherapy

Efficient method for events detection in phonocardiographic signals

The auscultation of the heart is still the first basic analysis tool used to evaluate the functional state of the heart, as well as the first indicator used to submit the patient to a cardiologist. In order to improve the diagnosis capabilities of auscultation, signal processing algorithms are currently being developed to assist the physician at primary care centers for adult and pediatric population. A basic task for the diagnosis from the phonocardiogram is to detect the events (main and additional sounds, murmurs and clicks) present in the cardiac cycle. This is usually made by applying a threshold and detecting the events that are bigger than the threshold. However, this method usually does not allow the detection of the main sounds when additional sounds and murmurs exist, or it may join several events into a unique one. In this paper we present a reliable method to detect the events present in the phonocardiogram, even in the presence of heart murmurs or additional sounds. The method detects relative maxima peaks in the amplitude envelope of the phonocardiogram, and computes a set of parameters associated with each event. Finally, a set of characteristics is extracted from each event to aid in the identification of the events. Besides, the morphology of the murmurs is also detected, which aids in the differentiation of different diseases that can occur in the same temporal localization. The algorithms have been applied to real normal heart sounds and murmurs, achieving satisfactory results.This work has been supported by Fundación Séneca of Región de Murcia and Ministerio de Ciencia y Tecnología of Spain, under grants PB/63/FS/02 and TIC2003-09400-C04-02, respectively

Corporate Governance And Accuracy Level Of Financial Distress Prediction Models

This investigation verifies the impact of corporate governance measure on the likelihood of financial distress on the Spanish Stock Exchange for the time period from 2007 to 2012. The authors applied an empirical study with panel data and conducted regression logistic models with the objective to calculate different measures of goodness of fit. The results of this study show that the prediction power of the financial distress models improves with the incorporation of some corporate governance measures

Inteligencia emocional en estudiantes del instituto de educación superior tecnológico público Ramiro Prialé Prialé de Chosica

El estudio tuvo como objetivo determinar los niveles de Inteligencia Emocional en estudiantes del Instituto de Educación Superior Tecnológico Público Ramiro Prialé Prialé de Chosica. Investigación descriptiva y diseño transversal, muestreo no probabilístico intencional, conformada por 141 estudiantes, se utilizó la técnica de encuesta y el Inventario de Inteligencia Emocional de Bar-On ICE.The study aimed to determine the levels of Emotional Intelligence in students of the Institute of Higher Education Technological Public Ramiro Prialé Prialé de Chosica. A descriptive and cross - sectional study with a not probabilistic of the intentional type, of 141 students used the survey technique and the Bar Emotional Intelligence Inventory -On ICE

Inteligencia emocional en estudiantes del instituto de educación superior tecnológico público Ramiro Prialé Prialé de Chosica

El estudio tuvo como objetivo determinar los niveles de Inteligencia Emocional en estudiantes del Instituto de Educación Superior Tecnológico Público Ramiro Prialé Prialé de Chosica. Investigación descriptiva y diseño transversal, muestreo no probabilístico intencional, conformada por 141 estudiantes, se utilizó la técnica de encuesta y el Inventario de Inteligencia Emocional de Bar-On ICE.The study aimed to determine the levels of Emotional Intelligence in students of the Institute of Higher Education Technological Public Ramiro Prialé Prialé de Chosica. A descriptive and cross - sectional study with a not probabilistic of the intentional type, of 141 students used the survey technique and the Bar Emotional Intelligence Inventory -On ICE

Pembrolizumab Plus Gemcitabine in the Subset of Triple-Negative Advanced Breast Cancer Patients in the GEICAM/2015-04 (PANGEA-Breast) Study

Bomarkers; Breast cancer; PembrolizumabBiomarcadores; Cáncer de mama; PembrolizumabBiomarcadors; Càncer de mama; PembrolizumabThe PANGEA-Breast trial evaluated a new chemo-immunotherapeutic combination that would synergistically induce long-term clinical benefit in HER2-negative advanced breast cancer patients. Treatment consisted of 21-day cycles of 200 mg of pembrolizumab (day 1) plus gemcitabine (days 1 and 8). The primary objective was the objective response rate (ORR). The tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumor, and the myeloid-derived suppressor cells (MDSCs) level in peripheral blood, were analyzed to explore associations with treatment efficacy. Considering a two-stage Simon’s design, the study recruitment was stopped after its first stage as statistical assumptions were not met. A subset of 21 triple-negative breast cancer (TNBC) patients was enrolled. Their median age was 49 years; 15 patients had visceral involvement, and 16 had ≤3 metastatic locations. Treatment discontinuation due to progressive disease (PD) was reported in 16 patients. ORR was 15% (95% CI 3.2–37.9). Four patients were on treatment >6 months before PD. Grade ≥3 treatment-related adverse events were observed in 8 patients, where neutropenia was the most common. No association was found between TILs density, PD-L1 expression or MDSCs levels and treatment efficacy. ORR in TNBC patients also did not meet the assumptions, but 20% were on treatment >6 months.The study was partially supported by a research grant from Merck’s (MSD in Europe) Investigator Initiated Studies Program, which also supplied the pembrolizumab

Pembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015–04 (PANGEA-Breast) study

Advanced breast cancer; Chemotherapy; PembrolizumabCáncer de mama avanzado; Quimioterapia; PembrolizumabCàncer de mama avançat; Quimioteràpia; PembrolizumabBackground We evaluated a new chemoimmunotherapy combination based on the anti-PD1 monoclonal antibody pembrolizumab and the pyrimidine antimetabolite gemcitabine in HER2- advanced breast cancer (ABC) patients previously treated in the advanced setting, in order to explore a potential synergism that could eventually obtain long term benefit in these patients. Methods HER2-negative ABC patients received 21-day cycles of pembrolizumab 200 mg (day 1) and gemcitabine (days 1 and 8). A run-in-phase (6 + 6 design) was planned with two dose levels (DL) of gemcitabine (1,250 mg/m2 [DL0]; 1,000 mg/m2 [DL1]) to determine the recommended phase II dose (RP2D). The primary objective was objective response rate (ORR). Tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumors and myeloid-derived suppressor cells (MDSCs) levels in peripheral blood were analyzed. Results Fourteen patients were treated with DL0, resulting in RP2D. Thirty-six patients were evaluated during the first stage of Simon’s design. Recruitment was stopped as statistical assumptions were not met. The median age was 52; 21 (58%) patients had triple-negative disease, 28 (78%) visceral involvement, and 27 (75%) ≥ 2 metastatic locations. Progression disease was observed in 29 patients. ORR was 15% (95% CI, 5–32). Eight patients were treated ≥ 6 months before progression. Fourteen patients reported grade ≥ 3 treatment-related adverse events. Due to the small sample size, we did not find any clear association between immune tumor biomarkers and treatment efficacy that could identify a subgroup with higher probability of response or better survival. However, patients that experienced a clinical benefit showed decreased MDSCs levels in peripheral blood along the treatment. Conclusion Pembrolizumab 200 mg and gemcitabine 1,250 mg/m2 were considered as RP2D. The objective of ORR was not met; however, 22% patients were on treatment for ≥ 6 months. ABC patients that could benefit of chemoimmunotherapy strategies must be carefully selected by robust and validated biomarkers. In our heavily pretreated population, TILs, PD-L1 expression and MDSCs levels could not identify a subgroup of patients for whom the combination of gemcitabine and pembrolizumab would induce long term benefit.The study was partially supported by a research grant from Merck (MSD in Europe) Investigator Initiated Studies Program, which also supplied pembrolizumab

Análisis de la implementación del modelo de turismo rural comunitario desde el enfoque de bienes de capital rural en tres regiones del sur de Perú.

The objective of the study was to identify the interrelations between the Rural Community Tourism Model (RCT) of the Ministry of Foreign Commerce and Tourism of Peru, and the framework of rural capital assets, based on the capacity of communities to generate strategies of territorial development. Nine rural communities were studied which have developed the RCT model with success in three touristic regions of the south of Peru: Cusco, Puno and Arequipa. A total of 45 interviews were applied to people devoted to farming tasks, handcrafts, lodging, tourism guides, gastronomy, and communication promoters; also, to business owners and municipal authorities. The results indicate that four communities have succeeded in generating the tourism strategies of the model, two communities have lost the view of social fabric and the RCT value chain, two more communities have difficulty with the accessibility to the place and the lack of tourism promotion; and one last community is starting to develop the RCT. The conclusion is that the socioeconomic activity of the rural capital of the RCT model allows the local development and welfare of rural families in Peru.El objetivo de la investigación fue identificar las interrelaciones entre el Modelo de Turismo Rural Comunitario (TRC) del Ministerio de Comercio Exterior y Turismo de Perú y el marco de bienes de capital rural, a partir de la capacidad de las comunidades para generar estrategias de desarrollo territorial. Se estudiaron nueve comunidades rurales que han desarrollado el modelo de TRC con éxito en tres regiones turísticas del sur del Perú: Cusco, Puno y Arequipa. Se aplicaron 45 entrevistas a personas dedicadas a labores de agricultura, artesanía, alojamiento, guías turísticos, gastronomía y promotores de difusión; así como a dueños de emprendimientos y autoridades municipales. Los resultados indican que cuatro comunidades han logrado generar las estrategias turísticas del modelo, dos comunidades han perdido la visión del tejido social y la cadena de valor de TRC, dos comunidades más tienen dificultad con la accesibilidad al lugar y falta de promoción turística; y una última comunidad comienza a desarrollar el TRC. Se concluye que la actividad socioeconómica del capital rural del modelo TRC permite el desarrollo local y el bienestar de las familias rurales en el Perú

Revisión sistemática de la eficiencia del grupo bacteriano Pseudomonas en la biorremediación de suelos contaminados con hidrocarburos

La contaminación de suelos con hidrocarburos es un problema que afecta a los ecosistemas por su difícil degradación y toxicidad, uno de estos medios afectados es el suelo, en consecuencia, las bacterias, hongos y plantas, se han utilizado para mitigar este problema. Esta investigación evaluó mediante una revisión sistemática la eficiencia del grupo bacteriano Pseudomonas en la biorremediación de suelos contaminados con hidrocarburos. El método de la investigación tuvo un enfoque cuantitativo de tipo aplicado, el diseño fue no experimental de revisión documental y de nivel descriptivo. Se recopilaron 485 estudios de las bases de datos como Scopus y Web of Science de 2018 a 2022. Los resultados mostraron que las especies de Pseudomonas de los estudios analizados trabajaron solas o en consorcios y crecieron a pH neutro entre 10°C y 37.5°C con periodos de incubación de 2 a 30 días y aplicabilidad en el suelo hasta 90 días, el mayor porcentaje de remoción encontrado fue 92.40% por Pseudomonas spp., la revisión también citó a otras especies de este género y su aplicabilidad, así como la caracterización de los suelos contaminados, es así que se demostró la eficiencia de este grupo bacteriano para consumir hidrocarburos del suelo