Safety and Effectiveness of Perioperative Hyperthermic Intraperitoneal Chemotherapy with Gemcitabine in Patients with Resected Pancreatic Ductal Adenocarcinoma: Clinical Trial EudraCT 2016-004298-41.

BACKGROUND: Despite the improvement in therapies, pancreatic cancer represents one of the most cancer-related deaths. In our hypothesis, we propose that Hyperthermic Intraperitoneal Chemotherapy with gemcitabine after pancreatic cytoreductive surgery could reduce tumor progression by reducing residual neoplastic volume and residual pancreatic cancer stem cells. MATERIALS AND METHODS: A randomized trial involving 42 patients. All patients were diagnosed with pancreatic ductal adenocarcinoma. Group I: R0 resection. Group II. R0 resection and HIPEC with gemcitabine (120 mg/m2 for 30 min). Effectiveness was measured with analysis of overall survival, disease-free survival, distant recurrence, locoregional recurrence, and measuring of pancreatic cancer stem cells (EpCAM+CXCR4+CD133+). RESULTS: From 2017 to 2023, 63 patients were recruited for our clinical trial; 21 patients were included in each group, and 21 were excluded. Locoregional recurrence, p-value: 0.022, was lower in the experimental group. There were no significant differences between the two groups in hospital mortality, perioperative complications, or hospital costs. We found a significant decrease in pancreatic cancer stem cells in patients in the experimental group after treatment, p -value of 0.018. CONCLUSIONS: The use of HIPEC with gemcitabine after surgery in patients with resectable pancreatic ductal adenocarcinoma reduces locoregional recurrence and may be associated with a significant decrease in pancreatic cancer stem cells.

Spanish version of the short European Health Literacy Survey Questionnaire HLS-Q12: Transcultural adaptation and psychometric properties.

BACKGROUND: Health literacy has a direct impact on the health of populations. It is related to education, capacity for self-care, and management of health resources. The Health Literacy Survey Questionnaire HLS-Q12 is one of the reference instruments but has not yet been adapted to Spanish. The aims of the study were to cross-culturally adapt and evaluate the psychometric properties of the Spanish version of the HLS-Q12. METHODS: Data was collected from June 2020 to March 2022. The sample consisted of 60 patients who initiated cancer treatment for the first time within a clinical trial. Double direct translation, back-translation, cognitive debriefing with a 10-patient sample, and an expert committee were used for cross-cultural adaptation. For validation of the HLS-Q12, a psychometric analysis was performed to assess feasibility, reliability, sensitivity to change and construct validity with other measures such as health-related quality of life, empowerment, and health needs. RESULTS: The HLS-Q12 is equivalent at the semantic, conceptual, and content level to the original version and its psychometric properties demonstrated good internal consistency with a Cronbach's alpha of 0.88 and a McDonald´s omega of 0.91, a high degree of fit for the confirmatory factor analysis, and a statistically significant sensitivity to change (p = 0.025). CONCLUSIONS: Based on robust psychometric values, the Spanish version of HLS-Q12 was found to be a good cross-culturally adapted tool for collecting correct information on health literacy in cancer patients regardless of tumour type or stage. Although more studies are needed, this version of HLS-Q12 could be used in research for collecting data on the health literacy needs of Spanish-speaking patients.

Impact of telenurse-led intervention in clinical trials on health literacy, empowerment, and health outcomes in patients with solid tumours: a pilot quasi-experimental study.

BACKGROUND: During the COVID-19 pandemic, decentralised clinical trials incorporated self-monitoring, self-reporting, and telenursing tools to address health literacy and health empowerment of patients enrolled in clinical trials. We aimed to determine the impact of an educational intervention using telenursing consultations on health literacy, health empowerment, and health-related quality of life in cancer patients enrolled in clinical trials by measuring the level of satisfaction with the care received and assessing the views of healthcare professionals concerning the advanced practice nurse (APN) role in oncology clinical trials. METHODS: In this pilot analytical, descriptive, longitudinal, quasi-experimental, and pre-post test study, an educational intervention was conducted by 5 visits with an APN using synchronous teleconsultation in patients starting cancer treatment for the first time in a clinical trial (n = 60), and health professionals working with the APN (n = 31). A descriptive analysis of the samples and questionnaires were utilised along with statistical comparisons. RESULTS: After the intervention, patients' health literacy (31.7%), health empowerment (18.3%), and health-related quality of life (33.3%) increased (p < 0.05), with a decrease and trend towards resolution of care needs (p < 0.05). Satisfaction with the quality and care received in terms of perceived convenience, transition, and continuity of care showed positive results in 64.9 ± 20.7, 77.6 ± 19.5, and 72.1 ± 20.4 of respondents, respectively. On the overall assessment of the APN role, healthcare professionals expressed a high level of agreement with the statements related to their work performance. CONCLUSIONS: The data indicates that a clinical trial APN-led telenursing educational intervention results in an overall increase in health literacy, an improvement in health empowerment and health-related quality of life, and a decrease in care needs of oncology clinical trials patients. Patients stated that they received a high quality of care and health professionals indicated high levels of acceptance with APNs. Based on these results, we suggest that the APN role should gain more recognition in the Spanish healthcare system and their professional competencies should be aligned with those of other countries.

Competencias profesionales de las enfermeras oncológicas: reconociendo la Práctica Avanzada en Enfermería / Professional competencies of oncology nurses: Recognizing advanced practice in nursing

Objetivo: Identificar el perfil competencial de las enfermeras de práctica avanzada que intervienen en el proceso asistencial del paciente oncológico. Método: Estudio descriptivo transversal. El estudio incluyó a todas las enfermeras que intervienen en el proceso asistencial del paciente oncológico en un hospital terciario de Barcelona. Se recogieron los datos del perfil competencial a través del instrumento de definición del rol de la enfermera de práctica avanzada (IDREPA), así como las variables sociodemográficas y laborales. Se compararon datos sociodemográficos y laborales con el desempeño de actividades de práctica avanzada. Resultados: Participaron un total de 29 (82,9%) enfermeras con una media de edad de 42,6± 12,54 años. Se han identificado 9 (31%) enfermeras que alcanzan el estándar en los 6 dominios en la escala IDREPA para considerarse enfermeras de práctica avanzada (EPA). De estas 9 (31%), cumplían los estándares de formación requeridos por el CIE, 7 (24,1%) con máster oficial y 2 (6,9%) con doctorado. Conclusiones: Existen enfermeras que desarrollan su actividad en el ámbito oncológico del Hospital del Mar con perfil de EPA. La identificación de EPA en nuestro sistema de salud es esencial para poder reconocer las competencias de dichas profesionales y crear puestos específicos que ayuden a abordar la cronicidad, la calidad de vida de los pacientes, su supervivencia y la optimización de los recursos sanitarios. Este estudio pone en relieve la importancia de la cronicidad y el cáncer como ámbitos para el desarrollo de la EPA.(AU)

Objective: To identify the competency profile of advanced practice nurses involved in the care process of cancer patients. Methods: Cross-sectional and descriptive study. The study included all nurses involved in the cancer patient care process in a tertiary hospital in Barcelona. Competence profile data were collected using the instrument for defining the role of the advanced practice nurse (APRD), as well as sociodemographic and occupational variables. Sociodemographic and occupational data were compared against the performance of advanced practice activities. Results: A total of 29 (82.9%) nurses participated with a mean age of 42.6±12.54 years. Nine (31%) nurses were identified as meeting the standard in all 6 domains on the APRD scale to be considered advanced practice nurses. Of these 9 (31%) nurses, 7 (24.1%) met the training standards required by the International Council of Nurses (ICN) with an official master's degree and 2 (6.9%) with a PhD. Conclusions: There are nurses who carry out their activity in the oncology field of the Hospital del Mar with the EPA profile. The identification of advanced practice nurses (APNs) in our health system is essential to be able to recognize the competencies of these professionals and create specific positions that help to address chronicity, patients’ quality of life, their survival, and the optimization of health resources. Our study highlights the importance of chronicity and cancer as areas for the development of the APNs.(AU)

The importance of CXCR4 expression in tumor stroma as a potential biomarker in pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the main causes of cancer mortality in the world. A characteristic feature of this cancer is that a large part of the tumor volume is composed of a stroma with different cells and factors. Among these, we can highlight the cytokines, which perform their function through binding to their receptors. Given the impact of the CXCR4 receptor in the interactions between tumor cells and their microenvironment and its involvement in important signaling pathways in cancer, it is proposed as a very promising prognostic biomarker and as a goal for new targeted therapies. Numerous studies analyze the expression of CXCR4 but we suggest focusing on the expression of CXCR4 in the stroma. METHODS: Expression of CXCR4 in specimens from 33 patients with PDAC was evaluated by immunohistochemistry techniques and matched with clinicopathological parameters, overall and disease-free survival rates. RESULTS: The percentage of stroma was lower in non-tumor tissue (32.4 ± 5.2) than in tumor pancreatic tissue (67.4 ± 4.8), P-value = 0.001. The level of CXCR4 expression in stromal cells was diminished in non-tumor tissue (8.7 ± 4.6) and higher in tumor pancreatic tissue (23.5 ± 6.1), P-value = 0.022. No significant differences were identified in total cell count and inflammatory cells between non-tumor tissue and pancreatic tumor tissue. No association was observed between CXCR4 expression and any of the clinical or pathological data, overall and disease-free survival rates. Analyzing exclusively the stroma of tumor samples, the CXCR4 expression was associated with tumor differentiation, P-value = 0.05. CONCLUSIONS: In this study, we reflect the importance of CXCR4 expression in the stroma of patients diagnosed with PDAC. Our results revealed a high CXCR4 expression in the tumor stroma, which is related to a poor tumor differentiation. On the contrary, we could not find an association between CXCR4 expression and survival and the rest of the clinicopathological variables. Focusing the study on the CXCR4 expression in the tumor stroma could generate more robust results. Therefore, we consider it key to develop more studies to enlighten the role of this receptor in PDAC and its implication as a possible biomarker.

Professional competencies of oncology nurses: Recognizing advanced practice in nursing.

OBJECTIVE: To identify the competency profile of advanced practice nurses involved in the care process of cancer patients. METHODS: Cross-sectional and descriptive study. The study included all nurses involved in the cancer patient care process in a tertiary hospital in Barcelona. Competence profile data were collected using the instrument for defining the role of the advanced practice nurse (APRD), as well as sociodemographic and occupational variables. Sociodemographic and occupational data were compared against the performance of advanced practice activities. RESULTS: A total of 29 (82.9%) nurses participated with a mean age of 42.6±12.54 years. 9 (31%) nurses were identified as meeting the standard in all 6 domains on the APRD scale to be considered advanced practice nurses. Of these 9 (31%) nurses, 7 (24.1%) met the training standards required by the International Council of Nurses (ICN) with an official master's degree and 2 (6.9%) with a PhD. CONCLUSIONS: There are nurses who carry out their activity in the oncology field of the hospital analyzed with the EPA profile. The identification of advanced practice nurses (APNs) in our health system is essential to be able to recognize the competencies of these professionals and create specific positions that help to address chronicity, patients' quality of life, their survival, and the optimization of health resources. Our study highlights the importance of chronicity and cancer as areas for the development of the APNs.

Salt-related practices and its association with 24-hour urinary sodium excretion in an Uruguayan population cohort.

Objectives: To evaluate the association between knowledge, attitudes, and behavior (KAB) towards sodium use and sodium intake measured by 24-hour urinary collection in an adult cohort from Uruguay (Genotype Phenotype and Environment of Hypertension Study, GEFA-HT-UY). Methods: In a cross-sectional study (n = 159), a single 24-hour urinary sample, participants' physical, biochemical and blood pressure measurements and questionnaire data were collected. The association between KAB and 24-hour urinary sodium excretion was assessed using general linear models. Results: Mean age of participants was 49.8±15.5 years, 67.9% were women, and mean 24-hour urinary sodium excretion was 3.6±1.7 g/day. Although 90.6% of participants exceeded the maximum recommended intake as indicated by urinary sodium excretion, more than half misperceived their actual intake, reporting consuming "the right amount." Almost three-quarters of the participants reported being concerned about the amount of sodium in their diet, but only 52.8% reported taking action to control it. Lack of procedural knowledge was observed. There was no association between KAB and sodium use and intake assessed by 24-hour urinary sodium excretion. Conclusions: The lack of association between KAB towards the use of sodium and intake measured by 24-hour urinary excretion reflects the need to support people with opportunities and motivations to reduce sodium consumption. Structural actions to promote an adequate food environment, such as the effective implementation of the front-of-package nutrition labeling in Uruguay, are positive steps.

Salt-related practices and its association with 24-hour urinary sodium excretion in an Uruguayan population cohort

[ABSTRACT]. Objectives. To evaluate the association between knowledge, attitudes, and behavior (KAB) towards sodium use and sodium intake measured by 24-hour urinary collection in an adult cohort from Uruguay (Genotype Phenotype and Environment of Hypertension Study, GEFA-HT-UY). Methods. In a cross-sectional study (n = 159), a single 24-hour urinary sample, participants' physical, bio- chemical and blood pressure measurements and questionnaire data were collected. The association between KAB and 24-hour urinary sodium excretion was assessed using general linear models. Results. Mean age of participants was 49.8±15.5 years, 67.9% were women, and mean 24-hour urinary sodium excretion was 3.6±1.7 g/day. Although 90.6% of participants exceeded the maximum recommended intake as indicated by urinary sodium excretion, more than half misperceived their actual intake, reporting consuming “the right amount.” Almost three-quarters of the participants reported being concerned about the amount of sodium in their diet, but only 52.8% reported taking action to control it. Lack of procedural knowl- edge was observed. There was no association between KAB and sodium use and intake assessed by 24-hour urinary sodium excretion. Conclusions. The lack of association between KAB towards the use of sodium and intake measured by 24-hour urinary excretion reflects the need to support people with opportunities and motivations to reduce sodium consumption. Structural actions to promote an adequate food environment, such as the effective implementation of the front-of-package nutrition labeling in Uruguay, are positive steps.

[RESUMEN]. Objetivos. Evaluar la relación entre conocimientos, actitudes y comportamientos en lo relativo a la ingesta de sodio medida por la recolección de orina de 24 horas en una cohorte de adultos en Uruguay (GEnotipo, Fenotipo y Ambiente de la HiperTensión Arterial en UruguaY, GEFA-HT-UY). Métodos. En un estudio transversal (n = 159), se obtuvo una muestra urinaria de 24 horas y los datos de un cuestionario y de las mediciones físicas, bioquímicas y de presión arterial de los participantes. Se evaluó la asociación entre conocimientos, actitudes y comportamientos y la excreción urinaria de sodio en 24 horas con modelos lineales generales. Resultados. La edad media de los participantes fue 49,8±15,5 años, 67,9% eran mujeres y la excreción urinaria media de sodio en 24 horas fue de 3,6±1,7 g/día. Aunque 90,6% de los participantes excedieron la ingesta máxima recomendada de acuerdo con la excreción urinaria de sodio, más de la mitad percibió su ingesta real incorrectamente al señalar que consumía “la cantidad correcta”. Casi tres cuartas partes de los participantes manifestaron estar preocupados por la cantidad de sodio en su dieta, si bien solo 52,8% declaró haber tomado medidas para controlarla. Se observó una falta de conocimiento sobre los procedimientos. No se encontró una asociación entre conocimientos, actitudes y comportamientos y la ingesta de sodio evaluada mediante la excreción urinaria de sodio en 24 horas. Conclusiones. La falta de relación entre conocimientos, actitudes y comportamientos respecto del consumo de sodio y su ingesta medida por excreción urinaria en 24 horas refleja la necesidad de apoyar a las perso- nas con oportunidades y motivaciones para reducir el consumo de sodio. Adoptar medidas estructurales que promuevan unas condiciones alimentarias adecuadas, como la aplicación efectiva del etiquetado nutricional frontal en Uruguay, constituye un paso en la dirección correcta.

[RESUMO]. Objetivos. Avaliar a associação entre conhecimento, atitudes e comportamento (KAB, sigla do inglês Knowl- edge, Attitudes, Behavior) e o uso e ingestão de sódio, medida pela coleta de urina de 24 horas em uma coorte de adultos do Uruguai (Estudo do Genótipo, Fenótipo e Ambiente da Hipertensão, GEFA-HT-UY). Métodos. Em um estudo transversal (n = 159), foi coletada uma única amostra de urina de 24 horas dos par- ticipantes, medidas físicas, bioquímicas e de pressão arterial, e dados de questionários. A associação entre KAB e excreção urinária de sódio nas 24 horas foi avaliada por meio de modelos lineares gerais. Resultados. A idade média dos participantes foi de 49,8±15,5 anos; 67,9% eram mulheres e a excreção média de sódio na urina de 24 horas foi de 3,6±1,7 g/dia. Embora 90,6% dos participantes excedessem a ingestão máxima recomendada, conforme indicado pela excreção urinária de sódio, mais da metade dos participantes não tinha percepção da real ingestão de sódio, relatando consumir "a quantidade correta". Quase três quartos dos participantes relataram estar preocupados com a quantidade de sódio na dieta, mas apenas 52,8% relataram ter implementado medidas para controlá-la. Observou-se falta de conhecimento de procedimentos. Não houve associação entre KAB e o uso e a ingestão de sódio avaliada pela excreção de sódio na urina de 24 horas. Conclusões. A falta de associação entre KAB e o uso e a ingestão do sódio avaliada pela excreção urinária de 24 horas reflete a necessidade de oferecer apoio aos indivíduos por meio de oportunidades e motivações para reduzir o consumo de sódio. Ações estruturais para promover um ambiente alimentar adequado, como a implementação efetiva de advertências na rotulagem frontal dos alimentos no Uruguai, são passos positivos.

Clinical features and mortality of COVID-19 patients admitted to ICU according to SOFA score.

The Sequential Organ Failure Assessment (SOFA) could function as an effective risk stratification tool in the admission of critically ill patients with COVID-19 and would allow stratification based on a risk assessment. We aimed to examine whether the SOFA score is useful to define 2 severity profiles in COVID-19 patients admitted to ICU: mild with SOFA < 5, and severe with SOFA ≥ 5. A retrospective cohort, multicenter study was conducted from February 11 to May 11, 2020. We analyzed patients admitted to all ICUs of the 14 public hospitals of the Castilla-La Mancha Health Service at the beginning of the pandemic and with SARS-CoV-2 infection. Patients were divided in 2 groups according to the level of severity by SOFA at admission to the ICU. Cox regression was used to evaluate factors associated with survival and Kaplan-Meier test to examine survival probability. In total, 405 patients with a complete SOFA panel were recruited in the 14 participating ICUs. SOFA <5 group showed that age above 60 years and D-dimer above 1000 ng/mL were risk factors associated with lower survival. In SOFA ≥ 5 it was found that high blood pressure was a risk factor associated with shorter survival. Kaplan-Meier showed lower survival in SOFA ≥ 5 in combination with high blood pressure, time since viral symptom onset to admission in ICU < 7 days, D-dimer ≥1000 ng/mL and respiratory pathology. However, SOFA < 5 showed only higher age (≥60 years) associated with lower survival. Age over 60 years and D-dimer over 1000 ng/mL were risk factors reflecting lower survival in patients with SOFA < 5. Moreover, SOFA ≥ 5 patients within a week after COVID-19 onset and comorbidities such as high blood pressure and previous respiratory pathology showed lower survival.

Aprotinin treatment against SARS-CoV-2: A randomized phase III study to evaluate the safety and efficacy of a pan-protease inhibitor for moderate COVID-19.

BACKGROUND: SARS-CoV-2 virus requires host proteases to cleave its spike protein to bind to its ACE2 target through a two-step furin-mediated entry mechanism. Aprotinin is a broad-spectrum protease inhibitor that has been employed as antiviral drug for other human respiratory viruses. Also, it has important anti-inflammatory properties for inhibiting the innate immunity contact system. METHODS: This was a multicentre, double-blind, randomized trial performed in four Spanish hospitals comparing standard treatment versus standard treatment + aprotinin for patients with COVID-19 between 20 May 2020 and 20 October 2021. The primary efficacy outcomes were length of hospital stay and ICU admission. The secondary endpoints were each of the primary efficacy outcomes and a composite of oxygen therapy, analytical parameters and death. Safety outcomes included adverse reactions to treatment during a 30-day follow-up period. Treatment was given for 11 days or till discharge. RESULTS: With almost identical analytical profiles, significant differences were observed in treatment time, which was 2 days lower in the aprotinin group (p = .002), and length of hospital admission, which was 5 days shorter in the aprotinin group (p = .003). The incidence of discharge was 2.19 times higher (HR: 2.188 [1.182-4.047]) in the aprotinin group than in the placebo group (p = .013). In addition, the aprotinin-treated group required less oxygen therapy and had no adverse reactions or side effects. CONCLUSION: Inhaled aprotinin may improve standard treatment and clinical outcomes in hospitalized patients with COVID-19, resulting in a shorter treatment time and hospitalization compared with the placebo group. The administration of aprotinin was safe.

Análisis de los pacientes menores de edad con sospecha de COVID-19 en un servicio de urgencias y su impacto en el estudio de contactos / Pediatric patients with suspected COVID-19 in an emergency department: analysis of characteristics and transmission to contacts

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Salt-related practices and its association with 24-hour urinary sodium excretion in an Uruguayan population cohort / Prácticas relacionadas con la sal y su asociación con la excreción urinaria de sodio en 24 horas en una cohorte de población en Uruguay / Práticas relacionadas ao uso do sal e sua associação com a excreção de sódio na urina de 24 horas em uma coorte populacional uruguaia

Abstract Objectives. To evaluate the association between knowledge, attitudes, and behavior (KAB) towards sodium use and sodium intake measured by 24-hour urinary collection in an adult cohort from Uruguay (Genotype Phenotype and Environment of Hypertension Study, GEFA-HT-UY). Methods. In a cross-sectional study (n = 159), a single 24-hour urinary sample, participants' physical, biochemical and blood pressure measurements and questionnaire data were collected. The association between KAB and 24-hour urinary sodium excretion was assessed using general linear models. Results. Mean age of participants was 49.8±15.5 years, 67.9% were women, and mean 24-hour urinary sodium excretion was 3.6±1.7 g/day. Although 90.6% of participants exceeded the maximum recommended intake as indicated by urinary sodium excretion, more than half misperceived their actual intake, reporting consuming "the right amount." Almost three-quarters of the participants reported being concerned about the amount of sodium in their diet, but only 52.8% reported taking action to control it. Lack of procedural knowledge was observed. There was no association between KAB and sodium use and intake assessed by 24-hour urinary sodium excretion. Conclusions. The lack of association between KAB towards the use of sodium and intake measured by 24-hour urinary excretion reflects the need to support people with opportunities and motivations to reduce sodium consumption. Structural actions to promote an adequate food environment, such as the effective implementation of the front-of-package nutrition labeling in Uruguay, are positive steps.

RESUMEN Objetivos. Evaluar la relación entre conocimientos, actitudes y comportamientos en lo relativo a la ingesta de sodio medida por la recolección de orina de 24 horas en una cohorte de adultos en Uruguay (GEnotipo, Fenotipo y Ambiente de la HiperTensión Arterial en UruguaY, GEFA-HT-UY). Métodos. En un estudio transversal (n = 159), se obtuvo una muestra urinaria de 24 horas y los datos de un cuestionario y de las mediciones físicas, bioquímicas y de presión arterial de los participantes. Se evaluó la asociación entre conocimientos, actitudes y comportamientos y la excreción urinaria de sodio en 24 horas con modelos lineales generales. Resultados. La edad media de los participantes fue 49,8±15,5 años, 67,9% eran mujeres y la excreción urinaria media de sodio en 24 horas fue de 3,6±1,7 g/día. Aunque 90,6% de los participantes excedieron la ingesta máxima recomendada de acuerdo con la excreción urinaria de sodio, más de la mitad percibió su ingesta real incorrectamente al señalar que consumía "la cantidad correcta". Casi tres cuartas partes de los participantes manifestaron estar preocupados por la cantidad de sodio en su dieta, si bien solo 52,8% declaró haber tomado medidas para controlarla. Se observó una falta de conocimiento sobre los procedimientos. No se encontró una asociación entre conocimientos, actitudes y comportamientos y la ingesta de sodio evaluada mediante la excreción urinaria de sodio en 24 horas. Conclusiones. La falta de relación entre conocimientos, actitudes y comportamientos respecto del consumo de sodio y su ingesta medida por excreción urinaria en 24 horas refleja la necesidad de apoyar a las personas con oportunidades y motivaciones para reducir el consumo de sodio. Adoptar medidas estructurales que promuevan unas condiciones alimentarias adecuadas, como la aplicación efectiva del etiquetado nutricional frontal en Uruguay, constituye un paso en la dirección correcta.

RESUMO Objetivos. Avaliar a associação entre conhecimento, atitudes e comportamento (KAB, sigla do inglês Knowledge, Attitudes, Behavior) e o uso e ingestão de sódio, medida pela coleta de urina de 24 horas em uma coorte de adultos do Uruguai (Estudo do Genótipo, Fenótipo e Ambiente da Hipertensão, GEFA-HT-UY). Métodos. Em um estudo transversal (n = 159), foi coletada uma única amostra de urina de 24 horas dos participantes, medidas físicas, bioquímicas e de pressão arterial, e dados de questionários. A associação entre KAB e excreção urinária de sódio nas 24 horas foi avaliada por meio de modelos lineares gerais. Resultados. A idade média dos participantes foi de 49,8±15,5 anos; 67,9% eram mulheres e a excreção média de sódio na urina de 24 horas foi de 3,6±1,7 g/dia. Embora 90,6% dos participantes excedessem a ingestão máxima recomendada, conforme indicado pela excreção urinária de sódio, mais da metade dos participantes não tinha percepção da real ingestão de sódio, relatando consumir "a quantidade correta". Quase três quartos dos participantes relataram estar preocupados com a quantidade de sódio na dieta, mas apenas 52,8% relataram ter implementado medidas para controlá-la. Observou-se falta de conhecimento de procedimentos. Não houve associação entre KAB e o uso e a ingestão de sódio avaliada pela excreção de sódio na urina de 24 horas. Conclusões. A falta de associação entre KAB e o uso e a ingestão do sódio avaliada pela excreção urinária de 24 horas reflete a necessidade de oferecer apoio aos indivíduos por meio de oportunidades e motivações para reduzir o consumo de sódio. Ações estruturais para promover um ambiente alimentar adequado, como a implementação efetiva de advertências na rotulagem frontal dos alimentos no Uruguai, são passos positivos.

Characteristics and Risk Factors Associated With Mortality in a Multicenter Spanish Cohort of Patients With COVID-19 Pneumonia.

INTRODUCTION: Spain is one of the countries with the highest number of COVID-19 patients. Unfortunately, few data for regions are available. OBJECTIVES: This study aimed to describe the characteristics and independent risk factors associated with COVID-19 mortality in Castilla-La Mancha, Spain. METHODS: Cohort and multicenter study in all 14 public hospitals of the Castilla-La Mancha Health Service. Baseline characteristics, preexisting comorbidities, symptoms, clinical features and treatments were included. Multivariable logistic regression was used to evaluate factors associated with death and Kaplan-Meier test to examine survival probability. Statistical significance was considered with p < 0.05 (95% CI). SPSS (version 24.0 for Windows) and R 4.0.2 (R Statistics) software were used. RESULTS: The cohort comprised 12,126 patients sequentially attended between February 11 and May 11, 2020. The mean age of patients was 66.4 years; 5667 (46.7%) were women. Six protective factors against exitus were defined: female sex, anosmia, cough, chloroquine and azithromycin. The risk factors were: age over 50, obesity, cardiac pathology, fever, dyspnea, lung infiltrates, lymphopenia, D-dimer above 1000 ng/mL, and mechanical ventilation requirement. Survival analysis showed higher survival rate in women (75.7%) than men (72.1%). Cumulative survival was 87.5% for non-hospitalized patients, 70.2% for patients admitted to hospital and 61.2% in ICU patients. Additionally, survival probability decreased with increasing age range. CONCLUSION: Determination of protective or death-promoting factors could be useful to stratify patients by severity criteria and to improve COVID-19 care management.

INTRODUCCIÓN: España es uno de los países con mayor número de pacientes con COVID-19. Desafortunadamente, se dispone de pocos datos por regiones. OBJETIVOS: Describir las características y los factores de riesgo independientes asociados a mortalidad por COVID-19 en Castilla-La Mancha, España. MÉTODOS: Estudio de cohorte, multicéntrico de los 14 hospitales públicos de Castilla-La Mancha. Se evaluaron las características clínicas, comorbilidades preexistentes, síntomas y tratamientos. Se utilizó una regresión logística multivariable para evaluar los factores asociados a muerte y Kaplan-Meier para medir supervivencia. Se consideró significación estadística con p < 0,05 (IC 95%). Se utilizaron los programas SPSS (versión 24.0 para Windows) y R 4.0.2 (R Statistics). RESULTADOS: Se estudiaron 12.126 pacientes atendidos secuencialmente entre el 11 de febrero y el 11 de mayo de 2020. La edad media fue de 66,4 años; 5.667 (46,7%) fueron mujeres. Se definieron seis factores protectores contra el exitus: sexo femenino, anosmia, tos, cloroquina y azitromicina. Los factores de riesgo fueron: edad superior a 50, obesidad, patología cardíaca, fiebre, disnea, infiltrados pulmonares, linfopenia, dímero-D > 1.000 ng/mL y necesidad de ventilación mecánica. Se observó mayor tasa de supervivencia en mujeres (75,7%) que en hombres (72,1%). La supervivencia acumulada fue del 87,5% para pacientes no hospitalizados, 70,2% para admitidos en planta hospitalaria y 61,2% en la Unidad de Cuidados Intensivos (UCI). Además, la probabilidad de supervivencia disminuyó con el aumento del rango de edad. CONCLUSIÓN: La determinación de los factores protectores o favorecedores de muerte podría ser útil para estratificar pacientes por criterios de gravedad y mejorar la atención frente a la COVID-19.

Characteristics and Risk Factors Associated With Mortality in a Multicenter Spanish Cohort of Patients With COVID-19 Pneumonia / Características y factores de riesgo asociados a mortalidad en una cohorte multicéntrica española de pacientes con neumonía por COVID-19

INTRODUCTION: Spain is one of the countries with the highest number of COVID-19 patients. Unfortunately, few data for regions are available. OBJECTIVES: This study aimed to describe the characteristics and independent risk factors associated with COVID-19 mortality in Castilla-La Mancha, Spain. METHODS: Cohort and multicenter study in all 14 public hospitals of the Castilla-La Mancha Health Service. Baseline characteristics, preexisting comorbidities, symptoms, clinical features and treatments were included. Multivariable logistic regression was used to evaluate factors associated with death and Kaplan-Meier test to examine survival probability. Statistical significance was considered with p < 0.05 (95% CI). SPSS (version 24.0 for Windows) and R 4.0.2 (R Statistics) software were used. RESULTS: The cohort comprised 12,126 patients sequentially attended between February 11 and May 11, 2020. The mean age of patients was 66.4 years; 5667 (46.7%) were women. Six protective factors against exitus were defined: female sex, anosmia, cough, chloroquine and azithromycin. The risk factors were: age over 50, obesity, cardiac pathology, fever, dyspnea, lung infiltrates, lymphopenia, D-dimer above 1000 ng/mL, and mechanical ventilation requirement. Survival analysis showed higher survival rate in women (75.7%) than men (72.1%). Cumulative survival was 87.5% for non-hospitalized patients, 70.2% for patients admitted to hospital and 61.2% in ICU patients. Additionally, survival probability decreased with increasing age range. CONCLUSION: Determination of protective or death-promoting factors could be useful to stratify patients by severity criteria and to improve COVID-19 care management

INTRODUCCIÓN: España es uno de los países con mayor número de pacientes con COVID-19. Desafortunadamente, se dispone de pocos datos por regiones. OBJETIVOS: Describir las características y los factores de riesgo independientes asociados a mortalidad por COVID-19 en Castilla-La Mancha, España. MÉTODOS: Estudio de cohorte, multicéntrico de los 14 hospitales públicos de Castilla-La Mancha. Se evaluaron las características clínicas, comorbilidades preexistentes, síntomas y tratamientos. Se utilizó una regresión logística multivariable para evaluar los factores asociados a muerte y Kaplan-Meier para medir supervivencia. Se consideró significación estadística con p < 0,05 (IC 95%). Se utilizaron los programas SPSS (versión 24.0 para Windows) y R 4.0.2 (R Statistics). RESULTADOS: Se estudiaron 12.126 pacientes atendidos secuencialmente entre el 11 de febrero y el 11 de mayo de 2020. La edad media fue de 66,4 años; 5.667 (46,7%) fueron mujeres. Se definieron seis factores protectores contra el exitus: sexo femenino, anosmia, tos, cloroquina y azitromicina. Los factores de riesgo fueron: edad superior a 50, obesidad, patología cardíaca, fiebre, disnea, infiltrados pulmonares, linfopenia, dímero-D > 1.000 ng/mL y necesidad de ventilación mecánica. Se observó mayor tasa de supervivencia en mujeres (75,7%) que en hombres (72,1%). La supervivencia acumulada fue del 87,5% para pacientes no hospitalizados, 70,2% para admitidos en planta hospitalaria y 61,2% en la Unidad de Cuidados Intensivos (UCI). Además, la probabilidad de supervivencia disminuyó con el aumento del rango de edad. CONCLUSIÓN: La determinación de los factores protectores o favorecedores de muerte podría ser útil para estratificar pacientes por criterios de gravedad y mejorar la atención frente a la COVID-19

Identification of a stemness-related gene panel associated with BET inhibition in triple negative breast cancer.

PURPOSE: Triple negative breast cancers (TNBCs) are enriched in cells bearing stem-like features, i.e., cancer stem cells (CSCs), which underlie cancer progression. Thus, targeting stemness may be an interesting treatment approach. The epigenetic machinery is crucial for maintaining the stemness phenotype. Bromodomain and extra-terminal domain (BET) epigenetic reader family members are emerging as novel targets for cancer therapy, and have already shown preclinical effects in breast cancer. Here, we aimed to evaluate the effect of the BET inhibitor JQ1 on stemness in TNBC. METHODS: Transcriptomic, functional annotation and qRT-PCR studies were performed on JQ1-exposed TNBC cells in culture. The results obtained were confirmed in spheroids and spheroid-derived tumours. In addition, limiting dilution, secondary and tertiary tumour sphere formation, matrigel invasion, immunofluorescence and flow cytometry assays were performed to evaluate the effect of JQ1 on CSC features. For clinical outcome analyses, the online tool Kaplan-Meier Plotter and an integrated response database were used. RESULTS: We found that JQ1 modified the expression of stemness-related genes in two TNBC-derived cell lines, MDA-MB-231 and BT549. Among these changes, the CD44 Antigen/CD24 Antigen (CD44/CD24) ratio and Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) expression level, i.e., both classical stemness markers, were found to be decreased by JQ1. Using a validated spheroid model to mimic the intrinsic characteristics of CSCs, we found that JQ1 decreased surface CD44 expression, inhibited self-renewal and invasion, and induced cell cycle arrest in G0/G1, thereby altering the stemness phenotype. We also found associations between four of the identified stemness genes, Gap Junction Protein Alpha 1 (GJA1), CD24, Epithelial Adhesion Molecule (EPCAM) and SRY-related HMG-box gene 9 (SOX9), and a worse TNBC patient outcome. The expression of another two of the stemness-related genes was found to be decreased by JQ1, i.e., ATP Binding Cassette Subfamily G Member 2 (ABCG2) and RUNX2, and predicted a low response to chemotherapy in TNBC patients, which supports a role for RUNX2 as a potential predictive marker for chemotherapy response in TNBC. CONCLUSIONS: We identified a stemness-related gene panel associated with JQ1 and describe how this inhibitor modifies the stemness landscape in TNBC. Therefore, we propose a novel role for JQ1 as a stemness-targeting drug. Loss of the stem cell phenotype via JQ1 treatment could lead to less aggressive and more chemo-sensitive tumours, reflecting a better patient prognosis. Thus, the identified gene panel may be of interest for the clinical management of patients with aggressive TNBC.

Autophagic cell death associated to Sorafenib in renal cell carcinoma is mediated through Akt inhibition in an ERK1/2 independent fashion.

OBJECTIVES: To fully clarify the role of Mitogen Activated Protein Kinase in the therapeutic response to Sorafenib in Renal Cell Carcinoma as well as the cell death mechanism associated to this kinase inhibitor, we have evaluated the implication of several Mitogen Activated Protein Kinases in Renal Cell Carcinoma-derived cell lines. MATERIALS AND METHODS: An experimental model of Renal Cell Carcinoma-derived cell lines (ACHN and 786-O cells) was evaluated in terms of viability by MTT assay, induction of apoptosis by caspase 3/7 activity, autophagy induction by LC3 lipidation, and p62 degradation and kinase activity using phospho-targeted antibodies. Knock down of ATG5 and ERK5 was performed using lentiviral vector coding specific shRNA. RESULTS: Our data discard Extracellular Regulated Kinase 1/2 and 5 as well as p38 Mitogen Activated Protein Kinase pathways as mediators of Sorafenib toxic effect but instead indicate that the inhibitory effect is exerted through the PI3K/Akt signalling pathway. Furthermore, we demonstrate that inhibition of Akt mediates cell death associated to Sorafenib without caspase activation, and this is consistent with the induction of autophagy, as indicated by the use of pharmacological and genetic approaches. CONCLUSION: The present report demonstrates that Sorafenib exerts its toxic effect through the induction of autophagy in an Akt-dependent fashion without the implication of Mitogen Activated Protein Kinase. Therefore, our data discard the use of inhibitors of the RAF-MEK-ERK1/2 signalling pathway in RCC and support the use of pro-autophagic compounds, opening new therapeutic opportunities for Renal Cell Carcinoma.

Synthetic Lethality Interaction Between Aurora Kinases and CHEK1 Inhibitors in Ovarian Cancer.

Ovarian cancer is characterized by frequent mutations at TP53. These tumors also harbor germline mutations at homologous recombination repair genes, so they rely on DNA-damage checkpoint proteins, like the checkpoint kinase 1 (CHEK1) to induce G2 arrest. In our study, by using an in silico approach, we identified a synthetic lethality interaction between CHEK1 and mitotic aurora kinase A (AURKA) inhibitors. Gene expression analyses were used for the identification of relevant biological functions. OVCAR3, OVCAR8, IGROV1, and SKOV3 were used for proliferation studies. Alisertib was tested as AURKA inhibitor and LY2603618 as CHEK1 inhibitor. Analyses of cell cycle and intracellular mediators were performed by flow cytometry and Western blot analysis. Impact on stem cell properties was evaluated by flow cytometry analysis of surface markers and sphere formation assays. Gene expression analyses followed by functional annotation identified a series of deregulated genes that belonged to cell cycle, including AURKA/B, TTK kinase, and CHEK1. AURKA and CHEK1 were amplified in 8.7% and 3.9% of ovarian cancers, respectively. AURKA and CHEK1 inhibitors showed a synergistic interaction in different cellular models. Combination of alisertib and LY2603618 triggered apoptosis, reduced the stem cell population, and increased the effect of taxanes and platinum compounds. Finally, expression of AURKA and CHEK1 was linked with detrimental outcome in patients. Our data describe a synthetic lethality interaction between CHEK1 and AURKA inhibitors with potential translation to the clinical setting. Mol Cancer Ther; 16(11); 2552-62. ©2017 AACR.

Prognostic Value of the VHL, HIF-1α, and VEGF Signaling Pathway and Associated MAPK (ERK1/2 and ERK5) Pathways in Clear-Cell Renal Cell Carcinoma. A Long-Term Study.

BACKGROUND: The prognostic value of molecular markers in renal cell carcinoma has been investigated in several studies. Although their value is still not confirmed, various proteins are important. We describe the effect on long-term survival of the status of the von Hippel-Lindau (VHL) hypoxia-inducible factor 1-α (HIF1-α) signaling pathway as well as associated mitogen-activated protein kinase (extracellular signal-regulated kinase [ERK]1/2 and ERK5). PATIENTS AND METHODS: A prospective, longitudinal cohort study was conducted with 50 patients diagnosed with clear-cell renal cell carcinoma to analyze VHL mutations and hypermethylation as well as VHL, HIF1-α, vascular endothelial growth factor (VEGF), ERK1/2, and ERK5 protein expression. Overall survival (OS), disease-specific survival (DSS), and progression- or recurrence-free survival (PFS) were analyzed using the Kaplan-Meier method. Mantel-Haenszel was used for comparisons, and Cox proportional risk models were also constructed. RESULTS: Follow-up was 66.9 months. There were 23 (46.0%) deaths, of which 17 (73.9%) were caused by the tumor. Mean periods were 85.6 months for OS and 94.3 months for DSS. A total of 22 (44.0%) patients showed progression (PFS, 78.1 months). VHL expression (P = .045) and > 10% of HIF1-α expression (P = .034) were associated with greater OS. DSS was greater in patients without VHL methylation (P = .012), with > 10% HIF1-α expression (P = .037), or with ERK5 protein underexpression. Greater PFS was associated with absence of VHL methylation (P = .045), presence of VHL expression (P < .0001), HIF1-α expression > 10% (P = .04), and ERK5 protein underexpression (P = .011). The presence of VHL mutation and/or methylation and VEGF expression had no prognostic value. Fuhrman nuclear grade and Tumor, Node, Metastases (TNM) stage were the only variables that remained in the Cox model. CONCLUSION: The HIF1-α and ERK5 pathway has prognostic value. Patients with no VHL or HIF1-α expression and ERK5 overexpression had a worse course of disease. VHL or VEGF status had no prognostic value. Only TNM stage and Fuhrman nuclear grade remained in the Cox model and, therefore, are still essential in prognostic biomarker panels.

Transcriptomic immunologic signature associated with favorable clinical outcome in basal-like breast tumors.

BACKGROUND: Most patients with early stage triple negative breast cancer (TNBC) receive adjuvant chemotherapy. Activation of the immune system is associated with tumor response and may help identify TNBC with favorable outcome. METHODS: Gene expression data were obtained from the GEO Dataset GDS2250/GSE3744. Affymetrix CEL files were downloaded and analyzed with Affymetrix Transcriptome Analysis Console 3.0. Functional genomics was implemented with David Bioinformatics Resources 6.8. Data contained at Oncomine were used to identify genes upregulated in basal-like cancer compared to normal breast tissue. Data contained at cBioportal were used to assess for molecular alterations. The KMPlotter online tool, METABRIC and GSE25066 datasets were used to associate gene signatures with clinical outcome. RESULTS: 1564 upregulated genes were identified as differentially expressed between normal and basal-like tumors. Of these, 16 genes associated with immune function were linked with clinical outcome. HLA-C, HLA-F, HLA-G and TIGIT were associated with both improved relapse-free survival (RFS) and overall survival (OS). The combination of HLA-F/TIGIT and HLA-C/HLA-F/TIGIT showed the most favorable outcome (HR for RFS 0.44, p<0.001; HR for OS 0.22, p<0.001; and HR for RFS 0.46, p<0.001; HR for OS 0.15, p<0.001; respectively). The association of HLA-C/HLA-F with outcome was confirmed using the METABRIC and GSE25066 datasets. No copy number alterations of these genes were identified. CONCLUSION: We describe a gene signature associated with immune function and favorable outcome in basal-like breast cancer. Incorporation of this signature in prospective studies may help to stratify risk of early stage TNBC.