Theoretical evaluation of the impact of diverse treatment conditions by calculation of the tumor control probability (TCP) of simulated cervical cancer Hyperthermia-Radiotherapy (HT-RT) treatments in-silico.

INTRODUCTION: Hyperthermia (HT) induces various cellular biological processes, such as repair impairment and direct HT cell killing. In this context, in-silico biophysical models that translate deviations in the treatment conditions into clinical outcome variations may be used to study the extent of such processes and their influence on combined hyperthermia plus radiotherapy (HT + RT) treatments under varying conditions. METHODS: An extended linear-quadratic model calibrated for SiHa and HeLa cell lines (cervical cancer) was used to theoretically study the impact of varying HT treatment conditions on radiosensitization and direct HT cell killing effect. Simulated patients were generated to compute the Tumor Control Probability (TCP) under different HT conditions (number of HT sessions, temperature and time interval), which were randomly selected within margins based on reported patient data. RESULTS: Under the studied conditions, model-based simulations suggested a treatment improvement with a total CEM43 thermal dose of approximately 10 min. Additionally, for a given thermal dose, TCP increased with the number of HT sessions. Furthermore, in the simulations, we showed that the TCP dependence on the temperature/time interval is more correlated with the mean value than with the minimum/maximum value and that comparing the treatment outcome with the mean temperature can be an excellent strategy for studying the time interval effect. CONCLUSION: The use of thermoradiobiological models allows us to theoretically study the impact of varying thermal conditions on HT + RT treatment outcomes. This approach can be used to optimize HT treatments, design clinical trials, and interpret patient data.

Prevalence and associated factors for asthma in adults in Quito: a cross-sectional study.

Background: Although several epidemiological studies of asthma have been carried out in Ecuador in the last two decades, none of these has estimated the prevalence of asthma in adult populations. Objective: To estimate the prevalence of asthma symptoms in adults in the city of Quito and to identify possible associated factors. Methods: A cross-sectional study was conducted on subjects older than 18 years residing in the Metropolitan District of Quito. The Global Asthma Network (GAN) questionnaire was applied to collect information on asthma symptoms and sociodemographic and lifestyle data. Bivariate and multivariate analyses with logistic regression were used to identify asthma-related factors. Results: 2,476 subjects answered the questionnaire (80.9% women, mean age 40 years). The prevalence of wheezing in the last 12 months, asthma ever, and asthma diagnosed by a doctor were 6.3%, 1.9% and 1.6%, respectively. The prevalence of rhinitis ever and eczema ever was 13.7% and 5.5%. The presence of mould at home (OR: 2.13; 95% CI: 1.48 -3.06; p <0.001), cat at home (OR: 1.06; 95% CI: 1.06 -2.13; p <0.022) and rhinitis at some time (OR: 3.65; 95% CI: 2.53 - 5.29; p <0.022) were associated with the presence of wheezing in the last 12 months. Conclusions: Our study shows that, compared to other cities in Latin America, the prevalence of asthma in adults in Quito is relatively low. Along with the presence of rhinitis, factors related to housing quality are closely linked to the occurrence of asthma in adult populations.

Antecedentes: Aunque en el Ecuador se han realizado varios estudios epidemiológicos de asma en las dos últimas décadas, ninguno de estos ha estimado la prevalencia de asma en poblaciones adultas. Objetivo: Estimar la prevalencia de síntomas de asma en adultos en Quito e identificar posibles factores asociados. Métodos: Se realizó un estudio transversal en sujetos mayores a 18 años residentes en la ciudad de Quito-Ecuador. Se aplicó el cuestionario Global Asthma Network para recolectar información sobre síntomas de asma y datos sociodemográficas y de estilo de vida. Para la identificación de factores asociados con asma se utilizó análisis bivariados y multivariados con regresión logística. Resultados: Un total de 2,476 sujetos respondieron el cuestionario (80.9% mujeres, edad media 40 años). La prevalencia de sibilancias en los últimos 12 meses, asma alguna vez y asma diagnosticado por un médico fue de 6.3%; 1.9% y 1.6%, respectivamente. La prevalencia de rinitis y eczema alguna vez fue de 13.7% y 5.5%. La presencia de moho en el hogar (OR: 2.13; 95% IC: 1.48-3.06; p <0.001), gato en casa (OR: 1.06; 95% IC: 1.06-2.13; p <0.022) y rinitis alguna vez (OR: 3.65; 95% IC: 2.53-5.29; p <0.022) estaban asociados con la presencia de sibilancias en los últimos 12 meses. Conclusiones: Nuestro estudio muestra que, en comparación con otras ciudades de América Latina, la prevalencia de asma en adultos en Quito es relativamente baja. Junto con la presencia de rinitis, factores relacionados con la calidad de la vivienda están estrechamente ligados con la ocurrencia de asma en poblaciones adultas.

Prevalence and associated factors for asthma in adults in Quito: a cross-sectional study / Prevalencia y factores asociados para asma en adultos en Quito: un estudio transversal

Abstract Background: Although several epidemiological studies of asthma have been carried out in Ecuador in the last two decades, none of these has estimated the prevalence of asthma in adult populations. Objective: To estimate the prevalence of asthma symptoms in adults in the city of Quito and to identify possible associated factors. Methods: A cross-sectional study was conducted on subjects older than 18 years residing in the Metropolitan District of Quito. The Global Asthma Network (GAN) questionnaire was applied to collect information on asthma symptoms and sociodemographic and lifestyle data. Bivariate and multivariate analyses with logistic regression were used to identify asthma-related factors. Results: 2,476 subjects answered the questionnaire (80.9% women, mean age 40 years). The prevalence of wheezing in the last 12 months, asthma ever, and asthma diagnosed by a doctor were 6.3%, 1.9% and 1.6%, respectively. The prevalence of rhinitis ever and eczema ever was 13.7% and 5.5%. The presence of mould at home (OR: 2.13; 95% CI: 1.48 -3.06; p <0.001), cat at home (OR: 1.06; 95% CI: 1.06 -2.13; p <0.022) and rhinitis at some time (OR: 3.65; 95% CI: 2.53 - 5.29; p <0.022) were associated with the presence of wheezing in the last 12 months. Conclusions: Our study shows that, compared to other cities in Latin America, the prevalence of asthma in adults in Quito is relatively low. Along with the presence of rhinitis, factors related to housing quality are closely linked to the occurrence of asthma in adult populations.

Resumen Antecedentes: Aunque en el Ecuador se han realizado varios estudios epidemiológicos de asma en las dos últimas décadas, ninguno de estos ha estimado la prevalencia de asma en poblaciones adultas. Objetivo: Estimar la prevalencia de síntomas de asma en adultos en Quito e identificar posibles factores asociados. Métodos: Se realizó un estudio transversal en sujetos mayores a 18 años residentes en la ciudad de Quito-Ecuador. Se aplicó el cuestionario Global Asthma Network para recolectar información sobre síntomas de asma y datos sociodemográficas y de estilo de vida. Para la identificación de factores asociados con asma se utilizó análisis bivariados y multivariados con regresión logística. Resultados: Un total de 2,476 sujetos respondieron el cuestionario (80.9% mujeres, edad media 40 años). La prevalencia de sibilancias en los últimos 12 meses, asma alguna vez y asma diagnosticado por un médico fue de 6.3%; 1.9% y 1.6%, respectivamente. La prevalencia de rinitis y eczema alguna vez fue de 13.7% y 5.5%. La presencia de moho en el hogar (OR: 2.13; 95% IC: 1.48-3.06; p <0.001), gato en casa (OR: 1.06; 95% IC: 1.06-2.13; p <0.022) y rinitis alguna vez (OR: 3.65; 95% IC: 2.53-5.29; p <0.022) estaban asociados con la presencia de sibilancias en los últimos 12 meses. Conclusiones: Nuestro estudio muestra que, en comparación con otras ciudades de América Latina, la prevalencia de asma en adultos en Quito es relativamente baja. Junto con la presencia de rinitis, factores relacionados con la calidad de la vivienda están estrechamente ligados con la ocurrencia de asma en poblaciones adultas.

The Effect of Hyperthermia and Radiotherapy Sequence on Cancer Cell Death and the Immune Phenotype of Breast Cancer Cells.

Hyperthermia (HT) is an accepted treatment for recurrent breast cancer which locally heats the tumor to 39-44 °C, and it is a very potent sensitizer for radiotherapy (RT) and chemotherapy. However, currently little is known about how HT with a distinct temperature, and particularly, how the sequence of HT and RT changes the immune phenotype of breast cancer cells. Therefore, human MDA-MB-231 and MCF-7 breast cancer cells were treated with HT of different temperatures (39, 41 and 44 °C), alone and in combination with RT (2 × 5 Gy) in different sequences, with either RT or HT first, followed by the other. Tumor cell death forms and the expression of immune checkpoint molecules (ICMs) were analyzed by multicolor flow cytometry. Human monocyte-derived dendritic cells (moDCs) were differentiated and co-cultured with the treated cancer cells. In both cell lines, RT was the main stressor for cell death induction, with apoptosis being the prominent cell death form in MCF-7 cells and both apoptosis and necrosis in MDA-MB-231 cells. Here, the sequence of the combined treatments, either RT or HT, did not have a significant impact on the final outcome. The expression of all of the three examined immune suppressive ICMs, namely PD-L1, PD-L2 and HVEM, was significantly increased on MCF-7 cells 120 h after the treatment of RT with HT of any temperature. Of special interest for MDA-MB-231 cells is that only combinations of RT with HT of both 41 and 44 °C induced a significantly increased expression of PD-L2 at all examined time points (24, 48, 72, and 120 h). Generally, high dynamics of ICM expression can be observed after combined RT and HT treatments. There was no significant difference between the different sequences of treatments (either HT + RT or RT + HT) in case of the upregulation of ICMs. Furthermore, the co-culture of moDCs with tumor cells of any treatment had no impact on the expression of activation markers. We conclude that the sequence of HT and RT does not strongly affect the immune phenotype of breast cancer cells. However, when HT is combined with RT, it results in an increased expression of distinct immune suppressive ICMs that should be considered by including immune checkpoint inhibitors in multimodal tumor treatments with RT and HT. Further, combined RT and HT affects the immune system in the effector phase rather than in the priming phase.

The Effects of Heat Stress on the Transcriptome of Human Cancer Cells: A Meta-Analysis.

Hyperthermia is clinically applied cancer treatment in conjunction with radio- and/or chemotherapy, in which the tumor volume is exposed to supraphysiological temperatures. Since cells can effectively counteract the effects of hyperthermia by protective measures that are commonly known as the heat stress response, the identification of cellular processes that are essential for surviving hyperthermia could lead to novel treatment strategies that improve its therapeutic effects. Here, we apply a meta-analytic approach to 18 datasets that capture hyperthermia-induced transcriptome alterations in nine different human cancer cell lines. We find, in line with previous reports, that hyperthermia affects multiple processes, including protein folding, cell cycle, mitosis, and cell death, and additionally uncover expression changes of genes involved in KRAS signaling, inflammatory responses, TNF-a signaling and epithelial-to-mesenchymal transition (EMT). Interestingly, however, we also find a considerable inter-study variability, and an apparent absence of a 'universal' heat stress response signature, which is likely caused by the differences in experimental conditions. Our results suggest that gene expression alterations after heat stress are driven, to a large extent, by the experimental context, and call for a more extensive, controlled study that examines the effects of key experimental parameters on global gene expression patterns.

Theoretical Evaluation of the Impact of Hyperthermia in Combination with Radiation Therapy in an Artificial Immune-Tumor-Ecosystem.

There is some evidence that radiotherapy (RT) can trigger anti-tumor immune responses. In addition, hyperthermia (HT) is known to be a tumor cell radio-sensitizer. How HT could enhance the anti-tumor immune response produced by RT is still an open question. The aim of this study is the evaluation of potential dynamic effects regarding the adaptive immune response induced by different combinations of RT fractions with HT. The adaptive immune system is considered as a trainable unit (perceptron) which compares danger signals released by necrotic or apoptotic cell death with the presence of tumor- and host tissue cell population-specific molecular patterns (antigens). To mimic the changes produced by HT such as cell radio-sensitization or increase of the blood perfusion after hyperthermia, simplistic biophysical models were included. To study the effectiveness of the different RT+HT treatments, the Tumor Control Probability (TCP) was calculated. In the considered scenarios, the major effect of HT is related to the enhancement of the cell radio-sensitivity while perfusion or heat-based effects on the immune system seem to contribute less. Moreover, no tumor vaccination effect has been observed. In the presented scenarios, HT boosts the RT cell killing but it does not fundamentally change the anti-tumor immune response.

Trends in hospital admissions and mortality rates for asthma in Ecuador: a joinpoint regression analysis of data from 2000 to 2018.

BACKGROUND: Although asthma has emerged as an important public health problem over recent decades in Latin America, there are limited published data on national hospital admission and mortality rates for asthma from countries in the region. OBJECTIVE: To analyse trends in asthma hospitalisation and mortality rates in Ecuador over a 19-year period from 2000 to 2018. METHODS: Hospital discharge and death certificates listing asthma, as defined in the International Classification of Diseases 10th Revision codes (J45 and J46), were used to analyse time trends in rates of hospital admissions and mortality for asthma. The data were obtained from the Ecuadorian National Institute of Statistics and Census. Crude and age-standardised rates were estimated for the entire population. Additionally, specific rates by sex, age and region were estimated. We used joinpoint analysis to identify national trends. RESULT: During 2000-2018, a total of 58 250 hospitalisations and 1328 deaths due to asthma were identified. The average annual rates for hospitalisation and mortality attributed to asthma were estimated to be 21 (95% CI 19.3 to 22.8) and 5.2 (95% CI 4.4 to 6.0) per 100 000 population, respectively, over this period. Asthma hospital admissions decreased from 28 to 13.7 per 100 000 population between 2000 and 2018, and asthma mortality decreased from 0.8 to 0.3 per 100 000 population over the same period. Based on jointpoint analysis, two temporal trends were identified for hospital admissions. Between 2000 and 2011, hospital admissions decreased 0.8% per year and between 2011 and 2018 decreased 6.6% per year (p<0.05). On average, hospitalisation rates decreased 3.1% per year (p<0.05) over the entire study period. Mortality rate decreased 5.6% per year (p<0.05) over the 19-year period. Hospitalisation rates were higher among females, those aged 5 to 19 years and those living in the Coast region. CONCLUSIONS: Our analysis shows a temporal trend of reduction in rates of hospitalisations and deaths attributed to asthma between 2000 and 2018 in Ecuador, consistent with similar trends elsewhere in the Latin American region. Health registration systems in Latin America need to be improved to provide reliable data for future between and within country comparisons of trends in asthma hospitalisations and deaths.

Artritis psoriática y cirrosis hepática / Psoariatic arthritis and hepatic cirrhosis

Se presenta un caso de artritis psoriásica acompañada de cirrosis hepática post-alcohólica en un sujeto de 73 años. Presenta una disminución relativa de la respuesta inmune celular (medida por pruebas in vivo) y aumento (relativo también) de la inmunidad humoral. La histocompatibilidad del paciente demuestra la presencia de HLA_Bw-56 (que cruza inmunológicamente con HLA-B27) y otros antígenos HLA-A2, HLA- A11 frecuentes en la raza mestiza. Aunque no se encontró fenómenos auto-inmunes se hace notar la relación que existe entre este tipo de enfermedades con alteraciones inmunológicas concomitantes

Inhibición por terfenadina de la respuesta cutánea histamínica / Inhibition by terfenadine of the cutaneous histamine response

Se valora la capacidad de inhibición de la respuesta cutánea a la histamina por parte de la terfenadina en relación al placebo en cuarenta pacientes atópicos asintomáticos del servicio de Alergología e Inmunología del HG-1, encontrándose que la terfenadina se muestra más efectiva para inhibir el desarrollo del habón urticario ocasionado por la administración intradérmica de una solución de histamina que el placebo, con una potencia bloqueadora de los receptores histamínicos periféricos H1 semejante a la clemastina y al ketotifeno, y sin efectos colaterales atribuibles a ella en los veinte pacientes que la recibieron