Long Noncoding RNA TALAM1 Is a Transcriptional Target of the RUNX2 Transcription Factor in Lung Adenocarcinoma.

BACKGROUND: Lung cancer is the leading cause of cancer death worldwide. It has been reported that genetic and epigenetic factors play a crucial role in the onset and evolution of lung cancer. Previous reports have shown that essential transcription factors in embryonic development contribute to this pathology. Runt-related transcription factor (RUNX) proteins belong to a family of master regulators of embryonic developmental programs. Specifically, RUNX2 is the master transcription factor (TF) of osteoblastic differentiation, and it can be involved in pathological conditions such as prostate, thyroid, and lung cancer by regulating apoptosis and mesenchymal-epithelial transition processes. In this paper, we identified TALAM1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) as a genetic target of the RUNX2 TF in lung cancer and then performed functional validation of the main findings. METHODS: We performed ChIP-seq analysis of tumor samples from a patient diagnosed with lung adenocarcinoma to evaluate the target genes of the RUNX2 TF. In addition, we performed shRNA-mediated knockdown of RUNX2 in this lung adenocarcinoma cell line to confirm the regulatory role of RUNX2 in TALAM1 expression. RESULTS: We observed RUNX2 overexpression in cell lines and primary cultured lung cancer cells. Interestingly, we found that lncRNA TALAM1 was a target of RUNX2 and that RUNX2 exerted a negative regulatory effect on TALAM1 transcription.

Prolongation of the QTc Interval at Admission is Associated with Increased Mortality in Patients with SARS-COV-2 during Hospitalization. / O Prolongamento do Intervalo QTc na Admissão está Associado ao Aumento da Mortalidade em Pacientes com SARS-COV-2 durante a Hospitalização.

BACKGROUND: Cardiovascular involvement associated with SARS-COV-2 infection is related to unfavorable outcomes during hospitalization. Therefore, the measurement at the admission of the QTc interval on the 12-lead electrocardiogram may be a prognostic marker. OBJECTIVE: To identify the relationship between QTc prolongation at admission during hospitalization and mortality from SARS-COV-2. METHOD: Observational study based on a retrospective cohort of patients with confirmed SARS-COV-2 infection from San Ignacio University Hospital, Bogotá (Colombia), between March 19, 2020, and July 31, 2021. Mortality was compared in patients with prolonged and normal QTc at admission after controlling by clinical variables and comorbidities using bivariate and multivariate logistic regression models. A p-value <0.05 was considered statistically significant. RESULTS: 1296 patients were analyzed, and 127 (9.8%) had prolonged QTc. Mortality was higher in patients with prolonged QTc (39.4% vs 25.3%, p=0.001), as was hospital stay (median 11vs.8 days; p=0.002). In the multivariate analysis, mortality was associated with prolonged QTc (OR 1.61, 95% CI: 1.02; 2.54, p=0.038), age (OR 1.03, 95% CI 1.02; 1.05, p<0.001), male sex (OR 2.15, 95% CI 1.60; 2.90, p <0.001), kidney disease (OR 1.32, 95% CI 1.05; 1.66, p =0.018) and Charlson comorbidity index > 3 (OR 1.49, 95% CI 1.03; 2.17, p=0.035). CONCLUSIONS: Hospital mortality due to SARS-COV-2 is associated with prolonging the QTc interval at the time of admission, even after adjusting for age, sex, comorbidities, and basal severity of infection. Additional research is needed to establish whether these findings are related to cardiac involvement by the virus, hypoxia, and systemic inflammation.

FUNDAMENTO: O envolvimento cardiovascular associado à infecção por SARS-COV-2 está relacionado a desfechos desfavoráveis durante a internação. Portanto, a medida na admissão do intervalo QTc no eletrocardiograma de 12 derivações pode ser um marcador prognóstico. OBJETIVO: Identificar a relação entre o prolongamento do QTc na admissão durante a hospitalização e a mortalidade por SARS-COV-2. MÉTODO: Estudo observacional baseado em uma coorte retrospectiva de pacientes com infecção confirmada por SARS-COV-2 do Hospital Universitário San Ignacio, Bogotá (Colômbia), entre 19 de março de 2020 e 31 de julho de 2021. A mortalidade foi comparada em pacientes com QTc prolongado e normal na admissão e controle das variáveis clínicas e comorbidades por meio de modelos de regressão logística bivariada e multivariada. Um valor de p <0,05 foi considerado estatisticamente significativo. RESULTADOS: Foram analisados 1.296 pacientes e 127 (9,8%) apresentaram QTc prolongado. A mortalidade foi maior em pacientes com QTc prolongado (39,4% vs. 25,3%, p=0,001), assim como o tempo de internação (mediana 11 vs. 8 dias; p=0,002). Na análise multivariada, a mortalidade foi associada a QTc prolongado (OR 1,61, IC 95%: 1,02; 2,54, p=0,038), idade (OR 1,03, IC 95% 1,02; 1,05, p<0,001), sexo masculino (OR 2,15, IC 95% 1,60; 2,90, p<0,001), doença renal (OR 1,32, IC 95% 1,05; 1,66, p=0,018) e índice de comorbidade de Charlson > 3 (OR 1,49, IC 95% 1,03; 2,17, p=0,035). CONCLUSÕES: A mortalidade hospitalar por SARS-COV-2 está associada ao prolongamento do intervalo QTc no momento da admissão, mesmo após ajuste para idade, sexo, comorbidades e gravidade basal da infecção. Pesquisas adicionais são necessárias para estabelecer se esses achados estão relacionados ao envolvimento cardíaco pelo vírus, hipóxia e inflamação sistêmica.

O Prolongamento do Intervalo QTc na Admissão está Associado ao Aumento da Mortalidade em Pacientes com SARS-COV-2 durante a Hospitalização / Prolongation of the QTc Interval at Admission is Associated with Increased Mortality in Patients with SARS-COV-2 during Hospitalization

Resumo Fundamento O envolvimento cardiovascular associado à infecção por SARS-COV-2 está relacionado a desfechos desfavoráveis durante a internação. Portanto, a medida na admissão do intervalo QTc no eletrocardiograma de 12 derivações pode ser um marcador prognóstico. Objetivo Identificar a relação entre o prolongamento do QTc na admissão durante a hospitalização e a mortalidade por SARS-COV-2. Método Estudo observacional baseado em uma coorte retrospectiva de pacientes com infecção confirmada por SARS-COV-2 do Hospital Universitário San Ignacio, Bogotá (Colômbia), entre 19 de março de 2020 e 31 de julho de 2021. A mortalidade foi comparada em pacientes com QTc prolongado e normal na admissão e controle das variáveis clínicas e comorbidades por meio de modelos de regressão logística bivariada e multivariada. Um valor de p <0,05 foi considerado estatisticamente significativo Resultados Foram analisados 1.296 pacientes e 127 (9,8%) apresentaram QTc prolongado. A mortalidade foi maior em pacientes com QTc prolongado (39,4% vs. 25,3%, p=0,001), assim como o tempo de internação (mediana 11 vs. 8 dias; p=0,002). Na análise multivariada, a mortalidade foi associada a QTc prolongado (OR 1,61, IC 95%: 1,02; 2,54, p=0,038), idade (OR 1,03, IC 95% 1,02; 1,05, p<0,001), sexo masculino (OR 2,15, IC 95% 1,60; 2,90, p<0,001), doença renal (OR 1,32, IC 95% 1,05; 1,66, p=0,018) e índice de comorbidade de Charlson > 3 (OR 1,49, IC 95% 1,03; 2,17, p=0,035). Conclusões A mortalidade hospitalar por SARS-COV-2 está associada ao prolongamento do intervalo QTc no momento da admissão, mesmo após ajuste para idade, sexo, comorbidades e gravidade basal da infecção. Pesquisas adicionais são necessárias para estabelecer se esses achados estão relacionados ao envolvimento cardíaco pelo vírus, hipóxia e inflamação sistêmica.

Abstract Background Cardiovascular involvement associated with SARS-COV-2 infection is related to unfavorable outcomes during hospitalization. Therefore, the measurement at the admission of the QTc interval on the 12-lead electrocardiogram may be a prognostic marker. Objective To identify the relationship between QTc prolongation at admission during hospitalization and mortality from SARS-COV-2. Method Observational study based on a retrospective cohort of patients with confirmed SARS-COV-2 infection from San Ignacio University Hospital, Bogotá (Colombia), between March 19, 2020, and July 31, 2021. Mortality was compared in patients with prolonged and normal QTc at admission after controlling by clinical variables and comorbidities using bivariate and multivariate logistic regression models. A p-value <0.05 was considered statistically significant. Results 1296 patients were analyzed, and 127 (9.8%) had prolonged QTc. Mortality was higher in patients with prolonged QTc (39.4% vs 25.3%, p=0.001), as was hospital stay (median 11vs.8 days; p=0.002). In the multivariate analysis, mortality was associated with prolonged QTc (OR 1.61, 95% CI: 1.02; 2.54, p=0.038), age (OR 1.03, 95% CI 1.02; 1.05, p<0.001), male sex (OR 2.15, 95% CI 1.60; 2.90, p <0.001), kidney disease (OR 1.32, 95% CI 1.05; 1.66, p =0.018) and Charlson comorbidity index > 3 (OR 1.49, 95% CI 1.03; 2.17, p=0.035). Conclusions Hospital mortality due to SARS-COV-2 is associated with prolonging the QTc interval at the time of admission, even after adjusting for age, sex, comorbidities, and basal severity of infection. Additional research is needed to establish whether these findings are related to cardiac involvement by the virus, hypoxia, and systemic inflammation.

Regulatory Role of the RUNX2 Transcription Factor in Lung Cancer Apoptosis.

Lung cancer is the leading cause of cancer death globally. Numerous factors intervene in the onset and progression of lung tumors, among which the participation of lineage-specific transcription factors stands out. Several transcription factors important in embryonic development are abnormally expressed in adult tissues and thus participate in the activation of signaling pathways related to the acquisition of the tumor phenotype. RUNX2 is the transcription factor responsible for osteogenic differentiation in mammals. Current studies have confirmed that RUNX2 is closely related to the proliferation, invasion, and bone metastasis of multiple cancer types, such as osteosarcoma, breast cancer (BC), prostate cancer, gastric cancer, colorectal cancer, and lung cancer. Thus, the present study is aimed at evaluating the role of the RUNX2 transcription factor in inhibiting the apoptosis process. Loss-of-function assays using sh-RNA from lentiviral particles and coupled with Annexin/propidium iodide (PI) assays (flow cytometry), immunofluorescence, and quantitative PCR analysis of genes related to cell apoptosis (BAD, BAX, BCL2, BCL-XL, and MCL1) were performed. Silencing assays and Annexin/PI assays demonstrated that when RUNX2 was absent, the percentage of dead cells increased, and the expression levels of the BCL2, BCL-XL, and MCL1 genes were downregulated. Furthermore, to confirm whether the regulatory role of RUNX2 in the expression of these genes is related to its binding to the promoter region, we performed chromatin immunoprecipitation (ChIP) assays. Here, we report that overexpression of the RUNX2 gene in lung cancer may be related to the inhibition of the intrinsic apoptosis pathway, specifically, through direct transcriptional regulation of the antiapoptotic gene BCL2 and indirect regulation of BCL-XL and MCL1.

Identification of the Transcriptional Regulatory Role of RUNX2 by Network Analysis in Lung Cancer Cells.

The use of a new bioinformatics pipeline allowed the identification of deregulated transcription factors (TFs) coexpressed in lung cancer that could become biomarkers of tumor establishment and progression. A gene regulatory network (GRN) of lung cancer was created with the normalized gene expression levels of differentially expressed genes (DEGs) from the microarray dataset GSE19804. Moreover, coregulatory and transcriptional regulatory network (TRN) analyses were performed for the main regulators identified in the GRN analysis. The gene targets and binding motifs of all potentially implicated regulators were identified in the TRN and with multiple alignments of the TFs' target gene sequences. Six transcription factors (E2F3, FHL2, ETS1, KAT6B, TWIST1, and RUNX2) were identified in the GRN as essential regulators of gene expression in non-small-cell lung cancer (NSCLC) and related to the lung tumoral process. Our findings indicate that RUNX2 could be an important regulator of the lung cancer GRN through the formation of coregulatory complexes with other TFs related to the establishment and progression of lung cancer. Therefore, RUNX2 could become an essential biomarker for developing diagnostic tools and specific treatments against tumoral diseases in the lung after the experimental validation of its regulatory function.

Enfermedad de la vía área central-estenosis traqueal posintubación orotraqueal / Central airway disease Post-intubation tracheal stenosis

Desde la aparición de la enfermedad por SARS-CoV-2, han cambiado paradigmas en la ciencia médica y actualmente nos enfrentamos a las repercusiones a largo plazo que algunos de los pacientes desarrollan. Entre el grupo de pacientes que han cursado con neumonía severa-síndrome de dificultad respiratoria aguda (SDRA) por SARS-CoV-2 y que requirieron intubación orotraqueal (IOT), se documentan complicaciones multisistémicas (1-4). En este artículo destacaremos las complicaciones relacionadas con la vía aérea que se presentan en forma de estenosis benignas, siendo las lesiones subglóticas tipo simples o complejas las más frecuentes. A continuación, presentamos el caso de un paciente que presentó estenosis traqueales pos-IOT a causa de una neumonía severa por COVID-19 con diagnóstico, seguimiento y manejo por un grupo multidisciplinario de vía aérea.

Since the appearance of SARSCoV-2 disease, paradigms have changed in medical science, and we are currently facing the long-term repercussions that some of the patients develop. Within the group of patients who have had severe pneumonia - Acute respiratory distress syndrome (ARDS) due to SARSCoV-2 and who required orotracheal intubation (OTI), multisystemic complications are documented (1-4), in In this article, we will highlight airway-related complications that occur in the form of benign stenosis, with simple or complex subglottic lesions being the most common. We present a case of a patient who presented tracheal stenosis post-OTI due to severe COVID-19 pneumonia as main diagnosis, follow-up, and management by a multidisciplinary airway group.

Transcriptional regulation of CDKN2A/p16 by sirtuin 7 in senescence.

Cell senescence is a state of limited cell proliferation during a stress response or as part of a programmed process. When a senescent cell stops dividing, maintaining metabolic activity contributes to cellular homeostasis maintenance. In this process, the cell cycle is arrested at the G0/G1 phase. p16INK4A protein is a key regulator of this process via its cyclin­dependent kinase inhibitor (CDKI) function. CDKI 2A (CDKN2A)/p16 gene expression is regulated by DNA methylation and histone acetylation. Sirtuins (SIRTs) are nicotinamide dinucleotide (NAD+)­dependent deacetylases that have properties which prevent diseases and reverse certain aspects of aging (such as immune, metabolic and cardiovascular diseases). By performing quantitative PCR, Western blot, ChIP, and siRNAs assays, in this study it was demonstrated that CDKN2A/p16 gene transcriptional activation and repression were accompanied by selective deposition and elimination of histone acetylation during the senescence of MRC5 cells. Specifically, significant H3K9Ac and H3K18Ac enrichment in cells with a senescent phenotype concomitant with CDKN2A/p16 gene overexpression was demonstrated compared with the non­senescent phenotype. Furthermore, the presence of H3K18Ac in deacetyl­transferase SIRT7 knockdown MRC5 cells allowed CDKN2A/p16 promoter activation. These results suggested that SIRT7 served as a critical component of an epigenetic mechanism involved in senescence mediated by the CDKN2A/p16 gene.

Identifying General Tumor and Specific Lung Cancer Biomarkers by Transcriptomic Analysis.

The bioinformatic pipeline previously developed in our research laboratory is used to identify potential general and specific deregulated tumor genes and transcription factors related to the establishment and progression of tumoral diseases, now comparing lung cancer with other two types of cancer. Twenty microarray datasets were selected and analyzed separately to identify hub differentiated expressed genes and compared to identify all the deregulated genes and transcription factors in common between the three types of cancer and those unique to lung cancer. The winning DEGs analysis allowed to identify an important number of TFs deregulated in the majority of microarray datasets, which can become key biomarkers of general tumors and specific to lung cancer. A coexpression network was constructed for every dataset with all deregulated genes associated with lung cancer, according to DAVID's tool enrichment analysis, and transcription factors capable of regulating them, according to oPOSSUM´s tool. Several genes and transcription factors are coexpressed in the networks, suggesting that they could be related to the establishment or progression of the tumoral pathology in any tissue and specifically in the lung. The comparison of the coexpression networks of lung cancer and other types of cancer allowed the identification of common connectivity patterns with deregulated genes and transcription factors correlated to important tumoral processes and signaling pathways that have not been studied yet to experimentally validate their role in lung cancer. The Kaplan-Meier estimator determined the association of thirteen deregulated top winning transcription factors with the survival of lung cancer patients. The coregulatory analysis identified two top winning transcription factors networks related to the regulatory control of gene expression in lung and breast cancer. Our transcriptomic analysis suggests that cancer has an important coregulatory network of transcription factors related to the acquisition of the hallmarks of cancer. Moreover, lung cancer has a group of genes and transcription factors unique to pulmonary tissue that are coexpressed during tumorigenesis and must be studied experimentally to fully understand their role in the pathogenesis within its very complex transcriptomic scenario. Therefore, the downstream bioinformatic analysis developed was able to identify a coregulatory metafirm of cancer in general and specific to lung cancer taking into account the great heterogeneity of the tumoral process at cellular and population levels.

Effectiveness of brief counselling in a hospital setting for smoking cessation and risky alcohol drinking reduction: randomised clinical trial protocol.

INTRODUCTION: Chronic diseases are a public health problem, and 80% of them are related to modifiable risk factors such as unhealthy diet, physical inactivity, smoking, and risky alcohol consumption. Although the intervention in smoking and hazardous alcohol drinking has proven to be effective in Primary Care, it is unknown whether it works in the same way in the hospital setting. OBJECTIVE: To evaluate the effectiveness of brief counselling in order to modify the stage of change in smokers and at-risk drinkers treated in a high complexity hospital. METHODS: A Randomised controlled trial to be conducted, in which an evaluation is made of four brief counselling strategies for smoking cessation and risky alcohol consumption compared to usual care, selected according to the patient's stage of change. The primary result will be the proportion of patients in each of the groups (intervention and control) with identified progress in the stage of change. The reduction of consumption will be also be analysed. Protocol registered at ClinicalTrials.gov (NCT03521622). RESULTS: The results will be published in scientific journals, and its application aims to generate behavioural intervention protocols for modifiable risk factors in high complexity hospitals. The trial was presented and approved by the Ethics and Research Committee of the Pontificia Universidad Javeriana and Hospital Universitario de San Ignacio, Bogota, Colombia (Approval 01/2018).

Efectividad de la consejería breve en el ámbito hospitalario para la cesación del tabaquismo y la disminución del consumo riesgoso de alcohol: Protocolo de un experimento clínico aleatorizado / Effectiveness of Brief Counseling in a Hospital Setting for Smoking Cessation and Risky Alcohol Drinking Reduction: Randomized Clinical Trial Protocol

Resumen Introducción: Las enfermedades crónicas son un problema de salud pública; el 80% de ellas se relacionan con factores de riesgo modificables, como una dieta poco saludable, la inactividad física, el tabaquismo y el consumo riesgoso de alcohol. La intervención en el tabaquismo y el consumo riesgoso de alcohol se ha demostrado efectiva en el cuidado primario, pero se desconoce si funciona de la misma manera en el contexto hospitalario. Objetivo: Evaluar la efectividad de la consejería breve para modificar el estadio de cambio en pacientes fumadores y bebedores en riesgo atendidos en un hospital de alta complejidad. Métodos: Experimento clínico aleatorizado, que evalúa la efectividad de 4 modalidades de consejería breve para la cesación de tabaquismo y el consumo riesgoso de alcohol en comparación con el cuidado habitual, seleccionadas según el estadio de cambio del sujeto. El resultado primario es la proporción de pacientes en cada uno de los grupos (intervención y control) en los cuales se identifica el avance en el estadio de cambio; además se analizará la reducción de consumos. Protocolo registrado en ClinicalTrials.gov (NCT03521622). Resultados: Los resultados se publicarán en revistas de literatura científica y su aplicación pretende generar protocolos de intervenciones conductuales en factores de riesgo modificables en hospitales de alta complejidad. El experimento fue presentado y aprobado por el Comité de Ética e Investigación de la Pontificia Universidad Javeriana y el Hospital Universitario de San Ignacio (aprobación 01/2018).

Abstrac Introduction: Chronic diseases are a public health problem, and 80% of them are related to modifiable risk factors such as unhealthy diet, physical inactivity, smoking, and risky alcohol consumption. Although the intervention in smoking and hazardous alcohol drinking has proven to be effective in Primary Care, it is unknown whether it works in the same way in the hospital setting. Objective: To evaluate the effectiveness of brief counselling in order to modify the stage of change in smokers and at-risk drinkers treated in a high complexity hospital. Methods: A Randomized controlled trial to be conducted, in which an evaluation is made of four brief counselling strategies for smoking cessation and risky alcohol consumption compared to usual care, selected according to the patient's stage of change. The primary result will be the proportion of patients in each of the groups (intervention and control) with identified progress in the stage of change. The reduction of consumption will be also be analyzed. Protocol registered at ClinicalTrials.gov (NCT03521622). Results: The results will be published in scientific journals, and its application aims to generate behavioral intervention protocols for modifiable risk factors in high complexity hospitals. The trial was presented and approved by the Ethics and Research Committee of the Pontificia Universidad Javeriana and Hospital Universitario de San Ignacio, Bogota, Colombia (Approval 01/2018).

RUNX1 gene expression changes in the placentas of women smokers.

The placenta can be affected by environmental factors, such as exposure to cigarette smoke. This exposure in the fetal context is considered a risk factor for the development of short-term postnatal diseases, such as asthma. Asthma is an inflammatory disease characterized by predominant acquisition of CD4 T lymphocytes (TLs) of the Th2 type. Transcription factors such as GATA binding protein 3 (GATA3) and STAT6 actively participate in the differentiation of virgin TLs towards the Th2 profile, while transcription factors such as STAT1, T-Box transcription factor 21 (T-BET), RUNX1 and RUNX3 participate in their differentiation towards the Th1 profile. The objective of the current study was to evaluate the impact of exposure to cigarette smoke on the gene expression of STAT1, T-BET, GATA3, IL-4, RUNX1 and RUNX3 during the gestation period, and to determine whether the expression levels of these genes are associated with changes in global methylation. STAT1, GATA3, RUNX1 and RUNX3 protein and mRNA expression levels in the placental tissue of women smokers and non-smoking women were determined via immunohistochemistry and quantitative PCR (qPCR) respectively. Additionally, T-BET and IL-4 mRNA expression levels were determined by qPCR. On the other hand, global methylation was determined via ELISA. In the present study, significant increases were observed in RUNX1 transcription factor expression in placentas from women smokers when compared with placentas of non-smoking women. Similarly, significant increases in the expression of GATA3, IL-4 and RUNX3 mRNA were observed. The changes in gene expression were not associated with changes in the global methylation levels. Finally, a higher frequency of low-birth-weight infants were identified in cases of exposure to cigarette smoke during pregnancy when compared with infants not exposed to cigarette smoke during pregnancy. Thus, the data of the present study contributed to the understanding of the genetic and clinical impacts of exposure to cigarette smoke during pregnancy and its importance in maternal and fetal health.

Influencia del tabaquismo en la infección por coronavirus. Documento posición Comité Anti-Tabaco / Influence of smoking habit in coronavirus infection. Anti-Tobacco Committee Position Statemen

No disponible

Effectiveness of Brief Counseling in a Hospital Setting for Smoking Cessation and Risky Alcohol Drinking Reduction: Randomized Clinical Trial Protocol. / Efectividad de la consejería breve en el ámbito hospitalario para la cesación del tabaquismo y la disminución del consumo riesgoso de alcohol: Protocolo de un experimento clínico aleatorizado.

INTRODUCTION: Chronic diseases are a public health problem, and 80% of them are related to modifiable risk factors such as unhealthy diet, physical inactivity, smoking, and risky alcohol consumption. Although the intervention in smoking and hazardous alcohol drinking has proven to be effective in Primary Care, it is unknown whether it works in the same way in the hospital setting. OBJECTIVE: To evaluate the effectiveness of brief counselling in order to modify the stage of change in smokers and at-risk drinkers treated in a high complexity hospital. METHODS: A Randomised controlled trial to be conducted, in which an evaluation is made of four brief counselling strategies for smoking cessation and risky alcohol consumption compared to usual care, selected according to the patient's stage of change. The primary result will be the proportion of patients in each of the groups (intervention and control) with identified progress in the stage of change. The reduction of consumption will be also be analysed. Protocol registered at ClinicalTrials.gov (NCT03521622). RESULTS: The results will be published in scientific journals, and its application aims to generate behavioural intervention protocols for modifiable risk factors in high complexity hospitals. The trial was presented and approved by the Ethics and Research Committee of the Pontificia Universidad Javeriana and Hospital Universitario de San Ignacio, Bogota, Colombia (Approval 01/2018).

Role of RUNX2 transcription factor in epithelial mesenchymal transition in non-small cell lung cancer lung cancer: Epigenetic control of the RUNX2 P1 promoter.

Lung cancer has a high mortality rate in men and women worldwide. Approximately 15% of diagnosed patients with this type of cancer do not exceed the 5-year survival rate. Unfortunately, diagnosis is established in advanced stages, where other tissues or organs can be affected. In recent years, lineage-specific transcription factors have been associated with a variety of cancers. One such transcription factor possibly regulating cancer is RUNX2, the master gene of early and late osteogenesis. In thyroid and prostate cancer, it has been reported that RUNX2 regulates expression of genes important in tumor cell migration and invasion. In this study, we report on RUNX2/ p57 overexpression in 16 patients with primary non-small cell lung cancer and/or metastatic lung cancer associated with H3K27Ac at P1 gene promoter region. In some patients, H3K4Me3 enrichment was also detected, in addition to WDR5, MLL2, MLL4, and UTX enzyme recruitment, members of the COMPASS-LIKE complex. Moreover, transforming growth factor-ß induced RUNX2/ p57 overexpression and specific RUNX2 knockdown supported a role for RUNX2 in epithelial mesenchymal transition, which was demonstrated through loss of function assays in adenocarcinoma A549 lung cancer cell line. Furthermore, RUNX2 increased expression of epithelial mesenchymal transition genes VIMENTIN, TWIST1, and SNAIL1, which reflected increased migratory capacity in lung adenocarcinoma cells.

Study of body fluid samples using flow cytometry: Six years of experience at the Hospital Universitario San Ignacio - Pontificia Universidad Javeriana, Bogota - Colombia / Estudio de muestras de fluidos corporales utilizando citometría de flujo: seis años de experiencia en el Hospital Universitario San Ignacio - Pontificia Universidad Javeriana Bogotá, Colombia / Estudo de amostras de fluídos corporais utilizando citometria de fluxo: seis anos de experiencia no Hospital Universitário San Ignacio - Pontificia Universidad Javeriana, Bogotá, Colômbia

Abstract Flow cytometry (FCM) was implemented in 2008 at the Pontificia Universidad Javeriana and later at the Hospital Universitario San Ignacio to examine special samples of patients with hematological malignancies and solid tumors other than bone marrow and peripheral blood for diagnosis and monitoring. This study describes the main findings of special sample evaluation over a six-year period. In all, 1070 samples of body fluids from patients with benign and malignant diseases were examined by FCM. These samples were stabilized with TransFixTM and stained with six-color immunophenotyping panels. Samples included cerebrospinal fluid, bronchoalveolar lavage, pleural fluid, pericardial fluid and ascite fluid from patients with acute and chronic leukemia, myelodysplastic syndromes, lymphomas, myeloma, autoimmune diseases, immunodeficiencies and solid tumors, among others. Flow cytometry provided important information for the classification and detection of minimal numbers of tumor cells in leukemia and lymphoma cases. This work represents the first national report describing FCM implementation in special samples for diagnosis and clinical monitoring of patients with malignant and benign pathologies.

Resumen La citometría de flujo fue implementada en 2008 en la Pontificia Universidad Javeriana y posteriormente en el Hospital San Ignacio con el fin de examinar, para diagnóstico y monitoreo, muestras especiales de pacientes con malignidades hematológicas y tumores sólidos, distintos de los de médula ósea y sangre periférica. Este estudio describe los principales hallazgos de la evaluación de estas muestras especiales en un periodo de seis años. En total, se examinaron por citometría de flujo 1070 muestras de fluidos corporales de pacientes con enfermedades malignas y benignas. Estas muestras se estabilizaron con TransFix™ y teñidas con paneles inmunofenotípicos de seis colores. Las muestras incluyeron líquido cefalorraquídeo, lavado broncoalveolar, fluido pleural, fluido pericárdico y fluido ascítico, provenientes de pacientes con leucemia aguda y crónica, síndromes mielodisplásicos, linfomas, mieloma, enfermedades autoinmunes, inmunodeficiencias y tumores sólidos, entre otras enfermedades. La citometría de flujo proporcionó información importante sobre la clasificación y detección de números mínimos de células tumorales en casos de leucemia y linfoma. Este trabajo representa el primer reporte nacional que describe la implementación de citometría de flujo en muestras especiales para diagnóstico y monitoreo clínico de pacientes con patologías malignas y benignas.

Resumo A citometria de fluxo foi implementada em 2008 na Pontificia Universidad Javeriana e posteriormente no Hospital San Ignacio com a finalidade de examinar amostras especiais de pacientes com malignidades hematológicas e tumores sólidos diferentes aos de medula óssea e sangue periférico para diagnóstico e monitoramento. Este estudo descreve as principais descobertas a partir da avaliação de amostras especiais em um período de 6 anos. Se examinaram por citometria de fluxo um total de 1.070 amostras de fluídos corporais de pacientes doenças malignas e benignas. Estas amostras se estabilizaram com TransFix™ e coradas com painéis imunofenotípicos de seis cores. As amostras incluíram fluído cérebro-espinhal, lavado broncoalveolar, fluído pleural, fluído pericárdico e fluído ascético, provenientes de pacientes com leucemias aguda e crónica, síndromes mielodisplásicos, linfomas, mielomas, doenças autoimunes, imunodeficiência, e tumores sólidos, entre outras doenças. A citometria de fluxo proporcionou informações importantes sobre a classificação e detecção de um número mínimo de células tumorais nos casos de leucemia e linfomas. Este trabalho representa o primeiro relato nacional que descreve a implementação de citometria de fluxo em amostras especiais para diagnóstico e monitoramento clínico de pacientes com patologias malignas e benignas.

Transición epitelio mesénquima: de lo molecular a lo fisiológico / Epitelial Mesenchymal Transition: From the Molecular to Physiologic

La transición epitelio mesénquima (EMT) es un proceso compuesto de diferentes fases, donde una célula epitelial adquiere un fenotipo mesenquimal. Dentro de los cambios involucrados se encuentran: pérdida de la polaridad celular, adquisición de una capacidad migratoria, capacidad invasora, resistencia a la apoptosis y aumento en la producción de componentes de la matriz extracelular. Todos estos cambios ocurren como una consecuencia de la activación y represión de genes involucrados con rutas de señalización específicas relacionadas con este evento. La EMT está relacionada con procesos fisiológicos y patológicos como el cáncer. Consta de tres fases: una de células no migratorias, células premigratorias y células migratorias; cada una de ellas producto de diferentes señales intra o extracelulares, factores de transcripción (TGF-B, Snail, TWIST, Sox, Slug, ZEB1, entre otras) y proteínas involucradas (E-cadherina, integrina, vimentina, ocludinas y claudinas).

Transition mesenchymal epithelium (EMT) is a process composed of different phases where an epithelial cell acquires a mesenchymal phenotype. Among the changes involved are: loss of cellular polarity, acquisition of a migratory capacity, invasive capacity, resistance to apoptosis, and increase in the production of components of the extracellular matrix. All these changes occur as a consequence of the activation and repression of genes involved with specific signaling pathways related to this event. EMT is related to physiological and pathological processes such as cancer. It consists of three phases: A phase of non-migratory cells, pre-migratory cells and migratory cells; (TGF-B, Snail, TWIST, Sox, Slug, ZEB1 among others), and proteins involved (E-cadherin, integrin, vimentin, occludins and claudins).

Eficacia y seguridad del uso de medicamentos para la cesación de la adicción al tabaco: revisión de guías de práctica clínica / Efficacy and safety of medication use for the cessation of tobacco addiction: Are view of Clinical Practice Guidelines

Objetivo Revisar la eficacia y seguridad de medicamentos para cesación del tabaquismo en el contexto de construcción de guías de práctica clínica (GPC). Métodos Revisión sistemática de GPC para adaptación mediante ADAPTE. Los desenlaces fueron cesación ≥6 meses y seguridad de las intervenciones. Las GPC se calificaron por pares con DELBI. Se extrajeron resultados de estudios agregativos incluidos en las guías seleccionadas. Resultados Los fármacos duplican la cesación comparados con placebo (tasas de 25,0 % hasta 27,0 % al combinarse con consejería). Los mayores incrementos en cesación se obtienen con ansiolíticos y antidepresivos (8,7% a 19,4%), y los menores con terapia de reemplazo nicotínico -TRN- (5,2% a 12,9%). La nortriptilina tiene eficacia similar al bupropion (aproximadamente 10,0 %). Con limitadas excepciones (parche e inhalador, tabletas y bupropion), las combinaciones de medicamentos no incrementan la abstinencia. Conclusiones TRN, vareniclina, bupropion y nortriptilina son eficaces para dejar de fumar. Las combinaciones de medicamentos requieren más evidencia y deberían restringirse a personas con alta dependencia o con falla terapéutica inicial. Serían deseables análisis de costo-efectividad para valorar implementación de programas en países en desarrollo.

Objective To review the efficacy and safety of pharmacotherapy for smoking cessation in the context of clinical practice guidelines (CPG). Methods A systematic review of CPGs was conducted, aimed at adapting recommendations for Colombia following the ADAPTE methodology. Outcomes comprised 6-months or higher smoking cessation rates and intervention safety. CPGs were peer-assessed based on DELBI. Results from aggregative studies included in selected CPGs were obtained. Results Pharmacotherapy doubles smoking cessation rates as compared with placebos (rates @25% and up to 27 % when combined with counseling). The highest efficacy was observed for ansyolitic and antidepressive drugs (8.7 % to 19.4 %), and the lowest for nicotine replacement therapy -NRT- (5.2 % to 12.9 %). Nortriptiline shows an efficacy similar to that of bupropion (@10%). With limited exceptions, combined pharmacotherapy for smoking cessation has shown no significant increase in cessation rates. Conclusions NRT, varenicline, bupropion and nortriptiline are effective treatments for smoking cessation. Combination of drugs deserves further clinical evidence and should be restricted to highly dependent smokers or initial therapeutic failure. Cost-effectiveness analyses might help to introduce smoking cessation programs in low and middle income countries.

[Efficacy and safety of medication use for the cessation of tobacco addiction: A review of Clinical Practice Guidelines]. / Eficacia y seguridad del uso de medicamentos para la cesación de la adicción al tabaco: revisión de guías de práctica clínica.

OBJECTIVE: To review the efficacy and safety of pharmacotherapy for smoking cessation in the context of clinical practice guidelines (CPG). METHODS: A systematic review of CPGs was conducted, aimed at adapting recommendations for Colombia following the ADAPTE methodology. Outcomes comprised 6-months or higher smoking cessation rates and intervention safety. CPGs were peer-assessed based on DELBI. Results from aggregative studies included in selected CPGs were obtained. RESULTS: Pharmacotherapy doubles smoking cessation rates as compared with placebos (rates @25% and up to 27 % when combined with counseling). The highest efficacy was observed for ansyolitic and antidepressive drugs (8.7 % to 19.4 %), and the lowest for nicotine replacement therapy -NRT- (5.2 % to 12.9 %). Nortriptiline shows an efficacy similar to that of bupropion (@10%). With limited exceptions, combined pharmacotherapy for smoking cessation has shown no significant increase in cessation rates. CONCLUSIONS: NRT, varenicline, bupropion and nortriptiline are effective treatments for smoking cessation. Combination of drugs deserves further clinical evidence and should be restricted to highly dependent smokers or initial therapeutic failure. Cost-effectiveness analyses might help to introduce smoking cessation programs in low and middle income countries.

Recomendaciones para la cesación de la adicción al tabaco en Colombia / Recommendations for smoking cessation in Colombia

Introducción. El tabaquismo es el principal factor de riesgo para enfermedades crónicas que constituyen la mayor carga en Colombia. Objetivos. Generar recomendaciones de práctica clínica sobre eficacia y seguridad del tratamiento para la cesación de la adicción al tabaco en adultos colombianos. Materiales y métodos. Se hizo una adaptación basada en la metodología ADAPTE. Se buscaron guías de práctica clínica en Medline, EMBASE, CINAHL, LILACS y Cochrane. Se evaluó la cesación a seis meses para consejería breve e intensiva, terapia de reemplazo nicotínico, bupropión, vareniclina, clonidina, nortriptilina, acupuntura, hipnosis, homeopatía y la combinación de tratamientos. Se utilizó el German Instrument for Methodological Guideline Appraisal (DELBI) para evaluar las guías de prácticalínica. Se seleccionaron las guías con puntaje mayor de 60 % en rigor metodológico y aplicabilidad en Colombia. Las preguntas sin evidencia fuerte se llevaron a consenso. Resultados. Se encontraron 925 referencias, se preseleccionaron 17 guías de práctica clínica y se escogieron 5 para adaptación. La consejería breve e intensiva, la terapia de reemplazo nicotínico, el bupropión, la nortriptilina y la vareniclina son eficaces en la cesación de tabaquismo (incrementó 5,1 % a 22,7 %). Los tratamientos alternativos no tienen eficacia demostrada en la cesación. El uso simultáneo de diferentes formas de terapia de reemplazo nicotínico es la única combinación con eficacia demostrada (OR 1,9; 95%: 1,3-2,7). Conclusiones. Existen diversas alternativas con eficacia demostrada para dejar de fumar. Los incrementos en las tasas de cesación son variables y la duración del efecto necesita mayor seguimiento. Para aplicar la consejería breve e intensiva en Colombia, se deben usar formatos estándar. Se requieren evaluaciones económicas para valorar el impacto y seleccionar las mejores intervenciones en el contexto colombiano.

Introduction: Chronic diseases represent the greatest burden of disease in Colombia for which smoking is the major risk factor. Objectives: To provide clinical practice recommendations based upon efficacy and safety of smoking cessation therapies for Colombian adults. Materials and methods: An adaptation of clinical practice guidelines (CPG) based on the ADAPT methodology was performed. We searched CPG on Medline, EMBASE, CINAHL, LILACS, and Cochrane databases. Six months’ cessation rates were appraised for brief and intensive counseling, nicotine replacement therapy (NRT), bupropion, varenicline, clonidine, nortriptyline, acupuncture, hypnosis, homeopathy, and combined treatments. CPG were evaluated with DELBI and selected when having a score above 60% for methodological rigor of development and applicability to the Colombian health system. Formal consensus was performed for questions without strong evidence. Results: 925 references were found, 17 CPG were pre-selected and 5 selected for adaptation. Brief and intensive counseling, NRT, bupropion, nortriptyline, and varenicline are effective for smoking cessation (cessation rates augment 5.1%-22.7%). Alternative therapies have not demonstrated cessation efficacy. Concomitant use of different NRT is the only combination with demonstrated efficacy (OR 1.9, 95%CI 1.3-2.7). Conclusions: Several alternatives for giving up tobacco smoking have confirmed efficacy. The absolute difference in cessation rates is variable among therapies and duration of effect requires further research. Brief and intensive counseling necessitate standardized formats for their implementation in Colombia. Economic evaluations are required to assess costs and benefits and to select the most suitable interventions for Colombia.

[Recommendations for smoking cessation in Colombia]. / Recomendaciones para la cesación de la adicción al tabaco en Colombia.

INTRODUCTION: Chronic diseases represent the greatest burden of disease in Colombia for which smoking is the major risk factor. OBJECTIVES: To provide clinical practice recommendations based upon efficacy and safety of smoking cessation therapies for Colombian adults. MATERIALS AND METHODS: An adaptation of clinical practice guidelines (CPG) based on the ADAPT methodology was performed. We searched CPG on Medline, EMBASE, CINAHL, LILACS, and Cochrane databases. Six months' cessation rates were appraised for brief and intensive counseling, nicotine replacement therapy (NRT), bupropion, varenicline, clonidine, nortriptyline, acupuncture, hypnosis, homeopathy, and combined treatments. CPG were evaluated with DELBI and selected when having a score above 60% for methodological rigor of development and applicability to the Colombian health system. Formal consensus was performed for questions without strong evidence. RESULTS: 925 references were found, 17 CPG were pre-selected and 5 selected for adaptation. Brief and intensive counseling, NRT, bupropion, nortriptyline, and varenicline are effective for smoking cessation (cessation rates augment 5.1%-22.7%). Alternative therapies have not demonstrated cessation efficacy. Concomitant use of different NRT is the only combination with demonstrated efficacy (OR 1.9, 95%CI 1.3-2.7). CONCLUSIONS: Several alternatives for giving up tobacco smoking have confirmed efficacy. The absolute difference in cessation rates is variable among therapies and duration of effect requires further research. Brief and intensive counseling necessitate standardized formats for their implementation in Colombia. Economic evaluations are required to assess costs and benefits and to select the most suitable interventions for Colombia.