Low miR200c expression in tumor budding of invasive front predicts worse survival in patients with localized colon cancer and is related to PD-L1 overexpression.

At the histological level, tumor budding in colon cancer is the result of cells undergoing at least partial epithelial-to-mesenchymal transition. The microRNA 200 family is an important epigenetic driver of this process, mainly by downregulating zinc-finger E-box binding homeobox (ZEB) and transforming growth factor beta (TGF-ß) expression. We retrospectively explored the expression of the miR200 family, and ZEB1 and ZEB2, and their relationship with immune resistance mediated through PD-L1 overexpression. For this purpose, we analyzed a series of 125 colon cancer cases and took samples from two different tumor sites: the area of tumor budding at the invasive front and from the tumor center. We found significant ZEB overexpression and a reduction in miR200 in budding areas, a profile compatible with epithelial-to-mesenchymal transition. In multivariate analysis of the cases with localized disease, low miR200c expression in budding areas, but not at the tumor center, was an adverse tumor-specific survival factor (hazard ratio: 0.12; 95% confidence interval: 0.03-0.81; p = 0.02) independent of the clinical stage of the disease. PD-L1 was significantly overexpressed in the budding areas and its levels correlated with a mesenchymal transition profile. These results highlight the importance of including budding areas among the samples used for biomarker evaluation and provides relevant data on the influence of mesenchymal transition in the immune resistance mediated by PD-L1 overexpression.

Rol de la Clorhexidina en sus Diferentes Formatos para la Prevención de la Alveolitis Seca: Revisión Sistemática Exploratoria

El objetivo de este estudio fue investigar el rol de la clorhexidina en sus diferentes formatos en la prevención de la alveolitis seca posterior a la extracción dental. Se realizó una búsqueda electrónica en las bases de datos de PubMed, Scopus, Web of Science. hasta el año 2021. Dos revisores de forma independiente realizaron el análisis de los artículos. La búsqueda inicial dio como resultado 192 artículos. Se descartaron 59 artículos duplicados y se realizó una revisión general inicial de títulos y resúmenes, verificando que se cumplan los criterios de inclusión y exclusión preestablecidos. De 192 estudios, 25 cumplieron con los criterios de inclusión. De los 25 artículos, 10 incluyeron pacientes con factores de riesgo asociados a alveolitis seca. Respecto al sitio de extracción dental, 19 artículos incluyeron pacientes con terceros molares mandibulares. Dentro de los artículos filtrados se utilizaron tres formatos de clorhexidina: enjuague, gel bioadhesivo e irrigante; estos en diferentes concentraciones, y comparadas con distintos grupos placebos. De los estudios incluidos, 18 informaron que la clorhexidina en sus diferentes formatos proporcionaba disminución en la incidencia de alveolitis seca versus el grupo control. El uso de clorhexidina en sus diferentes formatos después de la extracción dental es altamente efectivo en la prevención de la alveolitis seca. Sin embargo, inferimos que se necesitan nuevas líneas investigativas que incluyan pacientes con factores de riesgo asociados, y estudios que no utilicen terapias complementarias, puesto que, estos factores pueden conducir a confusión en los resultados obtenidos.

The objective of this study was to investigate the role of chlorhexidine in its different formats in the prevention of dry socket after dental extraction. The electronic search was performed using keywords and MeSH terms in the databases of PubMed, Scopus, Web of Science, until 2021. The reviewers independently performed the analysis of the articles. The initial search resulted in 192 articles. 59 duplicate articles were discarded, and an initial general review of titles and abstracts was performed, verifying that the pre-established inclusion and exclusion criteria were met. Of 192 studies, 25 met the inclusion criteria. Of the 25 articles, 10 included patients with risk factors associated with dry socket. Regarding the site of dental extraction, 19 articles included patients with mandibular third molars. Within the filtered articles, three formats of chlorhexidine were used: rinse, bioadhesive gel and irrigant, in different concentrations, and compared with different placebo groups. Of the included studies, 18 reported that chlorhexidine in its different formats provided a decrease in the incidence of dry socket versus the control group. The use of chlorhexidine in its different formats after dental extraction, is highly effective in preventing dry socket. However, we infer that new research lines are needed that include patients with associated risk factors, and studies that do not use complementary therapies.

Molecular profile in Paraguayan colorectal cancer patients, towards to a precision medicine strategy.

Somatic mutation analysis and evaluation of microsatellite instability (MSI) have become mandatory for selecting personalized therapy strategies for advanced colorectal cancer and are not available as routine methods in Paraguay. The aims of this study were to analyze the molecular profile as well as the microsatellite status in a series of advanced colorectal patients from two public hospitals from Paraguay, to introduce these methodologies in the routine practice to guide the therapeutic decisions. Thirty-six patients diagnosed with advanced colorectal cancer from two referent public hospitals from Paraguay were recruited from May 2017 to February 2018. Sequenom Mass spectrometry, Oncocarta Panel V.1 was applied to analyze the mutational profile from formalin-fixed paraffin-embedded samples. The microsatellite status was tested by immunohistochemistry (IHC). The mean age of the patients was 52 years with a range from 20 to 74 years. Eighty-three percent of the patients included in the study have advanced-stage tumors at the moment of the diagnosis. Sixteen patients (44.4%) were wild-type for all the oncogene regions analyzed with the Oncocarta panel. Thirty-two hot-spot pathogenic variants on seven oncogenes, among 20 patients (55.6%), were identified, including KRAS, NRAS, BRAF, PI3KCA, FGFR, epidermal growth factor receptor, and PDGFRA. Moreover, 14 (38.8%) of these patients presented pathogenic variants in KRAS/NRAS or BRAF genes that have implications in the clinical practice decisions. Five patients (14%) presented MSI. The IHC study for microsatellite status and the molecular profile analysis through Sequenom mass spectrometry are feasible and useful methods, due to identify those patient candidates for targeted therapies and for the budgetary calculations of the National Health Plans.

Effectiveness of intermittent fasting on biochemical and anthropometric markers in obese adults with cardiovascular risk. A systematic review / Efectividad del ayuno intermitente sobre marcadores bioquímicos y antropométricos en adultos obesos con riesgo cardiovascular. Una revisión sistemática.

Background. Obesity is a problem present in almost all societies, which has led to the search for different methods to combat it. One of them is intermittent fasting (IF), characterized by periods without eating (16 to 24 hours), limited or no caloric intake, combined with normal eating windows. Target. To determine the effectiveness of intermittent fasting on biochemical and anthropometric markers in obese adults. Materials and methods. A systematic review was proposed that postulated to study blinded or open clinical trials of IA interventions, compared with a control group. The response variables were: systolic and diastolic blood pressure, total cholesterol, LDL, HDL and triglycerides, blood glucose, fat mass, weight, waist circumference, BMI and heart rate. The search and identification of studies was masked. The risks of bias for the Cochrane collaboration were assessed. They underwent meta-analysis (random effect), with R 4.0.0. Results. Six studies were included, involving 10-48 weeks of intervention with alternate-day fasting and time-restricted feeding, reporting some statistically significant changes for different variables. Conclusion. Intermittent fasting could intervene in the reduction of cardiovascular risk due to improvement in BMI and biochemical parameters.

Antecedentes. La obesidad es un problema presente en casi todas las sociedades, lo que ha conllevado a buscar distintos métodos para combatirla. Uno de ellos es el ayuno intermitente (AI), caracterizado por periodos sin ingesta (16 a 24 hr), ingesta calórica limitada o nula, combinada con ventanas de alimentación normal. Objetivo. Determinar la efectividad del ayuno intermitente sobre los marcadores bioquímicos y antropométricos en adultos obesos. Materiales y Métodos. Se planteó una revisión sistemática que postuló estudiar ensayos clínicos enmascarados o abiertos de intervenciones de AI, comparado con grupo control. Las variables de respuesta fueron: presión arterial sistólica y diastólica, colesterol total, LDL, HDL y triglicéridos, glicemia, masa grasa, peso, circunferencia de cintura, IMC y frecuencia cardiaca. La búsqueda e identificación de los estudios fue enmascarada. Se evaluaron los riesgos de sesgo de la colaboración Cochrane. Se sometieron a meta-análisis (efecto aleatorio), con R 4.0.0. Resultados. Se incluyeron 6 estudios, de 10-48 semanas de intervención con ayuno en días alternos y alimentación con restricción de tiempo, reportándose algunos cambios estadísticamente significativos para distintas variables. Los meta-análisis obtenidos muestran diferencias de medias estadísticamente significativas.  Conclusión. Existe evidencia que respalda un beneficio de AI a nivel de indicadores bioquímicos.