CLCA1 is Poorly Expressed in Stomach Adenocarcinoma and Correlates with Immune Infiltration / CLCA1 se Expresa Deficientemente en el Adenocarcinoma de Estómago y se Correlaciona con la Infiltración Inmune

SUMMARY: Calcium-activated chloride channel regulator 1 (CLCA1) is associated with cancer progression. The expression and immunologic function of CLCA1 in stomach adenocarcinoma (STAD) remain unclear. In this investigation, the expression of CLCA1 in STAD tissues and its involvement in the progression and immune response of STAD were examined using databases such as cBioPortal, TISIDB, and UALCAN. In order to validate the expression level of CLCA1 protein in gastric adenocarcinoma, thirty clinical tissue specimens were gathered for immunohistochemical staining. The findings indicated a downregulation of CLCA1 in STAD patients, which was correlated with race, age, cancer grade, Helicobacter pylori infection, and molecular subtype. Through the examination of survival analysis, it was identified that diminished levels of CLCA1 within gastric cancer cases were linked to decreased periods of post-progression survival (PPS), overall survival (OS), and first progression (FP) (P<0.05). The CLCA1 mutation rate was lower in STAD, but the survival rate was higher in the variant group. The correlation between the expression level of CLCA1 and the levels of immune infiltrating cells in STAD, as well as the immune activating molecules, immunosuppressive molecules, MHC molecules, chemokines, and their receptor molecules, was observed. Gene enrichment analysis revealed that CLCA1 may be involved in STAD progression through systemic lupus erythematosus (SLE), proteasome, cell cycle, pancreatic secretion, and PPAR signaling pathways. In summary, CLCA1 is anticipated to function as a prognostic marker for patients with STAD and is linked to the immunization of STAD.

El regulador 1 del canal de cloruro activado por calcio (CLCA1) está asociado con la progresión del cáncer. La expresión y la función inmunológica de CLCA1 en el adenocarcinoma de estómago (STAD) aún no están claras. En esta investigación, se examinó la expresión de CLCA1 en tejidos STAD y su participación en la progresión y respuesta inmune de STAD utilizando bases de datos como cBioPortal, TISIDB y UALCAN. Para validar el nivel de expresión de la proteína CLCA1 en el adenocarcinoma gástrico, se recolectaron treinta muestras de tejido clínico para tinción inmunohistoquímica. Los hallazgos indicaron una regulación negativa de CLCA1 en pacientes con STAD, que se correlacionó con la raza, la edad, el grado del cáncer, la infección por Helicobacter pylori y el subtipo molecular. Mediante el examen del análisis de supervivencia, se identificó que los niveles reducidos de CLCA1 en los casos de cáncer gástrico estaban relacionados con períodos reducidos de supervivencia posterior a la progresión (PPS), supervivencia general (OS) y primera progresión (FP) (P <0,05). La tasa de mutación CLCA1 fue menor en STAD, pero la tasa de supervivencia fue mayor en el grupo variante. Se observó la correlación entre el nivel de expresión de CLCA1 y los niveles de células inmunes infiltrantes en STAD, así como las moléculas activadoras inmunes, moléculas inmunosupresoras, moléculas MHC, quimiocinas y sus moléculas receptoras. El análisis de enriquecimiento genético reveló que CLCA1 puede estar involucrado en la progresión de STAD a través del lupus eritematoso sistémico (LES), el proteasoma, el ciclo celular, la secreción pancreática y las vías de señalización de PPAR. En resumen, se prevé que CLCA1 funcione como un marcador de pronóstico para pacientes con STAD y está vinculado a la inmunización de STAD.

Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer / A regulação positiva de GINS1 destacou um bom potencial diagnóstico e prognóstico de sobrevivência em três subtipos diferentes de câncer humano

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados ​​usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados ​​no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.

El puntaje de Framingham ayudaría en la estratificación del riesgo de pacientes con ergometría positiva y SPECT normal / The Framingham score could help in risk stratification of patients with positive ergometry and normal SPECT

Antecedentes. El valor pronóstico de una ergometría positiva en el contexto de imágenes tomográficas de perfusión miocárdica de estrés y reposo (SPECT) normales no está bien establecido. Objetivos. Documentar la incidencia de infarto, muerte y revascularización coronaria en pacientes con una ergometría positiva de riesgo intermedio e imágenes de perfusión SPECT normales, y explorar el potencial valor del puntaje de riesgo de Framingham en la estratificación pronóstica de estos pacientes. Métodos. Cohorte retrospectiva integrada por pacientes que habían presentado síntomas o hallazgos electrocardiográficos compatibles con enfermedad arterial coronaria durante la prueba de esfuerzo, con criterios de riesgo intermedio en la puntuación de Duke y perfusión miocárdica SPECT normal. Fueron identificados a partir de la base de datos del laboratorio de cardiología nuclear del Instituto de Cardiología y Cirugía Cardiovascular de la ciudad de Posadas, Argentina. Resultados. Fueron elegibles 217 pacientes. El seguimiento fue de 3 1,5 años. La sobrevida libre de eventos (muerte,infarto de miocardio no fatal, angioplastia coronaria o cirugía de bypass de arteria coronaria) a uno, tres y cinco años fue significativamente menor (Log-rank test, p= 0,001) en el grupo con puntaje de Framingham alto o muy alto (77, 71y 59 %, respectivamente) que en el grupo de puntaje bajo o intermedio (89, 87 y 83 %). Tomando como referencia a los pacientes con riesgo bajo en el puntaje de Framingham, luego de ajustar por edad, sexo y puntaje de Duke, los pacientes categorizados en los estratos alto y muy alto riesgo del puntaje de Framingham presentaron una incidencia del evento combinado cercana al triple (hazard ratio [HR] 2,81; intervalo de confianza [IC] del 95 % 0,91 a 8,72; p= 0,07 y HR 3,61;IC 95 % 1,23 a 10,56; p= 0,019 respectivamente). Conclusiones. La estimación de riesgo con el puntaje de Framingham sería de ayuda en la estratificación pronóstica de los pacientes con ergometría positiva y SPECT normal. (AU)

Background. The prognostic value of positive exercise testing with normal SPECT myocardial perfusion imaging is not well established. Objectives. To document the incidence of infarction, death, and coronary revascularization in patients with a positive intermediate-risk exercise test and normal SPECT perfusion images and to explore the potential value of the Framingham Risk Score in the prognostic stratification of these patients. Methods. A retrospective cohort comprised patients who presented symptoms or electrocardiographic findings compatible with coronary artery disease during the stress test, with intermediate risk criteria in the Duke score and normal SPECT myocardial perfusion. They were identified from the database of the nuclear cardiology laboratory of the Instituto de Cardiología y Cirugía Cardiovascular of Posadas, Argentina. Results. 217 patients were eligible. Follow-up was 3 1.5 years. Event-free survival (death, non-fatal myocardial infarction, coronary angioplasty, or coronary artery bypass surgery) at one, three, and five years was significantly lower (Log-ranktest, p: 0.001) in the group with a score of Framingham high or very high (77, 71 and 59 %, respectively) than in the lowor intermediate score group (89, 87 and 83 %). Taking as reference the low-risk patients in the Framingham score, after adjusting for age, sex, and Duke score, the patients categorized in the high-risk and very high-risk strata showed about three times higher incidence of the combined event (hazard ratio [HR] 2.81; 95 % confidence interval [CI] 0.91 to 8.72;p=0.07 and HR 3.61; 95 % CI 1.23 to 10.56; p=0.019 respectively). Conclusions. Risk estimation with the Framingham score would be helpful in the prognostic stratification of patients with positive exercise testing and normal SPECT. (AU)

El dilema clínico frente a los pacientes con ergometría positiva y prueba de perfusión miocárdica con SPECT normal / The clinical dilemma facing patients with positive stress test and normal SPECT myocardial perfusion imaging

La evaluación de la perfusión miocárdica con SPECT combina una prueba de esfuerzo (ergometría o estrés farmacológico) junto a imágenes de perfusión con radioisótopos. Este estudio es útil para establecer el diagnóstico de enfermedad arterial coronaria, estratificar el riesgo de infarto y tomar decisiones terapéuticas. Un resultado normal aporta un alto valor predictivo negativo, es decir, una muy baja probabilidad de que el paciente presente eventos cardiovasculares. El hallazgo de signos de isquemia en la ergometría podría poner en jaque el valor predictivo negativo de una perfusión normal. En presencia de este resultado, el paso siguiente es evaluar los predictores de riesgo en la ergometría, el riesgo propio del paciente en función de los antecedentes clínicos y el puntaje cálcico coronario, cuando este se encuentra disponible. Ante la presencia concomitante de otros marcadores de riesgo se sugiere completar la evaluación con un estudio anatómico.El uso de nuevas tecnologías podría mejorar la precisión en la predicción de eventos. (AU)

Assessment of myocardial perfusion with SPECT combines a stress test (ergometry or pharmacological stress) with radioisotope perfusion imaging. This test is helpful to diagnose coronary artery disease, stratify the risk of heart attack, and make therapeutic decisions. A normal result provides a high negative predictive value; therefore, the probability of cardiovascular events is very low. Signs of ischemia on an ergometry could jeopardize the negative predictive value of normal perfusion. In this clinical setting, the next step is to evaluate the risk predictors in the stress test, the individual risk based on the clinical history, and the coronary calcium score when available. Given the simultaneous presence of other risk markers,completing the evaluation with an anatomical study is suggested. The use of new technologies could improve the accuracy of event prediction. (AU)

Factores de predicción relevantes en la supervivencia de pacientes con síndrome antifosfolípido / Relevants predictions factors in the survival of patients with antiphospholipid syndrome

Introducción: Los pacientes con síndrome antifosfolípido desarrollan morbilidad y mortalidad significativas a pesar del tratamiento actual. Es imperativo, identificar factores pronósticos y medidas terapéuticas para prevenir estas complicaciones. Objetivo: Determinar los factores relevantes en la predicción de la supervivencia en los pacientes con síndrome antifosfolípido. Métodos: Se realizó un estudio longitudinal analítico de una cohorte histórica de personas con síndrome antifosfolípido, diagnosticados, según los criterios de Sapporo/Sydney y colaboradores en la consulta de enfermedades autoinmunes sistémicas del Hospital Universitario Clínico-Quirúrgico «Arnaldo Milián Castro», Villa Clara, del año 2000 al 2015. Se estudiaron variables demográficas y clínicas. En cada caso se determinó el tiempo de supervivencia con relación al evento muerte. Se aplicó el método de Kaplan Meier para calcular la supervivencia global y determinar las variables predictoras de la mortalidad. Según el estudio de los estadígrafos de comparación interestratos(Log-Rank) se demostró la significación estadística con la prueba de Chi cuadrado de homogeneidad. Resultados: De los 128 pacientes estudiados, 118 fueron femeninos y 10 masculinos (111 de piel blanca y 17 no blancos). La supervivencia global fue de 67,1 % con una media de 13,37 años. Las variables más relevantes que aportaron a la mortalidad en relación con menor supervivencia fueron: leucopenia, linfopenia, color de la piel no blanca, y el no uso de aspirina, con medias de supervivencia de 8,83; 8,17; 10,72; 12,10 años, respectivamente. Conclusiones: La identificación temprana de los factores pronósticos de supervivencia permite implementar estrategias oportunas e individualizadas en pacientes con síndrome antifosfolípido.

Introduction: patients with antiphospholipid syndrome develop significant morbidity and mortality despite current treatment. Identifying prognostic factors and therapeutic measures to prevent these complications is indispensable. Objective: to determine relevant factors in the prediction of survival in patients with antiphospholipid syndrome. Methods: a longitudinal analytical study was carried out on cohorts with antiphospholipid syndrome who were diagnosed according to the Sapporo-Sydney criteria and collaborators in the systemic autoimmune disease consultation at "Arnaldo Milián Castro" Clinical and Surgical University Hospital in Villa Clara from 2000 to 2015. Demographic and clinical variables were studied. The survival time in relation to the death event was determined in each case. The Kaplan - Meier method was applied to calculate overall survival and determine the predictor variables for mortality. According to the study of inter-strata comparison statistics (Log-Rank), statistical significance was demonstrated with the Chi-square test of homogeneity. Results: a number of 118 patients were female and 10 male from the 128 studied (111 white-skinned and 17 non-white). Overall survival was 67.1% with a mean of 13.37 years. The most relevant variables that contributed to mortality in relation to lower survival were leukopenia, lymphopenia, non-white skin color and non-use of aspirin, with mean survival of 8.83; 8.17; 10.72; 12.10 years, respectively. Conclusions: the early identification of survival prognostic factors allows us the implementation of timely and individualized strategies in patients with antiphospholipid syndrome.

Índice leucocitos/eosinófilos como marcador pronóstico del choque séptico / Leukocyte/eosinophil Ratio as a Prognostic Marker of Septic Choque

Introducción: Se ha reconocido mundialmente el choque séptico como causa de una alta incidencia en la mortalidad. La incorporación de nuevos biomarcadores posibilita la obtención de un diagnóstico rápido y preciso. Objetivo: Evaluar la utilidad del índice leucocitos/eosinófilos como marcador pronóstico del choque séptico. Métodos: Se realizó una investigación en dos etapas: la primera descriptiva en la cual se detallaron las características clínicas, epidemiológicas y las variaciones de los estudios de laboratorio y la segunda explicativa de cohorte para estimar el valor predictivo del biomarcador leucocitos/eosinopenia en el choque séptico. Se realizó el recuento de eosinófilos y se obtuvo la media aritmética. Se consideró eosinopenia relativa con valores por debajo de la media de eosinófilos. Resultados: En el estudio se demostró que la leucocitosis fue de (27,4 células*mm3), la disminución del hematocrito (32,2 por ciento) y el descenso del número plaquetario (125,6 célula*mm3) prevalecen en el choque séptico. Además se refleja el descenso de los eosinófilos (18,5 células/mcl), aumento del índice leucocitos/eosinófilos (148,1) y empeoramiento del SOFA (2,8). El aumento del índice leucocitos/eosinófilos se correlaciona con el aumento de la proteína C reactiva y la procalcitonina. Conclusiones: La correlación de la leucocitosis y la eosinopenia mostró la utilidad del índice leucocitos/eosinopenia como factor de predicción del choque séptico(AU)

Introduction: Septic shock has been recognized worldwide as a cause of high incidence of mortality. The incorporation of new biomarkers makes it possible to obtain a rapid and accurate diagnosis. Objective: To evaluate the usefulness of the leukocyte/eosinophil ratio as a prognostic marker of septic shock. Methods: An investigation was carried out in two stages: in the first (the descriptive phase) the clinical and epidemiological characteristics and variations of the laboratory studies were detailed and in the second (the explanatory cohort phase), the predictive value of the leukocytes/eosinopenia biomarker in septic shock was estimated. The eosinophil count was performed and the arithmetic mean was obtained. Relative eosinopenia was considered with eosinophil values below the average. Results: The study showed that leukocytosis was 27.4 cells*mm3, hematocrit decreased in 32.2percent and decreased platelet number (125.6 cells*mm3) prevail in septic shock. In addition, a decrease in eosinophils (18.5 cells/mcl), an increase in the leukocyte/eosinophil ratio (148.1) and worsening of SOFA (2.8) are reflected. The increase in the leukocyte/eosinophil ratio is correlated with the increase in C-reactive protein and procalcitonin. Conclusions: The correlation of leukocytosis and eosinopenia showed the usefulness of the leukocyte/eosinopenia index as a predictor of septic shock(AU)

Comprehensive Analysis of CLCA1 Expression, Immune Infiltration and Immune Checkpoints in Colon Adenocarcinoma / Análisis Completo de la Expresión de CLCA1, Infiltración Inmune y Puntos de Control Inmunológico en Colonadenocarcinoma

SUMMARY: Colon adenocarcinoma (COAD) is a prevalent disease worldwide, known for its high mortality and morbidity rates. Despite this, the extent of investigation concerning the correlation between COAD's CLCA1 expression and immune cell infiltration remains insufficient. This study seeks to examine the expression and prognosis of CLCA1 in COAD, along with its relationship to the tumor immune microenvironment. These findings will offer valuable insights for clinical practitioners and contribute to the existing knowledge in the field. In order to evaluate the prognostic significance of CLCA1 in individuals diagnosed with colorectal cancers, we conducted a comprehensive analysis using univariate and multivariate Cox regression models along with receiver operating characteristic curve (ROC) analysis. This study was performed on the patient data of COAD obtained from The Cancer Genome Atlas (TCGA) database. Nomograms were developed to anticipate CLCA1 prognostic influence. Furthermore, the CLCA1 association with tumor immune infiltration, immune checkpoints, immune checkpoint blockade (ICB) response, interaction network, and functional analysis of CLCA1-related genes was analyzed. We found that Colon adenocarcinoma tissues significantly had decreased CLCA1 expression compared to healthy tissues. Furthermore, the study revealed that the group with high expression of CLCA1 demonstrated a significantly higher overall survival rate (OS) as compared to the group with low expression. Multivariate and Univariate Cox regression analysis revealed the potential of CLCA1 as a standalone risk factor for COAD. These results were confirmed using nomograms and ROC curves. In addition, protein-protein interaction (PPI) network analysis and functional gene enrichment showed that CLCA1 may be associated with functional activities such as pancreatic secretion, estrogen signaling and cAMP signaling, as well as with specific immune cell infiltration. Therefor, as a new independent predictor and potential biomarker of COAD, CLCA1 plays a crucial role in the advancement of colon cancer.

El adenocarcinoma de colon (COAD) es una enfermedad prevalente a nivel mundial, conocida por sus altas tasas de mortalidad y morbilidad. Sin embargo, el alcance de la investigación sobre la correlación entre la expresión de CLCA1 de COAD y la infiltración de células inmunes sigue siendo insuficiente. Este estudio busca examinar la expresión y el pronóstico de CLCA1 en COAD, junto con su relación con el microambiente inmunológico del tumor. Estos hallazgos ofrecerán conocimientos valiosos para los profesionales clínicos y contribuirán al conocimiento existente en el campo. Para evaluar la importancia de pronóstico de CLCA1 en personas diagnosticadas con cáncer colorrectal, realizamos un análisis exhaustivo utilizando modelos de regresión de Cox univariados y multivariados junto con un análisis de la curva característica operativa del receptor (ROC). Este estudio se realizó con los datos de pacientes de COAD obtenidos de la base de datos The Cancer Genome Atlas (TCGA). Se desarrollaron nomogramas para anticipar la influencia pronóstica de CLCA1. Además, se analizó la asociación de CLCA1 con la infiltración inmunitaria tumoral, los puntos de control inmunitarios, la respuesta de bloqueo de los puntos de control inmunitarios (ICB), la red de interacción y el análisis funcional de genes relacionados con CLCA1. Descubrimos que los tejidos de adenocarcinoma de colon tenían una expresión significativamente menor de CLCA1 en comparación con los tejidos sanos. Además, el estudio reveló que el grupo con alta expresión de CLCA1 demostró una tasa de supervivencia general (SG) significativamente mayor en comparación con el grupo con baja expresión. El análisis de regresión de Cox multivariado y univariado reveló el potencial de CLCA1 como factor de riesgo independiente de COAD. Estos resultados se confirmaron mediante nomogramas y curvas ROC. Además, el análisis de la red de interacción proteína- proteína (PPI) y el enriquecimiento de genes funcionales mostraron que CLCA1 puede estar asociado con actividades funcionales como la secreción pancreática, la señalización de estrógenos y la señalización de AMPc, así como con la infiltración de células inmunes específicas. Por lo tanto, como nuevo predictor independiente y biomarcador potencial de COAD, CLCA1 desempeña un papel crucial en el avance del cáncer de colon.

Perda de peso como preditor de mau prognóstico em pacientes hospitalizados com COVID-19 / Weight loss as a predictor of poor prognosis in patients hospitalized for COVID-19

Objetivo: Avaliar a relação entre a perda de peso com marcadores de mau prognóstico em pacientes hospitalizados com COVID-19 no estado de Pernambuco. Métodos: Estudo multicêntrico, transversal, acoplado a algumas variáveis de análise prospectiva envolvendo 71 indivíduos com COVID-19 admitidos para internação em 8 hospitais públicos de Recife, no Estado de Pernambuco. Foram incluídos indivíduos de ambos os sexos, com idade ≥ 20 anos, hospitalizados, no período de junho de 2020 a junho de 2021. Foram coletados dados sociodemográficos, clínicos, nutricionais e marcadores prognósticos. Resultados: A média de idade foi 54,6±15,6 anos, sendo 54,9% dos indivíduos do sexo masculino. Verificou-se que 26,8% dos pacientes eram diabéticos e 52,1% eram hipertensos. O perfil antropométrico indicou 56,3% de excesso de peso e 5,6% de baixo peso. Observou-se rastreio positivo para sarcopenia em 16,9%. A mediana da perda de peso foi 3,1% (0,0-6,6%), sendo uma perda > 5% evidenciada em 29,6% da amostra. Verificou-se que a perda de peso foi mais frequente nos homens (16 (41,0%) vs. 5 (15,6%); p = 0,020) e que as variáveis demográficas, clínicas e nutricionais não se associaram à redução do peso corporal. Não houve associação estatística entre a perda de peso e as variáveis prognósticas (p NS). Conclusão: embora o estudo não tenha demonstrado associação entre a perda de peso e variáveis prognósticas, esta deve ser considerada na avaliação do paciente com COVID-19, devendo ser investigada e tratada como uma importante medida de promoção à saúde.

Objective: To evaluate the relationship between weight loss and markers of poor prognosis in patients hospitalized with COVID-19 in the state of Pernambuco. Methods: A multicenter, cross-sectional study coupled with prospective analysis variables involving 71 individuals with COVID-19 admitted for hospitalization in 8 public hospitals in Recife, in the State of Pernambuco. Individuals of both sexes, aged ≥ 20 years, hospitalized from June 2020 to June 2021 were included. Sociodemographic, clinical, and nutritional data and prognostic markers were collected. Results: The average age was 54.6±15.6 years, with 54.9% of individuals being male. It was found that 26.8% of the patients were diabetic and 52.1% were hypertensive. The anthropometric profile indicated that 56.3% were overweight and 5.6% were underweight. Positive screening for sarcopenia was observed in 16.9%. The median weight loss was 3.1% (0.0-6.6%), with a loss > 5% evident in 29.6% of the sample. It was found that weight loss was more frequent in men (16 (41.0%) vs. 5 (15.6%); p = 0.020) and that demographic, clinical, and nutritional variables were not associated with body weight loss. There was no statistical association between weight loss and prognostic variables (p NS). Conclusion: Although the study did not demonstrate an association between weight loss and prognostic variables, this should be considered when assessing patients with COVID-19 and should be investigated and treated as an essential health promotion measure.

Comparative Analysis of the Tibial Component Migration After Cemented and Uncemented Total Knee Arthroplasty with a Hydroxyapatite Coating in Two, Five, and Ten Years: A Meta-Analysis / Análise comparativa da migração do componente tibial da artroplastia total do joelho cimentada versus não cimentada versus não cimentada com revestimento de hidroxapatita por dois, cinco e dez anos: uma metanálise

Abstract Objective This study evaluated and compared the tibial component migration in cemented and uncemented total knee arthroplasty (TKA) with no hydroxyapatite coating 2, 5, and 10 years after surgery. Methods This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) based on PubMed and MeSH database queries from June to July 2022. Results The meta-analysis included eight randomized clinical studies evaluating 668 knees undergoing TKA. The maximum total point motion (MTPM) in cemented TKAs was higher in 5 years, with a mean value of 0.67 mm (95% confidence interval [CI], 0.52 to 0.87). Uncemented TKAs also presented higher mean MTPM in 5 years (1 mm; 95% CI, 0.82 to 1.22). Uncemented coated ATKs had a higher mean MTPM in 10 years (1.30 mm; 95% CI, 0.70 to 2.39). MTPM was statistically similar in the short- and long-term for cemented and uncemented techniques, with a standardized mean difference of -0.65 (95% CI, -1.65 to 0.35). Conclusion Tibial component migration in TKA was statistically similar at 2, 5, and 10 years in cemented and uncemented techniques, either with or without coating. However, due to the scarce literature, further studies are required with a longer follow-up time.

Resumo Objetivo Avaliar e comparar a migração obtida pelo componente tibial na Artroplastia Total de Joelho (ATJ) cimentada, não cimentada sem revestimento e não cimentada com revestimento de hidroxapatita aos 2, 5 e 10 anos pós operatório. Métodos Esta metanálise foi conduzida de acordo com o Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Foi realizada busca a partir das bases de dados PubMed e MeSH no período de junho a julho de 2022. Resultados Oito ensaios clínicos randomizados foram incluídos. Um total de 668 joelhos submetidos a ATJ foram avaliados. Observou-se que a média de Maximun Total Point Motion (MTPM) nas ATJ cimentada foi maior em experimentos com cinco anos com média de 0,67 mm (IC95% - 0,52 a 0,87), as ATJ não cimentadas com revestimento de hidroxapatita também obtiveram maior média neste período (1mm; IC95% - 0,82 a 1,22). Em ATJ não cimentada sem revestimento o maior MTPM médio ocorreu no período de 10 anos (1,30mm; IC95% - 0,70 a 2,39). O MTPM foi estatisticamente semelhante no curto e longo prazo ao comparar as técnicas cimentada e não cimentada, com diferença média padronizada -0,65 (IC95%, -1,65 a 0,35). Conclusão A migração obtida pelo componente tibial na artroplastia total de joelho (ATJ) foi estatisticamente semelhante em 2, 5 e 10 anos ao comparar as técnicas cimentada e não cimentada (com e sem revestimento). Entretanto, devido ao pequeno número de artigos existentes, são necessários mais estudos clínicos sobre tais técnicas e com maior tempo de acompanhamento.

Morbilidad y mortalidad en pacientes llevados a gastrectomía por cáncer gástrico / Morbidity and mortality in patients undergoing gastrectomy for gastric cancer

Introducción. El cáncer gástrico es la cuarta causa de muerte por cáncer a nivel mundial, con más de un millón de casos diagnosticados cada año. La cirugía con intención curativa sigue siendo el pilar del manejo para los pacientes resecables. La identificación de pacientes con mayor riesgo de morbimortalidad es importante para el proceso de toma de decisiones, sin existir hasta el momento una herramienta ideal. La revisión y el análisis de la experiencia de un centro oncológico de referencia pueden generar información útil. Métodos. Estudio observacional de cohorte histórica, en el que se incluyeron los pacientes llevados a gastrectomía por adenocarcinoma gástrico en el Instituto Nacional de Cancerología, Bogotá, D.C., Colombia, entre el 1° de enero del 2010 y el 31 de diciembre del 2017. Resultados. Se evaluaron 332 pacientes, de los cuales el 57,2 % eran hombres con edad promedio de 61 años. La mortalidad en esta serie fue del 4,5 % y la morbilidad de 34,9 %. El factor asociado con mayor riesgo de muerte fue la edad, con un HR de 1,05 (p=0,021). Se encontró un mayor riesgo en el grupo de pacientes con ASA mayor a II (p=0,009).El 17,4 % presentaron complicaciones mayores a IIIA de la clasificación de Clavien-Dindo. Conclusiones. En el presente trabajo las cifras de morbilidad y mortalidad son similares a las reportadas en la literatura. Solo la edad y la clasificación de ASA mostraron asociación con valor estadístico significativo para complicaciones postoperatorias

Introduction. Gastric cancer is the fourth leading cause of cancer death worldwide with more than one million cases diagnosed each year. Surgery with curative intent remains the mainstay of management for resectable patients. Identify patients at increased risk of morbidity and mortality is important for the decision making process, with no ideal tool available yet. Review and analysis of the experience of a referral cancer center may generate useful information. Methods. Historical cohort observational study. Patients undergoing gastrectomy for gastric adenocarcinoma at the National Cancer Institute in Bogotá, Colombia, between January 1, 2010 and December 31, 2017 were included. Results. We included 332 patients of which 57.2% were men with mean age of 61 years. Mortality in this series was 4.5% and morbidity was 34.9%. The factor associated with higher risk of death was age with a HR of 1.05 statistically significant value (p=0.021). A higher risk was found in the group of patients with ASA greater than II (p=0.009). The 17.4% presented complications greater than IIIA of the Clavien Dindo classification. Conclusions. In this study morbidity and mortality seem similar to those reported in the literature. Only age and ASA score showed an association with significant statistical value for postoperative complications

Supervivencia a dos años en pacientes con cáncer gástrico localmente avanzado en una institución de Popayán entre 2018 y 2020 / Two-year survival in patients with locally advanced gastric cancer at an institution in Popayán between 2018 and 2020

Introducción. El tratamiento oncológico perioperatorio en pacientes con cáncer gástrico localmente avanzado está indicado; aun así, no siempre es posible. El objetivo de este estudio fue evaluar la supervivencia de los pacientes según la administración de quimioterapia perioperatoria. Métodos. Estudio observacional, tipo cohorte ambispectivo, incluyendo pacientes con cáncer gástrico localmente avanzado quienes recibieron o no quimioterapia perioperatoria. Resultados. Se incluyeron 33 pacientes, 90,9 % pertenecían al régimen subsidiado de salud y el 78,8 % en estadio T4. El grupo que recibió quimioterapia perioperatoria, que solo tuvo 5 pacientes (15,1 %), presentó mayor supervivencia global a 2 años (100 %), seguido del grupo de quimioterapia postoperatoria (58,8 %) y del grupo sin quimioterapia, que alcanzó una supervivencia global a 2 años de 54,5 %. Discusión. La supervivencia global fue mayor en el grupo de quimioterapia perioperatoria, consonante a lo descrito a nivel internacional, aunque los pacientes se encontraban en un estadío localmente más avanzado, la mayoría con T4 y N+ según AJCC VIII edición. Conclusiones. El estadío clínico es un factor pronóstico importante y, en nuestro medio, la mayoría de los pacientes consultan en estadíos localmente más avanzados. A eso se suman las dificultades en el acceso a la atención en salud. Aun así, la quimioterapia perioperatoria mostró una supervivencia mayor en pacientes con cáncer gástrico localmente avanzado

Introduction. Perioperative cancer treatment in patients with locally advanced gastric cancer is indicated; even so, it is not always possible. The objective was to evaluate survival according to time and receipt of perioperative chemotherapy. Methods. Observational study, ambispective cohort type, including patients with locally advanced gastric cancer who received or did not receive perioperative chemotherapy. Results. Thirty-three patients were included, 90.9% belonged to the subsidized regimen and 78.8% with TNM T4. The perioperative chemotherapy group, which only had five patients (15.1%), had a higher overall survival at 2 years (100%), followed by the postoperative chemotherapy group and by the group without chemotherapy, with an overall survival at 2 years of 58.8% and 54.5%, respectively. Discussion. Overall survival was higher in the perioperative chemotherapy group, consistent with what has been described internationally, although the patients were in a more advanced stage, most being with T4 and N+ according to the AJCC VIII edition. Conclusions. The clinical stage is an important prognostic factor and in our environment, most patients consult in more advanced stages, coupled with difficulties in accessing health care. Even so, perioperative chemotherapy showed a longer survival in patients with locally advanced gastric cancer, the data should not be extrapolated since the number of patients in each group is significantly different

Lesión cerebral post paro cardiaco: aspectos médicos, éticos y legales / Brain injury after cardiac arrest: Medical, ethical and legal issues disorder

RESUMEN Los sobrevivientes de la reanimación cardiopulmonar posterior a un paro cardiaco pueden tener un amplio rango de desenlaces y van desde recuperación neurológica completa, estado de vigilia sin respuesta, compromiso cognoscitivo diverso o la muerte. La lesión del tejido cerebral se presenta inmediatamente después del paro cardíaco, durante la reanimación y al retornar la circulación espontánea. La severidad y duración de la noxa isquémica determinarán el devenir neurológico. El examen clínico es el punto de partida en el abordaje multimodal del neuropronóstico. Se debe complementar con electroencefalograma, potenciales evocados somatosensoriales, neuroimágenes y biomar-cadores séricos. Entre un 10 a 15% de los pacientes con lesión cerebral posterior al paro cardiaco evolucionan hacia muerte por criterios neurológicos y son potenciales candidatos a la donación de órganos. Un retiro temprano de las terapias de sostenimiento de vida puede malograr la posibilidad de un potencial donante de órganos. Se puede estimar de manera temprana qué pacientes tienen mayor riesgo de evolucionar a muerte por criterios neurológicos. El neurólogo tiene un papel protagónico en el manejo de pacientes con lesión cerebral post paro cardiaco y sus decisiones tienen implicaciones éticas y legales.

ABSTRACT People who survive cardiopulmonary resuscitation (CPR) after cardiac arrest, have a wide range of outcomes including complete neurological recovery, coma, compromised cognitive function and death. Injury of the brain parenchyma starts immediately after a cardiac arrest, during CPR and return of spontaneous circulation. The severity of the ischemic injury will define the neurological outcome. The first step needed to determine a neurological prognosis is the clinical exam, with the help of electroencephalography, somatosensory evoked potentials, neuroimaging, and serum biomarkers. Between 10 and 15% of patients with brain injury after a cardiac arrest, develop brain death and become potential candidates for organ donation. A premature withdrawal of vital support can hamper the possibility of organ donation. The patients with higher risk of developing brain death can be identified early based on neurological criteria. The neurologist has a major role in the approach of patients with brain injury after cardiac arrest and the decision making with legal and ethical consequences.

Applicability of the acute leukemia (AL) - EBMT score as a prognostic model for allogeneic hematopoietic stem cell transplantation: a single-center, prospective, cohort study at a reference transplant center in Brazil

Abstract Introduction The Acute Leukemia-European Society for Blood and Marrow Transplantation (AL-EBMT) risk score was recently developed and validated by Shouval et al. Objective To assess the ability of this score in predicting the 2-year overall survival (OS-2), leukemia-free survival (LFS-2) and transplant-related mortality (TRM) in acute leukemia (AL) adult patients undergoing a first allogeneic hematopoietic stem cell transplant (HSCT) at a transplant center in Brazil. Methods In this prospective, cohort study, we used the formula published by Shouval et al. to calculate the AL-EBMT score and stratify patients into three risk categories. Results A total of 79 patients transplanted between 2008 and 2018 were analyzed. The median age was 38 years. Acute myeloid leukemia was the most common diagnosis (68%). Almost a quarter of the cases were at an advanced stage. All hematopoietic stem cell transplantations (HSCTs) were human leukocyte antigen-matched (HLA-matched) and the majority used familial donors (77%). Myeloablative conditioning was used in 92% of the cases. Stratification according to the AL-EBMT score into low-, intermediate- and high-risk groups yielded the following results: 40%, 12% and 47% of the cases, respectively. The high scoring group was associated with a hazard ratio of 2.1 (p= 0.007), 2.1 (p= 0.009) and 2.47 (p= 0.01) for the 2-year OS, LFS and TRM, respectively. Conclusion This study supports the ability of the AL-EBMT score to reasonably predict the 2-year post-transplant OS, LFS and TRM and to discriminate between risk categories in adult patients with AL, thus confirming its usefulness in clinical decision-making in this setting. Larger, multicenter studies may further help confirm these findings.

An elevated HScore is associated with poor clinical outcomes in COVID-19 / Un HScore elevado se asocia a mal pronóstico en pacientes con COVID-19

BACKGROUND: Patients with Coronavirus Disease 2019 (COVID-19) frequently experience a hyperinflammatory syndrome leading to unfavorable outcomes. This condition resembles Secondary Hemophagocytic Lymphohistiocytosis (sHLH) described in neoplastic, rheumatic and other infectious diseases. A scoring system (HScore) that evaluates underlying immunosuppression, temperature, organomegaly, cytopenias, ferritin, triglycerides, fibrinogen and AST was validated for sHLH, and recently proposed to evaluate hyperinflammation in COVID-19. AIM: To assess the presence of sHLH among patients with COVID-19 admitted for hospitalization and to evaluate Hscore as a prognostic tool for poor outcomes. MATERIAL AND METHODS: One hundred forty-three patients aged 21-100 years (64% males) admitted because of COVID-19 were enrolled in a prospective study. HScore was calculated within 72 hours admission. The incidence of sHLH during hospitalization was evaluated. Additionally, the relationship between a HScore ≥ 130 points and either the requirement of mechanical ventilation or 60-days mortality was explored. RESULTS: The median HScore was 96 (33-169). A SHLH was diagnosed in one patient (incidence 0.7%), whose HScore was 169. After adjusting for age, sex, comorbidities and obesity, HScore ≥ 130 was independently associated with the composite clinical outcome (Hazard rartio 2.13, p = 0.022). CONCLUSIONS: sHLH is not frequent among COVID-19 patients. HScore can be useful to predict the risk for poor outcomes.

ANTECEDENTES: Los pacientes con Enfermedad por Coronavirus 2019 (COVID-19), experimentan frecuentemente un síndrome hiperinflamatorio que lleva a resultados desfavorables. Esta situación se asemeja al Síndrome Hemofagocítico Secundario (sHLH) descrito en enfermedades neoplásicas, reumatológicas y por otros agentes infecciosos. Un sistema simple de puntaje (HScore) que evalúa inmunosupresión, temperatura organomegalia, citopenias, ferritina, triglicéridos, fibrinógeno y AST ha sido validado para el diagnóstico de sHLH y ha sido propuesto recientemente para evaluar la hiperinflamación en COVID-19. OBJETIVO: Medir la frecuencia de sHLH entre pacientes con COVID-19 hospitalizados, y evaluar a HScore como una herramienta pronóstica. MATERIAL Y MÉTODOS: Ciento cuarenta y tres pacientes de 21 a 100 años (64% hombres) fueron ingresados en este estudio de cohorte prospectivo, unicéntrico. Se calculó HScore dentro de las primeras 72 horas desde el ingreso, y se midió la incidencia de sHLH durante la hospitalización. Adicionalmente, se evaluó la relación entre HScore ≥ 130 puntos y un desenlace compuesto de ventilación mecánica o muerte a los 60 días. RESULTADOS: La mediana de HScore fue 96 (33-169) puntos. Un paciente fue diagnosticado con sHLH (incidencia 0,7%). Luego de ajustar por edad, sexo, comorbilidades y obesidad, un HScore ≥ 130 se asoció de manera independiente con el desenlace compuesto. CONCLUSIONES: El sHLH no es frecuente en los pacientes con COVID-19. El uso de HScore puede ser útil para predecir el riesgo de desenlaces clínicos desfavorables.

Identification of novel biomarkers with potential for diagnosis and prognosis of gastric cancer: a bioinformatics approach

INTRODUCTION: Gastric cancer (GC) is the fifth most diagnosed neoplasia and the third leading cause of cancer-related deaths. A substantial number of patients exhibit an advanced GC stage once diagnosed. Therefore, the search for biomarkers contributes to the improvement and development of therapies. OBJECTIVE: This study aimed to identify potential GC biomarkers making use of in silico tools. METHODS: Gastric tissue microarray data available in Gene Expression Omnibus and The Cancer Genome Atlas Program was extracted. We applied statistical tests in the search for differentially expressed genes between tumoral and non-tumoral adjacent tissue samples. The selected genes were submitted to an in-house tool for analyses of functional enrichment, survival rate, histological and molecular classifications, and clinical follow-up data. A decision tree analysis was performed to evaluate the predictive power of the potential biomarkers. RESULTS: In total, 39 differentially expressed genes were found, mostly involved in extracellular structure organization, extracellular matrix organization, and angiogenesis. The genes SLC7A8, LY6E, and SIDT2 showed potential as diagnostic biomarkers considering the differential expression results coupled with the high predictive power of the decision tree models. Moreover, GC samples showed lower SLC7A8 and SIDT2 expression, whereas LY6E was higher. SIDT2 demonstrated a potential prognostic role for the diffuse type of GC, given the higher patient survival rate for lower gene expression. CONCLUSION: Our study outlines novel biomarkers for GC that may have a key role in tumor progression. Nevertheless, complementary in vitro analyses are still needed to further support their potential.

Rendimiento de los índices predictores de gravedad en pacientes adultos hospitalizados por neumonía adquirida en la comunidad por coronavirus SARS-CoV-2 / Performance of severity indexes for the prediction of adverse events among patients hospitalized for SARS-CoV-2

BACKGROUND: Severity assessment in adult patients with community-acquired pneumonia (CAP) allows to guide the site of care (ambulatory or hospitalization), diagnostic workup and treatment. AIM: To examine the performance of twelve severity predictive indexes (CRB65, CURB65, PSI, SCAP, SMART-COP, REA-ICU, ATS minor criteria, qSOFA, CALL, COVID GRAM, 4C, STSS) in adult patients hospitalized for CAP associated with SARS-CoV-2. MATERIAL AND METHODS: Prospective clinical study conducted between April 1 and September 30, 2020 in adult patients hospitalized for CAP associated with COVID-19 in a clinical hospital. The recorded adverse events were admission to the critical care unit, use of mechanical ventilation (MV), prolonged length of stay, and hospital mortality. The predictive rules were compared based on their sensitivity, specificity, predictive values, and area under the receiver operator characteristic (ROC) curve. RESULTS: Adverse events were more common and hospital stay longer in the high-risk categories of the different prognostic indices. CURB-65, PSI, SCAP, COVID GRAM, 4 C and STSS predicted the risk of death accurately. PSI, SCAP, ATS minor criteria, CALL and 4 C criteria were sensitive in predicting the risk of hospital mortality with high negative predictive value. The performance of different prognostic indices decreased significantly for the prediction of ICU admission, use of mechanical ventilation, and prolonged hospital length of stay. CONCLUSIONS: The performance of the prognostic indices differs significantly for the prediction of adverse events in immunocompetent adult patients hospitalized for community-acquired pneumonia associated with COVID-19.

Relevancia y prevalencia de los parámetros histopatológicos y subtipos moleculares del cáncer de mama en mujeres del área costera de Ecuador atendidas en una institución de Salud Pública / Prevalence and significance of breast cancer pathologycal subtypes in Ecuador

BACKGROUND: The success of breast cancer (BC) treatment depends largely on the clinical-histological characteristics of the patient. Immunohistochemical (IHC) Breast Cancer Subtypes are crucial for therapeutic purposes. AIM: To determine the relevance and prevalence of the histopathological parameters and molecular subtypes of BC among women attending public health services. MATERIAL AND METHODS: A retrospective cross-sectional study was carried out in 199 female patients with histopathological diagnosis of breast cancer, treated at a Guayaquil city hospital in Ecuador, from January 2014 to December 2017. RESULTS: Luminal A carcinoma was the most prevalent tumor in the studied women (54%). Thirty seven percent of patients did not have nodal involvement, 40% had one to three lymph nodes involved and 2% had 10 or more nodes involved. Most patients had a tumor size > 2 and ≤ 5 cm (72%) and moderately differentiated specifications (57%). CONCLUSIONS: The study allowed the characterization of breast cancer according to the prevalence of molecular subtypes and clinical and histological characteristics. These factors determine therapeutic behaviors that optimize the use of the limited resources of the Public Health System.

TTYH3 is a prognostic biomarker and associates with immune cell infiltrations of lung adenocarcinoma / TTYH3 es un biomarcador pronóstico y se asocia con infiltraciones de células inmunitarias del adenocarcinoma de pulmón

SUMMARY: We investigated Tweety Family Member 3 (TTYH3) level in lung adenocarcinoma (LUAD) and its relationship with immune infiltration in tumors by bioinformatics. Differential expressions of TTYH3 in lung cancer were analyzed with Oncomine, TIMER, GEO, UALCAN and HPA. Relationship of TTYH3 mRNA/protein levels with clinical parameters was analyzed by UALCAN. Co-expressed genes of TTYH3 in LUAD were analyzed using Cbioportal. Its relationship with LUAD prognosis was analyzed by Kaplan-Meier plotter. GO and KEGG analysis were performed. Correlation between TTYH3 and tumor immune infiltration were tested by TIMER, TISIDB and GEPIA. We found that TTYH3 was significantly increased in LUAD tissues. TTYH3 high expression was closely related to poor overall survival, post progression survival and first progression in LUAD patients. TTYH3 mRNA/protein levels were significantly associated with multiple pathways. Specifically, TTYH3 up-regulation was mostly related to biological regulation, metabolic process, protein blinding, extracellular matrix organization and pathways in cancer. Moreover, TTYH3 was positively associated with immune cell infiltration in LUAD. Finally, TTYH3 was highly expressed in LUAD as revealed by meta-analysis. TTYH3 is closely related to the prognosis of LUAD and immune cell infiltration, and it can be used as a prognostic biomarker for LUAD and immune infiltration.

Investigamos por bioinformática el nivel de Tweety Family Member 3 (TTYH3) con adenocarcinoma de pulmón (LUAD) y su relación con la infiltración inmune en tumores. Las expresiones diferenciales de TTYH3 en cáncer de pulmón se analizaron con Oncomine, TIMER, GEO, UALCAN y HPA. Con UALCAN se analizó la relación de los niveles de ARNm/proteína de TTYH3 con los parámetros clínicos. Los genes coexpresados de TTYH3 en LUAD se analizaron utilizando Cbioportal. Su relación con el pronóstico LUAD se analizó mediante plotter de Kaplan- Meier. Se realizaron análisis GO y KEGG. TIMER, TISIDB y GEPIA probaron la correlación entre TTYH3 y la infiltración inmune tumoral. Encontramos que TTYH3 aumentó significativamente en los tejidos LUAD. La alta expresión de TTYH3 estuvo estrechamente relacionada con una supervivencia general deficiente, supervivencia posterior a la progresión y primera progresión en pacientes con LUAD. Los niveles de ARNm/ proteína de TTYH3 se asociaron significativamente con múltiples vías. Específicamente, la regulación positiva de TTYH3 se relacionó principalmente con la regulación biológica, el proceso metabólico, el cegamiento de proteínas, la organización de la matriz extracelular y las vías en el cáncer. Además, TTYH3 se asoció positivamente con la infiltración de células inmunitarias en LUAD. Finalmente, TTYH3 se expresó altamente en LUAD como lo reveló el metanálisis. TTYH3 está estrechamente relacionado con el pronóstico de LUAD y la infiltración de células inmunitarias, y se puede utilizar como biomarcador pronóstico para LUAD y la infiltración de células inmunitarias.

Prognostic Impact of AGR3 Protein Expression in Breast Cancer: A Systematic Review and Meta-analysis / Impacto prognóstico da expressão da proteína AGR3 no câncer de mama: Uma revisão sistemática e metanálise

Abstract Objective To investigate the clinicopathological significance and prognosis of the expression of the anterior gradient 3 (AGR3) protein in women with breast cancer. Data Sources The PubMed, CINAHL, EMBASE, Scopus, and Web of Science databases were searched for studies published in English and without restrictions regarding the year of publication. The search terms were: breast cancer AND anterior gradient 3 OR AGR3 expression. Study Selection We included observational or interventional studies, studies on AGR3 protein expression by immunohistochemistry, and studies on invasive breast cancer. Case reports, studies with animals, and reviews were excluded. In total, 4 studies were included, containing 713 cases of breast cancer. Data Collection Data were extracted on clinicopathological characteristics and survival. A meta-analysis of the prevalence of AGR3 expression was performed according to the clinicopathological characteristics, hazard ratios (HRs), and overall survival and disease-free survival. Data Synthesis The expression of AGR3 was found in 62% of the cases, and it was associated with histological grade II, positivity of estrogen and progesterone receptors, low expression of ki67, recurrence or distant metastasis, and lumen subtypes. In patients with low and intermediate histological grades, AGR3 expression was associated with worse overall survival (HR: 2.39; 95% confidence interval [95%CI]: 0.628-4.159; p= 0.008) and worse disease-free survival (HR: 3.856; 95%CI: 1.026-6.686; p= 0.008). Conclusion The AGR3 protein may be a biomarker for the early detection of breast cancer and predict prognosis in luminal subtypes. In addition, in patients with low and intermediate histological grades, AGR3 protein expression may indicate an unfavorable prognosis in relation to survival.

Resumo Objetivo Investigar o significado clinicopatológico e prognóstico da expressão da proteína anterior gradient 3 (AGR3) em mulheres com câncer de mama. Fontes de Dados Utilizamos as bases de dados PubMed, CINAHL, EMBASE, Scopus e Web of Science para pesquisar estudos em inglês, sem restrições quanto ao ano de publicação. Os termos buscados foram: breast cancer AND anterior gradient 3 OR AGR3 expression. Seleção dos Estudos Foram incluídos estudos observacionais ou intervencionais, estudos sobre a expressão da proteína AGR3 por imuno-histoquímica, e estudos sobre câncer de mama invasivo. Excluíram-se relatos de casos, estudos com animais e revisões. Quatro estudos foram selecionados, que continham 713 casos de câncer de mama. Coleta de Dados Foram extraídos dados relativos a características clinicopatológicas e sobrevida. A metanálise da prevalência da expressão de AGR3 foi realizada conforme as características clinicopatológicas, razões de risco (RRs) e sobrevida global (SG) e sobrevida livre de doença (SLD). Síntese dos Dados Encontrou-se expressão de AGR3 em 62% dos casos, que se associou com grau histológico II, positividade de receptores de estrogênio e progesterona, baixa expressão de ki67, recorrência ou metástase à distância e subtipos luminais. Em pacientes com graus histológicos baixo e intermediário, a expressão de AGR3 conferiu pior SG (RR: 2,39; intervalo de confiança de 95% [IC95%]: 0,628-4,159; p= 0,008) e pior SLD (RR: 3,856; IC95%: 1,026-6,686; p= 0,008). Conclusão A AGR3 pode ser um biomarcador para a detecção precoce do câncer de mama e predizer o prognóstico em subtipos luminais. Em graus histológicos baixo e intermediário, a expressão da proteína AGR3 pode indicar um prognóstico desfavorável em relação à sobrevida.