Nutrición enteral en pacientes críticos con COVID-19 ventilados en decúbito prono

Introducción: el SARS-CoV-2 desde el 2020 generó innumerables desafíos. El decúbito prono se utilizó para mejorar la oxigenación, y la terapia nutricional se adaptó para cubrir los requerimientos y reducir complicaciones. Objetivos: evaluar la tolerancia de la nutrición enteral y su adecuación energética en pacientes ventilados en decúbito prono con infección por SARS-CoV-2, en sala respiratoria del Departamento de Cuidados Intensivos Adultos del Hospital de Clínicas-Facultad de Ciencias Médicas - Universidad Nacional de Asunción, de marzo a julio 2021. Metodología: estudio observacional, descriptivo, retrospectivo, de corte transversal, de casos consecutivos, con información obtenida de fichas de pacientes de terapia intensiva, que recibieron soporte nutricional en posición prona. Se tomaron datos demográficos, clínicos y nutricionales. Se evaluó la tolerancia nutricional durante la posición prona, definiéndola como la presencia de un volumen de residuo gástrico < 500 mL cada 6 h.. La adecuación energética fue determinada teniendo en cuenta el porcentaje cumplido de la prescripción nutricional. Resultados: se reclutaron 41 pacientes. El 60,9 % eran hombres; la mediana de edad fue 55 años (RIC=23). Las principales comorbilidades fueron obesidad (57,3 %) e hipertensión arterial (43,9 %). El 85,4 % presentó buena tolerancia gástrica en posición prono, con residuo gástrico menor a 500 ml. El porcentaje de adecuación energética fue de 84 %. Conclusión: la terapia nutricional enteral en decúbito prono fue bien tolerada por la mayoría de nuestros pacientes, posibilitando alcanzar los requerimientos nutricionales indicados.

Introduction: SARS-CoV-2 since 2020 has generated countless challenges. Prone position was used to improve oxygenation, and nutritional therapy was adapted to meet requirements and reduce complications. Objectives: evaluate the tolerance of enteral nutrition and its energetic adequacy in ventilated patients in the prone position with SARS-CoV-2 infection, in the respiratory room of the Adult Intensive Care Department of the Hospital de Clínicas - Facultad de Ciencias Médicas - Universidad Nacional de Asunción, from March to July 2021. Methodology: observational, descriptive, retrospective, cross-sectional study of consecutive cases, with information obtained from records of intensive care patients, who received nutritional support in a prone position. Demographic, clinical and nutritional data were taken. Nutritional tolerance was evaluated during the prone position, defining it as the presence of a volume of gastric residue < 500 mL every 6 h. Energy adequacy was determined taking into account the percentage fulfilled of the nutritional prescription. Results: 41 patients were recruited. 60.9 % were men; the median age was 55 years (IQR=23). The main comorbidities were obesity (57.3 %) and high blood pressure (43.9 %). 85.4 % had good gastric tolerance in the prone position, with gastric residue less than 500 ml. The percentage of energy adequacy was 84 %. Conclusion: enteral nutritional therapy in the prone position was well tolerated by the majority of our patients, making it possible to achieve the indicated nutritional requirements.

Hipertensión portal no cirrótica por enfermedad vascular porto-sinusoidal: presentación de un caso y revisión de la literatura / Non-cirrhotic portal hypertension due to porto-sinusoidal vascular disease: Case presentation and literature review

La enfermedad vascular porto-sinusoidal es una causa infrecuente de hipertensión portal no cirrótica, fue descrita recientemente y es poco diagnosticada por el desconocimiento entre los médicos. Se considera en casos de hipertensión portal clínicamente significativa, en ausencia de cirrosis. El diagnóstico se basa en los hallazgos de la biopsia. El pronóstico de la enfermedad es mejor que el de los pacientes cirróticos, y el tratamiento es similar al de la hipertensión portal y al de las complicaciones que presentan los pacientes con cirrosis. Se presenta el caso de una paciente con várices esofágicas con estudios de imágenes no compatibles con cirrosis y hallazgos específicos en la biopsia de enfermedad vascular porto-sinusoidal. Este caso muestra el ejercicio diagnóstico en un caso de enfermedad vascular porto-sinusoidal de una paciente de Colombia, así como el resultado de las intervenciones terapéuticas y la evolución en el tiempo.

Porto-sinusoidal vascular disease is an uncommon cause of non-cirrhotic portal hypertension. It was recently described and is rarely diagnosed due to lack of knowledge among doctors. It is considered in cases of clinically significant portal hypertension in the absence of cirrhosis, and the diagnosis is based on biopsy findings. The prognosis of the disease is better than that of cirrhotic patients, and the treatment is similar to that of portal hypertension, including the management of complications associated with cirrhosis. We present the case of a patient with esophageal varices, whose imaging studies were not compatible with cirrhosis, alongside specific biopsy findings of porto-sinusoidal vascular disease. This case illustrates the diagnostic process in a patient from Colombia with portosinusoidal vascular disease, as well as the outcomes of therapeutic interventions and the patient´s evolution over time.

Visión general de las várices gástricas y su tratamiento / Overview of gastric varices and their treatment

Las várices gástricas (VG) son un complejo de colaterales vasculares entre la circulación portal y sistémica, condición que se desarrolla como resultado de la presión elevada en el sistema venoso portal. Se encuentran en el 20 % de los pacientes con cirrosis, y son menos frecuentes que las várices esofágicas. Según la clasificación de Sarin, las VG se dividen en cuatro tipos según su ubicación en el estómago y su relación con las várices esofágicas (GOV1, GOV2, IGV1 e IGV2). Entender su hemodinámica con respecto a las rutas de drenaje de las VG es importante para guiar su tratamiento.

Gastric varices (GV) are a complex of vascular collaterals between portal and systemic circulation, a condition that develops as a result of elevated pressure in the portal venous system. They are found in 20% of patients with cirrhosis, and are less common than esophageal varices. According to the Sarin classification, GV are divided into four types based on their location in the stomach and their relationship with esophageal varices (GOV1, GOV2, IGV1, and IGV2). Understanding their hemodynamics with respect to GV drainage routes is important to guide their treatment.

Resultados cardiometabólicos de largo plazo tras cirugía bariátrica: control de comorbilidades, pérdida y reganancia de peso a los 5 años de seguimiento / Long-term cardiometabolic results after bariatric surgery: Control of comorbidities, weight loss and regain at 5 years of follow-up

Introducción. La cirugía bariátrica y metabólica (CBM) es efectiva en lograr pérdida de peso a corto plazo. Sin embargo, existe evidencia limitada en desenlaces clínicos y metabólicos a largo plazo. Métodos. Estudio longitudinal retrospectivo con pacientes llevados a baipás gástrico en Y de Roux (BGYR) o gastrectomía en manga (MG) por laparoscopia en Bogotá, D.C., Colombia, entre 2013 y 2021. El cambio de peso, control de comorbilidades y resultados metabólicos se recopilaron al inicio del estudio, 3, 6 y 12 meses después de cirugía, y anualmente hasta el quinto año. Las tasas de control de comorbilidades se evaluaron mediante la prueba Kaplan-Meier. Se utilizó un modelo de riesgos proporcionales de Cox para evaluar el efecto de covariables en la reganancia de peso. Resultados. De 1092 pacientes con CBM (71,4 % MG y 28,6 % BGYR), 67 % eran mujeres, con mediana de edad 48 años e índice de masa corporal de 35,5 Kg/m2. Después de cinco años de seguimiento, la tasa de control en diabetes mellitus fue 65,5 %, en hipertensión 56,6 % y en dislipidemia 43,6 %. La tasa de reganancia de peso fue 28 %, sin diferencias entre MG vs BGYR (p=0,482). El tiempo promedio hasta peso nadir fue 14 meses. La edad al momento de CBM fue el mejor predictor independiente de reganancia (HR=1,02, IC95% 1,01-1,04), pero con efecto clínico modesto. Conclusión. La CBM es segura y muestra beneficios a largo plazo en la pérdida de peso y control de comorbilidades en población colombiana.

Introduction. Bariatric and metabolic surgery (BMS) has shown its efficacy in achieving short-term weight loss. However, there is limited evidence regarding long-term clinical and metabolic outcomes. Methods. Retrospective longitudinal study with patients who underwent laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) interventions in Bogotá, Colombia, between 2013 and 2021. Weight change, comorbidity control, and metabolic outcomes were collected at the onset, 3-, 6-, and 12-month post-surgery, and annually up to the fifth year. Comorbidity control rates were assessed using the Kaplan-Meier test. A Cox proportional hazards model was used to evaluate the effect of covariates on weight regain. Results. Of 1092 patients with BMS (71.4% SG and 28.6% RYGB), 67% were women, with a median age of 48 years, BMI 35.5 kg/m2. After five years of follow-up, the control rate in diabetes mellitus was 65.5%, in hypertension 56.6%, and dyslipidemia 43.6%. The weight regain rate was 28% with no differences between SG vs RYGB (p=0.482). The mean time to nadir weight was 14 months. Age at the time of BMS was the best independent predictor of weight regain (HR=1.02, 95%CI: 1.01-1.04), but with a modest clinical effect. Conclusion. BMS is safe and shows long-term benefits in weight loss and control of comorbidities in Colombian population.

Caracterización de los desenlaces quirúrgicos a corto plazo en gastrectomía por laparoscopia en un centro de alto volumen: 10 años de experiencia / Short-term surgical outcomes of laparoscopic gastrectomy in a high-volume center: 10-year experience

Introducción. El cáncer gástrico en Colombia es la segunda neoplasia más común en hombres y la cuarta en mujeres. En los últimos años se han descrito ampliamente los beneficios del abordaje laparoscópico en el cáncer gástrico frente a sangrado, recuperación postoperatoria y complicaciones, sin afectar los resultados oncológicos. Métodos. Estudio observacional retrospectivo de pacientes llevados a gastrectomía laparoscópica en la Clínica Universitaria Colombia durante un período de diez años, entre 2013 y 2023. Se describieron los resultados perioperatorios en cuanto a estancia hospitalaria, sangrado operatorio, duración del procedimiento, complicaciones, causas de reintervención y mortalidad en los primeros 30 días. Resultados. Se incluyeron 418 pacientes, 58,9 % hombres, con una edad promedio de 60,8 años. Se documentó un tiempo quirúrgico promedio de 228,7 minutos, con un sangrado de 150 ml. La media de ganglios linfáticos resecados fue de 26,1 ± 11,4. La estancia hospitalaria en promedio fue de 4 ± 4 días, y se registraron complicaciones en 104 sujetos, con una tasa promedio de 24 %, de las cuales 29 (27,4 %) obtuvieron una clasificación Clavien-Dindo IIIB. Conclusiones. La gastrectomía por laparoscopia en un centro de alto volumen y con cirujanos experimentados en Colombia, tiene resultados perioperatorios similares a lo reportado en la literatura mundial. Aún se requiere de estudios de mayor fuerza de asociación para establecer recomendaciones sobre el uso rutinario de este abordaje en patología maligna avanzada.

Introduction. Gastric cancer in Colombia is the second most common neoplasm in men and the fourth in women. In recent years, the benefits of the laparoscopic approach in gastric cancer against bleeding, postoperative recovery com and complications have been widely described, without affecting oncological results. Methods. Retrospective observational study of patients undergoing laparoscopic gastrectomy at the Clínica Universitaria Colombia over a period of ten years, between 2013 and 2023. Perioperative results were described in terms of hospital stay, operative bleeding, duration of the procedure, complications, causes of reintervention, and mortality in the first 30 days. Results. 418 patients were included, 58.9% men, with an average age of 60.88 years. An average surgical time of 228.7 minutes was documented, with a blood loss of 150 ml. The mean number of lymph nodes resected was 26.1 ± 11.4. The average hospital stay was 4 ± 4 days, and complications were recorded in 104 subjects, with an average rate of 24%, of which 29 (27.4%) obtained a Clavien-Dindo IIIB classification. Conclusions. Laparoscopic gastrectomy in a high-volume center and with experienced surgeons in Colombia has perioperative results similar to those reported in the world literature. Studies with greater strength of association are still required to establish recommendations on the routine use of this approach in advanced malignant pathology.

Infección por Helicobacter pylori y factores asociados en adultos de la sierra norte del Perú / Helicobacter pylori infection and associated factors in adults from the northern highlands of Peru

INTRODUCCIÓN: Helicobacter pylori afecta a más de 50% de la población mundial, siendo más prevalente en poblaciones de nivel socioeconómico bajo; esta bacteria constituye la principal causa de cáncer gástrico a nivel global. OBJETIVO: Determinar la frecuencia y los factores asociados a la infección por H. pylori en personas adultas que viven en el centro histórico de la ciudad de Cajamarca, en el norte del Perú. MATERIAL Y MÉTODO: Estudio descriptivo que incluyó 124 personas encuestadas mediante un cuestionario y evaluadas mediante endoscopía y cultivo de biopsia gástrica. Una biopsia por persona fue sometida a prueba de ureasa y los cultivos se confirmaron por reacción de polimerasa en cadena (RPC). RESULTADOS: La frecuencia de infección fue de 60,5 % (IC 95% 51,3 - 69,2). El análisis univariado demostró asociación significativa entre la infección y la edad (p = 0,002), y entre la infección y el antecedente de patología gástrica (p = 0,015). El análisis multivariado reveló dos factores asociados: edad (OR = 0,94; IC95% 0,90-0,97) y antecedente de infección por H. pylori (OR = 0,23; IC95% 0,08 - 0,67). CONCLUSIONES: Existe alta frecuencia de infección por H. pylori en esta población; la edad y el antecedente de infección constituyen factores asociados que deben evaluarse con mayor profundidad.

BACKGROUND: Helicobacter pylori affects more than 50% of the world's population, being more prevalent in populations of low socioeconomic status. H. pylori is the main cause of gastric cancer globally. AIM: To establish the frequency and factors associated with H. pylori infection in adults living in the historic center of Cajamarca City, in northern Peru. METHODS: This was a descriptive study that included 124 individuals surveyed through a questionnaire and evaluated through endoscopy and gastric biopsy culture. One biopsy per person underwent the urease test, and the cultures were confirmed by PCR. RESULTS: The frequency of infection was 60.5% (95% CI 51.3 - 69.2). In the univariate analysis, there was a significant association between the infection and age (p = 0.002), and between the infection and a history of gastric pathology (p = 0.015). The multivariate analysis revealed two associated factors: age (OR = 0.94; 95% CI 0.90 - 0.97), and history of H. pylori infection (OR = 0.23; 95% CI 0.08 - 0.67). CONCLUSIONS: There is a high frequency of H. pylori infection in this population, and the age and history of H. pylori infection are factors that should be further evaluated.

The lncRNA-MALAT1/miR-330-3p Axis Promotes Growth and Metastasis of Gastric Cancer Through Regulation of Vascular Endothelial Growth Factor A: A Genetic and Cell Evaluation Study

SUMMARY: Overexpression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in various tumor tissues and cell lines was found to promote tumor cell proliferation, migration, and invasion. However, the role of MALAT1 in gastric cancer (GC) is still unclear. We aimed to investigate the correlation between long-chain non-coding RNAs (lncRNAs), MALAT1, MicroRNAs (miRNA) and vascular endothelial growth factor A (VEGFA) in gastric cancer and to disclose underlying mechanism. The correlation between MALAT1 levels and clinical features was analyzed by bioinformatics data and human samples. The expression of MALAT1 was down regulated in AGS cells to detect the cell proliferation, migration, and invasion characteristics, as well as the effects on signal pathways. Furthermore, we validated the role of MALAT1/miR-330-3p axis in GC by dual luciferase reporter gene assays. Expression of MALAT1 was higher in cancer tissues than in para-cancerous tissues. The high MALAT1 level predicted malignancy and worse prognosis. Down-regulation of MALAT1 expression in AGS cells inhibited cell proliferation, migration, and invasion by targeting VEGFA. By dual luciferase reporter gene assay and miR-330-3p inhibitor treatment, we demonstrate that MALAT1 sponged miR-330-3p in GC, leading to VEGFA upregulation and activation of the mTOR signaling pathway. The MALAT1/miR-330-3p axis regulates VEGFA through the mTOR signaling pathway and promotes the growth and metastasis of gastric cancer.

Se descubrió que la sobreexpresión del transcrito 1 de adenocarcinoma de pulmón asociado a metástasis (MALAT1) en varios tejidos tumorales y líneas celulares promueve la proliferación, migración e invasión de células tumorales. Sin embargo, el papel de MALAT1 en el cáncer gástrico (CG) aún no está claro. Nuestro objetivo fue investigar la correlación entre los ARN no codificantes de cadena larga (lncRNA), MALAT1, los microARN (miARN) y el factor de crecimiento endotelial vascular A (VEGFA) en el cáncer gástrico y revelar el mecanismo subyacente. La correlación entre los niveles de MALAT1 y las características clínicas se analizó mediante datos bioinformáticos y muestras humanas. La expresión de MALAT1 se reguló negativamente en las células AGS para detectar las características de proliferación, migración e invasión celular, así como los efectos sobre las vías de señales. Además, validamos el papel del eje MALAT1/miR- 330-3p en GC mediante ensayos de genes indicadores de luciferasa dual. La expresión de MALAT1 fue mayor en tejidos cancerosos que en tejidos paracancerosos. El alto nivel de MALAT1 predijo malignidad y peor pronóstico. La regulación negativa de la expresión de MALAT1 en células AGS inhibió la proliferación, migración e invasión celular al apuntar a VEGFA. Mediante un ensayo de gen indicador de luciferasa dual y un tratamiento con inhibidor de miR-330-3p, demostramos que MALAT1 esponjaba miR-330-3p en GC, lo que lleva a la regulación positiva de VEGFA y la activación de la vía de señalización mTOR. El eje MALAT1/miR-330-3p regula VEGFA a través de la vía de señalización mTOR y promueve el crecimiento y la metástasis del cáncer gástrico.

Terapia de conversión en cáncer gástrico: experiencia del Instituto Nacional de Cancerología de Colombia / Conversion therapy in gastric cancer: experience at Instituto Nacional de Cancerología de Colombia

RESUMEN Antecedentes: el cáncer gástrico (CG) representa un problema de salud pública en Colombia y el mundo. Dado que la mayoría de los pacientes se encuentran en estadios avanzados en el momento del diagnóstico. desarrollar estrategias de manejo. como la terapia de conversión (TC). es una necesidad cada vez mayor en su tratamiento. Objetivo: estimar los resultados con la TC en el tratamiento de pacientes con CG avanzado en el Instituto Nacional de Cancerología de Colombia (INC). Material y métodos: serie de casos de pacientes con adenocarcinoma gástrico incurable llevados a quimioterapia de inducción y cirugía con intención curativa. entre los años 2010 y 2021. Se revisaron de forma retrospectiva los datos clínico-patológicos y de supervivencia. La supervivencia global (SG) se calculó desde la fecha de la primera quimioterapia hasta la muerte. Las funciones de supervivencia se estimaron con tablas de vida y por el método de Kaplan-Meier y se realizaron curvas de supervivencia a 3 y 5 años. Resultados: se analizaron los datos de 23 pacientes con edad promedio de 56 años. 17 (74%) fueron varones. El criterio de irresecabilidad más frecuente fue un tumor T4b en 13 casos (56.5%). Todos recibieron TC. La mediana de seguimiento fue de 28 meses. Se documentaron 11 recurrencias (52%). La mediana de supervivencia fue de 41.2 meses y la SG a 3 y 5 años de 57.7% y 38.5%. respectivamente. Conclusiones: la TC permitió obtener una SG aceptable de pacientes seleccionados con CG avanzado incurable. Esta estrategia requiere una cuidadosa selección y manejo multidisciplinario en centros oncológicos de referencia.

ABSTRACT Background: Gastric cancer (GC) represents a public health problem in Colombia and worldwide. Since most patients are at advanced stages at the time of diagnosis. it is necessary to develop management strategies as conversion therapy (CT). Objective: The aim of this study was to estimate the results of CT for treating patients with advanced and GC at Instituto Nacional de Cancerología de Colombia (INC). Material and methods: We included patients with incurable gastric cancer who underwent induction chemotherapy and intended curative surgery between 2010 and 2021. The clinical and pathological data and survival of the patients included were retrospectively reviewed. Overall survival (OS) was calculated from the time of initiation of chemotherapy until the date of death. Survival functions were estimated using the life table and Kaplan-Meier methods. and survival curves at 3 and 5 years were constructed. Results: 23 patients were analyzed; mean age was 56 years. and 17 (74%) were men. The most common criterion indicating unresectability was a T4b tumor in 13 cases (56.5%). All the patients underwent CT. Median follow-up was 28 months. Eleven patients developed disease recurrence (52%). Median survival was 41.2 months. and 3- and 5-year OS was 57.7% and 38.5%. respectively. Conclusions: CT provided an acceptable OS rate for selected patients with incurable advanced GC. This strategy requires an adequate selection of patients and multidisciplinary management in reference oncology centers.

Cáncer Gástrico Bifocal con Linfonodos Negativos en un Paciente con Cirrosis Hepática / Bifocal Gastric Cancer with Negative Lymph Nodes in a Hepatic Cirrhosis Patient

El cáncer gástrico (CG), es la primera causa de muerte por cáncer, en hombres, y la tercera en mujeres, en Chile. No obstante ello, el CG bifocal (CGB) es una situación poco frecuente. El objetivo de este manuscrito fue reportar un caso de CGB, con linfonodos negativos en un paciente con cirrosis hepática, que fue intervenido quirúrgicamente; y revisar la evidencia existente respecto de sus características morfológicas, terapéuticas y pronósticas. Caso clínico: Hombre de 74 años diabético, hipertenso, insuficiente cardíaco y cirrótico; portador de CGB (subcardial y antro-pilórico), diagnosticado por endoscopia y con confirmación histológica de ambas lesiones; operado en Clínica RedSalud Mayor Temuco en septiembre de 2023. En el intraoperatorio se verificó además la coexistencia de una lesión de aspecto metastásico en el segmento III del hígado, y adhesión de la región antro-pilórica a la vesícula biliar. Se realizó gastrectomía total, linfadenectomía D2, esófago-yeyuno anastomosis término-lateral, resección segmentaria hepática (segmento III) y colecistectomía. El paciente permaneció 6 días en la UCI debido a que desarrolló insuficiencia hepática (encefalopatía leve y ascitis). Se alimentó vía enteral por sonda naso-yeyunal. Posteriormente inició alimentación oral progresiva, la que fue bien tolerada. Completó 11 días de hospitalización en servicio médico-quirúrgico, donde mejoró actividad neurológica, hasta su alta domiciliaria. Actualmente, lleva dos meses desde su operación, se encuentra en buenas condiciones generales, y el Comité Oncológico decidió no dar quimioterapia adyuvante. Se presenta un caso inusual de CG de tipo bifocal, respecto de lo cual hay escasa información disponible. Se logró realizar cirugía con intención curativa en un paciente de alto riesgo, con un resultado exitoso.

SUMMARY: Gastric cancer (GC) is the first cause of death from cancer in men, and the third one in women, in Chile. However, a bifocal GC (BGC) is uncommon. The aim of this study was to report a case of CGB, with negative-lymph nodes in a patient with liver cirrhosis, who underwent surgery; and review the existing evidence regarding its morphological, therapeutic and prognostic characteristics. Clinical case: A 74-year-old male patient with a medical history of diabetes, hypertension, congestive heart failure, and cirrhosis underwent surgical intervention for GC located in subcardial and antro- pyloric regions. The diagnosis was established via endoscopy and confirmed histologically. Surgery was performed at the RedSalud Mayor Temuco Clinic in September 2023. During intraoperative assessment, the coexistence of a lesion with metastatic-like characteristics in segment III of the liver was also verified, along with adhesions between the antro-pyloric region and the gallbladder. Surgical approach encompassed total gastrectomy, D2 lymphadenectomy, esophago-jejunostomy, segmental hepatic resection, and cholecystectomy. Subsequently, the patient required a six-day stay in ICU due to the development of hepatic insufficiency, characterized by mild encephalopathy and ascites. Enteral nutrition was administered via a naso-jejunal tube, followed by a gradual transition to oral feeding, which was well-tolerated. The patient completed an 11-day hospitalization period in the medical-surgical ward, during which his neurological function improved significantly, resulting in his discharge. At present, 2 months post-surgery, the patient remains in satisfactory general health, and the Oncology Committee decided not to proceed with adjuvant chemotherapy. This case represents a rare instance of bifocal GC, for which there is limited available literature. Surgical intervention with curative intent was successfully carried out in a high-risk patient, yielding a positive outcome.

Moderate physical exercise and ATP modulate the P2X7 receptor and improve cisplatin-induced gastric emptying delay in rats

Patients undergoing chemotherapy with cisplatin commonly present gastrointestinal effects such as constipation and gastric emptying (GE) delay. Both the purinergic system and physical exercise modulate the gastrointestinal (GI) tract. In the current study, we investigated the role of ATP, physical exercise, and P2X7 receptor blocking on GE delay induced by cisplatin in rats. Male rats were divided into the following groups: control (C), cisplatin (Cis), exercise (Ex), Brilliant Blue G (BBG), ATP, Cis+Ex, Cis+ATP, Cis+BBG, Cis+Ex+BBG, Cis+Ex+BBG+ATP, and Cis+ATP+BBG. GE delay was induced by treatment with 1 mg/kg cisplatin (1 time/week for 5 weeks, ip). The moderate physical exercise was swimming (1 h/day, 5 days/week for 5 weeks). At the end of the treatment or exercise and 30 min before the GE assessment, some groups received BBG (50 mg/kg, sc) or ATP (2 mg/kg, sc). Then, GE was assessed after a 10-min postprandial period. Chronic use of Cis decreased GE delay (P<0.05) compared to the control group. Both exercise and ATP prevented (P<0.05) GE delay compared to Cis. The pretreatment with BBG significantly inhibited (P<0.05) the effect of exercise and ATP. On the other hand, the association between exercise and ATP reversed (P<0.05) the effect of the BBG and prevented GE delay. Therefore, we suggest that both exercise and treatment with ATP activate P2X7 receptors and prevent GE delay induced by cisplatin in rats.

Transcription Factor E2F7 Activates PKMYT1 to Partially Suppress Adriamycin Sensitivity in Gastric Cancer Through the MAPK Signaling Pathway

ABSTRACT Background: Adriamycin (ADM) resistance remains an obstacle to gastric cancer chemotherapy treatment. Objective: The objective of this study was to study the role and mechanism of transcription factor E2F7 in sensitivity to ADM chemotherapeutic agents in gastric cancer. Methods: Cell viability and cell sensitivity were assessed by CCK-8 and IC50 values of ADM were calculated. The impact of ADM on cellular proliferative capacity was assessed through colony formation assay. The binding relationship between E2F7 and PKMYT1 was then verified by dual luciferase assay and chromatin immunoprecipitation assay. ERK1/ERK2 and p-ERK1/p-ERK2 protein expression levels were detected by western blot. Results: In both gastric cancer tissue and ADM-resistant cells, a conspicuous upregulation of E2F7 and PKMYT1 was observed. Upregulated PKMYT1 was notably enriched in the MAPK signaling pathway. Enhanced levels of E2F7 were shown to not only drive gastric cancer cell proliferation but also engender a reduction in the sensitivity of these cells to ADM. Furthermore, PKMYT1 emerged as a downstream target of E2F7. Activation of E2F7 culminated in the transcriptional upregulation of PKMYT1, and silencing E2F7 reversed the inhibitory impact of PKMYT1 overexpression on ADM sensitivity in gastric cancer cells. Conclusion: E2F7/PKMYT1 axis might promote the proliferation and partially inhibit ADM sensitivity of gastric cancer cells by activating the MAPK pathway.

Reducción de la infección por Helicobacter pylori en pacientes derivados a endoscopia digestiva alta en Santiago de Chile entre 2010-2020 / Reduction in Helicobacter pylori infection among patients referred for upper gastrointestinal endoscopy in Santiago, Chile, between 2010-2020

RESUMEN Latinoamérica presenta una alta prevalencia de infección por Helicobacter pylori (Hp). Entre 1996-2003 la prevalencia en Santiago de Chile fue del 70%; estudios recientes presentan una disminución en esta infección. Actualizar la frecuencia de Hp es fundamental debido a su impacto en la salud asociado. Objetivo: Nuestro objetivo fue describir la tendencia de la infección por Hp en pacientes que asisten a endoscopía digestiva alta (EDA) ambulatoria en una población chilena. Materiales y métodos: Se realizó un estudio observacional retrospectivo de pacientes mayores de 18 años que asistieron a una primera EDA con test rápido de ureasa entre 2010-2020. La tendencia en el tiempo fue descrita mediante análisis de series de tiempo. Se construyó un modelo Poisson para estimar el riesgo de infección, ajustado por edad y sexo. Resultados: Se incluyeron 11 355 pacientes [66,9% mujeres; edad media 52 años; Hp 41,6%]. El sexo masculino presentó una mayor frecuencia de infección por Hp [RR 1,13; (IC95%:1,08-1,18)]. La frecuencia de Hp disminuyó significativamente desde 45,1% en 2010 hasta 29% en 2020, con 36% menor probabilidad de presentar infección por Hp en 2020 con respecto al 2010 [RR 0,64; (IC95%:0,55-0,74)]. Se proyectó un descenso progresivo en la tendencia de infección por Hp hasta valores cercanos al 25% para el año 2025. Conclusión: Se observó una reducción significativa en la infección por Hp entre los años 2010-2020. Esta disminución pudiese ser explicada mediante la incorporación de políticas públicas de salud en la última década asociadas a cambios sociosanitarios.

ABSTRACT Latin America presents a high prevalence of Helicobacter pylori (Hp) infection. Between 1996-2003, the prevalence in Santiago, Chile, was 70%; recent studies indicate a decrease in this infection. Updating the frequency of Hp is crucial due to its associated health impact. Objective: Our objective was to describe the trend in Hp infection in patients undergoing ambulatory esophagogastroduodenoscopy (EGD) in a Chilean population. Materials and methods: A retrospective observational study was conducted on patients over 18 years old who attended a first EGD with a rapid urease test between 2010-2020. Time trends were described through time series analysis. A Poisson model was constructed to estimate the risk of infection, adjusted for age and gender. Results: 11,355 patients were included [66.9% females; mean age 52 years; Hp 41.6%]. Male gender presented a higher frequency of Hp infection [RR 1.13; (95% CI: 1.08-1.18)]. Hp frequency infection decreased significantly from 45.1% in 2010 to 29% in 2020, with a 36% lower probability of Hp infection in 2020 compared to 2010 [RR 0.64; (95% CI: 0.55-0.74)]. A progressive decline in Hp infection trend was projected, reaching values close to 25% by year 2025. Conclusion: A significant reduction in Hp infection was observed between 2010-2020. This decrease could be explained by the implementation of public health policies in the last decade associated with socio-sanitary changes.

Treatment of gastric varices with cyanoacrylate complicated by systemic embolization / Tratamiento de várices gástricas con cianoacrilato complicado con embolización sistémica

ABSTRACT Acute gastric variceal bleeding is a life-threatening condition that could be effectively treated with endoscopic cyanoacrylate injection diluted with lipiodol. The mixture acts as a tissue adhesive that polymerizes when in contact with blood in a gastric varix. This work reports a patient that presented to the emergency department with upper gastrointestinal bleeding due to acute variceal bleeding, who developed systemic embolization following cyanoacrylate injection therapy. This complication culminated in cerebral, splenic and renal infarctions with a fatal outcome. Systemic embolization is a very rare, but the most severe complication associated with endoscopic cyanoacrylate injection and should be considered in patients undergoing this treatment.

RESUMEN La hemorragia digestiva por várices gástricas es una afección potencialmente mortal que puede tratarse eficazmente con la inyección endoscópica de cianoacrilato diluida con lipiodol. La mezcla actúa como un adhesivo tisular que se polimeriza cuando entra en contacto con la sangre de la várice gástrica. Este trabajo nos reporta un paciente que acudió al servicio de urgencias con hemorragia digestiva alta debido a hemorragia aguda por várices, que desarrolló embolización sistémica después de la terapia con inyección de cianoacrilato. Esta complicación culminó en infartos cerebrales, esplénicos y renales con desenlace fatal. La embolización sistémica es una complicación muy rara, pero con alta mortalidad, asociada con la inyección endoscópica de cianoacrilato y debe considerarse en pacientes sometidos a este tratamiento.

Cost-effectiveness analysis of tislelizumab combined with chemotherapy as first-line treatment for locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of tislelizumab combined with chemotherapy as first-line treatment for locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. METHODS The data of RATIONALE-305 study and related literature were used to establish a partitioned survival model from the perspective of China’s health system. The cycle was 3 weeks， the simulation time was set as 10 years， and the discount rate was 5%. The quality-adjusted life years （QALYs） were used as the health outcome indicator to evaluate the cost-effectiveness of tislelizumab combined with chemotherapy versus placebo combined with chemotherapy as first-line treatment for locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma， and one-way sensitivity analysis and probabilistic sensitivity analysis were also conducted. RESULTS The base analysis showed that the patients received more 0.268 QALYs with tislelizumab plus chemotherapy， compared with placebo plus chemotherapy， but the cost increased by 70 404.81 yuan with an incremental cost- effectiveness ratio （ICER） of 262 431.62 yuan/QALY， which was less than three times China’s gross domestic product （GDP） per capita in 2023 as the willingness-to-pay （WTP） threshold （268 074 yuan/QALY）. One-way sensitivity analysis showed that the efficacy value of progress free survive and the price of tislelizumab had a greater impact on the ICER value. The results of probability sensitivity analysis showed that when the WTP threshold was 3 times China’s GDP per capita in 2023， the probability of tislelizumab being cost-effective was 53.3%. CONCLUSIONS When the WTP threshold is 3 times China’s GDP per capita in 2023， tislelizumab plus chemotherapy is cost-effective for first-line treatment of locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma， compared with placebo plus chemotherapy.

Efficacy of endoscopic ultrasound-guided coil placement combined with tissue adhesive injection in treatment of gastric varices with spontaneous shunt / 临床肝胆病杂志

ObjectiveTo investigate the efficacy， safety， and cost-effectiveness of endoscopic ultrasound （EUS）-guided coil placement combined with tissue adhesive injection in the treatment of gastric varices with spontaneous shunt. MethodsA retrospective analysis was performed for the patients with acute gastric variceal bleeding and spontaneous portosystemic shunt who were hospitalized and received balloon-occluded retrograde transvenous obliteration （BRTO） combined with endoscopic tissue adhesive injection or EUS-guided coil placement combined with tissue adhesive injection in Xiangyang Central Hospital from March 2019 to September 2022. The two surgical procedures were compared in terms of efficacy （technical success rate， 5-day rebleeding rate， 1-year rebleeding rate， and time to rebleeding）， safety （the incidence rate of ectopic embolism， the amount of tissue adhesive used， and the amount of lauromacrogol used）， and cost-effectiveness （hospital costs and length of hospital stay）. The t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used to estimate the rebleeding. The chi-square test was used for comparison of categorical data between two groups. ResultsA total of 25 patients received successful EUS-guided coil placement and tissue adhesive injection， with a technical success rate of 100%， a median amount of 2.5 mL tissue adhesive used， a median amount of 11.0 mL lauromacrogol used， a mean length of hospital stay of 14.88±3.21 days， a mean hospital cost of 32 660.00±4 602.07 yuan， and a 5-day rebleeding rate of 0%； among these patients， 2 were lost to follow-up， and 23 patients with complete follow-up data had an incidence rate of ectopic embolism of 0% and a median time to rebleeding of 689 days. A total of 14 patients underwent modified BRTO combined with endoscopic tissue adhesive injection， with a technical success rate of 100%； a median amount of 5.0 mL tissue adhesive used during surgery， which was significantly higher than that used in EUS （U=39.000， P<0.001）； a median amount of 10.5 mL lauromacrogol used during surgery； a mean length of hospital stay of 15.38±4.94 days； a mean hospital cost of 57 583.47±18 955.40 yuan， which was significantly higher than that used in EUS （t=-6.310， P<0.001）； a 5-day rebleeding rate of 0%. No patient was lost to follow-up， and all 14 patients had an incidence rate of ectopic embolism of 0% and a median time to rebleeding of 244.50 days， with no significant difference between the two groups （χ2=1.448， P=0.229）. ConclusionEUS-guided coil placement combined with tissue adhesive injection is a relatively safe and effective technique for the treatment of gastric variceal bleeding and has a high technical success rate， a low incidence rate of serious adverse events， and similar efficacy to BRTO， with higher safety and cost-effectiveness.

The preliminary therapeutic effect of endoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips in treatment of cirrhotic patients with gastric varices and gastric-renal shunt / 临床肝胆病杂志

ObjectiveTo investigate the safety and efficacy of endoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips in the treatment of cirrhotic patients with gastric varices and gastric-renal shunt （GRS）. MethodsThe patients who attended Beijing Ditan Hospital， Capital Medical University， due to liver cirrhosis and gastric varices from February to June 2023 were enrolled， and all patients were confirmed to have GRS and received endoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips. The primary evaluation index was alleviation or disappearance of varicose veins after surgery， and the secondary evaluation indices were surgical completion and complications. ResultsA total of 11 patients were enrolled in this study， among whom there were 7 male patients and 4 female patients， with a median age of 55 years. Of all patients， 1 had Child class A liver function， 7 had Child class B liver function， and 3 had Child class C liver function. The maximum （median） diameter of the shunt was 8 mm， and the minimum （median） diameter of the shunt was 4 mm. The median blood flow velocity of the target vessel was 11 cm/s before treatment and 5 cm/s after occlusion with metal clips. The median amount of tissue adhesive injected was 2 mL， and the amount of lauromacrogol used was 1 mL. Disappearance of blood flow signals was observed in all patients after surgery （100%）， and the success rate of surgery was 100%. No patient experienced rebleeding after follow-up for 6 weeks. Gastroscopy at 1 month after surgery showed that gastric varices were eradicated or almost disappeared in 9 patients and were alleviated in 2 patients. ConclusionEndoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips is a feasible， safe， and effective treatment method for cirrhotic patients with gastric varices and GRS.

Mechanism of Sanhuang Xiexintang in Protecting Stress Gastric Ulcer in Rats / 中国实验方剂学杂志

ObjectiveTo explore the molecular mechanism of Sanhuang Xiexintang （SHXXT） in protecting stress gastric ulcer （SGU） in rats through network pharmacology， molecular docking， and animal experiments. MethodThe active ingredients and corresponding targets in SHXXT were collected and screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Information Database （TCMID）， Bioinformation Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）， and Swiss Target Prediction database. SGU-related targets were screened from the Online Mendelian Inheritance in Man （OMIM）， Therapeutic Target Database （TTD）， GeneCards database， and PharmGKB database. Herbal-ingredient-target （H-C-T） network was constructed by using Cytoscape 3.9.1 software. Protein-protein interaction （PPI） of drug and disease intersection targets was analyzed by using the Protein Interaction Platform （STRING） database. Gene ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis were conducted through the Database for Annotation Visualization and Integrated Discovery （DAVID）. The active ingredients and key targets were validated using AutodockVina 1.2.2 molecular docking software， and the experimental results were further validated through animal experiments. ResultThe 55 active ingredients were screened， and 255 potential target genes for SHXXT treatment of SGU were predicted. The PPI analysis showed that protein kinase B （Akt）， phosphatase and tensin homolog deleted on chromosome ten （PTEN）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and cyclooxygenase-2 （COX-2） are the core targets of SHXXT for protecting SGU. GO and KEGG analyses showed that SHXXT may affect the development of SGU by regulating various biological processes such as the phosphoinositide 3-kinase （PI3K）/Akt signaling pathway and inflammatory processes. The molecular docking results showed that both the active ingredients and key targets had good binding ability. Animal experiments showed that compared with the blank group， the ulcer index （UI） of the model group was significantly increased （P<0.01）， and the serum levels of TNF-α and IL-1β significantly increased （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly down-regulated （P<0.05）. The phosphorylation levels of PI3K， Akt， and nuclear factor kappa-B （NF-κB） were significantly up-regulated （P<0.05）. Compared with the model group， the UI of the treatment group was significantly reduced （P<0.01）， and the serum levels of TNF-α and IL-1β were significantly reduced （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly up-regulated （P<0.01）， and the phosphorylation levels of PI3K， Akt， and NF-κB were significantly downregulated （P<0.01）. ConclusionThe application of network pharmacology prediction， molecular docking simulation， and animal experimental validation confirms that SHXXT regulates the PI3K/Akt/NF-κB signaling pathway to regulate the inflammatory response of rats and thus protects the gastric mucosa of SGU rats.

Effects of the proliferation, migration and apoptosis of AHVAC - on gastric cancer MKN-28 cells / 中国临床药理学与治疗学

AIM: To investigate the effects of agkis-trodon halys venom anti-tumor component (AHVAC-) on the biological behavior of gastric cancer MKN-28 cells. METHODS: Gastric cancer MKN-28 cells were treated with the experimental concentrations (5, 10, 15 μg/mL) of AHAVC- for 24 h. Cell proliferation and toxicity assay (cell counting kit-8, CCK-8) was used to detect the inhibition rates of the cells in different concentrations of AHVAC-. The migration ability of the cells was evaluated by wound-healing and Transwell assay. The apoptosis were observed by laser confocal microscopy with annexin V-mCherry/DAPI double staining, and the apoptosis rates were analyzed by flow cytometry with annexin V-FITC/PI double fluorescence staining. The protein level of Caspease-3 was determined by Western blot. RESULTS: Compared with normal control group, the results of AHVAC- concentration groups showed that with the increase of AHVAC- concentration, the proliferative activity of MN-28 cells decreased gradually (P<0.01), the cell migration ability decreased gradually (P<0.01), and the cell apoptosis rate increased (P<0.05). The expression of apoptosis-related protein Caspease-3 was up-regulated (P<0.01). CONCLUSION: AHVAC- inhibits proliferation and migration of gastric cancer MSN-28 cells and induces apoptosis.

Diallyl disulfide augments sensitivity of DJ-1 overexpressed human gastric cells to 5-FU / 中国药理学通报

Aim To investigate whether diallyl disul-fide (DADS) augments the sensitivity of DJ-1 (protein/ nucleic acid deglycase) overexpressed human gastric SGC7901 cells to 5-FU (5-fluorouracil). Methods The experimental groups include control group, DADS group, VCR (vincristine) group, VCR + DADS group, DJ-1 group, DJ-1 + DADS group. MTT was used to analyze the effect of DADS on 5 -FU (5 -fluorou- racil) induced proliferation inhibition. Flow cytometry was performed to examine the effect of DADS on cell apoptosis. RT-PCR, Western blot, and immunofluo-rescence were used for determine the effect of DADS on the drug resistance associated gene expression. Results DADS enhanced the proliferation inhibitory effect of 5-FU on DJ-1 overexpressed cells and VCR resistant cells. DADS could induce apoptosis in VCR-resistant cells. DADS downregulated the expression of DJ-1 while inducing apoptosis in DJ-1 overexpressed cells. DJ-1 overexpression upregulated the expression of P-gp (P-glycoprotein), Bcl-2, and XIAP (X-linked inhibitor of apoptosis protein), downregulated the expression of caspase-3. DADS decreased the expression of P-gp, Bcl-2, and XIAP, while increased the expression of caspase-3 in DJ-1 overexpressed cells and VCR-resistant cells. Conclusions DADS can augment the sensitivity of DJ-1 overexpressed cells to 5-FU, which is related to its antagonism against DJ-1 mediated upregula- tion of P-gp, Bcl-2, XIAP, and downregulation of caspase-3.

Literature analysis of ADR after the listing of apatinib / 中国药房

OBJECTIVE To explore the characteristics and regulations of adverse drug reactions （ADR） caused by apatinib， and to provide a reference for the safe use of apatinib in clinic. METHODS Case and group reports on ADR and safety evaluation of apatinib were retrieved from Chinese and English databases such as CNKI， Wanfang medical network， VIP and PubMed since its listing in 2014， literature data were extracted and statistically analyzed after screening. RESULTS Totally 101 cases were included， involving 221 ADR. In the above cases， the male-to-female ratio was 1.24∶1， with the highest proportion of patients aged 51 to 70 years， most of the patients were given a dose of 500 mg or more， and the patients given low dose of apatinib combined with other antitumor drugs were also likely to have ADR. One to two types of adverse reaction were the most common， while the types could reach up to six. Most ADR occurred within 30 days after medication， and the systems/organs involved were mainly the cardiovascular system damage，skin and its accessories damage， gastrointestinal system damage and urinary system damage； the main clinical manifestations were hypertension/aggravation，hand-foot syndrome，abdominal pain diarrhea and albuminuria， etc. Hypertension/aggravation， hand-foot syndrome and myelosuppression were the most common serious ADR. Most ADR could be improved/cured by suspension of administration， dose downregulation and symptomatic treatment. All 4 patients who died had underlying diseases， and their ECOG scores all ≥2 points. Special ADR （such as reversible posterior encephalopathy syndrome， psychiatric disorders， and cognitive impairment） were mostly caused by apatinib itself， or may be caused by apatinib in combination with the primary or underlying disease. CONCLUSIONS Advanced age， large dose， combination medication， underlying diseases and poor physical condition might be the high risks for ADR caused by apatinib. It is recommended to monitor the blood pressure，urine protein and skin of hands and feet of all patients with medication on a daily basis，pay attention to the occurrence of special ADR， and timely detect abnormal states and give effective intervention，so as to avoid the aggravation of ADR and other secondary ADR.