Granulocyte-colony stimulating factor in acute-on-chronic liver failure: Systematic review and meta-analysis of randomized controlled trials / Factor estimulante de colonias de granulocitos en el fallo hepático agudo sobre crónico: revisión sistemática y metaanálisis de estudios aleatorizados controlados

Background and aims: A dysfunctional immune response is key to the pathogenesis of acute-on-chronic liver failure (ACLF). It has been suggested that treatment with granulocyte colony-stimulating factor (G-CSF) increases survival in patients with ACLF by improving immune cell dysfunction and promoting liver regeneration. The aim of the study is to evaluate the survival benefit associated with G-CSF administration compared with standard medical therapy (SMT) in ACLF. Methods: Systematic review and meta-analysis of randomized controlled trials. The primary outcome was survival at 60–90 days. We searched Ovid Medline, EMBASE, and Cochrane Central Register of Controlled Trials from inception to August 2021. Manual searches of reference lists in relevant articles and conference proceedings were also included. The revised Cochrane risk-of-bias tool was used for quality and risk of bias assessment. Two independent investigators extracted the data, and disagreements were solved by a third collaborator. Results: The initial search identified 142 studies. Four randomized controlled trials were selected for quantitative analysis including 310 patients (154 G-CSF and 156 SMT). Significant heterogeneity was observed (I2=74%, Chi2=11.57, p=0.009). G-CSF administration did not improve survival in patients with ACLF (random-effects model, risk ratio=0.64 [95% CI 0.39, 1.07]). However, when considering only the results from the studies performed in Asia, a significant decrease on mortality was observed (risk ratio=0.53 [95% CI 0.35, 0.81]). Severity scores (MELD and Child) and CD34+ peripheral cells mobilization did not significantly improve with G-CSF. Conclusion. In a systematic review and meta-analysis, G-CSF administration did not significantly improve overall survival compared to SMT in patients with ACLF...(AU)

Antecedentes y objetivos: La respuesta inmune disfuncional es clave en la patogénesis del fallo hepático agudo sobre crónico (ACLF). Se ha sugerido que la utilización de factor estimulante de colonias de granulocitos (G-CSF) aumenta la supervivencia de los pacientes con ACLF al mejorar la disfunción inmune y promover la regeneración hepática. El objetivo del estudio es evaluar el beneficio en supervivencia que proporciona la administración de G-CSF en comparación con el tratamiento médico estándar (SMT) en pacientes con ACLF. Métodos: Se llevó a cabo una revisión sistemática y meta-análisis de estudios aleatorizados y controlados. El objetivo principal fue analizar la supervivencia a los 60-90 días. Se realizó una búsqueda en Ovid Medline, EMBASE, y el registro central de estudios controlados de Cochrane desde su inicio hasta agosto 2021. También se realizaron búsquedas manuales en la bibliografía de artículos relevantes y presentaciones a congresos. Se utilizó la herramienta revisada de Cochrane para analizar la calidad y el riesgo de sesgos. Los datos fueron extraídos por dos investigadores independientes y las discrepancias fueron resueltas por un tercer investigador. Resultados: La búsqueda inicial identificó 142 estudios. De estos, 4 aleatorizados y controlados fueron elegidos para el análisis cuantitativo, incluyendo un total de 310 pacientes (154 G-CSF y 156 SMT). Se objetivó un alto grado de heterogeneidad entre los estudios (I2 = 74%, Chi 2 = 11.57, p = 0.009). La administración de G-CSF no aumentó la supervivencia en el grupo de pacientes con ACLF (modelo de efectos aleatorios, risk ratio = 0.64 [95% CI 0.39, 1.07]). Sin embargo, cuando se analizó el subgrupo de estudios realizados en Asia, sí se objetivó una disminución significativa de la mortalidad (risk ratio = 0.53 [95% CI 0.35, 0.81]). Las escalas de gravedad (MELD y Child) y la movilización de células CD34+ periféricas no mejoró significativamente tras la administración de G-CSF....(AU)

Granulocyte-colony stimulating factor in acute-on-chronic liver failure: Systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: A dysfunctional immune response is key to the pathogenesis of acute-on-chronic liver failure (ACLF). It has been suggested that treatment with granulocyte colony-stimulating factor (G-CSF) increases survival in patients with ACLF by improving immune cell dysfunction and promoting liver regeneration. The aim of the study is to evaluate the survival benefit associated with G-CSF administration compared with standard medical therapy (SMT) in ACLF. METHODS: Systematic review and meta-analysis of randomized controlled trials. The primary outcome was survival at 60-90 days. We searched Ovid Medline, EMBASE, and Cochrane Central Register of Controlled Trials from inception to August 2021. Manual searches of reference lists in relevant articles and conference proceedings were also included. The revised Cochrane risk-of-bias tool was used for quality and risk of bias assessment. Two independent investigators extracted the data, and disagreements were solved by a third collaborator. RESULTS: The initial search identified 142 studies. Four randomized controlled trials were selected for quantitative analysis including 310 patients (154 G-CSF and 156 SMT). Significant heterogeneity was observed (I2=74%, Chi2=11.57, p=0.009). G-CSF administration did not improve survival in patients with ACLF (random-effects model, risk ratio=0.64 [95% CI 0.39, 1.07]). However, when considering only the results from the studies performed in Asia, a significant decrease on mortality was observed (risk ratio=0.53 [95% CI 0.35, 0.81]). Severity scores (MELD and Child) and CD34+ peripheral cells mobilization did not significantly improve with G-CSF. CONCLUSION: In a systematic review and meta-analysis, G-CSF administration did not significantly improve overall survival compared to SMT in patients with ACLF. The beneficial effects observed in Asian studies, as opposed to the European region, suggest that specific populations may benefit from further research aiming to identify certain subgroups with favourable outcomes when using G-CSF.

Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis.

BACKGROUND: Early aggressive hydration is widely recommended for the management of acute pancreatitis, but evidence for this practice is limited. METHODS: At 18 centers, we randomly assigned patients who presented with acute pancreatitis to receive goal-directed aggressive or moderate resuscitation with lactated Ringer's solution. Aggressive fluid resuscitation consisted of a bolus of 20 ml per kilogram of body weight, followed by 3 ml per kilogram per hour. Moderate fluid resuscitation consisted of a bolus of 10 ml per kilogram in patients with hypovolemia or no bolus in patients with normovolemia, followed by 1.5 ml per kilogram per hour in all patients in this group. Patients were assessed at 12, 24, 48, and 72 hours, and fluid resuscitation was adjusted according to the patient's clinical status. The primary outcome was the development of moderately severe or severe pancreatitis during the hospitalization. The main safety outcome was fluid overload. The planned sample size was 744, with a first planned interim analysis after the enrollment of 248 patients. RESULTS: A total of 249 patients were included in the interim analysis. The trial was halted owing to between-group differences in the safety outcomes without a significant difference in the incidence of moderately severe or severe pancreatitis (22.1% in the aggressive-resuscitation group and 17.3% in the moderate-resuscitation group; adjusted relative risk, 1.30; 95% confidence interval [CI], 0.78 to 2.18; P = 0.32). Fluid overload developed in 20.5% of the patients who received aggressive resuscitation and in 6.3% of those who received moderate resuscitation (adjusted relative risk, 2.85; 95% CI, 1.36 to 5.94, P = 0.004). The median duration of hospitalization was 6 days (interquartile range, 4 to 8) in the aggressive-resuscitation group and 5 days (interquartile range, 3 to 7) in the moderate-resuscitation group. CONCLUSIONS: In this randomized trial involving patients with acute pancreatitis, early aggressive fluid resuscitation resulted in a higher incidence of fluid overload without improvement in clinical outcomes. (Funded by Instituto de Salud Carlos III and others; WATERFALL ClinicalTrials.gov number, NCT04381169.).

Anti-Hu-mediated paraneoplastic chronic intestinal pseudo-obstruction associated with extraskeletal myxoid chondrosarcoma.

Chronic intestinal pseudo-obstruction (CIPO) is characterized by symptoms and signs of bowel obstruction in the absence of an anatomical cause. Almost 50 % of cases are secondary to systemic diseases of neurological, paraneoplastic, autoimmune, metabolic, or infectious origin.