N-Formyl-methionyl-leucyl-phenylalanine (fMLP) and platelet-activating factor (PAF) induce similar intracellular signalling profiles; but only fMLP induces interleukin-8 (IL-8) release and nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase activity in neutrophils. Because the role of ROS on IL-8 release in neutrophils is until now controversial, we assessed if NADPH oxidase is involved in the IL-8 secretions and PI3K/Akt, MAPK, and NF-κB pathways activity induced by fMLP. Neutrophils were obtained from healthy volunteers. IL-8 was measured by ELISA, IL-8 mRNA by qPCR, and ROS production by luminol-amplified chemiluminescence, reduction of ferricytochrome c, and FACS. Intracellular pH changes were detected by spectrofluorescence. ERK1/2, p38 MAPK, and Akt phosphorylation were analysed by immunoblotting and NF-κB was analysed by immunocytochemistry. Hydroxy-3-methoxyaceto-phenone (HMAP), diphenyleneiodonium (DPI), and siRNA Nox2 reduced the ROS and IL-8 release in neutrophils treated with fMLP. HMAP, DPI, and amiloride (a Na+/H+ exchanger inhibitor) inhibited the Akt phosphorylation and did not affect the p38 MAPK and ERK1/2 activity. DPI and HMAP reduced NF-κB translocation induced by fMLP. We showed that IL-8 release induced by fMLP is dependent on NADPH oxidase, and ROS could play a redundant role in cell signalling, ultimately activating the PI3K/Akt and NF-κB pathways in neutrophils.
Background
There is an increasing interest in studying the impact of altered body composition parameters and colorectal cancer (CRC) treatment outcomes. The aim of this study is to explore the impact of computed tomography (CT)‐measured visceral obesity, sarcopenia and myosteatosis on survival of non‐metastatic CRC.
Methods
Consecutive patients with stage I–III CRC who underwent curative‐intent treatment between January 2010 and December 2015 were included. By measuring the visceral fat area, and the skeletal muscle index and radiodensity in the pre‐operative staging CT, patients were classified as visceral obese, sarcopenic or myosteatotic. The associations between CT‐based body composition parameters and survival were assessed using log‐rank tests and a Cox regression analysis.
Results
Of 359 patients, 263 (73.3%) were visceral obese, 85 (23.7%) sarcopenic and 80 (22.3%) myosteatotic. Overall (OS), cancer‐specific (CSS) and disease‐free survivals (DFS) at 5 years were 78.8%, 84.7% and 75%, respectively. Myosteatosis and the combination of myosteatosis and visceral obesity were associated with a reduced DFS (hazard ratio 1.67; 95% confidence interval 1.06–2.61 and hazard ratio 1.85; 95% confidence interval 1.15–2.96, respectively). However, after performing a multivariate analysis including other relevant clinicopathological factors, none of the body composition parameters were associated with any long‐term outcome measures, even after stratifying by cancer stage.
Conclusions
CT‐measured body composition parameters do not independently influence survival in non‐metastatic CRC. There is a need for larger cohort studies with standardized patient selection and methodology to confirm these findings.
Background: Trauma is one of the leading causes of death in the world and proper surgical care is critical to impact mortality. In Chile, trauma associated death ranks first as mortality cause in population between 20 and 59 years old. Appropriate surgical skills are required to deal with these complex patients. Self-confidence to practice trauma procedures after the General Surgery Residency have not been reported in our country. Aim: Describe the level of self-confidence to deal with trauma procedures of surgeons who recently graduated from a General Surgery Residency. Method: Descriptive cross-sectional study. We designed and applied a survey in 2015, 2016 and 2017 to recently graduated surgeons, to inquire about self-confidence of surgical skills to deal with trauma scenarios. Eighteen trauma surgery procedures (including cervical, thoracic, abdominal and vascular procedures) were evaluated using a 5-grade Likert scale. The number of procedures performed during the residency was also queried. Results: Eighty-eight recently graduated surgeons from 11 different training programs in Chile were included. The report of competencies was high in procedures such as intestinal injuries, were 98% felt competent or very competent in their repair. On the other hand, in complex traumas such as major vessel injury, up to 76% reported not being competent. Self-confidence on procedures was directly associated with the number of procedures performed during residency. Conclusions: Recently graduated surgeons from General Surgery Programs report high levels of confidence to deal with low and intermediate complexity traumas, but a lower level of confidence to treat high complexity cases.
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