Changes in intestinal immune system after training and exhausting physical exercise in rats

Podeu consultar el III Workshop anual INSA-UB complet a: http://hdl.handle.net/2445/118993Sessió 1. Pòster núm.

N-3 PUFA Supplementation Triggers PPAR-α Activation and PPAR-α/NF-κB Interaction: Anti-Inflammatory Implications in Liver Ischemia-Reperfusion Injury

Dietary supplementation with the n-3 polyunsaturated fatty acids (n-3 PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to rats preconditions the liver against ischemia-reperfusion (IR) injury, with reduction of the enhanced nuclear factor-κB (NF-κB) functionality occurring in the early phase of IR injury, and recovery of IR-induced pro-inflammatory cytokine response. The aim of the present study was to test the hypothesis that liver preconditioning by n-3 PUFA is exerted through peroxisone proliferator-activated receptor α (PPAR-α) activation and interference with NF-κB activation. For this purpose we evaluated the formation of PPAR-α/NF-κBp65 complexes in relation to changes in PPAR-α activation, IκB-α phosphorylation and serum levels and expression of interleukin (IL)-1β and tumor necrosis factor (TNF)-α in a model of hepatic IR-injury (1 h of ischemia and 20 h of reperfusion) or sham laparotomy (controls) in male Sprague Dawley rats. Animals were previously supplemented for 7 days with encapsulated fish oil (General Nutrition Corp., Pittsburg, PA) or isovolumetric amounts of saline (controls). Normalization of IR-altered parameters of liver injury (serum transaminases and liver morphology) was achieved by dietary n-3 PUFA supplementation. EPA and DHA suppression of the early IR-induced NF-κB activation was paralleled by generation of PPAR-α/NF-κBp65 complexes, in concomitance with normalization of the IR-induced IκB-α phosphorylation. PPAR-α activation by n-3 PUFA was evidenced by enhancement in the expression of the PPAR-α-regulated Acyl-CoA oxidase (Acox) and Carnitine-Palmitoyl-CoA transferase I (CPT-I) genes. Consistent with these findings, normalization of IR-induced expression and serum levels of NF-κB-controlled cytokines IL-lβ and TNF-α was observed at 20 h of reperfusion. Taken together, these findings point to an antagonistic effect of PPAR-α on NF-κB-controlled transcription of pro-inflammatory mediators. This effect is associated with the formation of PPAR-α/NF-κBp65 complexes and enhanced cytosolic IκB-α stability, as major preconditioning mechanisms induced by n-3 PUFA supplementation against IR liver injury

Endogenous Signaling by Omega-3 Docosahexaenoic Acid-derived Mediators Sustains Homeostatic Synaptic and Circuitry Integrity

The harmony and function of the complex brain circuits and synapses are sustained mainly by excitatory and inhibitory neurotransmission, neurotrophins, gene regulation, and factors, many of which are incompletely understood. A common feature of brain circuit components, such as dendrites, synaptic membranes, and other membranes of the nervous system, is that they are richly endowed in docosahexaenoic acid (DHA), the main member of the omega-3 essential fatty acid family. DHA is avidly retained and concentrated in the nervous system and known to play a role in neuroprotection, memory, and vision. Only recently has it become apparent why the surprisingly rapid increases in free (unesterified) DHA pool size take place at the onset of seizures or brain injury. This phenomenon began to be clarified by the discovery of neuroprotectin D1 (NPD1), the first-uncovered bioactive docosanoid formed from free DHA through 15-lipoxygenase-1 (15-LOX-1). NPD1 synthesis includes, as agonists, oxidative stress and neurotrophins. The evolving concept is that DHA-derived docosanoids set in motion endogenous signaling to sustain homeostatic synaptic and circuit integrity. NPD1 is anti-inflammatory, displays inflammatory resolving activities, and induces cell survival, which is in contrast to the pro-inflammatory actions of the many of omega-6 fatty acid family members. We highlight here studies relevant to the ability of DHA to sustain neuronal function and protect synapses and circuits in the context of DHA signalolipidomics. DHA signalolipidomics comprises the integration of the cellular/tissue mechanism of DHA uptake, its distribution among cellular compartments, the organization and function of membrane domains containing DHA phospholipids, and the precise cellular and molecular events revealed by the uncovering of signaling pathways regulated by docosanoids endowed with prohomeostatic and cell survival bioactivity. Therefore, this approach offers emerging targets for prevention, pharmaceutical intervention, and clinical translation involving DHA-mediated signaling

Cost-Effectiveness Mathematical Model to Evaluate the Impact of Improved Cardiac Ablation Strategies for Atrial Fibrillation Treatment

Atrial fibrillation (AF) is the most common form of cardiac arrhythmia. Despite the frequency of the disease, the treatment strategies for AF are inefficient. We developed a cost-effectiveness model to evaluate potential improvements in the application of cardiac ablations to treat AF. These are surgical procedures to terminate the arrhythmia and restore Sinus Rhythm. A Markov Model with a time horizon of five years was built to represent the management of patients in AF. A Montecarlo simulation was developed as a sensitivity analysis when the effectiveness increases the estimate of the potential impact of an improvement on the efficacy of cardiac ablation. The result of the analysis showed 44% of patients were untreated in any way. The base case ends up with 45% of patients having sinus rhythm restored after five years. The Montecarlo simulation estimates that in 58% of cases, the alternative of increasing ablation effectiveness by 25% would be cost-effective. If the number of performed ablations is doubled, the robustness increases to 86%. In conclusion, the model of management of AF highlights the importance of not only increasing effectiveness, but also treating more patients. Our study shows that investing in new screening technology to increase the effectiveness of ablations would be cost-effective

Clinical case report: endoluminal thermal ablation of main pancreatic duct for patients at high risk of postoperative pancreatic fistula after pancreaticoduodenectomy

Purpose: Multiple attempts have been made to manage the pancreatic stump and the pancreatic duct in order to reduce the rate of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD), however radiofrequency-based technologies could help to achieve this goal. Previous encouraging clinical and experimental results support the use of endoluminal thermal ablation (ETHA) of the main pancreatic duct to reduce pancreatic exocrine secretion and hence POPF. We here describe our initial clinical experience with ETHA of the main pancreatic duct in two cases at high risk of POPF. Methods: Two cases underwent PD for malignancy with a high risk of POPF (adenocarcinoma, obese patients, surgical difficulties with heavy intraoperative blood loss, soft pancreas or walled-off pancreatitis and a tight small pancreatic main duct). In both cases, ETHA of the main pancreatic duct was conducted intraoperatively just before Blumgart-type pancreatic-jejunal anastomosis using a ClosureFast catheter (Medtronic, Mansfield, MA, USA) normally used for varicose vein treatment (therefore an off-label use). Results: Although a clear radiological POPF was detected in the second case, the clinical postoperative course in both cases was uneventful. Little pancreatic fluid collected in the abdominal drainage with low levels of amylase enzyme, confirming low exocrine pancreatic function. No other procedure-related complications were detected. Conclusion: Endoluminal thermal ablation of the main pancreatic duct may be a feasible and safe technique to reduce the adverse effects of POPF after PD.This work was supported by the Spanish Ministerio de Ciencia, Innovación y Universidades under “Programa Estatal de I + D + i Orientada a los Retos de la Sociedad”, Grants RTI2018-094357-B-C21 and RTI2018-094357-B-C22

Changes in intestinal immune system after training and exhausting physical exercise in rats

Podeu consultar el III Workshop anual INSA-UB complet a: http://hdl.handle.net/2445/118993Sessió 1. Pòster núm.

Changes in intestinal immune system after training and exhausting physical exercise in rats

Podeu consultar el III Workshop anual INSA-UB complet a: http://hdl.handle.net/2445/118993Sessió 1. Pòster núm.

KRAS assessment following ESMO recommendations for colorectal liver metastases. Is it always worth it?

Background: Genetic evaluation is essential in assessing colorectal cancer (CRC) and colorectal liver metastasis (CRLM). The aim of this study was to determine the pragmatic value of KRAS on oncological outcomes after CRLM according to the ESMO recommendations and to query whether it is necessary to request KRAS testing in each situation. Methods: A retrospective cohort of 126 patients who underwent surgery for hepatic resection for CRLM between 2009 and 2020 were reviewed. The patients were divided into three categories: wild-type KRAS, mutated KRAS and impractical KRAS according to their oncological variables. The impractical (not tested) KRAS group included patients with metachronous tumours and negative lymph nodes harvested. Disease-free survival (DFS), overall survival (OS) and hepatic recurrence-free survival (HRFS) were calculated by the Kaplan-Meier method, and a multivariable analysis was conducted using the Cox proportional hazards regression model. Results: Of the 108 patients identified, 35 cases had KRAS wild-type, 50 cases had a KRAS mutation and the remaining 23 were classified as impractical KRAS. Significantly longer medians for OS, HRFS and DFS were found in the impractical KRAS group. In the multivariable analyses, the KRAS mutational gene was the only variable that was maintained through OS, HRFS and DFS. For HRFS (HR: 13.63; 95% confidence interval (CI): 1.35-100.62; p = 0.010 for KRAS), for DFS (HR: 10.06; 95% CI: 2.40-42.17; p = 0.002 for KRAS) and for OS (HR: 4.55%; 95% CI: 1.37-15.10; p = 0.013). Conclusion: Our study considers the possibility of unnecessary KRAS testing in patients with metachronous tumours and negative lymph nodes harvested. Combining the genetic mutational profile (i.e., KRAS in specific cases) with tumour characteristics helps patient selection and achieves the best prognosis after CRLM resection

Creation and implementation of a European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC registry)

International patient registries are of particular importance for rare disorders, as they may contribute to overcome the lack of knowledge derived from low number of patients and limited awareness of these diseases, and help to learn more about their geographical or population-based specificities, which is relevant for research purposes and for promoting better standards of care and diagnosis. Our objective was to create and implement a European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC) and to disseminate the knowledge of these disorders. Teams from nine different countries (United Kingdom, Spain, Italy, France, Germany, Denmark, Greece, Turkey and USA) created a consortium that developed the first European registry dedicated to rare muscle glycogenoses. A work plan was implemented to design the database and platform that constitute the registry, by choosing clinical, genetics and molecular variables of interest, based on experience gained from previous national registries for similar metabolic disorders. Among dissemination activities, several teaching events were organized in different countries, especially those where the consortium considered the awareness of these diseases needs to be promoted among health professionals and patients. EUROMAC represents a step forward in the knowledge of those disorders to which it is dedicated, and will have relevant clinical outcomes at the diagnostic, epidemiological, clinical and research leve

The impact of additional margin coagulation with radiofrequency in liver resections with subcentimetric margin: can we improve the oncological results? A propensity score matching study

Background: Whereas the usefulness of radiofrequency (RF) energy as haemostatic method in liver surgery has become well established in the last decades, its intentional application on resection margins with the aim of reducing local recurrence is still debatable. Our goal was to compare the impact of an additional application of RF energy on the top of the resection surface, namely additional margin coagulation (AMC), on local recurrence (LR) when subjected to a subcentimeter margin. Methods: We retrospectively analyzed 185 patients out of a whole cohort of 283 patients who underwent radical hepatic resection with subcentimetric margin. After propensity score adjustment, patients were classified into two balanced groups according to whether RF was applied or not. Results: No significant differences were observed within groups in baseline characteristics after PSM adjustment. The LR rate was significantly higher in the Control than AMC Group: 12 patients (14.5%) vs. 4 patients (4.8%) (p = 0.039). The estimated 1, 3, and 5-year LR-free survival rates of patients in the Control and AMC Group were: 93.5%, 86.0%, 81.0% and 98.8%, 97.2%, 91.9%, respectively (p = 0.049). Univariate Cox analyses indicated that the use of the RF applicator was significantly associated with lower LR (HR = 0.29, 95% confidence interval 0.093-0.906, p = 0.033). The Control Group showed smaller coagulation widths than the AMC group (p < 0.001). Conclusions: An additional application of RF on the top of the resection surface is associated with less local hepatic recurrence than the use of conventional techniques.This work was partially supported by the Spanish Ministerio de Ciencia, Innovación y Universidades under “Programa Estatal de I+D+i Orientada a los Retos de la Sociedad”, Grants Nº “ RTI2018-094357-B-C21 ” and “ RTI2018-094357-B-C22”