Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

"Neuroimmunomodulation in Major Depressive Disorder: Focus on Caspase 1, Inducible Nitric Oxide Synthase, and Interferon-Gamma"

"Major depressive disorder (MDD) is one of the leading causes of disability worldwide, and its incidence is expected to increase. Despite tremendous efforts to understand its underlying biological mechanisms, MDD pathophysiology remains elusive and pharmacotherapy outcomes are still far from ideal. Low-grade chronic inflammation seems to play a key role in mediating the interface between psychological stress, depressive symptomatology, altered intestinal microbiology, and MDD onset. We review the available pre-clinical and clinical evidence of an involvement of pro-inflammatory pathways in the pathogenesis, treatment, and remission of MDD. We focus on caspase 1, inducible nitric oxide synthase, and interferon gamma, three inflammatory systems dysregulated in MDD. Treatment strategies aiming at targeting such pathways alone or in combination with classical therapies could prove valuable in MDD. Further studies are needed to assess the safety and efficacy of immune modulation in MDD and other psychiatric disorders with neuroinflammatory components. © 2018, The Author(s).

Neuroimmunomodulation in Major Depressive Disorder: Focus on Caspase 1, Inducible Nitric Oxide Synthase, and Interferon-Gamma

Major depressive disorder (MDD) is one of the leading causes of disability worldwide, and its incidence is expected to increase. Despite tremendous efforts to understand its underlying biological mechanisms, MDD pathophysiology remains elusive and pharmacotherapy outcomes are still far from ideal. Low-grade chronic inflammation seems to play a key role in mediating the interface between psychological stress, depressive symptomatology, altered intestinal microbiology, and MDD onset. We review the available pre-clinical and clinical evidence of an involvement of pro-inflammatory pathways in the pathogenesis, treatment, and remission of MDD. We focus on caspase 1, inducible nitric oxide synthase, and interferon gamma, three inflammatory systems dysregulated in MDD. Treatment strategies aiming at targeting such pathways alone or in combination with classical therapies could prove valuable in MDD. Further studies are needed to assess the safety and efficacy of immune modulation in MDD and other psychiatric disorders with neuroinflammatory components. © 2018, The Author(s)

Leptin : Role over central nervous system in epilepsy

Adipose tissue is a dynamic organ with different effects on the body. Many of these effects are mediated by leptin, a hormone strongly involved in regulation of feeding and energy metabolism. It has an important role as a mediator of neuronal excitatory activity and higher brain functions. The aim of this study was to review the association between leptin and cerebral neuronal function, in particular its anticonvulsant or convulsant effects and the possible therapeutic role for treating epilepsy. For this purpose, the databases Pubmed, Science Direct, Elsevier, ResearchGate and Scielo were searched to identify experimental studies, reviews and systematic review articles, published in English, Spanish or Portuguese. Experimental studies and the presence of leptin receptors in nervous system sites other than the hypothalamus suggest an influence on higher brain functions. Indeed several animal studies have demonstrated a role of these channels in epileptiform activity as both anticonvulsive and convulsive effects have been found. The reason for these discrepancies is unclear but provides clear evidence of a potential role of leptin and leptin therapy in epileptiform activity. The association between leptin and brain function demonstrates the importance of peripheral metabolic hormones on central nervous system and opens a new way for the development of novel therapeutic interventions in diseases like epilepsy. Nevertheless further investigations are important to clarify the dynamics and diverse actions of leptin on excitatory regulation in the brain. © 2018 The Author(s)

Leptin : Role over central nervous system in epilepsy

Adipose tissue is a dynamic organ with different effects on the body. Many of these effects are mediated by leptin, a hormone strongly involved in regulation of feeding and energy metabolism. It has an important role as a mediator of neuronal excitatory activity and higher brain functions. The aim of this study was to review the association between leptin and cerebral neuronal function, in particular its anticonvulsant or convulsant effects and the possible therapeutic role for treating epilepsy. For this purpose, the databases Pubmed, Science Direct, Elsevier, ResearchGate and Scielo were searched to identify experimental studies, reviews and systematic review articles, published in English, Spanish or Portuguese. Experimental studies and the presence of leptin receptors in nervous system sites other than the hypothalamus suggest an influence on higher brain functions. Indeed several animal studies have demonstrated a role of these channels in epileptiform activity as both anticonvulsive and convulsive effects have been found. The reason for these discrepancies is unclear but provides clear evidence of a potential role of leptin and leptin therapy in epileptiform activity. The association between leptin and brain function demonstrates the importance of peripheral metabolic hormones on central nervous system and opens a new way for the development of novel therapeutic interventions in diseases like epilepsy. Nevertheless further investigations are important to clarify the dynamics and diverse actions of leptin on excitatory regulation in the brain. © 2018 The Author(s)

Temporal gene expression in the hippocampus and peripheral organs to endotoxin-induced systemic inflammatory response in caspase-1-deficient mice

Objectives: Caspase-1 (casp1), a key protease involved in the systemic inflammatory response syndrome (SIRS), controls the brain expression of a set of eight genes: Nos2 and Ptgs2 (nitric oxide synthase 2 and prostaglandin-endoperoxide synthase 2, two inducible enzymes), Cxcl1 and Cxcl10 (C-X-C motif chemokine ligand 1 and ligand 10), Tgtp and Gbp2 (T cell-specific GTPase 1 and guanylate-binding protein 2, two GTPases), Adamts1 (a disintegrin-like and metallopeptidase with thrombospondin type 1 motif, 1, a metalloprotease) and Il1rn (interleukin-1 receptor antagonist). Our objective was to ascertain whether casp1 also controlled the peripheral expression of these genes and, if so, to compare their central versus peripheral patterns of gene expression in immune and endocrine tissues during SIRS. Methods: Wild-type (wt) and casp1 knockout (casp1-/-) mice were injected with either saline or a high dose of endotoxin/lipopolysaccharide (LPS; 800 ?g/mice i.p.). Saline-injected mice were immediately euthanized after injection, whereas LPS-injected mice were sacrificed 6 and 12 h after LPS administration. Hippocampal, splenic and adrenal gene expressions were determined by real-time PCR. Results: Overall, casp1-/- mice showed a lower inflammatory response than wt mice. The expression levels of powerful proinflammatory factors such as Nos2 and Ptgs2 was reduced in casp1-/- mice. Moreover, a hierarchical clustering analysis aimed at studying patterns of gene coexpression revealed large alterations in the hippocampal pattern of casp1-/- mice. Surprisingly, the expression of Adamts1 was increased in the hippocampus and adrenals of casp1-/- mice. Conclusions: The resilience of casp1-/- mice to SIRS lethality is associated with a lower inflammatory response, loss of hippocampal gene coexpression patterns, and increased hippocampal Adamts1 gene expression. The latter might be beneficial for casp1-/- mice, since ADAMTS1 is likely to play a role in neuronal plasticity. The mechanisms described here may help the development of either novel biomarkers or therapeutic targets against SIRS/sepsis. © 2015 S. Karger AG, Basel

Temporal gene expression in the hippocampus and peripheral organs to endotoxin-induced systemic inflammatory response in caspase-1-deficient mice

Objectives: Caspase-1 (casp1), a key protease involved in the systemic inflammatory response syndrome (SIRS), controls the brain expression of a set of eight genes: Nos2 and Ptgs2 (nitric oxide synthase 2 and prostaglandin-endoperoxide synthase 2, two inducible enzymes), Cxcl1 and Cxcl10 (C-X-C motif chemokine ligand 1 and ligand 10), Tgtp and Gbp2 (T cell-specific GTPase 1 and guanylate-binding protein 2, two GTPases), Adamts1 (a disintegrin-like and metallopeptidase with thrombospondin type 1 motif, 1, a metalloprotease) and Il1rn (interleukin-1 receptor antagonist). Our objective was to ascertain whether casp1 also controlled the peripheral expression of these genes and, if so, to compare their central versus peripheral patterns of gene expression in immune and endocrine tissues during SIRS. Methods: Wild-type (wt) and casp1 knockout (casp1-/-) mice were injected with either saline or a high dose of endotoxin/lipopolysaccharide (LPS; 800 ?g/mice i.p.). Saline-injected mice were immediately euthanized after injection, whereas LPS-injected mice were sacrificed 6 and 12 h after LPS administration. Hippocampal, splenic and adrenal gene expressions were determined by real-time PCR. Results: Overall, casp1-/- mice showed a lower inflammatory response than wt mice. The expression levels of powerful proinflammatory factors such as Nos2 and Ptgs2 was reduced in casp1-/- mice. Moreover, a hierarchical clustering analysis aimed at studying patterns of gene coexpression revealed large alterations in the hippocampal pattern of casp1-/- mice. Surprisingly, the expression of Adamts1 was increased in the hippocampus and adrenals of casp1-/- mice. Conclusions: The resilience of casp1-/- mice to SIRS lethality is associated with a lower inflammatory response, loss of hippocampal gene coexpression patterns, and increased hippocampal Adamts1 gene expression. The latter might be beneficial for casp1-/- mice, since ADAMTS1 is likely to play a role in neuronal plasticity. The mechanisms described here may help the development of either novel biomarkers or therapeutic targets against SIRS/sepsis. © 2015 S. Karger AG, Basel

Divulgación Científica No.2

La Universidad del Rosario lidera, con acierto, diferentes temas de investigación desde los enfoques de cada una de las disciplinas que conforman la universidad, con miradas que buscan integrar a la discusión lo transdisciplinar y multidisciplinar. Los saberes que circulan por cada una de sus unidades académicas constituyen el punto de partida para asumir las preguntas que motivan cada uno de los frentes de investigación, dar respuestas a los problemas que nos aquejan y proponer nuevas rutas para trasegar como sociedad. Conscientes de la necesidad de un diálogo constante y abierto con amplios sectores que garanticen un público diverso y múltiple, la Universidad del Rosario presenta el segundo número de Divulgación Científica, que al igual que el primero, cuenta, por medio del periodismo científico, los retos y las posibilidades que como institución nos planteamos para pensar nuestro mundo.The Universidad del Rosario successfully leads different research topics from the approaches of each of the disciplines that make up the university, with views that seek to integrate the transdisciplinary and multidisciplinary discussion. The knowledge that circulates through each of its academic units constitutes the starting point to assume the questions that motivate each of the research fronts, provide answers to the problems that afflict us and propose new routes to move as a society. Aware of the need for a constant and open dialogue with broad sectors that guarantee a diverse and multiple audience, the Universidad del Rosario presents the second issue of Scientific Dissemination, which, like the first, tells, through scientific journalism, the challenges and the possibilities that as an institution we consider to think about our world