Clinical Reasoning Behind Antibiotic Use in PICUs: A Qualitative Study.

Objectives: To describe the reasoning processes used by pediatric intensivists to make antibiotic-related decisions.

Design: Grounded theory qualitative study.

Setting: Three Canadian university-affiliated tertiary medical, surgical, and cardiac PICUs.

Strategies for the Prevention and Treatment of Iatrogenic Withdrawal from Opioids and Benzodiazepines in Critically Ill Neonates, Children and Adults: A Systematic Review of Clinical Studies.

Background: Critically ill patients are at high risk of iatrogenic withdrawal syndrome (IWS), due to exposure to high doses or prolonged periods of opioids and benzodiazepines.

Purpose: To examine pharmacological management strategies designed to prevent and/or treat IWS from opioids and/or benzodiazepines in critically ill neonates, children and adults.

Methods: We included non-randomised studies of interventions (NRSI) and randomised controlled trials (RCTs), reporting on interventions to prevent or manage IWS in critically ill neonatal, paediatric and adult patients.

The impact of a quality improvement project to standardize pain, agitation, and withdrawal assessments on the use of morphine and midazolam in the Pediatric Intensive Care Unit.

Background: This study aims to assess the impact of a quality improvement initiative to increase assessments of pain, agitation, and iatrogenic withdrawal syndrome, on the use of sedative and analgesic medication in a pediatric intensive care unit.

Methods: This is a retrospective pre and post, observational, quality improvement study conducted in an 18-bed medical-surgical-cardiac, tertiary intensive care unit. We included patients consecutively admitted from October 1 to March 31 (pre-period 2015-2016, post-period 2016-2017) who were mechanically ventilated beyond 48 hours.

Frequency, risk factors and symptomatology of iatrogenic withdrawal from opioids and benzodiazepines in critically Ill neonates, children and adults: A systematic review of clinical studies.

What Is Known And Objective: Many critically ill patients are exposed to opioids and benzodiazepines at high doses for prolonged periods, and upon discontinuation of these drugs, they may be at risk for iatrogenic withdrawal. Although this syndrome was associated with worse outcomes in the critically ill, limited guidance exists regarding its evaluation, prevention and treatment. This systematic review examined the frequency, risk factors and symptomatology of iatrogenic withdrawal from opioids and/or benzodiazepines in critically ill neonates, children and adults.

Ability to Assent in Pediatric Critical Care Research: A Prospective Environmental Scan of Two Canadian PICUs.

Objectives: To determine the number of patients considered not appropriate to approach for assent within the first 24 hours of PICU admission.

Design: Exploratory prospective 1-month environmental scan.

Setting: Two tertiary Canadian PICUs.

The Interleukin (IL)-1R1 pathway is a critical negative regulator of PyMT-mediated mammary tumorigenesis and pulmonary metastasis.

Breast cancer is the most common cancer in women and the second leading cause of female cancer-related deaths worldwide. Inflammation is an established hallmark of tumorigenesis and an important determinant of tumor outcome and response to therapy. With advances in cancer immunotherapy, there is an urgent need to dissect the contribution of specific immune effectors in cancer development.

Linking cancer-induced Nlrp3 inflammasome activation to efficient NK cell-mediated immunosurveillance.

We have recently demonstrated that the Nlrp3 inflammasome can detect the presence of colorectal cancer (CRC) metastatic growth in the liver and limit its growth. Inflammasome signaling primed natural killer (NK) cells through Interleukin (IL)-18 and activated their ability to trigger FasL-induced apoptosis of the tumor.

The Nlrp3 Inflammasome Suppresses Colorectal Cancer Metastatic Growth in the Liver by Promoting Natural Killer Cell Tumoricidal Activity.

The crosstalk between inflammation and tumorigenesis is now clearly established. However, how inflammation is elicited in the metastatic environment and the corresponding contribution of innate immunity pathways in suppressing tumor growth at secondary sites are poorly understood. Here, we show that mice deficient in Nlrp3 inflammasome components had exacerbated liver colorectal cancer metastatic growth, which was mediated by impaired interleukin-18 (IL-18) signaling.

Role of programmed necrosis and cell death in intestinal inflammation.

Purpose Of Review: To critically review recent advances on the role of programmed necrosis and other cell death modalities in intestinal health and inflammatory bowel disease.

Recent Findings: Tight regulation of intestinal epithelial cell proliferation and cell death is required for intestinal physiology, and to maintain an integral barrier that restricts microbiota translocation and ensures immune tolerance. Apoptosis has long been considered as a normal part of intestinal epithelial cell turnover.

Cellular inhibitor of apoptosis protein cIAP2 protects against pulmonary tissue necrosis during influenza virus infection to promote host survival.

Cellular inhibitors of apoptosis proteins (cIAPs) are essential regulators of cell death and immunity. The corresponding contributions of IAPs to infectious disease outcomes are relatively unexplored. We find that mice deficient in cIAP2 exhibit increased susceptibility and mortality to influenza A virus infection.

Crosstalk between the intestinal microbiota and the innate immune system in intestinal homeostasis and inflammatory bowel disease.

: Inflammatory bowel diseases are a set of complex and chronic disorders that arise in genetically predisposed individuals due to a lack of tolerance to the gut microflora. Although the intestinal microbiota is required for the proper development of the host and the maintenance of intestinal homeostasis, its dysbiosis is associated with inflammatory bowel diseases pathogenesis. In this review, we focus the discussion on the crosstalk between the innate immune system and the microbiota.

Function of NOD-like receptors in immunity and disease.

Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are cytosolic pattern-recognition receptors that sense microbial invasion, cell stress and physiological perturbations, and elicit an inflammatory response to alert the system to the presence of danger. Most NLRs exert their functions by assembling inflammasomes that recruit and activate caspase-1, whereas a few engage the NFκB and MAPK pathways. In the past few years, significant insights have been gained into the regulatory mechanisms of these innate immunity effectors and their role in health and disease that, notably, have led to direct therapeutic applications in the clinic.