Prehospital Recognition and Management of Pediatric Sepsis: A Qualitative Assessment.

Background And Purpose: Sepsis is a life-threatening disease in children and is a leading cause of morbidity and mortality. Early prehospital recognition and management of children with sepsis may have significant effects on the timely resuscitation of this high-risk clinical condition. However, the care of acutely ill and injured children in the prehospital setting can be challenging.

Implementation of an Automated Sepsis Screening Tool in a Children's Hospital Emergency Department: A Cost Analysis.

Objective: To determine the effect of implementation of an automated sepsis screening tool on the median cost of affected patient encounters.

Study Design: This retrospective cohort study used propensity score-matched comparison groups to assess the difference in median cost for comparable affected patient encounters before and after the implementation of an automated sepsis screening tool in a large US children's hospital emergency department (ED) with >90 000 annual visits. All patient encounters in 2018 impacted by the automated sepsis screening tool were included and compared with a propensity score-matched comparison group drawn from patient encounters in 2012 that might have been affected by the screening tool had it been active at that time.

Association Between the First-Hour Intravenous Fluid Volume and Mortality in Pediatric Septic Shock.

Study Objective: To determine whether the receipt of more than or equal to 30 mL/kg of intravenous fluid in the first hour after emergency department (ED) arrival is associated with sepsis-attributable mortality among children with hypotensive septic shock.

Methods: This is a retrospective cohort study set in 57 EDs in the Improving Pediatric Sepsis Outcomes quality improvement collaborative. Patients less than 18 years of age with hypotensive septic shock who received their first intravenous fluid bolus within 1 hour of arrival at the ED were propensity-score matched for probability of receiving more than or equal to 30 mL/kg in the first hour.

Comparison of children receiving emergent sepsis care by mode of arrival.

Objective: To determine if differences in patient characteristics, treatments, and outcomes exist between children with sepsis who arrive by emergency medical services (EMS) versus their own mode of transport (self-transport).

Methods: Retrospective cohort study of patients who presented to the Emergency Department (ED) of two large children's hospitals and treated for sepsis from November 2013 to June 2017. Presentation, ED treatment, and outcomes, primarily time to first bolus and first parental antibiotic, were compared between those transported via EMS versus patients who were self-transported.

Coming Together to Save Babies: Our Institution's Quality Improvement Collaborative to Improve Infant Safe Sleep Practices.

Unlabelled: Many hospitalized infants are not observed in an American Academy of Pediatrics-recommended safe sleep environment, which can translate to unsafe sleep practices at home. We implemented this collaborative to reduce our county's sleep-related death rate by improving infant safe sleep practices in the freestanding children's hospital setting and increasing safe sleep screening and education in our clinics and emergency departments (EDs).

Methods: Physicians from our institution's primary care clinics, EDs, neonatal intensive care units, and general inpatient units created and led multidisciplinary safe sleep teams.

Discovery of a class of highly potent Janus Kinase 1/2 (JAK1/2) inhibitors demonstrating effective cell-based blockade of IL-13 signaling.

Disruption of interleukin-13 (IL-13) signaling with large molecule antibody therapies has shown promise in diseases of allergic inflammation. Given that IL-13 recruits several members of the Janus Kinase family (JAK1, JAK2, and TYK2) to its receptor complex, JAK inhibition may offer an alternate small molecule approach to disrupting IL-13 signaling. Herein we demonstrate that JAK1 is likely the isoform most important to IL-13 signaling.

Lung-restricted inhibition of Janus kinase 1 is effective in rodent models of asthma.

Preclinical and clinical evidence indicates that a subset of asthma is driven by type 2 cytokines such as interleukin-4 (IL-4), IL-5, IL-9, and IL-13. Additional evidence predicts pathogenic roles for IL-6 and type I and type II interferons. Because each of these cytokines depends on Janus kinase 1 (JAK1) for signal transduction, and because many of the asthma-related effects of these cytokines manifest in the lung, we hypothesized that lung-restricted JAK1 inhibition may confer therapeutic benefit.

Automating a Manual Sepsis Screening Tool in a Pediatric Emergency Department.

Objective: This article describes the method of integrating a manual pediatric emergency department sepsis screening process into the electronic health record that leverages existing clinical documentation and keeps providers in their current, routine clinical workflows.

Methods: Criteria in the manual pediatric emergency department sepsis screening tool were mapped to standard documentation routinely entered in the electronic health record. Data elements were extracted and scored from the medical history, medication record, vital signs, and physical assessments.

Lethal aggression in Pan is better explained by adaptive strategies than human impacts.

Observations of chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) provide valuable comparative data for understanding the significance of conspecific killing. Two kinds of hypothesis have been proposed. Lethal violence is sometimes concluded to be the result of adaptive strategies, such that killers ultimately gain fitness benefits by increasing their access to resources such as food or mates.

Identification and optimisation of a series of substituted 5-pyridin-2-yl-thiophene-2-hydroxamic acids as potent histone deacetylase (HDAC) inhibitors.

Further investigation of a series of thienyl-based hydroxamic acids that included ADS100380 and ADS102550 led to the identification of the 5-pyridin-2-yl-thiophene-2-hydroxamic acid 3c, which possessed modest HDAC inhibitory activity. Substitution at the 5- and 6-positions of the pyridyl ring of compound 3c provided compounds 5a-g, 7a, b, 9, and 13a. Compound 5b demonstrated improved potency, in vitro DMPK profile, and rat oral bioavailability, compared to ADS102550.

Identification and optimisation of a series of substituted 5-(1H-pyrazol-3-yl)-thiophene-2-hydroxamic acids as potent histone deacetylase (HDAC) inhibitors.

Optimisation of ADS100380, a sub-micromolar HDAC inhibitor identified using a virtual screening approach, led to a series of substituted 5-(1H-pyrazol-3-yl)-thiophene-2-hydroxamic acids (6a-i), that possessed significant HDAC inhibitory activity. Subsequent functionalisation of the pendent phenyl group of compounds 6f and 6g provided analogues 6j-w with further enhanced enzyme and anti-proliferative activity. Compound 6j demonstrated efficacy in a mouse xenograft experiment.

Identification of early-stage colorectal cancer patients at risk of relapse post-resection by immunobead reverse transcription-PCR analysis of peritoneal lavage fluid for malignant cells.

Purpose: Colorectal cancer patients diagnosed with stage I or II disease are not routinely offered adjuvant chemotherapy following resection of the primary tumor. However, up to 10% of stage I and 30% of stage II patients relapse within 5 years of surgery from recurrent or metastatic disease. The aim of this study was to determine if tumor-associated markers could detect disseminated malignant cells and so identify a subgroup of patients with early-stage colorectal cancer that were at risk of relapse.

Detection of occult metastasis in lymph nodes from colorectal cancer patients: a multiple-marker reverse transcriptase-polymerase chain reaction study.

Introduction: Lymph node status is a key factor for disease staging and is the main determinant for adjuvant therapy of colorectal cancer. The current staging procedure is unable to identify occult metastasis in lymph nodes, which is likely to be an important cause of treatment failure in some early-stage patients. The detection of occult metastasis could identify a patient subgroup at risk for disease relapse that would benefit from adjuvant therapy.