Hyperinflammatory syndrome resembling haemophagocytic lymphohistiocytosis following axicabtagene ciloleucel and brexucabtagene autoleucel.

Haemophagocytic lymphohistiocytosis-like toxicity following chimeric antigen receptor T cells (CAR-HLH) is being increasingly recognized, while published data are limited and criteria for recognition are elusive. We describe three patients who developed CAR-HLH after infusion of brexucabtagene autoleucel (n = 2) or axicabtagene ciloleucel (n = 1). All three patients presented following cytokine release syndrome, with fever, recurrent or worsening cytopenias, hyperferritinaemia, elevated soluble interleukin (IL)-2 receptor, hypofibrinogenaemia, hypertriglyceridaemia, elevated liver transaminases, and decreasing C-reactive protein and IL-6.

Evaluation of denosumab in adult oncology patients for the prevention of skeletal related events across a large academic health system.

Introduction: Denosumab (Xgeva) and zoledronic acid (Zometa) are widely utilized for prevention of skeletal related events (SREs) in oncology patients. Drug costs, renal function, ease and logistics of administration, and adverse effect profile are factors frequently considered by patients and/or providers when selecting an optimal agent. Given the significantly higher drug cost of denosumab compared to zoledronic acid, an evaluation of our institution's denosumab use and investigation into opportunities to shift denosumab administrations to zoledronic acid and/or to lower cost sites-of-care was warranted.

Development of a Statewide Antibiogram to Assess Regional Trends in Antibiotic-Resistant ESKAPE Organisms.

Background:: Hospitals and other facilities utilize antibiograms as tools for optimal antibiotic selection. Currently, no measures compare broad trends on the regional level, despite interest for more comprehensive data, particularly for antibiotic-resistant ESKAPE organisms.

Objective:: To collect and compare regional health-care facility antibiogram data for ESKAPE organisms to form a cumulative antibiogram.

Clinical Outcomes of Bronchiolitis After Implementation of a General Ward High Flow Nasal Cannula Guideline.

Objective: The goal of this study was to assess the association of the introduction of a ward's high-flow nasal cannula (HFNC) guideline with clinical outcomes of infants with bronchiolitis.

Methods: We conducted a retrospective, pre-post intervention study with an interrupted time series analysis of infants admitted with bronchiolitis between 2010 and 2014 at an urban, tertiary care children's hospital. Patients admitted in the 24 months before and after initiation of a guideline for HFNC use on the general wards were compared.

Chemical mediators of inflammation and resolution in post-operative abdominal aortic aneurysm patients.

Temporal-metabolomic studies of local mediators during inflammation and its resolution uncovered novel pathways and mediators, e.g., lipoxins, resolvins, and protectins that stimulate key resolution responses.

Small-molecule screen identifies reactive oxygen species as key regulators of neutrophil chemotaxis.

Neutrophil chemotaxis plays an essential role in innate immunity, but the underlying cellular mechanism is still not fully characterized. Here, using a small-molecule functional screening, we identified NADPH oxidase-dependent reactive oxygen species as key regulators of neutrophil chemotactic migration. Neutrophils with pharmacologically inhibited oxidase, or isolated from chronic granulomatous disease (CGD) patients and mice, formed more frequent multiple pseudopodia and lost their directionality as they migrated up a chemoattractant concentration gradient.

Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions.

The endogenous cellular and molecular mechanisms that control acute inflammation and its resolution are of wide interest. Using self-resolving inflammatory exudates and lipidomics, we have identified a new pathway involving biosynthesis of potent antiinflammatory and proresolving mediators from the essential fatty acid docosahexaenoic acid (DHA) by macrophages (MPhis). During the resolution of mouse peritonitis, exudates accumulated both 17-hydroxydocosahexaenoic acid, a known marker of 17S-D series resolvin (Rv) and protectin biosynthesis, and 14S-hydroxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid from endogenous DHA.

Rapid appearance of resolvin precursors in inflammatory exudates: novel mechanisms in resolution.

Resolution of inflammation is essential. Although supplementation of omega-3 fatty acids is widely used, their availability at sites of inflammation is not known. To this end, a multidisciplinary approach was taken to determine the relationship of circulating omega-3 to inflammatory exudates and the generation of resolution signals.

Resolvin E1 metabolome in local inactivation during inflammation-resolution.

Resolvin E1 (RvE1; 5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid) is a potent anti-inflammatory and proresolving mediator derived from the omega-3 eicosapentaenoic acid. In this study, we report the RvE1 metabolome, namely, the metabolic products derived from RvE1. RvE1 was converted to several novel products by human polymorphonuclear leukocytes and whole blood as well as in murine inflammatory exudates, spleen, kidney, and liver.

Models of Hydrogel Swelling with Applications to Hydration Sensing.

Hydrogels, polymers and various other composite materials may be used insensing applications in which the swelling or de-swelling of the material in response tosome analyte is converted via a transducer to a measurable signal. In this paper, we analyzemodels used to predict the swelling behavior of hydrogels that may be used in applicationsrelated to hydration monitoring in humans. Preliminary experimental data related toosmolality changes in fluids is presented to compare to the theoretical models.

An embedded polymer piezoresistive microcantilever sensor.

We have developed a new type of chemical microsensor based on piezoresistive microcantilever technology. In this embedded polymer microsensor, a piezoresistive microcantilever is partially "embedded" into a polymeric material. Swelling of the polymer upon analyte exposure is measured as a simple resistance change in the embedded cantilever.

Identification of CDH1 germline missense mutations associated with functional inactivation of the E-cadherin protein in young gastric cancer probands.

E-cadherin is involved in the formation of cell-junctions and the maintenance of epithelial integrity. Direct evidence of E-cadherin mutations triggering tumorigenesis has come from the finding of inactivating germline mutations of the gene (CDH1) in hereditary diffuse gastric cancer (HDGC). We screened a series of 66 young gastric cancer probands for germline CDH1 mutations, and two novel missense alterations together with an intronic variant were identified.

Contribution of cyclin d1 (CCND1) and E-cadherin (CDH1) polymorphisms to familial and sporadic colorectal cancer.

The molecular basis for most non-HNPCC familial colorectal cancer cases is unknown, but there is increasing evidence that common genetic variants may play a role. We investigated the contribution of polymorphisms in two genes implicated in the pathogenesis of colorectal cancer, cyclin D1 (CCND1) and E-cadherin (CDH1), to familial and sporadic forms of the disease. The CCND1 870A/G polymorphism is thought to affect the expression of CCND1 through mRNA splicing and has been reported to modify the penetrance of HNPCC.