The synthetic antimicrobial peptide LTX21 induces inflammatory responses in a human whole blood model and a murine peritoneum model

The global spread of antimicrobial resistance and the increasing number of immune‐compromised patients are major challenges in modern medicine. Targeting bacterial virulence or the human host immune system to increase host defence are important strategies in the search for novel antimicrobial drugs. We investigated the inflammatory response of the synthetic short antimicrobial peptide LTX21 in two model systems: a human whole blood ex vivo model and a murine in vivo peritoneum model – both reflecting early innate immune response. In the whole blood model, LTX21 increased the secretion of a range of different cytokines, decreased the level of tumour necrosis factor (TNF) and activated the complement system. In a haemolysis assay, we found 2.5% haemolysis at a LTX21 concentration of 500 mg/L. In the murine model, increased influx of white blood cells (WBCs) and polymorphonuclear neutrophils (PMNs) in the murine peritoneal cavity was observed after treatment with LTX21. In addition, LTX21 increased monocyte chemoattractant protein‐1 (MCP‐1). In conclusion, LTX21 affected the inflammatory response; the increase in cytokine secretion, complement activation and WBC influx indicates an activated inflammatory response. The present results indicate the impact of LTX21 on the host–pathogen interplay. Whether this will also affect the course of infection has to be investigated.     

Analysis of proximal bone margins in diabetic foot osteomyelitis by conventional culture,DNA sequencing and microscopy

Multiple approaches were employed to detect pathogens from bone margins associated with Diabetic Foot Osteomyelitis (DFO). Intra‐operative bone specimens of 14 consecutive subjects with suspected DFO were collected over a six‐month study period from Liverpool Hospital. Infected bone and a proximal bone margins presumed to be ‘clean/non‐infected’ were collected. Bone material was subjected to conventional culture, DNA sequencing and microscopy. In total, eight of 14 (57%) proximal bone margins had no growth by conventional culture but were identified in all proximal bone specimens by DNA sequencing. Proximal margins had lower median total microbial counts than infected specimens, but these differences were not statistically significant. Pathogens identified by sequencing in infected specimens were identified in proximal margins and the microbiomes were similar (ANOSIM = 0.02, p = 0.59). Using a combination of SEM and/or PNA‐FISH, we visualized the presence of microorganisms in infected bone specimens and their corresponding proximal margins of seven patients (50%) with DFO. We identify that bacteria can still reside in what seems to be proximal ‘clean’ margins. The significance and implications of clinical outcomes requires further analysis from a larger sample size that incorporates differences in surgical and post‐operative approaches, correlating any outcomes back to culture‐sequence findings.     

Ethnoracial Disparity in Hospital Survival following Transjugular Intrahepatic Portosystemic Shunt Creation for Acute Variceal Bleeding in the United States

PurposeTo investigate the magnitude of racial/ethnic differences in hospital mortality after transjugular intrahepatic portosystemic shunt (TIPS) creation for acute variceal bleeding and whether hospital care processes contribute to them.MethodsPatients aged ≥18 years undergoing TIPS creation for acute variceal bleeding in the United States (n = 10,331) were identified from 10 years (2007–2016) available in the National Inpatient Sample. Hierarchical logistic regression was used to examine the relationship between patient race and inpatient mortality, controlling for disease severity, treatment utilization, and hospital characteristics.ResultsA total of 6,350 (62%) patients were White, 1,780 (17%) were Hispanic, and 482 (5%) were Black. A greater proportion of Black patients were admitted to urban teaching hospitals (Black, n = 409 (85%); Hispanic, n = 1,310 (74%); and White, n = 4,802 (76%); P < .001) and liver transplant centers (Black, n = 215 (45%); Hispanic, n = 401 (23%); and White, n = 2,267 (36%); P < .001). Being Black was strongly associated with mortality (Black, 32% vs non-Black, 15%; odds ratio, 3.0 [95% confidence interval, 1.6–5.8]; P = .001), as assessed using the risk-adjusted regression model. This racial disparity disappeared in a sensitivity analysis including only patients with a maximum Child-Pugh score of 13 (odds ratio 1.2 [95% confidence interval, 0.4–3.6]; P = .68), performed to compensate for the absence of Model for End-stage Liver Disease scores. Ethnoracial differences in access to teaching hospitals, liver transplant centers, first-line endoscopy, and transfusion did not significantly contribute (P > .05) to risk-adjusted mortality.ConclusionsBlack patients have a 2-fold higher inpatient mortality than non-Black patients following TIPS creation for acute variceal bleeding, possibly related to greater disease severity before the procedure.     

Simulation-based training for trauma resuscitation among ACS TQIP-Pediatric centers: Understanding prevalence of use,associated center characteristics,training factors,and implementation barriers

Background

Simulation-based training (SBT) for pediatric trauma resuscitation can improve team performance. The purpose of this study was to describe the nationwide trend in SBT use and barriers to SBT implementation.