CCR2 mediates increased susceptibility to post-H1N1 bacterial pneumonia by limiting dendritic cell induction of IL-17.

Post influenza bacterial pneumonia is associated with significant mortality and morbidity. Dendritic cells (DCs) play a crucial role in host defense against bacterial pneumonia, but their contribution to post influenza-susceptibility to secondary bacterial pneumonia is incompletely understood. WT and CCR2-/- mice were infected with 100 plaque forming units (pfu) H1N1 intranasally alone or were challenged on day 5 with 7 × 107 colony forming units (cfu) methicillin-resistant Staphylococcus aureus intratracheally. WT mice express abundant CCL2 mRNA and protein post-H1N1 alone or dual infection. CCR2-/- mice had significantly higher survival as compared to WT mice, associated with significantly improved bacterial clearance at 24 and 48 h (10-fold and 14-fold, respectively) post bacterial challenge. There was robust upregulation of IL-23 and IL-17 as well as downregulation of IL-27 expression in CCR2-/- mice following sequential infection as compared to WT mice, which was also associated with significantly greater accumulation of CD103+ DC. Finally, WT mice treated with a CCR2 inhibitor showed improved bacterial clearance in association with similar cytokine profiles as CCR2-/- mice. Thus, CCR2 significantly contributes to increased susceptibility to bacterial infection after influenza pneumonia likely via altered dendritic cell responses and thus, CCR2 antagonism represents a potential therapeutic strategy.

A Contemporary Assessment of Mechanical Complication Rates and Trainee Perceptions of Central Venous Catheter Insertion.

BACKGROUND: Limited data exist regarding rates of mechanical complications of ultrasound-guided, nontunneled central venous catheters (CVC). Similarly, trainee perceptions surrounding CVC complications are largely unknown. OBJECTIVES: To evaluate contemporary CVC mechanical complication rates, associated risk factors, and trainee perspectives. DESIGN: A single-center retrospective review of CVC procedures between June 1, 2014, and May 1, 2015. Electronic survey distributed to internal medicine trainees. SETTING: Intensive care units and the emergency department at an academic hospital. MEASUREMENTS: Electronic health records of patients with CVC procedures were reviewed for complications. Demographic and procedural characteristics were compared for complicated vs uncomplicated procedures. Student t tests and chi-square tests were used to compare continuous and categorical variables, respectively. RESULTS: Of the 730 reviewed records, 14 serious mechanical complications occurred due to pneumothorax (n = 5), bleeding (n = 3), vascular injury (n = 3), stroke (n = 1), and death (n = 2). Risk factors for complicated vs uncomplicated CVC placement included subclavian location (21.4% vs 7.8%, 𝑃 = 0.001), number of attempts (2.2 vs 1.5, 𝑃 = 0.02), unsuccessful CVC (21.4% vs. 4.3%, 𝑃 = 0.001), attending supervision (61.5% vs 34.7%, 𝑃 = 0.04), low body mass index (mean 25.7 kg/ m² vs 31.5 kg/m², 𝑃 = 0.001), anticoagulation (28.6% vs 20.6%, 𝑃 = 0.048), and ventilation (78.5% vs 66.5%, 𝑃 = 0.001). Survey data suggested deficiencies in managing unsuccessful CVC procedures; specifically, only 35% (N = 21/60) of trainees regularly perform chest x-rays after failed CVC attempt. CONCLUSIONS: We observed a 1.9% rate of mechanical complications associated with CVC placement. Our study confirms historical data that unsuccessful CVC attempts are an important risk factor for complications. Education regarding unsuccessful CVC placement may improve patient safety.