The anti-Pseudomonas aeruginosa antibody Panobacumab is efficacious on acute pneumonia in neutropenic mice and has additive effects with meropenem

Pseudomonas aeruginosa ( P. aeruginosa ) infections are associated with considerable morbidity and mortality in immunocompromised patients due to antibiotic resistance. Therefore, we investigated the efficacy of the anti- P. aeruginosa serotype O11 lipopolysaccharide monoclonal antibody Panobacumab in a clinically relevant murine model of neutropenia induced by cyclophosphamide and in combination with meropenem in susceptible and meropenem resistant P. aeruginosa induced pneumonia. We observed that P. aeruginosa induced pneumonia was dramatically increased in neutropenic mice compared to immunocompetent mice. First, Panobacumab significantly reduced lung inflammation and enhanced bacterial clearance from the lung of neutropenic host. Secondly, combination of Panobacumab and meropenem had an additive effect. Third, Panobacumab retained activity on a meropenem resistant P. aeruginosa strain. In conclusion, the present data established that Panobacumab contributes to the clearance of P. aeruginosa in neutropenic hosts as well as in combination with antibiotics in immunocompetent hosts. This suggests beneficial effects of co-treatment even in immunocompromised individuals, suffering most of the morbidity and mortality of P. aeruginosa infections

Role of IL-1β in experimental cystic fibrosis upon P. aeruginosa Infection

Cystic fibrosis is associated with increased inflammatory responses to pathogen challenge. Here we revisited the role of IL-1β in lung pathology using the experimental F508del-CFTR murine model on C57BL/6 genetic background (Cftrtm1eur or d/d), on double deficient for d/d and type 1 interleukin-1 receptor (d/d X IL-1R1-/-), and antibody neutralization. At steady state, young adult d/d mice did not show any signs of spontaneous lung inflammation. However, IL-1R1 deficiency conferred partial protection to repeated P. aeruginosa endotoxins/LPS lung instillation in d/d mice, as 50% of d/d mice succumbed to inflammation, whereas all d/d x IL-1R1-/- double mutants survived with lower initial weight loss and less pulmonary collagen and mucus production, suggesting that the absence of IL-1R1 signaling is protective in d/d mice in LPS-induced lung damage. Using P. aeruginosa acute lung infection we found heightened neutrophil recruitment in d/d mice with higher epithelial damage, increased bacterial load in BALF, and augmented IL-1β and TNF-α in parenchyma as compared to WT mice. Thus, F508del-CFTR mice show enhanced IL-1β signaling in response to P. aeruginosa. IL-1β antibody neutralization had no effect on lung homeostasis in either d/d or WT mice, however P. aeruginosa induced lung inflammation and bacterial load were diminished by IL-1β antibody neutralization. In conclusion, enhanced susceptibility to P. aeruginosa in d/d mice correlates with an excessive inflammation and with increased IL-1β production and reduced bacterial clearance. Further, we show that neutralization of IL-1β in d/d mice through the double mutation d/d x IL-1R1-/- and in WT via antibody neutralization attenuates inflammation. This supports the notion that intervention in the IL-1R1/IL-1β pathway may be detrimental in CF patients

Inflamatory response to cold plasma in normal skin

International audienceAim Investigate the effect of dose of cold plasma on skin integrity.Background Cold plasma is an emerging novel therapeutic approach in medicine with a great potential in auto-immune skin disorders, cutaneous infections and tumors. Only limited data are available on the safety of such a therapy. Therefore we investigated the cutaneous response in mice exposed to cold plasma.Methods We used BL6 mice which were exposed to plasma DBD (dielectric barrier discharge) in air at 2 mm of the skin for increasing doses to define the threshold of safety. The skin was excised at 24h and analyzed for integrity, neutrophil recruitment and cytokine and chemokine production and histological analyses.Results A dose dependent reddening of the skin was observed with scales at the highest dose. The macroscopic changes correlated with increased neutrophil recruitment in the skin as assessed by myeloperoxidase (MPO) activity, microscopically neutrophil infiltration of the epidermis extending in the dermis and at the highest dose in the subcutaneous fat tissue. Further, microabcesses in the epidermis with necrosis were found at the highest exposure dose. The measurement of inflammatory cytokines and chemokines associated with the inflammatory response is ongoing.The effect of high dose plasma was comparable to a local intradermal injection of endotoxin in terms of neutrophils infiltration.We hypothesized that epidermal barrier was damaged by the plasma allowing the entrance of commensals and their products into skin resulting in TLR depending activation of the innate immunity and inflammation. To test this hypothesis, we have ongoing studies using TLR2-4 and IL-1R deficient mice, which may have attenuated inflammation.In conclusion, a safe dose of plasma needs to be defined which conserves the epidermal integrity and avoids an inflammatory response

Preoperative ct or pet/ct to assess pelvic and para-aortic lymph node status in epithelial ovarian cancer? A systematic review and meta-analysis

International audienceBackground: In advanced epithelial ovarian cancer (EOC), the LION trial restricted lym-phadenectomy indication to patients with suspect lymph nodes before and during surgery. Preoperative imaging is used to assess lymph node status, and particularly CT and PET/CT. The aim of this systematic review and meta-analysis was to evaluate the diagnostic accuracy of preoperative CT and PET/CT to detect lymph node metastasis (LNM) in patients with EOC;Methods: Databases were searched from January 1990 to May 2019 for studies that evaluated the diagnostic accuracy of preoperative CT and PET/CT to detect LNM in patients with EOC with histology as the gold standard. Pooled diagnostic accuracy was calculated using bivariate random-effects models and hierarchical summary receiver operating curve (HSROC). This study is registered with PROSPERO number CRD42020179214Results: A total of five studies were included in the meta-analysis: four articles concerned preoperative CT and four articles concerned preoperative PET/CT, involving 106 and 138 patients, respectively. For preoperative CT, pooled sensitivity was 0.47 95% CI [0.20–0.76], pooled specificity was 0.99 95% CI [0.75–1.00] and area under the curve (AUC) of the HSROC was 0.91 95% CI [0.88–0.93]. For preoperative PET/CT, pooled sensitivity was 0.81 95% CI [0.61–0.92], pooled specificity was 0.96 95% CI [0.91–0.99] and AUC of the HSROC was 0.97 95% CI [0.95–0.98]Conclusions: PET/CT has a very high diagnostic accuracy, especially for specificity, to detect LNM in EOC and should be realized systematically, additionally to CT recommended to evaluate peritoneal spread, in the preoperative staging of patients with an advanced disease

Evolution of temporal dynamic of volatile organic compounds (VOCs) and odors of hem stem during field retting

In the hemp industry, retting is an upstream bioprocessing applied to the plants to facilitate the decortication of fibres from the central woody part of the stem. This treatment is currently carried out in an empirical way on the ground which leads to variability in the hemp stems quality, and thus to the hemp fibres quality. Therefore, controlling retting treatment is a crucial step for high-performance hemp fibre. In this study, a new approach is used to assess the retting degree by following the evolution of VOCs emitted by plants during different retting durations. Either harvest time or retting induces a change in VOCs released by plants. During plant maturity, volatile compounds emitted decreased with a factor of about 2, in relation to VOCs released at the end of flowering. Regardless of the harvest period, the majority of VOCs and odor concentrations, monitored by olfactometric analysis, decrease gradually until some of them disappear at the end of retting. Likewise, the green plant odor disappears during retting with an increase of dry plants odor and an appearance of fermented odor at the end of retting. Following the evolution of VOCs emitted by plants during retting could be a tool for farmers to improve the retting management