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

Intraoperative Clinical Examination for Assessing Pelvic and Para-Aortic Lymph Node Involvement in Advanced Epithelial Ovarian Cancer: A Systematic Review and Meta-Analysis

After the publication of the Lymphadenectomy in Ovarian Neoplasms (LION) trial results, lymphadenectomy in advanced epithelial ovarian cancer with primary complete cytoreductive surgery is considered indicated only for women with suspicious lymph nodes. The aim of this meta-analysis was to evaluate the diagnostic accuracy of intraoperative clinical examination for detecting lymph node metastases in patients with advanced epithelial ovarian cancer during primary complete cytoreductive surgery. MEDLINE, EMBASE, Web of Science and the Cochrane Library were searched for January 1990 to May 2019 for studies evaluating the diagnostic accuracy of intraoperative clinical examination for detecting lymph node metastases in patients with advanced epithelial ovarian cancer during primary complete cytoreductive surgery, with histology as the gold standard. Methodological quality was assessed by using the QUADAS-2 tool. Pooled diagnostic accuracy was calculated, and hierarchical summary receiver operating curve was constructed. The potential sources of heterogeneity were analyzed by meta-regression analysis. Deek’s funnel plot test for publication bias and Fagan’s nomogram for clinical utility were also used. This meta-analysis included five studies involving 723 women. The pooled sensitivity of intraoperative clinical examination for detecting lymph node metastases was 0.79, 95% CI (0.67–0.87), and its specificity 0.85, 95% CI (0.67–0.94); the area under the hierarchical summary receiver operating curve was 0.86, 95% CI (0.83–0.89). In the meta-regression analysis, patient sample size, mean age, and type of cancer included were significant covariates explaining the potential sources of heterogeneity. Deek’s funnel plot test showed no evidence of publication bias (p = 0.25). Fagan’s nomogram indicated that intraoperative clinical examination increased the post-test probability of lymph node metastases to 79% when it was positive and reduced it to 16% when negative. This meta-analysis shows that the diagnostic accuracy of intraoperative clinical examination during primary complete cytoreductive surgery for detecting lymph node metastases in advanced epithelial ovarian cancer is good

Stress urinary incontinence 4 years after the first delivery: a retrospective cohort survey.

International audienceBACKGROUND: Our aim was to estimate the prevalence of stress urinary incontinence 4 years after the first delivery and analyze its risk factors. METHODS: A retrospective cohort survey was conducted in a French university hospital. The 669 primiparous women who delivered in our department in 1996 a singleton in a vertex position between 37 and 41 weeks of amenorrhea were included. A mailed questionnaire was sent 4 years after the indexed delivery. The main outcome measure was stress urinary incontinence 4 years after the first delivery. RESULTS: Three hundred and seven women replied, 274 had moved and 88 did not respond. Four years after the first delivery, prevalence of stress urinary incontinence was 29% (89/307). According to multiple logistic regression analysis, the independent risk factors were urine leakage before the first pregnancy [odds ratio (OR) 18.7; 95% confidence interval (CI) 3.6-96.4], urine leakage during the first pregnancy (OR 2.5; 95% CI 1.3-4.8), duration of first labor > or = 8 h (OR 3.1; 95% CI 1.7-5.7), mother's age > 30 years at the first delivery (OR 2.4; 95% CI 1.4-4.2) and cesarean section at the first delivery (OR 0.3; 95% CI 0.1-0.9). CONCLUSION: Our results suggest that stress urinary incontinence after pregnancy arises from a multifactorial condition. The main risk factors are: age, previous incontinence (before or during the first pregnancy), prolonged labor and vaginal delivery

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

The Micro-Immunotherapy Medicine 2LEID Exhibits an Immunostimulant Effect by Boosting Both Innate and Adaptive Immune Responses

This study aimed at evaluating the effects of the micro-immunotherapy medicine (MIM) 2LEID, both in vitro and in vivo, on several components of the innate and adaptive immune system. MIM increased the phagocytic activity of macrophages, and it augmented the expression of the activation markers CD69 and HLA-DR in NK cells and monocytes/macrophages, respectively. The effect of MIM was evaluated in a model of respiratory infection induced by influenza A virus administration to immunocompetent mice in which it was able to improve neutrophil recruitment within the lungs (p = 0.1051) and slightly increased the circulating levels of IgM (p = 0.1655). Furthermore, MIM stimulated the proliferation of CD3-primed T lymphocytes and decreased the secretion of the immunosuppressive cytokine IL-10 in CD14+-derived macrophages. Human umbilical vein endothelial cells were finally used to explore the effect of MIM on endothelial cells, in which it slightly increased the expression of immune-related markers such as HLA-I, CD137L, GITRL, PD-L1 and ICAM-1. In conclusion, the present study suggests that MIM might be a promising nonspecific (without antigen specificity) immunostimulant drug in preventing and early treating respiratory infections, but not only exclusively, as it would gently support several facets of the immune system and host defenses

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