Saint-Étienne, France
Saint-Étienne, France

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Philippart F.,Groupe Hospitalier Paris Saint Joseph | Bouroche G.,CNRS Gustave Roussy Institute | Timsit J.-F.,Joseph Fourier University | Timsit J.-F.,Groupe Hospitalier Bichat Claude Bernard | And 39 more authors.
PLoS ONE | Year: 2015

Rationale: Experimental studies suggest that intra-abdominal infection (IAI) induces biological alterations that may affect the risk of lung infection. Objectives: To investigate the potential effect of IAI at ICU admission on the subsequent occurrence of ventilator-associated pneumonia (VAP). Methods: We used data entered into the French prospective multicenter Outcomerea database in 1997-2011. Consecutive patients who had severe sepsis and/or septic shock at ICU admission and required mechanical ventilation for more than 3 days were included. Patients with acute pancreatitis were not included. Measurements and Main Results: Of 2623 database patients meeting the inclusion criteria, 290 (11.1%) had IAI and 2333 (88.9%) had other infections. The IAI group had fewer patients with VAP (56 [19.3%] vs. 806 [34.5%], P<0.01) and longer time to VAP (5.0 vs.10.5 days; P<0.01). After adjustment on independent risk factors for VAP and previous antimicrobial use, IAI was associated with a decreased risk of VAP (hazard ratio, 0.62; 95% confidence interval, 0.46-0.83; P<0.0017). The pathogens responsible for VAP were not different between the groups with and without IAI (Pseudomonas aeruginosa, 345 [42.8%] and 24 [42.8%]; Enterobacteriaceae, 264 [32.8%] and 19 [34.0%]; and Staphylococcus aureus, 215 [26.7%] and 17 [30.4%], respectively). Crude ICU mortality was not different between the groups with and without IAI (81 [27.9%] and 747 [32.0%], P = 0.16). Conclusions: In our observational study of mechanically ventilated ICU patients with severe sepsis and/or septic shock, VAP occurred less often and later in the group with IAIs compared to the group with infections at other sites. © 2015 Philippart et al.

Villeneuve L.,University of Lyon | Thivolet A.,University of Lyon | Thivolet A.,Center Hospitalier Lyon Sud | Bakrin N.,EMR 3738 | And 95 more authors.
European Journal of Surgical Oncology | Year: 2016

Based on the importance of assessing the true extent of peritoneal disease, PeRitOneal MalIgnancy Stage Evaluation (PROMISE) internet application ( has been developed to facilitate tabulation and automatically calculate surgically validated peritoneal cancer index (PCI), and other surgically validated scores as Gilly score, simplified peritoneal cancer index (SPCI), Fagotti and Fagotti-modified scores. This application offers computer-assistance to produce simple, quick but precise and standardized pre, intra and postoperative reports of the extent of peritoneal metastases and may help specialized and non-specialized institutions in their current practice but also facilitate research and multicentre studies on peritoneal surface malignancies. © 2016 Elsevier Ltd

PubMed | St Etienne University Hospital, University of Lyon, Oncovirologie etBiotherapies, Center Mediterraneen Of Medecine Moleculaire and 5 more.
Type: | Journal: Clinical cancer research : an official journal of the American Association for Cancer Research | Year: 2016

Azacitidine (AZA) inhibits DNA methyltransferases, including DNMT1, and is currently the standard of care for patients with higher risk myelodysplastic syndrome (HRMDS) or low blast count AML (AML).The expression of 754 microRNAs (miRNAs) was compared in AZA-resistant and AZA-sensitive MDS cells. We investigated the role of differentially expressed miRNAs on DNMT1 expression and AZA-resistance in vitro. We next evaluated anti-DNMT1 miRNAs expression in pretreatment bone marrow samples deriving from 75 patients treated with AZA for HRMDS or AML.Seven miRNAs, including 5 that in silico targeted the DNMT1 3 UTR, were repressed in AZA-resistant cells in which DNMT1 protein levels were significantly higher. Ectopic anti-DNMT1 miRNAs expression decreased DNMT1 expression and increased AZA sensitivity whereas specific inhibition of endogenous anti-DNMT1 miRNAs increased DNMT1 expression and triggered AZA-resistance. In patients treated with AZA, decreased expression of anti-DNMT1 miRNAs was associated with poor outcome. miR-126* had the strongest prognostic impact. Patients with miR-126*Low MDS had significantly lower response rates (p=0.04) and higher relapse rates (p=0.03), as well as shorter progression-free (PFS) (p=0.004) and overall survival (OS) (p=0.004). Multivariate analysis showed that age, miR-126* expression, and revised International Prognostic Scoring System (IPSS-R) risk independently predicted PFS and OS. In 15 patient samples collected over time, decreased miRNA expression levels were associated with secondary resistance.A decreased expression of anti-DNMT1 miRNAs might account for AZA-resistance in HRMDS and AML and that measuring miRNA expression before and during treatment might help predict primary or secondary AZA resistance.

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