Jacobson I.,New York Medical College |
Bourliere M.,Fondation HOpital Saint Joseph |
Hezode C.,University Paris Est Creteil |
Vierling J.M.,Baylor College of Medicine |
And 12 more authors.
Clinical Gastroenterology and Hepatology | Year: 2013
Background and Aims: The addition of boceprevir to therapy with peginterferon alfa-2b and ribavirin results in significantly higher rates of sustained virologic response (SVR) in previously treated patients with chronic hepatitis C virus (HCV) genotype-1 infection, compared with peginterferon alfa-2b and ribavirin alone. We assessed SVR with boceprevir plus peginterferon alfa-2-ribavirin (PEG2a/R) in patients with identical study entry criteria. Methods: In a double-blind, placebo-controlled trial, 201 patients with HCV genotype-1 who had relapsed or not responded to previous therapy were assigned to groups (1:2) and given a 4-week lead-in phase of PEG2a/R, followed by placebo plus PEG2a/R for 44 weeks (PEG2a/R) or boceprevir plus PEG2a/R for 44 weeks (BOC/PEG2a/R). The primary end point was SVR 24 weeks after therapy ended. Results: The addition of boceprevir after 4 weeks of lead-in therapy with PEG2a/R significantly increased the rate of SVR from 21% in the PEG2a/R group to 64% in the BOC/PEG2a/R group (P< .0001). Among patients with poor response to interferon therapy (<1-log 10 decline in HCV RNA at week 4), 39% in the BOC/PEG2a/R group had SVRs, compared with none of the patients in the PEG2a/R group. Among patients with good response to interferon (≥1-log 10 decline), 71% in the BOC/PEG2a/R group had SVRs, compared with 25% in the PEG2a/R group. A ≥1-log 10 decline in HCV RNA at treatment week 4 was the strongest independent predictor of SVR, exceeding that of IL-28Bgenotype. Among 8 patients who began the study with HCV amino acid variants associated with boceprevir resistance, 3 (38%) achieved SVRs. Fifty percent of patients in the BOC/PEG2a/R group developed anemia (hemoglobin <10.0 g/dL), compared with 27% in the PEG2a/R group; 43% vs 21%, respectively, developed neutropenia (neutrophil count <750/mm 3). © 2013 AGA Institute.
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2009-2.3.1-2 | Award Amount: 7.82M | Year: 2010
Many results drawn from previous studies of the effect of antibiotic use on emergence, selection and spread of antimicrobial resistance (AMR) have lacked a holistic view combining all aspects into one study. The SATURN project aims to study the impact of antibiotic exposure on AMR with a multidisciplinary approach that bridges molecular, epidemiological, clinical and pharmacological research. Two types of clinical studies will be conducted: First, a randomized trial will be performed to resolve an issue of high controversy (antibiotic cycling vs. mixing). Second, 3 observational studies will be conducted to rigorously study issues surrounding the effect of antibiotic use on AMR that are not easily assessable through randomized trials. These clinical studies will serve as a platform to 2 complementary workpackages (microbiology & pharmacology) that will perform important investigations relevant to this call. The work package focusing on molecular studies will generate new evidence about the changes effected by antibiotic therapy on commensal organisms or opportunistic pathogens in the oropharyngeal, nasal and gastro-intestinal flora and study AMR mechanisms and the dissemination of successful clones of fluoroquinolone-resistant, carbapenem-resistant or extended-spectrum beta-lactamase harboring Gram-negative bacteria, MRSA and fluoroquinolone-resistant viridans streptococci. The purpose of the pharmacodynamic study is to model the relationships between antibiotic exposure and AMR emergence over time for various classes of agents. In summary, the overarching rationale of SATURN is to improve methodological standards and conduct research that will help to better understand the impact of antibiotic use on acquisition, selection and transmission of AMR in different environments, by combining analyses of molecular, individual patient-level and ecologic data. The anticipated results may guide clinical and policy decisions to ultimately reduce the burden of AMR in Europe.
Denoiseux C.C.,Fondation Hopital Saint Joseph |
Denoiseux C.C.,University Paris - Sud |
Boulay-Coletta I.,Fondation Hopital Saint Joseph |
Nakache J.-P.,Fondation Hopital Saint Joseph |
And 2 more authors.
Journal of Magnetic Resonance Imaging | Year: 2013
Purpose To retrospectively compare image quality and lesion detectability with two T2-weighted sequences at 1.5 Tesla (T): respiratory-triggered three-dimensional fat sat fast-spin-echo with extended echo-train acquisition (3D FSE-XETA) and respiratory-triggered two-dimensional fat-sat fast recovery fast-spin-echo (2D FRFSE). Materials and Methods MR was performed at 1.5T in 53 consecutive patients. Two radiologists blinded to the sequence details reviewed the studies to determine: (i) signal and contrast to noise ratios, (ii) overall image quality, (iii) sensitivity for focal lesion detection. Results Image assessment scores for the 2D FRFSE sequence were significantly higher than those for the 3D FSE-XETA sequence for overall image quality (P < 0.01) and artifacts (P < 0.001). Sensitivity for liver lesion detection was higher with the 3D FSE-XETA sequence (69.3% versus 57.3%; P < 0.05) compared with the 2D FRFSE sequence. The 3D FSE-XETA sequence improves the reader confidence score (P < 0.01) for liver lesions detection. Inter-observer correlation was higher with the 3D FSE-XETA sequence. Conclusion For T2-weighted liver imaging at 1.5T, the 3D FSE-XETA sequence improves sensitivity, reader confidence score and interobserver correlation for focal liver lesion detection, but it suffers from a lower overall image quality and higher artifacts. © 2013 Wiley Periodicals, Inc. Copyright © 2013 Wiley Periodicals, Inc.
PubMed | Hopital Beaujon and Fondation Hopital Saint Joseph
Type: Journal Article | Journal: Abdominal radiology (New York) | Year: 2016
To evaluate the qualitative and quantitative benefit of multiple arterial phase acquisitions for the depiction of hypervascularity in FNH explored MR imaging using an extracellular contrast agent.Between 2007 and 2014, all patients who underwent MR imaging for the exploration of FNH were included. The protocol included a single or a triple arterial phase (single and triple group, respectively). Arterial phases were visually divided into four types: (1) angiographic, (2) early, (3) late, and (4) portal. Signal intensity on arterial phase images was visually recorded as intense, moderate, or low for each lesion. Lesion-to-liver contrast (LLC) and relative lesion enhancement (RE) were calculated and compared between the two groups using the Mann-Whitney test.Thirty-five women were included (mean 45-year old, range 20-66), with 50 FNH (mean size 30mm). Single and triple groups included 20 patients (30 FNH) and 15 patients (20 FNH), respectively. Signal intensity was intense in all lesions in the triple group and in 22/30 (73%) in the single group (p=0.041). Intense signals were more frequently found in the early arterial phase (p<0.001). RE was not significantly different (1.780.84 vs. 1.981.81 p=0.430, in the single and triple groups, respectively) but LLC was significantly higher in the triple group (0.320.10 vs. 0.220.10, p=0.005). LLC was significantly higher in the first two arterial phases in the triple group (p<0.001).Acquisition of three arterial phases improves the visualization of hypervascularity of FNH, as lesions show high visual signal intensity and contrast. Optimal visualization is obtained in the early arterial phase.
Loron G.,National Health Research Institute |
Olivier P.,National Health Research Institute |
See H.,National Health Research Institute |
See H.,University Paris Diderot |
And 16 more authors.
Annals of Neurology | Year: 2011
Objective Perinatal infections and the systemic inflammatory response to them are critical contributors to white matter disease (WMD) in the developing brain despite the use of highly active antibiotics. Fluoroquinolones including ciprofloxacin (CIP) have intrinsic anti-inflammatory effects. We hypothesized that CIP, in addition to its antibacterial activity, could exert a neuroprotective effect by modulating white matter inflammation in response to sepsis. Methods We adapted an Escherichia coli sepsis model to 5-day-old rat pups (P5), to induce white matter inflammation without bacterial meningitis. We then compared the ability of CIP to modulate inflammatory-induced brain damage compared with cefotaxime (CTX) (treatment of reference). Results Compared with CTX, CIP was associated with reduced microglial activation and inducible nitric oxide synthase (iNOS) expression in the developing white matter in rat pups subjected to E. coli sepsis. In addition to reducing microglial activation, CIP was able to prevent myelination delay induced by E. coli sepsis and to promote oligodendroglial survival and maturation. We found that E. coli sepsis altered the transcription of the guidance molecules semaphorin 3A and 3F; CIP treatment was capable of reducing semaphorin 3A and 3F transcription levels to those seen in uninfected controls. Finally, in a noninfectious white matter inflammation model, CIP was associated with significantly reduced microglial activation and prevented WMD when compared to CTX. Interpretation These data strongly suggest that CIP exerts a beneficial effect in a model of E. coli sepsis-induced WMD in rat pups that is independent of its antibacterial activity but likely related to iNOS expression modulation. 2011 Copyright © 2010 American Neurological Association.
PubMed | University of Paris Descartes and Fondation Hopital Saint Joseph
Type: Journal Article | Journal: European radiology | Year: 2015
To evaluate the diagnostic accuracy of CT in postoperative colorectal anastomotic leakage (AL).Two independent blinded radiologists reviewed 153 CTs performed for suspected AL within 60 days after surgery in 131 consecutive patients, with (n=58) or without (n=95) retrograde contrast enema (RCE). Results were compared to original interpretations. The reference standard was reoperation or consensus (a radiologist and a surgeon) regarding clinical, laboratory, radiological, and follow-up data after medical treatment.AL was confirmed in 34/131 patients. For the two reviewers and original interpretation, sensitivity of CT was 82 %, 87 %, and 71 %, respectively; specificity was 84 %, 84 %, and 92 %. RCE significantly increased the positive predictive value (from 40 % to 88 %, P=0.0009; 41 % to 92 %, P=0.0016; and 40 % to 100 %, P=0.0006). Contrast extravasation was the most sensitive (reviewers, 83 % and 83 %) and specific (97 % and 97 %) sign and was significantly associated with AL by univariate analysis (P<0.0001 and P<0.0001). By multivariate analysis with recursive partitioning, CT with RCE was accurate to confirm or rule out AL with contrast extravasation.CT with RCE is accurate for diagnosing postoperative colorectal AL. Contrast extravasation is the most reliable sign. RCE should be performed during CT for suspected AL. CT accurately diagnosed clinically suspected colorectal AL and showed good interobserver agreement Contrast extravasation was the most sensitive and specific CT sign Retrograde contrast enema during CT improved positive predictive value Retrograde contrast enema decreased false-negative or indeterminate original CT interpretations.
Geffroy Y.,Fondation Hopital Saint Joseph |
Boulay-Coletta I.,Fondation Hopital Saint Joseph |
Nakache S.,Fondation Hopital Saint Joseph |
Julles M.-C.,Fondation Hopital Saint Joseph |
And 2 more authors.
Radiology | Year: 2014
Purpose: To evaluate performance of increased bowel-wall attenuation on unenhanced 64-section multidetector computed tomographic (CT) images for diagnosing bowel-wall ischemia in patients with mechanical small-bowel obstruction (SBO) and to evaluate the diagnostic accuracy of multidetector CT in detecting small-bowel ischemia complicating SBO, with surgical and histopathologic findings as reference standard. Materials and Methods: The local institutional review board approved this retrospective study; informed consent requirement was waived. In 44 patients (10 men, 34 women; age range, 30-100 years) who were admitted because they were suspected of having SBO and treated surgically within the next 7 days, 45 multidetector CT scans were retrospectively reviewed. Two gastrointestinal radiologists performed independent blinded reviews of images to identify specific signs of ischemia; disagreements were resolved in consensus with a third gastrointestinal radiologist. Results were compared with both findings in prospective radiology reports and surgical and histopathologic findings. Fisher exact and χ2 tests were used to assess associations between CT signs and ischemia, and the κ statistic was used to assess interobserver agreement. Results: In 19 of 45 (42%) multidetector CT scans, ischemia was confirmed at surgery and/or histopathologic examination. Increased bowel-wall attenuation on unenhanced images was significantly associated with ischemia (P < .0001); in this highly selected population, this sign had a 100% (24 of 24) specificity and a 56% (10 of 18) sensitivity. Sensitivity and specificity of multidetector CT for ischemia were 63% (12 of 19) and 92% (24 of 26), respectively, for the prospective reports and 84% (16 of 19) and 96% (25 of 26), respectively, for the consensus review. Decreased segmental bowel-wall enhancement was the most accurate 64-section multidetector CT sign for diagnosing ischemia (sensitivity, 78% [14 of 18]; specificity, 96% [24 of 25]; P < .0001). The small-bowel feces sign was significantly associated with ischemia (P = .0308). Conclusion: Increased bowel-wall attenuation on unenhanced 64-section multidetector CT images is a specific sign for ischemia complicating SBO. Diagnostic accuracy of 64-section multidetector CT for ischemia associated with SBO was excellent. © RSNA, 2013.
Legrand L.,Fondation Hopital Saint Joseph |
Duchatelle V.,Fondation Hopital Saint Joseph |
Molinie V.,Fondation Hopital Saint Joseph |
Boulay-Coletta I.,Fondation Hopital Saint Joseph |
And 2 more authors.
Abdominal Imaging | Year: 2015
Purpose: To identify the MRI sequences producing the greatest pancreatic adenocarcinoma conspicuity and to assess correlations linking MRI signal intensity and apparent diffusion coefficient to histopathological findings. Methods: We retrospectively included 22 patients with pancreatic adenocarcinoma who underwent MRI (1.5 or 3 T) before surgical resection. Fat-suppressed (FS) T1- and T2-weighted sequences; 3D FS dynamic T1-weighted gadolinium-enhanced gradient-echo (GRE) imaging at the arterial, portal, and delayed phases; and diffusion-weighted imaging (DWI) with b values of 600–800 s/mm2 were reviewed. On each sequence, we assessed tumor conspicuity both qualitatively (3-point scale) and quantitatively (tumor-to-proximal and -distal pancreas contrast ratios), and we performed paired Wilcoxon tests to compare these data across sequences. We evaluated correlations between histopathological characteristics and MRI features. Results: 21/22 (95%) tumors were hypointense by 3D FS T1 GRE arterial phase imaging, which produced the greatest tumor conspicuity (p ≤ 0.02). By DWI, 5/20 (25%) of tumors were isointense. The correlation between size by histology and MRI was strongest with DWI. A progressive enhancement pattern was associated with extensive and dense fibrous stroma (p ≤ 0.03). Conclusions: 3D FS T1 GRE arterial phase imaging produces greater pancreatic adenocarcinoma conspicuity compared to DWI but underestimates tumor size. DWI provides the best size evaluation but fails to delineate the tumor in one-fourth of cases. © 2014, Springer Science+Business Media New York.
PubMed | Fondation Hopital Saint Joseph
Type: Journal Article | Journal: Abdominal imaging | Year: 2015
To identify the MRI sequences producing the greatest pancreatic adenocarcinoma conspicuity and to assess correlations linking MRI signal intensity and apparent diffusion coefficient to histopathological findings.We retrospectively included 22 patients with pancreatic adenocarcinoma who underwent MRI (1.5 or 3T) before surgical resection. Fat-suppressed (FS) T1- and T2-weighted sequences; 3D FS dynamic T1-weighted gadolinium-enhanced gradient-echo (GRE) imaging at the arterial, portal, and delayed phases; and diffusion-weighted imaging (DWI) with b values of 600-800s/mm(2) were reviewed. On each sequence, we assessed tumor conspicuity both qualitatively (3-point scale) and quantitatively (tumor-to-proximal and -distal pancreas contrast ratios), and we performed paired Wilcoxon tests to compare these data across sequences. We evaluated correlations between histopathological characteristics and MRI features.21/22 (95%) tumors were hypointense by 3D FS T1 GRE arterial phase imaging, which produced the greatest tumor conspicuity (p0.02). By DWI, 5/20 (25%) of tumors were isointense. The correlation between size by histology and MRI was strongest with DWI. A progressive enhancement pattern was associated with extensive and dense fibrous stroma (p0.03).3D FS T1 GRE arterial phase imaging produces greater pancreatic adenocarcinoma conspicuity compared to DWI but underestimates tumor size. DWI provides the best size evaluation but fails to delineate the tumor in one-fourth of cases.
PubMed | Hopital Europeen Georges Pompidou and Fondation Hopital Saint Joseph
Type: Journal Article | Journal: Orthopaedics & traumatology, surgery & research : OTSR | Year: 2016
Lumbar fusion is now a currently accepted treatment for degenerative lumbar spondylolisthesis (DLSP), but may induce adjacent segment degeneration (ASD). The present study hypothesis was that there are radiological parameters associated with ASD. The study objective was to determine predictive factors of ASD.A single-center retrospective study included patients operated on between 2006 and 2013 for DLSP. Radiological parameters were analyzed on preoperative, immediate postoperative and final follow-up lateral X-ray. ASD was defined by the following adjacent segment criteria:>3mm anteroposterior translation,>10 segmental kyphosis, or>50% loss of disc height.One hundred and seven patients were included: 79% female; mean age, 6710.2 years. Fusion involved 1 level in 67% of cases and 2 or more in 33%, with transforaminal lumbar interbody fusion (TLIF) in 27% of cases. There was overall significant gain in lumbar lordosis (mean, 3.1; P=0.04). At a mean 27.8 months follow-up, 29% of cases showed ASD and 10% required surgical reintervention. Preoperative anterior imbalance and long fusion (>2 levels) were significantly associated with ASD (OR=2.81, 95% CI [1.17-6.74] versus OR=2.76, 95% CI [1.15-6.63]). There were no significant differences according to postoperative radiological parameters, or to TLIF (OR=1.8, 95% CI [0.7-4.4]).Twenty-nine percent of patients developed ASD, with a surgical revision rate of 10%. ASD risk factors comprised high number of instrumented levels and preoperative sagittal imbalance.IV, retrospective cohort.