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Colombel J.-F.,Mount Sinai School of Medicine | Sandborn W.J.,University of California at San Diego | Allez M.,Saint Louis Hospital | Dupas J.,Center Hospitalier University Amiens | And 5 more authors.
Clinical Gastroenterology and Hepatology | Year: 2014

Background & Aims: Monitoring plasma concentrations of anti-tumor necrosis factor agents could optimize treatment of patients with Crohn's Disease (CD). In a post hoc analysis of data from a clinical trial, we compared the relationship between plasma concentrations of certolizumab pegol (CZP) and endoscopic and clinical responses and remission with CZP therapy in patients with moderate to severe ileocolonic CD. Methods: We analyzed data from the Endoscopic Mucosal Improvement in Patients with Active CD Treated with CZP trial, from 89 adult patients with active endoscopic CD (ulceration in ≥2 intestinal segments and CD Endoscopic Index of Severity [CDEIS] scores of ≥8 points). Patients received subcutaneous CZP (400 mg) at weeks 0, 2, and 4 and then every 4 weeks until week 52. Endoscopic evaluations were performed at weeks 0, 10, and 54. Blood samples were collected to measure CZP plasma concentrations at weeks 8 and 54. CZP quartiles at weeks 8 (n= 80) and 54 (n= 45) were correlated with endoscopic response (>5-point decrease in CDEIS from baseline) and remission (CDEIS, <6) at weeks 10 and 54, respectively. Results: Higher concentrations of CZP at week 8 were associated with endoscopic response (P= .0016) and remission (P= .0302) at week 10 (n= 45). At week 54, the rates of endoscopic remission correlated with plasma concentrations of CZP (P= .0206). There was a significant inverse relationship between plasma concentrations of CZP and baseline levels of C-reactive protein and body weight (P= .0014 and P= .0373, respectively). Conclusions: Endoscopic response and remission are associated with higher plasma concentrations of CZP in patients with moderate to severe ileocolonic CD. These results support the need to consider the pharmacokinetics of anti-tumor necrosis factor agents and therapeutic drug monitoring to optimize treatment. Clinicaltrials.gov Number, NCT00297648. © 2014 AGA Institute.


PubMed | Montpellier University, University of Nantes, Roubaix, Reanimation DRIS and 19 more.
Type: Journal Article | Journal: JAMA | Year: 2015

Noninvasive ventilation has been recommended to decrease mortality among immunocompromised patients with hypoxemic acute respiratory failure. However, its effectiveness for this indication remains unclear.To determine whether early noninvasive ventilation improved survival in immunocompromised patients with nonhypercapnic acute hypoxemic respiratory failure.Multicenter randomized trial conducted among 374 critically ill immunocompromised patients, of whom 317 (84.7%) were receiving treatment for hematologic malignancies or solid tumors, at 28 intensive care units (ICUs) in France and Belgium between August 12, 2013, and January 2, 2015.Patients were randomly assigned to early noninvasive ventilation (n=191) or oxygen therapy alone (n=183).The primary outcome was day-28 mortality. Secondary outcomes were intubation, Sequential Organ Failure Assessment score on day 3, ICU-acquired infections, duration of mechanical ventilation, and ICU length of stay.At randomization, median oxygen flow was 9 L/min (interquartile range, 5-15) in the noninvasive ventilation group and 9 L/min (interquartile range, 6-15) in the oxygen group. All patients in the noninvasive ventilation group received the first noninvasive ventilation session immediately after randomization. On day 28 after randomization, 46 deaths (24.1%) had occurred in the noninvasive ventilation group vs 50 (27.3%) in the oxygen group (absolute difference, -3.2 [95% CI, -12.1 to 5.6]; P=.47). Oxygenation failure occurred in 155 patients overall (41.4%), 73 (38.2%) in the noninvasive ventilation group and 82 (44.8%) in the oxygen group (absolute difference, -6.6 [95% CI, -16.6 to 3.4]; P=.20). There were no significant differences in ICU-acquired infections, duration of mechanical ventilation, or lengths of ICU or hospital stays.Among immunocompromised patients admitted to the ICU with hypoxemic acute respiratory failure, early noninvasive ventilation compared with oxygen therapy alone did not reduce 28-day mortality. However, study power was limited.clinicaltrials.gov Identifier: NCT01915719.


PubMed | Center Hospitalier Of Beauvais, Brest University Hospital Center, University of Bordeaux Segalen, French Institute of Health and Medical Research and 7 more.
Type: Journal Article | Journal: European heart journal cardiovascular Imaging | Year: 2015

The Food and Drug Administration (FDA) criteria for diagnosis of drug-induced valvular heart disease (DIVHD) are only based on the observation of aortic regurgitation mild and/or mitral regurgitation moderate. We sought to evaluate the diagnostic value of FDA criteria in a cohort of control patients and in a cohort of patients exposed to a drug (benfluorex) known to induce VHD.This prospective, multicentre study included 376 diabetic control patients not exposed to valvulopathic drugs and 1000 subjects previously exposed to benfluorex. Diagnosis of mitral or aortic DIVHD was based on a combined functional and morphological echocardiographic analysis of cardiac valves. Patients were classified according to the FDA criteria [mitral or aortic-FDA(+) and mitral or aortic-FDA(-)]. Among the 376 control patients, 2 were wrongly classified as mitral-FDA(+) and 17 as aortic-FDA(+) (0.53 and 4.5% of false positives, respectively). Of those exposed to benfluorex, 48 of 58 with a diagnosis of mitral DIVHD (83%) were classified as mitral-FDA(-), and 901 of the 910 patients (99%) without a diagnosis of the mitral DIVHD group were classified as mitral-FDA(-). All 40 patients with a diagnosis of aortic DIVHD were classified as aortic-FDA(+), and 105 of the 910 patients without a diagnosis of aortic DIVHD (12%) were classified aortic-FDA(+). Older age and lower BMI were independent predictors of disagreement between FDA criteria and the diagnosis of DIVHD in patients exposed to benfluorex (both P 0.001).FDA criteria solely based on the Doppler detection of cardiac valve regurgitation underestimate for the mitral valve and overestimate for the aortic valve the frequency of DIVHD. Therefore, the diagnosis of DIVHD must be based on a combined echocardiographic and Doppler morphological and functional analysis of cardiac valves.


Bardan G.,University Paul Sabatier | Plouraboue F.,University Paul Sabatier | Zagzoule M.,University Paul Sabatier | Baledent O.,Center Hospitalier University Amiens
IEEE Transactions on Biomedical Engineering | Year: 2012

From measurements of the oscillating flux of the cerebrospinal fluid (CSF) in the aqueduct of Sylvius, we elaborate a patient-based methodology for transmantle pressure (TRP) and shear evaluation. High-resolution anatomical magnetic resonance imaging first permits a precise 3-D anatomical digitalized reconstruction of the Sylviuss aqueduct shape. From this, a very fast approximate numerical flow computation, nevertheless consistent with analytical predictions, is developed. Our approach includes the main contributions of inertial effects coming from the pulsatile flow and curvature effects associated with the aqueduct bending. Integrating the pressure along the aqueduct longitudinal centerline enables the total dynamic hydraulic admittances of the aqueduct to be evaluated, which is the pre-eminent contribution to the CSF pressure difference between the lateral ventricles and the subarachnoidal spaces also called the TRP. The application of the method to 20 healthy human patients validates the hypothesis of the proposed approach and provides a first database for normal aqueduct CSF flow. Finally, the implications of our results for modeling and evaluating intracranial cerebral pressure are discussed. © 1964-2012 IEEE.


Belaid A.,Compiègne University of Technology | Boukerroui D.,Compiègne University of Technology | Maingourd Y.,Center Hospitalier University Amiens | Lerallut J.-F.,Compiègne University of Technology
IEEE Transactions on Information Technology in Biomedicine | Year: 2011

Ultrasonic image segmentation is a difficult problem due to speckle noise, low contrast, and local changes of intensity. Intensity-based methods do not perform particularly well on ultrasound images. However, it has been previously shown that these images respond well to local phase-based methods which are theoretically intensity invariant. Here, we use level set propagation to capture the left ventricle boundaries. The proposed approach uses a new speed term based on local phase and local orientation derived from the monogenic signal, which makes the algorithm robust to attenuation artifact. Furthermore, we use Cauchy kernels, as a better alternative to the commonly used log-Gabor, as pair of quadrature filters for the feature extraction. Results on synthetic and natural data show that the proposed method can robustly handle noise, and captures well the low contrast boundaries. © 2006 IEEE.


Perrault I.,French Institute of Health and Medical Research | Perrault I.,University of Paris Descartes | Hamdan F.F.,University of Montréal | Rio M.,University of Paris Descartes | And 20 more authors.
American Journal of Human Genetics | Year: 2014

Epileptic encephalopathies are increasingly thought to be of genetic origin, although the exact etiology remains uncertain in many cases. We describe here three girls from two nonconsanguineous families affected by a clinical entity characterized by dysmorphic features, early-onset intractable epilepsy, intellectual disability, and cortical blindness. In individuals from each family, brain imaging also showed specific changes, including an abnormally marked pontobulbar sulcus and abnormal signals (T2 hyperintensities) and atrophy in the occipital lobe. Exome sequencing performed in the first family did not reveal any gene with rare homozygous variants shared by both affected siblings. It did, however, show one gene, DOCK7, with two rare heterozygous variants (c.2510delA [p.Asp837Alafs*48] and c.3709C>T [p.Arg1237 *]) found in both affected sisters. Exome sequencing performed in the proband of the second family also showed the presence of two rare heterozygous variants (c.983C>G [p.Ser328*] and c.6232G>T [p.Glu2078*]) in DOCK7. Sanger sequencing confirmed that all three individuals are compound heterozygotes for these truncating mutations in DOCK7. These mutations have not been observed in public SNP databases and are predicted to abolish domains critical for DOCK7 function. DOCK7 codes for a Rac guanine nucleotide exchange factor that has been implicated in the genesis and polarization of newborn pyramidal neurons and in the morphological differentiation of GABAergic interneurons in the developing cortex. All together, these observations suggest that loss of DOCK7 function causes a syndromic form of epileptic encephalopathy by affecting multiple neuronal processes. © 2014 The American Society of Human Genetics.


Rusinaru D.,Center Hospitalier University Amiens | Rusinaru D.,Center Hospitalier Of Saint Quentin | Houpe D.,Center Hospitalier Of Saint Quentin | Szymanski C.,Center Hospitalier University Amiens | And 4 more authors.
European Journal of Heart Failure | Year: 2014

Aims The prognostic impact of coronary artery disease (CAD) in heart failure is debated. Whereas causes of death have been well described in patients with cardiomyopathy, little is known about how CAD influences causes of death in heart failure with preserved ejection fraction (HFPEF). We undertook a 10-year study and analysed causes of death in relation with CAD in HFPEF and in heart failure with reduced ejection fraction (HFREF).Methods and Results Our prospective analysis included 591 consecutive patients (320 HFPEF and 271 HFREF) hospitalized for the first time for heart failure during 2000 and followed for 10 years. History of CAD was documented in 25% of HFPEF and 39% of HFREF patients (P <0.001). Overall, CAD was independently predictive of all-cause and cardiovascular death. CAD had powerful prognostic impact in HFREF [adjusted hazard ratio (HR) 1.60 (1.19-2.15) for all-cause death, and adjusted HR 2.01 (1.38-2.92) for cardiovascular death]. In HFPEF, the association between CAD and cardiovascular death was no longer observed after adjustment [adjusted HR 1.01 (0.69-1.50)]. In HFREF, CAD was associated with increased risk of heart failure-related (adjusted HR 2.03 (1.21-3.43)] and myocardial infarction-related fatal events [adjusted HR 3.84 (1.16-12.7)], while HFPEF patients with CAD appeared at greater risk of sudden death [adjusted HR 2.22 (1.05-4.95)].Conclusion The prognostic impact of CAD is different in HFPEF compared with HFREF. Patients with HFPEF and CAD are at high risk of cardiovascular death, especially sudden death. © 2014 European Society of Cardiology.


Marechaux S.,Lille Catholic University | Guiot A.,Lille Catholic University | Castel A.L.,Lille Catholic University | Guyomar Y.,Lille Catholic University | And 7 more authors.
Journal of the American Society of Echocardiography | Year: 2014

Background Previous studies have demonstrated variable patterns of longitudinal septal deformation in patients with left ventricular (LV) dysfunction and left bundle branch block. This prospective single center study was designed to assess the relationship between septal deformation patterns obtained by two-dimensional speckle-tracking echocardiography and response to cardiac resynchronization therapy (CRT). Methods One hundred one patients with New York Heart Association class II to IV heart failure, LV ejection fractions ≤ 35%, and left bundle branch block underwent echocardiography before CRT. Longitudinal two-dimensional speckle-tracking strain analysis in the apical four-chamber view identified three patterns: double-peaked systolic shortening (pattern 1), early pre-ejection shortening peak followed by prominent systolic stretch (pattern 2), and pseudonormal shortening with a late systolic shortening peak and less pronounced end-systolic stretch (pattern 3). CRT response was defined as a relative reduction in LV end-systolic volume of ≥15% at 9-month follow-up. CRT super-response was defined as an absolute LV ejection fraction of ≥50% associated with a relative reduction in LV end-systolic volume of ≥15% and an improvement in New York Heart Association functional class. Cardiac death or hospitalization for heart failure during follow-up was systematically investigated. Results Ninety-two percent of patients with pattern 1 or 2 were responders to CRT compared with 59% with pattern 3 (P <0001). Thirty-six percent of patients with pattern 1 were super-responders compared with 15% of those with pattern 2 and 12% of those with pattern 3 (P =.037). The improvement in LV volumes, LV ejection fraction, and global longitudinal strain after CRT was better in patients with pattern 1 or 2 compared with those with pattern 3 (P <.0001 for all). Eighteen-month outcomes were excellent in patients with pattern 1 or 2, with event-free survival of 95 ± 3% compared with 75 ± 7% in patients with pattern 3 (P =.010). Conclusions Septal deformation strain pattern 1 or 2 is highly predictive of CRT response. Further studies are needed to identify predictors of "nonresponse" in patients with a pattern 3. Copyright © 2014 by the American Society of Echocardiography.


Millot F.,Center Hospitalier University Amiens | Clavel G.,Center Hospitalier University Amiens | Clavel G.,Rothschild | Etchepare F.,CHU Pitie Salpetriere | And 7 more authors.
Journal of Rheumatology | Year: 2011

Objective. To confirm the occurrence of bone erosions and synovitis in healthy subjects detectable by ultrasound (US) and to establish US criteria for early arthritis. Methods. Our study involved 127 healthy subjects matched with a cohort of patients with early arthritis (the ESPOIR cohort). The second and fifth metacarpophalangeal (MCP) joints and the fifth metatarsophalangeal (MTP) joint of both hands and feet were assessed with US to detect bone erosion; and the second, third, fourth, and fifth MCP and the fifth MTP were evaluated for synovial thickening in B-mode US and synovial vascularity in power Doppler. Bone erosion and synovitis were defined according to the Outcome Measures in Rheumatology Clinical Trials consensus. Results. Bone erosion and grade 2-3 synovial thickening in B-mode were detected in 11% and 9% of healthy subjects. To consider the diagnosis of early arthritis, a cutoff at 1 case of synovial thickening in B-mode enabled discrimination between patients with early arthritis and healthy subjects, with a good sensitivity of 74.8% (95% CI 67.2%-82.3%) and a high specificity of 90.5% (95% CI 85.4%-95.6%). If higher specificity is required to confirm the diagnosis of early arthritis, cutoff at 2 cases of synovial thickening in B-mode or at 2 cases of bone erosion gave optimal results, with specificity of 98.4% (95% CI 96.2%-100%) and 100%, respectively, and lower sensitivity of 59.8% (95% CI 51.2%-68.3%) and 17% (95% CI 10.5%-23.5%) (area under the curve = 0.85 for synovitis and 0.63 for bone erosion). Neither the combination of power Doppler signal plus bone erosion, nor bone erosions plus synovial thickening on the same joint, were seen in healthy subjects. Conclusion. A single case of bone erosion or synovial thickening in B-mode is common in healthy subjects. However, more than 1 case of synovial thickening in B-mode or bone erosion is a strong argument for the diagnosis of early inflammatory arthritis. The Journal of Rheumatology Copyright © 2011. All rights reserved.


PubMed | Center Hospitalier University Amiens, Hopital Henri Mondor, University of Paris Descartes and University Paris Diderot
Type: Journal Article | Journal: The British journal of surgery | Year: 2016

The impact of morbidity on long-term outcomes following liver resection for intrahepatic cholangiocarcinoma is currently unclear.This was a retrospective analysis of all consecutive patients who underwent liver resection for intrahepatic cholangiocarcinoma with curative intent in 24 university hospitals between 1989 and 2009. Severe morbidity was defined as any complication of Dindo-Clavien grade III or IV. Patients with severe morbidity were compared with those without in terms of demographics, pathology, management, morbidity, overall survival, disease-free survival and time to recurrence. Independent predictors of severe morbidity were identified by multivariable analysis.A total of 522 patients were enrolled. Severe morbidity occurred in 113 patients (216 per cent) and was an independent predictor of overall survival (hazard ratio 164, 95 per cent c.i. 121 to 223), as were age at resection, multifocal disease, positive lymph node status and R0 resection margin. Severe morbidity did not emerge as an independent predictor of disease-free survival. Independent predictors of time to recurrence included severe morbidity, tumour size, multifocal disease, vascular invasion and R0 resection margin. Major hepatectomy and intraoperative transfusion were independent predictors of severe morbidity.Severe morbidity adversely affects overall survival following liver resection for intrahepatic cholangiocarcinoma.

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