Thibault F.,University Pierre and Marie Curie |
Dromain C.,Institute Of Cancerologie Gustave Roussy |
Breucq C.,Universitair Ziekenhuis |
Balleyguier C.S.,Institute Of Cancerologie Gustave Roussy |
And 5 more authors.
European Radiology | Year: 2013
Objectives: To compare the diagnostic performance of single-view breast tomosynthesis (BT) with that of dual-view mammography (MX); to assess the benefit of adding the craniocaudal (CC) mammographic view to BT, and of adding BT to MX plus breast ultrasound, considered to be the reference work-up. Methods: One hundred and fifty-five consenting patients with unresolved mammographic and/or ultrasound findings or breast symptoms underwent conventional work-up plus mediolateral oblique-view BT of the affected breast. The final study set in 130 patients resulted in 55 malignant and 76 benign and normal cases. Seven breast radiologists rated the cases through five sequential techniques using a BIRADS-based scale: MX, MX + ultrasound, MX + ultrasound + BT, BT, BT + MX(CC). Multireader, multicase receiver operating characteristic (ROC) analysis was performed and performance of the techniques was assessed from the areas under ROC curves. The performance of BT and of BT + MX(CC) was tested versus MX; the performance of MX + ultrasound + BT tested versus MX + ultrasound. Results: Tomosynthesis was found to be non-inferior to mammography. BT + MX(CC) did not appear to be superior to MX, and MX + ultrasound + BT not superior to MX + ultrasound. Conclusions: Overall, none of the five techniques tested outperformed the others. Further clinical studies are needed to clarify the role of BT as a substitute for traditional work-up in the diagnostic environment. Key Points: • Digital breast tomosynthesis is a new adjunct to mammography and breast ultrasound. • We compared the diagnostic performance of these investigations in an experimental observer study. • Single-view breast tomosynthesis was confirmed as non-inferior to dual-view mammography. • None of the investigations (or combinations) tested outperformed the others. • Further prospective studies are needed to clarify precise role of tomosynthesis for diagnostic application. © 2013 European Society of Radiology.
Wolchok J.D.,Sloan Kettering Cancer Center |
Neyns B.,Universitair Ziekenhuis |
Linette G.,University of Washington |
Negrier S.,Center Leon Berard |
And 12 more authors.
The Lancet Oncology | Year: 2010
Background: Ipilimumab is a human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen 4 and has shown promising activity in advanced melanoma. We aimed to ascertain the antitumour efficacy of ipilimumab in patients with advanced melanoma. Methods: We undertook a randomised, double-blind, phase 2 trial in 66 centres from 12 countries. 217 patients with previously treated stage III (unresectable) or stage IV melanoma were randomly assigned a fixed dose of ipilimumab of either 10 mg/kg (n=73), 3 mg/kg (n=72), or 0·3 mg/kg (n=72) every 3 weeks for four cycles (induction) followed by maintenance therapy every 3 months. Randomisation was done with a permuted block procedure, stratified on the basis of type of previous treatment. The primary endpoint was best overall response rate (the proportion of patients with a complete or partial response, according to modified WHO criteria). Efficacy analyses were done by intention to treat, whereas safety analyses included patients who received at least one dose of ipilimumab. This study is registered with ClinicalTrials.gov, number NCT00289640. Findings: The best overall response rate was 11·1% (95% CI 4·9-20·7) for 10 mg/kg, 4·2% (0·9-11·7) for 3 mg/kg, and 0% (0·0-4·9) for 0·3 mg/kg (p=0·0015; trend test). Immune-related adverse events of any grade arose in 50 of 71, 46 of 71, and 19 of 72 patients at doses of 10 mg/kg, 3 mg/kg, and 0·3 mg/kg, respectively; the most common grade 3-4 adverse events were gastrointestinal immune-related events (11 in the 10 mg/kg group, two in the 3 mg/kg group, none in the 0·3 mg/kg group) and diarrhoea (ten in the 10 mg/kg group, one in the 3 mg/kg group, none in the 0·3 mg/kg group). Interpretation: Ipilimumab elicited a dose-dependent effect on efficacy and safety measures in pretreated patients with advanced melanoma, lending support to further studies at a dose of 10 mg/kg. Funding: Bristol-Myers Squibb. © 2010 Elsevier Ltd. All rights reserved.
Vincent J.-L.,Free University of Colombia |
Sakr Y.,Friedrich - Schiller University of Jena |
Groeneveld J.,VU University Amsterdam |
Zandstra D.F.,Onze Lieve Vrouwe Gasthuis |
And 4 more authors.
Chest | Year: 2010
Background: Differences in outcomes have been demonstrated for critically ill patients with late-onset compared with early-onset renal failure and late-onset compared with early-onset shock, which could cause a lead-time bias in clinical trials assessing potential therapies for these conditions. We used data from a large, multicenter observational study to assess whether late-onset ARDS was similarly associated with worse outcomes compared with early-onset ARDS. Methods: Data were extracted from the Sepsis Occurrence in Acutely Ill Patients (SOAP) study, which involved 198 ICUs from 24 European countries. All adult patients admitted to a participating ICU between May 1, 2002 and May 15, 2002, were eligible, except those admitted for uncomplicated postoperative surveillance. Early/late onset acute lung injury (ALI)/ARDS was defined as ALI/ARDS occurring within/after 48 h of ICU admission. Results: Of the 3,147 patients included in the SOAP study, 393 (12.5%) had a diagnosis of ALI/ARDS; 254 had early-onset ALI/ARDS (64.6%), and 139 (35.5%) late-onset. Patients with early-onset ALI/ARDS had higher Simplified Acute Physiology II scores on admission and higher initial Sequential Organ Failure Assessment scores. Patients with late-onset ALI/ARDS had longer ICU and hospital lengths of stay than patients with early-onset ALI/ARDS. ICU and hospital mortality rates were, if anything, lower in late-onset ALI/ARDS than in early-onset ALI/ARDS, but these differences were not statistically significant. Conclusions: There were no significant differences in mortality rates between early- and late-onset ARDS, but patients with late-onset ALI/ARDS had longer ICU and hospital lengths of stay. © 2010 American College of Chest Physicians.
Harton G.L.,Reprogenetics LLC |
Harton G.L.,Genetics and IVF Institute |
De Rycke M.,Universitair Ziekenhuis |
Fiorentino F.,Genoma Laboratories |
And 5 more authors.
Human Reproduction | Year: 2011
In 2005, the European Society for Human Reproduction and Embryology (ESHRE) PGD Consortium published a set of Guidelines for Best Practice PGD to give information, support and guidance to potential, existing and fledgling PGD programmes. The subsequent years have seen the introduction of a number of new technologies as well as the evolution of current techniques. Additionally, in light of recent advice from ESHRE on how practice guidelines should be written and formulated, the Consortium believed it was timely to revise and update the PGD guidelines. Rather than one document that covers all of PGD, as in the original publication, these guidelines are separated into four new documents that apply to different aspects of a PGD programme, i.e. Organization of a PGD centre, fluorescence in situ hybridization-based testing, Amplification-based testing and Polar Body and Embryo Biopsy for PGD/preimplantation genetic screening. Here, we have updated the sections that pertain to amplification-based PGD. Topics covered in this guideline include inclusion/exclusion criteria for amplification-based PGD testing, preclinical validation of tests, amplification-based testing methods, tubing of cells for analysis, set-up of local IVF centre and Transport PGD centres, quality control/quality assurance and diagnostic confirmation of untransferred embryos. © 2010 The Author.
De Benedetti F.,Instituto Of Ricovero E Cura A Carattere Scientifico Irccs Ospedale Pediatrico Bambino Gesu |
Brunner H.I.,Cincinnati Childrens Hospital Medical Center |
Ruperto N.,Irccs Instituto G Gaslini |
Kenwright A.,Hoffmann-La Roche |
And 23 more authors.
New England Journal of Medicine | Year: 2012
BACKGROUND: Systemic juvenile idiopathic arthritis (JIA) is the most severe subtype of JIA; treatment options are limited. Interleukin-6 plays a pathogenic role in systemic JIA. METHODS: We randomly assigned 112 children, 2 to 17 years of age, with active systemic JIA (duration of ≥6 months and inadequate responses to nonsteroidal antiinflammatory drugs and glucocorticoids) to the anti-interleukin-6 receptor antibody tocilizumab (at a dose of 8 mg per kilogram of body weight if the weight was ≥30 kg or 12 mg per kilogram if the weight was <30 kg) or placebo given intravenously every 2 weeks during the 12-week, double-blind phase. Patients meeting the predefined criteria for nonresponse were offered open-label tocilizumab. All patients could enter an open-label extension. RESULTS: At week 12, the primary end point (an absence of fever and an improvement of 30% or more on at least three of the six variables in the American College of Rheumatology [ACR] core set for JIA, with no more than one variable worsening by more than 30%) was met in significantly more patients in the tocilizumab group than in the placebo group (64 of 75 [85%] vs. 9 of 37 [24%], P<0.001). At week 52, 80% of the patients who received tocilizumab had at least 70% improvement with no fever, including 59% who had 90% improvement; in addition, 48% of the patients had no joints with active arthritis, and 52% had discontinued oral glucocorticoids. In the double-blind phase, 159 adverse events, including 60 infections (2 serious), occurred in the tocilizumab group, as compared with 38, including 15 infections, in the placebo group. In the double-blind and extension periods combined, 39 serious adverse events (0.25 per patient-year), including 18 serious infections (0.11 per patient-year), occurred in patients who received tocilizumab. Neutropenia developed in 19 patients (17 patients with grade 3 and 2 patients with grade 4), and 21 had aminotransferase levels that were more than 2.5 times the upper limit of the normal range. CONCLUSIONS: Tocilizumab was efficacious in severe, persistent systemic JIA. Adverse events were common and included infection, neutropenia, and increased aminotransferase levels. (Funded by Hoffmann-La Roche; ClinicalTrials.gov number, NCT00642460.) Copyright © 2012 Massachusetts Medical Society.
Doody K.,Center for Assisted Reproduction |
Devroey P.,Universitair Ziekenhuis |
Gordon K.,Schering |
Witjes H.,Schering Plough Research Institute |
Mannaerts B.,Schering Plough Research Institute
Reproductive BioMedicine Online | Year: 2010
The possible relationship between endogenous LH concentrations and clinical outcome was evaluated in 750 patients treated with a standardized gonadotrophin-releasing hormone (GnRH) antagonist and recombinant FSH (rFSH)-only protocol. Serum LH concentrations were measured during stimulation by a central laboratory and patients were stratified into quantiles of
Gonsette R.E.,National Center for Multiple Sclerosis |
Sindic C.,Cliniques Universitaires Saint Luc |
D'Hooghe M.B.,Nationaal Multiple Sclerose Centrum |
De Deyn P.-P.,Algemeen Ziekenhuis Midellheim |
And 4 more authors.
Multiple Sclerosis | Year: 2010
Anti-inflammatory drugs are effective on relapses, but neuroprotective agents to prevent disability are still unavailable. Uric acid has neuroprotective effects in experimental models including encephalomyelitis and appears to be involved in multiple sclerosis. Oral administration of inosine, a precursor of uric acid, increases serum uric acid levels and is well tolerated. Our objective was to test the possibility that a combination therapy associating an anti-inflammatory drug (interferon β) and an endogenous neuroprotective molecule (uric acid) would be more effective than interferon β alone on the accumulation of disability. Patients with relapsing-remitting multiple sclerosis on interferon β for at least 6 months were randomized to interferon β + inosine or interferon β + placebo for 2 years. The dose of inosine was adjusted to maintain serum uric acid levels in the range of asymptomatic hyperuricaemia (≤10mg/dl). The primary end points were percentage of patients with progression of disability and time to sustained progression (Kaplan-Meier analysis). The combination of interferon β and inosine was safe and well tolerated but did not provide any additional benefit on accumulation of disability compared with interferon β alone. We conclude that endogenous neuroprotective mechanisms recently identified in multiple sclerosis are complex and uric acid does not reflect the entire story. © The Author(s) 2010.
Ovarian response to recombinant human follicle-stimulating hormone: A randomized, antimüllerian hormone-stratified, dose-response trial in women undergoing in vitro fertilization/intracytoplasmic sperm injection
Arce J.-C.,11 Health |
Nyboe Andersen A.,Copenhagen University |
Fernandez-Sanchez M.,IVI Seville |
Visnova H.,IVF CUBE SE |
And 6 more authors.
Fertility and Sterility | Year: 2014
Objective: To evaluate the dose -response relationship of a novel recombinant human FSH (rhFSH; FE 999049) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment; and prospectively study the influence of initial antimüllerian hormone (AMH) concentrations. Design: Randomized, controlled, assessor-blinded, AMH-stratified (low: 5.0-14.9 pmol/L [0.7-< 2.1 ng/mL]; high: 15.0-44.9 pmol/L [2.1-6.3 ng/mL]) trial. Setting: Seven infertility centers in four countries. Patient(s): Two hundred sixty-five women aged ≤37 years. Intervention(s): Controlled ovarian stimulation with either 5.2, 6.9, 8.6, 10.3, or 12.1 μg of rhFSH, or 11 μg (150 IU) of follitropin alfa in a GnRH antagonist cycle. Main Outcome Measure(s): Number of oocytes retrieved. Result(s): The number of oocytes retrieved increased in an rhFSH dose-dependent manner, from 5.2 ± 3.3 oocytes with 5.2 μg/d to 12.2 ± 5.9 with 12.1 μg/d. The slopes of the rhFSH dose-response curves differed significantly between the two AMH strata, demonstrating that a 10% increase in dose resulted in 0.5 (95% confidence interval 0.2-0.7) and 1.0 (95% confidence interval 0.7-1.3) more oocytes in the low and high AMH stratum, respectively. Fertilization rate and blastocyst/oocyte ratio decreased significantly with increasing rhFSH doses in both AMH strata. No linear relationship was observed between rhFSH dose and number of blastocysts overall or by AMH strata. Five cases of ovarian hyperstimulation syndrome were reported for the three highest rhFSH doses and in the high AMH stratum. Conclusion(s): Increasing rhFSH doses results in a linear increase in number of oocytes retrieved in an AMH-dependent manner. The availability of blastocysts is less influenced by the rhFSH dose and AMH level. Copyright ©2014 The Authors.
De Baets F.,Universitair Ziekenhuis
Tijdschrift voor Geneeskunde | Year: 2013
Respiratory symptoms (wheezing, a cough, bronchorrea, etc.) are common problems in preschool children. The physiopathology differs in many ways from asthma in older children, adolescents and adults. Allergy is a minor problem, the impact of inflammation and aspecific bronchial hyperresponsiveness has not yet been cleared. Viral infections, the airway diameter and the collapsibility seem to exert a major influence, explaining the natural course. The treatment should follow specific guidelines, relying on evidence-based research. Because of the specific physiopathology in many preschool children, the natural course is different from genuine asthma and relies partly on the growth of the bronchial system. Copyright © 2012, Kowsar Corp.
Dreesman A.,Universitair Ziekenhuis |
Hoorens A.,Universitair Ziekenhuis |
Hachimi-Idrissi S.,Universitair Ziekenhuis
European Journal of Emergency Medicine | Year: 2010
Anticonvulsant hypersensitivity syndrome is a potentially life-threatening delayed hypersensitivity reaction characterized by the triad of fever, rash and multiorgan involvement, which usually occurs within the first weeks of introduction of an antiepileptic drug. It mimics several life-threatening diseases, which makes it potentially difficult to recognize. We describe the case of a 6-year-old boy admitted with anticonvulsant hypersensitivity syndrome after the association of lamotrigine treatment with sodium valproic acid for reluctant epilepsy. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.