Follow-up Study to Evaluate the Long-term Safety and Efficacy of Darvadstrocel (Mesenchymal Stem Cell Treatment) in Patients With Perianal Fistulizing Crohn’s Disease: ADMIRE-CD phase 3 randomized controlled trial

BACKGROUND: Darvadstrocel is an expanded allogeneic adipose-derived mesenchymal stem cell therapy for the treatment of complex perianal fistulas in patients with Crohn’s disease. Safety and efficacy outcomes from the clinical trial known as “Adipose derived mesenchymal stem cells for induction of remission in perianal fistulizing Crohn’s disease,” or ADMIRE-CD (NCT01541579), from up to 52 weeks posttreatment were previously reported. Here, the outcomes from an extended 104-week follow-up are reported. OBJECTIVE: The goal of this study was to assess the long-term safety and efficacy of darvadstrocel at 2 years post-treatment in patients with Crohn’s disease and complex perianal fistulas. DESIGN: This was a phase 3 double-blind randomized controlled study (ADMIRE-CD) in patients with perianal fistulizing Crohn’s disease. SETTINGS: This study extension was conducted in multiple hospitals across 7 European countries and Israel. PATIENTS: Forty patients entered the extended follow-up period: 25 patients in the darvadstrocel treatment group and 15 in the control group. INTERVENTIONS: Darvadstrocel or saline solution (control group) was administered once, locally, after fistula tract curettage and internal opening closure (with previous seton placement). All patients were permitted to continue ongoing medical treatments for fistulas. MAIN OUTCOME MEASURES: Treatment-emergent serious adverse events were recorded through week 104. Clinical remission, defined as closure of all treated external openings that were draining at baseline despite gentle finger compression, was assessed at week 104. RESULTS: Of 40 patients, 37 completed the extended follow-up. Through week 104, 7 treatment-emergent serious adverse events were reported, of which 4 occurred between weeks 52 and 104. At week 104, clinical remission was reported in 14/25 (56%) patients in the darvadstrocel group and 6/15 (40%) patients in the control group. LIMITATIONS: Limitations include the small number of patients who entered the extended follow-up period, and no imaging examinations were performed at the 104-week time point. CONCLUSIONS: Darvadstrocel was well tolerated and clinical remission after treatment with darvadstrocel may be sustained for up to 104 weeks in patients with perianal fistulizing Crohn’s disease

The mucosal addressin cell adhesion molecule antibody PF-00547,659 in ulcerative colitis: a randomised study

Background and aims: Leucocyte migration to gut mucosa, mediated by integrin binding to mucosal addressin cell adhesion molecule (MAdCAM), is a promising target for therapeutic intervention in inflammatory bowel disease. This first-in-human study of a monoclonal antibody to MAdCAM, PF-00547,659, aimed to explore the safety and preliminary efficacy of this gut-specific mechanism in ulcerative colitis. Methods: In this randomised, double-blind placebo-controlled study, 80 patients with active ulcerative colitis received single or multiple (three doses, 4-week intervals) doses of PF-00547,659 0.03–10 mg/kg IV/SC, or placebo. Safety was assessed by adverse events, laboratory tests, and immunogenicity. Exploratory efficacy analyses were based on Mayo score and endoscopic responder rates at weeks 4 and 12. Faecal calprotectin was quantified as a measure of disease activity, and the number of α4β7+ lymphocytes was measured to demonstrate drug activity. Results: No obvious drug-related side effects were observed in the PF-00547,659 group, while patient numbers, especially those fully exposed, were small. Overall responder/remission rates at 4 and 12 weeks were 52%/13% and 42%/22%, respectively with combined PF-00547,659 doses compared with 32%/11% and 21%/0%, respectively with placebo. Equivalent endoscopic responder rates were 50% and 42% versus 26% and 29%, respectively. Faecal calprotectin levels decreased to a greater extent with PF-00547,659 than placebo (week 4: 63% vs 18%). Despite variability, there was a trend for an increase in α4β7+ lymphocytes in patients receiving PF-00547,659. Conclusions: The favourable short-term safety profile and preliminary efficacy findings for PF-00547,659 in this first-in-human study pave the way for further investigation in larger trials, to establish the role of PF-00547,659 in ulcerative colitis treatment

Assessment of needs, health-related quality of life, and satisfaction with care in breast cancer patients to better target supportive care

Background This study assessed whether breast cancer (BC) patients express similar levels of needs for equivalent severity of symptoms, functioning difficulties, or degrees of satisfaction with care aspects. BC patients who did (or not) report needs in spite of similar difficulties were identified among their sociodemographic or clinical characteristics. Patients and methods Three hundred and eighty-four (73% response rate) BC patients recruited in ambulatory or surgery hospital services completed the European Organisation for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ)-C30 quality of life [health-related quality of life (HRQOL)], the EORTC IN-PATSAT32 (in-patient) or OUT-PATSAT35 (out-patient) satisfaction with care, and the supportive care needs survey short form 34-item (SCNS-SF34) measures. Results HRQOL or satisfaction with care scale scores explained 41%, 45%, 40% and 22% of variance in, respectively, psychological, physical/daily living needs, information/health system, and care/support needs (P < 0.001). BC patients' education level, having children, hospital service attendance, and anxiety/depression levels significantly predicted differences in psychological needs relative to corresponding difficulties (adjusted R2 = 0.11). Medical history and anxiety/depression levels significantly predicted differences in information/health system needs relative to degrees of satisfaction with doctors, nurses, or radiotherapy technicians and general satisfaction (adjusted R2 = 0.12). Unmet needs were most prevalent in the psychological domains across hospital services. Conclusions Assessment of needs, HRQOL, and satisfaction with care highlights the subgroups of BC patients requiring better supportive care targetin

Theoretical and Experimental Considerations for Neutrinoless Double Beta Decay

In the rst part of this work we show some theoretical aspects of the generation of the neutrino mass by means of a direct extension of the Standard Model of particles, which include the presence of heavy right-handed neutrinos and large Majorana mass terms. From these two new ingredients, it is possible to nd a mass for the light neutrinos which is naturally of the order of 1 eV or less. The idea is to put these theoretical aspects in the context of the search for neutrino mass values by the study of the signal from the Neutrinoless Double Beta Decay Process (0 ). In the second part, a brief summary is given of the experimental considerations required for the measurement of effective Majorana neutrino mass using (0 ). Measurement strategies and background considerations are introduced and an outline of both active and passive methods is given. Finally, current results are discussed with particular emphasis on the HeidelbergMoscow experiment. This note is based on the presentation given at the CERNCLAF 4th Latin American School on High-Energy Physics

Development of Red Flags Index for Early Referral of Adults with Symptoms and Signs Suggestive of Crohn's Disease: An IOIBD Initiative

International audience; BACKGROUND AND AIMS:Diagnostic delay is frequent in patients with Crohn's disease (CD). We developed a tool to predict early diagnosis.METHODS:A systematic literature review and 12 CD specialists identified 'Red Flags', i.e. symptoms or signs suggestive of CD. A 21-item questionnaire was administered to 36 healthy subjects, 80 patients with irritable bowel syndrome (non-CD group) and 85 patients with recently diagnosed (<18 months) CD. Patients with CD were asked to recall symptoms and signs they experienced during the 12 months before diagnosis. Multiple logistic regression analyses selected and weighted independent items to construct the Red Flags index. A receiver operating characteristic curve was used to assess the threshold that discriminated CD from non-CD. Association with the Red Flags index relative to this threshold was expressed as the odds ratios (OR).RESULTS:Two hundred and one subjects, CD and non-CD, answered the questionnaire. The multivariate analysis identified eight items independently associated with a diagnosis of CD. A minimum Red Flags index value of 8 was highly predictive of CD diagnosis with sensitivity and specificity bootstrap estimates of 0.94 (95% confidence interval 0.88-0.99) and 0.94 (0.90-0.97), respectively. Positive and negative likelihood ratios were 15.1 (9.3-33.6) and 0.066 (0.013-0.125), respectively. The association between CD diagnosis and a Red Flags index value of ≥8 corresponds to an OR of 290 (p < 0.0001).CONCLUSIONS:The Red Flags index using early symptoms and signs has high predictive value for the diagnosis of CD. These results need prospective validation prior to introduction into clinical practice

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011