Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): A randomised, double-blind, placebo-controlled, phase 3 trial
Moskowitz C.H.,Sloan Kettering Cancer Center |
Nademanee A.,City of Hope National Medical Center |
Masszi T.,Szent Istvan and Szent Laszlo Corporate Hospital Hematology |
Agura E.,Baylor University |
And 16 more authors.
The Lancet | Year: 2015
Background High-dose therapy followed by autologous stem-cell transplantation is standard of care for patients with relapsed or primary refractory Hodgkin's lymphoma. Roughly 50% of patients might be cured after autologous stem-cell transplantation; however, most patients with unfavourable risk factors progress after transplantation. We aimed to assess whether brentuximab vedotin improves progression-free survival when given as early consolidation after autologous stem-cell transplantation. Methods We did this randomised, double-blind, placebo-controlled, phase 3 trial at 78 sites in North America and Europe. Patients with unfavourable-risk relapsed or primary refractory classic Hodgkin's lymphoma who had undergone autologous stem-cell transplantation were randomly assigned, by fixed-block randomisation with a computer-generated random number sequence, to receive 16 cycles of 1·8 mg/kg brentuximab vedotin or placebo intravenously every 3 weeks, starting 30-45 days after transplantation. Randomisation was stratified by best clinical response after completion of salvage chemotherapy (complete response vs partial response vs stable disease) and primary refractory Hodgkin's lymphoma versus relapsed disease less than 12 months after completion of frontline therapy versus relapse 12 months or more after treatment completion. Patients and study investigators were masked to treatment assignment. The primary endpoint was progression-free survival by independent review, defined as the time from randomisation to the first documentation of tumour progression or death. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01100502. Findings Between April 6, 2010, and Sept 21, 2012, we randomly assigned 329 patients to the brentuximab vedotin group (n=165) or the placebo group (n=164). Progression-free survival by independent review was significantly improved in patients in the brentuximab vedotin group compared with those in the placebo group (hazard ratio [HR] 0·57, 95% CI 0·40-0·81; p=0·0013). Median progression-free survival by independent review was 42·9 months (95% CI 30·4-42·9) for patients in the brentuximab vedotin group compared with 24·1 months (11·5-not estimable) for those in the placebo group. We recorded consistent benefit (HR <1) of brentuximab vedotin consolidation across subgroups. The most frequent adverse events in the brentuximab vedotin group were peripheral sensory neuropathy (94 [56%] of 167 patients vs 25 [16%] of 160 patients in the placebo group) and neutropenia (58 [35%] vs 19 [12%] patients). At time of analysis, 28 (17%) of 167 patients had died in the brentuximab vedotin group compared with 25 (16%) of 160 patients in the placebo group. Interpretation Early consolidation with brentuximab vedotin after autologous stem-cell transplantation improved progression-free survival in patients with Hodgkin's lymphoma with risk factors for relapse or progression after transplantation. This treatment provides an important therapeutic option for patients undergoing autologous stem-cell transplantation. Funding Seattle Genetics and Takeda Pharmaceuticals International. © 2015 Elsevier Ltd.
Cirillo I.,Navy Medical Service |
Ricciardolo F.L.M.,University of Turin |
Medusei G.,Navy Medical Service |
Signori A.,University of Genoa |
Ciprandi G.,IRCCS Azienda Ospedaliera
International Archives of Allergy and Immunology | Year: 2013
Background: Nowadays it is possible to assess airway inflammation by measuring the fractional concentration of exhaled nitric oxide (FeNO) during an office visit and there is international consensus on the testing methodology. The aim of this study was to evaluate whether FeNO measurement may be a predictor of bronchial hyperreactivity (BHR) in patients with allergic rhinitis (AR). Methods: Two hundred eleven patients (196 males, median age 28.5 years) suffering from persistent AR were evaluated. Values for bronchial function (FVC, FEV1, and FEF25-75), bronchial provocation tests (methacholine), exhaled nitric oxide (FeNO), a visual analogue scale for nasal and bronchial symptoms, and sensitization were assessed. Results: A strong and inverse correlation between FeNO levels and BHR severity was found (r = -0.58). FeNO was a predictive factor for BHR, and 37 ppb was found to be the best cutoff (area under the curve 0.90) to define the presence of BHR in patients with AR. Conclusions: This study highlights the relevance of FeNO as a possible predictive marker for BHR in AR patients and underlines the close link between upper and lower airways. Thus, FeNO measurement could be a useful screening tool in identifying subjects with rhinitis at risk of developing asthma. © 2012 S. Karger AG, Basel.
Rouzier R.,University Pierre and Marie Curie |
Rouzier R.,Institute Paoli Calmette |
Pronzato P.,IRCCS Azienda Ospedaliera |
Chereau E.,Institute Paoli Calmette |
And 3 more authors.
Breast Cancer Research and Treatment | Year: 2013
Breast cancer is the most common female cancer and is associated with a significant clinical and economic burden. Multigene assays and molecular markers represent an opportunity to direct chemotherapy only to patients likely to have significant benefit. This systematic review examines published health economic analyses to assess the support for adjuvant therapy decision making. Literature searches of PubMed, the Cochrane Library, and congress databases were carried out to identify economic evaluations of multigene assays and molecular markers published between 2002 and 2012. After screening and data extraction, study quality was assessed using the Quality of Health Economic Studies instrument. The review identified 29 publications that reported evaluations of two assays: Oncotype DX® and MammaPrint. Studies of both tests provided evidence that their routine use was cost saving or cost-effective versus conventional approaches. Benefits were driven by optimal allocation of adjuvant chemotherapy and reduction in chemotherapy utilization. Findings were sensitive to variation in the frequency of chemotherapy prescription, chemotherapy costs, and patients' risk profiles. Evidence suggests that multigene assays are likely cost saving or cost-effective relative to current approaches to adjuvant therapy. They should benefit decision making in early-stage breast cancer in a variety of settings worldwide. © 2013 The Author(s).
Tagliafico A.,University of Genoa |
Cadoni A.,University of Genoa |
Fisci E.,University of Genoa |
Gennaro S.,IRCCS Azienda Ospedaliera |
And 4 more authors.
Seminars in Musculoskeletal Radiology | Year: 2012
Imaging studies including ultrasound (US) and magnetic resonance imaging may be required to evaluate the median nerve in patients with suspected carpal tunnel syndrome. However, the radial and ulnar nerves contribute to sensory and motor innervations to the hand as well. Compressive, traumatic, and iatrogenic events may damage the small terminal branches of these nerves. In the hand, US is able to identify injuries of the median, ulnar, radial nerve, and terminal branches. This article presents the role of imaging to evaluate the nerves of the hand with an emphasis on US. Due to its high-resolution capabilities, US is useful to determine the location, extent, and type of nerve lesion. Moreover, US is useful for a postsurgical assessment. The anterior interosseous nerve, Guyon's tunnel syndrome, and Wartenberg's syndrome are also described. Copyright © 2012 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.
Tocci G.,University of Rome La Sapienza |
Ferrucci A.,University of Rome La Sapienza |
Pontremoli R.,IRCCS Azienda Ospedaliera |
Ferri C.,University of L'Aquila |
And 6 more authors.
Journal of Human Hypertension | Year: 2015
This analysis is aimed to determine blood pressure (BP) levels and BP control rates in a large population of hypertensive patients in Italy. Data were taken from two large and inclusive cross-sectional surveys, which covered two distinct and subsequent time periods (2000-2005 and 2005-2011, respectively). Observational clinical studies and surveys, which reported average systolic/diastolic clinic BP levels, proportions of treated/untreated and controlled/uncontrolled patients, and prevalence of cardiovascular risk factors in hypertensive patients followed in either outpatient clinics, hypertension centres or general practice, were considered for the analyses. The overall sample included 211 591 hypertensive patients (119 997 (56.7%) women, age 57.0±10.0 years, body mass index 26.9±4.0 kg m -2, BP levels 146.9±16.7/88.7±9.6 mm Hg). BP levels were 148.2±15.4/87.5±9.3 mm Hg in patients followed by general practitioners (n=168 313, 79.5%), 148.1±17.3/90.1±9.7 mm Hg in those followed by hypertension centres (n=28 180, 13.3%), and 142.4±17.6/86.6±9.8 mm Hg in those followed by outpatient clinics and hospital divisions (n=15 098, 7.1%). Among treated hypertensive patients (n=128 079; 60.5%), 43 008 (33.6%) were reported to have controlled BP levels. Over one decade of observation, we reported that ∼60% of hypertensive patients were treated and among these only 33% achieved effective BP control. These findings highlight the need for more effective interventions to improve management of hypertension in Italy. © 2015 Macmillan Publishers Limited.
Tosca M.A.,Instituto Giannina Gaslini |
Silvestri M.,Instituto Giannina Gaslini |
Olcese R.,Instituto Giannina Gaslini |
Pistorio A.,Instituto Giannina Gaslini |
And 2 more authors.
Pediatric Allergy and Immunology | Year: 2012
Background: In children with asthma, discrepancies between objective indicators of airway obstruction and symptom perception are often observed. Although visual analogue scale (VAS) has been proposed as a useful tool for assessing accurate symptom perception, previous studies conducted in children with asthma included only small cohorts. A study was therefore designed to investigate the usefulness of VAS in establishing a reliable relationship between breathlessness perception and lung function in a large cohort of children with clinical diagnosis of asthma. Methods: A total of 703 children [470 boys and 233 girls, median age 10.29 (8.33-12.58)yr] with asthma were included in this cross-sectional, real-life study. Perception of breathlessness was assessed by using VAS, and lung volumes and expiratory flows were measured by spirometry. Results: Most children had intermittent or mild persistent asthma (93.3%), and only 46 children had a significant bronchial obstruction defined by FEV1 values <80% of predicted. Globally, VAS was significantly, even though weakly, related to lung function. Analyzing children with bronchial obstruction, a moderate relationship between both FEV1 (r=0.47) and FEF25-75 (r=0.42) and VAS was detected. A VAS value of 6 was found to be a reliable cutoff for discriminating children with bronchial obstruction (AUC 0.83 at ROC curve; OR 9.4). Conclusion: The present study demonstrates that VAS might be considered a useful tool to assess symptom perception, mainly in children with airflow limitation. © 2012 John Wiley & Sons A/S.
Ratto E.,I.R.C.C.S. Azienda Ospedaliera |
Viazzi F.,I.R.C.C.S. Azienda Ospedaliera |
Bonino B.,I.R.C.C.S. Azienda Ospedaliera |
Gonnella A.,I.R.C.C.S. Azienda Ospedaliera |
And 6 more authors.
Journal of Hypertension | Year: 2015
OBJECTIVE:: A new classification of left ventricular geometry based on left ventricular dilatation and concentricity has recently been developed. This classification identifies subgroups differing with regard to systemic haemodynamics, left ventricular function and cardiovascular prognosis. We investigated the relationship between the new classification of left ventricular geometry and subclinical renal damage, namely urine albumin excretion and early intrarenal vascular changes in primary hypertensive patients. METHODS:: A total of 449 untreated hypertensive patients were studied. Four different patterns of left ventricular hypertrophy (eccentric nondilated, eccentric dilated, concentric nondilated and concentric dilated hypertrophy) were identified by echocardiography. Albuminuria was measured as the albumin-to-creatinine ratio. Early intrarenal vascular changes, expressed as the renal volume to resistive index ratio, were evaluated by ultrasound and Doppler scan. RESULTS:: Patients with concentric dilated left ventricular hypertrophy had higher albumin excretion rates (P=0.0258) and prevalence of microalbuminuria (P<0.0001) and lower renal volume to resistive index ratio than patients with concentric nondilated hypertrophy (P=0.0093). Patients with eccentric dilated hypertrophy showed a higher prevalence of microalbuminuria than patients with eccentric nondilated hypertrophy (P<0.0001). Moreover, patients with chamber dilatation showed a higher prevalence of microalbuminuria (P=0.0002) and lower renal volume to resistive index ratio (P=0.0107) than patients without chamber dilatation. After adjusting for potentially confounding variables, left ventricular chamber dilatation was an independent predictor of subclinical renal damage. CONCLUSION:: Left ventricular dilatation is associated with subclinical renal damage in hypertension. These findings extend previous reports and provide a pathophysiological rationale for the observed unfavourable prognosis in patients with left ventricular dilatation. © 2015 Wolters Kluwer Health, Inc.
Knee instability signs: Preliminary comparison between conventional ana weight-bearing MRI in patients with complete anterior cruciate ligament tear [Instabilità di ginocchio: Confronto preliminare tra RM standard e in carico in pazienti con lesione completa del LCA]
Villosio N.,IRCCS Azienda Ospedaliera |
Villosio N.,Centro Provinciale Medicina Dello Sport Citta Of Cuneo |
Piccazzo R.,IRCCS Azienda Ospedaliera |
Paparo F.,IRCCS Azienda Ospedaliera |
And 3 more authors.
Medicina dello Sport | Year: 2013
Aim: Knee instability is a relevant issue in patients with a complete anterior cruciate ligament (ACL) tear. Magnetic resonance imaging (MRI) is effective in the evaluation of instability signs in such patients. However, conventional MRI cannot provide an effective analysis of knee instability in standing position. The purpose of our study was to evaluate indirect signs of knee instability comparing conventional and weight-bearing MRI in patients with ACL tear. Methods: Ten patients (7 males, 3 females; mean age 38.4±13.19 standard deviation) witn previous clinical and MRI diagnosis of ACL complete tear were evaluated performing two SE T1-weighted sequences (TR=890 ms, TE=24 ms; slice thickness=4.5 mm) both on sagittal and coronal planes. Scans were performed both in standard supine position and in weight-bearing position, using a low-field rotating MRI system (G-Scan, Esaote Biomedica, Genoa, Italy). For each patient, we evaluated signs of knee instability, i.e., verticalization of lateral collateral ligament on coronal images, posterior cruciate ligament buckling, and anterior displacement of the tibia on sagittal images. For each patient, one radiologist with 15 years experience in MSK MRI graded each item as follows: O=not present; 1=low-grade; 2=mild; 3=relevant, considering both conventional and weight-bearing examinations. K statistics were used. Results: Lateral collateral ligament verticalization was graded as a median number of 1 (0.25-1.75 25th-75th percentile) in standard position and 2 (1.25-2) in weight bearing position, posterior cruciate ligament buckling was 0.5 (0-1) and 1 (1-1.75), and anterior displacement of tne tibia was 1.5 (0.25-2) and 2.5 (1.25-3), respectively. Conclusion: Weight-bearing MRI allowed for an increase detection of knee instability signs in patients with complete ACL tear, compared to conventional MRI. Further investigations on a larger sample are needed to confirm our preliminary data. Reproducing the physiological condition of standing, weigntbearing MRI could be more effective in the detection of knee instability compared to standard MRI in patients with complete ACL rupture.
Rosa G.M.,IRCCS Azienda Ospedaliera |
Bianco D.,IRCCS Azienda Ospedaliera |
Parodi A.,IRCCS Azienda Ospedaliera |
Valbusa A.,IRCCS Azienda Ospedaliera |
And 4 more authors.
Expert Opinion on Drug Metabolism and Toxicology | Year: 2014
Introduction: Atrial fibrillation (AF) is the most common arrhythmia and is associated with increased morbidity and mortality. Dronedarone is a recent antiarrhythmic drug that has been developed for treatment of AF, with electrophysiological properties similar to amiodarone but with a lower incidence of side effects.Areas covered: This review evaluates the efficacy, safety, tolerability and side effects of dronedarone in the treatment of AF. In particular, the review includes studies comparing: dronedarone and placebo (ANDROMEDA, ATHENA, DAFNE, ERATO, EURIDIS/ADONIS, HESTIA, PALLAS trials), dronedarone and amiodarone (DIONYSOS trial), ranolazine and dronedarone given alone and in combination (HARMONY trial).Expert opinion: Dronedarone is an interesting antiarrhythmic agent in well-selected groups of patients. It also has several other pleiotropic effects that may potentially be beneficial in clinical practice, such as the reduction of the risk of stroke and acute coronary syndromes. In addition, combination therapies such as those with dronedarone and ranolazine, currently being investigated in the HARMONY trial, may provide another interesting approach to increase the antiarrhythmic efficacy and further reduce the incidence of side effects. A better understanding of the mechanisms underlying dronedarone's pleiotropic actions is expected to facilitate the selection of patients benefiting from dronedarone, as well as the development of novel antiarrhythmic drugs for AF. © 2014 Informa UK, Ltd.