Reggio nell'Emilia, Italy
Reggio nell'Emilia, Italy

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PubMed | Service des Maladies du Sang, National and Kapodistrian University of Athens, Fred Hutchinson Cancer Research Center, Hopital du Sacre Coeur de Montreal and 18 more.
Type: Clinical Trial, Phase III | Journal: Haematologica | Year: 2016

Renal impairment is associated with poor prognosis in myeloma. This analysis of the pivotal phase 3 FIRST trial examined the impact of renally adapted dosing of lenalidomide and dexamethasone on outcomes of patients with different degrees of renal impairment. Transplant-ineligible patients not requiring dialysis were randomized 1:1:1 to receive continuous lenalidomide and dexamethasone until disease progression (n=535) or for 18 cycles (72 weeks; n=541), or melphalan, prednisone, and thalidomide for 12 cycles (72 weeks; n=547). Follow-up is ongoing. Patients were grouped by baseline creatinine clearance into no ( 80 mL/min [n=389]), mild ( 50 to < 80 mL/min [n=715]), moderate ( 30 to < 50 mL/min [n=372]), and severe impairment (< 30 mL/min [n=147]) subgroups. Continuous lenalidomide and dexamethasone therapy reduced the risk of progression or death in no, mild, and moderate renal impairment subgroups vs. melphalan, prednisone, and thalidomide therapy (HR = 0.67, 0.70, and 0.65, respectively). Overall survival benefits were observed with continuous lenalidomide and dexamethasone treatment vs. melphalan, prednisone, and thalidomide treatment in no or mild renal impairment subgroups. Renal function improved from baseline in 52.6% of lenalidomide and dexamethasone-treated patients. The safety profile of continuous lenalidomide and dexamethasone was consistent across renal subgroups, except for grade 3/4 anemia and rash, which increased with increasing severity of renal impairment. Continuous lenalidomide and dexamethasone treatment, with renally adapted lenalidomide dosing, was effective for most transplant-ineligible patients with myeloma and renal impairment. Trial registration: ClinicalTrials.gov (NCT00689936); EudraCT (2007-004823-39). Funding: Intergroupe Francophone du Mylome and the Celgene Corporation.


Guitera P.,University of Sydney | Guitera P.,Melanoma Institute Australia | Menzies S.W.,University of Sydney | Longo C.,Arcispedale S Maria Nuova | And 5 more authors.
Journal of Investigative Dermatology | Year: 2012

We describe two algorithms to diagnose basal cell carcinomas (BCCs) and melanomas (MMs) using in vivo reflectance confocal microscopy (RCM). A total of 710 consecutive cutaneous lesions excised to exclude malignancy (216 MMs, 266 nevi, 119 BCCs, 67 pigmented facial macules, and 42 other skin tumors) were imaged by RCM. RCM features were correlated with pathology diagnosis to develop diagnostic algorithms. The diagnostic accuracy of the BCC algorithm defined on multivariate analysis of the training set (50%) and tested on the remaining cases was 100% sensitivity, 88.5% specificity. Positive features were polarized elongated features, telangiectasia and convoluted vessels, basaloid nodules, and epidermal shadowing corresponding to horizontal clefting. Negative features were non-visible papillae, disarrangement of the epidermal layer, and cerebriform nests. Multivariate discriminant analysis on the training set (excluding the BCCs) identified seven independently significant features for MM diagnosis. The diagnostic accuracy of the MM algorithm on the test set was 87.6% sensitivity, 70.8% specificity. The four invasive MMs that were misdiagnosed by RCM were all of nevoid subtype. RCM is a highly accurate non-invasive technique for BCC diagnosis. Good diagnostic accuracy was achieved also for MM diagnosis, although rare variants of melanocytic tumors may limit the strict application of the algorithm. © 2012 The Society for Investigative Dermatology.


Vaglio A.,University of Parma | Catanoso M.G.,Arcispedale S. Maria Nuova | Spaggiari L.,Arcispedale S. Maria Nuova | Magnani L.,Arcispedale S. Maria Nuova | And 9 more authors.
Arthritis and Rheumatism | Year: 2013

Objective Chronic periaortitis (CP) usually responds to glucocorticoids, but some patients have glucocorticoid-refractory disease or contraindications to glucocorticoid therapy. This study was undertaken to evaluate treatment with the anti-interleukin-6 receptor (anti-IL-6R) antibody tocilizumab in 2 patients with CP, one with refractory disease and the other with contraindications to glucocorticoids, and to assess IL-6 levels in an additional cohort of patients with CP. Methods Both patients were given intravenous tocilizumab (8 mg/kg) once every 4 weeks for 6 months. Serum IL-6 was measured in 22 patients with active CP and 16 healthy controls. Tissue IL-6 expression was assessed by confocal microscopy in biopsy specimens obtained from 6 patients with CP. Results In the first patient, whose disease was refractory to various immunosuppressive treatments, tocilizumab added to ongoing therapy with prednisone and methotrexate allowed prednisone withdrawal and induced resolution of symptoms, acute-phase reactant normalization, and reduction in 18F- fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography. The patient experienced a relapse 7 months later and was successfully retreated with tocilizumab. In the second patient, who was unable to tolerate glucocorticoids because of psychiatric side effects, tocilizumab monotherapy induced sustained clinical and laboratory remission, 18F-FDG uptake disappearance, and CP shrinkage. Serum IL-6 levels were significantly higher in patients with active CP than in controls (P < 0.0001), and IL-6 was abundantly expressed in biopsy specimens from CP patients, particularly by T cells, B cells, histiocytes, fibroblasts, and vascular smooth muscle cells. Conclusion Tocilizumab may be a therapeutic option for CP. The systemic and tissue up-regulation of IL-6 in CP, together with the clinical benefit of IL-6R blockade observed in our 2 patients, suggest that IL-6 may contribute to CP pathogenesis. Copyright © 2013 by the American College of Rheumatology.


Zulian F.,University of Padua | Balzarin M.,University of Padua | Falcini F.,University of Florence | Martini G.,University of Padua | And 4 more authors.
Arthritis Care and Research | Year: 2010

Objective. To evaluate the safety and efficacy of abatacept in patients with severe juvenile idiopathic arthritis (JIA)-related uveitis refractory or intolerant to immunosuppressive and anti-tumor necrosis factor α (anti-TNFα) agents. Methods. Patients with JIA-related uveitis refractory to immunosuppressive and anti-TNFα agents were treated with intravenous abatacept (10 mg/kg monthly). Side effects, frequency of uveitis flares, and ocular complications before and after treatment were reported. Results. Seven patients (6 females and 1 male) with a mean uveitis duration of 11.6 years entered the study. All patients had failed previous immunosuppressive therapy and ≥2 anti-TNFα treatments. All patients responded to abatacept and 6 maintained a clinical remission after a mean of 9.2 months of treatment. One patient withdrew from the study with oral mycosis and arthritis flare; no other patients had side effects. The mean frequency of uveitis flares during the 6 months before and after treatment decreased from 3.7 to 0.7 episodes. No new ocular complications or worsening of preexisting ones were reported. Conclusion. Abatacept treatment led to sustained improvement in severe anti-TNFα- resistant JIA-related uveitis and was well tolerated in all but 1 patient. These results provide new insights into a possible indication of abatacept for the treatment of uveitis. © 2010, American College of Rheumatology.


Gobbi P.G.,University of Pavia | Bassi E.,University of Pavia | Bergonzi M.,University of Pavia | Merli F.,Arcispedale S. Maria Nuova | And 5 more authors.
Hematological Oncology | Year: 2012

The purpose of the work was to investigate the factors predicting early resistance to treatment in Hodgkin lymphoma. Many staging parameters, including relative tumour burden (rTB), were analysed in 246 patients with Hodgkin lymphoma in relation to early failure, that is, less than complete remission (i.e. partial response, null response or progression) or occurrence of early relapse, as clinical expressions of resistance to treatment. Patients with early unfavourable disease were 129 and were treated with four to six cycles of ABVD + involved field radiotherapy; 117 patients with advanced stage disease received six cycles of ABVD + optional irradiation to no more than two sites. The rTB was volumetrically measured through the evaluation of staging computed tomography for all the lesions except bone marrow involvement, which was quantified by calculation. The relationship with early resistance was analysed with logistic regressions. The rTB demonstrated to be the best predictor of early failure in both patient subsets, being superior to the multiparameter International Prognostic Score. The rTB showed a significant exponential relationship with the relative risk of early failure, and with inclusion of the extranodal involvement into the model, a single equation became adequate to predict resistance in both early unfavourable and advanced stage patients. The conclusions are that the rTB is the best pretreatment factor related to the risk of resistance to combined ABVD + radiotherapy and that this relationship can be mathematically expressed in an easy way. A simplified assessment of rTB is highly desirable. © 2012 John Wiley & Sons, Ltd.


Brignole M.,Arrhythmologic Center | Deharo J.-C.,Timone University Hospital | De Roy L.,UCL Mont Godinne | Menozzi C.,Arcispedale S Maria Nuova | And 5 more authors.
Journal of the American College of Cardiology | Year: 2011

Objectives: We present data on patients with syncope due to paroxysmal atrioventricular (AV) block unexplainable in terms of currently known mechanisms. Background: Paroxysmal AV block is known to be due to intrinsic AV conduction disease or to heightened vagal tone. Methods: We evaluated 18 patients presenting with unexplained syncope who had: 1) normal baseline standard electrocardiogram (ECG); 2) absence of structural heart disease; and 3) documentation, by means of prolonged ECG monitoring at the time of syncopal relapse, of paroxysmal third-degree AV block with abrupt onset and absence of other rhythm disturbances before or during the block. Results: The study group consisted of 9 men and 9 women, mean age 55 ± 19 years, who had recurrent unexplained syncope for 8 ± 7 years and were subsequently followed up for as long as 14 years (4 ± 4 years on average). The patients had no structural heart disease, standard ECG was normal, and electrophysiological study was negative. In all patients, prolonged ECG monitoring documented paroxysmal complete AV block with 1 or multiple consecutive pauses (mean longest pause: 9 ± 7 s at the time of syncope); AV block occurred without P-P cycle lengthening or PR interval prolongation. During the observation time, no patient had permanent AV block; on permanent cardiac pacing, no patient had further syncopal recurrences. Conclusions: Common clinical and electrophysiological features define a distinct form of syncope due to idiopathic paroxysmal AV block characterized by a long history of recurrent syncope, absence of progression to persistent forms of AV block, and efficacy of cardiac pacing therapy. © 2011 American College of Cardiology Foundation.


Di Lernia V.,Arcispedale S. Maria Nuova
International Journal of Dermatology | Year: 2010

Progressive Multifocal Leukoencephalopathy (PML) is a rare and often fatal opportunistic demyelinating disorder secondary to central nervous system infection by the polyomavirus John Cunningham (JC), a common infecting agent in human populations, with 50-70% of healthy individuals having antibodies to the virus. Although human immunodeficiency virus (HIV) infection remains the most common predisposing factor for PML, which can occur also in association with hematologic malignant neoplasms or iatrogenic immunosuppression in the setting of organ transplantations, recently JC virus has been recognized as an important pathogen in patients with autoimmune and rheumatic diseases receiving immunosuppressive treatments. Following the availability of new biologic drugs, additional cases of PML have been reported in dermatologic patients as well. In particular, the occurrence of PML in psoriatic patients who had been taking efalizumab in the absence of any other concurrent immunosuppressive agents resulted in the decision of European Medicine Agency (EMEA) in February 2009 to recommend suspension of the marketing authorization for this drug in Europe. Some months later the manufacturer of the drug decided to voluntarily withdraw the product from the U.S. market. Since PML can occur as a potential side effect of different immunosuppressive drugs, including conventional treatments for psoriasis, and in consideration of the future development of new immunosuppressive biological agents, dermatologists need to become familiar with opportunistic infections including PML. © 2010 The International Society of Dermatology.


Lernia V.D.,Arcispedale S. Maria Nuova | Ricci C.,Arcispedale S. Maria Nuova
Journal of Dermatological Treatment | Year: 2011

Some of the traditional psoriasis therapies, such as PUVA therapy and ciclosporin, have been linked to an increased incidence of non-melanoma skin cancer. More recently, an increased risk of cancer has also been a concern with newly introduced biologic agents. The authors report a case of multiple cutaneous squamous cell carcinomas arising on the lower limbs of a patient receiving efalizumab first and subsequently infliximab following many years of treatment with conventional therapies including PUVA and ciclosporin. Both these previous therapies likely contributed to the development of the skin tumors of this patient. Several case reports have documented that the use of tumor necrosis factor (TNF)-α inhibitors may be associated with non-melanoma skin cancer, in particular squamous cell carcinoma. However, case reports, although numerous and well documented, do not fulfil the requirements for testing a causeeffect hypothesis. Since data from animal models indicate that TNF inhibition does not increase the incidence of malignancies, additional longer-term studies are necessary to ascertain whether a link exists between anti-TNF-α and non-melanoma skin cancer above that normally observed in psoriasis patients. © 2011 Informa Healthcare USA on behalf of Informa UK Ltd.


Bozzetti C.,Medical Oncology Unit | Negri F.V.,Medical Oncology Unit | Lagrasta C.A.,Centro Of Oncologia Molecolare Traslazionale | Crafa P.,Centro Of Oncologia Molecolare Traslazionale | And 10 more authors.
British Journal of Cancer | Year: 2011

Background:Trastuzumab has recently shown efficacy in the treatment of HER2-positive advanced gastric adenocarcinoma. Although antibody-based therapies target the metastatic disease, HER2 status is usually evaluated in the primary tumour because metastatic sites are rarely biopsied. The aim of this study was to compare HER2 status in primary and paired metastatic sites of gastric adenocarcinoma.Methods:The HER2 status was assessed by fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) in 72 secondary lesions of gastric adenocarcinoma and in the corresponding primary tumours.Results: Concordance of FISH results, evaluable in 68 primary and matched metastatic sites, was 98.5%. Concordance of IHC results, available in 39 of the 72 paired cases, was 94.9%. Only one case showed discordance between primary tumour and metastasis, being negative by both IHC and FISH in the primary and showing HER2 overexpression and amplification in the corresponding pancreatic lymph node metastasis.Conclusion:The high concordance observed between HER2 results obtained by both IHC and FISH on primary tumours and corresponding metastases suggests that in gastric cancer HER2 status is maintained in most cases unchanged during the metastatic process. © 2011 Cancer Research UK All rights reserved.


Becattini C.,University of Perugia | Agnelli G.,University of Perugia | Salvi A.,Medicina di Urgenza | Grifoni S.,Medicina di Urgenza | And 6 more authors.
Thrombosis Research | Year: 2010

Introduction: The clinical benefit of thrombolytic treatment over heparin in patients with pulmonary embolism without hemodynamic compromise remains controversial. In these patients bolus tenecteplase has the potential to provide an effective and safe thrombolysis. Methods: We evaluated the effect of tenecteplase on right ventricle dysfunction (RVD) assessed by echocardiography in hemodynamically stable patients with PE in a multicenter, randomized, double-blind, placebo-controlled study. RVD was defined as right/left ventricle end-diastolic dimension ratio > 1 in the apical 4-chamber view. Patients were randomized to receive weight-adjusted single-bolus tenecteplase or placebo. All patients received unfractionated heparin. Reduction of RVD at 24 hours was the primary efficacy end-point and was evaluated by an independent committee unaware of treatment allocation. Results: Overall, 58 patients were randomized. Echocardiograms were adequate for efficacy analysis in 51 patients, 23 randomized to tenecteplase and 28 to placebo. The reduction of right to left ventricle end-diastolic dimension ratio at 24 hours was 0.31 ± 0.08 in patients randomized to tenecteplase as compared to 0.10 ± 0.07 in patients randomized to placebo (p = 0.04). One patient randomized to tenecteplase suffered a clinical event (recurrent pulmonary embolism) in comparison to three patients randomized to placebo (1 recurrent pulmonary embolism; 1 clinical deterioration and 1 non pulmonary embolism-related death). Two non fatal major bleedings occurred with tenecteplase (1 intracranial) and one with placebo. Conclusion: In hemodynamically stable patients with PE, treatment with single bolus tenecteplase is feasible at the same dosages used for acute myocardial infarction and is associated with reduction of RVD at 24 hours. Whether this benefit is associated with an improved clinical outcome without excessive bleeding is currently explored in a large clinical trial. © 2009 Elsevier Ltd. All rights reserved.

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