Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib- melphalanprednisone (VMP) in untreated multiple myeloma patients with renal impairment
Morabito F.,Unita Operativa Complessa di Ematologia |
Gentile M.,Unita Operativa Complessa di Ematologia |
Mazzone C.,Unita Operativa Complessa di Ematologia |
Rossi D.,University of Piemonte Orientale |
And 21 more authors.
Blood | Year: 2011
We assessed efficacy, safety, and reversal of renal impairment (RI) in untreated patients with multiple myeloma given bortezomib-melphalan-prednisone- thalidomide followed by bortezomib-thalidomide (VMPT-VT) maintenance or bortezomib-melphalan- prednisone (VMP). Exclusion criteria included serum creatinine ≥ 2.5 mg/dL. In the VMPT-VT/VMP arms, severe RI (estimated glomerular filtration rate [eGFR] ≤ 30 mL/min), moderate RI (eGFR 31-50 mL/ min), and normal renal function (eGFR > 50 mL/min), were 6%/7.9%, 24.1%/24.9%, and 69.8%/67.2%, respectively. Statistically significant improvements in overall response rates and progression-free survival were observed in VMPT-VT versus VMP arms across renal cohorts, except in severe RI patients. In the VMPT group, severe RI reduced overall survival (OS). RI was reversed in 16/63 (25.4%) patients receiving VMPT-VT versus 31/77 (40.3%) receiving VMP. Multivariate analysis showed male sex (P ∇ .022) and moderate RI (P ∇ .003) significantly predicted RI recovery. VMP patients achieving renal response showed longer OS. In both arms, greater rates of severe hematologic adverse events were associated with RI (eGFR < 50 mL/min), however, therapy discontinuation rates were unaffected. VMPT-VT was superior to VMP for cases with normal renal function and moderate RI, whereas VMPT-VT failed to outperform VMP in patients with severe RI, although the relatively low number of cases analyzed preclude drawing definitive conclusions. VMPT-VT had no advantage in terms of RI reversal over VMP. This study is registered at http://www. clinicaltrials.gov as NCT01063179. © 2011 by The American Society of Hematology.
Low-dose dobutamine test associated with interventricular dyssynchrony: A useful tool to identify cardiac resynchronization therapy responders: Data from the LOw dose DObutamine stress-echo test in Cardiac Resynchronization Therapy (LODO-CRT) phase 2 study
Gasparini M.,Istituto Clinico Humanitas |
Muto C.,Ospedale Santa Maria di Loreto Mare |
Iacopino S.,SantAnna Hospital |
Dicandia C.,Anthea Hospital |
And 7 more authors.
American Heart Journal | Year: 2012
Background: Cardiac resynchronization therapy (CRT) is effective in patients with heart failure, but 30% to 50% of subjects are classified as nonresponders. Identifying responders remains a challenging task. Aims: The LODO-CRT trial investigated the association between left ventricular contractile reserve (LVCR) and clinical and echocardiographic long-term CRT response. Methods: This is a multicenter, prospective, observational study. Left ventricular contractile reserve was detected using a dobutamine stress echocardiography test, defined as an ejection fraction increase of >5 points. Clinical CRT response was defined as the absence of major cardiovascular events (ie, cardiovascular death or heart failure hospitalization). Echocardiographic response was defined as a left ventricle end-systolic volume reduction of >10%. Results: A total of 221 CRT-indicated patients were studied (80% presented LVCR). During a mean follow-up of 15 ± 5 months, 17 patients died and 16 were hospitalized due to heart failure. The proportion of clinical responders was 155 (88%) of 177 and 33 (75%) of 44 (P =.036) in the groups with and without LVCR, respectively. Kaplan-Meier analysis showed a significant difference in cardiac survival/hospitalization between patients with and without LVCR. The proportion of echocardiographic responders was 144 (87%) of 166 and 16 (42%) of 38 in the groups with and without LVCR (P <.001), respectively; LVCR showed 90% sensitivity and 87% positive predictive value to prefigure echocardiographic CRT responders. Multivariable analysis identified LVCR and interventricular dyssynchrony as independent predictors of CRT response. The concomitant presence of both factors showed 99% specificity and 83% sensitivity in detecting responders. Conclusion: The presence of LVCR helps in predicting a clinical and echocardiographic CRT response. Concomitant assessment of LVCR and interventricular dyssynchrony accurately stratifies responder and nonresponder patients. © 2012 Mosby, Inc. All rights reserved.
Tursi A.,Gastroenterology Service |
Brandimarte G.,Cristo Re Hospital |
Elisei W.,ASL RMH |
Picchio M.,P. Colombo Hospital ASL RMH |
And 17 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2013
Background Placebo-controlled studies in maintaining remission of symptomatic uncomplicated diverticular disease (SUDD) of the colon are lacking. Aim To assess the effectiveness of mesalazine and/or probiotics in maintaining remission in SUDD. Methods A multicentre, double-blind, placebo-controlled study was conducted. Two hundred and ten patients were randomly enrolled in a double-blind fashion in four groups: Group M (active mesalazine 1.6 g/day plus Lactobacillus casei subsp. DG placebo), Group L (active Lactobacillus casei subsp. DG 24 billion/day plus mesalazine placebo), Group LM (active Lactobacillus casei subsp. DG 24 billion/day plus active mesalazine), Group P (Lactobacillus casei subsp. DG placebo plus mesalazine placebo). Patients received treatment for 10 days/month for 12 months. Recurrence of SUDD was defined as the reappearance of abdominal pain during follow-up, scored as ≥5 (0: best; 10: worst) for at least 24 consecutive hours. Results Recurrence of SUDD occurred in no (0%) patient in group LM, in 7 (13.7%) patients in group M, in 8 (14.5%) patients in group L and in 23 (46.0%) patients in group P (LM group vs. M group, P = 0.015; LM group vs. L group, P = 0.011; LM group vs. P group, P = 0.000; M group vs. P group, P = 0.000; L group vs. P group, P = 0.000). Acute diverticulitis occurred in six group P cases and in one group L case (P = 0.003). Conclusion Both cyclic mesalazine and Lactobacillus casei subsp. DG treatments, particularly when given in combination, appear to be better than placebo for maintaining remission of symptomatic uncomplicated diverticular disease. (ClinicalTrials.gov: NCT01534754). © 2013 John Wiley & Sons Ltd.
Seminari E.,Servizio Biometria ed Epidemiologia Clinica Direzione Scientifica |
Tinelli C.,Servizio Biometria ed Epidemiologia Clinica Direzione Scientifica |
Ravasi G.,Servizio Biometria ed Epidemiologia Clinica Direzione Scientifica |
Ripamonti D.,Ospedali Riuniti |
And 7 more authors.
Current HIV Research | Year: 2010
Objective: The primary objective of this study was to investigate the impact of HCV infection and of HCV genotypes on immune restoration in HIV-infected patients on a successful HAART regimen. Methods: Patients from the MASTER Study were included in this current longitudinal study if they met the following criteria: being on any successful HAART, and availability of CD4+ cell count and HIV RNA level before starting the suppressive HAART and 12 months after suppressive therapy, and availability of HCV antibodies. The primary endpoints of the study were defined as achieving a difference above 100 cell/mmc between CD4+ at baseline and at time of HIV RNA suppression while on therapy (δCD4+early), or 12 month after a suppressive therapy (δCD4+late). Results: 844 HIV-positive patients were included in the analysis: 673 were HCV-negative and 171 were HCV-positive [92 (53.8%) subjects had HCV genotype 1; 58 (33.9%), genotype 3; 21 (12.3%), genotype 4]. Plasma HIV RNA (both baseline as highest value), nadir CD4+, being naïve, time to reach undetectable plasma HIV RNA, treatment with PI vs NNRTI being associated with an early immunological recovery; the occurrence of previous AIDS event, a history of injection drug use, and HCV infection being associated with failure to achieve an early immunological recovery. Variables associated with CD4+late immune recovery were baseline CD4+ value, plasma HIV RNA (both baseline as highest value), being naïve and time to reach undetectable plasma HIV RNA. HCV infection per se was not associated with a worse probability to reach late immunologic response, although among HCV infected patients, having a genotype 3 was associated with a worse immune recovery. At multivariable analysis, factors that remained associated with failure to achieve an early immunological response were being HCV infected and history of injection drug use, while those associated with a failure to achieve a late immunological response were infection with HCV genotype 3 and older age. Conclusions: A blunted early immune recovery was observed in HCV infected patients, compared with HCV negative subjects, while late immune recovery was not different among HCV infected as a whole and not infected subjects; only the subgroup of subjects infected with genotype 3 showed an impaired late immune recovery. © 2010 Bentham Science Publishers Ltd.
Torti C.,University of Brescia |
Prosperi M.,Catholic University of the Sacred Heart |
Motta D.,University of Brescia |
Digiambenedetto S.,Catholic University of the Sacred Heart |
And 11 more authors.
Clinical Microbiology and Infection | Year: 2012
We evaluated factors associated with normalization of the absolute CD4+ T-cell counts, per cent CD4+ T cells and CD4+/CD8+ T-cell ratio. A multicentre observational study was carried out in patients with sustained HIV-RNA <50copies/mL. Outcomes were: CD4-count >500/mm 3 and multiple T-cell marker recovery (MTMR), defined as CD4+ T cells >500/mm 3plus%CD4 T cells >29%plus CD4+/CD8+ T-cell ratio >1. Kaplan-Meier survival analysis and Cox regression analyses to predict odds for achieving outcomes were performed. Three hundred and fifty-two patients were included and followed-up for a median of 4.1 (IQR 2.1-5.9) years, 270 (76.7%) achieving a CD4+ T-cell count >500cells/mm 3 and 197 (56%) achieving MTMR. Using three separate Cox models for both outcomes we demonstrated that independent predictors were: both absolute CD4+ and CD8+ T-cell counts, %CD4+ T cells, a higher CD4+/CD8+ T-cell ratio, and age. A likelihood-ratio test showed significant improvements in fitness for the prediction of either CD4+ >500/mm 3 or MTMR by multivariable analysis when the other immune markers at baseline, besides the absolute CD4+ count alone, were considered. In addition to baseline absolute CD4+ T-cell counts, pretreatment %CD4+ T cells and the CD4+/CD8+ T-cell ratio influence recovery of T-cell markers, and their consideration should influence the decision to start antiretroviral therapy. However, owing to the small sample size, further studies are needed to confirm these results in relation to clinical endpoints. © 2011 European Society of Clinical Microbiology and Infectious Diseases.