Ospedale Santa Maria Della Misericordia
Ospedale Santa Maria Della Misericordia
Mok T.S.K.,Chinese University of Hong Kong |
Crino L.,Ospedale Santa Maria della Misericordia |
Felip E.,University of Barcelona |
Salgia R.,City of Hope |
And 3 more authors.
Cancer Treatment Reviews | Year: 2017
The discovery of anaplastic lymphoma kinase (ALK)-rearranged non–small-cell lung cancer (NSCLC) in 2007 led to the development and subsequent approval of the ALK inhibitor crizotinib in 2011. However, despite its clinical efficacy, resistance to crizotinib invariably develops. There is now a next generation of ALK inhibitors, including two that have been approved—ceritinib and alectinib—and others that are in development—brigatinib, lorlatinib and X-396. Ceritinib and the other next-generation ALK inhibitors are more potent than crizotinib and can overcome tumor cell resistance mechanisms. Ceritinib gained US Food and Drug Administration approval in 2014 following accelerated review for the treatment of patients with ALK-positive (ALK+) metastatic NSCLC who have progressed on or are intolerant to crizotinib. In pre-clinical studies, it demonstrated more potent inhibition of ALK than crizotinib in enzymatic assays, more durable responses in xenograft models and the ability to potently overcome crizotinib resistance mutations in vitro (including the gatekeeper mutation). There is also evidence for ceritinib penetration across the blood-brain barrier. In clinical trials, ceritinib has demonstrated durable responses and progression-free survival in ALK-inhibitor–pre-treated and –naïve NSCLC patients, including high overall and intracranial response rates in those with central nervous system metastases. Selective gastrointestinal toxicity of ceritinib, such as diarrhea, nausea and vomiting is generally manageable with prophylactic medication and prompt dose reduction or interruption. Future progress in treating ALK+ NSCLC will focus on determining the optimal sequencing of therapies and strategies to overcome acquired resistance, an ongoing challenge in treating ALK-mutation–driven tumors. © 2017 The Authors
Passweg J.R.,University of Basel |
Baldomero H.,University of Basel |
Bregni M.,San Raffaele Scientific Institute |
Cesaro S.,Paediatric Haematology Oncology |
And 12 more authors.
Bone Marrow Transplantation | Year: 2013
In all, 651 from 680 centers in 48 countries reported 35 660 hematopoietic SCT (HSCT) in 32 075 patients (13 470 allogeneic (42%), 18 605 autologous (58%)) to the 2011 survey. Main indications were: leukemias; 10 113 (32%; 94% allogeneic); lymphoid neoplasias; non-Hodgkin's lymphoma, Hodgkin's lymphoma, plasma cell disorders; 18 433 (57%; 12% allogeneic); solid tumours; 1573 (5%; 5% allogeneic); and non-malignant disorders; 1830 (6%; 92% allogeneic). There were more unrelated donors than HLA identical sibling donors (54% versus 39%); proportion of peripheral blood as stem cell source was 99% for autologous and 73% for allogeneic HSCT. Cord blood was only used in allogeneic transplants (6% of total). In the past 10 years, the overall number of transplants has increased by 53%. Allogeneic HSCT have doubled (from 7272 to 14 549) while, autologous have increased by 32% and continue to increase by about 1100 HSCT per year since 2001. In the past 2 years, an increase of >2000 HSCT per year was seen. Transplant activity is shown by team size. For allogeneic HSCT, we show use of reduced-intensity conditioning versus myeloablative conditioning across Europe and use of post-transplant donor lymphocyte infusions with considerable variation across different countries. © 2013 Macmillan Publishers Limited.
Gianni L.,Fondazione IRCCS Instituto Nazionale Tumori |
Eiermann W.,Frauenklinik vom Roten Kreuz |
Semiglazov V.,N N Petrov Research Institute of Oncology |
Manikhas A.,City Oncology Hospital |
And 16 more authors.
The Lancet | Year: 2010
Background: The monoclonal antibody trastuzumab has survival benefit when given with chemotherapy to patients with early, operable, and metastatic breast cancer that has HER2 (also known as ERBB2) overexpression or amplification. We aimed to assess event-free survival in patients with HER2-positive locally advanced or inflammatory breast cancer receiving neoadjuvant chemotherapy with or without 1 year of trastuzumab. Methods: We compared 1 year of treatment with trastuzumab (given as neoadjuvant and adjuvant treatment; n=117) with no trastuzumab (118), in women with HER2-positive locally advanced or inflammatory breast cancer treated with a neoadjuvant chemotherapy regimen consisting of doxorubicin, paclitaxel, cyclophosphamide, methotrexate, and fluorouracil. Randomisation was done with a computer program and minimisation technique, taking account of geographical area, disease stage, and hormone receptor status. Investigators were informed of treatment allocation. A parallel cohort of 99 patients with HER2-negative disease was included and treated with the same chemotherapy regimen. Primary endpoint was event-free survival. Analysis was by intention to treat. This study is registered, number ISRCTN86043495. Findings: Trastuzumab significantly improved event-free survival in patients with HER2-positive breast cancer (3-year event-free survival, 71% [95% CI 61-78; n=36 events] with trastuzumab, vs 56% [46-65; n=51 events] without; hazard ratio 0·59 [95% CI 0·38-0·90]; p=0·013). Trastuzumab was well tolerated and, despite concurrent administration with doxorubicin, only two patients (2%) developed symptomatic cardiac failure. Both responded to cardiac drugs. Interpretation: The addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy should be considered for women with HER2-positive locally advanced or inflammatory breast cancer to improve event-free survival, survival, and clinical and pathological tumour responses. Funding: F Hoffmann-La Roche. © 2010 Elsevier Ltd. All rights reserved.
Brignole M.,Arrhythmologic Center |
Occhetta E.,Ospedale Maggiore della Carita |
Bongiorni M.G.,Ospedale Cisanello |
Proclemer A.,Ospedale Santa Maria della Misericordia |
And 15 more authors.
Journal of the American College of Cardiology | Year: 2012
Objectives: The purpose of this study is to assess the effectiveness of defibrillation testing (DT) in patients undergoing implantable cardioverter-defibrillator (ICD) insertion. Background: Although DT is considered a standard procedure during ICD implantation, its usefulness has not been definitively proven. Methods: The SAFE-ICD (Safety of Two Strategies of ICD Management at Implantation) study is a prospective observational study designed to evaluate the outcome of 2 strategies: performing defibrillation testing (DT+) versus not performing defibrillation testing (DT-) during de novo ICD implants. No deviation from the centers' current practice was introduced. In all, 2,120 consecutive patients (836 DT+ and 1,284 DT-) age <18 years were enrolled at 41 Italian centers from April 2008 to May 2009 and followed up for 24 months until June 2011. The primary endpoint was a composite of severe complications at ICD implant and sudden cardiac death or resuscitation at 2 years. Results: The primary endpoint occurred in 34 patients: 12 intraoperative complications (8 in DT+ group; 4 in DT- group) and 22 during follow-up (10 in DT+ group; 12 in DT- group). Overall, the estimated yearly incidence (95% confidence interval) was DT+ 1.15% (0.73 to 1.83) and DT- 0.68% (0.42 to 1.12). The difference between the 2 groups was negligible: 0.47% per year (-0.15 to 1.10). Mortality from any cause was similar at 2 years (adjusted hazard ratio: 0.97 [0.76 to 1.23], p = 0.80). Conclusions: In this large cohort of new ICD implants, event rates were similar and extremely low in both groups. These data indicate a limited clinical relevance for DT testing, thus supporting a strategy of omitting DT during an ICD implant. (Safety of Two Strategies of ICD Management at Implantation [SAFE-ICD]; NCT00661037) © 2012 American College of Cardiology Foundation.
Biffi M.,University of Bologna |
Zanon F.,Ospedale Santa Maria della Misericordia |
Bertaglia E.,Ospedale Civile |
Padeletti L.,University of Florence |
And 4 more authors.
Heart Rhythm | Year: 2013
Background: Phrenic nerve stimulation (PNS), occurring in 33%-37% of the patients with cardiac resynchronization therapy (CRT), is a limiting factor when implanting left ventricular (LV) leads from coronary veins. Objective: To test the hypothesis that PNS occurence is related to bipolar electrode spacing. Methods: During standard CRT defibrillator implant procedures, a 5-F diagnostic electrophysiology catheter with 10 electrodes, spaced 2-5-2 mm, was positioned in a cardiac vein suitable for permanent LV lead placement. Pacing in the unipolar configuration identified the site with the lowest PNS threshold. PNS and left ventricular pacing (LVP) thresholds were then measured in different configurations at 0.5 ms: unipolar, each LV electrode served as the cathode in turn; and bipolar with different electrode spacing, cathode being the electrode with the lowest unipolar PNS threshold. Results: From February to September 2010, 40 patients undergoing CRT implantation were enrolled in 4 centers in Italy. It was possible to identify PNS and perform a complete set of measurements in 23 patients. A bipolar electrode spacing of 2 mm resulted in higher PNS thresholds in bipolar configurations han did a bipolar electrode spacing of≥5 mm. However, no significant increase in the LVP threshold was observed (P = ns). Conclusions: This experience suggests that LVP with a bipolar electrode spacing of 2 mm significantly increases the PNS threshold without affecting the LVP threshold, thereby increasing the possibility of delivering CRT when the LV lead is placed in proximity to the phrenic nerve. © 2013 Heart Rhythm Society.
PubMed | AO Niguarda Ca Granda, Ospedale Santa Maria della Misericordia, Fondazione IRCCS Policlinico S. Matteo, Ospedale S. Maria della Misericordia and 3 more.
Type: Journal Article | Journal: Trials | Year: 2016
Despite an intensive search for predictors of the response to cardiac resynchronization therapy (CRT), the QRS duration remains the simplest and most robust predictor of a positive response. QRS duration of130ms is considered to be a prerequisite for CRT; however, some studies have shown that CRT may also be effective in heart failure (HF) patients with a narrow QRS (<130ms). Since CRT can now be performed by pacing the left ventricle from multiple vectors via a single quadripolar lead, it is possible that multipoint pacing (MPP) might be effective in HF patients with a narrow QRS. This article reports the design of the MPP Narrow QRS trial, a prospective, randomized, multicenter, controlled feasibility study to investigate the efficacy of MPP using two LV pacing vectors in patients with a narrow QRS complex (100-130ms).Fifty patients with a standard ICD indication will be enrolled and randomized (1:1) to either an MPP group or a Standard ICD group. All patients will undergo a low-dose dobutamine stress echo test and only those with contractile reserve will be included in the study and randomized. The primary endpoint will be the percentage of patients in each group that have reverse remodeling at 12months, defined as a reduction in left ventricular end-systolic volume (LVESV) of >15% from the baseline.This feasibility study will determine whether MPP improves reverse remodeling, as compared with standard ICD, in HF patients who have a narrow QRS complex (100-130ms).ClinicalTrials.gov, NCT02402816 . Registered on 25 March 2015.
Losito A.,Ospedale Santa Maria Della Misericordia |
Del Vecchio L.,Ospedale Manzoni |
Lusenti T.,Arcispedale Santa Maria Nuova |
Del Rosso G.,Ospedale Giuseppe Mazzini |
And 2 more authors.
Journal of Clinical Hypertension | Year: 2013
Studies on the relationship between blood pressure (BP) and mortality among hemodialysis patients have yielded conflicting results. Reports have come mostly from North America and have dealt with dialysis patients as a homogenous population and differed in methods and time of BP measurement and the optimal BP target. In a prospective nationwide study in 3674 unselected Caucasian patients with end-stage renal disease undergoing chronic hemodialysis from 73 dialysis units, the authors sought to examine the relationship between the different measurements of BP and mortality according to antihypertensive treatment. The mean age of patients was 67.2±14.1 years and the prevalence of diabetes was 19.5%. During follow-up (26.5±10.5 months), 977 deaths were recorded. In the whole cohort, BP was not associated with mortality. After grouping the patients according to antihypertensive treatment, the analysis showed that only in patients who did not take antihypertensive medications (1613) was there an inverse relationship between postdialysis systolic BP and mortality. These patients differed from the others in BP, dialysis vintage, prevalence of diabetes, and type of dialysis technique. This study suggests that with respect to the relationship of BP with mortality, dialysis patients are not a homogenous population. Differences in demographic characteristics and in dialysis technique may therefore explain the reported variability of previous results. © 2013 Wiley Periodicals, Inc.
PubMed | Ospedale Santa Maria della Misericordia, University of Perugia and New Hill
Type: | Journal: The Psychiatric quarterly | Year: 2016
The aim of this study was to understand which of a number of factors are most associated with psychiatric inpatient length of stay (LoS). We hypothesized that a longer LoS would be predicted by: older age, male gender, unmarried marital status, foreign nationality, more than one hospitalization, being hospitalized involuntarily, psychotic symptoms and behavioral dyscontrol at admission, discharge diagnosis of psychotic and personality disorders, not having a substance use disorder, treatment with more than one class of medications, and being discharged to a community residential facility. All admissions to the Psychiatric Inpatient Unit of Santa Maria della Misericordia, Perugia Hospital, Umbria, Italy, from June 2011 to June 2014, were included in a medical record review. Bivariate analyses were performed and a multiple linear regression model was built using variables that were associated (p<.05) with LoS in bivariate tests. The study sample included 1236 patients. In the final, most parsimonious regression model, five variables independently explained 18% of variance in LoS: being admitted involuntarily, being admitted for thought disorders, not having a substance-related disorder, having had more than one hospitalization, and being discharged to a community residential facility. LoS on this inpatient psychiatric unit in Umbria was associated with a number of sociodemographic and clinical characteristics. Knowledge of these and other predictors of LoS will be increasingly important to, when possible, reduce the length of restrictive, costly hospitalizations and embrace community-based services.
Losito A.,Ospedale Santa Maria della Misericordia |
Del Vecchio L.,Ospedale A. Manzoni |
Del Rosso G.,Ospedale Giuseppe Mazzini |
Malandra R.,Ospedale Giuseppe Mazzini
American Journal of Hypertension | Year: 2014
Background:In patients chronically treated with hemodialysis, the prevalence of heart failure is high with a consequently poor prognosis. The role played by blood pressure (BP) on cardiovascular (CV) mortality of these patients has not been clearly defined.Methods:In this follow-up study, we investigated the relationship of pre-and postdialysis measurements of BP with CV and all-cause mortality in a cohort of 557 dialysis patients with a left ventricular (LV) ejection fraction <50%.Results:During the follow-up (mean = 21.6±8.8 months), 179 deaths were recorded. Ninety-eight patients died from CV causes. By the Cox multivariable analysis, we constructed a predictive model of CV mortality including age, duration on dialysis, diabetes, serum albumin, diffusive dialysis technique, predialysis mean arterial pressure (MAP) (hazard ratio (HR) = 0.978; 95% confidence interval (CI) = 0.956-0.999), and postdialysis MAP (HR = 1.035; 95% CI = 1.010-1.061). The relationship with mortality was inverse for predialysis MAP and direct for postdialysis MAP. In a subsequent analysis, we found that pre-and postdialysis systolic BP, but not diastolic BP, were predictive of CV mortality. Predialysis MAP was in a direct relationship with body mass index. Postdialysis MAP had an inverse relationship with weight loss during dialysis session.Conclusions:CV mortality in dialysis patients with LV dysfunction is associated with both pre-and postdialysis BP interacting in a complex relationship. Nutritional state and fluid balance and removal are possible clues to this relationship. © 2013 American Journal of Hypertension, Ltd.
Losito A.,Ospedale Santa Maria Della Misericordia
Giornale italiano di nefrologia : organo ufficiale della Società italiana di nefrologia | Year: 2010
Between 1971 and 1977 eight DASCO meetings were held in different cities in Italy. The meetings dealt with the technical aspects of renal dialysis, then in its early days. They were organized as round tables and the proceedings were published timely. Lively discussion among the audience was a characteristic feature. Most of the attendants, who came from all over Italy, later pursued careers in nephrology and held posts in the Italian Society of Nephrology. The meetings contributed to the development of national standards for dialysis and ended in 1977 with the definitive establishment of renal dialysis in Italy.