Catholic University of the Sacred Heart

About: Catholic University of the Sacred Heart is a education organization based out in Milan, Lombardia, Italy. It is known for research contribution in the topics: Population & Medicine. The organization has 13592 authors who have published 31048 publications receiving 853961 citations.

Phase III Trial of Gemcitabine Compared With Pegylated Liposomal Doxorubicin in Progressive or Recurrent Ovarian Cancer

Abstract: Purpose We aimed at investigating the efficacy, tolerability, and quality of life (QOL) of gemcitabine (GEM) compared with pegylated liposomal doxorubicin (PLD) in the salvage treatment of recurrent ovarian cancer. Patients and Methods A phase III randomized multicenter trial was planned to compare GEM (1,000 mg/m2 on days 1, 8, and 15 every 28 days) with PLD (40 mg/m2 every 28 days) in ovarian cancer patients who experienced treatment failure with only one platinum/paclitaxel regimen and who experienced recurrence or progression within 12 months after completion of primary treatment. Results One hundred fifty-three patients were randomly assigned to PLD (n = 76) or GEM (n = 77). Treatment arms were well balanced for clinicopathologic characteristics. Grade 3 or 4 neutropenia was more frequent in GEM-treated patients versus PLD-treated patients (P = .007). Grade 3 or 4 palmar-plantar erythrodysesthesia was documented in a higher proportion of PLD patients (6%) versus GEM patients (0%; P = .061). The overa...

Germline BRAF mutations in noonan, LEOPARD, and cardiofaciocutaneous Syndromes: Molecular diversity and associated phenotypic spectrum

Abstract: Noonan, LEOPARD, and cardiofaciocutaneous syndromes (NS, LS, and CFCS) are developmental disorders with overlapping features including distinctive facial dysmorphia, reduced growth, cardiac defects, skeletal and ectodermal anomalies, and variable cognitive deficits. Dysregulated RAS–mitogen-activated protein kinase (MAPK) signal traffic has been established to represent the molecular pathogenic cause underlying these conditions. To investigate the phenotypic spectrum and molecular diversity of germline mutations affecting BRAF, which encodes a serine/threonine kinase functioning as a RAS effector frequently mutated in CFCS, subjects with a diagnosis of NS (N=270), LS (N=6), and CFCS (N=33), and no mutation in PTPN11, SOS1, KRAS, RAF1, MEK1, or MEK2, were screened for the entire coding sequence of the gene. Besides the expected high prevalence of mutations observed among CFCS patients (52%), a de novo heterozygous missense change was identified in one subject with LS (17%) and five individuals with NS (1.9%). Mutations mapped to multiple protein domains and largely did not overlap with cancer-associated defects. NS-causing mutations had not been documented in CFCS, suggesting that the phenotypes arising from germline BRAF defects might be allele specific. Selected mutant BRAF proteins promoted variable gain of function of the kinase, but appeared less activating compared to the recurrent cancer-associated p.Val600Glu mutant. Our findings provide evidence for a wide phenotypic diversity associated with mutations affecting BRAF, and occurrence of a clinical continuum associated with these molecular lesions. Hum Mutat 0:1–8, 2009. © 2009 Wiley-Liss, Inc.

Acute myocardial infarction with no obstructive coronary atherosclerosis: mechanisms and management

Abstract: Myocardial infarction (MI) with no obstructive coronary atherosclerosis (MINOCA) is a syndrome with different causes. Its prevalence ranges between 5 and 25% of all MIs. The prognosis is extremely variable, depending on the causes of MINOCA. Clinical history, echocardiography, coronary angiography, and left ventriculography represent the first-level diagnostic investigations. Nevertheless, additional tests are required in order to establish its specific cause, thus allowing an appropriate risk stratification and treatment. We review pathogenesis, diagnosis, prognosis, and therapy of MINOCA and propose an algorithm for its management.

Development and validation of a score to assess risk of adverse drug reactions among in-hospital patients 65 years or older: the GerontoNet ADR risk score

Abstract: BACKGROUND The aim of the present study was to develop and validate a method of identifying elderly patients who are at increased risk for an adverse drug reaction (ADR). METHODS Data from the Gruppo Italiano di Farmacoepidemiologia nell'Anziano (Italian Group of Pharmacoepidemiology in the Elderly) were used to develop an ADR risk score. Variables associated with ADRs were identified by a stepwise logistic regression analysis and used to compute the ADR risk score. The ADR risk score was then validated in a sample of older adults who were admitted to 4 university hospitals in Europe (validation study). RESULTS Of 5936 patients (mean [SD] age, 78.0 [7.2] years) in the Gruppo Italiano di Farmacoepidemiologia nell'Anziano sample, 383 (6.5%) experienced an ADR. The number of drugs and a history of an ADR were the strongest predictors of ADRs, followed by heart failure, liver disease, presence of 4 or more conditions, and renal failure. These variables were used to compute the ADR risk score. The area under the receiver operator characteristic curve, which assesses the ability of the risk score to predict ADRs, was 0.71 (95% confidence interval, 0.68-0.73). Overall, 483 patients entered the validation study (mean [SD] age, 80.3 [7.6] years), and 56 (11.6%) experienced an ADR. The area under the receiver operator characteristic curve in this sample was 0.70 (95% confidence interval, 0.63-0.78). CONCLUSIONS This study proposes a practical and simple method of identifying patients who are at an increased risk of an ADR. This approach may be useful in clinical practice as a tool to identify patients at risk and in research to target a population that can benefit from interventions aimed to reduce drug-related illness.