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San Raffaele Cimena, Italy

Zambon M.,Vita-Salute San Raffaele University | Biondi-Zoccai G.,University of Rome La Sapienza | Bignami E.,Vita-Salute San Raffaele University | Ruggeri L.,Vita-Salute San Raffaele University | And 2 more authors.
Journal of Anesthesia | Year: 2012

Purpose Millions of patients worldwide who undergo surgical procedures face significant morbidity and mortality risks. Several systematic reviews have been performed on ancillary treatments aimed at improving surgical outcomes, but their features and scholarly impact are unclear. We describe characteristics of meta-analyses on ancillary treatments aimed at improving surgical outcomes and explore factors associated with scholarly citations. Methods Systematic reviews published up to 2008 were searched without language restrictions in MEDLINE/Pub- Med. Reviews focusing on nonsurgical treatments aimed at decreasing mortality or major cardiac complications were included. Associations between content, quality, and bibliometric details and scholarly citations in several indexes were systematically appraised. Results From 2,239 citations, 84 systematic reviews were identified. Patients most commonly underwent cardiovascular surgery (40.2 %), and were tested for cardiovascular drugs (25.8 %), with placebo acting as control (38.1 %). Internal validity appeared largely robust, as most (50.5 %) reviews were at low risk of bias. Normalized yearly citations for the included reviews ranged between 5.6 in Google Scholar and 4.3 in Web of Science. Multivariable analysis showed that citations were significantly and positively associated with number of authors, North American corresponding author, number of studies included, number of patients included, noncardiothoracic surgical scope, explicit funding, and lack of competing interests (all P < 0.05). Conclusions Systematic reviews currently represent a key element in defining state of the art ancillary treatments of patients undergoing surgery. However, the citation success of available meta-analyses is not significantly associated with prognostically relevant findings or quality features. © Japanese Society of Anesthesiologists 2012.

Bregni M.,Istituto Scientifico San Raffaele | Herr W.,Johannes Gutenberg University Mainz | Blaise D.,Institute Paoli Calmettes
Expert Review of Anticancer Therapy | Year: 2011

Allogeneic hematopoietic stem cell transplantation from a compatible donor has been utilized as adoptive immunotherapy in metastatic, cytokine-refractory renal cell carcinoma (RCC). Since the year 2000, several investigators have established that RCC is susceptible to a graft-versus-tumor effect: they reported that patients with renal cancer may have partial or complete disease responses, in the 20-40% range, after allogeneic transplantation following a reduced-intensity regimen. However, transplant-related mortality is still high in the 10-20% range, and responses are rarely durable. Experimental evidence suggests that donor-derived T cells and natural killer cells are the main mediators of the graft-versus-RCC effect upon allogeneic hematopoietic stem-cell transplantation. Isolation of CD8+ cytotoxic T lymphocyte clones recognizing several target antigens of graft-versus-RCC effect (minor histocompatibility antigens on RCC cells; a peptide epitope derived from human endogenous retrovirus type E; the tumor-associated antigen encoded by the Wilms' tumor 1 gene) has increased our knowledge of the disease and has opened up the possibility of antigen-specific adoptive cell therapy. The introduction in the clinic of molecularly targeted agents that interfere with neoangiogenesis, both monoclonal antibodies and small tyrosine-kinase inhibitor molecules (e.g., sunitinib, sorafenib and bevacizumab), has decreased the use of allogeneic transplantation. Although not curative, novel targeted agents may be combined with allogeneic transplantation or with adoptive cell therapy in order to maximize the chances of cure. © 2011 Expert Reviews Ltd.

Moncini S.,University of Milan | Bonati M.T.,Istituto Auxologico Italiano | Morella I.,Istituto Scientifico San Raffaele | Ferrari L.,University of Milan | And 2 more authors.
European Journal of Human Genetics | Year: 2015

Noonan syndrome (NS) is a genetic condition characterized by congenital heart defects, short stature and characteristic facial features. We here present the case of a girl with moderate learning disabilities, delayed language development, craniofacial features and skin anomalies reminiscent of NS. After a mutation screening of the known NS genes PTPN11, SOS1, RAF1, KRAS, GRB2, BRAF and SHOC2 we found the heterozygous c.755T>C variant in SOS1 causing the p.I252T amino-acid substitution, which was considered possibly pathogenetic by bioinformatic predictions. The same variant was present in the proband's mother, displaying some NS features, and mateRNAl grandfather showing no NS traits, but also by a healthy subject in 1000 genomes project database without phenotype informations. The functional analysis revealed that SOS1 c.755C activated the RAS-ERK intracellular pathway, whereas no effects on RAC-JNK cascade have been detected. After a comparison between the sequence of SOS1 cDNA from peripheral blood and SOS1 genomic DNA, we showed for the first time a differential allelic expression of the SOS1 gene in healthy individuals, thus occurring as a physiologic condition. Interestingly, we found that the mutated allele C was 50% more expressed than the wild-type allele T in all familial carriers. The comparable amount of SOS1 mRNA between mutated individuals and the controls indicates that the variant does not affect SOS1 expression. The present study provides a first evidence of allelic imbalance of SOS1 and pinpoints this condition as a possible mechanism underlying a different penetrance of some SOS1-mutated alleles in unrelated carriers. © 2015 Macmillan Publishers Limited.

Rossi A.,University of Verona | Dini F.L.,University of Pisa | Faggiano P.,University of Brescia | Agricola E.,Istituto Scientifico San Raffaele | And 7 more authors.
Heart | Year: 2011

Background: Functional mitral regurgitation (FMR) is a common finding in patients with heart failure (HF), but its effect on outcome is still uncertain, mainly because in previous studies sample sizes were relatively small and semiquantitative methods for FMR grading were used. Objective: To evaluate the prognostic value of FMR in patients with HF. Methods and results: Patients with HF due to ischaemic and non-ischaemic dilated cardiomyopathy (DCM) were retrospectively recruited. The clinical end point was a composite of all-cause mortality and hospitalisation for worsening HF. FMR was quantitatively determined by measuring vena contracta (VC) or effective regurgitant orifice (ERO) or regurgitant volume (RV). Severe FMR was defined as ERO >0.2 cm 2 or RV >30 ml or VC >0.4 cm. Restrictive mitral filling pattern (RMP) was defined as E-wave deceleration time <140 ms. The study population comprised 1256 patients (mean age 67±11; 78% male) with HF due to DCM: 27% had no FMR, 49% mild to moderate FMR and 24% severe FMR. There was a powerful association between severe FMR and prognosis (HR=2.0, 95% CI 1.5 to 2.6; p<0.0001) after adjustment of left ventricular ejection fraction and RMP. The independent association of severe FMR with prognosis was confirmed in patients with ischaemic DCM (HR=2.0, 95% CI 1.4 to 2.7; p<0.0001) and nonischaemic DCM (HR=1.9, 95% CI 1.3 to 2.9; p=0.002). Conclusion: In a large patient population it was shown that a quantitatively defined FMR was strongly associated with the outcome of patients with HF, independently of LV function.

Zangrillo A.,Istituto Scientifico San Raffaele | Testa V.,Istituto Scientifico San Raffaele | Aldrovandi V.,Istituto Scientifico San Raffaele | Tuoro A.,Vita-Salute San Raffaele University | And 5 more authors.
Journal of Cardiothoracic and Vascular Anesthesia | Year: 2011

Objective: Volatile anesthetics reduce the risk of myocardial infarction and mortality in coronary artery surgery. Recently, the American College of Cardiology/American Heart Association Guidelines suggested the use of volatile anesthetic agents for the maintenance of general anesthesia during noncardiac surgery in patients at risk for perioperative myocardial ischemia, but no randomized experience to document the cardioprotective effects of these agents exists in this setting. Therefore, the authors performed a prospective, randomized, controlled trial to compare the effects of sevoflurane versus total intravenous anesthesia, in terms of postoperative cardiac troponin I release in patients undergoing noncardiac surgery. Design: A randomized, controlled trial. Setting: A teaching hospital. Participants: Eighty-eight consecutive patients undergoing noncardiac surgery. Interventions: Patients were allocated randomly to receive either volatile anesthetic (44 patients) as the main anesthetic agent or total intravenous anesthesia (TIVA) (44 patients). Measurements: Postoperative cardiac troponin I release was measured as a marker of myocardial necrosis. Patients with detectable postoperative troponin I in the sevoflurane group (12/44, 27.3%) were similar to those in the propofol group (9/44, 20.5%; p = 0.6). There was no significant reduction of postoperative median peak cTnI release (0.16 ± 0.71 ng/mL in the sevoflurane group compared with the TIVA group, 0.03 ± 0.08 ng/mL; p = 0.4). Three patients died at the 1-year follow-up for noncardiac causes (2 in the TIVA group). Conclusions: In the authors' experience, patients undergoing noncardiac surgery did not benefit from anesthesia based on halogenated anesthetics. Further studies are necessary to evaluate the cardioprotective effects of volatile agents in noncardiac surgery. © 2011 Elsevier Inc. All rights reserved.

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