San Raffaele Cimena, Italy
San Raffaele Cimena, Italy

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Pupillo E.,Mario Negri Institute for Pharmacological Research | Messina P.,Mario Negri Institute for Pharmacological Research | Giussani G.,Mario Negri Institute for Pharmacological Research | Logroscino G.,University of Bari | And 17 more authors.
Annals of Neurology | Year: 2014

Objective To assess whether physical activity is a risk factor for amyotrophic lateral sclerosis (ALS). Methods From February 2008 to April 2012, 652 patients with ALS from European population-based registries (France, Ireland, Italy, United Kingdom, Serbia) and 1,166 population controls (matched for age, sex, and residency) were assessed. Upon direct interview, data were collected on occupation and history of sport and leisure activities, physical activity, and accidental injuries. Physical exercise was defined as having spent time doing activities that caused an individual to breath hard at least once per month and was coded as none, job-related, and/or sport-related. Sport-related and work-related physical exercise were quantified using metabolic equivalents (METs). Risks were calculated using conditional logistic regression models (adjusting for age, country, trauma, and job-related physical activity) and expressed as odds ratios (ORs) and adjusted ORs (Adj ORs) with 95% confidence intervals (CIs). Results Overall physical activity was associated with reduced odds of having ALS (Adj OR = 0.65, 95% CI = 0.48-0.89) as were work-related physical activity (Adj OR = 0.56, 95% CI = 0.36-0.87) and organized sports (Adj OR = 0.49, 95% CI = 0.32-0.75). An inverse correlation was observed between ALS, the duration of physical activity (p = 0.0041), and the cumulative MET scores, which became significant for the highest exposure (Adj OR = 0.34, 95% CI = 0.21-0.54). An inverse correlation between ALS and sport was found in women but not in men, and in subjects with repeated traumatic events. Interpretation Physical activity is not a risk factor for ALS and may eventually be protective against the disease. © 2014 American Neurological Association.


Zerbinati N.,University of Insubria | Serati M.,University of Insubria | Origoni M.,IRCCS San Raffaele Hospital | Candiani M.,IRCCS San Raffaele Hospital | And 4 more authors.
Lasers in Medical Science | Year: 2014

Vaginal atrophy occurring during menopause is closely related to the dramatic decrease in ovarian estrogens due to the loss of follicular activity. Particularly, significant changes occur in the structure of the vaginal mucosa, with consequent impairment of many physiological functions. In this study, carried out on bioptic vaginal mucosa samples from postmenopausal, nonestrogenized women, we present microscopic and ultrastructural modifications of vaginal mucosa following fractional carbon dioxide (CO2) laser treatment. We observed the restoration of the vaginal thick squamous stratified epithelium with a significant storage of glycogen in the epithelial cells and a high degree of glycogen-rich shedding cells at the epithelial surface. Moreover, in the connective tissue constituting the lamina propria, active fibroblasts synthesized new components of the extracellular matrix including collagen and ground substance (extrafibrillar matrix) molecules. Differently from atrophic mucosa, newly-formed papillae of connective tissue indented in the epithelium and typical blood capillaries penetrating inside the papillae, were also observed. Our morphological findings support the effectiveness of fractional CO2 laser application for the restoration of vaginal mucosa structure and related physiological trophism. These findings clearly coupled with striking clinical relief from symptoms suffered by the patients before treatment. © 2014, Springer-Verlag London.


Sigismondi C.,IRCCS San Raffaele Hospital | Gadducci A.,University of Pisa | Lorusso D.,Catholic University of the Sacred Heart | Candiani M.,IRCCS San Raffaele Hospital | And 4 more authors.
Gynecologic Oncology | Year: 2012

Objective: To evaluate clinicopathologic features and to investigate the outcome of patients with ovarian Sertoli-Leydig cell tumors (SLCTs). Methods: Data concerning 21 patients treated in 11 MITO centers were retrospectively reviewed. Results: Median age was 37 (range 16-76). FIGO stage was: 17 (81%) IA, 1 (4.8%) IC, 1 (4.8%) IIB and 2 (9.5%) IIIC. Five patients (23.8%) had G1 tumor, ten (47.6%) had G2, and six (28.6%) had G3. Fertility-sparing operation was performed in 11 patients, while hysterectomy with bilateral salpingo-oophorectomy was executed in 10 patients; five patients received adjuvant chemotherapy (G2-3). Seven patients (33.3%) relapsed with a median time to recurrence of 14 months. Six recurrent patients had G2-3 disease, while one had G1. Four patients had stage IA disease, one IC and 2 stage IIIC. Patients with stage IA disease did not receive adjuvant chemotherapy. Two patients had pelvic recurrence, 4 abdominal (one with lymph nodal involvement), one on the contralateral ovary and the trocar access. Five patients underwent salvage surgery plus chemotherapy, while one received only salvage chemotherapy and one palliation. Five patients died of disease, four had received first treatment not in a MITO center. 5 year overall survival was 100% for patients with G1 disease and 77.8% for G2-3. 5 year overall survival was 92.3% for stage I and 33.3% for stage > I. Conclusions: The prognosis of patients with grade 1 SLCT is excellent without adjuvant chemotherapy. Patients with advanced stage or grade 2-3 tumors appear to benefit from postoperative chemotherapy. © 2012 Elsevier Inc. All rights reserved.


D'Addio F.,Harvard University | D'Addio F.,IRCCS San Raffaele Hospital | Vasquez A.V.,IRCCS San Raffaele Hospital | Nasr M.B.,Harvard University | And 8 more authors.
Diabetes | Year: 2014

Type 1 diabetes (T1D) is one of the major autoimmune diseases affecting children and young adults worldwide. To date, the different immunotherapies tested have achieved insulin independence in <5% of treated individuals. Recently, a novel hematopoietic stem cell (HSC)-based strategy has been tested in individuals with new-onset T1D. The aim of this study was to determine the effects of autologous nonmyeloablative HSC transplantation in 65 individuals with new-onset T1D who were enrolled in two Chinese centers and one Polish center, pooled, and followed up for 48 months. A total of 59% of individuals with T1D achieved insulin independence within the first 6 months after receiving conditioning immunosuppression therapy (with antithymocyte globulin and cyclophosphamide) and a single infusion of autologous HSCs, and 32% remained insulin independent at the last time point of their follow-up. All treated subjects showed a decrease in HbA1c levels and an increase in C-peptide levels compared with pretreatment. Despite a complete immune system recovery (i.e., leukocyte count) after treatment, 52% of treated individuals experienced adverse effects. Our study suggests the following: 1) that remission of T1D is possible by combining HSC transplantation and immunosuppression; 2) that autologous nonmyeloablative HSC transplantation represents an effective treatment for selected individuals with T1D; and 3) that safer HSC-based therapeutic options are required. © 2014 by the American Diabetes Association.


Serati M.,University of Insubria | Bauer R.,Ludwig Maximilians University of Munich | Cornu J.N.,University Paris - Sud | Cattoni E.,University of Insubria | And 6 more authors.
European Urology | Year: 2013

Background: Inside-out tension-free vaginal transobturator tape (TVT-O) is currently one of the most effective and popular procedures for the surgical treatment of female stress urinary incontinence (SUI), but data reporting long-term outcomes are scarce. Objective: To evaluate the efficacy and safety of TVT-O 5-yr implantation for management of pure SUI in women. Design, setting, and participants: A prospective observational study was conducted in four tertiary reference centers. Consecutive women presenting with urodynamically proven, pure SUI treated by TVT-O were included. Patients with mixed incontinence and/or anatomic evidence of pelvic organ prolapse were excluded. Intervention: TVT-O implantation without any associated procedure. Outcome measurements and statistical analysis: Data regarding subjective outcomes (International Consultation on Incontinence-Short Form [ICIQ-SF], Patient Global Impression of Improvement, patient satisfaction scores), objective cure (stress test) rates, and adverse events were collected during follow-up. Multivariable analyses were performed to investigate outcomes. Results and limitations: Of the 191 women included, 21 (11.0%) had previously undergone a failed anti-incontinence surgical procedure. Six (3.1%) patients were lost to follow-up. The 5-yr subjective and objective cure rates were 90.3% and 90.8%, respectively. De novo overactive bladder (OAB) was reported by 24.3% of patients at 5-yr follow-up. Median ICIQ-SF score significantly improved from 17 (interquartile range [IQR]:16-17) preoperatively to 0 (IQR: 0-2) (p < 0.0001). Failure of a previous anti-incontinence procedure was the only independent predictor of subjective recurrence of SUI (hazard ratio [HR]: 4.4; p = 0.009) or objective (HR: 3.7; p = 0.02). No predictive factor of de novo OAB was identified. Conclusions: TVT-O implantation is a highly effective option for the treatment of women with pure SUI, showing a very high cure rate and a low incidence of complications after 5-yr follow-up. © 2012 European Association of Urology.


Di Resta C.,Vita-Salute San Raffaele University | Pietrelli A.,CNR Institute of Biomedical Technologies | Pietrelli A.,University of Milan | Sala S.,IRCCS San Raffaele Hospital | And 6 more authors.
Human Molecular Genetics | Year: 2015

Brugada syndrome (BrS) is an inherited cardiac arrhythmic disorder that can lead to sudden death, with a prevalence of 1:5000 in Caucasian population and affecting mainly male patients in their third to fourth decade of life. BrS is inherited as an autosomal dominant trait; however, to date genetic bases have been only partially understood. Indeed most mutations are located in the SCN5A gene, encoding the alpha-subunit of the Na+ cardiac channel, but >70% BrS patients still remain genetically undiagnosed. Although 21 other genes have been associated with BrS susceptibility, their pathogenic role is still unclear. A recent nextgeneration sequencing study investigated the contribution of 45 arrhythmia susceptibility genes in BrS pathogenesis, observing a significant enrichment only for SCN5A. In our study, we evaluated the distribution of putative functional variants in a wider panel of 158 genes previously associated with arrhythmic and cardiac defects in a cohort of 91 SCN5A-negative BrS patients. In addition, to identify genes significantly enriched in BrS, we performed a mutation burden test by using as control dataset European individuals selected from the 1000Genomes project. We confirmed BrS genetic heterogeneity and identified new potential BrS candidates such as DSG2 and MYH7, suggesting a possible genetic overlap between different cardiac disorders. © The Author 2015.


Mangili G.,IRCCS San Raffaele Hospital | Sigismondi C.,IRCCS San Raffaele Hospital | Lorusso D.,Catholic University of the Sacred Heart | Cormio G.,University of Bari | And 5 more authors.
Gynecologic Oncology | Year: 2011

Objective: Conservative surgery followed by platinum-based chemotherapy is considered the standard approach for pure ovarian dysgerminoma (POD), except for correctly staged IA patients. The aim of study was to evaluate the outcome of IA POD patients with incomplete surgical staging in order to define the proper management. Methods: Data concerning primary treatment and recurrence were reviewed for 26 patients with stage IA POD treated in MITO (Multicenter Italian Trials in Ovarian Cancer) centers. Results: Median age was 22.5 years. Primary surgery was fertility sparing for 17 patients (65.4%) and radical surgery was performed in 9 patients due to older age or gonadal dysgenesis. Only five patients (19.2%) had complete surgical staging; 38.5% had lymph node dissection, 46.2% had peritoneal biopsies and/or omentectomy and 65.4% had peritoneal washing. Seven patients received adjuvant chemotherapy. Overall recurrence rate was 11.5%: all recurrences occurred in the group submitted to incomplete staging procedure. No patients treated with adjuvant chemotherapy relapsed. One patient had pelvic recurrence, one patient relapsed in the abdomino-pelvic peritoneum and lymph nodes and the third patient showed a peritoneum, lymph nodal and residual ovary relapse. All patients with recurrence were cured by salvage therapy: 2 patients were treated with surgery plus chemotherapy and one only with chemotherapy. After a median follow-up of 100 months all patients are alive without evidence of disease. Six patients opted for conception and delivered healthy infants, two with IVF with donor oocyte. Conclusions: IA POD prognosis is excellent. Conservative surgery with a complete surgical staging is the gold standard. Patients with incomplete staging could undergo surgical restaging or surveillance. Chemotherapy should be reserved to relapse with excellent chances of therapeutic success. © 2010 Elsevier Inc. All rights reserved.


Serati M.,University of Insubria | Ghezzi F.,University of Insubria | Cattoni E.,University of Insubria | Braga A.,University of Insubria | And 5 more authors.
European Urology | Year: 2012

Background: One of the most effective and popular current procedures for the surgical treatment of stress urinary incontinence (SUI) is tension-free midurethral slings. Objective: To evaluate the outcomes of women with retropubic tension-free vaginal tape (TVT) for urodynamic stress incontinence (USI) after 10-yr follow-up. Design, setting, and participants: This was a prospective observational study. Consecutive women with proven USI were treated with TVT. Patients with mixed incontinence and/or anatomic evidence of pelvic organ prolapse were excluded. Intervention: Standard retropubic TVT. Measurements: Patients underwent preoperative clinical and urodynamic evaluations. During follow-up examinations, women were assessed for subjective satisfaction and objective cure rates. Multivariable analyses were performed to investigate outcomes. Results and limitations: A total of 63 women were included. After 10 yr, 5 patients (8%) were lost or no longer evaluable. The 10-yr subjective, objective, and urodynamic cure rates were 89.7%, 93.1%, and 91.4%, respectively. These rates were stable across the whole study period (p > 0.99). De novo overactive bladder was reported by 30.1% and 18.9% of patients at 3-mo and 10-yr follow-up, respectively (p for trend = 0.19). A total of 84.2% of women with detrusor overactivity received antimuscarinic drugs, but 43.8% were nonresponders 12 wk later. At multivariable analysis, maximum detrusor pressure during the filling phase >9 cm H 2O (hazard ratio [HR]: 16.2; p = 0.01) and maximum detrusor pressure during the voiding phase ≤29 cm H 2O (HR: 8.0; p = 0.01) were independent predictors for the recurrence of SUI, as well as obesity was for the recurrence of objective SUI (HR: 17.1; p = 0.01) and of USI (HR: 8.9; p = 0.02), respectively. Intraoperatively, bladder perforation occurred in two cases; no severe bleeding or other complications occurred. Conclusions: The 10-yr results of this study seem to demonstrate that TVT is a highly effective option for the treatment of female SUI, recording a very high cure rate with low complications after a 10-yr follow-up. © 2012 European Association of Urology.


Serati M.,University of Insubria | Bogani G.,University of Insubria | Sorice P.,University of Insubria | Braga A.,University of Insubria | And 5 more authors.
European Urology | Year: 2014

Context Surgery represents the mainstay of treatment for pelvic organ prolapse (POP). Among different surgical procedures, abdominal sacrocolpopexy (SC) is the gold standard for apical or multicompartmental POP. Research has recently focused on the role of robot-assisted sacrocolpopexy (RASC). Objective To conduct a systematic review on the outcomes of RASC. Evidence acquisition PubMed, Scopus, and Web of Science databases as well as ClinicalTrials.gov were searched for English-language literature on RASC. A total of 509 articles were screened; 50 (10%) were selected, and 27 (5%) were included. Studies were evaluated per the Grading of Recommendations, Assessment, Development, and Evaluation system and the European Association of Urology guidelines. Evidence synthesis Overall, data on 1488 RASCs were collected from 27 studies, published from 2006 to 2013. Objective and subjective cures ranged from 84% to 100% and from 92% to 95%, respectively. Conversion rate to open surgery was <1% (range: 0-5%). Intraoperative, severe postoperative complications, and mesh erosion rates were 3% (range: 0-19%), 2% (range: 0-8%), and 2% (range: 0-8%), respectively. Surgical-related outcomes have improved with increased experience, with an estimated learning curve of about 10-20 procedures. Laparoscopic SC is less costly than RASC, although the latter has lower costs than abdominal SC. Conclusions RASC is a safe and feasible procedure for POP; it allows the execution of complex surgical steps via minimally invasive surgery without medium- and long-term anatomic detriments. Further prospective studies are needed to confirm these findings. Patient summary We looked at the outcomes of robotic sacrocolpopexy for prolapse. We found that the use of robotic technology is safe and effective for the treatment of prolapse in women. © 2014 European Association of Urology.


Ratti F.,IRCCS San Raffaele Hospital | Schadde E.,University of Zürich | Masetti M.,Maggiore Hospital | Massani M.,Hepatopancreatobiliary Surgery Unit | And 7 more authors.
Annals of Surgical Oncology | Year: 2015

Background: Two-stage hepatectomy (TSH) is well established for the treatment of patients who have colorectal cancer liver metastases (CRLM) with a small liver remnant. The technique of associating liver partitioning and portal vein occlusion for staged hepatectomy (ALPPS) has been advocated as a novel tool to increase resectability. Using a case-match design, this study aimed to compare TSH and ALPPS for patients with CRLM.Methods: All patients undergoing ALPPS for CRLM at three major hepatobiliary centers in Italy (ALPPS group) were compared in a case-match analysis with patients undergoing TSH (TSH group) at a single institution. The groups were matched with a 1:3 ratio using propensity scores based on covariates representing severity of metastatic disease. The main end points of the study were feasibility of complete resection and intra- and postoperative outcomes.Results: The two treatments did not differ significantly in feasibility. Two patients in the TSH group dropped out compared with no patients in the ALPPS group. A comparable volume gain in future liver remnant (FLR) was obtained in the ALPPS and TSH groups (47 vs. 41 %, nonsignificant difference) but during a shorter interval in ALPPS group. The overall and major complication rate was significantly higher after stage 2 in the ALPPS group (Clavien ≥ 3a: 41.7 vs. 17.6 % in TSH group; p = 0.025).Conclusion: The feasibility of resection using ALPPS compared with TSH for CRLM was not significantly greater, but perioperative complications were increased. Therefore, ALPPS should be proposed to patients with caution and warnings. Currently, TSH remains the standard approach for performing R0 resection in patients with advanced CRLM and inadequate FLR. © 2014, Society of Surgical Oncology.

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