Tinterri C.,Instituto Clinico Humanitas |
Gatzemeier W.,Instituto Clinico Humanitas |
Zanini V.,Maugeri Foundation |
Regolo L.,Maugeri Foundation |
And 11 more authors.
Annals of Surgical Oncology | Year: 2014
Objectives: Breast-conserving therapy (BCT), including postoperative whole breast irradiation (WBI), is generally accepted as the treatment of choice for most patients with early-stage breast cancer. The question whether WBI is mandatory in all patients remains one of the most controversial issues in BCT. To answer this question, a randomized, prospective, multicentre study was launched in January 2001. Primary endpoints of the study were to assess the cumulative incidence of in-breast-recurrences (IBR) and overall survival (OAS) after conservative surgery (BCS) with or without WBI. Methods: From January 2001 until December 2005, 749 patients with unifocal infiltrating breast cancer up to 25 mm, 0-3 positive axillary lymph nodes, no extensive intraductal component or lymphvascular invasion from 11 centres in Italy, were randomly assigned to BCS+WBI (arm 1:373 patients) or BCS alone (arm 2:376 patients). Treatment arms were well balanced in terms of baseline characteristics. Systemic adjuvant therapy was administered according to the institutional policies. Kaplan-Meier method was used for survival analysis and log-rank test to evaluate the difference between the two arms. Results (Last Analysis 31.12.2012): After median follow-up of 108 months, 12 (3.4 %) IBR were observed in arm 1 and 16 (4.4 %) in arm 2. OAS was 81.4 % in arm 1 and 83.7 % in arm 2. There was no statistically significant difference regarding IBR and death in the two treatment groups. Conclusions: These data are promising and suggest that WBI after BCS can be omitted in selected patients with early stage breast cancer without exposing them to an increased risk of local recurrence and death. Longer follow-up is needed to further consolidate these results. © 2013 Society of Surgical Oncology.
Chio A.,University of Turin |
Mora G.,Instituto Scientifico Of Milan |
Sabatelli M.,Catholic University And Icomm Association For Als Research |
Caponnetto C.,Maternal and Child Health |
And 94 more authors.
Neurobiology of Aging | Year: 2016
There are indications that both familial amyotrophic lateral sclerosis (ALS) and sporadic ALS phenotype and prognosis are partly regulated by genetic and environmental factors, supporting the theory that ALS is a multifactorial disease. The aim of this article was to assess the role of ATXN2 intermediate length repeats in a large series of Italian and Sardinian ALS patients and controls carrying a pathogenetic C9ORF72 GGGGCC hexanucleotide repeat. A total of 1972 ALS cases were identified through the database of the Italian ALS Genetic consortium, a collaborative effort including 18 ALS centers throughout Italy. The study population included: (1) 276 Italian and 57 Sardinian ALS cases who carried the C9ORF72 expansion; (2) 1340 Italian and 299 Sardinian ALS cases not carrying the C9ORF72 expansion. A total of healthy 1043 controls were also assessed. Most Italian and Sardinian cases and controls were homozygous for 22/22 or 23/23 repeats or heterozygous for 22/23 repeats of the ATXN2 gene. ATXN2 intermediate length repeats alleles (≥28) were detected in 3 (0.6%) Italian ALS cases carrying the C9ORF72 expansion, in none of the Sardinian ALS cases carrying the expansion, in 60 (4.3%) Italian cases not carrying the expansion, and in 6 (2.0%) Sardinian ALS cases without C9ORF72 expansion. Intermediate length repeat alleles were found in 12 (1.5%) Italian controls and 1 (0.84%) Sardinian controls. Therefore, ALS patients with C9ORF72 expansion showed a lower frequency of ATXN2 polyQ intermediate length repeats than both controls (Italian cases, p = 0.137; Sardinian cases, p = 0.0001) and ALS patients without C9ORF72 expansion (Italian cases, p = 0.005; Sardinian cases, p = 0.178). In our large study on Italian and Sardinian ALS patients with C9ORF72 GGGGCC hexanucleotide repeat expansion, compared to age-, gender- and ethnic-matched controls, ATXN2 polyQ intermediate length does not represent a modifier of ALS risk, differently from non-C9ORF72 mutated patients. © 2016 Elsevier Inc.
Cerrone M.,New York University |
Novelli V.,Maugeri Foundation |
Kim C.,Sanford Burnham Institute for Medical Research |
Kim C.,Sejong University |
And 7 more authors.
Circulation | Year: 2014
BACKGROUND - : Brugada syndrome (BrS) primarily associates with the loss of sodium channel function. Previous studies showed features consistent with sodium current (INa) deficit in patients carrying desmosomal mutations, diagnosed with arrhythmogenic cardiomyopathy (or arrhythmogenic right ventricular cardiomyopathy). Experimental models showed correlation between the loss of expression of desmosomal protein plakophilin-2 (PKP2) and reduced INa. We hypothesized that PKP2 variants that reduce INa could yield a BrS phenotype, even without overt structural features characteristic of arrhythmogenic right ventricular cardiomyopathy. METHODS AND RESULTS - : We searched for PKP2 variants in the genomic DNA of 200 patients with a BrS diagnosis, no signs of arrhythmogenic cardiomyopathy, and no mutations in BrS-related genes SCN5A, CACNa1c, GPD1L, and MOG1. We identified 5 cases of single amino acid substitutions. Mutations were tested in HL-1-derived cells endogenously expressing NaV1.5 but made deficient in PKP2 (PKP2-KD). Loss of PKP2 caused decreased INa and NaV1.5 at the site of cell contact. These deficits were restored by the transfection of wild-type PKP2, but not of BrS-related PKP2 mutants. Human induced pluripotent stem cell cardiomyocytes from a patient with a PKP2 deficit showed drastically reduced INa. The deficit was restored by transfection of wild type, but not BrS-related PKP2. Super-resolution microscopy in murine PKP2-deficient cardiomyocytes related INa deficiency to the reduced number of channels at the intercalated disc and increased separation of microtubules from the cell end. CONCLUSIONS - : This is the first systematic retrospective analysis of a patient group to define the coexistence of sodium channelopathy and genetic PKP2 variations. PKP2 mutations may be a molecular substrate leading to the diagnosis of BrS. © 2013 American Heart Association, Inc.
Van Dam P.A.,University of Antwerp |
Tomatis M.,Data Center |
Marotti L.,EUSOMA |
Heil J.,University of Heidelberg |
And 38 more authors.
European Journal of Surgical Oncology | Year: 2015
Aim of the study The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast units to establish minimum standards and ensure specialist multidisciplinary care. In the present study we assess the impact of EUSOMA certification for all breast units for which sufficient information was available before and after certification. Materials and methods For 22 EUSOMA certified breast units data of 30,444 patients could be extracted from the EUSOMA database on the evolution of QI's before and after certification. Results On the average of all units, the minimum standard of care was achieved for 12/13 QI's before and after EUSOMA certification (not met for DCIS receiving just one operation). There was a significant improvement of 5 QI's after certification. The proportion of patients with invasive cancer undergoing an axillary clearance containing >9 lymph nodes (91.5% vs 89.4%, p 0.003) and patients with invasive cancer having just 1 operation (83.1% vs 80.4%, p < 0.001) dropped, but remained above the minimum standard. The targeted standard of breast care was reached for the same 4/13 QI's before and after EUSOMA certification. Conclusion Although the absolute effect of EUSOMA certification was modest it further increases standards of care and should be regarded as part of a process aiming for excellence. Dedicated units already provide a high level of care before certification, but continuous monitoring and audit remains of paramount importance as complete adherence to guidelines is difficult to achieve. © 2015 Elsevier Ltd.
Leonardi M.C.,Oncology and Radiotherapy Institute |
Morra A.,Oncology and Radiotherapy Institute |
Santoro L.,Italian National Cancer Institute |
Balduzzi A.,Italian National Cancer Institute |
And 13 more authors.
Tumori | Year: 2015
Purpose: To evaluate the tolerance of concomitant administration of anthracycline-based chemotherapy (CHT) and 3-dimensional conformal radiotherapy (RT) after breast-conserving surgery. Methods and Materials: Sixty-seven patients, treated with conservative surgery followed by 3-dimensional whole breast RT and concomitant CHT regimens including "Canadian modified" CEF (5-fluorouracil, epirubicin, cyclophosphamide) or AC (doxorubicin, cyclophosphamide) were evaluated for toxicity. They were compared in terms in compliance and acute toxicity with 67 patients irradiated sequentially after having received anthracyclines. Results: Acute grade ≥2 skin toxicity was significantly higher in the concomitant group compared to the sequential group, although the incidence of Grade 3 desquamation showed no statistical difference (9% vs. 3%, p = 0.14). Haematological toxicity represented the main cause of treatment discontinuation, reporting higher rate of grade 3-4 leuco-neutropenia in the concomitant group (20.9% vs. 6%, p = 0.01). Mean RT duration was longer in the concomitant group (51 days vs. 45 days) owing to RT breaks. Late toxicity was acceptable. No symptomatic lung and heart events were reported. Radiological lung hyperdensity was detected in 27.7% of the patients in the concomitant group. Post-treatment left ventricular ejection fraction significantly decreased compared with baseline, but cardiac function remained within the normal range, without any difference between left or right-sided RT. Conclusions: Although there was more acute grade ≥2 skin toxicity in the concomitant group, the rate of grade 3 dermatitis was lower than expected, suggesting some advantages of 3-D CRT over older techniques. Haematological toxicity exerted a significant impact on both RT and CHT delivery. © 2015 INTM, Italy. Published by Wichtig Publishing.
PubMed | Breast Unit, Centro Senologia Multimedica Castellanza, EUSOMA, University of Duisburg - Essen and 22 more.
Type: Journal Article | Journal: European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology | Year: 2015
The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast units to establish minimum standards and ensure specialist multidisciplinary care. In the present study we assess the impact of EUSOMA certification for all breast units for which sufficient information was available before and after certification.For 22 EUSOMA certified breast units data of 30,444 patients could be extracted from the EUSOMA database on the evolution of QIs before and after certification.On the average of all units, the minimum standard of care was achieved for 12/13 QIs before and after EUSOMA certification (not met for DCIS receiving just one operation). There was a significant improvement of 5 QIs after certification. The proportion of patients with invasive cancer undergoing an axillary clearance containing >9 lymph nodes (91.5% vs 89.4%, p 0.003) and patients with invasive cancer having just 1 operation (83.1% vs 80.4%, p < 0.001) dropped, but remained above the minimum standard. The targeted standard of breast care was reached for the same 4/13 QIs before and after EUSOMA certification.Although the absolute effect of EUSOMA certification was modest it further increases standards of care and should be regarded as part of a process aiming for excellence. Dedicated units already provide a high level of care before certification, but continuous monitoring and audit remains of paramount importance as complete adherence to guidelines is difficult to achieve.
Quaranta D.,Catholic University of the Sacred Heart |
Piccininni C.,Catholic University of the Sacred Heart |
Carlesimo G.A.,IRCCS Santa Lucia Foundation |
Luzzi S.,Marche Polytechnic University |
And 6 more authors.
Neurological Sciences | Year: 2016
Several anatomo-clinical investigations have shown that familiar face recognition disorders not due to high level perceptual defects are often observed in patients with lesions of the right anterior temporal lobe (ATL). The meaning of these findings is, however, controversial, because some authors claim that these patients show pure instances of modality-specific ‘associative prosopagnosia’, whereas other authors maintain that in these patients voice recognition is also impaired and that these patients have a ‘multimodal person recognition disorder’. To solve the problem of the nature of famous faces recognition disorders in patients affected by right ATL lesions, it is therefore very important to verify with formal tests if these patients are or are not able to recognize others by voice, but a direct comparison between the two modalities is hindered by the fact that voice recognition is more difficult than face recognition. To circumvent this difficulty, we constructed a test battery in which subjects were requested to recognize the same persons (well-known at the national level) through their faces and voices, evaluating familiarity and identification processes. The present paper describes the ‘Famous People Recognition Battery’ and reports the normative data necessary to clarify the nature of person recognition disorders observed in patients affected by right ATL lesions. © 2015, Springer-Verlag Italia.
Bonforte G.,S Anna Hospital |
Rossi E.,University of Milan Bicocca |
Auricchio S.,University of Milan Bicocca |
Pogliani D.,University of Milan Bicocca |
And 4 more authors.
Journal of Vascular Surgery | Year: 2010
Background American and European guidelines recommend the distal radial-cephalic fistula (dRCF) as the first and best hemodialysis access in patients with end-stage renal disease (ESRD). However, this kind of arteriovenous fistula (AVF) shows a limited primary unassisted patency and frequently needs surgical revisions or angiographic procedures, or both. When dRCF is not feasible, guidelines suggest a proximal brachiocephalic AVF. The middle-arm fistula (MAF), or autogenous forearm radial-median direct access, has been suggested as a possible alternative approach. This study evaluated MAF primary unassisted patency, the most frequent causes of MAF failure, and the possible related factors. Methods Data on patients with a MAF placed from January 1991 until June 2008 were retrospectively collected. The probability of MAF failure overall and by the main subgroups was estimated according to Kaplan-Meier with Greenwood standard error (SE). Comparison of failure among different subgroups was performed using the log rank test in univariate analyses. The Cox regression model was used to investigate factors that independently affected the overall hazard of failure and cause-specific hazard of thrombosis. Results At the end of follow-up, 14.0% of MAF failed (11.6% thrombosis, 1.7% stenosis, 0.7% failed maturation), and 44.2% of MAF were still working. Cumulative probability of MAF unassisted primary patency after 4 years from the creation was 79%. Univariate analyses highlighted that women (P = .019), underweight patients (P = .010), and MAF implantation after starting hemodialysis (P < .001) had a higher risk of MAF failure for any cause than men, normal and overweight patients, and MAF implanted before starting hemodialysis. Results of the Cox multivariate analysis for overall MAF failure confirmed that only MAF implantation before starting hemodialysis is a protective factor against any failure (P = .003), whereas female gender (P = .016) was associated with an increase of the thrombosis hazard ratio to 2.04 (95% confidence interval, 1.14-3.63). Conclusion Our data demonstrate that MAF has a good unassisted primary patency and suggest that this kind of AVF could be a valuable alternative surgical approach when dRCF is not feasible in ESRD patients. Copyright © 2010 by the Society for Vascular Surgery.