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Background and Purpose: Data are reported from the Italian CMT Registry., Methods: The Italian CMT Registry is a dual registry where the patient registers and chooses a reference center where the attending clinician collects a minimal dataset of information and administers the Charcot-Marie-Tooth (CMT) Examination/Neuropathy Score. Entered data are encrypted., Results: Overall, 1012 patients had registered (535 females) and 711 had received a genetic diagnosis. Demyelinating CMT (65.3%) was more common than axonal CMT2 (24.6%) and intermediate CMT (9.0%). The PMP22 duplication was the most frequent mutation (45.2%), followed by variants in GJB1 and MPZ (both ~10%) and MFN2 (3.3%) genes. A relatively high mutation rate in some "rare" genes (HSPB1 1.6%, NEFL 1.5%, SH3TC2 1.5%) and the presence of multiple mutation clusters across Italy was observed. CMT4A was the most disabling type, followed by CMT4C and CMT1E. Disease progression rate differed depending on the CMT subtype. Foot deformities and walking difficulties were the main features. Shoe inserts and orthotic aids were used by almost one-half of all patients. Scoliosis was present in 20% of patients, especially in CMT4C. Recessive forms had more frequently walking delay, walking support need and wheelchair use. Hip dysplasia occurred in early-onset CMT., Conclusions: The Italian CMT Registry has proven to be a powerful data source to collect information about epidemiology and genetic distribution, clinical features and disease progression of CMT in Italy and is a useful tool for recruiting patients in forthcoming clinical trials., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objectives: To validate the predictive value on time to first treatment (TTFT) of AIPS-E and IPS-E evaluated in an independent cohort of newly diagnosed and non-referred Binet stage A CLL patients enrolled in the O-CLL1-GISL protocol (clinicaltrial.gov identifier: NCT00917540)., Methods: A cohort of 292 newly diagnosed Binet A CLL cases has been enrolled in the study. Patients from several Italian Institutions were prospectively enrolled within 12 months of diagnosis into the O-CLL1-GISL protocol., Results: The majority of patients were male (62%); median age was 60.4 years, 102 cases (34.9%) showed unmutated IGHV genes, 8 cases (2.8) the presence of del(11q)/del(17p), 142 cases (48.6%) the presence of palpable lymph nodes and 146 cases (50%) and ALC > 15 × 10 9 /l. After a median follow-up of 7.2 years, 130 patients underwent treatment. According to the AIPS-E, 96 patients were classified as low-risk, 128 as intermediate-risk, and 68 as high-risk. These groups showed significant differences in terms of TTFT. The C-statistic was 0.71 (P < .0001) for predicting TTFT. According to IPS-E, 77 patients were classified as low-risk, 135 as intermediate-risk, and 80 as high-risk. These groups showed significant differences in terms of TTFT. The C-statistic was 0.705 (P < .0001) for predicting TTFT., Conclusions: Our data confirm an accurate prognostic utility of both AIPS-E and IPS-E at the individual patient level. These data may be useful for a precise stratification of early-stage patients., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We present a laboratory-based prognostic calculator (designated CRO score) to risk stratify treatment-free survival in early stage (Rai 0) chronic lymphocytic leukemia (CLL) developed using a training-validation model in a series of 1,879 cases from Italy, the United Kingdom and the United States. By means of regression analysis, we identified five prognostic variables with weighting as follows: deletion of the short arm of chromosome 17 and unmutated immunoglobulin heavy chain gene status, 2 points; deletion of the long arm of chromosome 11, trisomy of chromosome 12, and white blood cell count >32.0x10 3 /microliter, 1 point. Low-, intermediate- and high-risk categories were established by recursive partitioning in a training cohort of 478 cases, and then validated in four independent cohorts of 144 / 395 / 540 / 322 cases, as well as in the composite validation cohort. Concordance indices were 0.75 in the training cohort and ranged from 0.63 to 0.74 in the four validation cohorts (0.69 in the composite validation cohort). These findings advocate potential application of our novel prognostic calculator to better stratify early-stage CLL, and aid case selection in risk-adapted treatment for early disease. Furthermore, they support immunocytogenetic analysis in Rai 0 CLL being performed at the time of diagnosis to aid prognosis and treatment, particularly in today's chemofree era., (Copyright© 2020 Ferrata Storti Foundation.)

Introduction: Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disease. Thanks to the advances of the latest generation sequencing, more than 80 causative genes have been reported to date., Methods: In this retrospective, observational study, we have analyzed clinical, electrophysiological, and genetic data of CMT patients in care at Neuromuscular Center of Messina University Hospital, Messina, Italy, for at least 22 years (from 1994 to 2016). Our center is the only reference center for genetic neuropathies in Sicily and in the southern part of Calabria., Results: We reviewed the clinical records of 566 patients with the aim to evaluate how many patients received a genetic diagnosis and the distribution of the genetic subtypes. About 352/566 (62.19%) received a genetic diagnosis. The most frequent genetic diagnoses were CMT1A/PMP22 duplication (51.13%), followed by HNPP/PMP22 deletion (15.05%), CMT1B/MPZ mutation (10.22%), CMTX/GJB1 mutation (9.37%), and CMT2F/HSPB1 (4%). Other rare mutations included MFN2 mutation (n. 8 pts), BSCL2 mutation (n.8 pts), PMP22 point mutation (n.7 pts), GDAP1 mutation (n.4 pts), GARSmutation (n. 2 pts), TRPV4 mutation (n. 2 pts), LITAF mutation (n.1 pt), and NEFL mutation (n. 1 pt)., Conclusions: Our study provides further data on frequency of CMT genes, subtypes in a wide Mediterranean area and contributes to help clinicians in addressing the genetic testing workup.

Alliance Against Cancer (ACC) was established in Rome in 2002 as a consortium of six Italian comprehensive cancer centers (Founders). The aims of ACC were to promote a network among Italian oncologic institutions in order to develop specific, advanced projects in clinical and translational research. During the following years, many additional full and associate members joined ACC, that presently includes the National Institute of Health, 17 research-oriented hospitals, scientific and patient organizations. Furthermore, in the last three years ACC underwent a reorganization process that redesigned the structure, governance and major activities. The present goal of ACC is to achieve high standards of care across Italy, to implement and harmonize principles of modern personalized and precision medicine, by developing cost effective processes and to provide tailored information to cancer patients. We herein summarize some of the major initiatives that ACC is currently developing to reach its goal, including tumor genetic screening programs, establishment of clinical trial programs for cancer patients treated in Italian cancer centers, facilitate their access to innovative drugs under development, improve quality through an European accreditation process (European Organization of Cancer Institutes), and develop international partnerships. In conclusion, ACC is a growing organization, trying to respond to the need of networking in Italy and may contribute significantly to improve the way we face cancer in Europe.

Accreditation and designation procedures by the Organisation of European Cancer Institutes (OECI) have represented a considerable challenge for most of the Italian cancer centers. We summarize the experience of the San Martino-IST in Genoa, which, on the whole, was satisfactory, albeit demanding for the staff. The reorganization of most oncology/hematology operations within the disease management teams was probably the key point that allowed us to obtain approval as it brought about the possibility of bringing in uniform methods of diagnosis/treatment, increasing patient recruitment in clinical trials, and fostering translational research by promoting collaboration between clinicians and laboratory investigators. The creation of a more cohesive supportive and terminal care team facilitated both the OECI procedures as well as the operations within the institution. Finally, some considerations are added to the doctor and nurse management roles in Italian hospitals characterized by noticeable differences from northern Europe. These differences may represent an extra challenge for hospital management and evaluator teams more used to the northern European type of organization.

Objectives: Triple valve surgery (TVS) is still a challenge for surgeons because of prolonged cardiopulmonary bypass (CPB) and myocardial ischaemic times. The reported operative mortality rate for TVS ranges between 2.5 and 25%; long-term survival is also diminished, with reported survival rates at 5 and 10 years of 75-82 and 61-75%, respectively. The objective of our study is to define early and late clinical outcomes, reporting the initial experience in the treatment of triple valve disease through a minimally invasive approach., Methods: A retrospective, observational, cohort study was undertaken of prospectively collected data on 106 patients who underwent TVS at our institution between October 2001 and June 2013. A total of 101 procedures were done through the standard median sternotomy; however, in 5 patients, the surgical procedure was carried out through a right minithoracotomy. Univariate analysis was performed to identify predictors of early and late survival., Results: The in-hospital mortality rate was 5.6% (6 of 107 patients). Predictors of early mortality were: previous cardiac surgery [odds ratio (OR) 4, 95% confidence interval (CI) 1.08-5.2, P = 0.04], preoperative left ventricular ejection fraction (LVEF) (OR 0.9, 95% CI 0.8-1.1, P = 0.003), prolonged CPB time (OR 1.02, 95% CI 1.01-1.04, P = 0.01) and postoperative pulmonary complications (OR 8, 95% CI 5.8-41, P = 0.0001). Five- and 10-year survival rates were 85 ± 3 and 65 ± 9%, respectively. In univariate analysis, diabetes [hazard ratio (HR) 2.5, 95% CI 1-6.2, P = 0.045], preoperative dialysis (HR 3, 95% CI 2-4.7, P = 0.001), unstable angina (HR 4.8, 95% CI 1-18, P = 0.03), preoperative LVEF (HR 0.9, 95% CI 0.8-1.1, P = 0.02), concomitant coronary artery bypass grafting (CABG) (HR 2.5, 95% CI 1.5-5.7, P = 0.006), prolonged CPB time (HR 1.02, 95% CI 1.01-1.13, P = 0.006), postoperative pacemaker (PMK) implantation (HR 6.2, 95% CI 1.3-18, P = 0.01) and postoperative pulmonary complications (HR 3.3, 95% CI 2.1-7.3, P = 0.002) were found to be significant predictors of late mortality following TVS. The freedom rates from valve-related complications and reoperation at 10 years were 95 ± 2 and 97 ± 2%, respectively. The 10-year freedom rates from thromboembolism and anticoagulation-related haemorrhage were 88 ± 5 and 88 ± 4%, respectively., Conclusions: TVS offers encouraging short-term and long-term patient survival; these good results after TVS in patients with advanced valvular heart disease justify aggressive surgical therapy in these patients. TVS with a minimally invasive approach is feasible and could be another treatment option., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: The impact of sutureless prosthesis on the clinical outcome in minimally invasive aortic valve replacement is still unclear. We assessed mid-term outcomes of the sutureless and conventional valves implanted through right anterior minithoracotomy., Methods: Five hundred fifteen patients undergoing primary aortic valve replacement through a right anterior minithoracotomy (269 conventional versus 246 sutureless prostheses) between 2004 and 2014 were reviewed. The most common sutured prostheses were Carpentier-Edwards Perimount and Medtronic Mosaic, and the Sorin Perceval S mainly composed the sutureless prosthesis group. One hundred thirty-three pairs of patients were propensity matched and retrospectively analyzed., Results: Cardiopulmonary bypass (p<0.0001) and cross-clamping (p<0.0001) times were shorter in the sutureless group (S group). We observed the same in-hospital mortality (1 versus 2; p=0.62) and incidence of postoperative stroke and pacemaker implant between the groups, but shorter duration of mechanical ventilation (6 versus 7 hours; p=0.001) in the S group. Generally, larger prostheses were implanted in the S group (p<0.0001). Follow-up was longer (p<0.0001) for sutured valves: 52 versus 15 months (overall median, 21 months). Overall Kaplan-Meier survival rate was 87.2% versus 97.0% (p=0.33) and 50% versus 100% (p=0.02) in elderly patients for sutured versus sutureless prostheses, respectively. Freedom from reoperation at follow-up (p=0.64) and transaortic gradients (12 versus 11 mm Hg; p=0.78) did not differ in the two groups., Conclusions: In the present limited cohort of patients, sutureless prostheses reduced operative times for aortic valve replacement and the duration of mechanically assisted ventilation and might have influenced early and mid-term survival. Larger studies are needed to confirm our data and compare long-term outcomes., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

A panel of experts from Italian Comprehensive Cancer Centers defines the recommendations for external quality control programs aimed to accreditation to excellence of these institutes. After definition of the process as a systematic, periodic evaluation performed by an external agency to verify whether a health organization possesses certain prerequisites regarding structural, organizational and operational conditions that are thought to affect health care quality, the panel reviews models internationally available and makes final recommendations on aspects considered of main interest. This position paper has been produced within a special project of the Ministry of Health of the Italian Government aimed to accredit, according to OECI model, 11 Italian cancer centers in the period 2012-2014. The Project represents the effort undertaken by this network of Comprehensive Cancer Centers to find a common denominator for the experience of all Institutes in external quality control programs. Fourteen shared "statements" are put forth, designed to offer some indications on the main aspects of this subject, based on literature evidence or expert opinions. They deal with the need for "accountability" and involvement of the entire organization, the effectiveness of self-evaluation, the temporal continuity and the educational value of the experience, the use of indicators and measurement tools, additionally for intra- and inter-organization comparison, the system of evaluation models used, the provision for specific requisites for oncology, and the opportunity for mutual exchange of evaluation experiences.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common form of familial vascular dementia, is caused by mutations of the NOTCH3 gene. Approximately two hundred pathogenic mutations have been reported within five exons (exons 3, 4, 6, 11 and 19) which accounted for 78% of known mutations in worldwide series. We reported twenty-one NOTCH3 pathogenic mutations (including five novel ones) identified in 53 index Italian patients. Exons 4 (28%), 7 (21%) and 19 (24%) were the most frequently involved. To dissect genetic heterogeneity, we analyzed five haplotyped tagging single nucleotide polymorphisms (rs1044009, rs4809030, rs10426042, rs10423702 and rs3815188) in 95 patients, 39 unaffected pedigree members and 50 healthy controls. SNPs were analyzed using the Illumina VeraCode Universal Capture Beads technology by Allele Specific Primer Extension (ASPE). We identified ten different haplotypes named H1-H10; H1 was the most common haplotype in patients and controls and it was associated with at least twelve out of the twenty-one mutations. Detected mutations were not associated to specific haplotypes while genotyping was compatible with a possible founder effect for the novel p.S396C mutation which clustered in a restricted geographical area of northeast Italy. The results added on to the genetic heterogeneity of CADASIL and emphasized difficulties in designing algorithms for molecular diagnosis., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement. We studied an Italian family with a CMT2 phenotype with pyramidal signs that had subclinical sensory involvement on sural nerve biopsy. Direct sequencing analysis of the BSCL2 gene in the three affected siblings revealed an S90L mutation. This report confirms the variability of clinical phenotypes associated with a BSCL2 Ser90Leu mutation and describes the first Italian family with this mutation.

The effects of maternal active and passive smoking during pregnancy on childhood central nervous system (CNS) tumours were assessed in a population-based case-control study. The mothers of 244 children aged 0-15 years with CNS tumours and 502 control mothers were interviewed about their smoking habits. All families were resident in the region of Lombardy, Italy. Risk estimates were calculated by unconditional logistic regression, adjusted for age, sex and area of residence. Active smoking by the parents before pregnancy was not associated with increased risk of CNS tumours in the children. Active smoking by the mother during early pregnancy (approximately the first 5 weeks) was associated with a slightly increased risk of the child developing a CNS tumour (odds ratio [OR] 1.5 [95% CI 1.0, 2.3]). An increased risk of CNS tumours was found in the children of non-smoking mothers exposed regularly to tobacco smoke both in early pregnancy (OR 1.8 [95% CI 1.2, 2.6]) and in late pregnancy (OR 1.7 [95% CI 1.2, 2.5]). Although this study was retrospective, the results confirm our previous findings and suggest an association between the risk of developing CNS tumours in children and regular passive smoking by the mother during pregnancy.

Incidence rates for CNS tumours in children of age 0-14 years in the Region of Lombardy, Italy, during the period 1988-93 were analysed; survival probability updated to December 1995 was also estimated. CNS tumours defined according to the International Classification of Diseases for Oncology codes were actively searched for. CNS tumours were diagnosed in 296 children. The age-standardized rates were 40.0 per million child years for both sexes together, and 45.3 for boys and 34.4 for girls. In all age groups, boys had a higher incidence than girls. The annual incidences were 13.7, 7.0, 5.8 for astrocytoma, medulloblastoma and ependymoma, respectively. The overall survival percentages at 5 and 8 years after diagnosis were 68 and 66, respectively. Prognosis was good for astrocytoma (5-year survival, 81%), and declined in the order: other gliomas (5-year survival, 76%); ependymoma (5-year survival, 62%), and medulloblastoma (5-year survival, 43%). The histological type of the tumour was the most powerful independent predictor of survival in children with a CNS tumour. Medulloblastoma/primitive neuroectodermal tumours appeared to have the highest risk of a poor prognosis compared with astrocytoma (relative risk, 3.27; 95% confidence interval, 1.81-5.91). Age at diagnosis and sex had no significant effect on survival. The incidence of childhood CNS tumours found in this study is higher than previously reported in Italy, and is one of the highest in the world from population-based data. Survival of children with brain tumours has improved greatly in recent years. These results suggest that children in Lombardy with CNS tumours had a good survival experience compatible with high quality of care.