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Vulnerability during the coronavirus disease 2019 (COVID-19) pandemic is an emotional state that affects all of us globally. The Italian experience shows that our general practitioners (GPs) seem to have a higher rate of death due to COVID-19 infection than other physicians. This article discusses clinical ethics questions related to the vulnerability of GPs and the communityduringthepandemic inItaly: the total lackof, or the inadequateprotectionofpersonal protective equipment, the increased use of virtual medicine, and the value of a solid synergy between hospitals and territorial systems. We provide a few examples of experiences in other affected countries and populations (Indigenous communities in Brazil, Australia and Germany). In conclusion, we offer some reflections on the crucial role of communication in dealing with vulnerability issues during this COVID-19 pandemic period. [ABSTRACT FROM AUTHOR]

Background: The Italian External Quality Control Programme for cystic fibrosis molecular diagnosis started in 2001; public laboratories distributed throughout Italy participated on a voluntary basis. Methods: The Italian Public Health Institute (Istituto Superiore di Sanità) sent six validated DNA samples to participating laboratories: technical and clinical information was provided for each sample. Laboratories were required to analyse all six samples. For each sample the laboratories had to provide the results (including raw data) and a report of molecular analysis within 2 months using current methods and nomenclature. Raw data and reports were evaluated by a Steering Committee and their comments were sent to each laboratory. Results: Genotyping results indicated a general good level of quality for all laboratories, i.e., ∼1% of alleles were incorrectly assigned each year due to analytical (45%) and misinterpretation (45%) errors. During the first 2 years, more than 70% of laboratories did not test for some regional Italian mutations. Commercial kits for reverse dot-blot and oligonucleotide ligation assay PCR were used to detect mutations by 52.8% and 29.5%, respectively, of the participating laboratories. Reporting of results was still inadequate; in 2004 a model for the written report was introduced, but not all laboratories used it. Conclusions: Our data show that few genotyping errors were made by laboratories and were principally due to misinterpretation and analytical reasons. However, reports are still inadequate and it will be interesting to evaluate the introduction of the reporting model in future years. Clin Chem Lab Med 2007;45:254–60. [ABSTRACT FROM AUTHOR]

Background: For a number of persons with rare diseases (RDs) a definite diagnosis remains undiscovered with relevant physical, psychological and social consequences. Undiagnosed RDs (URDs) require other than specialised clinical centres, outstanding molecular investigations, common protocols and dedicated actions at national and international levels; thus, many "Undiagnosed RDs programs" have been gradually developed on the grounds of a well-structured multidisciplinary approach. Methods: The Italian Undiagnosed Rare Diseases Network (IURDN) was established in 2016 to improve the level of diagnosis of persons with URD living in Italy. Six Italian Centres of Expertise represented the network. The National Centre for Rare Diseases at the Istituto Superiore di Sanità coordinates the whole project. The software PhenoTips was used to collect the information of the clinical cases. Results: One hundred and ten cases were analysed between March 2016 and June 2019. The age of onset of the diseases ranged from prenatal age to 51 years. Conditions were predominantly sporadic; almost all patients had multiple organs involvements. A total of 13/71 family cases were characterized by WES; in some families more than one individual was affected, so leading to 20/71 individuals investigated. Disease causing variants were identified in two cases and were associated to previously undescribed phenotypes. In 5 cases, new candidate genes were identified, although confirmatory tests are pending. In three families, investigations were not completed due to the scarce compliance of members and molecular investigations were temporary suspended. Finally, three cases (one familial) remain still unsolved. Twelve undiagnosed clinical cases were then selected to be shared at International level through PhenomeCentral in accordance to the UDNI statement. Conclusions: Our results showed a molecular diagnostic yield of 53,8%; this value is comparable to the diagnostic rates reported in other international studies. Cases collected were also pooled with those collected by UDNI International Network. This represents a unique example of global initiative aimed at sharing and validating knowledge and experience in this field. IURDN is a multidisciplinary and useful initiative linking National and International efforts aimed at making timely and appropriate diagnoses in RD patients who still do not have a confirmed diagnosis even after a long time. [ABSTRACT FROM AUTHOR]

According to Law 91/1999, art. 18, in Italy, health care professionals and administrative staff involved in the process of organ collection and transplantation are required to ensure anonymity of both the donor and the recipient. Against this backdrop, in 2018, the Italian Committee for Bioethics (ICB) released an official opinion titled "Opinion on the preservation of the anonymity of donor and receiver in the transplantation of organs" that offers a new perspective on the topic, effectively opening the possibility of anonymity ending at certain conditions. The relevance of anonymity within the transplant network is a globally recognized principle with a strong ethical value. In this article, based on the experience of one author directly involved in the ICB opinion drafting, we examine the document and discuss how such a proposal could be implemented at the legislative level. • Italian regulations require anonymity between the family of the deceased donor and the recipient. • According to the ICB, identification could be possible if both parties express an intention to come into contact with each other. • Any contact between the donor's family and recipient must be managed by a third-party body pertaining to the National Health Service. [ABSTRACT FROM AUTHOR]

Introduction: Italian Cystic Fibrosis Registry (ICFR) collects data of patients with cystic fibrosis (CF) through the collaboration with Italian CF referral and support Centres (Italian law 548/93). It aims at analysing medium and long-term clinical and epidemiological trends, identifying healthcare needs at regional and national levels, contributing to healthcare programmes, and resource allocation. Italian data are also compared at international level through the collaboration with the European CF Registry for sharing epidemiological data on general aspects like CF epidemiology and specific topics such as the use of CFTR modulators., Objectives: The purpose of this Report is to provide updated demographic and clinical data of the Italian FC population for the years 2021 and 2022, to contribute essential information for the implementation of projects aimed at improving the management of patients affected by this disease., Design: Analyses and results presented in this Report pertain to patients currently under care at Italian National Referral and Support Centres for Cystic Fibrosis and Paediatric Hospital 'Bambino Gesù' in the 2021-2022 period. Data were submitted by clinical Centres through a dedicated web-based software and underwent dual quality control (QC) measures: automated quantitative QC within the software and secondary QC at the European level before the integration into the European Cystic Fibrosis Registry. These measures ensure data completeness, accuracy, and longitudinal consistency with European core data., Setting and Participants: A total of 27 CF Centres, including referral and support centres, as well as 'Bambino Gesù' Children's Hospital CF centre, submitted their data to ICFR for the years 2021-2022. Althourgh CF Centres in Verona and Messina do not use the ICFR software, their data are centrally collected and subsequently forwarded to the European Registry. Data from service centres in Treviso and Rovereto are transmitted via the Verona CF Centre. Data from Sardinia Centre are currently unavailable., Results: The results section provides a comprehensive overview of various aspects of CF epidemiology and patient characteristics. 1.Demography: in 2021 and 2022, 5,977 and 6,077 CF patients were respectively included in the ICFR, with median ages of 23.3 and 23.7 years. The prevalence rates were 10.1 and 10.3 per 100,000 residents in Italy for the respective years, with males comprising 51.6% on average. The distribution by age showed a higher frequency among patients aged 7 to 35 years; adult patients constituted 63.5% on average in both years. 2. Diagnosis: most CF patients were diagnosed before the age of two (mean value 57.9%), with a significant percentage diagnosed in adult age (35.4% in 2021 and 25.6% in 2022). 3.New diagnoses: there were 113 new diagnoses in 2021 and 121 in 2022, with estimated incidences of 1 in 9,097 living births in 2021 and 1 in 6,232 in 2022. 4. Genetics: genetic analyses were conducted on 99.9% of patients, revealing CFTR gene mutations in over 98% of cases. The F508del mutation was the most common (44% of alleles in 2021), with 18% of patients having at least one "residual function" mutation. Gating mutations were present in 3.4% of Italian patients, while 20% had at least one-stop codon mutation. 5.Lung function: lung function, measured by percent predicted (pp)FEV1 (Forced Expiratory Volume in the first second) progressively declined before adulthood, with the majority of paediatric patients (92.8% in 2021 and 93.8% in 2022) maintaining a ppFEV1≥70%. 6.Nutrition: critical periods for nutrition were identified as the first 6 months of life and adolescence, with higher prevalence of malnourished male adolescents compared to females. Suboptimal BMI values were more common in adult females (28.7% in 2021 and 26.9% in 2022) compared to males (14.2% in 2021 and 12.6% in 2022). 7. Complications: CF-related liver disease without cirrhosis was prevalent in patients under 18 years (21.9% in 2021 and 21.2 in 2022), while CF-related diabetes was most frequent in adults (24.2%). 8.Transplantation: over the two-year period, 28 patients underwent double-lung transplantation, with median ages of 29.1 in 2021 and 35.3 in 2022, respectively. Median waiting times ranged from 9.4 to 11.6 months. 9.Microbiology: chronic Pseudomonas aeruginosa infection affected 37.2% of adult patients in 2021 and 36.0% in 2022, compared to 7.4% and 6.5% in paediatric patients. Staphylococcus aureus infection rates were 34.6% and 42.2% in 2021 among adults and 34.4% and 36.7% in 2022 among paediatric patients. 10. Mortality: a total of 34 patients died during the 2021-22 period (19 females, 15 males), with median ages at death of 43.7 years in 2021 and 46 years in 2022 (excluding transplanted patients)., Conclusions: The present Report is an update of the data published in the past years and summarizes the main epidemiological and clinical data regarding Italian CF subjects in the years 2021 and 2022. The number of patients registered in 2021 was 5,977, while in 2022 was 6,077. The population coverage estimates for 2022 to be around 97%. In 2020, 60.5% of patients were older than 18 years, in 2022 adult patients account for 63.5% of the Italian CF population. Over the years, therefore, an increase in the median age of Italian CF patients has been observed, reaching 23.7 years in 2022. The absolute number of new diagnoses per year remains substantially unchanged over the years (a total of 234 in the period under review). The median age at diagnosis in 2022 was 2.5 months, 62.6% of subjects are really diagnosed within the first year of life and almost 90% of them are diagnosed through neonatal screening. In 2022, almost all patients underwent genetic analysis (99.9%). Data collected confirm the great variability among Italian CF patients. As regards respiratory function, what is reported in previous reports is here confirmed, with an ever-increasing percentage of subjects under the age of 18 having normal respiratory function, moreover, less than 1% of paediatric patients has a severe lung function (ppFEV1<40). The marked improvement in this indicator in the adult population seems to be mainly due to the introduction from 2021 in Italy of therapy with highly effective CFTR modulators. At the same time, the close positive correlation between nutritional status and respiratory function is confirmed for the adult population. As regards chronic infection by Pseudomonas aeruginosa, in 2022, a reduction in the percentage of chronic infection is observed both among adults (36% vs 38.8% in 2020) and in paediatric patients (6.5% vs 7.6% in 2020). The most frequent complication in both paediatric and adult populations is liver disease (respectively, in 24.2% and 41.3% of subjects). In the two-year period, 34 patients died; their median age at death was between 43 and 46 years (transplant patients excluded); only two patients under the age of 18 died in the period 2021 and 2022, confirming once again that mortality in paediatric age is a rare event. The data presented in this Report shows how the register can be a national and international point of reference for CF patients and the scientific community, a tool for describing the Italian CF population over the years, and a starting point for planning epidemiological studies and clinical studies.

Introduction: Italian cystic fibrosis registry (ICFR) collects data from cystic fibrosis (CF) patients through the collaboration with Italian CF referral and support Centres (Italian law 548/93). ICFR contributes: • to the analysis of medium and long term clinical and epidemiological trends of the disease; • to the identification of the main health care needs at regional and national level to contribute to the Health Care programmes and to the distribution of resources; • to the comparison of the Italian data with international ones. This latter is based on the collaboration with the European CF registry and, due the COVID-19 pandemic emergency, with important global projects., Objectives: The purpose of this Report is to update the demographic and clinical data of the Italian FC population in the years 2019 and 2020, contributing to the information necessary to implement projects to improve the management of patients affected by this disease., Design: Analyses and results described in the present Report are referred to patients currently followed at the Italian National Referral and Support Centres for Cystic Fibrosis in the 2019-2020 period. Data were sent by clinical Centres through a dedicated web-based software. Data undergo a double quality control (QC): the first is automatically performed by the software (quantitative QC), the second is performed at a European level (before the inclusion of the Italian data within the European Cystic Fibrosis Registry). These QCs assure the completeness and the accuracy of data as well as their longitudinal consistency with the European core data., Setting and Participants: A total of 29 CF Centres (referral and support centres and 'Bambino Gesù' Children's Hospital CF centre) sent to ICFR their data referred referred to years 2019-2020. CF Centres of Verona, Messina, and Palermo (this latter only for 2019) do not use the ICFR software; however, their data are firstly collected in a centralized manner, then sent to the European Registry. Data from support centres of Treviso and Rovereto are sent through the Verona CF Center. Finally, data from Sardinia Centre are still missing., Results: The present Report has been organized into 10 sections. 1. Demography: in 2019, 5,585 CF patients were registered in the ICFR and 5,801 in 2020; median age was 21.6 years in 2019 and 22.4 years in 2020. Prevalence was 9.36/100,000 and 9.79/100,000 residents in Italy in 2019 and in 2020, respectively. Male percentage was 51.5% in 2019 and 2020 and CF distribution by age range showed higher frequency in patients aged 7 to 35 years. Adult patients (aged more than 18 years) were 59.5% on average in both years. 2. Diagnoses: most of the CF patients were diagnosed before two years of age (median value 68.5%); a significant percentage of patients (12.9% in 2019 and 13.4% in 2020) was diagnosed in adult age. 3. New diagnoses: new diagnoses were 136 in 2019 and 96 in 2020. Estimated incidence was 1/5.568 living births in 2019 and 1/7.369 in 2020. 4. Genetics: 99.9% of patients underwent genetic analyses and in 98.2% of these patients a mutation in Cystic Fibrosis Transmembrane Regulator (CFTR) gene was identified. The F508del mutation was the most frequent (identified in 44.7% allele; 2019 data). Furthermore, on average 17.3% of patients had at least one ‘residual function’ mutation. At least one gating mutation is present in 3.3% of Italian patients. Finally, 20.5% of patients had at least one stop codon mutation (class 1). 5. Lung function: percent predicted FEV1 (Forced Expiratory Volume in the first second) progressively declined before adult age, in accordance with the natural history of the disease. The majority of paediatric patients (6-17 years of age), i.e., 86.7% in 2019 and 90.5% in 2020, had percent predicted FEV1 >=70%; whereas paediatric patients with a FEV1% >=40% are less than 2% in the study period. 6. Nutrition: the two most critical periods are the first 6 months of life and adolescence. Prevalence of malnourished adolescent males (12-17 years of age) is higher than the prevalence observed in females. Increasing percentages of female patients with a suboptimal BMI value (33.5% and 31.4%, respectively, in 2019 and 2020) are observed in adult age. 7. Complications: in 2019, CF-related liver disease without cirrhosis was the main complication both in patients aged less than 18 years (20.3% on average) and in adults (37.5%). CF-related diabetes was also frequent in CF adults (23.4%). 8. Transplantation: in 2019-2020, 64 patients received a double-lung transplantation. Median and range of age were 33 years (12.29-57.46) in 2017 and 32.9 (16.5-53.6) years in 2020. Median waiting times for lung transplantation in the two-year period ranged from 6 to 8 months. 9. Microbiology: percentage of adult patients with chronic Pseudomonas aeruginosa infection was 41.6% in 2019 and 38.8% in 2020 vs 14.3% in 2019 and 7.6% in 2020 in paediatric age. Staphylococcus aureus infection is present in 31.1% and 35.9% of adult patients in 2019 and in 33.5% and 34.7% of paediatric patients in 2020. 10. Mortality: a total of 51 patients died in the 2019-2020 period (28 females and 23 males); median age at death was 35.7 years in 2019 and 39 years in 2020 (transplanted patients are not included)., Conclusions: The present report shows that the Italian CF population is growing (4,159 in 2010 vs 5,801 in 2020). Median age of patients increased in the 2010-2020 period (17 years in 2010 vs 22.4 years in 2020). Prevalence of adult patients is increasing (in 2020, 60.5% of patients is more than 18 years old). About 68.5% of new patients is diagnosed within the second year of life and median age at death (transplanted patients not included) increased in 2020 up to 39 years (in 2018 this value was 35.8). Some statistical differences between 2019 and 2020 are mainly due to the absence of about 200 patients not included in 2019 data by a participating centre for a technical problem.

Introduction: On the 15th of November 2020, the National Centre for Rare Diseases of the Italian National Health Institute, clinicians of the Italian National Referral and Support Centres for Cystic Fibrosis, Children's Hospital "Bambino Gesù", Italian Cystic Fibrosis Society, Italian League for Cystic Fibrosis renewed the agreement about CF data flow for a 3-year period. The possibility to access data by third parties is among the most important innovation introduced within the agreement., Objectives: Aim of the present Report is to improve the know-how of cystic fibrosis (CF) through a better characterization of Italian patients. Furthermore, the present Report aims at improving the care of CF patient. In particular, this Report should contribute to the following objectives: • to analyse the medium- and long-term clinical and epidemiological trends of the disease; • to identify the main healthcare needs at regional and national level, in order to contribute to the healthcare programmes and to the distribution of resources; • to compare Italian data with international ones., Design: Analyses and results described in the present Report are referred to patients currently followed at the Italian National Referral and Support Centres for Cystic Fibrosis in the 2017-2018 period. Data were sent by clinical Centres through a new-committed software. Data underwent a double quality control (QC): the first is automatically performed by the software (quantitative QC), the second is performed at a European level (before the inclusion of the Italian data within the European Cystic Fibrosis Registry). These QCs assure the completeness and the accuracy of data as well as their consistency with the European core data., Setting and Participants: The present Report has been organized into 10 sections. 1. Demography: in the ICFR, 5,565 CF patients were registered in 2017 and 5,501 in 2018; median age was 21.4 years in 2017 and 21.2 years in 2018. Prevalence was 9.20/100,000 residents in Italy in 2017 and in 2018. Male percentage was 51.65% in 2017 and 2018, CF distribution by age range showed higher frequency in patients aged 7 to 35 years. Adult patients (aged more than 18 years) were 56.4% on average in 2017 and 2018. 2. Diagnoses: most of the CF patients were diagnosed before two years of age (median value 66.4%); a significant percentage of patients (21.6% in 2017 and 18.3% in 2018) was diagnosed in adult age. 3. New diagnoses: new diagnoses were 162 in 2017 and 142 in 2018. Estimated incidence was 1/5.214 living births in 2017 and 1/5.442 in 2018. 4. Genetics: 99.8% of patients underwent genetic analyses and in 97.1% of these patients a mutation in Cystic Fibrosis Transmembrane Regulator (CFTR) gene was identified. The F508del mutation was the most frequent (44.6% in 2018). Furthermore, 16.3% of patients in 2017 and 16.9% of patients in 2018 had at least one 'residual function' mutation. At least one gating mutation is present in 3.3% of Italian patients. Finally, 20.5% of patients had at least one stop codon mutation (class 1). 5. Lung function: percent predicted FEV1 (Forced Expiratory Volume in the first second) progressively declined before adult age, in accordance with the natural history of the disease. The majority of paediatric patients (6-17 years of age), i.e., 86.70% in 2017 and 90.50% in 2018, had percent predicted FEV1 ≥70%; whereas paediatric patients with a FEV1% ≤40% are less than 2% in the 2017-2018 period. 6. Nutrition: the two most critical periods are the first 6 months of life and adolescence. Prevalence of malnourished adolescent males (12-17 years of age) is higher than the prevalence observed in females. Increasing percentages of adult female patients with a suboptimal BMI value (39.1% and 36.1%, respectively, in 2017 and 2018) are observed. 7. in 2018, CF-related liver disease without cirrhosis was the main complication both in patients aged less than 18 years (17.0% on average) and in adults (31.5%). CF-related diabetes was also frequent in CF adults (23.4%). 8. Transplantation: in 2017-2018, 83 patients received a double-lung transplantation. Median and range of age were 29.3 years (11.8-60.2) in 2017 and 29.1 (7.8-45.6) years in 2018. Median waiting times for lung transplantation in the two considered years were 8.6 and 7.7, respectively. 9. Microbiology: percentage of adult patients with chronic Pseudomonas aeruginosa infection was 51.3% in 2017 and 46.3% in 2018 vs 15.6% in 2017 and 10.2% in 2018 in paediatric age. Staphylococcus aureus infection is present in 53.4% and 53.5% of adult patients in 2017 and in 41.6% and 37.5% of paediatric patients in 2018. 10. Mortality: a total of 89 patients died in the 2017-2018 period (49 females); median age at death was 33.9 years in 2017 and 35.8 years in 2018 (transplanted patients are not included)., Conclusions: The present report shows that the Italian CF population is growing (4,159 in 2010 vs 5,501 in 2018; +1,342). Quality of data collected has been improved by the drastic reduction of missing data, thanks to the new software for data collection. Median age of patients increased in the 2010-2018 period (17 years in 2010 vs 21.2 years in 2018). Paediatric death is a very rare event. A very low percentage of paediatric population was characterized by severe lung disease (FEV1% <40). Prevalence of adult patients is increasing (56.4% in 2018). Age at diagnosis is decreasing (4.2 months in 2017 vs 3.8 months in 2018). Median age at death (transplanted patients not included) was 33.9 in 2017 and 35.8 in 2018. RIFC is completely compliant with the GDPR (UE 2016/679 regulation) and its role in national and international CF communities is confirmed., Competing Interests: None

(1) Background: Diagnostic testing for cystic fibrosis (CF) is based on a sweat chloride test (SCT) considering the appropriate signs and symptoms of the disease and results of a gene mutation analysis. In 2014, the Istituto Superiore di Sanità (ISS) established a pilot Italian external quality assessment program for CF SCT (Italian EQA-SCT), which is now a third party service carried out by the ISS. (2) Methods: The ongoing scheme is prospective, enrollment is voluntary, and the payment of a fee is required. Results are shared through a dedicated web-facility. Assessment covers the analysis, interpretation, and reporting of results. (3) Results: Thirteen, fifteen, sixteen, and fifteen different laboratories, respectively, participated from 2015 to 2016 and from 2018 to 2019 in the Italian EQA-SCT scheme. Eleven different laboratories participated each year in all four rounds of the Italian EQA-SCT. (4) Conclusions: The overall results obtained from the laboratories participating constantly clearly show that their qualitative and quantitative performance improved significantly. This is due to the opportunity-after receiving the EQA results-to constantly review their performance and address any inconsistencies. We firmly believe that participation in the EQA program will improve the quality of participating laboratories and that EQA participation should become mandatory as a fundamental requirement for laboratory accreditation.

In order to bridge the gap between available organs and patients needing transplants, donor selection criteria for donors are increasingly being extended; the possibility of using organs from nonstandard risk donors has been introduced in many countries. This clearly poses considerable ethical issues that should be analyzed and taken into consideration by the competent bodies and institutions. In this article, we illustrate the Italian situation regarding the possibility of using organs from anti-hepatitis C virus (HCV) and HCV RNA-positive donors (anti-HCV+ve) in negative recipients (healthy subjects who have never come into contact with the hepatitis C virus) in light of the availability of new direct-acting antiviral drugs (DAAs) for hepatitis C treatment. We discuss the motivations behind the both favorable opinions of the Ethics Committee of the Italian National Institute of Health (Istituto Superiore di Sanità) and the Italian National Bioethics Committee (Comitato Nazionale per la Bioetica) discussing the main implications from an ethical point of view., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: On the 27th of October 2017 the National Center for Rare Diseases of the Italian National Health Institute (NHI), clinicians of the Italian National Referral and Support Centres for Cystic Fibrosis, Paediatric Hospital "Bambino Gesù", Italian Cystic Fibrosis Society, and the Italian League for Cystic Fibrosis renewed the agreement about FC data flow for a 3 years period. The possibility to access data by third parties is among the most important new introduced within the agreement., Objectives: Aim of the present report is to improve the know-how on cystic fibrosis (CF) through a better characterization of Italian patients. Furthermore, the present Report aims at improving the care of CF patient. In particular, the Report should contribute to the following objectives: * to analize medium- and long-term clinical and epidemiological trends of the disesase; * to identify the main health care needs at regional and national level in order to contribute to the healthcare programmes and to the distribution of resources; * to compare Italian data with international ones., Design: Analyses and results described in the present Report are referred to patients in charge to the Italian National Referral and Support Centers for Cystic Fibrosis in the period 2015-2016. Data were sent by Centres by means of a specific software (Camilla, Ibis Informatica). Data underwent to a double quality control (QC): the first by NHI and the second at a European level (before the inclusion of the italian data within the European Cystic Fibrosis Registry). These QCs assure the completeness and the accuracy of data as well as their consistency with European core data. Finally, in 2017, an additional CQ was performed to further reduce the number of missing data and consequently improve the precision and the consistency in the nomenclature adopted for genetic mutations., Setting and Participants: A total of 29 different CF Centres (referral, support, and Paediatric Hospital "Bambino Gesù") sent their data referred to 2015-2016 years to ICFR . Data regarding Sardinia (Southern Italy) are missing and those from Treviso (Veneto Region, Northern Italy) and Rovereto (Trentino-Alto Adige Region, Northern Italy) are sent through Verona CF Centre., Results: The present Report has been organized into 10 sections. 1. Demography: estimated CF patients is 5,204 in 2015 and 5,362 in 2016; median age is 20.6 and 21.0, respectively. Prevalence is 8.6/100,000 residents in Italy in 2015 and 8.8 in 2016. Male percentage is 51.6% on average for 2015 and 2016; CF distribution showed higher frequency in patients aged from 7 to 35 years. The mean of patients aged more than 18 years is 56.5% on average in 2015 and 2016. 2. Diagnoses: most of the CF patients were diagnosed before 2 years of age (median value: 68%); a significant percentage of patients (median value: 13%) was diagnosed in adult age. 3. New diagnoses: new diagnoses were 169 in 2015 and 153 in 2016. Estimated incidence in 2015 was 1/4,176 living births in 2015 and 1/5,510 in 2016. 4. Genetics: 99.5% of patients underwent genetic analyses and in 96% of patients a mutation in Cystic Fibrosis Transmembrane Regulator (CFTR) gene was identified. [delta]508F was the most frequent mutation (44,7% in 2016). Furthermore, 16.0% and 3.4% of patients was characterized by the presence of at least one "residual function" mutation and gating, respectively. Finally, 21% of patients was a stop codons (class 1 mutation) carrier. 5. Lung function: FEV1 (forced expiratory volume in the first second) scores progressively decreased before adult age, in accordance with the natural history of the disease. FEV1% values in patients between 6 and 17 years of age is ≥70%; patients with a FEV1% value of 40% are less than 2% in the period 2015-2016. 6. Nutrition: most critical periods are during the first 6 months of life and during adolescence. Prevalence of malnourished male aged 12-17 years is constant in 2015-2016 and is always more than the prevalence observed in female. An increasing percentage of female patient with a suboptimal BMI value (35.5%) is observed among patients aged more than 18 years 7., Complications: it was estimated that, in 2016, hepatopathies without cirrhosis (17.7%) is the principal complications in patients aged less than 18 years; in patients aged more than 18 years the principal complication was due to hepatopathies without cirrhosis (29.5%) and diabetes (23.3%). 8. Transplantation: in 2015-2016, 74 patients were bipulmunary transplanted; age was comprised between 8 and 52 years, median age at transplantation was 29,6 years. Median waiting times for transplantation is estimated in 17 months (24 months in 2015 and 14 months in 2016). 9. Microbiology: analyses were referred to test performed in 2016. Percentage of adult patients with chronic Pseudomonas aeruginosa infection is 52.1% compared to 15.2% of paediatric patients; Staphylococcus aureus infection is present in 53.2% of adult patients and 52.8% of paediatric ones; Burkholderia Cepacia complex is present almost exclusively in adult patients (4.3%); Nontuberculous mycobacteria is present in 1.2% and 0.4% of adult and paediatric patients, respectively; Stenotrophomonas maltophilia infection is present in the 6.1% of adult patients and 4.9 of paediatric patients. 10. Mortality: 102 patients (49 males and 53 females; median age 36.9 years in 2015 and 36.5 in 2016) died in 2015-2016 (transplanted patients are not included)., Conclusions: The present Report shows that Italian CF population is growing (median age) and paediatric mortality is decreasing. A very low percentage of paediatric population is characterized by complication of pulmonary function; adult patients are characterized by an increase of age at death (more than 36 years of age in 2016).

Familial adenomatous polyposis is a rare autosomal dominant inherited disease (incidence, 1/8000). More than 90% of families affected by familial adenomatous polyposis have a mutation in the tumor suppressor gene adenomatous polyposis coli (APC). Mutations in this gene are characterized by 100% penetrance, although there is a variation in phenotypic expression of the disease. According to a 2004 survey of the Italian Human Genetic Society, about 264 APC gene molecular genetic tests were performed by Italian laboratories per year. The Italian External Quality Assessment (IEQA), financially supported by the Ministry of Health and coordinated by the Istituto Superiore di Sanità, was started in 2000 to improve the quality of molecular genetic tests in Italy. In the frame of the IEQA, about 50% of public laboratories performing APC gene tests have been monitored. The number of responding public laboratories during the 5 years was 6, 7, 7, 7, and 5 from 2001 to 2006, respectively; on average, 96.3% of samples completely analyzed were correctly genotyped. Methods used by laboratories to detect mutation were direct sequencing, single-strand conformation polymorphism, protein truncation test, and denaturing high-performance liquid chromatography. Written reports were not homogeneous among laboratories, although a new form of written report was proposed to laboratories in 2004. It will be interesting to monitor the effects of the reporting model and the output of this educational action in the future.

The Italian scheme of External Quality Assessment for beta-thalassemia started in 2001 as part of a project twice funded by the Italian Ministry of Health and coordinated by the Istituto Superiore di Sanità. To date, five trials have been performed (2001-2004 and 2006). The aim of the Italian scheme is to help public laboratories in improving and reaching a high standard of quality when performing a molecular test. Many laboratories took part in the 5-year project, and their participation was constant during the whole period. The aims of this paper are to describe the genotyping and reporting results as well as focusing on the techniques and the testing strategies adopted to detect mutations. Almost 99% of the alleles analyzed were correctly detected by laboratories, while 0.33% of the analyses gave a wrong result. Reverse dot blot was the most used technique, and it was always used in the strategies adopted by laboratories to detect mutations. The reports sent by laboratories showed incompleteness and heterogeneity; thus, a new model for written reports has been introduced since 2004. It will be interesting to monitor the effects of the reporting model and the output of this educational action in the future.

The Italian External Quality Assessment scheme for fragile X syndrome started in 2001 as an activity funded by the National Health System and coordinated by the National Institute of Public Health. The aim of this work is to present the data of 5 years (2001--2004 and 2006) of survey. The External Quality Assessment scheme was designed to cover the following points: (a) genotyping and (b) interpretation and reporting of results. Overall, the scheme covered about 65% of all Italian public laboratories. The average reporting of results was 91.6%, with an overall success rate of 76%. The rate of diagnostic errors observed was on average 5%. Inaccuracy in sizing of CGG repeats of normal and premutated alleles was reported. During the survey the proportion of laboratories using a Southern blotting, polymerase chain reaction, and ABI sizing kit in combination rose from 36.8% to 70.6%. The reports from laboratories showed incompleteness and considerable variations in expected outcomes. For this reason, in 2004 a model for written reports was introduced. In conclusion, these data underscore the need to participate in External Quality Assessment schemes as an educational resource to ensure quality in molecular genetic testing.

The first Italian national trial of external quality assessment in genetic testing was organised within the framework of the "Italian National Project for Standardisation and Quality Assurance of Genetic Tests". Sixty-eight Public Health Service laboratories volunteered for the trial, which involved molecular genetic tests (cystic fibrosis, beta-thalassaemia, familial adenomatous polyposis coli and fragile-X syndrome) and cytogenetic tests (prenatal and postnatal, the latter included cancer cytogenetics). The response rate was high (88.2%). The level of analytical accuracy was good, i.e., the percentage of laboratories that correctly genotyped all samples was 89.3% for cystic fibrosis, 90.9% for beta-thalassaemia, 100% for familial adenomatous polyposis coli (despite two laboratories did not complete the analysis because the amount of DNA was considered insufficient), and 90.5% for fragile-X syndrome. Written reports differed widely and were judged "inadequate" in over 50% of cases. Most laboratories from the present study already have experience in previous European external quality assessments for at least one genetic test; this can explain the higher analytical accuracy in the Italian external quality assessment with respect to quality control programmes in other countries. Collaborative networks are strongly suggested to improve the quality of the reports.