Italian Cohort
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Francesca Pasqualin ◽  
Carolina Barnett ◽  
Silvia Vittoria Guidoni ◽  
Elisa Albertini ◽  
Mario Ermani ◽  

Abstract Objective To validate the Italian version of the Myasthenia Gravis Impairment Index (MGII). Introduction MGII is a recent promising measure developed for MG patient evaluation. It includes a clinical severity evaluation and a patient-reported questionnaire. It has been developed in English and has demonstrated feasibility, reliability, and construct validity. Recently, its Dutch translation has been validated. Methods MGII was translated to Italian with a multi-step forward process. We assessed correlations with the following scores: Istituto Nazionale Carlo Besta score for Myasthenia Gravis (INCB-MG), the MG Activities of Daily Living (MG-ADL), the Myasthenia Gravis Composite (MGC), the Quality of Life 15 for Myasthenia Gravis (QOL15-MG), and the Myasthenia Gravis Disability (MGDIS). We also assessed differences in MGII scores by disease severity with the ANOVA Kruskal–Wallis test. Results One hundred forty-one patients were enrolled. The mean MGII total score was 13.3 ± 11.9 (range 0–49), with a mean ocular subscore of 3.7 ± 4.7 and a mean MGII generalized subscore of 9.6 ± 9.0. As expected, the MGII had a good correlation with the other severity scores. The MGII had a lower floor effect (3.5%) than the other measures. Twenty-five patients were assessed in follow-up; as expected, the MGII change scores had moderate correlations with change in other MG severity measures and lower correlations with quality of life measures. Conclusions The MGII score was cross-culturally validated in an Italian cohort of MG patients. We confirmed its lower floor effect and the correlations with other MG measures including INCB-MG that was not evaluated in previous studies.

2021 ◽  
I Bestetti ◽  
C Barbieri ◽  
A Sironi ◽  
V Specchia ◽  
S A Yatsenko ◽  

Abstract STUDY QUESTION Can a targeted whole exome sequencing (WES) on a cohort of women showing a primary ovarian insufficiency (POI) phenotype at a young age, combined with a study of copy number variations, identify variants in candidate genes confirming their deleterious effect on ovarian function? SUMMARY ANSWER This integrated approach has proved effective in identifying novel candidate genes unveiling mechanisms involved in POI pathogenesis. WHAT IS KNOWN ALREADY POI, a condition occurring in 1% of women under 40 years of age, affects women’s fertility leading to a premature loss of ovarian reserve. The genetic causes of POI are highly heterogeneous and several determinants contributing to its prominent oligogenic inheritance pattern still need to be elucidated. STUDY DESIGN, SIZE, DURATION WES screening for pathogenic variants of 41 Italian women with non-syndromic primary and early secondary amenorrhoea occurring before age 25 was replicated on another 60 POI patients, including 35 French and 25 American women, to reveal statistically significant shared variants. PARTICIPANTS/MATERIALS, SETTING, METHODS The Italian POI patients’ DNA were processed by targeted WES including 542 RefSeq genes expressed or functioning during distinct reproductive or ovarian processes (e.g. DNA repair, meiosis, oocyte maturation, folliculogenesis and menopause). Extremely rare variants were filtered and selected by means of a Fisher Exact test using several publicly available datasets. A case-control Burden test was applied to highlight the most significant genes using two ad-hoc control female cohorts. To support the obtained data, the identified genes were screened on a novel cohort of 60 Caucasian POI patients and the same case-control analysis was carried out. Comparative analysis of the human identified genes was performed on mouse and Drosophila melanogaster by analysing the orthologous genes in their ovarian phenotype, and two of the selected genes were fruit fly modelled to explore their role in fertility. MAIN RESULTS AND THE ROLE OF CHANCE The filtering steps applied to search for extremely rare pathogenic variants in the Italian cohort revealed 64 validated single-nucleotide variants/Indels in 59 genes in 30 out of 41 screened women. Burden test analysis highlighted 13 ovarian genes as being the most enriched and significant. To validate these findings, filtering steps and Burden analysis on the second cohort of Caucasian patients yielded 11 significantly enriched genes. Among them, AFP, DMRT3, MOV10, FYN and MYC were significant in both patient cohorts and hence were considered strong candidates for POI. Mouse and Drosophila comparative analysis evaluated a conserved role through the evolution of several candidates, and functional studies using a Drosophila model, when applicable, supported the conserved role of the MOV10 armitage and DMRT3 dmrt93B orthologues in female fertility. LARGE SCALE DATA The datasets for the Italian cohort generated during the current study are publicly available at ClinVar database ( accession numbers SCV001364312 to SCV001364375. LIMITATIONS, REASONS FOR CAUTION This is a targeted WES analysis hunting variants in candidate genes previously identified by different genomic approaches. For most of the investigated sporadic cases, we could not track the parental inheritance, due to unavailability of the parents’ DNA samples; in addition, we might have overlooked additional rare variants in novel candidate POI genes extracted from the exome data. On the contrary, we might have considered some inherited variants whose clinical significance is uncertain and might not be causative for the patients’ phenotype. Additionally, as regards the Drosophila model, it will be extremely important in the future to have more mutants or RNAi strains available for each candidate gene in order to validate their role in POI pathogenesis. WIDER IMPLICATIONS OF THE FINDINGS The genomic, statistical, comparative and functional approaches integrated in our study convincingly support the extremely heterogeneous oligogenic nature of POI, and confirm the maintenance across the evolution of some key genes safeguarding fertility and successful reproduction. Two principal classes of genes were identified: (i) genes primarily involved in meiosis, namely in synaptonemal complex formation, asymmetric division and oocyte maturation and (ii) genes safeguarding cell maintenance (piRNA and DNA repair pathways). STUDY FUNDING/COMPETING INTEREST(S) This work was supported by Italian Ministry of Health grants ‘Ricerca Corrente’ (08C621_2016 and 08C924_2019) provided to IRCCS Istituto Auxologico Italiano, and by ‘Piano Sostegno alla Ricerca’ (PSR2020_FINELLI_LINEA_B) provided by the University of Milan; M.P.B. was supported by Telethon-Italy (grant number GG14181). There are no conflicts of interest.

2021 ◽  
Roberta Naddei ◽  
Renata Alfani ◽  
Martina Bove ◽  
Valentina Discepolo ◽  
Filomena Mozzillo ◽  

2021 ◽  
pp. 135245852110353
Maria Pia Sormani ◽  
Irene Schiavetti ◽  
Doriana Landi ◽  
Luca Carmisciano ◽  
Nicola De Rossi ◽  

Background: The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, serological tests became routinely available. Objective: To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test. Methods: We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model. Results: Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20, p = 0.002). Conclusion: Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination.

2021 ◽  
Vol 10 (15) ◽  
pp. 3391
Silvia Nozza ◽  
Laura Timelli ◽  
Annalisa Saracino ◽  
Nicola Gianotti ◽  
Claudia Lazzaretti ◽  

Background: We aimed to describe the change in the incidence and causes of hospitalization between 2008 and 2018 among persons living with HIV (PLWHIV) who started antiretroviral therapy (ART) from 2008 onwards in Italy. Methods: We included participants in the ICONA (Italian Cohort Naïve Antiretrovirals) cohort who started ART in 2008. All the hospitalizations occurring during the first 30 days from the start of ART were excluded. Hospitalizations were classified as due to: AIDS-defining conditions (ADC), non-ADC infections and non-infections/non-ADC (i.e., cardiovascular, pulmonary, renal-genitourinary, cancers, gastrointestinal-liver, psychiatric and other diseases). Comparisons of rates across time were assessed using Poisson regression. The Poisson multivariable model evaluated risk factors for hospitalizations, including both demographic and clinical characteristics. Results: A total of 9524 PLWHIV were included; 6.8% were drug users, 48.9% men-who-have sex with men (MSM), 39.6% heterosexual contacts; 80.8% were males, 42.3% smokers, 16.6% coinfected with HCV and 6.8% with HBV (HBsAg-positive). During 36,157 person-years of follow-up (PYFU), there were 1058 hospitalizations in 747 (7.8%) persons; they had HIV-RNA >50 copies mL in 34.9% and CD4 < 200/mmc in 27%. Causes of hospitalization were 23% ADC, 22% non-ADC infections, 55% non-infections/non-ADC (11% cancers; 9% gastrointestinal-liver; 6% cardiovascular; 5% renal-genitourinary; 5% psychiatric; 4% pulmonary; 15% other). Over the study period, the incidence rate (IR) decreased significantly (from 5.8 per 100 PYFU in 2008–2011 to 2.21 per 100 PYFU in 2016–2018). Age > 50 years, intravenous drug use (IDU), family history of cardiovascular disease, HIV-RNA > 50, CD4 < 200, were associated with a higher hospitalization risk. Conclusions: In our population of PLWHIV, the rate of hospitalization decreased over time.

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