Italian Prospective Study Research Articles

Association of circulating T lymphocytes and their functional states with pathologic complete response (pCR) in breast cancer (BC). A prospective Italian study.

559 Background: In BC, pCR is associated with substantial survival benefit. Hence, escalated neoadjuvant treatments (NATs) are being increasingly employed to improve pCR rates, warranting biomarkers for better patients’ selection. T-cell exhaustion and senescence are dysfunctional states that coexist in patients with cancer, impairing antitumor immunity and sustaining a suppressive immune microenvironment. Here, we assessed the impact of such states on pCR across different BC subtypes and NATs. Methods: This is a prospective study on patients undergoing NAT for BC at the Maggiore Hospital of Novara, Italy. Blood was collected at baseline and after NAT. Circulating T lymphocytes were characterized with exhausted (CD28, PD1, LAG3) and senescent (CD57, KLRG-1) biomarkers utilizing flow cytometry. Neutrophiles/lymphocytes ratio (NLR) and lymphocytes/monocytes ratio (LMR) were also retrieved. Subpopulations with frequency <1% were normalized for total CD3+ cells. Results: From October 2020 to January 2024, 134 patients were enrolled and 115 completed NAT (85.8%). Fifty-one (38,1%) had adequate samples for analysis, 16 (31,4%) with hormone receptor positive HER2 negative BC (HR+HER2-), 15 (29,4%) with HER2+, and 20 (39,2%) with triple negative BC (TN). At baseline, patients with TNBC had the lowest NLR (p=0.018) and lowest senescent CD4+CD28- (p=0.042). Associations with pCR are shown in the Table. Overall, LMR associated with increased pCR (OR 1.34 [95% CIs 1.00-1.89]), and NLR with decreased pCR (OR 0.67 [0.39-1.04]). Both associations were driven by HR+ status (interaction p = 0.061 and 0.060). Senescent CD4+ predicted lower pCR in both HR-HER2+ (OR 0.10 [0.01-0.36]) and TNBC (OR 0.10 [0.01-0.5]). In TNBC, exhausted CD8+ predicted higher pCR (OR 1.78 [1.08-3.79]). When assessed separately in patients who received NAT with or without pembrolizumab, exhausted CD8+ remained predictor of pCR in chemotherapy + pembrolizumab (OR 1.84 [1.03-5.00]), but not with chemotherapy alone (p=0.203). The dynamics of paired pre-NAT and post-NAT TNBC samples revealed significant differences. Senescent CD4+ increased after chemotherapy, but not with chemotherapy + pembrolizumab (p=0.007). Pembrolizumab was associated with depletion of PD1-positive CD8+, while chemotherapy alone was not (p=0.020). Conclusions: The characterization of circulating T lymphocytes could help identify patients who benefit more in terms of pCR from specific NATs, including chemoimmunotherapy. [Table: see text]

Understanding Patterns of Adherence to Antifibrotic Treatment in Idiopathic Pulmonary Fibrosis: Insights from an Italian Prospective Cohort Study.

Background: Pirfenidone and Nintedanib have significantly improved the prognosis of patients with idiopathic pulmonary fibrosis (IPF), reducing mortality risk and exacerbations. This study aimed to analyze antifibrotic treatment utilization and its association with clinical outcomes (i.e., acute exacerbation or death) during 2014-2021 in newly diagnosed IPF patients, using Healthcare Utilization Databases of the Marche Region, Italy. Methods: The first 12-month adherence to antifibrotic was estimated using the Proportion of Days Covered (PDC), defining adherence as PDC ≥ 75%. State Sequence Analysis over the initial 52 weeks of treatment was used to identify adherence patterns. The role of adherence patterns on acute exacerbations/death, adjusted by demographic, clinical features, and monthly adherence after the 52-week period (time-dependent variable), was assessed with Cox regression. Results: Among 667 new IPF cases, 296 received antifibrotic prescriptions, with 62.8% being adherent in the first year. Three antifibrotic utilization patterns emerged-high adherence (37.2%), medium adherence (42.5%), and low adherence (20.3%)-with median PDCs of 95.3%, 79.5%, and 18.6%, respectively. These patterns did not directly influence three-year mortality/exacerbation probability, but sustained adherence reduced risk over time. Conclusions: Good adherence was observed in in this population-based study, emphasizing the importance of continuous antifibrotics therapy over time to mitigate adverse outcomes.

Management of pregnancy in autoimmune rheumatic diseases: maternal disease course, gestational and neonatal outcomes and use of medications in the prospectiveItalian P-RHEUM.it study

ObjectivesTo investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it.MethodsPregnant women with different ARD were enrolled for up to 20 gestational weeks...

Underdilation strategy for TIPS placement reduces incidence of overt hepatic encephalopathy without affecting clinical efficacy and survival: results of a multicenter prospective Italian study

Underdilation strategy for TIPS placement reduces incidence of overt hepatic encephalopathy without affecting clinical efficacy and survival: results of a multicenter prospective Italian study

Comparison of first-tier whole-exome sequencing with a multi-step traditional approach for diagnosing paediatric outpatients: An Italian prospective study.

The recent guidelines suggest the use of genome-wide analyses, such as whole exome sequencing (WES), at the beginning of the diagnostic approach for cases with suspected genetic conditions. However, in many realities it still provides for the execution of a multi-step pathway, thus requiring several genetic tests to end the so-called 'diagnostic odyssey'. We reported the results of GENE Project (Genomic analysis Evaluation NEtwork): a multicentre prospective cohort study on 125 paediatric outpatients with a suspected genetic disease in which we performed first-tier trio-WES, including exome-based copy number variation analysis, in parallel to a 'traditional approach' of two/three sequential genetic tests. First-tier trio-WES detected a conclusive diagnosis in 41.6% of patients, way above what was found with routine genetic testing (25%), with a time-to-result of about 50 days. Notably, the study showed that 44% of WES-reached diagnoses would be missed with the traditional approach. The diagnostic rate (DR) of the two approaches varied in relation to the phenotypic class of referral and to the proportion of cases with a defined diagnostic suspect, proving the major difference for neurodevelopmental disorders. Moreover, trio-WES analysis detected variants in candidate genes of unknown significance (EPHA4, DTNA, SYNCRIP, NCOR1, TFDP1, SPRED3, EDA2R, PHF12, PPP1R12A, WDR91, CDC42BPG, CSNK1D, EIF3H, TMEM63B, RIPPLY3) in 19.4% of undiagnosed cases. Our findings represent real-practice evidence of how first-tier genome-wide sequencing tests significantly improve the DR for paediatric outpatients with a suspected underlying genetic aetiology, thereby allowing a time-saving setting of the correct management, follow-up and family planning.

Outcome of Patients with Chronic Myeloid Leukemia in Chronic Phase Showing Clinical Resistance to Frontline Treatment with Second Generation Tyrosine Kinase Inhibitors. an Italian Prospective Study from the CML Campus

BACKGROUND: Frontline treatment with second generation tyrosine-kinase inhibitors (2G-TKIs) in patients with chronic myeloid leukemia in chronic phase (CP-CML) demonstrated higher efficacy as compared to imatinib therapy in inducing deeper molecular responses. However, its ability to reduce treatment failure and progressive disease is debated. Furthermore, limited information is currently available on the outcome of those CML patients showing clinical resistance to first-line treatment with a 2G-TKI. AIM: To describe the clinical outcome of CP-CML patients showing resistance to a frontline 2G-TKI and that switched to alternative TKIs therapy. PATIENTS AND METHODS: We performed this investigation on patients drawn from a web-based database (www.epiclin.it/lmc) used to collect clinical and biological data of CML patients enrolled in 24 Italian Hematology Centers from January 2013 onwards. Definitive information about first-line TKI treatment was available in 1277 prospective and consecutive CP-CML patients: 607 received imatinib and 670 dasatinib or nilotinib (2G-TKIs) as frontline therapy. Main inclusion criteria were: i) diagnosis of CP-CML; ii) first-line treatment with a 2G-TKI; iii) switch to second-line treatment in case of clinical resistance (i.e. failure according to ELN 2020 recommendations). Exclusion criteria was switch to second-line treatment for intolerance or for low adherence to therapy. Patients were treated according to the Center policy and the molecular data were obtained in accordance to the IS% parameters. RESULTS: Fifty-four CML patients met the inclusion/exclusion criteria and were identified as failure according to the ELN 2020 recommendations. The median age of these patients was 48.5 (20-81) years; male sex in 30 (55.5%) and female 24 (44.4%), Sokal risk score was low in 16 (29.6%), intermediate in 22 (40.7%) and high in 16 (29.6%) patients respectively;ELTS score was low in 26 (48.1%), intermediate in 14 (25.9%) and high in 14 (25.9%) patients. Additional chromosomal abnormalities were present at diagnosis in 4 out of 54 patients (7.4%: 3 additional Ph-chromosome and 1 trisomy 8). Nilotinib was administered in 27 (50%) and dasatinib in 27 (50%) of the patients.At 6 months, 30 out of 50 evaluable patients (60%) had BCR::ABL1 transcript values >1% and at 12 months 9 of 33 evaluable patients (28%) had BCR::ABL1 values still >1%. Second-line treatment after 2G-TKIs frontline failure started in all patients after a median time of 12 months (3-83) with ponatinib (30 pts, 55.5%), dasatinib (8 pts, 14.8%), nilotinib (4 pts, 7.4%), bosutinib (7 pts, 12.9%) or imatinib (5 pts, 9.2%).At 12 months the switch to second-line treatment induced the achievement of BCR::ABL1 values <1% in 45% of the evaluable cases. Eighteen patients (in which no mutations were found) switched to third-line treatment after a median time of 11 months (0-45) (ponatinib, 8 pts; nilotinib, 1 pt; dasatinib, 3 pts; imatinib, 3 pts; bosutinib, 1 pts; asciminib, 2 pts). MMR or a better response was reached by 6 of these patients and allogeneic stem-cell transplantation (SCT) was performed in 7 patients.Progression to CML advanced phase occurred in 8 pts. After a median follow-up of 59.9 months (15.6 - 99.3) 44 patients were still alive and death occurred in 10 pts (18.5%) (7 CML-related and 3 unrelated). Overall survival (OS) at 5 years was 82% (see Figure below). Indeed, OS at 5 years was 94% for the total 670 patients treated frontline with 2G-TKIs. In this population, 12 out of 32 observed deaths were CML-related and all were recorded in patients who changed TKI therapy, whereas in 19 cases the death was CML-unrelated and in 1 case was not specified. However, those patients who maintained the same therapy for 5 years showed an OS of 96%, whereas those who had to change treatment for any cause showed an OS of 89% at 5 years. CONCLUSION: Our findings, collected from the prospective cohort of the CML Italian observational registry, show that CP-CML patients failing frontline 2G-TKI therapy, despite a complex management, may have still an acceptable prognosis and survival due to the availability of both multiple TKI options and SCT.

ECG/echo indexes in the diagnostic approach to amyloid cardiomyopathy: A head-to-head comparison from the AC-TIVE study

Background and aimsThe discordance between QRS voltages on electrocardiogram (ECG) and left ventricle (LV) wall thickness (LVWT) on echocardiogram (echo) is a recognized red flag (RF) of amyloid cardiomyopathy (AC) and can be measured by specific indexes. No head-to-head comparison of different ECG/echo indexes among subjects with echocardiographic suspicion of AC has yet been undertaken. The study aimed at evaluating the performance and the incremental diagnostic value of different ECG/echo indexes in this subset of patients. MethodsElectrocardiograms of subjects with LV hypertrophy, preserved ejection fraction and ≥ 1 echocardiographic RF of AC participating in the AC-TIVE study, an Italian prospective multicenter study, were independently analyzed by two cardiologists. Low QRS voltages and 8 different ECG/echo indexes were evaluated. Cohort specific cut-offs were computed. ResultsAmong 170 patients, 55 (32 %) were diagnosed with AC. Combination of low QRS voltages with interventricular septum ≥ 1,6 cm was the most specific (specificity 100 %, positive predictive value 100 %) ECG/echo index, while the ratio between the sum of all QRS voltages and LVWT <7,8 was the most sensitive and accurate (sensitivity 94 %, negative predictive value 97 %, accuracy 82 %). When the latter index was added to a model using easily-accessible clinical variables, the diagnostic accuracy for AC greatly increased (AUC from 0,84 to 0,95; p = 0,007). ConclusionsAmong patients with non-dilated hypertrophic ventricles with normal ejection fraction and echocardiographic RF of AC, easily-measurable ECG/echo indexes, mainly when added to few clinical variables, can help the physician orient second level investigations. External validation of the results is warranted.

SAT-430 - Burden of non-alcoholic fatty liver disease and usefulness of non-invasive tests to identify advanced liver disease in patients with type 2 diabetes mellitus: interim analysis of an Italian prospective multicentre study

SAT-430 - Burden of non-alcoholic fatty liver disease and usefulness of non-invasive tests to identify advanced liver disease in patients with type 2 diabetes mellitus: interim analysis of an Italian prospective multicentre study

Particulate matter exposure from motorized traffic and risk of conversion from mild cognitive impairment to dementia: An Italian prospective cohort study

BackgroundBased on epidemiologic and laboratory studies, exposure to air pollutants has been linked to many adverse health effects including a higher risk of dementia. In this study, we aimed to evaluate the effect of long-term exposure to outdoor air pollution on risk of conversion to dementia in a cohort of subjects with mild cognitive impairment (MCI). MethodsWe recruited 53 Italian subjects newly-diagnosed with MCI. Within a geographical information system, we assessed recent outdoor air pollutant exposure, by modeling air levels of particulate matter with equivalent aerodynamic diameter ≤10 μm (PM10) from motorized traffic at participants’ residence. We investigated the relation of PM10 concentrations to subsequent conversion from MCI to any type of dementia. Using a Cox-proportional hazards model combined with a restricted cubic spline model, we computed the hazard ratio (HR) of dementia with its 95% confidence interval (CI) according to increasing PM10 exposure, adjusting for sex, age, and educational attainment. ResultsDuring a median follow up of 47.3 months, 34 participants developed dementia, in 26 cases diagnosed as Alzheimer's dementia. In non-linear restricted spline regression analysis, mean and maximum annual PM10 levels positively correlated with cerebrospinal fluid total and phosphorylated tau proteins concentrations, while they were inversely associated with β-amyloid. Concerning the risk of dementia, we found a positive association starting from above 10 μg/m3 for mean PM10 levels and above 35 μg/m3 for maximum PM10 levels. Specific estimates for Alzheimer's dementia were substantially similar. Adding other potential confounders to the multivariable model or removing early cases of dementia onset during the follow-up had little effect on the estimates. ConclusionsOur findings suggest that exposure to outdoor air pollutants, PM10 in particular, may non-linearly increase conversion from MCI to dementia above a certain ambient air concentration.

Mode of Delivery in Women with Stillbirth: Results of an Area-Based Italian Prospective Cohort Study

Introduction: The choice of the mode of delivery, in case of stillbirth (SB) (fetus non-viable &gt;22 weeks’ gestation), should consider maternal preference, gestational age, bishop score, the clinical condition of the woman, and her previous obstetric history. However, despite these clear indications, data on the effective implementation of the latter are lacking. The aim of our study is to evaluate the different modes of delivery in an Italian population of SBs, according to gestational age, parity, causes of death, obstetric history, and maternal characteristics. Material and Methods: This is an area-based, prospective cohort study conducted in Emilia Romagna, Italy between January 2014 to December 2020. Data included all cases of SB (&gt;22 weeks). Results: From 2014 to 2020, 783 SB occurred out of a total of 232.506 births, with a SB rate of 3.3 per 1000. Labor was spontaneous in 85 (11%). Of remnant, 567 (73.6%) were induced and 118 (15.3%) had no labor. The mode of delivery was vaginal in most of the cases (649/770, 84.3%) and by cesarean section in 121/770 (15.7%) of cases. Emergency CS was most frequent and performed in 89/121 (73.5%) of total CS, representing 11.5% of SB deliveries. Mode of induction did not differ in relation to gestational age at stillbirth, while vaginal delivery was significantly higher in women induced with prostaglandins (p = 0.000) respect to other methods. Nulliparous women had a significantly higher need for multiple methods of induction (p = 0.000) respect multiparous and obese women used more frequently prostaglandins (p = 0.03) than other methods. Women with a history of previous CS presented a significantly higher rate of repeated elective CS (p = 0.000). Moreover, emergency CS was performed more frequent in obese (p = 0.02), diabetic (p = 0.04) and hypertensive (p = 0.04) women and in SB caused by placenta disorders, namely in abruptio placentae (p = 0.000). In the case of chorioamnionitis and funisitis women significantly were induced with prostaglandin (p = 0.000) and delivered vaginally (p = 0.000). Conclusions: The method of induction of labor and the mode of delivery in case of SB did not depend on gestational age at the diagnosis of death, while they are related to placenta disorders representing a relevant condition leading to emergency CS also after diagnosis of fetal death. These data could help obstetric providers in managing the deliveries of stillborn infants.

Use of cangrelor in patients with acute coronary syndromes undergoing percutaneous coronary intervention: Study design and interim analysis of the ARCANGELO study.

BackgroundThe itAlian pRospective Study on CANGrELOr (ARCANGELO) was aimed to assess the safety of using cangrelor during percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS) in the daily practice.HypothesisThe safety of cangrelor after the transition to oral P2Y12 inhibitors was evaluated as the incidence of bleeding outcomes in the 30 days following PCI according to postauthorization safety study guidelines.MethodsAdults with ACS who were treated with cangrelor in one of the 28 centers involved in the study. Patients who consented to participate were followed in the 30 days following their PCI. Bleedings (Bleeding Academic Research Consortium [BARC] classification), major adverse cardiac events (MACEs), and adverse events were recorded. The interim results at two‐thirds of the enrollment period are presented.ResultsA total of 17 bleedings were observed in the 320 patients who completed the study at this stage. All bleedings were classified as BARC Type 1–2, except for one case of Type 3a (vessel puncture site hematoma). Four patients experienced MACEs (2 acute myocardial infarctions, 1 sudden cardiac death, 1 noncardiovascular death due to respiratory distress, and multiorgan failure). None of the bleedings was rated as related to cangrelor.ConclusionsThe interim results of the ARCANGELO study provide a preliminary confirmation that the use of cangrelor on patients with ACS undergoing PCI is not associated with severe bleedings.

COVID-19 in liver transplant recipients: incidence, hospitalization and outcome in an Italian prospective double-centre study

Liver transplant (LT) recipients are vulnerable to SARS-CoV-2-infection (COVID-19), due to immunosuppression and comorbidities. This study aimed to evaluate the impact of COVID-19 on LT recipients compared to general population in the Campania region. In this prospective double-centre study, we enrolled all consecutive adult LT recipients with confirmed SARS-CoV-2-infection. Data were collected at diagnosis of COVID-19 and during follow-up and compared with the regional population. Thirty LT recipients (3.28%) developed SARS-CoV-2-infection (76.66% male, median age 62.61 years). Sixteen (53.33%) were symptomatic. Common symptoms were fever, cough, fatigue, and anosmia. Twenty-five (83.33%) were outpatients, 5 (16.66%) required hospitalization (6.66% admitted to Intensive Care Unit, 6.62% developed Acute Respiratory Distress Syndrome and 6.66% died). Immunosuppressors were in 3 (10%) patients. Incidence rate of COVID-19 was similar between LT patients and general population (3.28% vs 4.37%, p = 0.142) with higher rate of symptoms in LT patients (53.33% vs 15.87%, p < 0.000). At univariate analysis, hospitalization and case fatality rates were higher in LT patients compared to general population (16.66% vs 4.54%, p = 0.001; and 6.66% vs 1.76%, p = 0.041, respectively). At multivariable logistic regression analysis, LT patients with COVID-19 were more frequently symptomatic (OR 5.447 [95% CI 2.437–12.177], p < 0.000), whereas hospitalization and death for COVID-19 were not significatively associated with LT condition (p = 0.724 and p = 0.462, respectively) and were comparable with general population. LT is not a risk factor for acquiring COVID-19. Nonetheless, LT patients are more frequently symptomatic, although comparable to the general population for hospitalization rate and mortality.

CD26/DPP-4 in Chronic Myeloid Leukemia.

Simple SummaryCD26/dipeptidylpeptidase IV (DPP-4) is a membrane-bound multifunctional protein expressed in many primary solid tumors and in hematological diseases. Recent investigations demonstrated its specific expression on leukemic stem cells (LSCs) of Chronic Myeloid Leukemia (CML) bone marrow (BM) and peripheral blood (PB) samples. Thanks to this evidence, CD26 has been considered a novel exclusive stem cell marker of CML. The aim of this review is to describe and analyze the role of CD26 in the context of hematological malignancies and specifically of CML and to highlight its potential clinical application for the management of this disease.CD26 expression is altered in many solid tumors and hematological malignancies. Recently, it has been demonstrated that it is a specific marker expressed on LSCs of CML, both in BM and PB samples, and absent on CD34+/CD38− stem cells in normal subjects or on LSCs of other myeloid neoplasms. CD26+ LSCs have been detected by flow-cytometry assays in all PB samples of Chronic-Phase CML patients evaluated at diagnosis. Additionally, it has been demonstrated that most CML patients undergoing Tyrosine Kinase Inhibitors (TKIs) treatment still harbored circulating measurable residual CD26+ LSCs, even when displaying a consistent deep molecular response without any significant association among the amounts of BCR-ABL transcript and CD26+ LSCs. Preliminary data of our Italian prospective multicenter study showed that CML patients with a poorer response presented with a higher number of CD26+ LSCs at diagnosis. These data confirmed that CD26 is a specific marker of CML and suggest that it could be considered for the monitoring of therapeutic responses.

Boswellia resin extract and propolis derived polyphenols in patients with type III chronic prostatitis/chronic pelvic pain syndrome: An Italian prospective multicenter study

ObjectiveTo assess the efficacy and safety of a treatment regimen based on rectal administration of Boswellia resin extract and propolis derived polyphenols in patients with type IIIa and type IIIb chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS). MethodsPatients with type IIIa and type IIIb CP/CPPS received one rectal suppository a day for 15 days per month for 3 consecutive months. Participants were evaluated with National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), the International Prostate Symptom Scores (IPSS), International Index of Erectile Function (IIEF), four-glass test, uroflowmetry, and prostate-specific antigen assessments at baseline and at Week 4, and Week 12. Primary endpoints were improvement in pain domain of NIH-CPSI and improvement of NIH-CPSI total score. Secondary outcomes included improvement of micturition and quality of life (QoL) domains of NIH-CPSI questionnaire. ResultsA total of 61 males were enrolled. No adverse events were reported. Significant improvements from baseline to Day 30 were reported for NIH-CPSI total score (mean difference: −9.2; p<0.01), NIH-CPSI pain domain (mean difference: −5.5; p<0.01), NIH-CPSI micturition domain, NIH-CPSI QoL domain, and IPSS total score (mean difference: −5.6; p<0.01). No significant changes from baseline in terms of IIEF score or maximum flow rate were observed. At final follow-up (Day 90), further significant improvements in terms of NIH-CPSI total score (mean difference: −12.2; p<0.01), NIH-CPSI pain domain (mean difference: −6.6; p<0.01), NIH-CPSI micturition domain, NIH-CPSI QoL domain, and IPSS total score were reported. ConclusionRectal administration of Boswellia resin extract and propolis derived polyphenols is well tolerated and delivers a significant symptomatic improvement in most patients with type IIIa and type IIIb CP/CPPS.

Autism spectrum disorder and anorexia nervosa: an Italian prospective study

BackgroundPotential overlaps exist between psychopathological features of Anorexia Nervosa (AN) and Autism Spectrum Disorder (ASD). The impact of malnutrition on autistic traits in patients with AN should be considered. This study investigates possible associations among the psychopathology of Eating Disorders (EDs), ASD traits and BMI in a group of young patients with AN, using the EDI-3 (Eating Disorder Inventory-3) test and gold-standard measures for ASD.MethodsProspective study involving 23 inpatients admitted to an Italian Centre for paediatric ED. ASD traits and ED psychopathology were assessed administering the ADOS-2 (Autism Diagnostic Observation Schedule-2), AQ (Autism Quotient) and EDI-3 tests. Both present and past autistic traits were investigated using different versions of AQ. Correlations were adjusted for BMI, Obsessive Compulsive Disorder (OCD) comorbidity and concurrent antipsychotic treatments.ResultsAn ASD diagnosis was possible in 22% of patients. Significant correlations were documented between ASD traits and ED psychopathology: AQ total-Interpersonal problems (IPC) (p = 0.041); AQ total-Global psychological maladjustment (GMPC) (p = 0.027); AQ social skills-Ineffectiveness (IC) (p = 0.018); AQ social skills-IPC (p = 0.019); AQ social skills-Affective problems (APC) (p = 0.025); AQ social skills-GMPC (p = 0.007); AQ attention switching-IPC (p = 0.020); ADOS-2 imagination-IC (p = 0.035). These correlations were independent of BMI, OCD and antipsychotic treatments.ConclusionsASD traits presented high prevalence in a group of young inpatients with AN. These traits were significantly correlated to 4 specific EDI-3 subscales and independent of BMI. This is the first study to investigate the relationship between ASD traits as measured with gold-standard measures, EDI-3 scores, and BMI.

Validation of the performance of “Fast Lung Ultrasound Teaching Program” for gynecologists/obstetricians dealing with pregnant women with suspicion of COVID-19 infection: an Italian prospective multicenter study

Validation of the performance of “Fast Lung Ultrasound Teaching Program” for gynecologists/obstetricians dealing with pregnant women with suspicion of COVID-19 infection: an Italian prospective multicenter study

Azole resistance in Aspergillus isolates by different types of patients and correlation with environment - An Italian prospective multicentre study (ARiA study).

A wide range of frequency of azole-resistance in A fumigatus in different patient populations worldwide was observed threatening to reduce therapeutic options. Estimate the prevalence of azole-resistance, investigate the molecular mechanisms of resistance, compare the genotypes of resistant clinical isolates with those from the surrounding environment. Aspergillus isolates were collected by seven Italian hospital microbiology laboratories. Strains were isolated from different clinical samples from unselected patients. The azole-resistance was evaluated using screening test and microdilution EUCAST method. The molecular mechanism of resistance was performed sequencing the cyp51A gene. Resistant isolates were genotyped by microsatellite analysis and their profiles compared with those of azole-resistant isolates from previous Italian studies. 425 Aspergillus isolates from 367 patients were analysed. The azole-resistance rates were 4.9% and 6.6% considering all Aspergillus spp. isolates and the A fumigatus sensu stricto, respectively. All resistant isolates except one were from a single hospital. Two rare azole-resistant species were identified: A thermomutatus and A lentulus. The predominant resistance mechanism was TR34 /L98H. No correlation between the clinical resistant strains and environmental isolates from patients' home/work/ward was observed. The analysis of the molecular correlation between the resistant clinical strains collected in the present study and those of environmental and clinical origin collected in previous Italian studies reveals a progressive diversification of azole-resistant genotypes starting from a founder azole-resistant genotype. This study confirms the trend of azole-resistance rate in Italy, showing a geographical difference. Data reinforce the importance of surveillance programmes to monitor the local epidemiological situation.

EPEN-03. LONG-TERM FOLLOW-UP OF AIEOP 2ND SERIES OF CHILDREN AND ADOLESCENT WITH PRIMARY INTRACRANIAL (ST:SUPRATENTORIAL; PF: POSTERIOR FOSSA) EPENDYMOMA AND METHYLATION GROUPS RE-ANALYSES

BACKGROUNDThis 2002–2014 Italian prospective study stratified 160 patients by surgical resection (complete=NED/incomplete=ED) and centrally-reviewed grade. Grade2/NED patients received focal radiotherapy (RT) up to 59.4Gy, Grade3/NED received 4 courses of VEC(vincristine,etoposide,cyclophosphamide) after RT.ED patients received 1–4 VEC courses, second-look surgery, 59.4 Gy+8Gy boost on measurable residue.METHODSWe re-analyzed data at 115 months follow-up including methylation profile on available samples.RESULTSGlobal PFS/OS at 5/10 years were 66/59% and 80/74%, respectively. Of the 64 relapsers at median 20 months, 53 died at median 37/18 months after diagnosis/relapse, respectively.10/64 relapsed after 5 years (66–126 months); 4 died, relapse was local in 8/10, metastatic 1, combined 1;5/10 patients were below age 3, 5 females, 8 PF tumors. Their survival post-relapse was not longer than earlier relapsers’. At univariable analysis, age over 3 years, female sex, complete surgery, grade 2, no shunt confirmed better PFS/OS. 66/95 analyzed tumors received a score >0.80 through the DNA methylation-based central nervous system tumor classifier: 41/8 as PFA/PFB, respectively,14/17 ST as RELA-positive (3 scored for other molecular entities i.e. anaplastic PXA, LGG MYB, HGNET). Prognostic factors were equally distributed among PFA/PFB groups,1 only group B patient relapsed locally at 96 months.CONCLUSIONSAlready published prognostic factors remained at long-term follow-up;6.2% patients had late relapses. OS after relapse was not better in late relapsers. Group B confirmed better prognosis but all patients had received «at least» adjuvant RT. Modern ependymoma trials need long follow-up to draw firm conclusions.

Safety profile of biologic drugs for psoriasis in clinical practice: An Italian prospective pharmacovigilance study.

Psoriasis is an inflammatory and chronic skin disorder associated with physical and psychological burden impairing patients’ quality of life. In the last decade, biologic drugs have widely changed treatment of moderate-severe psoriasis and their number is increasing overtime. To early identify expected/unexpected adverse events (AEs) with biologic treatments, pharmacovigilance programs are needed. We designed a post-marketing active pharmacovigilance program to monitor and analyse AEs and/or serious adverse events (SAEs) reports. All consecutive patients treated with one biologic drug during a two-years period and satisfying inclusion criteria have been enrolled in five Dermatology tertiary units. Demographic and clinical features of patients, type of treatment used, therapy discontinuation, failures, switch/swap to another biologic, and possible onset of AEs were collected. Overall, 512 patients with a diagnosis of psoriasis (286; 55.9%) or arthropathic psoriasis (226; 44.1%) have been enrolled. Eighty-two (16%) patients with AEs and 5 (1%) with SAEs have been identified. Further, 59 (11.5%) had a primary/secondary failure (mainly on infliximab and etanercept). The adverse events and SAEs were reported with golimumab (4/12), adalimumab (32/167), infliximab (9/48), etanercept (31/175) and ustekinumab (11/73), no adverse events have occurred with secukinumab (0/37). Infliximab and etanercept were significantly associated with primary/secondary failures, whereas no differences have been highlighted for AEs insurgence. On the other hand, ustekinumab seems to be associated with a low rate of AEs (p = 0.01) and no adverse events or failures have been reported with secukinumab (p = 0.04 and 0.03, respectively). Our study, even though limited by a small sample size and a brief follow-up period, provide useful data on widely used biologic drugs and their tolerability, discontinuation rate and the incurrence of severe adverse events. Further studies are necessary to include the recently approved biologic drugs and to increase the sample size for more detailed analysis.

A Prospective Italian Study on Baseline NS3 and NS5A Resistance to Direct-Acting Antivirals in a Real-World Setting of HIV-1/HCV Coinfected Patients and Association with Treatment Outcome.

We prospectively evaluated the frequency of natural resistance-associated substitutions (RASs) in the NS3 and NS5A regions according to different HCV genotypes and their possible effect on treatment outcome in HIV-1/HCV patients treated with direct-acting antivirals (DAAs). Baseline RASs in the NS3 and NS5A domains were investigated in 62 HIV-1/HCV patients treated with DAAs: 23 patients harbored HCV-GT1a, 26 harbored GT3a, and 13 harbored GT4d. A higher occurrence of RASs was found in the NS3 domain within GT1a (13/23) than GT3a (0/26) or GT4d (2/13). With regard to treatment outcome, NS3 RASs were detected in 14/56 patients with sustained virological response (SVR) and in 1/6 non-responder (NR) patients. Occurrence of RASs of NS5A domain was lower in SVR (4/56, had RASs) than in NR (3/6, had RASs). Evaluation of RASs at baseline instead of at virological failure, especially in the NS5A domain, could positively influence the choice of new DAA combinations for the treatment of HIV-1/HCV patients.