Journal articles on the topic 'Associazione statistica'

L'analisi è stata effettuata individuando le argomentazioni comuni o comunque assai similari esistenti fra i differenti commenti operati dai Nefrologi intervenuti nella discussione sulle scarsità della DP, considerati gli items di base. Ad essi è stato dato un punteggio arbitrario fra 0 e 2 per ogni singolo autore a seconda della rilevanza espressa dall'autore, la cui somma ha dato il peso totale dell'item, espresso in percento sulla somma totale degli items. Ciò ha dato luogo a due classificazioni delle cause individuate, la prima secondo i 13 items individuati, la seconda per associazione logica fra gli items. In ambedue le classificazioni il minor punteggio è dovuto ad un'ipotizzata non necessità della DP in Italia, mentre le classificazioni si diversificano per il punteggio più elevato, legato a responsabilità dei nefrologi stessi per varie cause nella prima classificazione e nella seconda a palese responsabilità dello Stato. Punteggi significativi sono legati ad un'insufficiente formazione ed informazione dei nefrologi, e nella prima classificazione all'intervento del privato nella terapia dialitica.

Il presente studio retrospettivo a singolo cieco si pone come obbiettivo quello di valutare in che percentuale di casi di pazienti che si presentano con sintomatologia compatibile con neurite vestibolare acuta, con e senza perdita oggettiva della funzione vestibulare (VFL), sia presente un conflitto neurovascolare fra il nervo vestibolococleare e la arteria cerebellare anteroinferiore (AICA). 58 pazienti con sintomatologia suggestiva per neurite vestibolare acuta, valutati con RMN presso un centro di terzo livello, sono stati confrontati con 61 pazienti asintomatici. I radiologi hanno dato valutato la presenza di conflitto neurovascolare, in assenza di dati clinici, conferendo ai rilievi oggettivi una valutazione in una scala da 0 a 3 a seconda che il contatto fosse: nesuno; inferiore a 2 mm; superiore ai 2 mm; presenza di vacular loop. I reperti neurootologici sono stati quindi raccolti all’oscuro del risultato dell’imaging. La funzione vestibolare è stata testata con prova calorica bitermica. Alla prova calorica 26 casi (45%) hanno mostrato segni oggettivi di deficit vestibolare (Gruppo A), 32 casi (55%) non hanno invece mostrato alcun deficit labirintico (Gruppo B). Il gruppo A ha incluso 13 casi (50%) con evidenza di conflitto neurovascolare (NVC), il gruppo B ha incluso 26 casi con NVC (82%) (p = 0.012) mentre i controlli hanno incluso 16 casi con NVC (26%). La differenza fra i tre gruppi ha mostrato significatività statistica (p<0.001). Il Gruppo B ha mostrati un associazione con un grading di conflitto piu elevato rispetto al Gruppo A (p = 0.009). La presenza di NVC non ha avuto un associazione statisticamente significativa ne con la presenza di SNHL ne con la presenza di acufene (p > 0.05). I nostri dati indicano che la presenza di conflitti neurovascolari a livello dell’angolo pontocerebellare è superiore in quei pazienti che in presenza di una sintomatologia compatibile con neurite vestibolare acuta abbiano una funzionalità simmetrica alla prova calorica.

Le malattie rare raggruppano un numero elevato di patologie molto diverse tra loro, accumunate, dalla bassissima frequenza statistica nella popolazione (penetranza). Ne consegue una scarsissima numerosità di pazienti per ogni singola patologia e una loro distribuzione in diverse aree geografiche, fattori che comportano oggettive difficoltà nel reclutamento dei pazienti in studi sperimentali e nel coordinamento e organizzazione della ricerca con conseguente ridotta possibilità di effettuare studi clinici e ricerche di carattere genetico. In tale quadro, al fine di fare fronte alle drammatiche necessità di assistenza socio-sanitaria, cura e riabilitazione dei malati rari, sono sorte, in gran parte per merito degli stessi familiari, le associazioni di malati rari. Attualmente tali associazioni svolgono un’attività significativa nella proposizione, organizzazione, partecipazione diretta e pubblicazione dei risultati di ricerche scientifiche. Tale ruolo, rende le associazioni dei pazienti protagoniste anche nel sostegno all’organizzazione e realizzazione di studi clinici e sperimentazioni di farmaci in modo del tutto autonomo e indipendente da controlli da parte delle autorità sanitarie e dei comitati etici. Tale fenomeno noto come “Research Led by Participants” è stato reso possibile dalle enormi potenzialità di contatto e organizzazione offerte dalla rete che ha consentito la creazione di comunità virtuali di pazienti, di siti e blog dedicati all’informazione e comunicazione, e più recentemente, alla raccolta di dati, alla pubblicazione di risultati di ricerche condotte dai malati, nonché al reclutamento degli stessi per la conduzione di tali studi, secondo il modello proposto, ad esempio, dal sito PatientsLikeMe. Non possono tuttavia essere trascurati gli importanti aspetti etici implicati dalla ricerca condotta dai partecipanti. Tali aspetti concernono, come evidente, sia la validità scientifica di tali studi che la protezione dei soggeti che aderiscono alla sperimentazione. Si tratta di una forma di sperimentazione del tutto nuova che richiede la capacità di proporre una modalità di gestione condivisa tra cittadini/pazienti, “terzo settore”, ricercatori, istituzioni e comitati etici in grado di valorizzarne i potenziali benefici conoscitivi creando regole etiche “misurate” su tali circostanze. Nell’articolo sarà proposto un modello teorico di governance del fenomeno e saranno indicati possibili criteri etici operativi. ---------- Rare diseases gather up a large number of different pathologies, all very different among them but similar for the low statistical attendance of population (penetrance). Therefore there is a very low number of patients sick of the same pathology and their presence in different geographical areas makes objectively difficult to recruit patients in order to study their disease and coordinate and organize the research of the pathology. As a consequence there is a very reduced possibility to carry on clinical studies and genetic researches. In this framework, in order to face the dramatic necessity of sociological and sanitary assistance, treatment and rehabilitation of the rare patients, families members generally organize Rare Diseases Patient Organizations. At the moment these organizations develop an important activity with regard to organization, proposals, direct participation and publication of the scientific research results. These organizations also play an important part in supporting the organization and the realization of clinical trials. They play in total autonomy and are independent from every ethical and scientific oversight by the sanitary authorities and ethical committees. This extraordinary event known as “Research Led by Participants”, has been realized thanks to the large contacts possibilities and organization offered by the web which made possible the creation of virtual communities of patients, of blog and web site for information and communication and, more recently, for collecting statistical data, publication of the patients research results and the recruitment of patients in order to manage the studies following the rules and models proposed, for example, by the web site “PatientsLikeMe”. We must however put in evidence the important ethical issues involved in the research led by the participants. These aspects concern, obviously, either the scientific validity of these studies or the protection of the subjects who accept to be submitted to the experimentation. It is a completely new way of experimentation that requires the capacity to propose and follow a governance that must be accepted and shared by citizens/patients, “third sector”, research workers, institutions and ethical committees able to exploit the potential advantageous knowledge and create ethical rules inspired to those new situations. In this article it will be proposed a theoretical model of governance of this phenomenon and also it will be outlined ethical rules for operative plans.

Anesthesiologists consider professional insurance and its medico-legal problems as a remarkable aspect of their job. “Associazione Anestesisti Rianimatori Ospedalieri Italiani—Emergenza ed Area Critica” (AAROI-EMAC) is the Italian professional association of anesthesiologists and intensivists that works to train its subscribers on safety measures. This is a retrospective observational study on an insurance complaints database for anesthetic accidents that result in injuries to patients. The analyzed period runs from 1 January 2014 to 31 December 2016. A total of 1309 complaints related to 873 insurance claims were analyzed. Criminal complaints comprised 805 (64.4%) of the total, and civil complaints were 445 (35.6%). The iatrogenic damage claimed included: death (58% of the cases); peripheral nerve damage (8%); spinal cord injuries (5%); unspecified injuries (7%); dental damage (4%); infections (3%); needing second surgical procedure (2%); and other injuries (13%). There is a statistical significance between the size of the hospital and the number of the claims: small hospital complaints comprised 40.1% of the cases, while complaints against medium-sized and large hospitals constituted 20.6% of the cases (χ2GL = 8 = 39.87, p = 0.00). In Italy, anesthesiologists and intensivists are often involved in litigation even when they are not directly responsible for iatrogenic injuries, and the most frequent claims in ICU are related post-operative complications.

Objetivou-se estimar os parâmetros genéticos e fenotípicos de características reprodutivas de fêmeas bovinas da raça Chianina criadas em diferentes rebanhos participantes da Associazione Nazionale Allevatori Bovini Italiani da Carne (ANABIC). As características estudadas foram idade ao primeiro parto (IPP), primeiro intervalo de partos (IDP1) e intervalo médio de partos (IMDP). As análises estatísticas foram realizadas pelo procedimento General Linear Model (GLM) do programa estatístico SAS (Statistical Analysis System) e os componentes de variância foram estimados pelo método de máxima verossimilhança restrita utilizando-se o software MTDFREML sob modelo animal. Os números de observações utilizados para IPP, IDP1 e IMDP foram, respectivamente, 31.023; 23.998 e 94.497 e as médias encontradas, em dias, 1.037,69 ± 186,37; 457,93 ± 96,80 e 436,26 ± 90,83 para IPP, IDP1, IDPM. Todas as características avaliadas foram influenciadas pelo rebanho. Verificou-se efeito de estação e ano de nascimento da vaca sobre a IPP. O IDP1 e o IDPM foram influenciados por rebanho, estação e ano do parto precedente, observando-se efeito também da ordem de parição sobre o IDPM. As estimativas de herdabilidade para IPP, IDP1 e IDPM foram, respectivamente de 0,36 ± 0,014; 0,13 ± 0,014 e 0,05 ± 0,004. A repetibilidade para IDPM foi de 0,075 ± 0,004. A utilização de IPP e IDP1 em programas de melhoramento genético pode resultar em maior precocidade e mais alto potencial para longevidade nestes rebanhos.

AbstractItalian physicians who, from Oct. 1979 to April 1981 directed an emergency medical team in the Ogaden refugee camps of the Qorioley district of Somalia, report on location, general set-up, vital statistics, health aspects, water and food supply, sanitation, disposal of waste matter, health hazards, spread and control of diseases, health education, and planning of health services and health teams.Invited by the Caritas of Somalia and the United Nations High Commissioner for Refugees (UNHCR) office in Mogadishu, Somalia, from October 15, 1979 to December 31, 1980, two Italian medical teams of the Associazione Universitaria per la Cooperazione Internazionale (AUCI) worked among the Ogaden Refugees in 3 camps of the Qorioley District, lower Shabelli Region of Somalia. Each team consisted of one physician and 2 registered nurses. The Qorioley district, about 140 km SW of Mogadishu, has high day-time temperatures and high humidity throughout the year. The day to night temperature gradients are high. Strong winds are blowing to and from the Indian Ocean.The 3 camps had been set up in the bush, on the right bank of the Shabelli river, about 8 km NW of Qorioley Town. The refugees in these camps were of Somali extraction and of Muslin culture and religion. They were housed in large military tents, aqal (round roofed skin covered hut of nomads), “mundul” (circular grass-thatched hut built around a central pole) and “arysh” (rectangular hut, corrugated iron tile roofs), aggregated at a very high density. More than 5000 people lived on one hectar. It was so crowded lhat there was no more space than 1.5 m2 of shelter per person. They lacked all hygienic services.Each camp had a food storage hut (mud walled with corrugated iron roof) and 2-3 water collection ponds, fed from the river. At the time of our arrival, two “arysh” with a total of 20 beds were in use for non-ambulatory patients. Scattered in the camps there were 6 “medical posts.”

Abstract Abstract 2478 Diffuse large B cell lymphoma (DLBCL) is one of the most common types of non-Hodgkin's lymphoma. Approximately half of patients will be cured of their disease by primary therapy, including the R-CHOP regimen (rituximab, doxorubicin, cyclophosphamide, vincristine, desamethasone). The remaining die of the disease, mainly because of the occurrence of tumor drug resistance. Many efforts have been made to explain the biochemical and molecular mechanisms involved in resistance to the drugs used in the treatment of cancer patients, including those with DLBCL. A dose-intense therapy regimen (e.g. R-CHOP14) may help to improve the treatment outcome of DLBCL patients. We have carried out a retrospective study aimed at correlating the mRNA expression levels of genes involved in metabolism, mechanisms of action and resistance to doxorubicin (i.e. MDR1, GSTP1, TOPO-2a, Bcl-2, PKC-b2) that represents the backbone of the R-CHOP regimen with treatment outcome data of 54 patients at various stages of disease. The expression of the 5 above mentioned genes was determined in formalin-fixed paraffin-embedded samples from DLBCL using real time RT-PCR. A threshold analysis to identify a cut-off distinguishing recurrent or non-recurrent disease was used. The correlations between gene expression data and clinical/pathological characteristics as well as survival parameters have been evaluated by standard statistical tests. The case series included 32 males and 22 females; 6 patients had follicular lymphoma grade IIIb and 48 diffuse large B cell lymphoma; 19 presented symptoms at diagnosis. Thirty patients showed abnormal LDH values, the IPI was intermediate-high risk or high risk in 14 patients. Forty-six patients (85.2%) obtained a complete remission and 8 (14.8%) a partial response. The median overall survival (OS) as well as the median progression free survival (PFS) have not yet been reached after a median follow-up of 43.6 months. The mRNA expression levels of TOPO-2a and GSTP1 were detectable in all samples, that of PKC-b2 in 52 samples, that of MDR1 and bcl-2 in 34 and 29 samples, respectively. A high degree of interpatient variation in relative tumor expression of the study gene was observed: from 0.008 for TOPO-2a to >100.000 for PKCbII. Threshold analysis indicated significant inverse relationships between PKC-b2 and PFS (p=0.046): higher gene expression was associated with shorter PFS. Conversely, higher expression of ABCB1 was associated with prolonged PFS (p=0.039). This kind of analysis also showed associations between OS and TOPO-2a, GSTP1and PKC-b2: higher gene expression was associated with shorter OS. Overall, our results confirm that the high expression of some genes such as TopoIIa, GSTP1 and PKCβII may represent a prognostic factor in case of an intensified anthracycline-based chemotherapy with immunotherapy. Moreover, our results suggest that intensified immunochemotherapy could affect the role of bcl2, ABCB1, GSTP1 and TopoIIa in predicting tumor response. These results and others from related studies may help to identify gene profiles useful for selecting patients eligible for more intensified or personalized chemotherapy. Prospective larger studies are warranted. Supported by a grant from Associazione Giacomo Onlus, Castiglioncello (LI). Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 2605 Poster Board II-581 Background. Annexin II (ANXA2) is a member of a peripheral membrane-binding protein family acting in a calcium-dependent manner, is involved in many cellular mechanisms, as cell proliferation and membrane physiology and is related to cancer progression. The aim of this study was to assess the ANXA2 expression in B cell precursor acute lymphoblastic leukemia (Bcp-ALL), in the attempt to finally evaluate it as a new potential therapeutic target. Materials and Methods. The ANXA2 expression was tested in 77 newly diagnosed pediatric Bcp-ALL diagnosed and treated in our centers, according with LLA-2000 protocol of Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP). Diagnostic samples and 3 B-ALL cell lines (REH, SEM, 697) were studied by reverse phase protein array (RPPA), western blot and real-time PCR (RQ-PCR) analyses. Furthermore, immunofluorescence on bone marrow smears and cytofluorimetric studies were performed, in order to visualize the protein subcellular location. The associations between the ANXA2 expression, molecular features and prognosis were evaluated. For statistical purpose, multivariate analyses with Wilcoxon test and t-Test with conservative Bonferroni corrections and Kaplan-Mayer analysis were performed. Pearson correlation was used to compare mRNA and protein levels. Results. Our analyses demonstrated a positive correlation between mRNA and protein ANXA2 expression (Pearson correlation or index 0.6). Comparing ANX2 expression and molecular features, we found a statistically significant difference between patients with unfavourable [t(9;22), t(4;11)] and favourable translocations [t(12;21)], showing a higher level of ANXA2 in the former group (p-value <0.05). Additionally ANXA2 resulted upregulated at both mRNA and protein levels in 24 out of 77 patients included in the study, and in the group presenting with high ANXA2 expression, 8 (33%) patients relapsed; in contrast, in the group with low ANXA2 expression only 8 out of 53 cases (15%) suffered from a relapse. Interestingly, 5 patients (21%) with high ANXA2 expression died of progressive disease, while with only one case (2%) in the group with low ANXA2 expression. A multivariate analysis also showed that ANXA2 is an independent predictor of disease's aggressiveness. Due to the heterogeneity of response to treatment among our patients, which imply a stratification based on detection of minimal residual disease (MRD), the correlation between high expression level of ANXA2 with prognosis resulted not statistically significant (Kaplan-Mayer p-value >0.05). However, our data strongly suggested a correlation with a worst prognosis in those cases with high ANXA2 expression. Furthermore, immunofluorescence and cytofluorimetric analyses performed on SEM and 697 cell lines showed that ANXA2 is localized on the cellular membrane's surface, where the protein is usually involved in many cell functions. Conclusions. To date, our study reports on ANXA2 expression and location in pediatric ALL. Our findings suggest that ANXA2 expression represents a marker of aggressiveness in Bcp-ALL, confirmed by the correlation with unfavourable molecular rearrangement such as MLL/AF4. Although the prognostic impact of ANXA2 expression needs to be evaluated with a further retrospective study including a larger and selected population, our data already strongly suggest that ANXA2 expression could be considered as a new potential therapeutic target in pediatric Bcp-ALL. Disclosures: No relevant conflicts of interest to declare.

Background: The project “Homeopathy for L’Aquila” was developed in order to provide humanitarian and professional assistance to the people of L’Aquila, who were the victims of a devastating earthquake during the night of April 6th, 2009. This project was promoted by the Federazione Italiana Associazioni Medici Omeopati (FIAMO) and supported by the governmental organization for Emergencies (Protezione Civile). Aim: This paper is the report of that experience in the state of absolute emergency, which lasted 17 months. It aims to be a feasibility study as well as a model for further emergencies. Methodology: A medical office was located in a container of 60 square meters which was open from Monday to Friday, beginning in August 2009 and lasting until December 2010. This was provided by Protezione Civile with all the basic equipment, including a reception with a secretary. There were 16 homeopathic physicians and 2 acupuncturists, coming from all over Italy. Every month they rotated to offer free consultations of Classical Homeopathy, as well as Acupuncture and Neuraltherapy. Only people coming from the earthquake area were admitted: all of them signed an informed consent. An operational protocol was defined for the data collection. Each consultation was reported in a special register. The follow-up period lasted 17 months. The protocol consisted of the first consultation and at least 3 control visits, when possible at 30, 60 and 120 day intervals. As a primary outcome the main complaint of the patient was considered in its relation to the quality of life. This evaluation followed a slightly modified criterion of a qualitative scale: Outcome in Relation to Impact on Daily Living (ORIDL). A statistical analysis with some non parametric tests was carried out (Kolmogorof, ). Even the most frequently prescribed homeopathic medicines were taken into consideration. Results: 674 patients were visited from August 2009 to December 2010. In total 1,542 medical visits and treatments were carried out (1,070 as Homeopathy; 280 as Neuraltherapy; 192 as Acupuncture). 366 patients received Classical Homeopathy. The most frequently treated syndromes were of the “psychiatric” type (162 cases=44%), prevalently due to the consequences of the earthquake, such as sleeping disturbances, phobic states, anxious-depressive syndromes, etc. The drop-outs were 235 out of 366 (=64%). 107 patients presented for a minimum 3 follow-ups. Here are the results: cured (52%), major improvement (33%), moderate and slight improvement (12%), no change (3%), deterioration (0%). The statistical analysis (D = 51 > 1,949; = 48,039 > 10,83) showed a significance higher than 1‰. Within this group, 68 patients suffering from psychiatric syndromes, who came for a 3rd follow up, showed a similar trend: cured (50%), major improvement (24%), moderate and slight improvement (19%), no change (7%), deterioration (0%). Also in this case the statistical analysis indicated a significance higher than 1‰ (D = 30 > 1,949). The most frequently prescribed medicines were Pulsatilla, Sepia, Arsenicum Album, Argentum Nitricum and Lycopodium. Discussion: The numerous inconveniences due to the emergency certainly did not permit the usual control visits. Moreover a strict observance of the protocol was not always possible, which could explain such a high number of drop-outs. Those patients who completed the therapy had an incremental improvement in their health between the 1st and the 3rd follow-up visit. In the final analysis a series of “strengths” and “weaknesses” in the project were noted. This knowledge could be helpful for future emergencies. Conclusions: The project “Homeopathy for L’Aquila” allowed, for the first time in Italy, an official implementation of Homeopathy in an emergency plan of great impact, on the one hand; and, on the other hand, made a precious human and professional experience possible. Moreover the results obtained have demonstrated that Homeopathy can play an important role socially as well as therapeutically. To the present date there have neither been internationally recognized guidelines nor publications with similar data concerning emergencies. Therefore this project could represent an important reference point for similar events.

Abstract Introduction: Standard chemotherapy represented by the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) regimen is successful in about 60% of patients (pts) with diffuse large B-cell lymphoma (DLBCL). Pts who do not benefit from this treatment, due to the development of tumor drug resistance, have a very poor prognosis. Currently, knowledge on reasons of treatment related failures in DLBCL are scanty and predictive biomarker of response are largely unknown. We hypothesized that polymorphisms of gene involved in the pharmacokinetics and pharmacodynamics of drugs included in R-CHOP regimen may play a role in predicting the outcome in DLBCL pts.Thus, we designed a multicentre prospective pharmacogenetic trial aimed at identifying gene polymorphisms potentially predictive of drug efficacy/resistance in DLBCL pts treated with R-CHOP. An interim analysis on the first 80 enrolled ptswas planned and has been performed. Methods: The study included chemonaive DLBCL pts at various stages of disease candidate to an R-CHOP standard treatment. The Ethical Committee of each participating centre approved the pharmacogenetic protocol, and all pts signed a written informed consent. According to the aims of this interim analysis, the impact of single nucleotide polymorphisms (SNPs) on R-CHOP efficacy was evaluated by objective response (OR) rate at the end of treatment. The efficacy of R-CHOP was evaluated according to the Cheson criteria by performing standard hematochemical and instrumental (TC and FDFG-PET) tests and defining complete remission (CR), partial remission (PR), non response or progressive disease (PD). Genomic DNA wasextracted from peripheral blood of 80 pts. Twentysingle nucleotide polymorphisms (SNPs) from18candidate genes (ABCB1, ABCC1, ABCC2, ABCG2, CYBA, CYP2C9, FCGR2A, GSTP1, IL2, MLH1, NCF4, NQO1, NQO2, RAC2, TNF, TOP2A, TP53, TUBB)involved in pharmacokinetics and pharmacodynamics of R-CHOP (www.pharmgkb.org) have been analysed by a genotyping array based on Affimetrix methodology. Univariate analysis was performed to evaluate associations between polymorphisms and clinical/pathological characteristics or OR (Fisher exact test). Multivariate logistic regression analysis was performed to estimate adjusted odds ratios along with the corresponding 95% confidence intervals for the polymorphisms and OR. Results: Median age was 63 years. There were 37 men and 43 women. 47.5 % of pts were in stage I-II,52.5 % of pts in stage III-IV. 27.5% of ptshad bulky disease, 43.8 % of pts had involvement of extranodal site. 47.5% of pts had pathological LDH value. According to the revised IPI, 15 % pts were in the low risk group, 58.7 % in the intermediate risk group, and 26.3 % in the high risk group.Overall, 468 courses of R-CHOP had been administered (mean: 5.85 courses, range: 4-6). 81% of pts had CR to R-CHOP whereas the remaining showed PR (14%) or PD(5%). No statistically significant correlation was found between OR and clinical characteristics of pts.However, stage III-IV pts showed a worst OR than stage I-II pts (77% vs 87% of CR, respectively); pts with bulky disease had worst OR than non-bulky disease pts(73% vs 84.5% of CR, respectively); ptswith R-IPI 3-5 a worst OR than pts with R-IPI 0-2 (71.5% vs 85% of CR, respectively). Univariate and multivariateanalysis identified TOPOII rs13695as a predictor of OR (p=0.042). Pts with CT or TT genotypesshowed worst OR than CC wild-type homozygous pts (odds ratio 3.070, CI95% 1.113-13.457). Also, a statistical trend toward significance was observed for MLH1 rs1800734 polymorphism (p=0.062): ptswith homozygous genotype for the mutant allele showed a better OR than wild-type and heterozygous pt genotypes. Conclusions: No significant relationship between clinical/pathological characteristics and OR was observed. Our preliminary data show that SNPs affecting a gene involved in doxorubicin pharmacodynamics, i.e. the drug target TOPOII, as well asone of the major components of DNA mismatch repair, i.e. MLH1 gene,may predict response in DLBCL pts treated with R-CHOP. These preliminary results from the interim analysis are promising and warrant completion of pt accrual to reach the planned number of cases at the end of our study. Acknowledgments This work was supported by a grant from the Associazione Giacomo Onlus, Castiglioncello (LI), Italy to E.M. and Cassa di Risparmio di Firenze, Firenze, Italy to S.N. Disclosures No relevant conflicts of interest to declare.

Abstract Introduction: The role of minimal residual disease (MRD) in Multiple Myeloma (MM) as a surrogate biomarker of patients' outcome, as well as the prognostic information of functional imaging response after treatment have been established in recent years. Furthermore, the predictive relevance of sustained MRD negativity assessed by marrow and imaging techniques and its association with an excellent outcome is emerging in clinical trials. Diffusion-weighted whole-body MRI (DW-MRI) is increasingly used in the management of MM patients, but data regarding the predictive role of sustained DW-MRI response after treatment are lacking. The Myeloma Response Assessment and Diagnosis System (MY-RADS) recommendations have established criteria for Response Assessment Category (RAC) (Messiou C et al, Radiology 2019) with a 5 point scale defining the probability of complete imaging response (i.e. RAC 1) or progressive disease after treatment (i.e. RAC 5). We implemented the RAC criteria in our clinical practice and DW-MRI at 1-year in MM patients treated with autologous stem cell transplantation (ASCT) followed by maintenance therapy. Patients and methods: We retrospectively analyzed the outcome of 57 newly diagnosed MM patients (median age 61 years) diagnosed at our institution from January 2015 to December 2019 receiving maintenance therapy after ASCT. Patients underwent DW-MRI evaluation according to MY-RADS criteria at day +100 after ASCT, before maintenance, and after 1 year with the aim of monitoring imaging residual disease. Bone marrow samples were collected for MRD assessment by 8-color FCM (sensitivity 10-5) at day +100 after ASCT, before maintenance, and after 1 year. We focused on sustained 1-year DW-MRI negativity evaluated according to RAC response, and its potential predictive role at that timepoint on progression free survival (PFS) and overall survival (OS). In patients with available 1-year MRD evaluations, concordance between 1-year MRD and DW-MRI results was calculated and the level of agreement was expressed by Cohen's kappa statistics. Results: Out of 57 patients, 23 (40%) were ISS stage 3 and 14 (25%) showed high risk cytogenetics. Patients were treated with the following induction regimens: VTD 42, VRD 5, Dara-VRD 6, KRD 3, KCD 1. Single ASCT with MEL200 conditioning was performed in 33 patients (58%), whereas 24 patients (42%) received double ASCT. Subsequent maintenance was performed with lenalidomide (49 patients, 86%) or daratumumab-lenalidomide (8 patients, 14%). Response rates after ASCT were PR 9%, VGPR 23%, CR 51% and sCR 17%. According to MY-RADS, a complete imaging response (RAC1) at day +100 after ASCT was observed in 34 patients (60%). Sustained 1 year complete imaging response during maintenance therapy was observed in 43 patients (75%). Some residual disease was identified at that timepoint in 14 patients (25%) [RAC 2: 6 (11%), RAC &gt; 2: 8 (14%)]. After a median follow up of 36 months, PFS and OS were significantly longer in patients with sustained 1-year imaging negativity, compared to patients with imaging residual disease (RAC 1 vs RAC ≥2): median PFS 56 vs 24,1 months, p &lt;0,0001, HR 0,11 (95% CI: 0,030-0,382); median OS NR vs 40,5 months, p &lt; 0,0001, HR 0,05 (95% CI: 0,006-0,364). MRD at 1-year timepoint was available in 30 patients and was negative in 28 (93%) cases. Concordance between 1-year DW-MRI and MRD results was high (97%, kappa 0,783: 7% both positive, 90% both negative). Conclusion: Our real-life data analysis confirms the predictive value of imaging residual disease assessment with DW-MRI after ASCT and highlights the importance of achieving sustained imaging MRD negativity during maintenance therapy regardless of different treatment strategies. Moreover, given the high rates of CR seen in patients with MM with novel effective treatment combinations, the detection of residual disease with the combined evaluation of marrow and functional imaging techniques during maintenance therapy can help the physician to identify patients with increased risk of early relapse and particularly poor prognosis. Our preliminary data regarding the high concordance observed between DW-MRI and MRD results during maintenance therapy suggest that DW-MRI could represent a reliable non-invasive technique to monitor residual disease. Disclosures Belotti: Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; GSK: Membership on an entity's Board of Directors or advisory committees. Ribolla: Janssen: Membership on an entity's Board of Directors or advisory committees. Cancelli: Amgen: Membership on an entity's Board of Directors or advisory committees. Roccaro: Amgen, Celgene, Janssen, Takeda: Membership on an entity's Board of Directors or advisory committees; AstraZeneca,: Research Funding; Associazione Italiana per la Ricerca sul Cancro (AIRC): Research Funding; European Hematology Association: Research Funding; Fondazione Regionale per la Ricerca Biomedica (FRRB), Transcan-2 ERA-NET: Research Funding. Rossi: Sanofi: Honoraria; Jazz: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; Astellas: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Tucci: janssen: Membership on an entity's Board of Directors or advisory committees; Gentili: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees.

Abstract Iron overload and chronic viral hepatitis underlie the increased incidence of hepatocellular carcinoma in patients with Beta thalassemia, as recently emerged due to the prolonged survival. Conversely, there are very few studies examining the relationship between thalassemia and other malignancies. Although some Authors have indicated an increase in incidence of hematologic and solid tumours such as thyroid cancer and renal cell carcinoma, there are not enough data to make a conclusion. Moreover, there is even less data on a possible relationship between other Hemoglobinopathies and tumors risk. Seven Italian Specialized Centres for the treatment of Hemoglobinopathies, with the patronage of the "Società Italiana Talassemie ed Emoglobinopatie" (SITE), evaluated the incidence of malignant neoplasms in Hemoglobinopathies, their site and features. Each Center considered all consecutive patients of its own historical series; the cohort included 4104 patients (48% males), followed between 1970 and 2021 (Figure 1A), for a total of 143255 person-years of observation. The most common diagnosis was Transfusion-Dependent Beta Thalassemia (TDT) with 2122 subjects (51.7%), followed by Non-Transfusion-Dependent Beta Thalassemia (NTDT, 789 subjects, 19.2%), Sickle Cell Disease (SCD, 787, 19.2%), Hemoglobin H Disease (HbH, 375, 9.1%) and Other (34, 0.8%). Two-hundred-sixty-two patients had undergone bone marrow transplantation (BMT). A total of 157 diagnoses of cancer (153 patients, 52% males) was reported during the period of observation, corresponding to a prevalence of 3.8%, with the mean age at the diagnosis of 47±13 years. Hepatocellular carcinoma (HCC) was the most frequent site (62 cases) in both sexes (males 50%, females 32%) contributing to 41% of total number of cases, excluding non-melanoma skin cancer, and in all type of hemoglobinopathies (except HbH). No significant differences were found in the age of diagnosis of HCC stratifying for gender (males 48±14 years, females 51±9 years) and types of Hemoglobinopathies (TD 48±9 years, NTDT 51±10 years, SCD 50±14 years). After HCC, hematologic tumours (11), kidney (6), and lung (6) were the most frequent sites in men, accounting for 29% of all male cancers. For women, the most common incident cancers were breast (9), thyroid (8) and kidney (7), these representing 33% of all female cancer cases (Figure 1B). The first diagnoses of cancer dated back to the 1980s and their number sharply increased after the 2000s with a peak in the five-year period 2008-2012 and a (not significant) reduction in recent years. A similar trend may be noted considering HCC alone but in this specific case, the reduction reaches the level of significance (Figure 1C). The overall age-adjusted incidence rate of cancer in Hemoglobinopathies was estimated to be 391 cases/100000 person-years (95% C.I. 290-650) which was not statistically different from that of the Italian general population (632 cases/100000 person-years), both considering Hemoglobinopathies in total and each subgroup of patients. However, age-adjusted incidence rate of HCC was more than 7 times lower in general population (22 cases/100000 person-years) than in patients with Hemoglobinopathies (153 cases/100000 person-years, 95% C.I. 96-222, p&lt;0.05). TDT patients had the highest HCC incidence rate and therefore the greatest difference with general population (462 cases/100000 person-years, 95% C.I. 114-899, p&lt;0.05), followed by NTDT patients (94 cases/100000 person-years, 95% C.I. 33-188, p&lt;0.05). The comparison between the age-adjusted incidence rate of HCC patients with SCD and general population did not reach the statistical significance. No other malignancies had a higher incidence in patients with Hemoglobinopathy than in the general population. Although preliminary, these findings provide novel insights into the relationship between cancer and Hemoglobinopathies, suggesting that the overall cancer risk is not increased in these patients. HCC is confirmed as the most frequent tumor, especially in patients with Beta Thalassemia (TD and NTDT), but advances in chelation, with renewed attention to hepatic iron, and the new drugs that have led to the eradication of hepatitis C even in these patients, may explain the recent reduction in the number of diagnoses that we have reported in this study. Acknowledgment. We would like to thank ALT (Associazione per la Lotta alla Talassemia R.Vullo - Ferrara). Figure 1 Figure 1. Disclosures Origa: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; BlueBird Bio: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria. Longo: Bristol Myers Squibb: Honoraria; BlueBird Bio: Honoraria. Pinto: BlueBird Bio: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Quarta: Sanofi - Genzyme: Membership on an entity's Board of Directors or advisory committees, Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; Speaker at conferences; Blue Bird Bio: Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; Celgene: Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; Speaker at conferences; Takeda: Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; speaker at conferences; Bristol Meyer Squibb: Membership on an entity's Board of Directors or advisory committees, Other: Speaker at conferences. Casale: Novartis Farma SpA: Honoraria, Membership on an entity's Board of Directors or advisory committees. Maggio: Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene Corp: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees. Perrotta: Novartis Farma SpA: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Blue Bird Bio: Honoraria, Membership on an entity's Board of Directors or advisory committees. Forni: Celgene: Membership on an entity's Board of Directors or advisory committees; Bluebirdbio: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

Abstract Background: CTCs may be responsible for MM spreading and accordingly, their numbers in peripheral blood (PB) could be a potential surrogate marker for the rate of dissemination and overall tumor burden in bone marrow (BM). In such case, CTCs may be a powerful biomarker of malignant transformation and disease aggressiveness. Aim: To investigate the clinical significance of CTCs in patients with smoldering (SMM), newly diagnosed (NDMM) and relapsed/refractory MM (RRMM), and to compare the transcriptional profile of CTCs across the disease spectrum. Methods: Next-generation flow (NGF) cytometry was used to assess the percentage of CTCs in PB of 1,157 patients: 316 with SMM, 650 with NDMM and 191 with RRMM. In each disease setting, patients were sub-classified into three groups with undetectable, low and high percentage of CTCs. Cutoffs were defined using maximally selected rank statistics adjusted for time to progression (TTP) in SMM and progression free survival (PFS) in NDMM/RRMM. A subset of SMM patients (n=86) was enrolled in GEM-CESAR. Transplant eligible (n=374) and ineligible (n=276) NDMM, as well as RRMM patients, were homogenously treated according to the GEM2012MENOS65, GEM-CLARIDEX and GEM-KYCYDEX clinical trials, respectively. In 40 patients (2 SMM, 33 NDMM and 5 RRMM) paired CTCs and BM tumor cells were FACSorted and their transcriptional profile was analyzed using RNAseq. Differentially expressed genes were investigated using DESeq2. Results: CTCs were detected in 248/316 (78%), 597/650 (92%) and 170/192 (89%) of SMM, NDMM and RRMM patients. Median CTC frequencies were: 0.001% (0.05 CTCs/µL), 0.01% (0.64 CTCs/µL) and 0.005% (0.22 CTCs/µL), respectively. There were 79 genes differentially expressed between patient-matched CTCs and BM tumor cells (e.g., FLNA, EMP3, LGALS9, MUC1). These were functionally related with TNFα signaling and inflammatory response (enriched in CTCs), as well as to cell cycle and MYC targets (enriched in BM tumor cells). Interestingly, the enrichment of these signatures in CTCs and BM tumor cells was progressively more pronounced from SMM to NDMM and RRMM. Altogether, these data suggest that the CTC-based dissemination potential peaks at the stage of NDMM, which could be related to greater inflammation in BM and cell cycle arrest driving tumor cell egression into PB. There were significant associations between the percentage of CTCs and the 2/20/20 IMWG risk model in SMM, the ISS in NDMM, and high-risk cytogenetics in all three-disease settings. Untreated SMM patients (n=230) with high CTC levels (≥0.02%) showed ultra-high risk of transformation vs those with low and undetectable CTCs (median TTP of 11 months vs not reached [NR] in both; P &lt; .0001). Notably, SMM patients with ≥0.02% CTCs enrolled in GEM-CESAR have not reached a median TTP; thus, early intervention abrogated the poor prognosis of high CTC levels. Transplant-eligible NDMM patients stratified by undetectable, low and high (≥0.2%) CTC levels showed median PFS of NR, 78 and 47 months, respectively (P &lt; .0001). Significant risk stratification was further observed in transplant ineligible NDMM (median PFS: NR, 31 and 14 months, respectively, P = .002) and RRMM (median PFS: NR, 24 and 7 months, respectively, P = .004). In untreated SMM, multivariate analysis of TTP including CTCs, serum M-component (&gt;2 g/dL), sFLC ratio (&gt;20) and BM plasma cells (&gt;20%) selected CTCs as an independent prognostic factor (hazard ratio [HR]: 1.61, P = .015) together with the M-component and sFLC ratio. In NDMM, multivariate analysis of PFS including CTCs, BM plasma cells counts by morphology and flow cytometry, ISS, LDH, cytogenetics and transplant eligibility showed that high CTC levels had independent prognostic value (HR: 1.43, P = .003). Only the achievement of undetectable measurable residual disease (MRD) abrogated the poor prognosis of high CTC levels. Conclusions: This is the largest study investigating the role of CTCs in smoldering and active MM. Our results show that tumor cells are continuously trafficking in PB, possibly through a dynamic mechanism of egression that peaks in NDMM. Evaluation of CTCs in PB outperformed quantification of BM tumor burden in SMM and NDMM, and showed prognostic value in all three-disease stages. Thus, CTC assessment should be part of the diagnostic workup of MM. Early intervention in high risk SMM and undetectable MRD in NDMM may abrogate dismal outcomes associated with high CTC levels. Disclosures Puig: Amgen, Celgene, Janssen, Takeda: Consultancy; Celgene: Speakers Bureau; Celgene, Janssen, Amgen, Takeda: Research Funding; Amgen, Celgene, Janssen, Takeda and The Binding Site: Honoraria. Cedena: Janssen, Celgene and Abbvie: Honoraria. Oriol: GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Sureda: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Consultancy, Honoraria, Speakers Bureau; Roche: Other: Support for attending meetings and/or travel; Bluebird: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy; MSD: Consultancy, Honoraria, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding, Speakers Bureau. De Arriba: Amgen: Consultancy, Honoraria; Glaxo Smith Kline: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; BMS-Celgene: Consultancy, Honoraria, Speakers Bureau. Moraleda: Pfizer: Other: Educational Grants, Research Funding; Sanofi: Other: Educational Grants, Research Funding; MSD: Other: Educational Grants, Research Funding; ROCHE: Consultancy, Honoraria, Other: Educational Grants, Research Funding; Takeda: Consultancy, Honoraria, Other: Educational Grants, Research Funding; Sandoz: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Educational Grants, Research Funding; Gilead: Consultancy, Honoraria, Other: Educational Grants, Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Educational Grants, Research Funding; NovoNordisk: Other: Educational Grants, Research Funding; Janssen: Other: Educational Grants, Research Funding; Celgene: Other: Educational Grants, Research Funding; Amgen: Other: Educational Grants, Research Funding. Terpos: GSK: Honoraria, Research Funding; Genesis: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Novartis: Honoraria; Janssen-Cilag: Consultancy, Honoraria, Research Funding; BMS: Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Goldschmidt: Incyte: Research Funding; Adaptive Biotechnology: Consultancy; BMS: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Celgene: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Chugai: Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; GSK: Honoraria; Novartis: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Johns Hopkins University: Other: Grant; Molecular Partners: Research Funding; MSD: Research Funding; Mundipharma: Research Funding; Dietmar-Hopp-Foundation: Other: Grant; Sanofi: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Takeda: Consultancy, Research Funding; Amgen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding. Avet-Loiseau: Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Roccaro: AstraZeneca,: Research Funding; Amgen, Celgene, Janssen, Takeda: Membership on an entity's Board of Directors or advisory committees; Associazione Italiana per la Ricerca sul Cancro (AIRC): Research Funding; European Hematology Association: Research Funding; Fondazione Regionale per la Ricerca Biomedica (FRRB), Transcan-2 ERA-NET: Research Funding. Martinez-Lopez: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lahuerta: Celgene: Other: Travel accomodations and expenses; Celgene, Takeda, Amgen, Janssen and Sanofi: Consultancy. Ocio: Amgen: Consultancy, Honoraria; Bristol-Myers Squibb/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria; Karyopharm: Consultancy; MSD: Honoraria; Oncopeptides: Consultancy, Honoraria; Pfizer: Consultancy; Secura-Bio: Consultancy. Rosinol: Janssen, Celgene, Amgen and Takeda: Honoraria. Bladé Creixenti: Janssen, Celgene, Takeda, Amgen and Oncopeptides: Honoraria. Mateos: AbbVie: Honoraria; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bluebird bio: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene - Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria; Sea-Gen: Honoraria, Membership on an entity's Board of Directors or advisory committees. San-Miguel: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Karyopharm, Merck Sharpe & Dohme, Novartis, Regeneron, Roche, Sanofi, SecuraBio, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Paiva: Adaptive, Amgen, Bristol-Myers Squibb-Celgene, Janssen, Kite Pharma, Sanofi and Takeda: Honoraria; Bristol-Myers Squibb-Celgene, Janssen, and Sanofi: Consultancy; Celgene, EngMab, Roche, Sanofi, Takeda: Research Funding.

<p>High blood pressure and cognitive impairment often coexist in old age, but their pathophysiological association is complex. Several longitudinal studies have shown that high blood pressure at midlife is a risk factor for cognitive impairment and dementia, although this association is much less clear in old age. The effect of blood pressure lowering in reducing the risk of dementia is only borderline significant in clinical trials of older subjects, partly due to the insufficient follow-up time. Conversely, dementia onset is associated with a decrease of blood pressure values, probably secondary to neurodegeneration. Prognostic effect of blood pressure values in cognitively impaired older subjects is still unclear, with aggressive blood pressure lowering being potentially harmful in this patients category. Brief cognitive screening, coupled with simple motor assessment, are warranted to identify frail older subjects who need a more cautious approach to antihypertensive treatment. Values obtained with ambulatory blood pressure monitoring seem more useful than clinical ones to predict the outcome of cognitively impaired older subjects. Future studies should identify the most appropriate blood pressure targets in older subjects with cognitive impairment. </p><p><strong>Riassunto</strong></p><p>Ipertensione arteriosa e decadimento cognitivo spesso coesistono in età avanzata, sebbene la loro associazione sia complessa dal punto di vista fisiopatologico. Diversi studi longitudinali hanno mostrato che elevati valori pressori in età adulta rappresentano un fattore di rischio per decadimento cognitivo e demenza, sebbene tale associazione sia molto meno chiara in età avanzata. L’effetto della terapia antiipertensiva è risultato ai limiti della significatività statistica nel ridurre il rischio di demenza negli studi di intervento su soggetti anziani, in parte a causa della durata insufficiente del follow-up. D’altra parte, l’insorgenza di demenza è associata con una riduzione dei valori pressori, probabilmente secondaria alla neurodegenerazione. L’effetto prognostico dei valori pressori in anziani con decadimento cognitivo non è stato ancora chiarito, in presenza di un possibile effetto dannoso di un trattamento antiipertensivo aggressivo in questa categoria di pazienti. Un breve screening cognitivo, associato con una semplice valutazione motoria, è raccomandato per identificare gli anziani fragili, che necessitano di un approccio più cauto alla terapia antiipertensiva. I risultati del monitoraggio della pressione arteriosa nelle 24 ore sembrano più utili della misurazione clinica per predire la prognosi degli anziani cognitivamente compromessi. Studi futuri dovrebbero identificare gli obiettivi pressori più appropriati nel trattamento di anziani con decadimento cognitivo.</p>

Foreign language didactics is a field which, notwithstanding the many centuries of application and development, is still very methodologically problematic. Statistics clearly show that, in certain countries, the educational system provides foreign language instruction that is not apt and does not deliver effective linguistic competence; a few methods, however, have been developed to contravene this problem. In the specific case of Italy, a country which is renowned for its general monolingualism, Associazione Culturale Linguistica Educational (ACLE) has developed an innovative language teaching method (Rational, Emotional, Affective Learning) to attempt to fill the lacunae of the Italian school system, especially in regards to the teaching of English as a foreign language. This paper seeks to briefly outline the REAL method and its applications, describe its affinity to didactic and cognitive theories, and speculate on its potential effectiveness.

Abstract STUDY QUESTION Is the Subjective Impact of Dyspareunia Inventory (SIDI) a reliable tool to examine the experience of dyspareunia in the context of endometriosis? SUMMARY ANSWER In this study, the SIDI showed good structural and psychometric properties, and thus can be used as a reliable questionnaire to assess the impact of endometriosis-related dyspareunia on multiple dimensions, such as sexuality and intimate relationships. WHAT IS KNOWN ALREADY In the endometriosis population, dyspareunia has a tremendous negative impact on psychological health, overall sexual function and couple relationships. However, there is a paucity of tools that can be effectively used in either research or clinical practice to assess the subjective components of the dyspareunia experience, including coping strategies to deal with the pain. STUDY DESIGN, SIZE, DURATION In this cross-sectional study, the validity of the SIDI was examined by considering the responses provided by 638 participants with endometriosis and dyspareunia, who participated in an online survey conducted between 8 November and 21 December 2021. Participants were recruited using snowball sampling that involved posting the invitation to participate in the study on the social media of a patient association. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants were women aged ≥18 with clinical or surgical diagnosis of endometriosis. The SIDI measures the subjective impact of dyspareunia and is composed of 16 items focused on the frequency of dyspareunia-related experiences in the last 6 months, rated on a 5-point Likert scale. Sexuality was assessed using the Female Sexual Function Index. Psychological health was measured using the Hospital Anxiety and Depression Scale and the Rosenberg Self-Esteem Scale. Sociodemographic and endometriosis-related information was collected using a researcher-made questionnaire. Statistical significance was set at P &lt; 0.05. MAIN RESULTS AND THE ROLE OF CHANCE Factor analysis revealed that the SIDI has a four-factor structure and allows for examining the impact of dyspareunia in terms of Sexual Concerns (Factor 1), Relationship Concerns (Factor 2), Partner Support (Factor 3) and Endurance of Pain (Factor 4). The SIDI showed good structural and psychometric properties (including internal consistency), was associated with sexual function and psychological health and was able to discriminate between participants with and without sexual dysfunction. LIMITATIONS, REASONS FOR CAUTION Reasons for caution are related to the risk of self-selection bias depending on the study population and recruitment strategy. Moreover, all the information provided by the participants was self-reported, which may have affected the accuracy of the data collected, especially with regards to endometriosis-specific information. WIDER IMPLICATIONS OF THE FINDINGS This study may provide a new brief tool that can be used by clinicians and researchers to assess the impact of dyspareunia from a multidimensional perspective and to consider subjective aspects that can be usefully integrated with information about pain severity, timing and localization. STUDY FUNDING/COMPETING INTEREST(S) There was no funding for this study. A.F. is the President of APE-Odv (Associazione Progetto Endometriosi-Organizzazione di volontariato (Endometriosis Project Association-Volunteer Organization)), the largest nonprofit endometriosis patient association in Italy. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.