BALB/c and C57BL/6 Mice Differ in Polyreactive IgA Abundance, which Impacts the Generation of Antigen-Specific IgA and Microbiota Diversity.

The interrelationship between IgAs and microbiota diversity is still unclear. Here we show that BALB/c mice had higher abundance and diversity of IgAs than C57BL/6 mice and that this correlated with increased microbiota diversity. We show that polyreactive IgAs mediated the entrance of non-invasive bacteria to Peyer's patches, independently of CX3CR1(+) phagocytes. This allowed the induction of bacteria-specific IgA and the establishment of a positive feedback loop of IgA production. Cohousing of mice or fecal transplantation had little or no influence on IgA production and had only partial impact on microbiota composition. Germ-free BALB/c, but not C57BL/6, mice already had polyreactive IgAs that influenced microbiota diversity and selection after colonization. Together, these data suggest that genetic predisposition to produce polyreactive IgAs has a strong impact on the generation of antigen-specific IgAs and the selection and maintenance of microbiota diversity.

Oral tolerance can be established via gap junction transfer of fed antigens from CX3CR1⁺ macrophages to CD103⁺ dendritic cells.

Antigen-presenting cells (APCs) in the gut are apt at oral tolerance establishment at steady state and immunity after infection; complex tasks in an environment exposed to the inflammatory burden of the microbiota. Here we show an unanticipated division of labor among APCs for the establishment of oral tolerance. Chemokine receptor CX3CR1(+) macrophages were found to take up soluble fed antigens and quickly transfer them to CD103(+) dendritic cells (DCs). Antigen transfer occurred via a mechanism that was Connexin 43-dependent and required membrane transfer, indicating a physiological role of gap junctions in antigen presentation. Deletion of Connexin 43 in APCs affected antigen transfer and resulted in the inability of CD103(+) DCs to acquire and present antigens in vivo, to drive T regulatory cell differentiation and to induce tolerance to food antigens. This functional cooperation between intestinal phagocytes might be a mechanism to avoid the exposure of tolerogenic DCs to the intestinal microbiota.

Adaptation of the Core Set for Vocational Rehabilitation for Cancer Survivors: A Qualitative Consensus-Based Study.

PURPOSE: The Core Set for Vocational Rehabilitation (CS-VR) of the International Classification of Functioning, Disability and Health (ICF) describes the work functioning of individuals in need of VR. We aimed to adapt the CS-VR from the perspective of cancer survivors (CSs) and stakeholders, developing a CS-VR-Onco. METHODS: We held five focus groups with 17 CSs who were employed at the time of diagnosis, to discuss their work reintegration experiences. After analyzing the focus group conversations, the CS-VR-Onco was developed. During a group interview, eleven stakeholders explored barriers/facilitations in assessing the work functioning of CSs by using the CS-VR-Onco. We applied the framework method and thematic analysis. RESULTS: For the focus groups, the CS-VR-Onco of 85 categories emerged, and the ICF chapters of Mental functions, Exercise and tolerance functions, Interpersonal interactions and relationships, Major life areas, General tasks and demands, Mobility, Support and relationships, and Attitudes were prioritized. For the group interview, stakeholders' perspectives can be synthetized into two themes: close to the lived experience and usability criteria. Stakeholders confirmed the categories of the CS-VR-Onco, a checklist that should be used through an integrated approach across multiple disciplines. CONCLUSIONS: The adapted CS-VR-Onco reflects the CSs' lived experiences of work reintegration and the factors that have influenced this process. The CS-VR-Onco was described as complete and usable through an integrated approach.

Physical exercise for bone health in men with prostate cancer receiving androgen deprivation therapy: a systematic review.

PURPOSE: Androgen deprivation therapy (ADT) is a treatment used in men with prostate cancer (PCa); however it is responsible for many adverse effects, with negative impact on quality of life. ADT causes loss of bone mineral density (BMD) and skeletal muscle mass, alteration of body composition, and cognitive function, which altogether lead to increased risk of accidental falls and fractures. This systematic review analyses the effectiveness of physical exercise (PE) in preventing accidental falls and fractures and reducing the loss of BMD in men with PCa receiving ADT. METHODS: We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library for articles between database inception and September 2, 2020. Eligible studies included randomized controlled trials (RCTs) investigating the effects of exercise on bone health in men with PCa receiving ADT. RESULTS: Nine RCTs were included. Experimental PE consisted in multicomponent programmes that involved aerobic, resistance, impact-loading exercise, and football training. None of the RCTs investigated the risk of accidental falls and fractures, while two trials reported beneficial effects of PE on lumbar spine, hip, and femoral shaft BMD. No further significant difference was detected in the outcomes investigated. CONCLUSION: Evidence of the effectiveness of PE to prevent the risk of accidental falls and fractures and BMD loss is lacking. Nevertheless, clinical guidelines recommend PE as a part of the clinical management of men with PCa receiving ADT due to its known numerous health benefits. Research should focus on PE strategies to prevent accidental falls, a clinically relevant outcome in this vulnerable population. TRIAL REGISTRATION: The study protocol was registered with International Prospective Register of Systematic Reviews (PROSPERO, number CRD 42020158444 ) on 04/28/2020.

A focused ethnography in the context of a European cancer research hospital accreditation program.

BACKGROUND: A quality accreditation program (AP) is designed to guarantee predefined quality standards of healthcare organizations. Evidence of the impact of quality standards remains scarce and somewhat challenging to document. This study aimed to investigate the accreditation of a cancer research hospital (Italy), promoted by the Organization of European Cancer Institutes (OECI), by focusing on the individual, group, and organizational experiences resulting from the OECI AP. METHODS: A focused ethnography study was carried out to analyze the relevance of participation in the accreditation process. Twenty-nine key informants were involved in four focus group meetings, and twelve semistructured interviews were conducted with professionals and managers. Inductive qualitative content analysis was applied to examine all transcripts. RESULTS: Four main categories emerged: a) OECI AP as an opportunity to foster diversity within professional roles; b) OECI AP as a possibility for change; c) perceived barriers; and d) OECI AP-solicited expectations. CONCLUSIONS: The accreditation process is an opportunity for improving the quality and variety of care services for cancer patients through promoting an interdisciplinary approach to care provision. Perceiving accreditation as an opportunity is a prerequisite for overcoming the barriers that professionals involved in the process may report. Critical to a positive change is sharing the values and the framework, which are at the basis of accreditation programs. Improving the information-sharing process among managers and professionals may limit the risk of unmet expectations and prevent demotivation by future accreditation programs. Finally, we found that positive changes are more likely to happen when an accreditation process is considered an activity whose results depend on managers' and professionals' joint work.

The signaling adaptor Eps8 is an essential actin capping protein for dendritic cell migration.

Dendritic cells (DCs) flexibly adapt to different microenvironments by using diverse migration strategies that are ultimately dependent on the dynamics and structural organization of the actin cytoskeleton. Here, we have shown that DCs require the actin capping activity of the signaling adaptor Eps8 to polarize and to form elongated migratory protrusions. DCs from Eps8-deficient mice are impaired in directional and chemotactic migration in 3D in vitro and are delayed in reaching the draining lymph node (DLN) in vivo after inflammatory challenge. Hence, Eps8-deficient mice are unable to mount a contact hypersensitivity response. We have also shown that the DC migratory defect is cell autonomous and that Eps8 is required for the proper architectural organization of the actin meshwork and dynamics of cell protrusions. Yet, Eps8 is not necessary for antigen uptake, processing, and presentation. Thus, we have identified Eps8 as a unique actin capping protein specifically required for DC migration.

Factors influencing return to work of cancer survivors: a population-based study in Italy.

PURPOSE: Little is known about return to work (RTW) of cancer survivors (CSs) in Central and Southern Europe. This study investigates the RTW rate of Italian CSs, describes their sick leave (SL) pattern, and explores factors affecting their RTW process. METHODS: A population-based cross-sectional survey involving CSs registered at the Cancer Registry of Reggio Emilia Province (Italy) was launched in July 2016. Eligibility was restricted to individuals with first diagnosis of cancer in 2012 (stages I-III), aged 20-59, and employed at the time of diagnosis. RESULTS: Of the 266 individuals interviewed, 140 (52.6%) were reintegrated without difficulty, 113 (42.5%) returned to work with some difficulty, and 13 did not RTW (4.9%). The majority of CSs (56%) took SL for some periods during treatment. Age > 50 years and higher income seemed to facilitate RTW (RR = 0.65, 95% CI 0.49-0.88 and RR = 0.72, 95% CI 0.54-0.97, respectively), while being divorced acted as a barrier compared to being married (RR = 1.45, 95% CI 1.04-2.01). Individuals uncertain about the type of company they were working for reported greater difficulty in RTW (RR = 1.68, 95% CI 1.03-2.72). Individuals who had undergone chemotherapy and those perceiving physical limitations had a higher risk of difficulty in the RTW process (RR = 1.79, 95% CI 1.42-2.24 and RR = 1.59, 95% CI 1.25-2.02, respectively). CONCLUSIONS: Most CSs did RTW, with 2/3 combining work and treatment. However, almost half reported difficulty in RTW process. Factors affecting this process should be addressed throughout context-specific social and healthcare pathways aimed at preventing difficulties and potential job loss in this population.

Return to work in European Cancer survivors: a systematic review.

PURPOSE: Return to work (RTW) of cancer survivors (CSs) fluctuates in different contexts. This systematic review searched for recent data on the RTW rate of CSs in Europe, investigating associated factors. METHODS: Bibliographic search covered the period from January 2010 to February 2018, with no language restrictions. European population-based studies assessing RTW rate after cancer diagnosis were included. We excluded studies focusing on a specific cancer diagnosis. RESULTS: Twelve observational studies were selected. The cohorts investigated included 280 to 46,720 individuals from Northwestern and Central Europe diagnosed with cancer from 1987 to 2010. The median interval between diagnosis and documented RTW was 2 years (0.2-23.4 years). RTW rates of CSs ranged from 39 to 77%. RTW of individuals employed at the time of diagnosis ranged from 60 to 92%, the latter registered in a sample with good prognosis. Personal factors, work-related factors, and cancer-related factors were all associated with RTW. Healthcare team interventions facilitated reintegration to work. CONCLUSIONS: Data from Mediterranean and Central European countries are urgently needed to understand whether RTW is an issue for CSs there as well and whether socio-rehabilitative interventions are required to mitigate the potential negative impact of cancer on individuals and society.

Bacterial sensor triggering receptor expressed on myeloid cells-2 regulates the mucosal inflammatory response.

BACKGROUND AND AIMS: Triggering receptor expressed on myeloid cells (TREM)-2 is a surface receptor detected on macrophages, dendritic cells, and microglia that binds repeated anionic motifs on yeast and Gram-positive and Gram-negative bacteria. Little is known about TREM-2 expression and function in the intestine or its role in inflammatory bowel disease (IBD). We investigated the expression of TREM-2 in the intestinal lamina propria and its role in the development of colonic inflammation. METHODS: We measured levels of TREM-2 in lamina propria mononuclear cells from surgical specimens collected from patients with IBD or cancer (controls). We analyzed the development of colitis in TREM-2 knockout and wild-type mice. Colon samples were isolated from mice and analyzed for cytokine expression, phagocytosis of bacteria, proliferation in colonic crypts, lamina propria mononuclear cell function, and T-cell activation by ovalbumin. RESULTS: TREM-2 was virtually absent from colon samples of control patients, but levels were significantly higher in within the inflamed mucosa of patients with IBD; it was mainly expressed by CD11c(+) cells. Levels of TREM-2 increased as acute or chronic colitis was induced in mice. TREM-2 knockout mice developed less severe colitis than wild-type mice; the knockout mice lost less body weight, had a lower disease activity index, and had smaller mucosal lesions in endoscopic analysis. Colon dendritic cells from TREM-2 knockout mice produced lower levels of inflammatory cytokines and had reduced levels of bacterial killing and T-cell activation than cells from wild-type mice. CONCLUSIONS: TREM-2 contributes to mucosal inflammation during development of colitis in mice. Levels of TREM-2 are increased within the inflamed mucosa of patients with IBD, indicating its potential as a therapeutic target.

Activities Carried Out during the First COVID-19 Lockdown by Italian Citizens.

The SARS-CoV-2 pandemic has altered how citizens engage in activities. This study describes the new activities citizens engaged in during the first lockdown, factors that helped them cope with the confinement, the supports they used the most, and which supports they would have liked to receive. This cross-sectional study consists of an online survey made of 49 questions that was completed by the citizens of the province of Reggio Emilia (Italy) from 4 May until 15 June 2020. The outcomes of this study were explored by focusing on four of the survey questions. Of the 1826 citizens who responded, 84.2% had started new leisure activities. Males, participants who lived in the plain or foothills, and those who experienced nervousness engaged less in new activities, while those whose employment status changed, whose lifestyle worsened, or whose use of alcohol increased engaged in more activities. The support of family and friends, leisure activities, continuing to work, and an optimistic attitude were perceived to be of help. Grocery delivery and hotlines providing any type of information and mental health support were used frequently; a lack of health and social care services and of support in reconciling work with childcare was perceived. Findings may help institutions and policy makers to better support citizens in any future circumstances requiring prolonged confinement.

Impact of COVID-19 on cancer care pathways in a comprehensive cancer center in northern Italy.

The COVID-19 pandemic burdened health care systems worldwide. Health services were reorganized with the dual purpose of ensuring the most adequate continuity of care and, simultaneously, the safety of patients and health professionals. The provision of care to patients within cancer care pathways (cCPs) was not touched by such reorganization. We investigated whether the quality of care provided by a local comprehensive cancer center has been maintained using cCP indicators. A retrospective single-cancer center study was conducted on eleven cCPs from 2019 to 2021 by comparing three timeliness indicators, five care indicators and three outcome indicators yearly calculated on incident cases. Comparisons of indicators between 2019 and 2020, and 2019 and 2021, were performed to assess the performance of cCP function during the pandemic. Indicators displayed heterogeneous significant changes attributed to all cCPs over the study period, affecting eight (72%), seven (63%) and ten (91%) out of eleven cCPs in the comparison between 2019 and 2020, 2020 and 2021, and 2019 and 2021, respectively. The most relevant changes were attributed to a negative increase in time-to-treatment surgery-related indicators and to a positive increase in the number of cases discussed by cCP team members. No variations were found attributed to outcome indicators. Significant changes did not account for clinical relevance once discussed by cCP managers and team members. Our experience demonstrated that the CP model constitutes an appropriate tool for providing high levels of quality care, even in the most critical health situations.

Learning from Adaptations to the COVID-19 Pandemic: How Teleconsultation Supported Cancer Care Pathways at a Comprehensive Cancer Center in Northern Italy.

Multidisciplinary team (MDT) meetings are recognized as the gold standard for care management of cancer patients, and during the COVID-19 pandemic they were considered a priority to be maintained. Due to pandemic-related restrictions, MDT meetings were forcibly converted from in-person to telematic format. This retrospective study evaluated the annual performance of four MDT meeting indicators (MDT members' attendance, number of discussed cases, frequency of MDT meetings, and duration) between 2019 and 2022 to report on the implementation of teleconsultation in MDT meetings related to 10 cancer care pathways (CCPs). Over the study period, MDT member participation and the number of discussed cases improved or did not change in 90% (9/10) and 80% (8/10) of the CCPs, respectively. We did not observe significant differences in any of the CCPs included in the study regarding the annual frequency and duration of MDT meeting. Considering the rapidity, extent, and intensity with which telematic tools were adopted due to the COVID-19 pandemic, the results of this study showed that MDT teleconsultation supported the CCPs, and consequently, the delivery of cancer care in COVID-19 times, helping to understand the effects of telematic tools on health care performance and the parties involved.

Patient-reported outcome measure to implement routine assessment of cancer survivors' unmet needs: An overview of reviews and COSMIN analysis.

As the number of cancer survivors (CSs) is increasing worldwide, providing services relevant to the specific, unmet needs of these individuals is crucial. There are currently various patient-reported outcome measures (PROMs) whose aim is to identify the unmet needs of CSs. Still, limited guidance supports healthcare providers in choosing the most valid and reliable PROMs for this purpose. We conducted this overview of systematic reviews (SRs) on the psychometric properties of PROMs addressing the unmet needs of adult CSs suffering from non-cutaneous cancers. We searched databases for SRs published between 2012 and January 2023. Two SRs were included, covering 14 PROMs tested on 19,151 CSs. These were assessed according to the COSMIN methodology for SRs of PROMs for the quality of their measurement properties and risk of bias, thus providing guidance in selecting PROMs that appropriately reflect the unmet needs of CSs.

Return to work of Italian cancer survivors: A focus on prognostic work-related factors.

BACKGROUND: Return to work (RTW) enhances the general well-being and social participation of cancer survivors (CSs). OBJECTIVE: To describe the predictive value of work-related factors on the RTW process of CSs. The work accommodations, the perceived workload, and the barriers and facilitations of RTW are also reported. METHODS: This population-based cross-sectional survey was conducted in the Province of Reggio Emilia from July 2016 to July 2017. CSs who were 20-59 years old, first diagnosed with cancer, and employed at diagnosis were recruited. RESULTS: The majority of CSs (140/266, 53%) returned to work without difficulties, 42% reported difficulties, and 5% did not RTW. CSs who were shift workers (sex and age-adjusted Relative Risk [adj-RR] 1.30; 95% CI 0.94 -1.78) and who worked at night (adj-RR 1.36 95% CI 0.99 -1.86), in the evening (adj-RR 1.23; 95% CI 0.95 -1.57) and on Sundays (adj-RR 1.15; 95% CI 0.81 -1.63) perceived more difficulties. Physically demanding work and a long commute seemed to negatively impact RTW. Accommodations in work tasks (37%) or schedule (26%) were implemented. Workload was not acceptable for 18% of CSs. The main barriers concerned energy and drive functions, whereas remunerative employment was the foremost facilitation. CONCLUSIONS: Healthcare professionals should address work-related factors that might influence RTW with personalized interventions of vocational rehabilitation.

Gut CD103+ dendritic cells express indoleamine 2,3-dioxygenase which influences T regulatory/T effector cell balance and oral tolerance induction.

OBJECTIVE: CD103(+) gut dendritic cells (DCs) have been shown to be required for de novo conversion of adaptive T regulatory (Treg) cells. Indoleamine 2,3-dioxygenase (IDO) is an enzyme involved in tryptophan catabolism that is expressed by DCs isolated from tumour-draining lymph nodes. IDO-expressing DCs sustain and differentiate Tregs. The aim of this study was to investigate the expression and the possible physiological role of IDO in the tolerogenic properties of intestinal DCs. DESIGN: The expression level of IDO in CD103(+) and CD103(-) DCs was analysed by qRT-PCR, western blot and immunofluorescence. CD103(+) and CD103(-) DCs were sorted from mesenteric lymph nodes (MLNs) and the small intestinal lamina propria, and the role of IDO in the conversion of Tregs and Th effector cell development was evaluated via specific inhibition or gene deletion. Oral tolerance, experimental colitis and T cell differentiation in vivo were assessed upon IDO inactivation. RESULTS: We show that, primarily, CD103(+) but not CD103(-) gut DCs express IDO whose inhibition results in reduced CD4(+)Foxp3(+) T regulatory cell conversion and enhanced T cell proliferation. When IDO was inhibited or genetically deleted there was an increase in Th1 and Th17 differentiation both in vitro and in vivo. Finally, in vivo IDO blockade affected the development of Tregs specific for orally administered antigens, impaired oral tolerance induction and exacerbated colitis. CONCLUSIONS: We identified a new IDO-dependent pathway leading to acquisition of tolerogenic functions in mucosal CD103-expressing DCs, indicating IDO as a possible therapeutic target for gut disorders.

A social-healthcare pathway to facilitate return to work of cancer survivors in Italy: The UNAMANO project.

BACKGROUND: Return to work (RTW) is a major goal to promote cancer survivors' social participation. OBJECTIVE: This study describes the multidisciplinary social-healthcare pathway called UNAMANO, conceived to support RTW in this population. METHODS: UNAMANO was developed by the Azienda USL-IRCCS di Reggio Emilia, in partnership with the local branch of the Italian Medical Association, nonprofit associations, vocational training institutions, social cooperatives, a labour union, and a chartered accounting firm. RESULTS: UNAMANO is directed towards employed individuals diagnosed with cancer living in the province of RE. It was developed through four actions: A) training healthcare professionals on work-related occupational rehabilitation; B) dissemination among community and stakeholders; C) recruitment and training of volunteers; D) cancer survivor engagement and provision of a personalized comprehensive intervention. This consists in providing information and either occupational therapy to overcome barriers and facilitate RTW or social support through re-training and tailored job search strategies based on individual risk of job loss. CONCLUSIONS: UNAMANO is the first Italian multidisciplinary social-healthcare pathway supporting RTW of cancer survivors. Addressing a wide area of cancer survivors' needs, it provides personalized intervention to resolve work-related issues. We propose this patient-centred RTW model to promote an easier transition from hospital to community.

Poor Sleep during the First Peak of the SARS-CoV-2 Pandemic: A Cross-Sectional Study.

The restrictions enacted during lockdown to limit the spread of the novel coronavirus (SARS-CoV-2) have led to changes in people's lifestyle habits. In Italy, these restrictions have dramatically changed the way people work and spend their leisure time, also with repercussions on diet and physical activity. An anonymous survey was disseminated via websites and social media to a convenience sample of the Italian population during and immediately after the first lockdown (10 March-18 May 2020). Data collected on 1826 individuals show that lockdown might have worsened the quality of sleep of almost half of the participants in this cross-sectional study. This worsening was associated with a deterioration in crucial determinants of health, such as physical activity and diet (OR 1.68; 95% CI 1.18-2.40 and OR 4.19; 95% CI 2.51-6.96, respectively), with symptoms of psychological distress, such as tension (OR 3.88; 95% CI 2.74-5.52) and loneliness (OR 3.27; 95% CI 2.23-4.79), and with the presence of financial problems (some OR 1.86; 95% CI 1.27-2.72; many OR 7.27; 95% CI 3.59-14.73). The multivariate regression analysis models confirmed these associations. This impact on sleep quality was seen especially among females, those with low education level, and those who experienced financial problems.

Beyond Lockdown: The Potential Side Effects of the SARS-CoV-2 Pandemic on Public Health.

Lockdowns to contain the spread of the SARS-CoV-2 have disrupted routines and behaviors, which could lead to a worsening of lifestyle and an increase in the burden of non-communicable diseases. This study aimed to describe the changes in physical activity, diet, alcohol drinking, and cigarette smoking during lockdown. A self-administered online survey addressing adults living in a province in northern Italy was advertised through websites and social media. Citizens could access the survey in anonymity from 4 May until 15 June 2020. A total of 1826 adults completed the survey, with a worsening of physical activity (35.1%), diet (17.6%), alcohol drinking (12.5%), and cigarette smoking (7.7%) reported. In contrast, 33.5% reported an improvement in diet, 12.6% in alcohol drinking, 5.3% in physical activity and 4.1% in cigarette smoking. Female sex, young adult age, suspension of work activity, and symptoms of psychological distress were the factors associated with a greater likelihood of change, which was frequently for the worse. Lockdown had an impact on lifestyle, with some net beneficial effects on diet and mostly negative effects on physical activity. Public health measures should be implemented to avoid long-term negative effects of the lockdown, supporting individuals more prone to change for the worse.

Long-term sustainability of a quality improvement program on cancer pain management: a complex intervention in an inpatient setting.

BACKGROUND: Several approaches towards pain control for admitted cancer patients have been suggested by the literature without achieving satisfactory results. In this quality improvement project, we proposed a multicomponent intervention. MEASURES: A set of indicators was established for each component of the project. The feasibility of both the intervention and its evaluation system was measured. According to the literature review and the analysis of the local context, 5 active components were identified, piloted, and assessed: training of ward professionals, education of patients and nonprofessional caregivers, regular pain assessment, specialist-level pain consultation procedures, and involvement of hospital management. RESULTS: Multiprofessional training programs with daily discussions, daily pain assessment, and a readily available specialized palliative care service seem to be the active components of this complex intervention. The quality improvement project achieved 2 years sustainability. CONCLUSION: Consolidated educational and organizational methodologies support the feasibility of this complex intervention.

Knowledge, Opinion, and Attitude About the Italian Law on Advance Directives: A Population-Based Survey.

CONTEXT: Advance directives are legal documents which individuals draw up to declare their treatment preferences and to appoint well-informed proxies to safeguard patient autonomy in critical situations when that individual is temporarily or no longer able to communicate these preferences. On December 22, 2017, the Italian Parliament approved the first law on end of life ("Provisions for informed consent and advance directives" L.219/2017), after a heated public and political debate lasting almost 20 years. OBJECTIVE: The aim of this study was to investigate the awareness, knowledge, opinions, and attitudes regarding Italian Law 219/2017 and advance directives among the Italian population 15 months after its entry into force. METHODS: A nationwide population-based survey was conducted by a certified public opinion survey company. A sample size of 2000 interviews was planned. A structured questionnaire was developed to investigate awareness, opinions, and attitudes concerning the law by a multiprofessional research team. The agreed-on version was pretested on a sample of 70 selected participants. RESULTS: The sample included 2000 valid interviews; 70.1% of respondents declared they had heard about the law on informed consent and advance directives. Respondents were asked to express their overall opinion on the law's utility and importance: 88% declared that the law was quite or very important and 76% had a positive attitude toward making/registering advance directives. CONCLUSION: The principles of Italian Law 219/2017 are aligned with the ethical sentiment of the vast majority of the Italian population. It is crucial to stimulate discussion to increase knowledge and awareness to increase the number of advance directives.