The descriptive epidemiology of melanoma in Italy has changed - for the better.

A recent research project using data from a total of 40 cancer registries has provided new epidemiologic insights into the results of efforts for melanoma control in Italy between the 1990s and the last decade. In this article, the authors present a summary and a commentary of their findings. Incidence increased significantly throughout the study period in both sexes. However, the rates showed a stabilization or a decrease in men and women aged below 35 years. The risk of disease increased for successive cohorts born until 1973 (women) and 1975 (men) while subsequently tending to decline. The trend towards decreasing tumor thickness and increasing survival has continued, but a novel favorable prognostic factor has emerged since 2013 for patients - particularly for males - with thick melanoma, most likely represented by molecular targeted therapies and immune checkpoint inhibitors. Due to this, the survival gap between males and females has been filled out. In the meanwhile, and despite the incidence increase, dermatologists have not lowered their threshold to perform skin biopsy. Skin biopsy rate has increased because of the increasingly greater volume of dermatologic office visits, but the proportion of skin biopsies out of dermatologic office visits has remained constant. In summary, an important breakthrough in melanoma control in Italy has taken place. Effective interventions have been implemented across the full scope of care, which involve many large local populations - virtually the whole national population. The strategies adopted during the last three decades represent a valuable basis for further steps ahead in melanoma control in Italy.

Optimizing the risk stratification of astrocytic tumors by applying the cIMPACT-NOW Update 3 signature: real-word single center experience.

Our work reports implementation of a useful genetic diagnosis for the clinical managment of patients with astrocytic tumors. We investigated 313 prospectively recruited diffuse astrocytic tumours by applying the cIMPACT-NOW Update 3 signature. The cIMPACT-NOW Update 3 (cIMPACT-NOW 3) markers, i.e., alterations of TERT promoter, EGFR, and/or chromosome 7 and 10, characterized 96.4% of IDHwt cases. Interestingly, it was also found in 48,5% of IDHmut cases. According to the genomic profile, four genetic subgroups could be distinguished: (1) IDwt/cIMPACT-NOW 3 (n = 270); (2) IDHwt/cIMPACT-NOW 3 negative (= 10); (3) IDHmut/cIMPACT-NOW 3 (n = 16); and 4) IDHmut/cIMPACT-NOW 3 negative (n = 17). Multivariate analysis confirmed that IDH1/2 mutations confer a favorable prognosis (IDHwt, HR 2.91 95% CI 1.39-6.06), and validated the prognostic value of the cIMPACT-NOW 3 signature (cIMPACT-NOW 3, HR 2.15 95% CI 1.15-4.03). To accurately identify relevant prognostic categories, overcoming the limitations of histopathology and immunohistochemistry, molecular-cytogenetic analyses must be fully integrated into the diagnostic work-up of astrocytic tumors.

How Teaching and Internship Influence the Evidence-Based Practice Approach of Nursing Students: A Longitudinal Study.

AIM: The study aimed to analyze students' approach to evidence-based practice and evaluate the effect of teaching (based on lessons in statistics, epidemiology, evidence-based nursing, bioengineering, English language) and internship experiences on the attitude of nursing students to evidence-based practice. METHOD: In 2019,one hundred nineteen second-year nursing students from an Italian university were involved in a pre-post longitudinal study. The Italian version of the Student-Evidence Based Practice Questionnaire was administered to nursing student in four moments of one academic year. RESULTS: The Student-Evidence Based Practice Questionnaire showed different mean scores based on the four moments of the survey with a significant increase after the experience of planning clinical cases with an online simulation system. In particular, the aptitude subscale does not have significant improvements in the various phases of the study. Conversely, the support of the clinical tutor affects student performance. The didactic module on evidence-based nursing develops the ability to assess the quality of the information found and its sharing. Basic English proficiency is not significantly correlated. CONCLUSION: To develop evidence-based practice knowledge, aptitude, and skills in nursing students, it is necessary to strengthen the learning opportunities both in classroom lessons and in simulation and internship experiences.

Socio-Economic Factors Associated with Ethnic Disparities in SARS-CoV-2 Infection and Hospitalization.

BACKGROUND: There is evidence that non-Italians presented higher incidence of infection and worse health outcomes if compared to native populations in the COVID-19 pandemic. The aim of the study was to compare Italian- and non-Italian-born health outcomes, accounting for socio-economic levels. METHODS: We analyzed data relative to 906,463 people in Umbria (Italy) from 21 February 2020 to 31 May 2021. We considered the National Deprivation Index, the Urban-Rural Municipalities Index and the Human Development Index (HDI) of the country of birth. We used a multilevel logistic regression model to explore the influence of these factors on SARS-CoV-2 infection and hospitalization rates. Diagnosis in the 48 h preceding admission was an indicator of late diagnosis among hospitalized cases. RESULTS: Overall, 54,448 persons tested positive (6%), and 9.7% of them were hospitalized. The risk of hospital admission was higher among non-Italians and was inversely related to the HDI of the country of birth. A diagnosis within 48 h before hospitalization was more frequent among non-Italians and correlated to the HDI level. CONCLUSIONS: COVID-19 had unequal health outcomes among the population in Umbria. Reduced access to primary care services in the non-Italian group could explain our findings. Policies on immigrants' access to primary healthcare need to be improved.

Long-Term Impacts of the COVID-19 Pandemic on Drug/Alcohol Use Prevalence in a Population with Substance Use Disorders.

As time passes, the long-term effects of the COVID-19 pandemic are becoming increasingly apparent. The extreme restrictions imposed during the pandemic have had detrimental impacts on the most vulnerable groups, such as individuals suffering from substance and/or alcohol disorders (SUDs). This study reports quarterly laboratory data on alcohol and drug use in 150 subjects with SUDs that were examined using hair analysis for 2 years before the start of pandemic until after the end of the Italian health emergency. Overall, it was found that the number of subjects who used heroin, cocaine, and MDMA all decreased during the 2020 and 2021 lockdowns, increasing during reopening and subsequently stabilizing close to pre-COVID levels. Cannabis use was less impacted, remaining stable throughout the pandemic. Alcohol and benzodiazepine use both increased significantly during the lockdowns, displaying an opposing trend. While benzodiazepine use progressively returned to baseline levels, alcohol remained at significantly increased levels, even in September 2022. Long-term heavy drinking combined with substance use should be seriously considered, since these results in several health and social problems alongside alcohol-related comorbidities. Thus, appropriate response plans should be implemented both during and after the pandemic, whilst focusing on those who are most vulnerable.

BRAFV600 variant allele frequency predicts outcome in metastatic melanoma patients treated with BRAF and MEK inhibitors.

BACKGROUND: The prognostic impact of variant allele frequency (VAF) on clinical outcome in BRAFV600 mutated metastatic melanoma patients (MMPs) receiving BRAF (BRAFi) and MEK inhibitors (MEKi) is unclear. MATERIALS AND METHODS: A cohort of MMPs receiving first line BRAFi and MEKi was identified by inspecting dedicated databases of three Italian Melanoma Intergroup centres. VAF was determined by next generation sequencing in pre-treatment baseline tissue samples. Correlation between VAF and BRAF copy number variation was analysed in an ancillary study by using a training and a validation cohort of melanoma tissue samples and cell lines. RESULTS: Overall, 107 MMPs were included in the study. The VAF cut-off determined by ROC curve was 41.3%. At multivariate analysis, progression-free survival (PFS) was significantly shorter in patients with M1c/M1d [HR 2.25 (95% CI 1.41-3.6, p < 0.01)], in those with VAF >41.3% [HR 1.62 (95% CI 1.04-2.54, p < 0.05)] and in those with ECOG PS ≥1 [HR 1.82 (95% CI 1.15-2.88, p < 0.05)]. Overall survival (OS) was significantly shorter in patients with M1c/M1d [HR 2.01 (95% CI 1.25-3.25, p < 0.01)]. Furthermore, OS was shorter in patients with VAF >41.3% [HR 1.46 (95% CI 0.93-2.29, p = 0.06)] and in patients with ECOG PS ≥1 [HR 1.52 (95% CI 0.94-2.87, p = 0.14)]. BRAF gene amplification was found in 11% and 7% of samples in the training and validation cohort, respectively. CONCLUSIONS: High VAF is an independent poor prognostic factor in MMP receiving BRAFi and MEKi. High VAF and BRAF amplification coexist in 7%-11% of patients.

A New Medium (HistoCold) for Surgical Specimens Preserving to Improve the Preanalytic Issues in Histopathological Samples Handling: Morphologic and Antigenic Analysis.

Introduction: The onset of precision medicine has led to the integration of traditional morphologic tissues evaluation with biochemical and molecular data for a more appropriate pathological diagnosis. The preanalytic phase and, particularly, timing of cold ischemia are crucial to guarantee high-quality biorepositories of formalin-fixed paraffin-embedded (FFPE) tissues for patients' needs and scientific research. However, delayed fixation using the gold-standard and carcinogenic fixative neutral-buffered formalin (NBF) can be a significant limitation to diagnosis and biopathological characterization. HistoCold (patented; Bio-Optica Milano S.p.A., Milano, Italy) is a nontoxic, stable, and refrigerated preservative solution for tissue handling. This study examined HistoCold's potential role in improving the preanalytic phase of the pathological diagnostic process. Materials and Methods: Breast, lung, or colorectal cancers (20, 25, and 10 cases, respectively) that were to be surgically resected were recruited between 2019 and 2021. Once specimens were surgically removed, three residual samples for each patient were first promptly immersed into HistoCold for 24, 48, and 72 hours and then FFPE. These were compared with routine specimens regarding morphologic features (hematoxylin and eosin) and tissue antigenicity (immunohistochemical stains). Results: Good concordance regarding both the morphologic characteristics of the neoplasms and their proteins expression between the routine and HistoCold handled tissues were found. The tissue handling with the solution never affected the histopathological diagnosis. Conclusions: The use of HistoCold for samples transporting is easy, allows for improving the management of cold ischemia time, and monitoring the fixation times in NBF, resulting in good quality tissue blocks for biobanking. Moreover, it could be a candidate to eliminate formalin from operating theaters. HistoCold looks very promising for the preanalytic phase of human tissues handling in the era of precision medicine, to provide the best service to patients, and to scientific research.

Quality of life, Stress, and Burnout of Italian nurses during the outbreak of COVID-19: a cross-sectional study / La qualità della vita, stress e burnout negli infermieri durante il periodo della Pandemia da Covid-19 in Italia: uno studio trasversale.

INTRODUCTION: The COVID-19 pandemic was a whispered problem for nurses, causing feelings of anxiety, stress, and burnout. Many studies investigated the pandemic's negative effects on nurses, but the relationship between burnout and the quality of life (QoL) in Italian nurses was lacking. AIM: To describe Italian nurses quality of life and stress during the Covid-19 outbreak. METHODS: METHODS: We conducted a cross-sectional study between March 25, 2020, to May 15, 2020. The MBI scale was used to detect burnout, while the SVQI was for nurses' quality of life (QoL). We used descriptive and correlational statistical tests between the scales and risk factors. The significance level was set at P. 0.05. RESULTS: A total of 384 nurses were assessed, 58.1% (223) were female, 41.9% (161) were male. Depersonalization appeared in 85% of cases, emotional exhaustion in 52.3%, and personal accomplishment in 17.4%. Overall, nurses report a dissatisfaction with the physical, emotional and social QoL. The factors that contribute to onset of the syndrome was: gender (p = 0.003), ward (p = 0.03), care to COVID-19 patients (p = 0.02). Women are dissatisfied with physical (p = 0.001), emotional (p = 0.001) and social (p =0.002) QoL. Statistically significant differences by department (p = 0.01) and geographical area of Northern Italy (p = 0.02). CONCLUSION: During the COVID-19 outbreak, some factors studied are associated with high-stress levels and low physical and social QoL. Women were the gender most affected by the effects of the pandemic.

Immediate reinfection with Omicron variant after clearance of a previous SARS-CoV-2 infection.

SARS-CoV-2 Omicron variant is spreading worldwide, causing unprecedented epidemic peaks due to its transmissibility and immune evasion. We searched in the archive of the Regional Microbiology Laboratory (Umbria, Italy) for immediate reinfection (i.e. infection occurring 25-60 days from primary infection) among 454,764 RT-PCR tests from 261,217 individuals. Lineage heterogeneity was assessed by S gene target failure phenomenon or whole genome sequencing. We found that BA.1 Omicron variant may cause immediate reinfection of patients just recovered from Delta infection. Immediate reinfection was not observed for any other combination of variants, including Delta over Alpha variant and BA.2 over BA.1 Omicron lineage.

Nursing students and COVID-19 vaccination. ESitA Study An Observational Study.

BACKGROUND AND AIM: Vaccine hesitancy is an important problem in terms of health policy. This historical moment leads us to wonder if vaccine hesitancy is also present among nursing students who should be particularly sensitive to the subject Methods: Between February 10 to February 17 2021, 1080 students enrolled in the Bachelor of Science in Nursing in the Department of Medicine and Surgery of the University of Perugia, were invited to reply to an online questionnaire sent to their university email accounts. RESULTS AND CONCLUSIONS: A certain amount of vaccination hesitancy was detected among the students in our study. It can be assumed that the issues surrounding the AstraZeneca vaccine, which occurred at the start of the vaccination campaign, may have led to an increase in people's hesitancy. Boosting vaccination campaigns, including appropriate use of social media, may lead to greater acceptance. Also, it would be useful to assess the cultural basis of the recent anti-Vax controversy, particularly for students of nursing or other health professions, who should be able to evaluate, source and recognize the most validated data.

Patients who leave the Emergency Department without being seen. Has COVID-19 affected this phenomenon?

BACKGROUND AND AIM: Patients who present to an Emergency Department (ED) and leave without being seen by a physician represent a safety concern because they may become severely ill and experience adverse events as a result of lacking or delayed ED treatment. Prior to the COVID-19 outbreak, the increasing number of patients accessing care through the ED in Italy and throughout the world has had implications for health policies. METHODS: A retrospective cohort study that included all ED visits from 1st January 2013 to 31st December 2018 in the Perugia University Hospital has been carried out. RESULTS: During the 5 years investigated 26,344 out of 300,372 (8.77%) patients who attended the ED left the triage area before being seen with an average of 439 patients per month. The same phenomenon has been analysed from February to October 2020. During these 9 months there were a total of 1,824 out of 30,990 (5.88%) patients who left the ED without being seen with an average of 202 per month. The latter value is one third lower than the one related to the period investigated prior to the COVID-19 outbreak. CONCLUSIONS: Such investigation could help to differentiate actual essential demand from non-essential demand within the ED, which could inform quality-improvement policies. Several strategies could be implemented to lower the proportion of patients who leave the department without being seen. Reorganising the activities in the ED with different paths should be implemented with the aim of reducing waiting times and in turn patients' satisfaction.

Patterns of Prescription Medicine, Illicit Drugs, and Alcohol Misuse among High-Risk Population: A Factor Analysis to Delineate Profiles of Polydrug Users.

Polydrug use is a serious health and social problem worldwide. Treatment remains a challenge because it requires planning based on estimates of the nature and extent of drug consumption and the characteristics of the population in need. To this end, 103 subjects, who voluntarily asked to begin rehabilitation treatment, were monitored through hair analysis to investigate the nature and extent of their polydrug use. A factor analysis was carried out to delineate polydrug user profiles based on the following variables: age, sex, type of illicit drug use, type of prescription drug misuse, and amount of alcohol consumption. Twenty-three percent of subjects tested positive to more than one illicit drug (mainly cocaine), 44% to unprescribed drugs (mainly benzodiazepines), and 66% were hard drinkers. The profiles of drug users outlined included "single drug cocaine user", and "single drug opiate user". Moreover, a particularly problematic profile of cocaine users, common between genders and age groups, who combine high levels of alcohol and unprescribed benzodiazepines and opiates, emerged ("hard polydrug abusers"). From a treatment policy perspective, these findings support the importance of preventive analysis before rehabilitation treatment begins in order to identify different patterns of drug abusers to implement personalized multidisciplinary measures.

Role of Nucleocapsid Protein Antigen Detection for Safe End of Isolation of SARS-CoV-2 Infected Patients with Long Persistence of Viral RNA in Respiratory Samples.

BACKGROUND: In SARS-CoV-2 infection, viral RNA may persist in respiratory samples for several weeks after the resolution of symptoms. Criteria to assess the end of infectivity are not unequivocally defined. In some countries, time from diagnosis is the unique criterion used, in addition to symptom cessation. This study evaluates the role of the Lumipulse® Antigen Assay (LAA) for the safe end of isolation of patients ≥21 days after the diagnosis of infection. METHODS: A total of 671 nasopharyngeal swabs from patients diagnosed with infection at least 21 days before were assessed by RT-PCR and LAA, and the role of LAA in predicting the absence of infectivity was evaluated by virus cell culture. RESULTS: Viable virus was present in 10/138 cultured samples. Eight out of ten infective patients suffered from a concomitant disease, predisposing them to long-term shedding of infective virus. In particular, infectious virus was isolated from 10/20 RT-PCR+/LAA+ cultured samples, whereas no viable virus was found in all 118 RT-PCR+/LAA- cultured swabs. LLA and RT-PCR agreed in 484/671 (72.1%) samples, with 100% and 26.7% concordance in RT-PCR negative and positive samples, respectively. CONCLUSIONS: Viable virus can be found ≥21 days after diagnosis in immunocompromised or severely ill patients. LAA better than RT-PCR predicts non-infectivity of patients and can be safely used to end isolation in cases with long persistence of viral RNA in the respiratory tract.

Accuracy and Impact on Patient Management of New Tools for Diagnosis of Sepsis: Experience with the T2 Magnetic Resonance Bacteria Panel.

The rapid and accurate identification of pathogens responsible for sepsis is essential for prompt and effective antimicrobial therapy. Molecular technologies have been developed to detect the most common causative agents, with high sensitivity and short time to result (TTR). T2 Bacteria Panel (T2), based on a combination of PCR and T2 magnetic resonance, can identify directly in blood samples Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, and Acinetobacter baumannii pathogens. This study evaluates the role of T2 in the diagnosis of sepsis and its impact on patient management, specifically in terms of TTR and the switch from empirical to directed therapy, comparing results of blood culture (BC) and T2 assay in 82 patients with sepsis. T2 significantly improved the detection of the causative agents of sepsis. For pathogens included in the panel, T2 sensitivity was 100% (95% CI 86.3-100.0), significantly higher than that of BC (54.8%, 95% CI 36.0-72.7). The TTR (median, IQR) of positive T2 (3.66 h, 3.59-4.31) was significantly shorter than that of the positive BC (37.58 h, 20.10-47.32). A significant reduction in the duration of empiric therapy and an increase in the percentage of patients with switched therapy was observed in patients with a positive T2 result. In conclusion, T2 can shorten and improve the etiological diagnosis of sepsis with a positive impact on patient management.

Higher TLR7 Gene Expression Predicts Poor Clinical Outcome in Advanced NSCLC Patients Treated with Immunotherapy.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of lung cancer. However, their clinical benefit is limited to a minority of patients. To unravel immune-related factors that are predictive of sensitivity or resistance to immunotherapy, we performed a gene expression analysis by RNA-Seq using the Oncomine Immuno Response Assay (OIRRA) on a total of 33 advanced NSCLC patients treated with ICI evaluating the expression levels of 365 immune-related genes. We found four genes (CD1C, HLA-DPA1, MMP2, and TLR7) downregulated (p < 0.05) and two genes (IFNB1 and MKI67) upregulated (p < 0.05) in ICI-Responders compared to ICI-Non-Responders. The Bayesian enrichment computational analysis showed a more complex interaction network that involved 10 other genes (IFNA1, TLR4, CD40, TLR2, IL12A, IL12B, TLR9, CD1E, IFNG, and HLA-DPB1) correlated with different functional groups. Five main pathways were identified (FDR < 0.0001). High TLR7 expression levels were significantly associated with a lack of response to immunotherapy (p < 0.0001) and worse outcome in terms of both PFS (p < 0.001) and OS (p = 0.03). The multivariate analysis confirmed TLR7 RNA expression as an independent predictor for both poor PFS (HR = 2.97, 95% CI, 1.16-7.6, p = 0.023) and OS (HR = 2.2, 95% CI, 1-5.08, p = 0.049). In conclusion, a high TLR7 gene expression level was identified as an independent predictor for poor clinical benefits from ICI. These data could have important implications for the development of novel single/combinatorial strategies TLR-mediated for an efficient selection of "individualized" treatments for NSCLC in the era of immunotherapy.

Sensitivity to Immune Checkpoint Blockade in Advanced Non-Small Cell Lung Cancer Patients with EGFR Exon 20 Insertion Mutations.

Besides platinum-based chemotherapy, no established treatment option exists for advanced non-small-cell lung cancer (NSCLC) patients with EGFR exon 20 (Ex20ins) insertion mutations. We sought to determine the clinical outcome of patients with this EGFR mutation subtype in the immunotherapy era. Thirty NSCLCs with EGFR Ex20ins mutations were identified, of whom 15 had received immune checkpoint blockade (ICB) treatment as monotherapy (N = 12), in combination with chemotherapy (N = 2) or with another immunotherapeutic agent (N = 1). The response rate was observed in 1 out of 15 patients (6.7%), median progression-free survival (PFS) was 2.0 months and median overall survival (OS) was 5.3 months. A trend towards an inferior outcome in terms of PFS and OS was observed for patients receiving ICB treatment in the first versus second line setting (PFS: 1.6 months versus 2.7 months, respectively, p = 0.16-OS: 2.0 months versus 8.1 months, respectively, p = 0.09). Median OS from the time of diagnosis of advanced disease was shorter for patients treated with ICB versus those who did not receive immunotherapy (12.9 months versus 25.2 months, respectively, p = 0.08), which difference remained associated with a worse survival outcome at multivariate analysis (p = 0.04). Treatment with ICB is poorly effective in NSCLCs with EGFR Ex20ins mutations, especially when given in the first-line setting. This information is crucial in order to select the optimal treatment strategy for patients with this subtype of EGFR mutation.

Changes in Drug Use Patterns during the COVID-19 Pandemic in Italy: Monitoring a Vulnerable Group by Hair Analysis.

From 22 March until 18 May 2020, a complete lockdown in Italy was ordered as a countermeasure against the COVID-19 pandemic. Social isolation measures affect some populations more than others, and people with drug and/or alcohol disorders (SUDs) are more likely to be adversely affected. This study presents, for the first time, laboratory data on the use of alcohol and drugs in a high-risk population during Italy's first wave of the COVID-19 pandemic. Thirty subjects with SUDs were monitored for the use of illicit drugs and alcohol every 3 months before, during and after the lockdown, by hair analysis. The number of samples positive for heroin, cocaine, MDMA and cannabis fell considerably during the lockdown and then resumed to pre-lockdown levels when the period of confinement was over. Interestingly, the consumption of benzodiazepines and alcohol followed the opposite trend; both the number of benzodiazepine-positive samples and the level of alcohol consumption increased and remained high, even at the end of the lockdown. The confinement measures produced significant changes in drug/alcohol use patterns, with a shift toward the use of substances that were more easily accessible, used as self-medication for negative feelings, and used to alleviate the effects of abstinence from drugs that were no longer readily available.