Can we predict adolescent cannabis use? A Bayesian semi-parametric approach to project future trends.

Despite its decrease in many Western countries, cannabis remains the most used illicit substance among adolescents. This study aims to summarize cannabis consumption during the last two decades and project trends among 15-year-olds in the 2021-22 HBSC survey. A Bayesian semi-parametric hierarchical model was adopted to estimate the trend of cannabis consumption using data of about 287,000 adolescents from the 2001/2002 to the 2017/2018 HBSC wave and the 38 countries that met the inclusion criteria. Data show an overall decline in most countries for both boys and girls. However, in 22 countries of 38 cannabis use is expected to increase again in our projection. The discussion of these findings should take into account cultural, policy, social factors and unpredictable events such as the Covid-19 pandemic, that can significantly impact future trends leading to discrepancies between the projected and observed values. However, these discrepancies can provide insight into understanding the potential impact of preventive strategies and the underlying processes responsible for changes in cannabis use over time.

Loss of Personal Autonomy and Dignity-Related Distress in End-Of-Life Cancer Patients.

The objective of this cross-sectional study is to investigate Dignity-Related Loss of Personal Autonomy (DR-LPA) intended as loss of relational independence causing dignity-related distress. Moreover, it analyzes its possible relationships with demoralization, spirituality, quality of life, hope, and coping styles in a sample composed of 207 end-of-life cancer patients. These variables have been assessed through the following rating scales: Patient Dignity Inventory - Italian version, Demoralization Scale - Italian version, Functional Assessment of Cancer Therapy Scale - General Measure, Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being, Brief Coping Orientation to Problem Experienced, and Herth Hope Index. The results have shown that most of the DR-LPA items were considered a problem by most patients. Functional, social, emotional, and spiritual wellbeing, disheartenment, age, and sex emerged as significant predictors of DR-LPA. In conclusion, this study showed that DR-LPA can be a relevant concern for patients at the end-of-life and for this reason it becomes necessary for psychosocial provides to consider it to deliver better dignity conserving care.

Surgical treatment of popliteomeniscal fascicles tears is associated with better patient-reported outcome measures. A systematic review and meta-analysis.

PURPOSE: Popliteomeniscal fascicles (PMFs) are a component of the popliteal hiatus complex in the knee, and their injury primarily affects young athletes participating in sports activities involving twisting movements. The identification of PMFs tears presents a challenge, often accompanied by lateral pain and a locking sensation. The objective of this systematic review (SR) and meta-analysis is to enhance the suspicion and recognition of PMFs tears, aiming to facilitate the treatment of this condition, particularly in symptomatic young patients. METHODS: A comprehensive search, focused on studies examining PMFs injuries and their treatment, was conducted in four databases, PubMed, Scopus, Embase, and Web of Science. The ROBINS-I tool was used to evaluate the risks of bias. The PRISMA flow diagram was used to conduct the research and select the included studies. A meta-analysis was conducted for the Lysholm score, the Tegner Activity Scale, and the subjective IKDC score. The present SR and meta-analysis was registered on PROSPERO. RESULTS: Five clinical studies were included in the final analysis, comprising 96 patients. All the patients underwent a preoperative MRI assessment and a diagnostic arthroscopy to detect the PMFs tears, with a subsequent surgical procedure either open or arthroscopically performed. Surgery was associated with the resolution of symptoms. A statistically significant improvement in the Lysholm score (p: 0.0005) and the subjective IKDC score (p: 0.003) after the surgical procedure with respect to the preoperative evaluation was found. CONCLUSION: This SR and meta-analysis showed a significant improvement in the Lysholm score and subjective IKDC score following surgery for PMFs tears. However, controversy persists regarding the optimal surgical approach, with current literature favoring arthroscopic procedures. LEVEL OF EVIDENCE: IV.

Risk Behaviors among Migrant Adolescents in Italy.

Adolescence is a critical period for engaging in health risk behaviors. Migrant adolescents may face unique challenges due to acculturation stress. This study aims to monitor substance use and problem gambling among migrant adolescents living in Italy. Data from the 2017/18 Health Behavior in School-Aged Children survey in Italy were analyzed. The 18,794 participants included 15-year-olds, categorized as native or migrants, with ethnic backgrounds from Western, Eastern European, or non-Western/non-European countries. Girls had higher smoking rates, while boys exhibited higher prevalence of alcohol-related risk behaviors, cannabis use, and gambling. Boys from Eastern European countries displayed a greater risk of drunkenness (OR: 1.58, 95% CI: 1.06-2.37), particularly in the first generation, while those from Western countries showed a higher risk of multiple substance use (OR: 1.44, 95% CI: 1.05-1.96). Girls from Eastern European and non-Western/non-European countries had a lower risk of alcohol consumption (OR: 0.50, 95% CI: 0.29-0.85; OR: 0.55, 95% CI: 0.33-0.91, respectively). Finally, boys, especially those from Eastern European and non-Western/non-European countries, had a significantly higher risk of problem gambling (OR: 1.83, 95% CI: 1.04-3.22; OR: 2.10, 95% CI: 1.29-3.42, respectively). This disparity was more pronounced in the first generation, possibly due to acculturation challenges and socio-economic factors. Risk behaviors in adolescents are influenced by complex interplays of gender, cultural factors, and migration generation. Preventive strategies should consider these factors to effectively address substance use and gambling in this heterogeneous population.

Cytotoxic pathways activated by multifunctional thiosemicarbazones targeting sigma-2 receptors in breast and lung carcinoma cells.

BACKGROUND: Multifunctional thiosemicarbazones (TSCs) able to bind sigma receptors and chelate metals are considered as a promising avenue for the treatment of pancreatic cancer due to the encouraging results obtained on in vitro and in vivo models. Here, we assessed the biochemical mechanism of these TSCs also on lung (A549) and breast (MCF7) cancer cells. METHODS: The density of sigma-2 receptors in normal (BEAS-2B and MCF10A) and in lung and breast (A549 and MCF7) cancer cells was evaluated by flow cytometry. In these cells, cytotoxicity (MTT assay) and activation of ER- and mitochondria-dependent cell death pathways (by spectrofluorimetric assays to measure Caspases 3/7/9; qRT-PCR detection of GRP78, ATF6, IRE1, PERK; MitoSOX, DCFDA-AM and JC-1 staining), induced by the TSCs FA4, MLP44, PS3 and ACThio1, were evaluated. RESULTS: FA4 and PS3 exerted more potent cytotoxicity than MLP44 and ACThio1 in all cancer cell lines, where the density of sigma-2 receptors was higher than in normal cells. Remarkably, FA4 promoted ER- and mitochondria-dependent cell death pathways in both cell models, whereas the other TSCs had variable, cell-dependent effects on the activation of the two proapoptotic pathways. CONCLUSIONS: Our data suggest that FA4 is a promising compound that deserves to be further studied for lung and breast cancer treatment. However, the other multifunctional TSCs also hold promise for the development of therapies towards a personalized medicine approach. Indeed, the presence of the sigma-2 receptor-targeting moiety would lead to a more specific tumor delivery embracing the characteristics of individual tumor types.

Fitting Early Phases of the COVID-19 Outbreak: A Comparison of the Performances of Used Models.

The COVID-19 outbreak involved a spread of prediction efforts, especially in the early pandemic phase. A better understanding of the epidemiological implications of the different models seems crucial for tailoring prevention policies. This study aims to explore the concordance and discrepancies in outbreak prediction produced by models implemented and used in the first wave of the epidemic. To evaluate the performance of the model, an analysis was carried out on Italian pandemic data from February 24, 2020. The epidemic models were fitted to data collected at 20, 30, 40, 50, 60, 70, 80, 90, and 98 days (the entire time series). At each time step, we made predictions until May 31, 2020. The Mean Absolute Error (MAE) and the Mean Absolute Percentage Error (MAPE) were calculated. The GAM model is the most suitable parameterization for predicting the number of new cases; exponential or Poisson models help predict the cumulative number of cases. When the goal is to predict the epidemic peak, GAM, ARIMA, or Bayesian models are preferable. However, the prediction of the pandemic peak could be made carefully during the early stages of the epidemic because the forecast is affected by high uncertainty and may very likely produce the wrong results.

Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study.

BACKGROUND: Adjuvant treatment with mitotane is commonly used after resection of adrenocortical carcinoma; however, treatment remains controversial, particularly if risk of recurrence is not high. We aimed to assess the efficacy and safety of adjuvant mitotane compared with surveillance alone following complete tumour resection in patients with adrenocortical carcinoma considered to be at low to intermediate risk of recurrence. METHODS: ADIUVO was a multicentre, open-label, parallel, randomised, phase 3 trial done in 23 centres across seven countries. Patients aged 18 years or older with adrenocortical carcinoma and low to intermediate risk of recurrence (R0, stage I-III, and Ki67 ≤10%) were randomly assigned to adjuvant oral mitotane two or three times daily (the dose was adjusted by the local investigator with the target of reaching and maintaining plasma mitotane concentrations of 14-20 mg/L) for 2 years or surveillance alone. All consecutive patients at 14 study centres fulfilling the eligibility criteria of the ADIUVO trial who refused randomisation and agreed on data collection via the European Network for the Study of Adrenal Tumors adrenocortical carcinoma registry were included prospectively in the ADIUVO Observational study. The primary endpoint was recurrence-free survival, defined as the time from randomisation to the first radiological evidence of recurrence or death from any cause (whichever occurred first), assessed in all randomly assigned patients by intention to treat. Overall survival, defined as time from the date of randomisation to the date of death from any cause, was a secondary endpoint analysed by intention to treat in all randomly assigned patients. Safety was assessed in all patients who adhered to the assigned regimen, which was defined by taking at least one tablet of mitotane in the mitotane group and no mitotane at all in the surveillance group. The ADIUVO trial is registered with ClinicalTrials.gov, NCT00777244, and is now complete. FINDINGS: Between Oct 23, 2008, and Dec 27, 2018, 45 patients were randomly assigned to mitotane and 46 to surveillance alone. Because the study was discontinued prematurely, 5-year recurrence-free and overall survival are reported instead of recurrence-free and overall survival as defined in the protocol. 5-year recurrence-free survival was 79% (95% CI 67-94) in the mitotane group and 75% (63-90) in the surveillance group (hazard ratio 0·74 [95% CI 0·30-1·85]). Two people in the mitotane group and five people in the surveillance group died, and 5-year overall survival was not significantly different (95% [95% CI 89-100] in the mitotane group and 86% [74-100] in the surveillance group). All 42 patients who received mitotane had adverse events, and eight (19%) discontinued treatment. There were no grade 4 adverse events or treatment-related deaths. INTERPRETATION: Adjuvant mitotane might not be indicated in patients with low-grade, localised adrenocortical carcinoma considering the relatively good prognosis of these patients, and no significant improvement in recurrence-free survival and treatment-associated toxicity in the mitotane group. However, the study was discontinued prematurely due to slow recruitment and cannot rule out an efficacy of treatment. FUNDING: AIFA, ENSAT Cancer Health F2-2010-259735 programme, Deutsche Forschungsgemeinschaft, Cancer Research UK, and the French Ministry of Health.

Healthcare Professional Communication on Sexual Health: A Report from the Italian Working Group on Adolescents and Young Adults with Cancer.

BACKGROUND: Sexual function is an important concern for adolescent and young adult (AYA) with cancer. The aim of this study was to explore the attitude of Italian health care professionals who deal with AYA patients with cancer toward sexual health communication. MATERIALS AND METHODS: A 11-question survey was developed by the AIOM (Associazione Italiana di Oncologia Medica) and AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) AYA workgroup and sent to AIOM and AIEOP members. RESULTS: The sample comprised 360 respondents, 54.2% AIEOP and 45.8% AIOM members. Eighty percent were physicians, 14.5% nurses, 4.7% psychologists, and 0.8% other professionals. Medical oncologists are more used to investigate about AYA sexual health than pediatric oncologists (58.2% vs. 46.2%), even if pediatrics more frequently refer patients to specific and shared protocol (40% vs. 26.1%). Both AIOM and AIEOP participants mostly talk about sexual health only on request or occasionally (78.8% and 79%, respectively). Clinician-reported barriers to communication identified in this study are lack of preparation and embarrassment for both the categories, plus the presence/interference of parents for pediatrics and lack of time for medical oncologists. Overall, less than 5% of clinicians in our survey received specific training on potential sexual health issues in AYA patients with cancer and only 2% felt adequately prepared to speak about it. CONCLUSION: Sexual health is a key component of comprehensive care for AYA with cancer during treatments. This study highlighted the need of Italian providers for specific training and guidelines on sex-related health issues encountered by AYA patients.

Interventions to Promote End-of-Life Conversations: A Systematic Review and Meta-Analysis.

CONTEXT: Although several interventions aimed to promote end-of-life conversations are available, it is unclear whether and how these affect delivery of end-of-life conversations. Measuring the processes associated with high-quality end-of-life care may trigger improvement. OBJECTIVES: To estimate the effect of interventions aimed to promote end-of-life conversations in clinical encounters with patients with advanced chronic or terminal illness or their family, on process indicators of end-of-life conversations. METHODS: Systematic review with meta-analysis (PROSPERO no. CRD42021289471). Four databases (PubMed, CINAHL, PsycINFO, and Scopus) were searched up to September 30, 2021. The primary outcomes were any process indicators of end-of-life conversations. Results of pairwise meta-analyses were presented as Risk Ratio (RR) for occurrence, standardized mean difference (SMD) for quality and ratio of means (ROM) for duration. Meta-analysis was not performed when fewer than four studies were available. RESULTS: A total of 4,663 articles were scanned. Eighteen studies were included in the systematic review and 16 entered at least one meta-analysis: documented occurrence (n = 8), patient-reported occurrence (n = 4), patient-reported-quality (n = 4), duration (n = 4). There was significant variability in settings, patients' clinical conditions, and professionals. No significant effect of interventions on documented occurrence (RR 1.54, 95% CI 0.84-2.84; I2 91%), patient-reported occurrence (RR 1.52, 95% CI 0.80-2.91; I2 95%), patient-reported quality (SMD 0.83, 95% CI -1.06 to 2.71; I2 99%), or duration (ROM 1.20, 95% CI 0.95-1.51; I2 65%) of end-of-life conversations was found. Data on frequency were conflicting. Interventions targeting multiple stakeholders promoted earlier and more comprehensive conversations. CONCLUSION: Heterogeneity was considerable, but findings suggest no significant effect of interventions on occurrence, patient-reported quality and duration of end-of-life conversations. Nevertheless, we found indications for interventions targeting multiple stakeholders to promote earlier and more comprehensive conversations.

Who Stays, Who Moves on and the Host Population: A Picture of Adolescents' Perceived Well-Being and Risk Behaviours.

The study aims to evaluate the health profile of first- and second-generation Romanian immigrants living in Italy compared to their adolescent peers in the country of origin (Romania) and the host population (Italian-borns). Analyses were performed on the 2013/2014 Health Behaviour in School-aged Children (HBSC) survey data. Romanian natives showed lower levels of health complaints and higher life satisfaction than Romanian migrants, who were similar to the host population, especially the second-generation ones. A comparable prevalence of being bullied was registered among Romanians, both native and immigrant, with significantly lower levels among Italian natives. Bullying others showed the second-generation migrants share a similar prevalence with the host population. The prevalence of liking school a lot was three times higher among the Romanian natives than among their peers living in Italy. Thanks to the HBSC data, this study is the first to examine the health of adolescent migrants from both the perspective of the host country and the population of origin. The results highlight the need for a more nuanced approach to studying immigrant populations, taking into account both the host country's perspective and the health patterns of the population of origin.

Impact of Hypothermic Oxygenated Machine Perfusion on Hepatocellular Carcinoma Recurrence after Liver Transplantation.

BACKGROUND: Machine perfusion may be able to mitigate ischemia-reperfusion injury (IRI), which increases hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). This study aimed to investigate the impact of dual-hypothermic oxygenated machine perfusion (D-HOPE) on HCC recurrence in LT. METHODS: A single-center retrospective study was conducted from 2016 to 2020. Pre- and postoperative data of HCC patients undergoing LT were analyzed. Recipients of a D-HOPE-treated graft were compared to those of livers preserved using static cold storage (SCS). The primary endpoint was recurrence-free survival (RFS). RESULTS: Of 326 patients, 246 received an SCS-preserved liver and 80 received a D-HOPE-treated graft (donation after brain death (DBD), n = 66; donation after circulatory death (DCD), n = 14). Donors of D-HOPE-treated grafts were older and had higher BMI. All DCD donors were treated by normothermic regional perfusion and D-HOPE. The groups were comparable in terms of HCC features and estimated 5-year RFS according to the Metroticket 2.0 model. D-HOPE did not reduce HCC recurrence (D-HOPE 10%; SCS 8.9%; p = 0.95), which was confirmed using Bayesian model averaging and inverse probability of treatment weighting-adjusted RFS analysis. Postoperative outcomes were comparable between groups, except for lower AST and ALT peak in the D-HOPE group. CONCLUSIONS: In this single-center study, D-HOPE did not reduce HCC recurrence but allowed utilizing livers from extended criteria donors with comparable outcomes, improving access to LT for patients suffering from HCC.

New Findings on Presentation and Outcome of Patients With Adrenocortical Cancer: Results From a National Cohort Study.

CONTEXT: Because of the rarity of adrenocortical cancer (ACC), only a few population-based studies are available, and they reported limited details in the characterization of patients and their treatment. OBJECTIVE: To describe in a nationwide cohort the presentation of patients with ACC, treatment strategies, and potential prognostic factors. METHODS: Retrospective analysis of 512 patients with ACC, diagnosed in 12 referral centers in Italy from January 1990 to June 2018. RESULTS: ACC diagnosed as incidentalomas accounted for overall 38.1% of cases, with a frequency that increases with age and with less aggressive pathological features than symptomatic tumors. Women (60.2%) were younger than men and had smaller tumors, which more frequently secreted hormones. Surgery was mainly done with an open approach (72%), and after surgical resection, 62.7% of patients started adjuvant mitotane therapy. Recurrence after tumor resection occurred in 56.2% of patients. In patients with localized disease, cortisol secretion, ENSAT stage III, Ki67%, and Weiss score were associated with an increased risk of recurrence, whereas margin-free resection, open surgery, and adjuvant mitotane treatment were associated with reduced risk. Death occurred in 38.1% of patients and recurrence-free survival (RFS) predicted overall survival (OS). In localized disease, age, cortisol secretion, Ki67%, ENSAT stage III, and recurrence were associated with increased risk of mortality. ACCs presenting as adrenal incidentalomas showed prolonged RFS and OS. CONCLUSION: Our study shows that ACC is a sex-related disease and demonstrates that an incidental presentation is associated with a better outcome. Given the correlation between RFS and OS, RFS may be used as a surrogate endpoint in clinical studies.

Enhanced Recovery after Surgery (ERAS) Program for Patients with Peritoneal Surface Malignancies Undergoing Cytoreductive Surgery with or without HIPEC: A Systematic Review and a Meta-Analysis.

Enhanced recovery after surgery (ERAS) program refers to a multimodal intervention to reduce the length of stay and postoperative complications; it has been effective in different kinds of major surgery including colorectal, gynaecologic and gastric cancer surgery. Its impact in terms of safety and efficacy in the treatment of peritoneal surface malignancies is still unclear. A systematic review and a meta-analysis were conducted to evaluate the effect of ERAS after cytoreductive surgery with or without HIPEC for peritoneal metastases. MEDLINE, PubMed, EMBASE, Google Scholar and Cochrane Database were searched from January 2010 and December 2021. Single and double-cohort studies about ERAS application in the treatment of peritoneal cancer were considered. Outcomes included the postoperative length of stay (LOS), postoperative morbidity and mortality rates and the early readmission rate. Twenty-four studies involving 5131 patients were considered, 7 about ERAS in cytoreductive surgery (CRS) + HIPEC and 17 about cytoreductive alone; the case histories of two Italian referral centers in the management of peritoneal cancer were included. ERAS adoption reduced the LOS (-3.17, 95% CrI -4.68 to -1.69 in CRS + HIPEC and -1.65, 95% CrI -2.32 to -1.06 in CRS alone in the meta-analysis including 6 and 17 studies respectively. Non negligible lower postoperative morbidity was also in the meta-analysis including the case histories of two Italian referral centers. Implementation of an ERAS protocol may reduce LOS, postoperative complications after CRS with or without HIPEC compared to conventional recovery.

Diagnostic and Therapeutic Algorithm for Appendiceal Tumors and Pseudomyxoma Peritonei: A Consensus of the Peritoneal Malignancies Oncoteam of the Italian Society of Surgical Oncology (SICO).

Aim: Pseudomyxoma peritonei (PMP) is an uncommon pathology, and its rarity causes a lack of scientific evidence, precluding the design of a prospective trial. A diagnostic and therapeutic algorithm (DTA) is necessary in order to standardize the disease treatment while balancing optimal patient management and the correct use of resources. The Consensus of the Italian Society of Surgical Oncology (SICO) Oncoteam aims at defining a diagnostic and therapeutic pathway for PMP and appendiceal primary tumors applicable in Italian healthcare. Method: The consensus panel included 10 delegated representatives of oncological referral centers for Peritoneal Surface Malignancies (PSM) affiliated to the SICO PSM Oncoteam. A list of statements regarding the DTA of patients with PMP was prepared according to recommendations based on the review of the literature and expert opinion. Results: A consensus was obtained on 33 of the 34 statements linked to the DTA; two flowcharts regarding the management of primary appendiceal cancer and peritoneal disease were approved. Conclusion: Currently, consensus has been reached on pathological classification, preoperative evaluation, cytoreductive surgery technical detail, and systemic treatment; some controversies still exist regarding the exclusion criteria for HIPEC treatment. A shared Italian model of DTA is an essential tool to ensure the appropriateness and equity of treatment for these patients.

The management of postoperative disease recurrence in patients with adrenocortical carcinoma: a retrospective study in 106 patients.

OBJECTIVE: The management of adrenocortical carcinoma (ACC) recurrences remains controversial, and we present herein our experience with postoperative ACC recurrences. DESIGN AND METHODS: Retrospective analysis in a single reference center of 106 patients with ACC recurrence. RESULTS: The median follow-up was 45 months, the median recurrence-free survival (RFS) 12 months (IQR 6-23), and the median overall survival (OS) 45 months (IQR 29-75). ACC recurrences occurred as a unique lesion (group A) in 35.8%, multiple lesions in a single organ (group B) in 20.8%, and affecting multiple organs (group C) in 43.4% of patients. Baseline characteristics of patients stratified by the type of recurrence did not differ between them, except RFS, which was significantly longer in group A. Locoregional treatments were used in 100% of patients of group A, 68.2% in group B, and 26.1% in group C. After treatment of recurrence, 60.4% of patients became free of disease attaining a second RFS of 15 months (IQR 6-64). Margin status RX and R1, percent increase in Ki67, and recurrence in multiple organs were associated with an increased risk of mortality, while adjuvant mitotane treatment and longer time to first recurrence were associated with reduced risk. Recurrence in multiple organs and systemic treatment of recurrence had a negative impact on survival from the treatment of recurrence. CONCLUSIONS: This study shows that patients with ACC have a better prognosis when the disease recurs as a single lesion and supports the use of locoregional treatments to treat disease recurrence.

Effectiveness of Workplace Health Promotion (WHP) interventions in university employees: a scoping review.

Workplace Health Promotion (WHP) interventions proved to be effective in several workplace contexts. Currently, the effectiveness of such interventions in the academic workplace is lacking, albeit evidence suggests similar patterns to those occurring in other workplace sectors. The aim of this study was to review WHP interventions in the university workplace that led to improve health- and work-related outcomes. Articles were selected using Pubmed, Web of Science, Scopus, Embase, PsycInfo, Cinhal and FSTA, using search strings focused on health- and/or work-related outcomes and involving University WHP interventions published between January 2010 and July 2021. The majority of the 12 studies selected reported positive results in their individuality, especially regarding health-related outcomes [biological such as weight loss, physical activity, mental health and lifestyle habits] and work-related outcomes concerning improvements either for the employee or for the working system. Studies on economic advantage and Return on Investment were limited and reported contrasting results. In conclusion, we have highlighted how the studies on effectiveness of WHP interventions in the university context are few and heterogeneous and need to be encouraged further research in order to build specific guidelines that are effective.

Interventions concerning prevention promotion in the workplace, involving activities targeting lifestyle habits, nutrition and/or physical activity as well as general wellbeing, are growing and becoming more common due to their benefits on health and work outcomes. The aim of this review was to investigate the effectiveness of such interventions in the university workplace context to help create directed guidelines for their correct implementation in this setting. Although it was difficult to draw peculiar conclusions due to the heterogeneity of the programs described in the studies, the overall positivity of the results and the perspective university environment, outlook that the implementation of multicomponent and multilevel interventions would improve employees' wellness and favor universities' welfare.

Visuospatial Deficits Are Associated with Pisa Syndrome and not Camptocormia in Parkinson's Disease.

Background: Pisa syndrome (PS) and camptocormia (CC) are postural abnormalities frequently associated with Parkinson's disease (PD). Their pathophysiology remains unclear, but the role of cognitive deficits has been postulated. Objectives: To identify differences in the neuropsychological functioning of patients with PD with PS or CC compared with matched patients with PD without postural abnormalities. Methods: We performed a case-control study including 57 patients with PD with PS (PS+) or CC (CC+) and 57 PD controls without postural abnormalities matched for sex, age, PD duration, phenotype, and stage. Patients were divided into four groups: PS+ (n = 32), PS+ controls (PS-, n = 32), CC+ (n = 25), and CC+ controls (CC-, n = 25). We compared PS+ versus PS- and CC+ versus CC- using a neuropsychological battery assessing memory, attention, executive functions, visuospatial abilities, and language. Subjective visual vertical (SVV) perception was assessed by the Bucket test as a sign of vestibular function; the misperception of trunk position, defined as a mismatch between the objective versus subjective evaluation of the trunk bending angle >5°, was evaluated in PS+ and CC+. Results: PS+ showed significantly worse visuospatial performances (P = 0.025) and SVV perception (P = 0.038) than their controls, whereas CC+ did not show significant differences compared with their control group. Reduced awareness of postural abnormality was observed in >60% of patients with PS or CC. Conclusions: Low visuospatial performances and vestibular tone imbalance are significantly associated with PS but not with CC. These findings suggest different pathophysiology for the two main postural abnormalities associated with PD and can foster adequate therapeutic and prevention strategies.

Highly cross-linked polyethylene versus conventional polyethylene in primary total knee arthroplasty: comparable clinical and radiological results at a 10-year follow-up.

PURPOSE: Highly crosslinked polyethylene (HXLPE) was introduced in total knee arthroplasty (TKA) to reduce wear and consequent revisions for loosening due to conventional polyethylene (CPE) wear. This study aims to analyse whether HXLPE is as safe as CPE and could improve the TKA clinical and radiological results in a long-term follow-up. METHODS: This retrospective study included all consecutive starting series of 223 patients with severe primary knee osteoarthritis (OA), with a minimum follow-up of 10 years treated between July 1st, 2007, and July 31st, 2010. After excluding patients who did not respect the inclusion and exclusion criteria, 128 patients were included in the analysis of this study. The patients were then divided into two groups according to the type of polyethylene (PE) implanted: CPE or HXLPE liners. All patients were evaluated for clinical and radiological parameters, causes and revision rates related to the type of PE implanted. RESULTS: HXLPE appears to be as safe as CPE in TKA, reporting no higher revisions for osteolysis, prosthesis loosening, infection, and mechanical failure. Nevertheless, no statistically significant differences were found between the two groups in the clinical and radiological outcomes evaluated. CONCLUSIONS: Clinical, radiological results, and revision rates are similar between HXLPE and CPE in TKA after 10 years of follow-up, although HXLPE benefits remain controversial. LEVEL OF EVIDENCE: III.

Off-label and compassionate use of targeted anticancer therapies: The experience of an Italian pediatric cancer center.

INTRODUCTION: In Europe, despite recent advances in clinical development, most of the drugs currently used to treat childhood cancers are adult medicines, prescribed outside of the authorized indication. In this context, a monocentric retrospective cohort analysis was conducted, evaluating pediatric, adolescent, and young adult patients affected by onco-hematologic disease, treated with targeted therapies used off-label or as compassionate use. METHODS: The analysis was conducted on 45 patients aged less than or equal to 30 years with cancer, having received at least one targeted therapy prescribed as off-label or compassionate use at a large Italian pediatric center between January 1, 2016 and June 30, 2021. Data collected included information on the patient and tumor, data on off-label/compassionate treatment, and data on safety and efficacy. RESULTS: Total 25 out of 45 patients treated with off-label or compassionate targeted therapies were affected by onco-hematological diseases. Overall, 22 out of the 52 agents (42%) were prescribed in patients with relapsed neoplasm and 39% (20/52) in patients with refractory diseases. Complete response was observed in more than half (27/52) of treatments. At least one adverse reaction occurred in 76% (n = 22) of agents administered to patients with onco-hematological tumor and in 43% (n = 10) of agents prescribed to patients with solid tumor. CONCLUSION: This work aims to provide a snapshot of off-label and compassionate use prescriptions in a large Italian pediatric cancer center. This study confirms that targeted agents for unauthorized indications are often prescribed in pediatric patients with cancer, especially after disease relapse and that these treatments are mostly tolerable and effective.

The Mental Well-Being of Italian Adolescents in the Last Decade through the Lens of the Dual Factor Model.

(1) Background: In Italy, the components of adolescents' mental well-being (psychological symptomatology and cognitive perception of life satisfaction) showed different temporal trends, suggesting the adoption of a multidimensional conceptualization. We aimed to assess temporal patterns and provide additional insights into Italian adolescents' mental well-being in the last decade by adopting the Dual Factor Model; (2) Methods: We used nationally representative samples of Italian students (n = 165,000) aged 11, 13, and 15 years across the three more recent Italian Health Behaviour in School-aged Children (HBSC) surveys. Two measures of mental well-being were used: life satisfaction (LS, indicator of positive subjective well-being) and psychological health complaints (PHC, indicator of mental illness); (3) Results: Our study showed that the overall sample has been moving from a Complete Mental Health (Flourishing) to an Incomplete Mental Illness (Struggling) condition. Among 13- and 15-year-old girls, a jump from one to the other mental condition was observed in the 2014-2018 and 2010-2014 time periods, respectively; (4) Conclusions: Our findings suggest that Italian adolescents, especially older girls, have been shifting from Complete Mental Health to Incomplete Mental Illness in the last decade. Further research is needed to investigate this breaking up of the connection between psychological symptomatology and cognitive perception of life satisfaction.