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Background: Prior epidemiologic studies on the association between diabetes and gastric cancer risk provided inconclusive findings, while traditional, aggregate data meta-analyses were characterized by high between-study heterogeneity., Objective: To investigate the association between type 2 diabetes and gastric cancer using data from the 'Stomach Cancer Pooling (StoP) Project', an international consortium of more than 30 case-control and nested case-control studies, which is large and provides harmonized definition of participants' characteristics across individual studies. The data have the potential to minimize between-study heterogeneity and provide greater statistical power for subgroup analysis., Methods: We included 5592 gastric cancer cases and 12 477 controls from 14 studies from Europe, Asia, North America, and South America in a two-stage individual-participant data meta-analysis. Random-effect models were used to estimate summary odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) by pooling study-specific ORs., Results: We did not find an overall association between diabetes and gastric cancer (pooled OR = 1.01, 95% CI, 0.94-1.07). However, the risk of cardia gastric cancer was significantly higher among individuals with type 2 diabetes (OR = 1.16, 95% CI, 1.02-1.33). There was no association between diabetes and gastric cancer risk in strata of Helicobacter pylori infection serostatus, age, sex, BMI, smoking status, alcohol consumption, fruit/vegetable intake, gastric cancer histologic type, and source of controls., Conclusion: This study provides additional evidence that diabetes is unrelated to gastric cancer overall but may be associated with excess cardia gastric cancer risk., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Previous studies show that consuming foods preserved by salting increases the risk of gastric cancer, while results on the association between total salt or added salt and gastric cancer are less consistent and vary with the exposure considered. This study aimed to quantify the association between dietary salt exposure and gastric cancer, using an individual participant data meta-analysis of studies participating in the Stomach cancer Pooling (StoP) Project., Methods: Data from 25 studies (10,283 cases and 24,643 controls) from the StoP Project with information on salt taste preference (tasteless, normal, salty), use of table salt (never, sometimes, always), total sodium intake (tertiles of grams/day), and high-salt and salt-preserved foods intake (tertiles of grams/day) were used. A two-stage approach based on random-effects models was used to pool study-specific adjusted (sex, age, and gastric cancer risk factors) odds ratios (aORs), and the corresponding 95% confidence intervals (95% CI)., Results: Gastric cancer risk was higher for salty taste preference (aOR 1.59, 95% CI 1.25-2.03), always using table salt (aOR 1.33, 95% CI 1.16-1.54), and for the highest tertile of high-salt and salt-preserved foods intake (aOR 1.24, 95% CI 1.01-1.51) vs. the lowest tertile. No significant association was observed for the highest vs. the lowest tertile of total sodium intake (aOR 1.08, 95% CI 0.82-1.43). The results obtained were consistent across anatomic sites, strata of Helicobacter pylori infection, and sociodemographic, lifestyle and study characteristics., Conclusion: Salty taste preference, always using table salt, and a greater high-salt and salt-preserved foods intake increased the risk of gastric cancer, though the association was less robust with total sodium intake., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The effectiveness of virtual reality (VR) in the motor and cognitive rehabilitation of patients with severe acquired brain injury (sABI) is unclear. This randomized, controlled, crossover, single-blinded, pilot study investigates the cognitive and motor effects of lower limb robotic therapy with and without VR visual feedback in a group of patients with ABI. A total of 23 patients with ABI were randomized into two groups: one group (VR-NVR) underwent a 2-week rehabilitation for the lower limbs training with a robotic device (Omego ® ) with VR feedback, followed by 2 weeks without VR; the other group (NVR-VR) performed the protocol in the opposite order. Patients were evaluated at baseline, after two and four weeks of treatment using the Level of Cognitive Functioning scale (LCF), Disability Rating Scale (DRS), and Motricity Index for Lower Limb (MI-LL) in the most affected limb. At the end of the intervention, both groups significantly improved in all the outcomes. A significant difference was found between VR treatment versus non-VR treatment for LCF ( p = 0.024) and for DRS ( p = 0.043) after the second week, while no significant differences were found in the group NVR-VR at T1. Our study indicates how the combination of robotic treatment with VR is effective in enhancing the recovery of cognitive function in patients with ABI, also improving disability and muscular function. Further, VR seems to enhance the early recovery process of motor and cognitive functions.

Objective: To evaluate the effect of volume guarantee (VG) combined with high-frequency oscillatory ventilation (HFOV) on respiratory and other physiological parameters immediately after lung recruitment and surfactant administration in HFOV elective ventilated extremely low gestational age newborns (ELGAN) with respiratory distress syndrome (RDS)., Design: Observational study., Setting: Tertiary neonatal intensive care unit., Patients: Twenty-two ELGANs of 25.5 ± 1.1 weeks of gestational age requiring invasive mechanical ventilation and surfactant administration for RDS during the first 6 h of life., Interventions: All infants intubated in delivery room, were managed with elective HFOV and received surfactant after a lung recruitment manoeuver. Eleven infants received HFOV + VG and were compared with a control group of 11 infants receiving HFOV alone. HFOV was delivered in both groups by Dräger Babylog VN500 ventilator (Dräger, Lubeck, Germany)., Main Outcome Measures: Variations and fluctuations of delivered high-frequency tidal volume (VT hf ), fluctuation of pressure amplitude (ΔP) and partial pressure of CO 2 (pCO 2 ) levels after recruitment manoeuver and immediately after surfactant administration, in HFOV + VG vs. HFOV ventilated infants., Results: There were no significant differences in the two groups at starting ventilation with or without VG. The mean applied VT hf per kg was 1.7 ± 0.3 ml/kg in the HFOV group and 1.7 ± 0.1 ml/kg in the HFOV + VG group. Thirty minutes after surfactant administration, HFOV group had a significant higher VT hf /Kg than HFOV + VG (2.1 ± 0.3 vs. 1.6 ± 0.1 ml/kg, p < 0.0001) with significantly lower pCO 2 levels (43.1 ± 3.8 vs. 46.8 ± 1.5 mmHg, p = 0.01), 54.4% of patients having pCO 2 below 45 mmHg. Measured post-surfactant ΔP values were higher in HFOV group (17 ± 3 cmH 2 O) than in HFOV + VG group (13 ± 3 cmH 2 O, p = 0.01)., Conclusion: HFOV + VG maintains pCO 2 levels within target range and reduces VT hf delivered variations more consistently than HFOV alone after surfactant administration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tana, Paladini, Tirone, Aurilia, Lio, Bottoni, Costa, Tiberi, Pastorino and Vento.)

Costello syndrome (CS) is a rare disorder caused by activating dominantly acting germline variants in the HRAS gene. CS is defined by a clinical phenotype characterized by a distinctive gestalt, multiple congenital anomalies, and increased risk to develop tumors. Hypoglycemia and hypercholesterolemia have been reported to occur in affected individuals, but the underlying molecular events remain to be characterized. Here, we provided data on glucose/lipid metabolism and amino acid profile of a large single-center cohort of individuals affected by CS to systematically assess the extent of metabolic dysregulation characterizing this disorder and optimize patient management., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Objectives: Most countries initially deployed COVID-19 vaccines preferentially in elderly populations. We aimed to evaluate whether population-level vaccine effectiveness is heralded by an increase in the relative proportion of deaths among non-elderly populations that were less covered by vaccination programs., Eligible Data: We collected data from 40 countries on age-stratified COVID-19 deaths during the vaccination period (1/14/2021-5/31/2021) and two control periods (entire pre-vaccination period and excluding the first wave)., Main Outcome Measures: We meta-analyzed the proportion of deaths in different age groups in vaccination versus control periods in (1) countries with low vaccination rates; (2) countries with age-independent vaccination policies; and (3) countries with standard age-dependent vaccination policies., Results: Countries that prioritized vaccination among older people saw an increasing share of deaths among 0-69 year old people in the vaccination versus the two control periods (summary proportion ratio 1.32 [95 CI% 1.24-1.41] and 1.35 [95 CI% 1.26-1.44)]. No such change was seen on average in countries with age-independent vaccination policies (1.05 [95 CI% 0.78-1.41 and 0.97 [95 CI% 0.95-1.00], respectively) and limited vaccination (0.93 [95 CI% 0.85-1.01] and 0.95 [95 CI% 0.87-1.03], respectively). Proportion ratios were associated with the difference of vaccination rates in elderly versus non-elderly people. No significant changes occurred in the share of deaths in age 0-49 among all 0-69 deaths in the vaccination versus pre-vaccination periods., Conclusions: The substantial shift in the age distribution of COVID-19 deaths in countries that rapidly implemented vaccination predominantly among elderly provides evidence for the population level-effectiveness of COVID-19 vaccination and a favorable evolution of the pandemic towards endemicity with fewer elderly deaths., (Copyright © 2021. Published by Elsevier Inc.)

Background: Risk prediction models incorporating single nucleotide polymorphisms (SNPs) could lead to individualized prevention of colorectal cancer (CRC). However, the added value of incorporating SNPs into models with only traditional risk factors is still not clear. Hence, our primary aim was to summarize literature on risk prediction models including genetic variants for CRC, while our secondary aim was to evaluate the improvement of discriminatory accuracy when adding SNPs to a prediction model with only traditional risk factors., Methods: We conducted a systematic review on prediction models incorporating multiple SNPs for CRC risk prediction. We tested whether a significant trend in the increase of Area Under Curve (AUC) according to the number of SNPs could be observed, and estimated the correlation between AUC improvement and number of SNPs. We estimated pooled AUC improvement for SNP-enhanced models compared with non-SNP-enhanced models using random effects meta-analysis, and conducted meta-regression to investigate the association of specific factors with AUC improvement., Results: We included 33 studies, 78.79% using genetic risk scores to combine genetic data. We found no significant trend in AUC improvement according to the number of SNPs (p for trend = 0.774), and no correlation between the number of SNPs and AUC improvement (p = 0.695). Pooled AUC improvement was 0.040 (95% CI: 0.035, 0.045), and the number of cases in the study and the AUC of the starting model were inversely associated with AUC improvement obtained when adding SNPs to a prediction model. In addition, models constructed in Asian individuals achieved better AUC improvement with the incorporation of SNPs compared with those developed among individuals of European ancestry., Conclusions: Though not conclusive, our results provide insights on factors influencing discriminatory accuracy of SNP-enhanced models. Genetic variants might be useful to inform stratified CRC screening in the future, but further research is needed., (© 2022. The Author(s).)

Recent studies estimated an incidence of 4-25% of disease rebound after withdrawal of fingolimod (FTY) for any reason, but specific data on disease reactivation after FTY withdrawal due to pregnancy are limited. The aim of the study was to evaluate the frequency and predictors of disease reactivation in patients who stopped FTY for pregnancy. A multicentre retrospective cohort study was conducted in four Italian MS centres in 2013-2019. Both planned and unplanned pregnancies were included. The annualized relapse rate (ARR) was calculated before FTY treatment, during FTY treatment, during pregnancy and during the year after delivery. In total, 27 patients (mean age 29 years) were included. The ARR 1 year before FTY treatment was 1.3. Patients were exposed to FTY for a median of 2.9 years. The ARR was 0.04 during the last year before conception (p < 0.001 compared with the ARR before FTY treatment). Eleven patients became pregnant after a mean of 88 days following FTY discontinuation, whereas 16 patients stopped FTY after pregnancy confirmation. Relapses were observed in 22% of patients during pregnancy and in 44% in the postpartum period. ARR increased both during pregnancy (0.49; p = 0.027) and in the first year after delivery (0.67; p < 0.001) compared to the last year before pregnancy. Compared with radiological assessment before pregnancy, more patients showed new or enlarging T2 lesions (63% vs 30%; p = 0.02) and gadolinium-enhancing lesions (44% vs 0; p = 0.0001) on brain Magnetic Resonance Imaging. Relapses during pregnancy were the only significant predictor for postpartum relapses (OR 1.9, 95% CI 1.11-3.1). One case of spontaneous abortion and no cases of abnormal foetal development were observed. Despite adequate and prolonged control of disease activity, women who discontinue FTY because of pregnancy are at risk for disease reactivation. In patients who relapsed during pregnancy, the initiation of high-efficacy disease modifying drugs (DMDs) soon after delivery is advisable to prevent postpartum relapses., (© 2021. The Author(s).)

We conducted an umbrella review which synthetizes the findings of systematic reviews available in the literature that investigate the prognostic role of miRNAs as potential biomarkers in the field of tertiary prevention of head and neck Cancer (HNC). We selected systematic reviews in English related to HNC, with meta-analysis of observational studies that reported quantitative prognostic measures, hazard ratios (HRs), overall survival (OS) or disease-free survival (DFS). The methodological quality of the included reviews was assessed by using the AMSTAR-2 tool. The most reported miRNAs were the following: miRNA2, Let7 family and miR17, etc. Four out of six reviews particularly emphasized the link between miRNA21 expression and HNC patients. Recently the cumulative effects of sets of miRNAs have been increasingly studied and might be a stronger predictor of survival than single miRNA.

The aim of this work is to explore the suitability of adaptive methods for state estimators based on multibody dynamics, which present severe non-linearities. The performance of a Kalman filter relies on the knowledge of the noise covariance matrices, which are difficult to obtain. This challenge can be overcome by the use of adaptive techniques. Based on an error-extended Kalman filter with force estimation (errorEKF-FE), the adaptive method known as maximum likelihood is adjusted to fulfill the multibody requirements. This new filter is called adaptive error-extended Kalman filter (AerrorEKF-FE). In order to present a general approach, the method is tested on two different mechanisms in a simulation environment. In addition, different sensor configurations are also studied. Results show that, in spite of the maneuver conditions and initial statistics, the AerrorEKF-FE provides estimations with accuracy and robustness. The AerrorEKF-FE proves that adaptive techniques can be applied to multibody-based state estimators, increasing, therefore, their fields of application.

The objectives of the study were to calculate the standardised mortality rates (SMRs) for COVID-19 in European Union/European Economic Area countries plus the UK and Switzerland and to evaluate the correlation between SMRs and selected indicators in the first versus the subsequent waves until 23 June 2021. We used indirect standardisation (using Italy as the reference) to compute SMRs and considered 16 indicators of health and social well-being, health system capacity and COVID-19 response. The highest SMRs were in Belgium, the UK and Spain in the first wave (1.20-1.84) and in Hungary, Czechia and Slovakia in the subsequent waves (2.50-2.69). Human Development Index (HDI), life expectancy, urbanisation and healthcare expenditure had positive correlations with SMR in the first wave (rho=0.30-0.46), but negative correlations (rho=-0.67 to -0.47) in the subsequent waves. Retail/recreation mobility and transit mobility were negatively correlated with SMR in the first wave, while transit mobility was inversely correlated with SMR in the subsequent waves. The first wave hit most hard countries with high HDI, high life expectancy, high urbanisation, high health expenditures and high tourism. This pattern may reflect higher early community seeding and circulation of the virus. Conversely, in the subsequent waves, this pattern was completely inversed: countries with more resources and better health status did better than eastern European countries. While major SMR differences existed across countries in the first wave, these differences largely dissipated by 23 June 2021, with few exceptions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Although there is a clear relationship between family history (FH) and the risk of gastric cancer (GC), quantification is still needed in relation to different histological types and anatomical sites, and in strata of covariates. The objective was to analyze the risk of GC according to first-degree FH in a uniquely large epidemiological consortium of GC. This investigation includes 5946 cases and 12,776 controls from 17 studies of the Stomach Cancer Pooling (StoP) Project consortium. Summary odds ratios (OR) and the corresponding 95% confidence intervals (CIs) were calculated by pooling study-specific ORs using fixed-effect model meta-analysis techniques. Stratified analyses were carried out by sex, age, tumor location and histological type, smoking habit, socioeconomic status, alcohol intake and fruit consumption. The pooled OR for GC was 1.84 (95% CI: 1.64-2.04; I2 = 6.1%, P heterogeneity = 0.383) in subjects with vs. those without first-degree relatives with GC. No significant differences were observed among subgroups of sex, age, geographic area or study period. Associations tended to be stronger for non-cardia (OR = 1.82; 95% CI: 1.59-2.05 for subjects with FH) than for cardia GC (OR = 1.38; 95% CI: 0.98-1.77), and for the intestinal (OR = 1.92; 95% CI: 1.62-2.23) than for the diffuse histotype (OR = 1.62; 95% CI: 1.28-1.96). This analysis confirms the effect of FH on the risk of GC, reporting an approximately doubled risk, and provides further quantification of the risk of GC according to the subsite and histotype. Considering these findings, accounting for the presence of FH to carry out correct prevention and diagnosis measures is of the utmost importance.

Breast Cancer (BC) is the leading cause of death due to cancer in women. Ensuring equitable, quality-assured and effective care has increased the complexity of BC management. This systematic review reports on the state-of-the art of available literature investigating the enactment of personalized treatment and patient-centered care models in BC clinical practice, building a framework for the delivery of personalized BC care within a Patient-Centered model. Databases were searched for articles (from the inception to December 2020) reporting on Patient-Centered or Personalized Medicine BC management models, assessing success factors or limits. Out of 1885 records, 25 studies were included in our analysis. The main success factors include clearly defined roles and responsibilities within a multi-professional collaboration, appropriate training programs and adequate communication strategies and adopting a universal genomic language to improve patients' involvement in the decision-making process. Among detected barriers, delays in the use of genetic testing were linked to the lack of public reimbursement schemes and of clear indications in timing and appropriateness. Overall, both care approaches are complementary and necessary to effectively improve BC patient management. Our framework attempts to bridge the gap in assigning a central role played by shared decision-making, still scarcely investigated in literature.

Introduction: Precision health requires citizens that are empowered to orient health decisions towards their personal values, aware of the benefits and risks, and committed to sharing their personal data to trustful institutions. Effective citizen engagement initiatives are fundamental for the success of a precision health approach., Objective: To provide an overview of citizen engagement initiatives in precision health in European Union (EU) member states., Design: Scoping review., Methods: The electronic databases PubMed, Web of Science, CINAHL and Embase were searched to include articles published in English. Furthermore, desk research was conducted in English, Dutch, French, Italian and Spanish. Articles or reports regarding ongoing initiatives of citizen engagement in precision health conducted in EU member states and published from January 2015 to July 2020 were considered eligible. A quality assessment of the retrieved entries using Critical Appraisal Skills Programme tool was conducted., Results: We identified nine documents, which reported eight ongoing citizen engagement initiatives, with substantial variability. Government agencies, non-governmental organisations and scientific societies were the main organisers and funders. Most of the initiatives were conducted in the UK. Genomics was the most emphasised aspect of precision health in these initiatives. Among the identified initiatives, both in-person and digital means were reported., Conclusion: Our work provides an overview of current citizen engagement initiatives in the EU that can be useful for stakeholders interested in designing and developing precision health projects enriched by meaningful citizen participation., Prospero Registration Number: CRD42020193866., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In order to reduce the burden on healthcare systems and to support differential diagnosis with COVID-19, influenza and pneumococcal vaccinations were strongly recommended during the COVID-19 pandemic, especially in vulnerable groups. However, no univocal and conclusive evidence on the relationship between influenza and pneumococcal vaccinations and COVID-19 outcomes exists. We evaluated the association between such vaccinations, COVID-19 hospitalization, intensive care unit admissions and deaths in a cohort (N = 741) of COVID-19 patients who had access to the emergency room of a large Italian University hospital between March 1, 2020 and June 1, 2020. Results show that influenza and pneumococcal vaccinations did not affect hospitalization, intensive care unit admission and deaths in COVID-19 patients in the overall sample and in those ≥65 years. The same pattern of results was confirmed considering timing of influenza vaccine administration, vaccination type, and number of uptakes in the last five vaccination campaigns. In conclusion, our study does not support an impact of influenza and pneumococcal vaccinations on COVID-19 outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Head and Neck Cancer (HNC) survivors are at increased risk of developing a second primary cancer (SPC). Along with the environmental risk factors, genetic factors have been associated with a potential increased susceptibility to SPC development. We aim to identify the Single Nucleotide Polymorphisms (SNPs) that contribute to SPC development among HNC survivors through a systematic review and meta-analysis., Methods: We searched PubMed, Scopus and ISI Web of Science for eligible studies published in English until January 31st, 2020. We included studies reporting primary data that evaluated the association between SNPs and SPC risk in HNC patients. Data were pooled in a random-effect meta-analyses, when at least two studies on the same SNP evaluated the same genotype model. Heterogeneity was assessed using the χ2-based Q-statistics and the I 2 statistics. Quality of the included studies was assessed using the Q-Genie tool., Results: Twenty-one studies, of moderate to good quality, were included in the systematic review. Fifty-one genes were reported across the included studies to have significant associations with an increased SPC risk. Overall, 81 out of 122 investigated SNPs were significantly associated with the SPC risk. Seven studies were included in the meta-analysis, which showed five SNPs associated with an increased risk of SPC: p21C70T, CT + TT (HR = 1.76; 95% CI: 1.28-2.43); FASLG -844C > T, CT + TT (HR = 1.82; 95% CI: 1.35-2.46), P21 C98A, CA + AA (HR = 1.75; 95% CI: 1.28-2.38); FAS -670A > G (HR = 1.84; 95% CI: 1.28-2.66) and GST-M1, Null genotype (HR = 1.54; 95% CI: 1.13-2.10)., Conclusions: The identified SNPs in our systematic review and meta-analysis might serve as potential markers for identification of patients at high risk of developing SPC after primary HNC., Prospero Registration Number: CRD42019135612 .

The development and implementation of the approaches of personalized medicine for disease prevention are still at infancy, although preventive activities in healthcare represent a key pillar to guarantee health system sustainability. There is an increasing interest in finding informative markers that indicate the disease risk before the manifestation of the disease (primary prevention) or for early disease detection (secondary prevention). Recently, the systematic collection and study of clinical phenotypes and biomarkers consented to the advance of Rehabilomics in tertiary prevention. It consents to identify relevant molecular and physiological factors that can be linked to plasticity, treatment response, and natural recovery. Implementation of these approaches would open avenues to identify people at high risk and enable new preventive lifestyle interventions or early treatments targeted to their individual genomic profile, personalizing prevention and rehabilitation. The integration of personalized medicine into prevention may benefit citizens, patients, healthcare professionals, healthcare authorities, and industry, and ultimately will seek to contribute to better health and quality of life for Europe's citizens.

Background: Italy was the first European country to implement a national lockdown because of the COVID-19 pandemic. Worldwide, this pandemic had a huge impact on the mental health of people in many countries causing similar reaction in terms of emotions and concerns at the population level. Our study investigated the impact of the COVID-19 pandemic on psychological well-being in a cohort of Italian university students., Methods: We conducted a cross-sectional survey in the period immediately after the first lockdown through the administration of a questionnaire on the personal websites of students attending their undergraduate courses at the Università Cattolica del Sacro Cuore. We used the Patient-Health-Engagement-Scale, Self-Rating-Anxiety-Scale, and Self-Rating-Depression-Scale to assess engagement, anxiety symptoms, and depression symptoms of our sample., Results: The sample size was 501 subjects, of which 35.33% were classified as anxious and 72.93% as depressed. Over 90% of respondents had good understanding of the preventive measures despite over 70% suffered from the impossibility of physically seeing friends and partners. Around 55% of students would have been willing to contribute much more to face the pandemic. An increase in the occurrences of anxiety was associated with being female, being student of the Rome campus, suffering from the impossibility of attending university, being distant from colleagues, and being unable of physically seeing one's partner. Performing physical activity reduced this likelihood., Conclusion: University students are at risk of psychological distress in the case of traumatic events. The evolution of the pandemic is uncertain and may have long-term effects on mental health. Therefore, it is crucial to study the most effective interventions to identify vulnerable subgroups and to plan for acute and long-term psychological services to control and reduce the burden of psychological problems.

Healthcare workers are at the forefront against COVID-19, worldwide. Since Fondazione Policlinico Universitario A. Gemelli (FPG) IRCCS was enlisted as a COVID-19 hospital, the healthcare workers deployed to COVID-19 wards were separated from those with limited/no exposure, whereas the administrative staff were designated to work from home. Between 4 June and 3 July 2020, an investigation was conducted to evaluate the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin (IgG) antibodies among the employees of the FPG using point-of-care (POC) and venous blood tests. Sensitivity, specificity, and predictive values were determined with reverse-transcription polymerase chain reaction on nasal/oropharyngeal swabs as the diagnostic gold standard. The participants enrolled amounted to 4777. Seroprevalence was 3.66% using the POC test and 1.19% using the venous blood test, with a significant difference ( p < 0.05). The POC test sensitivity and specificity were, respectively, 63.64% (95% confidence interval (CI): 62.20% to 65.04%) and 96.64% (95% CI: 96.05% to 97.13%), while those of the venous blood test were, respectively, 78.79% (95% CI: 77.58% to 79.94%) and 99.36% (95% CI: 99.07% to 99.55%). Among the low-risk populations, the POC test's predictive values were 58.33% (positive) and 98.23% (negative), whereas those of the venous blood test were 92.86% (positive) and 98.53% (negative). According to our study, these serological tests cannot be a valid alternative to diagnose COVID-19 infection in progress.

Background: The importance of lung recruitment before surfactant administration has been shown in animal studies. Well designed trials in preterm infants are absent. We aimed to examine whether the application of a recruitment manoeuvre just before surfactant administration, followed by rapid extubation (intubate-recruit-surfactant-extubate [IN-REC-SUR-E]), decreased the need for mechanical ventilation during the first 72 h of life compared with no recruitment manoeuvre (ie, intubate-surfactant-extubate [IN-SUR-E])., Methods: We did a randomised, unblinded, controlled trial in 35 tertiary neonatal intensive care units in Italy. Spontaneously breathing extremely preterm neonates (24 + 0 to 27 + 6 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 h of life were randomly assigned (1:1) with a minimisation algorithm to IN-REC-SUR-E or IN-SUR-E using an interactive web-based electronic system, stratified by clinical site and gestational age. The primary outcome was the need for mechanical ventilation in the first 72 h of life. Analyses were done in intention-to-treat and per-protocol populations, with a log-binomial regression model correcting for stratification factors to estimate adjusted relative risk (RR). This study is registered with ClinicalTrials.gov, NCT02482766., Findings: Of 556 infants assessed for eligibility, 218 infants were recruited from Nov 12, 2015, to Sept 23, 2018, and included in the intention-to-treat analysis. The requirement for mechanical ventilation during the first 72 h of life was reduced in the IN-REC-SUR-E group (43 [40%] of 107) compared with the IN-SUR-E group (60 [54%] of 111; adjusted RR 0·75, 95% CI 0·57-0·98; p=0·037), with a number needed to treat of 7·2 (95% CI 3·7-135·0). The addition of the recruitment manoeuvre did not adversely affect the safety outcomes of in-hospital mortality (19 [19%] of 101 in the IN-REC-SUR-E group vs 37 [33%] of 111 in the IN-SUR-E group), pneumothorax (four [4%] of 101 vs seven [6%] of 111), or grade 3 or worse intraventricular haemorrhage (12 [12%] of 101 vs 17 [15%] of 111)., Interpretation: A lung recruitment manoeuvre just before surfactant administration improved the efficacy of surfactant treatment in extremely preterm neonates compared with the standard IN-SUR-E technique, without increasing the risk of adverse neonatal outcomes. The reduced need for mechanical ventilation during the first 72 h of life might facilitate implementation of a non-invasive respiratory support strategy., Funding: None., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Artificial Intelligence (AI) is increasingly used for process management in daily life. In the medical field AI is becoming part of computerized systems to manage information and encourage the generation of evidence. Here we present the development of the application of AI to IT systems present in the hospital, for the creation of a DataMart for the management of clinical and research processes in the field of breast cancer., Materials and Methods: A multidisciplinary team of radiation oncologists, epidemiologists, medical oncologists, breast surgeons, data scientists, and data management experts worked together to identify relevant data and sources located inside the hospital system. Combinations of open-source data science packages and industry solutions were used to design the target framework. To validate the DataMart directly on real-life cases, the working team defined tumoral pathology and clinical purposes of proof of concepts (PoCs)., Results: Data were classified into "Not organized, not 'ontologized' data", "Organized, not 'ontologized' data", and "Organized and 'ontologized' data". Archives of real-world data (RWD) identified were platform based on ontology, hospital data warehouse, PDF documents, and electronic reports. Data extraction was performed by direct connection with structured data or text-mining technology. Two PoCs were performed, by which waiting time interval for radiotherapy and performance index of breast unit were tested and resulted available., Conclusions: GENERATOR Breast DataMart was created for supporting breast cancer pathways of care. An AI-based process automatically extracts data from different sources and uses them for generating trend studies and clinical evidence. Further studies and more proof of concepts are needed to exploit all the potentials of this system.

Flu vaccination for the general population, and specifically for vulnerable subgroups, brings the potential to reduce the impact of the COVID-19 pandemic in terms of mobility, mortality, and hospitalizations. In Italy, flu vaccination is recommended to all ≥6 months of age, even if it is only free of charge for specific categories. We investigated the intentions towards flu and COVID-19 vaccinations from a sample of 436 Italian university students. Results of a web-based survey show that 77.52% of them were willing to get the flu vaccine and 94.73% were willing to be vaccinated against COVID-19 when available. We identified positive predictive factors to undertake flu vaccination as being a medical student, having undertaken a previous vaccination against flu, and having a high level of concern and perceived vulnerability to the COVID-19 pandemic. Reinforced public health activities might consider engaging university students a as possible "positive influencer" towards flu and COVID-19 vaccination programs., Competing Interests: The authors declare no conflict of interest.

Background and Aim: Increased intestinal permeability plays a key role in the pathogenesis of fat deposition in the liver. The aim of our study was to assess whether a single nucleotide polymorphism of protein tyrosine phosphatase non-receptor type 2 (PTPN2) (rs2542151 T→G), involved in intestinal permeability, may be associated with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM)., Methods and Results: We recruited a prospective cohort of NAFLD subjects and matched controls. Clinical data, PTPN2 genotype and laboratory data were collected for each patient. Results were stratified according to liver histology and diabetes. We enrolled 566 cases and 377 controls. PTPN2 genotype distribution did not significantly differ between patients and controls. In the entire population, patients with PTPN2 rs2542151 T→G (dominant model) have a higher prevalence of diabetes; 345 patients (60.9%) underwent liver biopsy: 198 (57.4%) had steatohepatitis and 75 (21.7%) had advanced fibrosis. At multiple logistic regression analysis PTPN2 rs2542151 T→G was associated with T2DM (OR 2.14, 95% CI 1.04-4.40, P = 0.03). Patients who underwent liver biopsy, rs2542151 T→G of PTPN2 was independently associated with severe steatosis (OR 2.00, 95% CI 1.17-3.43, p = 0.01) and severe fibrosis (OR 2.23, 95% CI 1.06-4.72, P = 0.03)., Conclusion: Our study shows that NAFLD patients with rs2542151 T→G of PTPN2 have a higher severity of fatty liver disease and a higher prevalence of T2DM. These results suggest that individual genetic susceptibility to intestinal permeability could play a role in liver disease progression., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: A summary indicator for evaluating the breast cancer network has never been measured at the regional level. The aim is to design treemaps providing a summary description of hospitals (including breast units) and Local Health Units (LHUs) in terms of their levels of performance within the breast cancer network of the Lazio region (central Italy). The treemap structure has an intuitive design and displays information from both general and specific analyses., Methods: Patients admitted to the regional hospitals for malignant breast cancer (MBC) surgery in 2010-2017 were selected in a population-based cohort study. These quality indicators were calculated based on the international guidelines (EUSOMA, ESMO) to assess the performance in terms of volume of activity, surgery procedure, post-surgery assistance and timeliness of medical therapy or radiotherapy beginning. The quality indicators were calculated using administrative health data systematically collected at the regional level and were included in the treemap to represent the surgery or the post-surgery areas of the breast cancer clinical pathway. In order to allow aggregation of scores for different indicators belonging to the same clinical area, up to five evaluation classes were defined using the "Jenks Natural Breaks" algorithm. A score and a colour were assigned to each clinical area based on the ranking of the indicators involved. The analyses were performed on an annual basis, by the LHU of residence and by the hospital which performed the surgical intervention., Results: In 2017, 6218 surgical interventions for MBC were performed in the hospitals of Lazio. The results showed a continuous increase of the level of performance over the years. Hospitals showed higher variability in the levels of performance than the LHUs. 36% of the evaluated hospitals reached a high level of performance. An audit of the S. Filippo Neri breast unit revealed incorrect coding of the input data. For this reason, the score for the indicator for the volume of wards was re-calculated and re-evaluated, with a subsequent improvement of the level of performance. Most LHUs achieved at least an average overall level of performance, with 20% of the LHUs reaching a high level of performance., Conclusions: This is the first attempt to apply the treemap logic to a single clinical network, in order to obtain a summary indicator for the evaluation of the breast cancer care network. Our results supply decision makers with a transparent instrument of governance for heterogeneous users, directing efforts improving and promoting equity of care. The treemaps could be reproduced and adapted for other local contexts, in order to limit inappropriateness and ensure uniform levels of breast cancer care within local areas. The next step is the evaluation of audit and feedback interventions to improve the quality of care and to guarantee homogeneous levels of care throughout the region., Competing Interests: The authors have declared that no competing interests exist.

Objective: Head and neck cancer (HNC) is the sixth leading cancer worldwide with approximately 600,000 new cases per year. Several studies suggest that HNC survivors may have an increased risk of developing second primary cancers (SPCs). A systematic review and meta-analysis was performed aiming to quantify the overall and site-specific risk of metachronous SPCs in HNC survivors., Methods: PubMed, Web of Science and Scopus were searched to identify studies published until October 2019. Studies investigating the standardised incidence ratio (SIR) of metachronous SPC were included. A random-effects meta-analysis was performed to calculate the overall and site-specific SIRs. Newcastle-Ottawa Scale was used to assess the study's quality. Heterogeneity was quantified using the I 2 statistics and explored using meta-regression., Results: Twenty-six studies were included in the systematic review. Studies differed by the definition of metachronous SPC used. For the meta-analyses, the studies were grouped according to these definitions. In the three groups, the overall risk of metachronous SPC was increased. The highest SPC risk was for oropharynx, oesophagus and lung., Conclusions: Head and neck cancer survivors are at increased overall risk of metachronous SPCs. The canonical upper aerodigestive sites, HNLE (head and neck, oesophagus and lung), were the SPC sites with the highest risk., Implication for Cancer Survivors: Our results emphasise the importance of targeted surveillance strategies aimed at early detection and tertiary preventive interventions., (© 2020 John Wiley & Sons Ltd.)

Objective: This study aimed to analyze the effectiveness of root-shape inserts mounted on a reciprocating handpiece during the procedure of root surface debridement (RSD) on extracted teeth. Three different approaches were compared: ultrasonic scaling, employment of root-shape inserts mounted on a reciprocating handpiece, and a combination of both., Materials and Methods: A total of 51 extracted teeth were divided into three groups. The first group was instrumented with an ultrasonic scaler, the second group with flexible root-shape inserts mounted on a reciprocating handpiece (grain size 40, 15, and 4 μm), whereas the final group underwent a combination of both approaches. The time required for the instrumentation was taken. The specimens were subjected to optical and scanning electron microscopy (SEM), and the photographs were evaluated by three examiners who were blinded to the study. The parameters included were: SEM roughness index (SRI) for the roughness calculation, remaining calculus Index (RCI) to evaluate the residual calculus deposits, and loss of tooth substance index (LTSI) to evaluate the loss of tooth substance caused by instrumentation., Result: The results revealed that the time taken for the instrumentation was on average longer when the root-shape inserts were employed alone, meanwhile the combined approach did not show significant difference in comparison with the ultrasonic scaling. The lower average RCI was obtained with a combined approach. The use of root-shape inserts seems to cause a moderate increase in LTSI, especially in a combined approach, whereas it resulted in a better average SRI., Conclusion: The employment of root-shape inserts seems to be effective in the RSD for its ability to obtain a smooth and calculus-free instrumented surface, especially when used in combination with an ultrasonic scaler, and their use can so represent a valid approach to be tested in further in vivo studies., (© 2020 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Lynch syndrome (LS) is an autosomal dominant condition caused by pathogenic variants in mismatch repair (MMR) genes that predispose individuals to different malignancies, such as colorectal cancer (CRC) and endometrial cancer. Current guidelines recommended testing for LS in individuals with newly diagnosed CRC to reduce cancer morbidity and mortality in relatives. Economic evaluations in support of such approach, however, are not available in Italy. We developed a decision-analytic model to analyze the cost-effectiveness of LS screening from the perspective of the Italian National Health System. Three testing strategies: the sequencing of all MMR genes without prior tumor analysis (Strategy 1), a sequential IHC and MS-MLPA analysis (Strategy 2), and an age-targeted strategy with a revised Bethesda criteria assessment before IHC and methylation-specific MLPA for patients ≥ than 70 years old (Strategy 3) were analyzed and compared to the "no testing" strategy. Quality Adjusted Life Years (QALYs) in relatives after colonoscopy, aspirin prophylaxis and an intensive gynecological surveillance were estimated through a Markov model. Assuming a CRC incidence rate of 0.09% and a share of patients affected by LS equal to 2.81%, the number of detected pathogenic variants among CRC cases ranges, in a given year, between 910 and 1167 depending on the testing strategy employed. The testing strategies investigated, provided one-time to the entire eligible population (CRC patients), were associated with an overall cost ranging between €1,753,059.93-€10,388,000.00. The incremental cost-effectiveness ratios of the Markov model ranged from €941.24 /QALY to €1,681.93 /QALY, thus supporting that "universal testing" versus "no testing" is cost-effective, but not necessarily in comparison with age-targeted strategies. This is the first economic evaluation on different testing strategies for LS in Italy. The results might support the introduction of cost-effective recommendations for LS screening in Italy., Competing Interests: The authors have declared that no competing interests exist.

Background: Gastric cancer pathogenesis represents a complex interaction of host genetic determinants, microbial virulence factors and environmental exposures. Our primary aim was to determine the association between occupations/occupational exposures and odds of gastric cancer., Methods: We conducted a pooled-analysis of individual-level data harmonized from 11 studies in the Stomach cancer Pooling Project. Multivariable logistic regression was used to estimate the odds ratio (OR) of gastric cancer adjusted for relevant confounders., Results: A total of 5279 gastric cancer cases and 12 297 controls were analysed. There were higher odds of gastric cancer among labour-related occupations, including: agricultural and animal husbandry workers [odds ratio (OR) 1.33, 95% confidence interval (CI): 1.06-1.68]; miners, quarrymen, well-drillers and related workers (OR 1.70, 95% CI: 1.01-2.88); blacksmiths, toolmakers and machine-tool operators (OR 1.41, 95% CI: 1.05-1.89); bricklayers, carpenters and construction workers (OR 1.30, 95% CI: 1.06-1.60); and stationary engine and related equipment operators (OR 6.53, 95% CI: 1.41-30.19). The ORs for wood-dust exposure were 1.51 (95% CI: 1.01-2.26) for intestinal-type and 2.52 (95% CI: 1.46-4.33) for diffuse-type gastric cancer. Corresponding values for aromatic amine exposure were 1.83 (95% CI: 1.09-3.06) and 2.92 (95% CI: 1.36-6.26). Exposure to coal derivatives, pesticides/herbicides, chromium, radiation and magnetic fields were associated with higher odds of diffuse-type, but not intestinal-type gastric cancer., Conclusions: Based on a large pooled analysis, we identified several occupations and related exposures that are associated with elevated odds of gastric cancer. These findings have potential implications for risk attenuation and could be used to direct investigations evaluating the impact of targeted gastric cancer prevention/early detection programmes based on occupation., (© The Author(s) 2020; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Healthcare systems around the world are facing incredible challenges due to the ageing population and the related disability, and the increasing use of technologies and citizen's expectations. Improving health outcomes while containing costs acts as a stumbling block. In this context, Big Data can help healthcare providers meet these goals in unprecedented ways. The potential of Big Data in healthcare relies on the ability to detect patterns and to turn high volumes of data into actionable knowledge for precision medicine and decision makers. In several contexts, the use of Big Data in healthcare is already offering solutions for the improvement of patient care and the generation of value in healthcare organizations. This approach requires, however, that all the relevant stakeholders collaborate and adapt the design and performance of their systems. They must build the technological infrastructure to house and converge the massive volume of healthcare data, and to invest in the human capital to guide citizens into this new frontier of human health and well-being. The present work reports an overview of best practice initiatives in Europe related to Big Data analytics in public health and oncology sectors, aimed to generate new knowledge, improve clinical care and streamline public health surveillance., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Public Health Association.)

This clinical study retrospectively analyzed cone beam computed tomography (CBCT) images to determine the potential influence of implant inclination on peri-implant marginal bone loss after 18 to 24 months of functional loading. Twenty-five consecutive patients presenting with an edentulous or partially edentulous maxilla or mandible and an adequate bone volume for receiving oral implants were selected for analysis of the marginal bone loss around tilted and/or axial implants. The study population included patients rehabilitated with Toronto bridges (TBs), fixed partial dentures (FPDs), or single crowns (SCs) on axial and/or tilted implants. The primary outcome was the CBCT analysis of peri-implant marginal bone level change, depending on inclination of implants and type of prostheses. The secondary outcome was analysis of survival and success rates of tilted and axial implants. A significant difference was observed for peri-implant buccal bone loss (mean of axials 0.42 ± 0.06; mean of tilted 0.70 ± 0.09) (P = .009). The difference in peri-implant lingual/palatal/mesial/distal bone loss was not significant between axial and tilted implants (P > .05). No significant difference was observed between the marginal bone level and the type of prostheses for both tilted and axial implants in all the assessed sites (P > .05). The success rate for both tilted and axial implants was 100%, and no complications were observed for all the prosthetic rehabilitations, with a 100% survival rate. Compared to axial implants, tilted implants showed a significant statistical difference for peri-implant buccal bone loss, but no other differences were observed for peri-implant bone loss or for implant survival and success rate. Fixed partial or total rehabilitation using tilted or axial implants, or with tilted and axial implants, could be a reliable technique with advantages to patients and operators.

Acid-sensing ion channels (ASICs) are proton-gated channels involved in multiple biological functions such as: pain modulation, mechanosensation, neurotransmission, and neurodegeneration. Earlier, we described the genetic association, within the Nuoro population, between Multiple Sclerosis (MS) and rs28936, located in ASIC2 3'UTR. Here we investigated the potential involvement of ASIC2 in MS inflammatory process. We induced experimental autoimmune encephalomyelitis (EAE) in wild-type (WT), knockout Asic1 -/- and Asic2 -/- mice and observed a significant reduction of clinical score in Asic1 -/- mice and a significant reduction in the clinical score in Asic2 -/- mice in a limited time window (i.e., at days 20-23 after immunization). Immunohistochemistry confirmed the reduction in adaptive immune cell infiltrates in the spinal cord of EAE Asic1 -/- mice. Analysis of mechanical allodynia, showed a significant higher pain threshold in Asic2 -/- mice under physiological conditions, before immunization, as compared to WT mice and Asic1 -/- . A significant reduction in pain threshold was observed in all three strains of mice after immunization. More importantly, analysis of human autoptic brain tissue in MS and control samples showed an increase of ASIC2 mRNA in MS samples. Subsequently, in vitro luciferase reporter gene assays, showed that ASIC2 expression is under possible miRNA regulation, in a rs28936 allele-specific manner. Taken together, these findings suggest a potential role of ASIC2 in the pathophysiology of MS., (© 2018 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: We aimed to survey Delivery Room and Neonatal Intensive Care Unit (NICU) respiratory strategies dedicated to the extremely low gestational age newborn (ELGAN - GA < 28 wks) in Italy., Methods: A questionnaire was sent to 113 Italian level III centres. A lead physician and a nurse with expertise in mechanical ventilation (MV) were identified in each unit to answer. Information about those aspects of ventilatory support considered by center's staff as needing improvement was also collected., Results: A 100% response rate was obtained. In the Delivery Room, sustained lung inflation was performed in 74.8% of centres, and 89.2% used NCPAP. For ELGANs who need invasive MV, conventional MV was the most used strategy. Volume-targeted ventilation and High-frequency oscillatory ventilation (HFOV) were considered as primary mode in < 30% of centres. Among non-invasive strategies, NCPAP was the most utilized, followed by BiPAP, High-flow nasal cannula and nasal intermittent positive pressure ventilation. Nurses more commonly recorded in the nursing charts the ventilator's setting parameters rather than measured ones. HFOV and non-invasive ventilation were the most quoted aspects of neonatal ventilation felt as to be improved., Conclusion: The routine respiratory support practices in Italy showed marked variations among units. Focused interventions are largely required to improve clinical practice.

Background: In Italy, the National Immunization Prevention Plan recommends for adolescents between ages 11 and 18 several vaccines, however their adherence is below the expected coverage. School-based delivery strategies might represent an alternative to primary care settings. This study aims to evaluate the impact of a school-based intervention aimed to increase the vaccination uptake among Italian secondary class students., Methods: One of the four schools in which a school-based multicomponent intervention was previously carried out has been matched with a control school in the same geographical area. Students' coverage for mandatory and recommended vaccinations was assessed before and after an 8 months period using the Local Health Authority Immunization Register., Results: Seven hundred and fifty-five resident students in the RM Local Health Authority were included: 265 from the intervention school, 490 from the control school. At baseline, the two schools were comparable for grades and sex distribution; the intervention school had significant higher immunization rates for Meningococcal B, but lower ones for the 4th dose of dTap. After eight months, higher percentage of students received the HPV (30.5% vs 13.8% of females; p = 0.003) Meningococcal C (6.0% vs 2.0%; p = 0.005) and Meningococcal B (14.7% vs 0.3%; p <0.001) vaccines in the intervention school compared with control. The pre-post differences between the two schools in the immunization rates were significantly higher in the intervention school for the HPV, Meningococcal C and B vaccines., Conclusions: This study demonstrates that a school-based health promotion project was effective in improving the recommended vaccines uptake among adolescents with potential interesting implication for the national target attainment. Considering the importance of informing and educating, innovative school-based health promotion programs could represent an excellent opportunity for the Local Health Authorities to get in touch with a hard-to-reach target. Performance in offering the vaccination in school facilities should be evaluated.

Objective: The early identification of gastric cancer (GC) represents a major clinical challenge. We conducted a systematic review of studies evaluating the miRNA expression profiling as a diagnostic tool in GC., Methods: We performed a search of PubMed, ISI Web of Science and SCOPUS databases for studies on diagnostic miRNAs and GC, published in English up to October 2017. Eligibility criteria included case-control studies evaluating blood or tissue-based miRNA expression profiles, and incorporating at least two detection phases (screening and validation)., Results: We included 27 eligible studies, that reported on 97 deregulated miRNAs either in blood or tissue, out of which 30 were reported in at least two studies. Among 22 studies on tissue-diagnostic miRNAs, 13 consistently upregulated miRNAs (miR-214, miR-21, miR-103, miR-107, miR-196a, miR-196b, miR-7, miR-135b, miR-222, miR-23b, miR-25, miR-92 and miR-93), and six consistently downregulated miRNAs (miR-148a, miR-375, miR-133b, miR-30a, miR-193a and miR-204) were reported. Ten miRNAs with inconsistent direction of expression in tissues were identified. Among the five studies performed on blood samples, only one miRNA was consistently upregulated (miR-20a)., Conclusions: This review shows that some tissue or blood miRNAs may be considered as potential biomarkers for GC diagnosis, that urgently needs to be confirmed from large prospective studies.

Background: Lynch syndrome (LS) is the most frequent form of hereditary colorectal cancer (CRC; up to 3-5% of the total CRC burden) and predisposes to the development of other cancers. Multidisciplinary diagnostic strategies are relevant both to the index cases and to their at-risk relatives, but their implementation is still limited. Our study aimed to explore LS testing practices in Italy., Methods: In order to ascertain the current practice of LS diagnosis and management, we conducted a qualitative assessment by sending a questionnaire to health care professionals at 4 Italian hospitals selected as "models" representing different hospital settings. Based on the surveys, we reconstructed the management pathways for CRC patients in terms of diagnostic strategies and health professionals involved., Results: Seven of the 8 invited professionals filled in the questionnaire. Noncompliance with the latest guidelines was reported, as no tumor "screening" was performed on CRC cases. The lack of a structured multidisciplinary team who manages CRC patients from risk assessment to diagnosis and follow-up was reported. The availability of professionals and laboratory technologies differ widely between hospitals. As for cascade testing of at-risk relatives, a systematic and active approach was absent in all the considered hospitals., Conclusions: Our study shows that no structured and standardized pathways for the diagnosis and management of LS patients are currently in place in Italy. We envisage that by extending our research to further experiences and countries, an increasing awareness of the topic can be translated into a health gain for hereditary CRC patients and their at-risk relatives., (© 2019 S. Karger AG, Basel.)

Medical practitioners are increasingly adopting a personalized medicine (PM) approach involving individually tailored patient care. The Personalized Prevention of Chronic Diseases (PRECeDI) consortium project, funded within the Marie Skłodowska Curie Action (MSCA) Research and Innovation Staff Exchange (RISE) scheme, had fostered collaboration on PM research and training with special emphasis on the prevention of chronic diseases. From 2014 to 2018, the PRECeDI consortium trained 50 staff members on personalized prevention of chronic diseases through training and research. The acquisition of skills from researchers came from dedicated secondments from academic and nonacademic institutions aimed at training on several research topics related to personalized prevention of cancer and cardiovascular and neurodegenerative diseases. In detail, 5 research domains were addressed: (1) identification and validation of biomarkers for the primary prevention of cardiovascular diseases, secondary prevention of Alzheimer disease, and tertiary prevention of head and neck cancer; (2) economic evaluation of genomic applications; (3) ethical-legal and policy issues surrounding PM; (4) sociotechnical analysis of the pros and cons of informing healthy individuals on their genome; and (5) identification of organizational models for the provision of predictive genetic testing. Based on the results of the research carried out by the PRECeDI consortium, in November 2018, a set of recommendations for policy makers, scientists, and industry has been issued, with the main goal to foster the integration of PM approaches in the field of chronic disease prevention., (© 2019 S. Karger AG, Basel.)

Background: A wealth of single-nucleotide polymorphisms (SNPs) responsible for multiple sclerosis (MS) susceptibility have been identified; however, they explain only a fraction of MS heritability., Objectives: We contributed to discovery of new MS susceptibility SNPs by studying a founder population with high MS prevalence., Methods: We analyzed ImmunoChip data from 15 multiplex families and 94 unrelated controls from the Nuoro Province, Sardinia, Italy. We tested each SNP for both association and linkage with MS, the linkage being explored in terms of identity-by-descent (IBD) sharing excess and using gene dropping to compute a corresponding empirical p -value. By targeting regions that are both associated and in linkage with MS, we increase chances of identifying interesting genomic regions., Results: We identified 486 MS-associated ( p  < 1 × 10 -4 ) and 18,426 MS-linked ( p  < 0.05) SNPs. A total of 111 loci were both linked and associated with MS, 18 of them pointing to 14 non-major histocompatibility complex (MHC) genes, and 93 of them located in the MHC region., Conclusion: We discovered new suggestive signals and confirmed some previously identified ones. We believe this to represent a significant step toward an understanding of the genetic basis of MS.

Recurrence and second primary cancer (SPC) continue to represent major obstacles to long-term survival in head and neck cancer (HNC). Our aim was to evaluate whether established demographics, lifestyle-related risk factors for HNC and clinical data are associated with recurrence and SPC in HNC. We conducted a multicentre study by using data from five studies members of the International Head and Neck Cancer Epidemiology consortium-Milan, Rome, Western Europe, Sao Paulo, and Japan, totalling 4005 HNC cases with a median age of 59 (interquartile range 52-67). Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for recurrence and SPC. During follow-up, 1161 (29%) patients had recurrence and 343 (8.6%) developed SPC. Advanced tumour stage was associated with increased risk of recurrence in HNC overall (HR = 1.76, 95% CI 1.41-2.19). Women with laryngeal cancer had a reduced risk of recurrence compared to men (HR = 0.39, 95% CI: 0.24-0.74). Concerning predictors of SPC, advanced age (HR = 1.02; 95% CI: 1.00-1.04) and alcohol consumption (> 1 drink per day, HR = 2.11; 95% CI: 1.13-3.94) increased the risk of SPC among patients with laryngeal cancer. Additionally, women were at higher risk of SPC, in HNC overall group (HR = 1.68; 95% CI: 1.13-2.51) and oropharyngeal cancer group (HR = 1.74; 95% CI: 1.02-2.98). Tumour stage and male gender (larynx only) were positive predictors of cancer recurrence in HNC patients. Predictors of SPC were advanced age and alcohol use among laryngeal cancer cases, and female gender for oropharyngeal and HNC overall.

Objective: To evaluate if weaning from high-frequency oscillatory ventilation (HFOV) directly to a non-invasive mode of respiratory support is feasible and results in successful extubation in extremely low birth weight (ELBW) infants., Design: Prospective observational study., Setting: Tertiary neonatal intensive care unit., Patients: One hundred and eight ELBW infants of 26.2±1.4 weeks of gestational age (GA) directly extubated from HFOV., Interventions: All infants were managed with elective HFOV and received surfactant after a recruitment HFOV manoeuvre. Extubation was attempted at mean airways pressure (MAP) ≤6 cm H 2 O with FiO 2 ≤0.25. After extubation, all infants were supported by nasal continuous positive airway pressure (6-8 cm H 2 O)., Main Outcome Measures: Extubation failure (clinical deterioration requiring reintubation) was defined as shorter than 7 days., Results: Ninety patients (83%) were successfully extubated and 18 (17%) required reintubation. No significant differences were found between the two groups in terms of birth weight, day of life and weight at the time of extubation. Multivariable analysis showed that GA (OR 1.71; 95% CI 1.04, 2.08) and higher MAP prior to surfactant (OR 1.51; 95% CI 1.06, 2.15) were associated with successful extubation., Conclusions: In ELBW infants, direct extubation from HFOV at MAP ≤6 cm H 2 O with FiO 2 ≤0.25 is feasible. Our extubation success rate (83%) is higher than conventional mechanical ventilation in this very vulnerable class of infants., Competing Interests: Competing interests: None declared.

Objective Various genome-wide association studies (GWASs) identified new head and neck cancer (HNC) susceptibility loci, although the evidence has not been systematically summarized. We performed a systematic review and meta-analyses of the GWASs to identify the most commonly reported genetic loci associated with a risk of HNC. Data Sources We searched the PubMed, ISI Web of Science, SCOPUS, and GWAS databases to retrieve eligible studies, in English or Italian, published until June 1, 2017. Review Methods Only GWASs reporting data on the association between single-nucleotide polymorphisms (SNPs) and HNC were included. The quality of included studies was evaluated using the Q-Genie tool. Random-effect meta-analyses were performed considering only SNPs with at least 1 significant result from the included articles, and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results Seven studies of case-control design were included in the review. Five studies on nasopharyngeal cancer (NPC) in Chinese, reporting on 27 different SNPs, were included in meta-analyses. Results show that 6 SNPs ( rs2076483, rs2975042, rs9258122, rs29232, and rs9510787) had an increased pooled estimates for A risk alleles (OR [95% CI]: 1.55 [1.36-1.77], 1.90 [1.69-2.14], 1.47 [1.31-1.65], 1.52 [1.32-1.76], and 1.22 [1.13-1.31], respectively) while G risk allele of rs3129055 reported an OR of 1.49 (95% CI, 1.33-1.67). Conclusion Our systematic review identified 5 SNPs located on chromosome 6 ( rs2076483, rs2975042, rs3129055, rs9258122, and rs29232) and 1 ( rs9510787) on chromosome 13 as significantly associated with an increased risk of NPC in Chinese.

Purpose: Lynch syndrome (LS) screening can significantly reduce cancer morbidity and mortality in mutation carriers. Our aim was to identify cost-effective LS screening programs that can be implemented in the "real world.", Methods: We performed a systematic review of full economic evaluations of genetic screening for LS in different target populations; health outcomes were estimated in life-years gained or quality-adjusted life-years., Results: Overall, 20 studies were included in the systematic review. Based on the study populations, we identified six categories of LS screening program: colorectal cancer (CRC)-based, endometrial cancer-based, general population-based, LS family registry-based, cascade testing-based, and genetics clinic-based screening programs. We performed an in-depth analysis of CRC-based LS programs, classifying them into three additional subcategories: universal, age-targeted, and selective. In five studies, universal programs based on immunohistochemistry, either alone or in combination with the BRAF test, were cost-effective compared with no screening, while in two studies age-targeted programs with a cutoff of 70 years were cost-effective when compared with age-targeted programs with lower age thresholds., Conclusion: Universal or <70 years-age-targeted CRC-based LS screening programs are cost-effective and should be implemented in the "real world."

Objective: To compare short-term application of nasal high-frequency oscillatory ventilation (nHFOV) with nasal continuous positive airway pressure (nCPAP)., Working Hypothesis: nHFOV improves CO 2 removal with respect to nCPAP in preterm infants needing noninvasive respiratory support and persistent oxygen supply after the first 72 h of life., Study Design: Multicenter non-blinded prospective randomized crossover study., Patient Selection: Thirty premature infants from eight tertiary neonatal intensive care units, of mean ± SD 26.4 ± 1.8 weeks of gestational age and 921 ± 177 g of birth weight., Methodology: Infants were randomly allocated in a 1:1 ratio to receive a starting treatment mode of either nCPAP or nHFOV delivered by the ventilator CNO (Medin, Germany), using short binasal prongs of appropriate size. A crossover design with four 1-h treatment periods was used, such that each infant received both treatments twice. The primary outcome was the mean transcutaneous partial pressure of CO 2 (TcCO 2 ) value during the 2-h cumulative period of nHFOV compared with the 2-h cumulative period of nCPAP., Results: Significantly lower TcCO 2 values were observed during nHFOV compared with nCPAP: 47.5 ± 7.6 versus 49.9 ± 7.2 mmHg, respectively, P = 0.0007. A different TcCO 2 behavior was found according to the random sequence: in patients starting on nCPAP, TcCO 2 significantly decreased from 50.0 ± 8.0 to 46.6 ± 7.5 mmHg during nHFOV (P = 0.001). In patients starting on nHFOV, TcCO 2 slightly increased from 48.5 ± 7.8 to 49.9 ± 6.7 mmHg during nCPAP (P = 0.13)., Conclusions: nHFOV delivered through nasal prongs is more effective than nCPAP in improving the elimination of CO 2 ., (© 2018 Wiley Periodicals, Inc.)

This study aims to summarize the current knowledge on the relationship between genetic polymorphisms, occupational exposures, and urinary tract cancers. We searched MEDLINE, ISI Web of science, and SCOPUS online databases for all articles published in English language up to September 2016. A meta-analysis was performed to provide summary estimates for the association between a certain genetic polymorphism, occupational exposure and bladder cancer (BC) or kidney cancer (KC), when appropriate. Fifteen studies on BC and six on KC were deemed eligible for the review. With regard to BC, an overall odds ratio (OR) of 2.07 [95% confidence interval (CI): 1.38-3.09] for those with GSTM1 and an OR of 2.07 (95% CI: 1.38-3.09) for those with GSTT1 null genotype were reported when exposed to polycyclic aromatic hydrocarbons (PAHs). NAT2 slow genotype carriers had an OR of 3.59 (95% CI: 2.62-4.93) for BC when exposed to aromatic amines and an OR of 2.07 (95% CI: 1.36-3.15) when exposed to PAHs. With regard to KC and pesticide exposure, the meta-analysis reported an OR of 4.38 (95% CI: 2.28-8.41) for GSTM1 present genotype, an OR of 2.59 (95% CI: 1.62-4.15) for GSTT1-present genotype and an OR of 6.51 (95% CI: 2.85-14.89) for combined effects of GSTM1 and GSTT1 active genotypes. This meta-analysis indicates a possible association between the variant genotypes of GSTM1, GSTT1, NAT2 and SULT1A1, occupational exposure to aromatic amines or PAHs, and development of BC. Our results suggest that polymorphisms in GSTM1 and GSTT1 genes could influence the risk for developing KC in individuals occupationally exposed to pesticides.

The risk of Helicobacter pylori (HP) infection, as well as gastric cancer (GC), in association with genetic polymorphisms of gene encoding for mucins, has been investigated with contradictory results. We carried out this systematic review and meta-analysis to summarize the relationship between MUC1, MUC5AC, and MUC6 polymorphisms and HP infection, as well as GC risk. We searched MEDLINE, ISI Web of Science, Scopus bibliographic databases and the HuGE Navigator database. Odds ratios (ORs) and 95% confidence interval (CI) were calculated to assess the association between the genetic polymorphisms, and HP/GC risk. A random-effect model was used to calculate the pooled ORs, overall and by ethnicity. Twenty-one studies were included, of which five on HP and 18 on GC, of which two were in common. The meta-analysis of 10 studies on the MUC1 rs4072037 polymorphism and GC risk reported an OR of 0.66 (95% CI: 0.57-0.78) for the dominant model (AG/GG vs. AA). When stratifying for ethnicity, an OR of 0.73 (95% CI: 0.62-0.86) was reported for the Asian population and an OR of 0.48 (95% CI: 0.38-0.61) was reported for the White population. Our study confirms the protective effect of MUC1 rs4072037 polymorphism on the risk of GC under the dominant model. Further studies reporting information on HP status in cases and controls would be required to evaluate whether the protective effect of MUC1 protein might be attributable to a protective effect towards the HP infection, or through different mechanisms.

Background: Individual participant data pooled analyses allow access to non-published data and statistical reanalyses based on more homogeneous criteria than meta-analyses based on systematic reviews. We quantified the impact of publication-related biases and heterogeneity in data analysis and presentation in summary estimates of the association between alcohol drinking and gastric cancer., Methods: We compared estimates obtained from conventional meta-analyses, using only data available in published reports from studies that take part in the Stomach Cancer Pooling (StoP) Project, with individual participant data pooled analyses including the same studies., Results: A total of 22 studies from the StoP Project assessed the relation between alcohol intake and gastric cancer, 19 had specific data for levels of consumption and 18 according to cancer location; published reports addressing these associations were available from 18, 5 and 5 studies, respectively. The summary odds ratios [OR, (95%CI)] estimate obtained with published data for drinkers vs. non-drinkers was 10% higher than the one obtained with individual StoP data [18 vs. 22 studies: 1.21 (1.07-1.36) vs. 1.10 (0.99-1.23)] and more heterogeneous (I 2 : 63.6% vs 54.4%). In general, published data yielded less precise summary estimates (standard errors up to 2.6 times higher). Funnel plot analysis suggested publication bias., Conclusion: Meta-analyses of the association between alcohol drinking and gastric cancer tended to overestimate the magnitude of the effects, possibly due to publication bias. Additionally, individual participant data pooled analyses yielded more precise estimates for different levels of exposure or cancer subtypes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Tobacco smoking is one of the main risk factors for gastric cancer, but the magnitude of the association estimated by conventional systematic reviews and meta-analyses might be inaccurate, due to heterogeneous reporting of data and publication bias. We aimed to quantify the combined impact of publication-related biases, and heterogeneity in data analysis or presentation, in the summary estimates obtained from conventional meta-analyses. We compared results from individual participant data pooled-analyses, including the studies in the Stomach Cancer Pooling (StoP) Project, with conventional meta-analyses carried out using only data available in previously published reports from the same studies. From the 23 studies in the StoP Project, 20 had published reports with information on smoking and gastric cancer, but only six had specific data for gastric cardia cancer and seven had data on the daily number of cigarettes smoked. Compared to the results obtained with the StoP database, conventional meta-analyses overvalued the relation between ever smoking (summary odds ratios ranging from 7% higher for all studies to 22% higher for the risk of gastric cardia cancer) and yielded less precise summary estimates (SE ≤2.4 times higher). Additionally, funnel plot asymmetry and corresponding hypotheses tests were suggestive of publication bias. Conventional meta-analyses and individual participant data pooled-analyses reached similar conclusions on the direction of the association between smoking and gastric cancer. However, published data tended to overestimate the magnitude of the effects, possibly due to publication biases and limited the analyses by different levels of exposure or cancer subtypes.

With the aim to dissect the effect of adult height on head and neck cancer (HNC), we use the Mendelian randomization (MR) approach to test the association between genetic instruments for height and the risk of HNC. 599 single nucleotide polymorphisms (SNPs) were identified as genetic instruments for height, accounting for 16% of the phenotypic variation. Genetic data concerning HNC cases and controls were obtained from a genome-wide association study. Summary statistics for genetic association were used in complementary MR approaches: the weighted genetic risk score (GRS) and the inverse-variance weighted (IVW). MR-Egger regression was used for sensitivity analysis and pleiotropy evaluation. From the GRS analysis, one standard deviation (SD) higher height (6.9 cm; due to genetic predisposition across 599 SNPs) raised the risk for HNC (Odds ratio (OR), 1.14; 95% Confidence Interval (95%CI), 0.99-1.32). The association analyses with potential confounders revealed that the GRS was associated with tobacco smoking (OR = 0.80, 95% CI (0.69-0.93)). MR-Egger regression did not provide evidence of overall directional pleiotropy. Our study indicates that height is potentially associated with HNC risk. However, the reported risk could be underestimated since, at the genetic level, height emerged to be inversely associated with smoking.

Background: Bioelectrical impedance analysis (BIA) is an inexpensive, non-invasive and fast method to assess body composition. Little is known of the interaction between anti IL 12/23 treatment and body composition. The aim of this study was to evaluate 6- and 12-month changes in body weight, Body Mass Index (BMI) and body composition assessed by BIA in psoriatic patients treated with anti-IL-12/23., Research Design and Methods: Demographic and clinical data were collected for each enrolled patient. Physical examination, anthropometric assessment, Psoriasis Area and Severity Index (PASI) assessment and body composition by BIA (single-frequency 50 kHz), were assessed at baseline and at 6 and 12 months of treatment., Results: A significant decrease in body weight, compared to baseline, in BMI, Fat Mass at month 6 and a significant increase at month 12 for body cellular mass (BCM) and Phase Angle (PhA) were observed. In addition, a significant increase was found for intracellular water., Conclusion: At baseline, psoriatic patients showed a lower BCM and a lower mean PhA score. During ustekinumab treatment, the mean PhA and BCM scores increased with an improvement in psoriatic disease. Thus, ustekinumab can be an effective drug for improving not only psoriasis but also the general clinical status of patients.