The prevalence and incidence of thrombotic primary antiphospholipid syndrome in adults aged 18-49 years: A population-based study in a mountain community in northern Italy.

OBJECTIVE: To estimate prevalence and incidence of thrombotic Primary Antiphospholipid Syndrome (PAPS) in the general population aged 18-49 years. METHODS: The study was carried out in Valtrompia, a valley in northern Italy, in 2011-2015. The identification of PAPS cases leveraged three integrated sources: 1) Rheumatology Unit at the University Hospital; 2) General Practitioners; 3) hospital discharge codes of patients admitted for thrombotic events. RESULTS: Prevalence and incidence were estimated as 22.9 (95% C.I. 11.4-41.0) and 5.0 (2.6-8.7) cases per 100,000 individuals, respectively. The estimates were 28.3 and 4.8, and 17.2 and 5.1 in males and females, respectively. The type of disease onset was mainly of arterial type in men and venous in women. CONCLUSIONS: Thrombotic PAPS was found to be a rare disease in this population-based study. Prevalence and incidence were not significantly different between males and females aged 18-49 years, but a different type of onset was observed.

Public risk perception of air pollution in the general population of Italy and Sweden during the COVID-19 pandemic: Environmental and socio-demographic drivers.

Air pollution is an important anthropogenic hazard due to its effect on human health and the environment. Understanding how the population perceives the risk associated with air pollution is a crucial aspect to inform future policies and communication strategies. The aim of this study is to examine the association between air pollution concentrations and public risk perception of air pollution, also exploring socio-demographic patterns in the general population of Italy and Sweden. To this end, we derived 3-year PM10 average concentrations from ground monitoring stations and integrated with a population-based survey carried out in August 2021 in both countries. Relative perceived likelihood and impact on the individual were considered as domains of risk perception. In addition this, information on direct experience and socio-demographic factors were included as possible determinants of risk perception. Linear regression models were performed to examine the association of PM10 average concentrations at regional level and individual level factors with risk perception domains. In both countries, respondents who live in the most densely populated regions report a higher perceived likelihood of air pollution. Direct experience is the main driver of risk perception in both countries. Being male and smokers in Italy, older age and having left/centre-left political orientation in both countries are associated with a higher perceived likelihood and impact of air pollution. These findings will inform future health and environmental studies regarding the public risk perception of air pollution highlighting individual's awareness and the socio-demographic patterns.

Microsurgical transcranial approaches to the posterior surface of petrosal portion of the temporal bone: quantitative analysis of surgical volumes and exposed areas.

Different microsurgical transcranial approaches (MTAs) have been described to expose the posterior surface of the petrous bone (PPB). A quantitative, anatomical comparison of the most used MTAs, for specific areas of the PPB, is not available. Anatomical dissections were performed on five formalin-fixed, latex-injected cadaver heads (10 sides). Six MTAs were analyzed: Kawase approach (KWA), retrosigmoid approach (RSA), retrosigmoid approach with suprameatal extension (RSAS), retrolabyrinthine approach (RLA), translabyrinthine approach (TLA), and transcochlear approach (TCA). Surgical volumes and exposed areas of each approach were quantified with a dedicated neuronavigation system (ApproachViewer, part of GTx-Eyes II, University Health Network, Toronto, Canada) and adjuvant software (ITK-SNAP and Autodesk Meshmixer 3.5). Areas and volumes were compared using linear mixed models. TCA provided the best exposure of Trautmann's triangle and the retromeatal, suprameatal, meatal, and premeatal regions. RSAs provided the best exposure of the inframeatal region, with RSAS gaining significant exposure of the suprameatal region. KWA had the highest surgical volume, and RLA the lowest. Transpetrosal approaches offer the widest exposure of PPB proportionally to their invasiveness. Retrosigmoid approaches, which get to the studied region through a postero-lateral path, are paramount for the exposure of the inframeatal and suprameatal region and, given the adequate exposure of the remaining PPB, represent an effective approach for the cerebellopontine angle (CPA). These anatomical findings must be considered with approach-related morbidity and the pathological features in order to choose the most appropriate approach in clinical practice.

Country differences in the cross-sectional associations between smoking and depressive symptoms in adolescence.

BACKGROUND: The aim of the present study was to compare the cross-sectional association between smoking and depressive symptoms among adolescents between Sweden and Italy, two countries historically characterized by different norms about tobacco use and different tobacco control efforts. METHODS: A cross-sectional study including 3283 adolescents 15-16 years of age participating in the Swedish KUPOL study and 1947 same-age adolescents from the Italian BE-TEEN study. Current smoking was defined as any smoking in the past 30 days. Depressive symptoms were assessed using the Centre for Epidemiological Studies Depression Scale for Children (CES-DC) and the internalizing score of the Strengths and Difficulties Questionnaire (SDQ). Country differences were explored in stratified and interaction analyses. RESULTS: Current smoking was associated with a 2- to 3-fold increased odds of depressive symptoms among Swedish adolescents using both CES-DC and SDQ internalizing scale. Among Italian adolescents, slightly lower increased odds of 1.5-2.5 for depressive symptoms with smoking were found using the CES-DC but not the SDQ scale. Both multiplicative and additive interactions for country were significant. The association between smoking and depressive symptoms was weaker among Italian compared with Swedish adolescents for both scores. CONCLUSIONS: Countries with different tobacco norms and control show different associations between smoking and depressive symptoms in adolescence, probably due to different psychosocial profiles of smokers. These findings need to be considered when planning tobacco prevention programmes, e.g. by focusing on early detection of mental health distress among adolescents in settings with declining smoking prevalence and restrictive tobacco control environments.

Quantitative Anatomic Comparison of Endoscopic Transnasal and Microsurgical Transcranial Approaches to the Anterior Cranial Fossa.

BACKGROUND: Several microsurgical transcranial approaches (MTAs) and endoscopic transnasal approaches (EEAs) to the anterior cranial fossa (ACF) have been described. OBJECTIVE: To provide a preclinical, quantitative, anatomic, comparative analysis of surgical approaches to the ACF. METHODS: Five alcohol-fixed specimens underwent high-resolution computed tomography. The following approaches were performed on each specimen: EEAs (transcribriform, transtuberculum, and transplanum), anterior MTAs (transfrontal sinus interhemispheric, frontobasal interhemispheric, and subfrontal with unilateral and bilateral frontal craniotomy), and anterolateral MTAs (supraorbital, minipterional, pterional, and frontotemporal orbitozygomatic approach). An optic neuronavigation system and dedicated software (ApproachViewer, part of GTx-Eyes II-UHN) were used to quantify the working volume of each approach and extrapolate the exposure of different ACF regions. Mixed linear models with random intercepts were used for statistical analyses. RESULTS: EEAs offer a large and direct route to the midline region of ACF, whose most anterior structures (ie, crista galli, cribriform plate, and ethmoidal roof) are also well exposed by anterior MTAs, whereas deeper ones (ie, planum sphenoidale and tuberculum sellae) are also well exposed by anterolateral MTAs. The orbital roof region is exposed by both anterolateral and lateral MTAs. The posterolateral region (ie, sphenoid wing and optic canal) is well exposed by anterolateral MTAs. CONCLUSION: Anterior and anterolateral MTAs play a pivotal role in the exposure of most anterior and posterolateral ACF regions, respectively, whereas midline regions are well exposed by EEAs. Furthermore, certain anterolateral approaches may be most useful when involvement of the optic canal and nerves involvement are suspected.

Salvage surgery in recurrent sinonasal cancers: Proposal for a prognostic model based on clinicopathologic and treatment-related parameters.

BACKGROUND: Evidence on survival and major prognosticators after salvage surgery in recurrent sinonasal cancers (SNC) is limited. METHODS: A retrospective, single-center study of recurrent SNC treated with salvage surgery between 1997 and 2019 was conducted. Univariate and multivariable analyses were performed to define a prognostic score for overall survival (OS). RESULTS: One hundred and eighteen patients were included. Recurrent SNC originated mostly in the naso-ethmoidal box (67.8%) and were mainly epithelial (76.2%), high-grade (49.2%), and locally advanced (rpT4, 60.1%) malignancies. Negative margins were achieved in 56.6% of cases. Two- and 5-year OS were 71.7% and 56%, respectively. The prognostic model included treatment modality for primary tumor, histology, rpT class, margin status, perineural invasion, and adjuvant radiotherapy and stratified patients into three prognostic groups (5-year OS: 84.4%, 44.9%, and 0%, respectively). CONCLUSIONS: Treatment of recurrent SNC can result in good long-term survival estimates with limited morbidity. Our score can provide excellent prognostic stratification.

COVID-19 vaccine hesitancy in Sweden and Italy: The role of trust in authorities.

BACKGROUND: The success of vaccination campaigns against COVID-19 infection is vital for moving from a COVID-19 pandemic to an endemic scenario. We aimed to unravel the influence of the risk perception of epidemics along with individual and contextual factors on adherence to COVID-19 vaccination campaigns in Italy and Sweden. METHODS: We compared the results of two nationwide surveys carried out in August 2021 across four domains of epidemic risk perception: perceived likelihood, perceived impact on the individual and perceived individual and authority knowledge. The roles of individual and contextual determinants were also explored. RESULTS: The survey included 2144 participants in Sweden (52.3% women) and 2010 in Italy (52.6% women). In both countries, we found that trust in authorities was one of the main drivers of this process, with two-fold increased odds of being vaccinated. Being highly educated and having a higher relative income were associated with a higher adherence to the vaccination campaign (for relative income OR = 1.44, 95% CI 1.23-1.67 in Sweden and OR = 1.18, 95% CI 1.04-1.34 in Italy; for education OR = 1.90, 95% CI 1.30-2.77 in Sweden and OR = 1.47, 95% CI 1.09-1.97 in Italy), whereas a right and centre-right compared with a left and centre-left political orientation was negatively related to vaccination adherence (OR = 0.41, 95% CI 0.25-0.67 in Sweden and OR = 0.47, 95% CI 0.33-0.68 in Italy). CONCLUSIONS: Increasing trust in authorities, along with an equal global distribution of vaccine doses, can contribute to accelerating vaccination campaigns around the world and, in turn, to move towards an endemic scenario.

The MUSES∗: a prognostic study on 1360 patients with sinonasal cancer undergoing endoscopic surgery-based treatment: ∗MUlti-institutional collaborative Study on Endoscopically treated Sinonasal cancers.

BACKGROUND: Over the last 2 decades, transnasal endoscopic surgery (TES) has become the most frequently employed surgical technique to treat sinonasal malignancies. The rarity and heterogeneity of sinonasal cancers have hampered large non-population-based analyses. METHODOLOGY: All patients receiving TES-including treatment between 1995 and 2021 in 5 referral hospitals were included. A prognostic study was performed, and multivariable models were transformed into nomograms. Training and validation sets were based on results from 3 European and 2 non-European centres, respectively. RESULTS: The training and validation set included 940 and 420 patients, respectively. The mean age at surgery, primary-versus-recurrent presentation, histology distribution, type of surgery, T category and type of adjuvant treatment were differently distributed in the training and validation set. In the training set, 5-year overall survival and recurrence-free survival with a 95%-confidence interval were 72.7% (69.5-76.0%) and 66.4% (63.1-69.8%), respectively, significantly varying with histology. At multivariable analyses, age, gender, previous treatment, the extent of resection on the cranial, lateral and posterolateral axes, grade/subtype, T category, nodal status, margin status and adjuvant treatment were all associated with different prognostic outcomes, displaying a heterogeneous significance and effect size according to histology. The internal and external validation of nomograms was satisfactory (optimism-corrected C-index >0.7 and cumulative area under curve >0.7) for all histologies but mucosal melanoma. CONCLUSIONS: Outcomes of TES-based treatment of sinonasal cancers vary substantially with histology. This large, non-population-based study provides benchmark data on the prognosis of sinonasal cancers that are deemed suitable for treatment including TES.

Epidemic risk perceptions in Italy and Sweden driven by authority responses to COVID-19.

Understanding public risk perception is an essential step to develop effective measures reducing the spread of disease outbreaks. Here we compare epidemic risk perceptions during two different periods of the COVID-19 pandemic in Italy and Sweden. To this end, we analyzed the results of two nationwide surveys carried out in both countries in two periods characterized by different infection rates: August (N = 4154) and November 2020 (N = 4168). Seven domains of epidemic risk perception were considered: likelihood along with (individual and population) impact, preparedness, and knowledge. The role of the context and period was explored in stratified and formal interaction analyses. In both countries, we found an intensification in epidemic risk perception from August to November 2020. Being male, older and having a higher relative income were associated with a lower perception of the likelihood of epidemics, while excess mortality was marginally related to higher odds. Compared to Sweden, Italy had a higher increase in perception of likelihood and impact, and a concurrent decrease in preparedness and knowledge. The different authority response to the COVID-19 pandemic is associated with a different change over time in risk perception. Regional differences in terms of excess mortality only marginally explained differences in risk perception.

Do the Benefits of School Closure Outweigh Its Costs?

School closure has been a common response to COVID-19. Yet, its implementation has hardly ever been based on rigorous analysis of its costs and benefits. We aim to first illustrate the unintended consequences and side effects of school closure, and then discuss the policy and research implications. This commentary frames evidence from the most recent papers on the topic from a public-health epidemiology and disaster risk reduction perspective. In particular, we argue that the benefits of school closure in terms of reduced infection rates should be better compared with its costs in terms of both short- and long-term damage on the physical, mental, and social well-being of children and society at large.

DNA methylation of the glucocorticoid receptor gene predicts substance use in adolescence: longitudinal data from over 1000 young individuals.

Early life stress has been linked to increased methylation of the Nuclear Receptor Subfamily 3 Group C Member 1 (NR3C1) gene, which codes for the glucocorticoid receptor. Moreover, early life stress has been associated with substance use initiation at a younger age, a risk factor for developing substance use disorders. However, no studies to date have investigated whether NR3C1 methylation can predict substance use in young individuals. This study included adolescents 13-14 years of age that reported no history of substance use at baseline, (N = 1041; males = 46%). Participants contributed saliva DNA samples and were followed in middle adolescence as part of KUPOL, a prospective cohort study of 7th-grade students in Sweden. Outcome variables were self-reports of (i) recent use, (ii) lifetime use, and (iii) use duration of (a) alcohol, (b) tobacco products, (c) cannabis, or (d) any substance. Outcomes were measured annually for three consecutive years. The predictor variable was DNA methylation at the exon 1 F locus of NR3C1. Risk and rate ratios were calculated as measures of association, with or without adjustment for internalizing symptoms and parental psychiatric disorders. For a subset of individuals (N = 320), there were also morning and afternoon salivary cortisol measurements available that were analyzed in relation to NR3C1 methylation levels. Baseline NR3C1 hypermethylation associated with future self-reports of recent use and use duration of any substance, before and after adjustment for potential confounders. The overall estimates were attenuated when considering lifetime use. Sex-stratified analyses revealed the strongest association for cigarette use in males. Cortisol analyses revealed associations between NR3C1 methylation and morning cortisol levels. Findings from this study suggest that saliva NR3C1 hypermethylation can predict substance use in middle adolescence. Additional longitudinal studies are warranted to confirm these findings.

Quantitative Anatomic Comparison of Microsurgical Transcranial, Endoscopic Endonasal, and Transorbital Approaches to the Spheno-Orbital Region.

BACKGROUND: The spheno-orbital region (SOR) is a complex anatomic area that can be accessed with different surgical approaches. OBJECTIVE: To quantitatively compare, in a preclinical setting, microsurgical transcranial approaches (MTAs), endoscopic endonasal transpterygoid approach (EEA), and endoscopic transorbital approaches (ETOAs) to the SOR. METHODS: These approaches were performed in 5 specimens: EEA, ETOAs (superior eyelid and inferolateral), anterolateral MTAs (supraorbital, minipterional, pterional, pterional-transzygomatic, and frontotemporal-orbitozygomatic), and lateral MTAs (subtemporal and subtemporal transzygomatic). All specimens underwent high-resolution computed tomography; an optic neuronavigation system with dedicated software was used to quantify working volume and exposed area for each approach. Mixed linear models with random intercepts were used for statistical analyses. RESULTS: Anterolateral MTAs offer a direct route to the greater wings (GWs) and lesser wings (LWs); only they guarantee exposure of the anterior clinoid. Lateral MTAs provide access to a large area corresponding to the GW, up to the superior orbital fissure (SOF) anteriorly and the foramen rotundum medially. ETOAs also access the GW, close to the lateral portion of SOF, but with a different angle of view as compared to lateral MTAs. Access to deep and medial structures, such as the lamina papyracea and the medial SOF, is offered only by EEA, which exposes the LW and GW only to a limited extent. CONCLUSION: This is the first study that offers a quantitative comparison of the most used approaches to SOR. A detailed knowledge of their advantages and limitations is paramount to choose the ideal one, or their combination, in the clinical setting.

Symptoms of mental health problems among Italian adolescents in 2017-2018 school year: a multicenter cross-sectional study.

BACKGROUND: Identifying individual and contextual factors that influence adolescent well-being is a research priority. This study aimed to assess the prevalence of symptoms of mental health problems and some related factors in Italian adolescents in 2017-2018. METHODS: The present study was a cross-sectional survey among 3002 students aged 15-16 years who resided in two Italian provinces, in North and South Italy. Symptoms of mental health problems were assessed using the SDQ and CES-DC, and students' risk-taking behaviors and school climate perception were assessed. All information was collected anonymously. Logistic regression models were used to assess the associations of tobacco and alcohol use, screen time, bullying, and school climate with symptoms of mental health problems. RESULTS: One student out of five reported symptoms of mental health problems, with a more than double proportion among girls than boys (28.7% vs 10.4% with depressive symptoms, respectively). Thirty percent and 40% of students smoked tobacco or drank alcoholic beverages at least once in the past month, and more than 40% reported being victims or authors of bullying in the past 6 months. Smoking behavior, alcohol consumption, screen time, bullying, and negative school climate had 1.2- to 3.3-fold increased odds of symptoms of mental health problems without substantial differences between sexes and geographical areas. CONCLUSIONS: Tobacco and alcohol use, screen time, bullying, and school climate were independently associated with symptoms of mental health problems in a large sample of 15-16-year-old Italian adolescents without substantial gender and geographical differences.

No association of cigarette smoking and depressive symptoms with cortisol concentration in adolescents. Results from a population-based Swedish cohort.

Several studies have shown that smoking increases the risk of depressive symptoms, and suggested a possible role of the hypothalamic-pituitary-adrenal axis in the smoking-depression pathway. This study aimed to assess if smokers have higher cortisol levels than non-smokers, and if higher cortisol levels are associated with depressive symptoms. Saliva samples were collected from a subgroup of 409 participants at enrolment (13-14 years old) and two years later (15-16 years old). First, we examined the association between smoking phenotypes and cortisol concentration. Second, we evaluated whether these associations differed between adolescents with and without depressive symptoms. The mean difference between smokers and non-smokers in cortisol concentrations was close to zero at both time points. For instance, the adjusted mean difference for morning cortisol concentration between current and non-current smokers was 0.000 µg/dl [95% CI -0.055, 0.056]. In addition, there were no differences in cortisol concentration at the second time-point between those who had smoked and those who did not during the two previous years. Moreover, cortisol levels were not associated with depressive symptoms. The hypothesis that dysregulation of the hypothalamic-pituitary-adrenal axis might be involved in the association between smoking behavior and depressive symptoms during adolescence was not supported by this data.

Is survival for hepatocellular carcinoma increasing? A population-based study on survival of hepatocellular carcinoma patients in the 1990s and 2000s.

BACKGROUND: Improvement of survival rates for hepatocellular carcinoma during the last two decades and related factors are still debated. This study aimed to evaluate the risk of death and the role of prognostic factors in patients with hepatocellular carcinoma diagnosed in 1995-2001 and 2004-2006. METHODS: We performed univariate and multivariable survival analyses of subjects with a first hepatocellular carcinoma diagnosis in 1995-2001 and in 2004-2006, all residing in Brescia province, Italy. Mediation analysis of treatment role in survival was conducted. RESULTS: During follow-up (median 21.1 months) 913 subjects died (95.5%). The 1-, 3- and 5-year survival rates were higher for cases diagnosed in 2004-2006 (64.4%, 35.9% and 24.3%) than in 1995-2001 (60.8%, 34.5% and 20.7%). T stage, metastasis, cirrhosis, Child-Pugh class, portal vein invasion, serum creatinine level, treatment approach and diabetes were survival predictors in both periods. Patients with diagnosis in 2004-2006 had 36% lower risk of death than those with diagnosis in 1995-2001 using adjusted Cox proportional hazard model. The association between diagnosis period and risk of death was mediated by changes in treatment approach. CONCLUSION: We observed a decreased risk of death for first hepatocellular carcinoma diagnosis from 2004-2006 to 1995-2001, which was partially attributable to improvements in treatment approach.

Cortisol Concentration as Predictor of Tobacco Initiation in Adolescents: Results From a Population-Based Swedish Cohort.

PURPOSE: Stress potentiates the smoking reward, decreases the ability to resist smoking, and increases the risk of smoking relapse in adulthood. This study aimed to clarify if salivary cortisol, as an indicator of stress, may be prospectively associated with the onset and phenotype of tobacco use in adolescents. METHODS: This study was based on a cohort of Swedish adolescents, among whom saliva specimens were collected from a nested sample. We included adolescents with salivary cortisol measurements and without a history of tobacco use (n = 381, aged 13-14 years). Quartiles of morning and afternoon cortisol concentration and cortisol area under the curve were considered as predictors. We categorized tobacco use according to the product mainly used: cigarette smoking, snus use, or either type of tobacco. For each product use, two outcomes were considered: initiation and duration of use. Poisson regression models were used to calculate rate ratios. RESULTS: A quartile increase in morning cortisol levels and cortisol area under the curve was consistently associated with a 1.2- to 1.4-fold increased risk of initiation of cigarette smoking snus use, or any tobacco use. Similar results were obtained examining the dose-response relationship and using the duration of use as outcome. No associations were apparent between afternoon cortisol concentration and any of the outcomes. All associations were similar between sexes. CONCLUSIONS: Morning cortisol concentration, an indicator of hypothalamic-pituitary-adrenal axis activation, is prospectively associated with tobacco use in adolescents. Whether this activation indicates the cumulative effect of stressors during the life course remains to be elucidated.

Guggulu and Triphala for the Treatment of Hypercholesterolaemia: A Placebo-Controlled, Double-Blind, Randomised Trial.

BACKGROUND: Several herbs are used for lowering high blood cholesterol levels in traditional medicines including Indian Medicine (Ayurveda). We aimed to assess the short-term effects of the combination of Guggulu (Commiphora mukul) and Triphala (Terminalia chebula, Terminalia belerica, and Phyllanthus emblica) on serum cholesterol in healthy subjects with hypercholesterolaemia. PATIENTS AND METHODS: This was a parallel randomised double-blind controlled trial that included 90 individuals at low-moderate cardiovascular risk. The main outcome measures were serum levels of total and low- and high-density lipoprotein cholesterol (LDL-C, HDL-C). Secondary outcome measures included BMI, waist circumference, and adverse events. Subjects were administered either Guggulu and Triphala or placebo three times daily for 3 months, with 3 months of follow-up after the end of treatment. RESULTS: At intention-to-treat analysis, from baseline to 3 months, total serum cholesterol decreased by 1.9% in the placebo (n = 44) and 3.3% (p = 0.01) in the intervention (n = 46) group. Serum LDL-C decreased by 4.9% (p = 0.03) and 4.8% (p = 0.02) in the placebo and intervention group, respectively, without differences between them. Two participants in the intervention group developed hypersensitivity rash (4.3%) as compared with none in the placebo group. CONCLUSIONS: Three months of treatment with Guggulu and Triphala did not show better effects than placebo on serum levels of total and LDL cholesterol, BMI, and waist circumference.

The impact of nodal status in major salivary gland carcinoma: A multicenter experience and proposal of a novel N-classification.

OBJECTIVES: Despite differences in oncological behavior, the 8th edition of AJCC TNM staging currently proposes the same N-classification for major salivary glands (MSG) carcinoma and squamous cell carcinoma of the upper aerodigestive tract. The present study aims to investigate a more reliable definition of N-categories for MSG carcinoma. MATERIALS AND METHODS: A retrospective multicenter study was performed, including 307 patients treated for primary MSG carcinoma from 1995 to 2019. Outcome measures included overall survival (OS), disease specific survival, and local, regional, and distant recurrence. Survival analysis was performed using log-rank test and Cox proportional-hazards model. Overall number (ON) and largest diameter (LD) of nodal metastases, including intra-parotid metastases, were considered to develop three novel proposals of N-classification; their performance were compared with the current TNM staging using Akaike information criterion (AIC), Bayesian information criterion (BIC), and Nagelkerke pseudo-R2. RESULTS: Intra-parotid nodes, ON and LD of nodal metastases emerged as major prognosticators for OS, while extra-nodal extension did not impact on any survival. The current N-classification did not show a satisfactory OS stratification. Three novel N-classifications were developed according to number of metastatic nodes (0 vs 1-3 vs ≥ 4) and/or their maximum diameter (<20 mm vs ≥ 20 mm). They all showed better accuracy in OS stratification, and achieved better AIC, BIC and Nagelkerke pseudo-R2 indices when compared to current N-classification. CONCLUSION: All the proposed N-classifications improved OS stratification and could help in defining a specific N-classification for MSG carcinoma. Their validation and assessment in an external cohort is needed.

Association between exposure to polychlorinated biphenyls and risk of hypertension: A systematic review and meta-analysis.

Experimental and epidemiological studies have suggested an association between exposure to polychlorinated biphenyls (PCBs), ubiquitous environmental toxic compounds, and the risk of hypertension. We conducted a systematic review and meta-analysis of epidemiological studies of the association between PCB exposure and the risk of hypertension. Studies were identified by searching PubMed, Embase and Web of Science and by reviewing reference lists. Study-specific risk estimates comparing the highest versus lowest quantile of PCB distribution were combined using random-effects models. We identified 10 cross-sectional studies, 6 cohort studies, and 1 nested case-control study. A pooled excess risk of hypertension was found for total PCBs (OR 1.70, 95% CI 1.28-2.26), dioxin-like (DL)-PCBs (OR 1.46, 1.19-1.79), but not for non-dioxin like (NDL)-PCBs (OR 1.19, 0.81-1.73) comparing the highest with the lowest quartile of the distribution. According to a dose-response meta-analysis, a linear dose-effect relationship was found for total PCBs [OR 2.23 (95% CI: 1.59-3.14) for 1000 ng PCB/g lipid increase]. This positive association remained when stratifying the analyses by study design (cohort vs cross-sectional studies) and population (general population vs high exposed workers/residents). Among single PCB congeners, DL-PCB 105 and 118, and non-DL-PCB138 and 153 were related to hypertension. In conclusion, this meta-analysis suggests that exposure to PCBs, particularly to DL-PCBs, may be a risk factor for hypertension, independently of other risk factors.

Polychlorinated biphenyls (PCBs) and risk of dementia and Parkinson disease: A population-based cohort study in a North Italian highly polluted area.

BACKGROUND: Serum polychlorinated biphenyls (PCBs) have been associated with some chronic diseases, but little evidence exists on their possible relationship with neurodegenerative diseases. We aimed to assess the relationship between PCB exposure and the occurrence of dementia and Parkinson disease in a prospective cohort study in a highly polluted area (Brescia-Caffaro). METHODS: PCB exposure was assessed by measuring serum levels of 24 congeners. Data on the onset of dementia and Parkinson disease were retrieved by the Brescia Health Protection Agency Database. We used Poisson regression models adjusted for possible confounders to calculate rate ratios (RRs). A mediation analysis was performed to evaluate the mediatory role of cardiovascular diseases. RESULTS: 699 subjects without neurologic diseases at baseline were enrolled (48.1% males, 63.2 years of mean age) in 2001-2013 and followed up to 2018. During a mean follow-up of 8.8 years, 36 and 20 subjects developed dementia and Parkinson disease. Subjects in the 2nd and 3rd tertiles of the total PCBs distribution, compared with those in the 1st tertile, had a higher risk of dementia (RR = 2.30 and RR = 4.35). The estimates for Parkinson disease included the null value with wide confidence intervals. In the mediation analysis, the association between PCB exposure and dementia was dominated by the direct pathway and not by the hypertension-mediated pathway. CONCLUSIONS: We observed a positive association between total PCBs serum levels and the onset of dementia not mediated by hypertension. For Parkinson, the unstable risk estimates did not allow to draw a conclusion on a possible association.