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Abstract Background Data on survival and prognosis factors in incident cohorts are scarce in systemic sclerosis (SStc). To describe survival, standardized mortality ratio (SMR), and prognosis factors in systemic sclerosis (SSc), we analyzed a multicenter French cohort of incident patients and performed a systematic review of the literature and meta-analysis. Methods A multicenter, French cohort study was conducted between January 1, 2000, and December 31, 2013. Patients were followed-up until July 1, 2016. A systematic review of the literature was carried out in MEDLINE and EMBASE up to July 2017. Meta-analysis was performed using all available data on SMR and hazard ratios of prognosis factors. Results A total of 625 patients (493 females, 446 lcSSc) were included. During the study period, 104 deaths (16.6%) were recorded and 133 patients were lost to follow-up. Overall survival rates at 1, 3, 5, and 10 years from diagnosis were 98.0%, 92.5%, 85.9%, and 71.7% respectively in the French cohort. Overall SMR was 5.73 (95% CI 4.68–6.94). Age at diagnosis > 60 years, diffuse cutaneous SSc, scleroderma renal crisis, dyspnea, 6-min walking distance (6MWD), forced vital capacity 8 mg/l were associated with a poorer survival after adjustment. Eighteen studies (11,719 patients) were included in the SMR meta-analysis and 36 studies (26,187 patients) in the prognosis factor analysis. Pooled SMR was 3.45 (95%CI 3.03–3.94). Age at disease onset, male sex, African origin, diffuse cutaneous SSc, anti-Scl70 antibodies, cardiac and renal involvement, interstitial lung disease, PH, and malignancy were significantly associated with a worse prognosis. Anti-centromere antibodies were associated with a better survival. Conclusions Overall, our study highlights a high mortality rate in SSc patients and confirms previously described prognosis factors related to skin extension and organ involvement while identifying additional prognosis factors such as autoantibody status, telangiectasia, 6MWD, and valvular disease.

Objectives: First, this registry-based study aimed to comprehensively analyze patients' medical histories and treatments based on ischemic strokes' etiology. We focused on the management of atrial fibrillation among patients diagnosed with cardioembolic stroke. Then, our objective was to identify prognostic factors associated with 28-day mortality., Materials and Methods: All ischemic strokes occurring in adults between 2014 and 2021 in Lille, France, were categorized using the TOAST classification. Comparative analyses of patients' medical characteristics were conducted across subtypes. Survival rates within 28 days post-stroke were assessed, and factors influencing mortality were identified using a multivariate Cox model., Results: 1912 ischemic strokes were recorded, due to cardioembolism (36%), large-artery atherosclerosis (9%), small-artery occlusion (9%), other determined causes (6%), or undetermined causes (39%). The median NIHSS score after cardioembolic stroke (6, IQR: 3-13) was twice that after small-artery occlusion (3, IQR: 2-5). Among patients with cardioembolic stroke, 26% were diagnosed post-admission with atrial fibrillation. For the 42% diagnosed pre-admission, only 54% had prior prescriptions for oral anticoagulants. Reperfusion therapies were administered in 21% of cases, with significant variations across subtypes. Mortality rates were higher after cardioembolic strokes (17%) than after small-artery occlusions (3%). Prognostic factors included etiology, high NIHSS score, atrial fibrillation, and previous heparin prescription., Conclusions: While atrial fibrillation was underdiagnosed and undertreated, patients with cardioembolic stroke exhibited high severity and elevated mortality rates. Etiology emerged as an independent predictor of early mortality, regardless of NIHSS score upon admission. These findings underscore the importance of targeted prevention to improve patient outcomes after ischemic stroke., Competing Interests: Declaration of competing interest The Authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the effect of combined exposure to different air pollutants on mortality in dialysis patients. This study aimed to investigate the association of multiple exposures to air pollutants with all-cause and cause-specific death in dialysis patients., Materials and Methods: This registry-based nationwide cohort study included 90,373 adult kidney failure patients initiating maintenance dialysis between 2012 and 2020 identified from the French REIN registry. Estimated mean annual municipality levels of PM 2.5 , PM 10 , and NO 2 between 2009 and 2020 were combined in different composite air pollution scores to estimate each participant's exposure at the residential place one to 3 years before dialysis initiation. Adjusted cause-specific Cox proportional hazard models were used to estimate hazard ratios (HRs) per interquartile range (IQR) greater air pollution score. Effect measure modification was assessed for age, sex, dialysis care model, and baseline comorbidities., Results: Higher levels of the main air pollution score were associated with a greater rate of all-cause deaths (HR, 1.082 [95% confidence interval (CI), 1.057-1.104] per IQR increase), regardless of the exposure lag. This association was also confirmed in cause-specific analyses, most markedly for infectious mortality (HR, 1.686 [95% CI, 1.470-1.933]). Sensitivity analyses with alternative composite air pollution scores showed consistent findings. Subgroup analyses revealed a significantly stronger association among women and fewer comorbid patients., Discussion: Long-term multiple air pollutant exposure is associated with all-cause and cause-specific mortality among patients receiving maintenance dialysis, suggesting that air pollution may be a significant contributor to the increasing trend of CKD-attributable mortality worldwide., 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 © 2024 Hamroun, Génin, Glowacki, Sautenet, Leffondré, De Courrèges, Dauchet, Gauthier, Bayer, Lassalle, Couchoud, Amouyel and Occelli.)

The Script Concordance Tests (SCTs) are an examination modality introduced by decree in the French National Ranking Exam for medical students in 2024. Their objective is to evaluate clinical reasoning in situations of uncertainty. In practice, SCTs assess the impact of new information on the probability of a hypothesis formulated a priori based on an authentic clinical scenario. This approach resembles probabilistic (or Bayesian) reasoning. Due to the uncertainty associated with the explored clinical situation, SCTs do not compare the student's response to an expected one in a theoretical knowledge reference. Instead, the distribution of responses from a panel of experienced physicians is used to establish the question's scoring scale. Literature data suggest that physicians, even experienced ones, like most humans, often exhibit biased intuitive probabilistic reasoning. These biases raise questions about the relevance of using expert panel responses as scoring scales for SCTs., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: Although several risk factors of kidney cancer have already been well-addressed, many remain underappreciated, such as chronic exposure to air pollution. This systematic review and meta-analysis aims to assess the association between air pollutant exposure and the risk of kidney cancer., Methods: With an exhaustive search equation including keywords related to air pollution and kidney cancer on EMBASE, PubMed, Web of science, Cochrane Library and CINAHL database, we identified all relevant articles published before March 23rd, 2023 (Prospero registration number: CRD42020187956). Using random-effects meta-analysis, we present pooled hazard ratios (with their respective 95% confidence interval) associated with a 10 µg/m 3 increase in each pollutant level. Heterogeneity was quantified by the I 2 statistic. Risks of methodological and publication bias were also both assessed using appropriate tools., Results: Of the 1919 records identified, our review included 19 articles (13 cohort, 5 registry-based and 1 case-control studies), of which 9 were suitable for the meta-analysis. We found a significantly increased risk of kidney cancer incidence for a 10 μg/m 3 elevation of both particulate matter of less than 10 µm (PM 10 ) (HR = 1.29 [1.10; 1.51], I 2  = 0%, p = 0.002) and nitrogen dioxide (NO 2 ) (HR = 1.10 [1.03; 1.18], I 2  = 20%, p = 0.004). Secondary analyses also suggest an increased risk of kidney cancer-related morbidity-mortality associated with PM 10 exposure., Conclusions: Overall, our findings suggest a potential association between exposure to increased levels of PM 10 and NO 2 and the risk of kidney cancer. These results should nonetheless be interpreted with caution due to the limited number of included studies and their significant risk of methodological bias., (© 2024. The Author(s).)

Air pollution is associated with elevated cardiovascular mortality and an increase in cardiovascular risk factors. However, the literature data on associations between air pollution and cardiovascular risk factors are contradictory. To explore the relationship between residential exposure to atmospheric pollutants and cardiovascular risk factors (lipid biomarker and blood pressure levels). We studied a sample of 2339 adult participants in the ELISABET study from the Dunkirk and Lille urban areas of France. The mean annual exposure to atmospheric pollutants (PM 10 , NO 2 and SO 2 ) at the home address was estimated via an air dispersion model. The associations were probed in multivariate linear regression models. The mean NO 2 level was 26.05 μg/m 3 in Lille and 19.96 µg/m 3 in Dunkirk. The mean PM 10 level was 27.02 μg/m 3 in Lille and 26.53 μg/m 3 in Dunkirk. We detected a significant association between exposure to air pollutants and the high-density lipoprotein (HDL) (which is a protective factor against cardiovascular diseases) level: for a 2 µg/m 3 increment in PM 10 , the HDL level decreased by 1.72% (p = 0.0037). None of the associations with other lipid variables or with blood pressure were significant. We didn't find evidence significant associations for most of the risk factors but, long-term exposure of adults to moderate levels of ambient air pollution was associated with a decrement in HDL., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: Estimate the global prevalence of anti-Ro52-kDa/SSA (TRIM21) autoantibodies in systemic sclerosis (SSc), and describe the associated clinical phenotype, through a systematic review and meta-analysis of published reports and new data from our French cohort., Methods: Anti-TRIM21 seropositivity and associated SSc characteristics were assessed in a cross-sectional study including 300 patients of Lille University Hospital. A systematic review of the literature was performed in Pubmed and Embase, followed by a meta-analysis, using data on prevalence, clinical/demographical/biological characteristics of SSc patients and the type of assay used for anti-TRIM21 antibodies detection (PROSPERO n° CRD42021223719)., Findings: In the cross-sectional study, anti-TRIM21 antibodies prevalence was 26% [95%CI: 21; 31]. Anti-centromere antibodies were the most frequent SSc specific autoantibodies coexisting with anti-TRIM21. Patients with anti-TRIM21 antibodies were more frequently women (91% vs 77%, p = 0.006), more likely to present an associated Sjögren's syndrome (19% vs 7%, p < 0.001), had a higher rate of pulmonary arterial hypertension (PAH) (15% vs 6%, p = 0.017) and a greater frequency of digestive complications such as dysphagia (12% vs 5%, p = 0.038) or nausea/vomiting (10% vs 3%, p = 0.009) than anti-TRIM21 negative patients. Thirty-five articles corresponding to a total of 11,751 SSc patients were included in the meta-analysis. In this population, the overall seroprevalence of anti-TRIM21 antibodies was 23% [95%CI: 21; 27] with a high degree of heterogeneity (I 2 : 93% Phet: <0.0001), partly explained by the methods of detection. Anti-TRIM21 seropositivity was positively associated with female sex (OR: 1.60 [95%CI: 1.25, 2.06]), limited cutaneous subset (OR: 1.29 [1.04, 1.61]), joint manifestations (OR: 1.33 [1.05, 1.68]), pulmonary hypertension (PH) (OR: 1.82 [1.42, 2.33]), and interstitial lung disease (ILD) (OR: 1.31 [1.07, 1.60])., Interpretation: Anti-TRIM21 antibodies frequently co-exist with usual SSc antibodies, but are independently associated to a higher risk of cardio-pulmonary complications. The presence of these autoantibodies should therefore be considered when assessing the risk of developing PH and ILD, and deserves further studies on appropriate screening and follow-up of patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Amelie Leurs reports a relationship with CSL Vifor that includes: travel reimbursement. Dr. Amelie Leurs reports a relationship with NOVARTIS that includes: board membership. Prof David Launay reports a relationship with Takeda Pharmaceutical Company Limited that includes: consulting or advisory and funding grants. Prof David Launay reports a relationship with Biocryst Pharmaceuticals, Inc. that includes: consulting or advisory and funding grants. Prof David Launay reports a relationship with CSL Behring LLC that includes: consulting or advisory and funding grants. Prof David Launay reports a relationship with GSK that includes: funding grants. Prof David Launay reports a relationship with Octapharma that includes: funding grants. Prof David Launay reports a relationship with Pfizer Inc. that includes: funding grants. Dr. Luc Dauchet reports a relationship with FEDER ECRIN that includes: funding grants. Dr. Luc Dauchet reports a relationship with ADEM French environment agency that includes: funding grants. Prof Vincent Sobanski reports equipment, drugs, or supplies was provided by Euroimmun. Prof Vincent Sobanski reports equipment, drugs, or supplies was provided by D-Tek. Prof Vincent Sobanski reports financial support was provided by Lille University Hospital. Prof Vincent Sobanski reports a relationship with Grifols Inc. that includes: consulting or advisory and funding grants. Prof Vincent Sobanski reports a relationship with Boehringer Ingelheim GmbH that includes: consulting or advisory. Prof Vincent Sobanski reports a relationship with Ultragenyx Pharmaceutical Inc. that includes: consulting or advisory. If there are other authors, they 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This paper presented a national register for esophageal atresia (EA) started in January 2008. We report our experience about the conception of this database and its coordination. Data management and data quality are also detailed. In 2023, more than 2,500 patients with EA are included. Prevalence of EA in France was calculated at 1.8/10,000 live birth. Main clinical results are listed with scientific publications issued directly from the register., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To describe the proportions of subjects exposed to crystalline silica and the sectors of activity concerned between 1965 and 2010 in a sample of the general French population., Methods: We included 2942 participants aged 40 to 65 years, recruited at random from electoral rolls, from the French general population in the cross-sectional ELISABET study between 2011 and 2013. The proportions of subjects exposed to crystalline silica and their sectors of activity were determined on the basis of their career history and the use of the Matgéné job-exposure matrix., Results: In the total sample, occupational exposure to crystalline silica was found for 291 subjects (9.9%) between 1965 and 2010, with a predominance of men (20.2% of exposed subjects among men (282 out of 1394) versus 0.6% among women (9 out of 1548)). The highest proportion of participants exposed to crystalline silica was reached in 1980 with 6.1% and then decreases to 4.4% in 2010. Among men, the most frequently exposed sectors of activity were manufacture of basic metals (41.5% of exposed men (117 out of 282)), specialised construction activities (23.1% of exposed men (65 out of 282)) and construction of buildings (14.2% of exposed men (40 out of 282))., Conclusions: Although the proportion of workers exposed to crystalline silica has been decreasing since the 1980s, it is still significant at least until 2010, particularly in the construction sector, and further research is needed to improve the monitoring of workers who are or have been exposed to crystalline silica., (© 2024. The Author(s).)

Introduction: MicroRNAs are epigenetic regulatory factors capable of silencing the expression of target genes and might mediate the effects of air pollution on health. The objective of the present population-based study was to investigate the association between microRNA expression and long-term, residential exposure to atmospheric PM 10 and NO 2 ., Method: We included 998 non-smoking adult participants from the cross-sectional ELISABET survey (2010-2014) in the Lille urban area of France. The mean residential annual pollution levels were estimated with an atmospheric dispersion modelling system. Ten microRNAs were selected on the basis of the literature data, together with two housekeeping microRNAs (miR-93-5p and miR-191-5p) and were quantified with RT-qPCRs. Multivariate linear regression models were used to study the association between microRNAs and air pollution. The threshold for statistical significance (after correction for the FDR) was set to p < 0.1., Results: The mean annual exposure between 2011 and the year of inclusion was 26.4 ± 2.0 µg/m 3 for PM 10 and 24.7 ± 5.1 µg/m 3 for NO 2 . Each 2 µg/m 3 increment in PM 10 exposure was associated with an 8.6% increment (95%CI [3.1; 14.3]; p FDR  = 0.019) in miR-451a expression. A 5 µg/m 3 increment in NO 2 exposure was associated with a 5.3% increment ([0.7; 10]; p FDR  = 0.056) in miR451a expression, a 3.6% decrement (95%CI [-6.1; -1.1]; p FDR  = 0.052) in miR-223-3p expression, a 3.8% decrement (95%CI[-6.8; -0.7]; p FDR  = 0.079) in miR-28-3p expression, a 4.3% decrement (95%CI [-7.7; -0.8]; p FDR  = 0.055) in miR-146a-5p expression, and a 4.0% decrement (95% CI[-7.4; -0.4]; p FDR  = 0.059) in miR-23a-5p expression. The difference between the two housekeeping microRNAs miR-93-5p and miR-191-5p was also associated with PM 10 and NO 2 exposure., Conclusion: Our results suggest that circulating miRNAs are potentially valuable biomarkers of the effects of air pollution., 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 © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Although several studies have studied the relationship between occupational exposure to crystalline silica dust and respiratory mortality, few have examined the relationship with impairments in respiratory function and the exposure threshold triggering spirometric monitoring in exposed workers. The objective of the present study was to evaluate the impact of exposure to crystalline silica dust on respiratory function., Methods: We included 1428 male participants (aged 40 to 65) recruited from the French general population, at random from electoral rolls, in the cross-sectional ELISABET study and for whom data on forced expiratory flow-volume curve indices z-scores (calculated using the Global Lung Function Initiative 2012 equations) and exposure (via a questionnaire) were available. A cumulative exposure index (CEI) for crystalline silica dust (CEI silica , expressed in mg.m -3 .year) was calculated using the Matgéné occupational exposure matrix., Results: 293 of the 1428 participants (20.52%) reported exposure to silica dust. We found that the adjusted z-scores for the forced expiratory volume in the first second/forced vital capacity (FEV 1 /FVC) ratio decreased significantly as CEI silica increased. After adjustment, the adjusted z-scores for FEV 1 /FVC (β: -0.426 (95% confidence interval (CI): -0.792, -0.060) per 1 mg m -3 .year increment) and the mean forced expiratory flow between 25 and 75% of the forced vital capacity (FEF 25-75 ) (β: -0.552 (95% CI: -0.947, -0.157)) were significantly lower in the participants with CEI silica ≥1 mg m -3 .year than in non-exposed participants. The likelihoods of having airway obstruction (odds ratio (OR): 3.056 (95% CI: 1.107, 7.626)) or having an impaired FEF 25-75 (OR: 4.305 (95% CI: 1.393, 11.79)) were also significantly higher in participants with CEI silica ≥1 mg m -3 .year., Conclusion: Our results emphasize the importance of spirometry-based monitoring in workers exposed to more than 1 mg m -3 .year of crystalline silica dust, in order to identify small airway obstruction or airway obstruction as early as possible., 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 © 2023. Published by Elsevier Inc.)

Introduction: Air pollution has an impact on health, and low-grade inflammation might be one of the underlying mechanisms. The objective of the present study of adults from northern France was to assess the associations between short-term and residential exposure to air pollution and levels of various inflammatory biomarkers., Methods: The cross-sectional Enquête Littoral Souffle Air Biologie Environnement (ELISABET) study was conducted from 2011 to 2013 in the Lille and Dunkirk urban areas of northern France. Here, we evaluated the associations between PM 10 , NO 2 and O 3 exposure (on the day of the blood sample collection and on the day before, and the mean annual residential level) and levels of the inflammatory biomarkers high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-17A, IL-22, and tumor necrosis factor α., Results: We assessed 3074 participants for the association with hsCRP and a subsample of 982 non-smokers from Lille for the association with plasma cytokine levels. A 10 μg/m 3 increment in PM 10 and NO 2 levels on the day of sample collection and on the day before was associated with a higher hsCRP concentration (3.43% [0.68; 6.25] and 1.75% [-1.96; 5.61], respectively, whereas a 10 μg/m 3 increment in O 3 was associated with lower hsCRP concentration (-1.2% [-3.95; 1.64]). The associations between mean annual exposure and the hsCRP level were not significant. Likewise, the associations between exposure and plasma cytokine levels were not statistically significant., Conclusion: Short-term exposure to air pollution was associated with higher serum hsCRP levels in adult residents of two urban areas in northern France. Our results suggest that along with other factors, low-grade inflammation might explain the harmful effects of air pollution on health., Competing Interests: Declaration of competing interest LD, RM and JMLG have contributed to an expert report (commissioned by Lille European Metropole) entitled “Rapport d'expertise à propos de la localisation de la piscine du projet d'aménagement de la gare Saint Sauveur à Lille” [Expert report on the location of the swimming pool in the Saint Sauveur station development project in Lille] but did not receive any personal fees. Other authors declare that they have no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: As phase III trials have shown interest in innovative but expensive drugs in the treatment of neuromyelitis optica spectrum disorder (NMOSD), data are needed to clarify strategies in the treatment of neuromyelitis optica (NMO). This meta-analysis compares the efficacy of first-line strategies using rituximab (RTX), mycophenolate mofetil (MMF), or azathioprine (AZA), which are still widely used., Methods: Studies identified by the systematic review of Huang et al. (2019) were selected if they considered at least two first-line immunosuppressants among RTX, MMF, and AZA. We updated this review. The Medline, Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials databases were queried between November 2018 and April 2020. To be included, the hazard ratio (HR) [95% CI] for the time to first relapse after first-line immunosuppression had to be available, calculable, or provided by the authors., Results: We gathered data from 919 NMO patients (232 RTX-, 294 MMF-, and 393 AZA-treated patients). The risk of first relapse after first-line immunosuppression was 1.55 [1.04, 2.31] (p = 0.03) for MMF compared with RTX, 1.42 [0.87, 2.30] (p = 0.16) for AZA compared with RTX, and 0.94 [0.58, 1.54] (p = 0.08) for MMF compared with AZA., Interpretation: The findings suggest that RTX is more efficient than MMF as a first-line therapy. Even if the results of our meta-analysis cannot conclude that RTX has a better efficacy in delaying the first relapse than AZA, the observed effect difference between both treatments combined with the results of previous studies using as outcome the annualized relapse rate may be in favor of RTX., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Carotenoids and docosahexaenoic acid (DHA) were identified as essential components for eye health and are both naturally present in eggs., Objective: We aimed to evaluate the effect of the daily consumption of two eggs enriched with lutein/zeaxanthin and DHA on macular pigment optical density (MPOD) and on circulating xanthophyll and fatty acid concentrations in healthy participants., Methods: Ninety-nine healthy volunteers consumed either two standard eggs or two enriched eggs per day for 4 months. MPOD was measured at baseline (V0) and at follow-up (V4) using a modified confocal scanning laser ophthalmoscope (primary outcome). Blood samples were collected to determine total plasma and lipoprotein fatty acids and lutein/zeaxanthin compositions at V0 and V4 (secondary outcomes)., Results: A slight but significant increase in MPOD was observed for all study participants consuming two eggs per day for 4 months at all eccentricities (0.5°, 1°, 2°, and 4°). Plasma and lipoprotein lutein, zeaxanthin, and DHA concentrations significantly increased in both groups but were greater in the enriched group (for the enriched group (V0 vs. V4): lutein, 167 vs. 369 ng/mL; zeaxanthin, 17.7 vs. 29.2 ng/mL; DHA, 1.89 vs. 2.56% of total fatty acids). Interestingly, lutein from high-density lipoprotein (HDL) was strongly correlated with MPOD at 0.5 and 1° eccentricities (rho = 0.385, p = 0.008, and rho = 0.461, p = 0.001, respectively)., Conclusions: MPOD was slightly increased in both groups. Lutein, zeaxanthin, and DHA plasma concentrations were strongly enhanced in the enriched group compared with the standard group. A significant correlation was found between MPOD level and lutein concentration in HDL.

Background: Although walkability is known to be associated with obesity and hypertension through increased physical activity; data on cardiovascular risk factors (especially in the Europe) are scarce. We assessed the relationship between neighbourhood walkability and cardiometabolic factors (including obesity, hypertension, the blood lipid profile, and serum glycated haemoglobin (HbA1c) levels) among adults living in northern France., Methods: Data were extracted from the ELISABET study database (2011-2013). The participants (aged between 40 and 65) resided in or around the cities of Lille and Dunkirk. For each residential address, we determined a neighbourhood walkability index (using a geographic information system) and the Walk Score®. Multilevel linear and logistic models were used to assess the relationships between neighbourhood walkability on one hand and body mass index (BMI), obesity, blood pressure, hypertension, serum HDLC, LDL-C, triglyceride and HbA1c levels, and physical activity level on the other., Results: 3218 participants were included. After adjusting for individual and neighbourhood variables, we found that a higher neighbourhood walkability index was associated with a lower BMI (-0.23 kg.m -2 ; 95% confidence interval (CI) [-0.44;-0.01] for a one interquartile range (IQR) increment), a lower systolic blood pressure (-1.66 mmHg; 95% CI [-2.46;-0.85] per IQR), a lower prevalence of hypertension (% of increase: -7.12, 95% CI [-13.56;-0.52] per IQR), and a higher prevalence of moderate or high physical activity (% of increase = 6.9; 95% CI [1.2;12.72] per IQR). The walkability index was not significantly associated with other cardiovascular risk factors. Similar results were observed for the Walk Score®., Conclusion: Our results showed that residence in a more walkable neighbourhood was associated with a lower prevalence of vascular risk factors. Promoting neighbourhood walkability might help to improve the population's cardiovascular health., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Luc Dauchet contributed to an expert report commissioned by Lille European metropole “Rapport d’expertise à propos de la localisation de la piscine du projet d’aménagement de la gare Saint Sauveur à Lille” [Expert report on the location of the swimming pool in the Saint Sauveur station development project in Lille] but did not receive any personal fees. The other authors declare that they have no competing interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in cholesterol homeostasis. A common variant, the G allele in position c.1420 (c.1420G), has been associated with a decrease of both plasma PCSK9 and LDL-cholesterol concentrations. However, the functional effect of this variant is currently not well understood. We hypothesized that it could be explained by functional variants in linkage disequilibrium (LD), more specifically, by variants located in the PCSK9 3' UTR as targets for miR regulation of PCSK9 expression., Methods: Variations in LD with c.1420G were studied in 1029 patients followed for dyslipidaemia. In silico studies identified potential miRNA binding sites induced by PCSK9 3'UTR variants in LD with c.1420G. Their functionality was studied with a luciferase reporter assay in HuH-7 cells and confirmed by cotransfection of anti-miRNAs., Results: The c.*571C and c.*234T variants located in the PCSK9 3'UTR were found in tight LD with c.1420G (D' = 0.962; LOD = 163.06). The haplotype carrying c.*571C showed a 6.7% decrease in luciferase activity (p = 0.003). Inhibition of hsa-miR-1228-3p and hsa-miR-143-5p counteracted their effect on the haplotype carrying c.*571C allele, suggesting that PCSK9 expression was decreased by the endogenous binding of hsa-miR-1228-3p and hsa-miR-143-5p on its 3'UTR., Conclusions: This post-transcriptional regulation might contribute towards the association between plasma PCSK9 levels and c.1420G. Such regulation of PCSK9 expression may open new perspectives for the treatment of hypercholesterolemia and atherosclerosis cardiovascular diseases., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: During aging, individuals can be classified as being in one of 3 different states: robust, frail or dependent. Frailty is described as reversible, so early detection offers the potential of returning the subject to a robust status. There are multiple clinical frailty scales but no gold standard and frailty is not systematically assessed in clinicians' daily practice. Reliable biomarkers of frailty are lacking, however, while their identification and systematic use would make this simple scale a useful clinical tool., Objective: To conduct a review of the literature concerning the biomarkers associated with frailty and to compare in a meta-analysis the plasmatic values of each biomarker in the frail with the robust group., Results: 503 articles were identified on PubMed, 467 on Scopus and 369 on Web Of Science. 67 articles were included, collecting a total of 32,934 robust subjects and 6864 frail subjects. C-reactive protein (CRP) (Standardized Mean Difference (SMD): 0.49 CI 95% [0.37-0.61]) was significantly higher in the frail group whereas hemoglobin (SMD: -0.67[-0.90; -0.44]), albumin (SMD: -0.62[-0.84; -0.41]), 25-hydroxyvitamin D (25OHD) (SMD: -0.43 [-0.64; -0.21]) and, in men, free testosterone (SMD: -0.77 [-1.05; -0.49]) were significantly lower in the frail group., Conclusion: We found 5 biomarkers that were associated with frailty (CRP, hemoglobin, albumin, 25OHD and free testosterone in men) belonging to multiple physiological systems. Further cohort studies are needed to verify their ability to screen for frailty., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Geographical variations in cardiovascular disease rates have been linked to individual air pollutants. Investigating the relation between cardiovascular disease and exposure to a complex mixture of air pollutants requires holistic approaches. We assessed the relationship between exposure to multiple air pollutants and the incidence of coronary heart disease (CHD) in a general population sample. We collected data in the Lille MONICA registry (2008-2011) on 3268 incident cases (age range: 35-74). Based on 20 indicators, we derived a composite environmental score (SEnv) for cumulative exposure to air pollution. Poisson regression models were used to analyse associations between CHD rates on one hand and SEnv and each single indicator on the other (considered in tertiles, where T3 is the most contaminated). We adjusted models for age, sex, area-level social deprivation, and neighbourhood spatial structure. The incidence of CHD was a spatially heterogeneous (p=0.006). There was a significant positive association between SEnv and CHD incidence (trend p=0.0151). The relative risks [95%CI] of CHD were 1.08 [0.98-1.18] and 1.16 [1.04-1.29] for the 2nd and 3rd tertile of SEnv exposure. In the single pollutant analysis, PM 10 , NO 2 , cadmium, copper, nickel, and palladium were significantly associated with CHD rates. Multiple air pollution was associated with an increased risk of CHD. Single pollutants reflecting road traffic pollution were the most strongly associated with CHD. Our present results are consistent with the literature data on the impact of road traffic on the CHD risk in urban areas., 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 © 2020. Published by Elsevier B.V.)

Background: A large yet heterogeneous body of literature exists suggesting that endothelial dysfunction appears early in type 1 diabetes, due to hyperglycemia-induced oxidative stress. The latter may also affect vascular smooth muscles (VSM) function, a layer albeit less frequently considered in that pathology. This meta-analysis aims at evaluating the extent, and the contributing risk factors, of early endothelial dysfunction, and of the possible concomitant VSM dysfunction, in type 1 diabetes. Methods: PubMed, Web of Sciences, Cochrane Library databases were screened from their respective inceptions until October 2019. We included studies comparing vasodilatory capacity depending or not on endothelium (i.e., endothelial function or VSM function, respectively) in patients with uncomplicated type 1 diabetes and healthy controls. Results: Fifty-eight articles studying endothelium-dependent function, among which 21 studies also assessed VSM, were included. Global analyses revealed an impairment of standardized mean difference (SMD) (Cohen's d) of endothelial function: -0.61 (95% CI: -0.79, -0.44) but also of VSM SMD: -0.32 (95% CI: -0.57, -0.07). The type of stimuli used (i.e., exercise, occlusion-reperfusion, pharmacological substances, heat) did not influence the impairment of the vasodilatory capacity. Endothelial dysfunction appeared more pronounced within macrovascular than microvascular beds. The latter was particularly altered in cases of poor glycemic control [HbA 1c > 67 mmol/mol (8.3%)]. Conclusions: This meta-analysis not only corroborates the presence of an early impairment of endothelial function, even in response to physiological stimuli like exercise, but also highlights a VSM dysfunction in children and adults with type 1 diabetes. Endothelial dysfunction seems to be more pronounced in large than small vessels, fostering the debate on their relative temporal appearance., (Copyright © 2020 Lespagnol, Dauchet, Pawlak-Chaouch, Balestra, Berthoin, Feelisch, Roustit, Boissière, Fontaine and Heyman.)

Although a growing body of evidence suggests that chronic exposure to outdoor air pollution is linked to a decline in lung function, data on flow at low lung volumes that may be more specific of small airway obstruction are still scarce. We aimed to study the associations between residential exposure to air pollution and lung function, with specific focus on small airways obstruction. We assessed 2995 French participants (aged between 40 and 65) in the ELISABET cross-sectional survey. Residential exposures to nitrogen dioxide (NO 2 ), particulate matter with a diameter <10 μm (PM 10 ) and sulphur dioxide (SO 2 ) were assessed. The spirometric parameters were forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and forced expiratory flow between 25% and 75% of FVC (FEF25-75) and at 75% of FVC (FEF75). Coefficients in linear regression models were expressed as the z-score [95% confidence interval] for an increment of 5 μg/m 3 in NO 2 and 2 μg/m 3 in PM 10 and SO 2 . NO 2 was associated with significantly lower values of FEV1 (-0.10 [-0.15;-0.05]), FVC (-0.06 [-0.11;-0.02]), FEV1/FVC (-0.07 [-0.11;-0.03]), FEF25-75 (-0.09 [-0.14;-0.05]) and FEF75 (-0.08 [-0.12;-0.04]). PM 10 was associated with significantly lower values of FEV1 (-0.10 [-0.15;-0.04]), FVC (-0.06 [-0.11;-0.01]), FEV1/FVC (-0.06 [‒0.11;-0.01]), FEF25-75 (-0.08 [-0.13;-0.03]) and FEF75 (-0.08 [-0.12;-0.04]). SO 2 was associated with significantly lower values of FEV1 (-0.09 [-0.16;-0.02]), FEV1/FVC (-0.07 [-0.13;-0.01]), FEF25-75 (-0.09 [-0.15;-0.02]) and FEF75 (-0.08 [-0.14;-0.03]) but not FVC (-0.05 [-0.11; 0.009]). Even though spatial variations in pollutant levels were low, residential exposure to outdoor air pollution was associated with lower lung function, including lower FEF25-75 and FEF75 suggesting small airway obstruction., Competing Interests: Declaration of competing interest AH, SH, DC, MR, FO, NCK, JG, RM, JLE and LD declare that they have no conflicts of interest. PA reports personal fees from Servier, personal fees from Total, personal fees from Genoscreen, personal fees from Fondation Alzheimer, outside the submitted work. LD, RM and SH have contributed to an expert report ordered by the Lille European metropole « Rapport d'expertise à propos de la localisation de la piscine du projet d'aménagement de la gare Saint Sauveur à Lille » [Expert report on the location of the swimming pool of the development project of the Saint Sauveur station in Lille] with no personal fees, (Copyright © 2020. Published by Elsevier Inc.)

Background: Geographical variations in Crohn's disease (CD) suggest that the environment has a role in the pathogenesis of this condition., Aims: To describe the spatial distribution and the clustering of CD cases in France, and to assess the relationship between the prevalence of CD and environmental risk factors., Methods: We identified all patients with CD included in the French hospital discharge database from 2007 to 2014. Age- and gender-smoothed standardised prevalence ratios over this period were computed for 5610 spatial units. An ecological regression analysis was used to assess the relationship between the risk of CD and ecological variables (health care, latitude, socio-economic deprivation, urbanisation, proportion of agricultural surfaces and density of industries). Local spatial clusters of high-CD prevalence were searched for using elliptic spatial scan statistics and characterised in a hierarchical ascendant classification based on the same ecological variables., Results: About 129 089 patients with CD were identified, yielding a crude prevalence of 203 per 100 000 inhabitants. The overall spatial heterogeneity was statistically significant (P < .001). An elevated risk of CD was found to be significantly associated with high-social deprivation (relative risk [95% confidence interval] = 1.05 [1.02-1.08]) and high urbanisation (1.09 [1.04-1.14]). Sixteen significant spatial clusters of high-CD prevalence were identified; there were no common ecological variables., Conclusions: The geographical distribution of CD prevalence in France is not uniform, and is associated with high levels of social deprivation and urbanisation. Larger ecological databases integrating more detailed environmental and clinical information are needed., (© 2019 John Wiley & Sons Ltd.)

Introduction: The association between cadmium levels in the body and diabetes has been extensively studied, with sometimes contrasting results. Smoking is the primary non-occupational source of cadmium, and constitutes a risk factor for diabetes. One can therefore hypothesize that the putative association with cadmium is actually explained by tobacco. To fully control for this confounding factor, we studied the relationship between blood cadmium and glycated haemoglobin (HbA1c) levels separately in never-, former and current smokers., Methods: We studied a sample of 2749 middle-aged adults from the cross-sectional ELISABET survey in and around the cities of Lille and Dunkirk; none had chronic kidney disease or a history of haematological disorders, and none were taking antidiabetic medication. The blood cadmium level-HbA1c associations in never-, former and current smokers were studied in separate multivariate models. The covariables included age, sex, city, educational level, tobacco consumption (or passive smoking, for the never-smokers), body mass index, estimated glomerular filtration rate, and (to take account of the within-batch effect) the cadmium batch number., Results: In the multivariate analysis, a significant association between cadmium and HbA1c levels was found in all three smoking status subgroups. A 0.1 μg/L increment in blood cadmium was associated with an HbA1c increase [95% confidence interval] of 0.016% [0.003; 0.029] among never-smokers, 0.024% [0.010; 0.037] among former smokers, and 0.020% [0.012; 0.029] among current smokers., Conclusions: The observation of a significant association between the blood cadmium concentration and HbA1c levels in a group of never-smokers strengthens the hypothesis whereby diabetes is associated with cadmium per se and not solely with tobacco use. The small effect size observed in our population of never smokers with low levels of exposure to cadmium suggested that the risk attributable to this metal is not high. However, the impact of exposure to high cadmium levels (such as occupational exposure) on the risk of diabetes might be of concern., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Data on survival and prognosis factors in incident cohorts are scarce in systemic sclerosis (SStc). To describe survival, standardized mortality ratio (SMR), and prognosis factors in systemic sclerosis (SSc), we analyzed a multicenter French cohort of incident patients and performed a systematic review of the literature and meta-analysis., Methods: A multicenter, French cohort study was conducted between January 1, 2000, and December 31, 2013. Patients were followed-up until July 1, 2016. A systematic review of the literature was carried out in MEDLINE and EMBASE up to July 2017. Meta-analysis was performed using all available data on SMR and hazard ratios of prognosis factors., Results: A total of 625 patients (493 females, 446 lcSSc) were included. During the study period, 104 deaths (16.6%) were recorded and 133 patients were lost to follow-up. Overall survival rates at 1, 3, 5, and 10 years from diagnosis were 98.0%, 92.5%, 85.9%, and 71.7% respectively in the French cohort. Overall SMR was 5.73 (95% CI 4.68-6.94). Age at diagnosis > 60 years, diffuse cutaneous SSc, scleroderma renal crisis, dyspnea, 6-min walking distance (6MWD), forced vital capacity < 70%, diffusing capacity of the lungs for carbon monoxide < 70%, pulmonary hypertension (PH), telangiectasia, valvular disease, malignancy, anemia, and CRP > 8 mg/l were associated with a poorer survival after adjustment. Eighteen studies (11,719 patients) were included in the SMR meta-analysis and 36 studies (26,187 patients) in the prognosis factor analysis. Pooled SMR was 3.45 (95%CI 3.03-3.94). Age at disease onset, male sex, African origin, diffuse cutaneous SSc, anti-Scl70 antibodies, cardiac and renal involvement, interstitial lung disease, PH, and malignancy were significantly associated with a worse prognosis. Anti-centromere antibodies were associated with a better survival., Conclusions: Overall, our study highlights a high mortality rate in SSc patients and confirms previously described prognosis factors related to skin extension and organ involvement while identifying additional prognosis factors such as autoantibody status, telangiectasia, 6MWD, and valvular disease.

Introduction: Air pollution impacts health by increasing mortality and the incidence of acute events in unhealthy individuals. In contrast, the acute effects of pollution in healthy individuals are less obvious. The present study was designed to evaluate the associations between short-term exposure to air pollution on one hand and lung function, and inflammatory markers on the other in middle-aged, non-smoking adults with no respiratory disease, in two urban areas in northern France., Methods: A sample of 1506 non-smoking adults (aged from 40 to 65) with no respiratory disease was selected from the participants in the 2011-2013 cross-sectional Enquête Littoral Souffle Air Biologie Environnement (ELISABET) survey in two urban areas in the northern France. We evaluated the associations between (i) mean levels of particulate matter with aerodynamic diameter < 10 μm (PM 10 ), nitrogen dioxide (NO 2 ) and ozone (O 3 ) exposure on the day and the day before the study examination for each participant, and (ii) spirometry data and levels of inflammatory markers. Coefficients of multiple linear regression models were expressed (except for the forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio) as the percentage change [95% confidence interval] per 10 μg increment in each pollutant., Results: Levels of PM 10 , NO 2 and O 3 exposure were below or only close to the World Health Organization's recommended limits in our two study areas. An increment in NO 2 levels was significantly associated with a lower FEV1/FVC ratio (-0.38 [-0.64; -0.12]), a lower forced expiratory flow between 25% and 75% of FVC (FEF25-75%) (-1.70 [-3.15; -0.23]), and a lower forced expiratory flow measured at 75% of FVC (FEF75%) (-3.07 [-4.92; -1.18]). An increment in PM 10 levels was associated with lower FEF75% (-1.41 [-2.79; -0.01]) and a non-significant elevation in serum levels of high-sensitivity C-reactive protein (+3.48 [-0.25; 7.36], p = 0.07). Lastly, an increment in O 3 levels was associated with a significantly higher blood eosinophil count (+2.41 [0.10; 4.77]) and a non-significant elevation in fractional exhaled nitric oxide (+2.93 [-0.16; 6.13], p = 0.06)., Conclusion: A short-term exposure to air pollution was associated with a subclinical decrement in distal lung function and increment in inflammatory markers in healthy inhabitants of two urban areas in France. If these exploratory results are confirmed, this could suggest that even moderate levels of air pollution could have an impact on respiratory health on the general population, and not solely on susceptible individuals., (Copyright © 2018. Published by Elsevier Ltd.)

Objectives: Antiphospholipid antibodies (aPL) can be present in the sera of systemic sclerosis (SSc) patients. This study aimed to determine the prevalence of aPL in a cross-sectional study of SSc patients, to assess their clinical associations, to perform a systematic review of published reports and a meta-analysis to estimate the worldwide prevalence of aPL in SSc. Methods: Two-hundred and forty-nine SSc patients were consecutively tested once for lupus anticoagulant (LA), anticardiolipin (aCL), and anti-β2glycoprotein I (anti-β2GpI) antibodies. Clinical associations with aPL positivity were studied using a logistic regression model. A systematic review of the literature was carried out in PubMed and Embase. Meta-analysis was performed using number of aPL positive (at least one of the three antibodies positive) and negative patients. Meta-regression was used to study potential factors explaining the heterogeneity between studies. Results: In our cross-sectional study, aPL positivity was found in 16 patients (prevalence 6.4%; 95%CI [3.8-10.4]). In multivariate analysis, there was a significant association between aPL positivity and venous thrombosis (VT) (OR 6.25 [1.18-33.00]; p = 0.028) and miscarriage (OR 5.43; 95%CI [1.31-22.13]; p = 0.017). Twenty-four studies were included in the meta-analysis, representing a total population of 3036 SSc patients. The overall pooled prevalence of aPL in SSc was 14% (9-20) with a high degree of heterogeneity among studies. Conclusion: This study found a prevalence of aPL positivity in our SSc population of 6.4% (3.8-10.4) and an overall worldwide pooled prevalence of 14% (9-20). In our SSc population, aPL positivity was associated with VT and miscarriage. These data provide additional insights into the role of aPL in the vasculopathy observed in SSc.

Introduction: A growing body of evidence suggests that long-term exposure to air pollutants like nitrogen oxides (NO x ) and particulate matter (PM) is associated with the prevalence and incidence of type 2 diabetes mellitus. Serum glucose and glycosylated hemoglobin (HbA1c) levels are biomarkers of glucose homeostasis. Data on the association between glucose homeostasis biomarkers and air pollution are scarce. HbA1c and fasting blood glucose (FBG) concentrations have been linked to PM and NO 2 exposure in Taiwan, where mean pollution levels are 3 to 7 times higher than the guideline maximum annual mean values of 40 μg/m 3 (for NO 2 ) and 20 μg/m 3 (for PM10) set by the World Health Organization (WHO). However, this association is not consistently reported at lower levels of pollution. The objective of the present study was to investigate the relationships between long-term exposure to air pollution at the place of residence, diabetes biomarkers, and prevalent diabetes in two cities with relatively low level of pollution., Methods: Data were recorded for 2895 adults (aged 40 to 65) having participated in the 2011-2013 ELISABET cross-sectional survey of the Lille and Dunkirk urban areas in northern France. Using multiple logistic and generalized linear regression models, we analyzed the associations between individual exposure to pollution on one hand and HbA1c, FBG and prevalent diabetes mellitus (DM) on the other. An atmospheric dispersion modelling system was used to assess annual exposure at the place of residence to coarse particulate matter (PM10), NO 2 , and sulfur dioxide (SO 2 )., Results: The median pollutant levels were 21.96 μg/m 3 for NO 2 , 26.75 μg/m 3 for PM10, and 3.07 μg/m 3 for SO 2 . A 2 μg/m 3 increment in PM10 was associated with an HbA1c increment [95% confidence interval] of 0.044% [0.021; 0.067]. This association was still statistically significant after adjustment for the neighborhood's characteristics. A 5 μg/m 3 increment in NO 2 was associated with an HbA1c increment of 0.031% [0.010; 0.053]. Associations between DM or FBG and air pollution did not achieve statistical significance., Conclusion: Our study of a middle-aged, urban population evidenced an association between elevated HbA1c levels and long-term exposure to PM10 and NO 2 pollution levels that were relatively low but close to the WHO's guideline maximum values., (Copyright © 2018. Published by Elsevier Ltd.)

Introduction: The objective of the present study was to investigate the relationship between sources of household air pollution, respiratory symptoms and lung function., Methods: 3039 adults aged from 40 to 65 participated in the 2011-2013 ELISABET cross-sectional survey in northern France. Lung function was measured using spirometry. During a structured interview, respiratory symptoms, household fuels, exposure to moulds, and use of ventilation were recorded on a questionnaire., Results: The self-reported presence of mould in at least two rooms (not including the bathroom and the kitchen) was associated with a 2.5% lower predicted forced expiratory volume in 1 s (95% confidence interval, -4.7 to -0.29; p-trend <0.05) and a higher risk of wheezing (p-trend < 0.001). Visible condensation was associated with wheezing (p < .05) and chronic cough (p < .05). There were no significant associations with the type of household fuel or inadequate ventilation/aeration. Similar results were found when the analyses were restricted to participants without known respiratory disease., Conclusion: Our results suggest that the presence of mould (known to be associated with more severe asthma symptoms) could also have an impact on respiratory symptoms and lung function in the general population and in populations without known respiratory disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Biomarkers in exhaled breath condensate (EBC) are potentially sensitive indicators of early biochemical changes in airways following exposure to pneumotoxic substances, particularly in susceptible subjects. NOx are the stable end products of the nitrite-nitrate-NO oxidative stress pathway and can be used to monitor airway inflammatory diseases, especially in asthma. Nevertheless, population-based surveys are needed to better interpret EBC NOx levels in clinical studies. The aim of this study was to establish reference values of EBC NOx in a large group of middle-aged, healthy adults of a sample of the general population with particular focus on the smoking status., Methods: The EBC NOx levels were analysed from 2872 subjects among the ELISABET population-based cross sectional study including a representative sample of men and women aged from 40 to 66 years olds conducted in northern France, which included comprehensive questionnaires by interview and spirometry data. Healthy participants were defined as participants with no self-reported respiratory disease., Results: For the healthy subjects (n = 1251), the median NOx concentration (IQR) was equal to 7.2  μM (3.12) and concentrations of NOx in EBC did not differ significantly according to smoking status. The upper fifth percentile (95%) (ULN) of NOx concentrations among healthy subjects was equal to 13.6  μM, ranging from 12.7  μM (smokers) to 14.4  μM (ex smokers). Among subjects with EBC NOx values higher than the ULN and compared with subjects that had EBC NOx values lower than the ULN, we found a significant higher proportion of subjects with current asthma (10.5% vs 6.5%) or with chronic bronchitis symptoms (7.6% vs 3.3%)., Conclusion: This population-based study has provided the distribution and the upper limit reference value of a nitrosative stress biomarker (NOx) in EBC of middle aged, healthy adults. EBC NOx levels were not associated with smoking status., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: An association has been consistently found between diabetes mellitus and decreased lung function. We evaluated to what extent low-grade inflammation (as measured by the level of high-sensitivity C-reactive protein [hs-CRP]) could explain this relationship., Methods: A sample of 1878 middle-aged adults from the cross-sectional Enquête Littoral Souffle Air Biologie Environnement survey without self-reported pulmonary and atherosclerosis disease was included. A mediation analysis was performed to assess and quantify the hs-CRP level as a mediator of the relationship between diabetes and lung function., Results: Diabetes was associated with higher hs-CRP level (+22.9%, 95% confidence interval = [5.1, 43.6]). The hs-CRP (>4 vs. ≤1 mg/L) was associated with lower percentage predicted values for the forced expiratory volume in the first second (FEV1) (-4% [-6.1, -1.9]) and forced vital capacity (FVC) (-4.4% [-6.5, -2.3]). Diabetes was associated with FEV1 (-3.5% [-5.8, -1.3]) and FVC (-3.6% [-5.9, -1.3]). The proportion of the effect that is mediated by hs-CRP was 12% [2.4, 37] and 13% [3.7, 39.4] for FEV1 and FVC, respectively., Conclusions: Our results suggest that low-grade systemic inflammation could only explain a small part of the relationship between diabetes and lung function., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The long-term collection of population-based data should improve our knowledge of the contribution of trend in cardiovascular risk factors to the steady fall in mortality associated with coronary heart disease in high-income countries., Aims: To assess long-term time trends in the prevalence of cardiovascular risk factors, estimated coronary heart disease risk and mortality between 1986 and 2013 in the Lille urban area (northern France)., Methods: We studied representative samples of inhabitants of the Lille urban area (aged 40-64 years) in 1986-1988 (n=860), 1995-1996 (n=1021), 2005-2007 (n=1021) and 2011-2013 (n=1636), together with data from the Lille MONICA registry., Results: In men, the age-standardized prevalence fell between 1986 and 2013 from 70.5% to 42.5% for hypertension, from 71.1% to 58.3% for dyslipidaemia and from 44.1% to 24.7% for smoking (all P<0.001). The prevalence of being overweight increased from 59.6% to 65.1% (P<0.05). In women, the prevalences decreased from 56.6% to 34.3% for hypertension and from 60.9% to 42.2% for dyslipidaemia (both P<0.001). The prevalences of smoking (17%) and being overweight (50%) were stable. The mean 10-year (95% confidence interval) predicted risk of fatal coronary heart disease (estimated with the Systematic Coronary Risk Evaluation equation) decreased by 2.02% (1.78-2.25%) per year for men and by 1.55% (1.32-1.78%) for women. The observed coronary mortality rate fell by 2.6% (2.2-3.0%) in men and 2.8% (1.9-3.6%) in women., Conclusions: Prevalences of main risk factors and estimated coronary mortality risk decreased concomitantly with the observed coronary mortality - indicating that primary prevention made a major contribution to the decrease in mortality., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objectives: Cancer may be a complication of inflammatory bowel disease (IBD) or its treatment. In elderly onset IBD patients the risk of malignancy is of particular concern. We studied this risk in a population-based cohort of elderly onset IBD patients., Methods: In a French population-based cohort, we identified 844 patients aged >60 years at IBD diagnosis from 1988 to 2006, including 370 Crohn's disease (CD) and 474 ulcerative colitis (UC). We compared incidence of cancer among IBD patients with that observed in the French Network of population-based Cancer Registries (FRANCIM). Confidence interval (CI) was estimated assuming a Poisson-specific law for rare events. Results were expressed using the standardized incidence ratios (SIRs) and their CI 95%., Results: Median age at IBD diagnosis was 70 (65-76) years in CD and 69 (64-74) in UC. Median follow-up was 6 (2-11) years for both diseases with a number of person-years of 5,598. Among the 844 elderly onset IBD cases, 98 (11.6%; 42 CD and 56 UC) developed a cancer after IBD diagnosis (67 men and 31 women) corresponding to an overall SIR of 0.97 (0.80-1.18). These cancers occurred at a median age of 77 years (71-80) and 75 years (71-81) in patients with CD and UC, respectively. Median time between IBD diagnosis and cancers was 78 months (40-121). There was no significant increased risk of colorectal cancer in IBD (SIR=1.03 (0.62-1.70), CD (SIR=1.20 (0.57-2.52) nor in UC (SIR=0.91 (0.45-1.82) without significant protective role of 5-aminosalicylic acid (hazard ratio (HR)=0.7 (0.2-2.6)). No significant risk for other intestinal cancers was found, especially for small bowel carcinoma. An increased risk of malignant lymphoproliferative disorders was found in all IBD and in CD: SIR=2.49 (1.25-4.99) and SIR=3.09 (1.16-8.23), respectively. An increased risk of myeloproliferative disorders was found in all IBD (SIR=2.18 (1.09-4.35)). Thiopurines exposure, using a time-dependant Cox model, was not found as associated with an increased risk to develop cancer, HR=0.90 (0.48-1.68)., Conclusions: There is no increased risk for developing intestinal cancer among patients with elderly onset IBD in this population-based cohort. There are increased risks of developing lymphoproliferative and myeloproliferative disorders in all IBD. Thiopurines exposure was not found as associated with an increased risk to lymphoproliferative disorders. These data reinforce the difference between elderly onset IBD as compared with patients with younger age at IBD onset.