Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus.

BACKGROUND: Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active antiretroviral therapy (ART) and increase risk of malignancies. The prognostic role of low CD4:CD8 ratio and elevated CD8 cell counts on the risk of cancer remains unclear. METHODS: We investigated the association of CD4:CD8 ratio on the hazard of non-AIDS defining malignancy (NADM), AIDS-defining malignancy (ADM) and most frequent group of cancers in ART-treated people with HIV (PWH) with a CD4 and CD8 cell counts and viral load measurements at baseline. We developed Cox proportional hazard models with adjustment for known confounders of cancer risk and time-dependent cumulative and lagged exposures of CD4:CD8 ratio to account for time-evolving risk factors and avoid reverse causality. RESULTS: CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI }1.10-6.19] and 2.03 [95% CI 1.24-3.33], respectively). CD4 cell counts below 350 cells/µL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies. CONCLUSIONS: In ART-treated PWH low CD4:CD8 ratios were associated with ADM and infection-related cancers independently from CD4 and CD8 cell counts and may alert clinicians for cancer screening and prevention of NADM.

Enhancing multi-sectoral collaboration in health: the open arena for public health as a model for bridging the knowledge-translation gap.

Effective public health interventions at local level must involve communities and stakeholders beyond the health services spectrum. A dedicated venue for structured discussion will ensure ongoing multi-sectoral collaboration more effectively than convening ad hoc meetings. Such a venue can be created using existing resources, at minimal extra cost. The University Hospital in Nice (France) has established an Open Arena for Public Health which can serve as a model for promoting collaborative partnerships at local level. The Arena has been successful in implementing sustainable interventions thanks to a set of principles, including: non-hierarchical governance and operating, fair representation of stakeholders, consensus as to best available evidence internationally and locally, policy dialogues: open, free-flowing discussions without preconceived solutions, and an experimental approach to interventions.

Extension of the Clinicoradiologic Spectrum of Newly Described End-Truncating LAMB1 Variations.

Objectives: To refine the clinical spectrum of a very recently identified phenotype associated with LAMB1 end-truncating pathogenic variations. Methods: Detailed clinical, neuropsychological, and MRI investigation of 6 patients from 2 unrelated families segregating end-truncating LAMB1 variations. Results: All patients harbored a LAMB1 end-truncating pathogenic variation. The specific association of a hippocampal type episodic memory dysfunction and a diffuse leukoencephalopathy was observed in all 4 patients aged older than 50 years, slightly worsening over time in 2 patients with several years of follow-up. Additional unspecific neurologic symptoms are reported, such as episodes of numbness, language troubles, or faintness in these 4 patients and the 2 younger ones. Discussion: The association of an extensive leukoencephalopathy with an episodic memory dysfunction of the hippocampal type is strongly suggestive of a LAMB1 end-truncating variation in adults older than 50 years. Early cognitive complaints and imaging abnormalities might exist decades before. Additional transient manifestations can be observed, and this association should lead to LAMB1 screening to avoid unnecessary invasive investigations.

Nationwide Study in France To Predict One Year Major Bleeding and Validate the OAC3-PAD Score in Patients Undergoing Revascularisation for Lower Extremity Arterial Disease.

OBJECTIVE: Antithrombotic strategies are currently recommended for the treatment of lower extremity artery disease (LEAD) but specific scores to assess the risk of bleeding in these patients are scarce. To fill the gap, the OAC3-PAD bleeding score was recently developed and validated in German cohorts. The aim of this study was to determine whether this score performs appropriately in another real world nationwide cohort. METHODS: This 10 year retrospective, multicentre study based on French national electronic health data included patients who underwent revascularisation for LEAD between January 2013 and June 2022. The OAC3-PAD score was calculated and from this, the population was classified into four groups: low, low to moderate, moderate to high and high risk. A binary logistic regression model was applied, with major bleeding occurring at one year (defined using the International Classification of Diseases ICD-10) as the dependent variable. The performance of the OAC3-PAD bleeding score was investigated using a receiver operating characteristic curve. RESULTS: Among 161 205 patients hospitalised for LEAD treatment in French institutions, the one year incidence of major bleeding was 13 672 patients (8.5%). The distribution of the population according to the OAC3-PAD bleeding score was: 88 835 patients (55.1%), 34 369 (21.3%), 27 914 (17.3%), and 10 087 (6.3%) in the low, low to moderate, moderate to high, and high risk groups, respectively; with an incidence of one year major bleeding of 5.0%, 9.8%, 13.2%, and 21.3%. The OAC3-PAD model achieved an AUC of 0.650 to predict one year major bleeding following LEAD repair (95% CI 0.645 - 0.655), with a sensitivity of 0.67 and a specificity of 0.57. CONCLUSION: This nationwide analysis confirmed the accuracy of the OAC3-PAD model to predict one year major bleeding and served as external validation. Although further studies are required, it adds evidence and perspectives to further generalise its use to guide the management of patients with LEAD.

Factors influencing participation in breast cancer screening in an urban setting. A study of organized and individual opportunistic screening among potentially active and retired women in the city of Nice.

Participation in breast cancer screening in urban settings is poor. Identifying factors accounting for participation and non-participation is essential to target priority areas, tackle health inequalities and suggest innovative approaches. We studied organized and individual opportunistic participation in breast cancer screening within the 144 aggregated units for statistical information (Ilôts regroupés pour l'information statistique: IRIS) of the city of Nice from 2019 to 2021. In each IRIS was assessed a local human development index, among potentially active women aged 50 to 59 years and retired women aged 60 to 74 years. Modelling participation and non-participation in screening according to the IRIS units' socio-economical characteristics was performed using the SURE method (Seemingly Unrelated Regression Equations). Over a 2-year period, 24,396 breast screening tests were conducted (11,173 as organised screening, 13,223 as individual opportunistic screening). The local human development index was positively correlated with the two types of screening, respectively. Access to public transport facilitated participation. Managerial status was negatively correlated with organised screening. Single working women had a higher risk of non-participation. With regard to their socio-economic characteristics, screening rates were lower than expected in 16 IRIS units in the city of Nice. Local human development index, access to public transport, family and professional context appear to be associated with breast cancer screening in an urban setting. An innovative approach targeting these factors is called for to reduce health inequalities.

Real-life challenges using personalized prognostic scoring systems in acute myeloid leukemia.

Personalized medicine is a challenge for patients with acute myeloid leukemia (AML). The identification of several genetic mutations in several AML trials led to the creation of a personalized prognostic scoring algorithm known as the Knowledge Bank (KB). In this study, we assessed the prognostic value of this algorithm on a cohort of 167 real life AML patients. We compared KB predicted outcomes to real-life outcomes. For patients younger than 60-year-old, OS was similar in favorable and intermediate ELN risk category. However, KB algorithm failed to predict OS for younger patients in the adverse ELN risk category and for patients older than 60 years old in the favorable ELN risk category. These discrepancies may be explained by the emergence of several new therapeutic options as well as the improvement of allogeneic stem cell transplantation (aHSCT) outcomes and supportive cares. Personalized medicine is a major challenge and predictions models are powerful tools to predict patient's outcome. However, the addition of new therapeutic options in the field of AML requires a prospective validation of these scoring systems to include recent therapeutic innovations.

Air pollution exposure induces a decrease in type II interferon response: A paired cohort study.

BACKGROUND: While air pollution is a major issue due to its harmful effects on human health, few studies focus on its impact on the immune system and vulnerability to viral infections. The lockdown declared following the COVID-19 pandemic represents a unique opportunity to study the large-scale impact of variations in air pollutants in real life. We hypothesized that variations in air pollutants modify Th1 response represented by interferon (IFN) γ production. METHODS: We conducted a single center paired pilot cohort study of 58 participants, and a confirmation cohort of 320 participants in Nice (France), with for each cohort two samplings at six months intervals. We correlated the variations in the production of IFNγ after non-specific stimulation of participants' immune cells with variations in key regulated pollutants: NO2, O3, PM2.5, and PM10 and climate variables. Using linear regression, we studied the effects of variations of each pollutant on the immune response. FINDINGS: In the pilot cohort, IFNγ production significantly decreased by 25.7% post-lockdown compared to during lockdown, while NO2 increased significantly by 46.0%. After the adjustment for climate variations during the study period (sunshine and temperature), we observed a significant effect of NO2 variation on IFNγ production (P=0.03). In the confirmation cohort IFNγ decreased significantly by 47.8% and after adjustment for environmental factors and intrinsic characteristics we observed a significant effect of environmental factors: NO2, PM10, O3, climatic conditions (sunshine exposure, relative humidity) on variation in IFNγ production (P=0.005, P<0.001, P=0.001, P=0.002 and P<0.001 respectively) but not independently from the BMI at inclusion and the workplace P=0.007 and P<0.001 respectively). INTERPRETATION: We show a weakening of the antiviral cellular response in correlation with an increase of pollutants exposition. FUNDING: Agence Nationale de la Recherche, Conseil Départemental des Alpes-Maritimes and Region Sud.

Impact of antibiotic prophylaxis and conditioning modalities in per-oral endoscopic myotomy for esophageal motor disorders.

BACKGROUND AND AIMS: No recommendation regarding antibiotic prophylaxis and preparation modalities are available for patients with esophageal motor disorders who benefit from Per-Oral Endoscopic Myotomy (POEM). The aim of our study was to evaluate their impact on the POEM's safety. PATIENTS AND METHODS: This study was a comparative and multicentric retrospective analysis of a database prospectively collected. Patients over 18 years old with esophageal motor disorders confirmed by prior manometry, who underwent POEM were included. The primary endpoint was the occurrence of adverse events, as classified by Cotton, based on whether or not antibiotic prophylaxis was administered. RESULTS: A total of 226 patients (median age 52.9 ± 19.12 years [18-105], 116 women [51.3%]) were included. The indication for POEM was mainly type 2 achalasia (n = 135, 60.3%). Antibiotic prophylaxis was administered to 170 patients (75.2%) during 3.93 ± 3.46 days [1-21]. The overall adverse events rate was 9.3% (n = 21). Antibiotic prophylaxis was associated with the occurrence of adverse events (p = .003), but had no impact on their severity (p = .238). Antibiotic prophylaxis didn't influence the effectiveness of POEM (1 [0-4] vs 1 [0-9], p = .231). The use of a liquid diet in the 48 h prior to the procedure was significantly associated with a lower adverse events rate (3.1% vs 6.19%, p = .0002). CONCLUSION: The antibiotic prophylaxis during POEM does not prevent adverse events, had no impact on their severity and the efficacy of the procedure. A liquid diet before the procedure should be systematically proposed.

Impact of a Wearable Activity Tracker on Disease Flares in Spondyloarthritis: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the impact of a wearable activity tracker used to encourage physical activity, on disease flares in patients with spondyloarthritis (SpA). METHODS: This randomized controlled trial involved randomizing 108 patients with SpA into tracker and nontracker groups. The participants were then subjected to assessments of disease activity, performance (6-minute walk test), and quality of life (QOL; 36-item Short Form Health Survey) at the 12th, 24th, and 36th week. The primary outcome was the change in the frequency of flare episodes (categorized as no flare, flare in ≤ 3 days, and flare in > 3 days) between baseline and 12 weeks. RESULTS: The results of the study showed that at the 12th week, the mean change (∆) of the number of flares improved in both groups: -0.32 (95% CI -0.66 to 0.02) and -0.38 (95% CI -0.68 to -0.09) in the tracker and nontracker group, respectively. However, the between-group differences were insignificant (P = 0.87). Performance scores improved in both groups at the 12th, 24th, and 36th week (all P < 0.01). The different dimensions of QOL also improved at the 12th week (P < 0.01). Conversely, moderate flares (P < 0.01) and performance (P < 0.01) improved over time; however, the influence over time of a wearable activity tracker was not significant (P = 0.29 and P = 0.66, respectively). CONCLUSION: The use of a wearable activity tracker did not affect the number of flares, performance, or QOL of patients with SpA. Nevertheless, this study confirmed the benefits of physical activity on flares, disease activity, QOL, and physical performance in patients with SpA. (Move Your Spondyl "Better Live Its Rheumatism With the Physical Activity"; ClinicalTrials.gov: NCT03458026).

Impact of Female Sex on Outcomes of Patients Undergoing Thoracic Endovascular Aortic Aneurysm Repair: A Ten-Year Retrospective Nationwide Study in France.

The impact of sex on the outcomes of patients with cardiovascular disease is still incompletely understood. The aim of this nationwide multicenter observational study was to investigate the impact of sex on post-operative outcomes in patients undergoing thoracic endovascular aortic repair (TEVAR) for intact thoracic aortic aneurysm (iTAA). The French National Health Insurance Information System was searched to identify these patients over a ten-year retrospective period. Post-operative outcomes, 30-day and overall mortality were recorded. Among the 7383 patients included (5521 men and 1862 women), females were significantly older than males (66.8 vs. 64.8 years, p < 0.001). They were less frequently diagnosed with cardiovascular comorbidities. Post-operatively, women had less frequently respiratory (10.9 vs. 13.7%, p = 0.002) as well as cardiac complications (34.3 vs. 37.3%, p = 0.023), but they had more frequently arterial complications (52.8 vs. 49.8%, p = 0.024). There was no significant difference on overall mortality for a mean follow-up of 2.2 years (26.9 vs. 27.6%, p = 0.58). In the multivariable regression model, female sex was not associated with 30-day or overall mortality. Although women had a favorable comorbidity profile, the short-term and long-term survival was similar. The significantly higher rate of arterial complications suggests that women may be at higher risk of access-vessel-related complications.

Who Were Hospitalized Deceased Patients from COVID-19 During the First Year of Pandemic? Retrospective Analysis of 1104 Deceased Patients in South of France.

INTRODUCTION: Following the first year of the COVID-19 pandemic, a complete analysis of the characteristics of the deceased hospitalized patients was performed, to identify factors related to premature mortality and to compare patient profiles according to the epidemic periods. METHODS: Retrospective analysis of 1104 deceased patients in two University Hospitals in South-eastern France, between March 1, 2020 and March 12, 2021 from Hospital's electronic medical records was performed. RESULTS: Mean age was 80 years (± 11.1) and 10% of the deceased were younger than 65 years with specific comorbidities, e.g., genetic conditions, metastatic cancer, or massive obesity. Among the three clusters identified, two clusters (75% of deceased patients) include very elderly patients with numerous comorbidities, and differ by their proportion of dependent institutionalized patients. The third cluster is made up of younger patients with fewer but severe comorbidities. Deceased patients' profiles varied according to the epidemic periods: during the first period (March-June 2020), more patients were institutionalized. The second period (September-December2020) coincided with a higher mortality rate. CONCLUSIONS: This study confirmed that most patients hospitalized and dying from COVID-19 were frail, i.e., elderly and/or highly comorbid and that the small proportion of young patients had severe comorbidities.

Obesity, diabetes, hypertension and severe outcomes among inpatients with coronavirus disease 2019: a nationwide study.

OBJECTIVES: Initial studies of individuals with coronavirus disease 2019 (COVID-19) revealed that obesity, diabetes and hypertension were associated with severe outcomes. Subsequently, some authors showed that the risk could vary according to age, gender, co-morbidities and medical history. In a nationwide retrospective cohort, we studied the association between these co-morbidities and patients' requirement for invasive mechanical ventilation (IMV) or their death. METHODS: All French adult inpatients with COVID-19 admitted during the first epidemic wave (February to September 2020) were included. When patients were diagnosed with obesity, diabetes or hypertension for the first time in 2020, these conditions were considered as incident co-morbidities, otherwise they were considered prevalent. We compared outcomes of IMV and in-hospital death according to obesity, diabetes and hypertension, taking age, gender and Charlson's co-morbidity index score (CCIS) into account. RESULTS: A total of 134 209 adult inpatients with COVID-19 were included, half of them had hypertension (n = 66 613, 49.6%), one in four were diabetic (n = 32 209, 24.0%), and one in four were obese (n = 32 070, 23.9%). Among this cohort, IMV was required for 13 596 inpatients, and 19 969 patients died. IMV and death were more frequent in male patients (adjusted oods ratio (aOR) 2.0, 95% CI 1.9-2.1 and aOR 1.5, 95% CI 1.4-1.5, respectively), IMV in patients with co-morbidities (aOR 2.1, 95% CI 2.0-2.2 for CCIS = 2 and aOR 3.0, 95% CI 2.8-3.1 for CCIS ≥5), and death in patients aged 80 or above (aOR 17.0, 95% CI 15.5-18.6). Adjusted on age, gender and CCIS, death was more frequent among inpatients with obesity (aOR 1.2, 95% CI 1.1-1.2) and diabetes (aOR 1.2, 95% CI 1.1-1.2). IMV was more frequently necessary for inpatients with obesity (aOR 1.9, 95% CI 1.8-2.0), diabetes (aOR 1.4, 95% CI 1.3-1.4) and hypertension (aOR 1.7, 95% CI 1.6-1.8). Comparatively, IMV was more often required for patients with the following incident co-morbidities: obesity (aOR 3.5, 95% CI 3.3-3.7), diabetes (aOR 2.0, 95% CI 1.8-2.1) and hypertension (aOR 2.5, 95% CI 2.4-2.6). CONCLUSIONS: Among 134 209 inpatients with COVID-19, mortality was more frequent among patients with obesity and diabetes. IMV was more frequently necessary for inpatients with obesity, diabetes and hypertension. Patients for whom these were incident co-morbidities were particularly at risk. Specific medical monitoring and vaccination should be priorities for patients with these co-morbidities.

Nationwide study in France investigating the impact of diabetes on mortality in patients undergoing abdominal aortic aneurysm repair.

The aim of this nationwide study was to analyze the impact of diabetes on post-operative mortality in patients undergoing AAA repair in France. This 10-year retrospective, multicenter study based on the French National electronic health data included patients undergoing AAA repair between 2010 and 2019. In-hospital post-operative mortality was analyzed using Kaplan-Meier curve survival and Log-Rank tests. A multivariate regression analysis was performed to calculate Hazard Ratios. Over 79,935 patients who underwent AAA repair, 61,146 patients (76.5%) had at least one hospital-readmission after the AAA repair, for a mean follow-up of 3.5 ± 2.5 years. Total in-hospital mortality over the 10-year study was 16,986 (21.3%) and 4581 deaths (5.8%) occurred during the first hospital stay for AAA repair. Age over 64 years old, the presence of AAA rupture and hospital readmission at 30-day were predictors of post-operative mortality (AdjHR = 1.59 CI 95% 1.51-1.67; AdjHR = 1.49 CI 95% 1.36-1.62 and AdjHR = 1.92, CI 95% 1.84-2.00). The prevalence of diabetes was significantly lower in ruptured AAA compared to unruptured AAA (14.8% vs 20.9%, P < 0.001 for type 2 diabetes and 2.5% vs 4.0%, P < 0.001 for type 1 diabetes). Type 1 diabetes was significantly associated with post-operative mortality (AdjHR = 1.30 CI 95% 1.20-1.40). For type 2 diabetes, the association was not statistically significant (Adj HR = 0.96, CI 95% 0.92-1.01). Older age, AAA rupture and hospital readmission were associated with deaths that occurred after discharge from the first AAA repair. Type 1 diabetes was identified as a risk factor of post-operative mortality. This study highlights the complex association between diabetes and AAA and should encourage institutions to report long-term follow-up after AAA repair to better understand its impact.

Baseline and early functional immune response is associated with subsequent clinical outcomes of PD-1 inhibition therapy in metastatic melanoma patients.

BACKGROUND: Despite significant progress with antiprogrammed cell death protein 1 (PD-1) therapy, a substantial fraction of metastatic melanoma patients show upfront therapy resistance. Biomarkers for outcome are missing and the association of baseline immune function and clinical outcome remains to be determined. We assessed the in vitro nonspecific stimulation of immune response at baseline and during anti-PD-1 therapy for metastatic melanoma. METHODS: Previously untreated metastatic melanoma patients received nivolumab and radiotherapy as part of the multicentric phase II trial NIRVANA (NCT02799901). The levels of Th1, Th2 and Th17 cytokines on in vitro non-specific stimulation of innate and adaptive immune cells were measured in patient sera before treatment, and at week 2 and week 6 after the beginning of the treatment, and correlated with tumorous response, progression-free survival (PFS) and occurrence of immune-related adverse events (irAEs). The results in melanoma patients were compared with those of a cohort of 9 sex and age-matched healthy donors. RESULTS: Seventeen patients were enrolled in this ancillary study. Median follow-up was 16 months (2.2-28.4). The 12-month PFS rate was 67.7%. The incidence of irAEs of any grade was 58.8%. Without in vitro stimulation no differences in cytokines levels were observed between responders and non-responders. On in vitro stimulation, metastatic patients had lower Th1 cytokine levels than healthy donors at baseline for tumor necrosis factor-α and interferon-γ (IFN-γ) (1136 pg/mL vs 5558 pg/mL, p<0.0001; and 3894 pg/mL vs 17 129 pg/mL, p=0.02, respectively). Responders exhibited increasing cytokine levels from baseline to week 6. Non-responders had lower interleukin 17A (IL-17A) levels at baseline than responders (7 pg/mL vs 32 pg/mL, p=0.03), and lower IFN-γ levels at week 6 (3.3 ng/mL vs 14.5 ng/mL, p=0.03). A lower level of IL-17A at week 2 and a lower level of IFN-γ at week 6 correlated with worse PFS (p=0.04 and p=0.04 respectively). At baseline, patients who developed irAEs had higher IL-6 levels (19.3 ng/mL vs 9.2 ng/mL, p=0.03) and higher IL-17A levels (52.5 pg/mL vs 2.5 pg/mL, p=0.009) than those without irAEs. CONCLUSIONS: Our findings indicate that cytokine levels after in vitro non-specific stimulation could be a promising biomarker to predict the outcome of PD-1 inhibition therapy.

Heterogeneous NLRP3 inflammasome signature in circulating myeloid cells as a biomarker of COVID-19 severity.

Dysregulated immune response is the key factor leading to unfavorable coronavirus disease 2019 (COVID-19) outcome. Depending on the pathogen-associated molecular pattern, the NLRP3 inflammasome can play a crucial role during innate immunity activation. To date, studies describing the NLRP3 response during severe acute respiratory syndrome coronavirus 2 infection in patients are lacking. We prospectively monitored caspase-1 activation levels in peripheral myeloid cells from healthy donors and patients with mild to critical COVID-19. The caspase-1 activation potential in response to NLRP3 inflammasome stimulation was opposed between nonclassical monocytes and CD66b+CD16dim granulocytes in severe and critical COVID-19 patients. Unexpectedly, the CD66b+CD16dim granulocytes had decreased nigericin-triggered caspase-1 activation potential associated with an increased percentage of NLRP3 inflammasome impaired immature neutrophils and a loss of eosinophils in the blood. In patients who recovered from COVID-19, nigericin-triggered caspase-1 activation potential in CD66b+CD16dim cells was restored and the proportion of immature neutrophils was similar to control. Here, we reveal that NLRP3 inflammasome activation potential differs among myeloid cells and could be used as a biomarker of a COVID-19 patient's evolution. This assay could be a useful tool to predict patient outcome. This trial was registered at www.clinicaltrials.gov as #NCT04385017.

Cancer incidence in the vicinity of a waste incineration plant in the Nice area between 2005 and 2014.

INTRODUCTION: Few studies on cancer incidence have been conducted since the adoption of the EU 2000/76/EC waste incineration directive which aimed to limit dioxin emission levels to less than 0.1 ng TEQ/m3 before December 31, 2005. OBJECTIVE: To measure cancer incidence among the population exposed to atmospheric emissions from the waste incineration plant near the town of Nice (South-Eastern France), compared to the unexposed population of the Alpes-Maritimes department (A-M). METHODS: All primary invasive cancers and haematological malignancies diagnosed among AM residents between 2005 and 2014 were recorded. The exposed surface was modeled on an average dioxin deposition model ≥4.25 ng/m2/year. Each case was geolocated and assigned to one of 36 predefined geographic units of exposed area, or one of 462 units in the unexposed area. The adjusted incidence rate, the standardized incidence ratio and the Comparative Morbidity Figure were calculated for two periods: 2005-2009/2010-2014. RESULTS: We recorded 80,865 new cancers in the A-M population. Between 2005 and 2009, we observed a higher incidence among exposed women of acute myeloid leukaemia, myelodysplastic syndromes and myeloma and, among exposed men, of soft tissue sarcomas, myeloma and lung cancer. Between 2010 and 2014, there was no excess incidence among women, while among men incidence of myeloma and lung cancer remained higher. CONCLUSION: Only among men, the incidence of myeloma and lung cancer remained higher in the exposed area during the second period. The EU directive resulting in the limitation of atmospheric emissions from incinerators could explain the decrease in incidence of cancers with protracted latency. Consideration of other risk factors and further data collection will be necessary to validate this hypothesis.

Colorectal Cancer Risk Following Bariatric Surgery in a Nationwide Study of French Individuals With Obesity.

Importance: Although bariatric surgery is effective against morbid obesity, the association of this surgery with the risk of colorectal cancer remains controversial. Objective: To assess whether bariatric surgery is associated with altered risk of colorectal cancer among individuals with obesity. Design, Setting, and Participants: This retrospective, population-based, multicenter, cohort study based on French electronic health data included 1 045 348 individuals with obesity, aged 50 to 75 years, and free of colorectal cancer at baseline. All inpatients with obesity having data recorded during a hospital stay between 2009 and 2018 by the French national health insurance information system database were followed up for a mean (SD) of 5.3 (2.1) years for those who did not undergo bariatric surgery and 5.7 (2.2) years for those who underwent bariatric surgery. Two groups of patients comparable in terms of age, sex, body mass index, follow-up, comorbidities, and conditions who did or did not undergo surgery were also obtained by propensity score matching. Exposures: Bariatric surgery (n = 74 131), including adjustable gastric banding, sleeve gastrectomy, gastric bypass; or no bariatric surgery (n = 971 217). Main Outcomes and Measures: Primary outcome was incident colorectal cancer. Standardized incidence ratios were calculated using age-, sex-, and calendar year-matched colorectal cancer incidence among the general French population during the corresponding years. Secondary outcome was incident colorectal benign polyps. Results: Among a total of 1 045 348 patients, the mean (SD) age was 57.3 (5.5) years for the 74 131 patients in the surgical cohort vs 63.4 (7.0) years for the 971 217 patients in the nonsurgical cohort. The mean (SD) follow-up was 6.2 (2.1) years for patients who underwent adjustable gastric banding, 5.5 (2.1) years for patients who underwent sleeve gastrectomy, and 5.7 (2.2) years for patients who underwent gastric bypass. In total, 13 052 incident colorectal cancers (1.2%) and 63 649 colorectal benign polyps were diagnosed. The rate of colorectal cancer was 0.6% in the bariatric surgery cohort and 1.3% in the cohort without bariatric surgery. In the latter cohort, 9417 cases were expected vs 12 629 observed, a standardized incidence ratio of 1.34 (95% CI, 1.32-1.36). In the bariatric surgery cohort, 428 cases were expected and 423 observed, a standardized incidence ratio of 1.0 (95% CI, 0.90-1.09). Propensity score-matched hazard ratios in comparable operated vs nonoperated groups were 0.68 (95% CI, 0.60-0.77) for colorectal cancer and 0.56 (95% CI, 0.53-0.59) for colorectal benign polyp. There were fewer new diagnoses of colorectal cancer after gastric bypass (123 of 22 343 [0.5%]) and sleeve gastrectomy (185 of 35 328 [0.5%]) than after adjustable gastric banding (115 of 16 460 [0.7%]), and more colorectal benign polyps after adjustable gastric banding (775 of 15 647 [5.0%]) than after gastric bypass (639 of 20 863 [3.1%]) or sleeve gastrectomy (1005 of 32 680 [3.1%]). Conclusion and Relevance: The results of this nationwide cohort study suggested that following bariatric surgery, patients with obesity share the same risk of colorectal cancer as the general population, whereas for patients with obesity who do not undergo bariatric surgery, the risk is 34% above that of the general population.

Alzheimer's disease: Estimating its prevalence rate in a French geographical unit using the National Alzheimer Data Bank and national health insurance information systems.

BACKGROUND: Reliable epidemiological data on Alzheimer's disease are scarce. However, these are necessary to adapt healthcare policy in terms of prevention, care and social needs related to this condition. To estimate the prevalence rate in the Alpes-Maritimes on the French Riviera, with a population of one million, we present a capture-recapture procedure applied to cases of Alzheimer's disease, based on two epidemiological surveillance systems. METHODS: To estimate the total number of patients affected by Alzheimer's disease, a capture-recapture study included a cohort of patients with Alzheimer's disease or receiving medications only eligible for use for this condition, recorded by a specific health insurance information system (Health Insurance Cohort, HIC), and those registered in the French National Alzheimer's Data Bank ("Banque Nationale Alzheimer", BNA) in 2010 and 2011. We applied Bayesian estimation of the Mt ecological model, taking into account age and gender as covariates, i.e. factors of inhomogeneous catchability. RESULTS: Overall, 5,562 patients with Alzheimer's disease were recorded, of whom only 856 were common to both information systems. Mean age and F/M sex ratio differed between BNA and HIC surveillance systems, 81 vs 84 years and 2.7 vs 3.2, respectively. A Bayesian estimation, with age and gender as covariates, yields an estimate of 15,060 cases of Alzheimer's disease [95%HPDI: 14,490-15,630] in the Alpes-Maritimes. The completeness of the HIC and BNA databases were respectively of 25.4% and 17.2%. The estimated prevalence rate among the population over 65 years old was 6.3% in 2010-2011. CONCLUSIONS: This study demonstrates that it is possible to determine the number of subjects affected by Alzheimer's disease in a geographical unit, using available data from two existing surveillance systems in France, i.e. 15,060 cases in the Alpes-Maritimes. This is the first stage of a population-based approach in view of adapting available resources to the population's needs.

Preventive effect of bariatric surgery on type 2 diabetes onset in morbidly obese inpatients: a national French survey between 2008 and 2016 on 328,509 morbidly obese patients.

BACKGROUND: The association between bariatric surgery (BS) and the prevention of type 2 diabetes (T2D) and its complications in patients with obesity has been rarely addressed in large, nationwide database studies. OBJECTIVE: To estimate the preventive effect of BS against T2D and its vascular complications in patients with obesity without co-morbidity at baseline. SETTING: All French public and private hospitals. METHODS: Data were extracted from the French National Health Service database between 2008 and 2016. All patients with obesity aged 18- to 60-years old, free of T2D and major co-morbidities, and with at least 1 year of follow-up were analyzed. Patients who had undergone gastric bypass (GB), sleeve gastrectomy (SG), or adjustable gastric banding (AGB) were included in the BS group, and patients with obesity with no history of BS were considered as controls. RESULTS: Of 328,509 patients with obesity, 102,627 had BS. Between 2009 and 2016, 9.7% (31,946/328,509) of patients had a diagnosis of T2D associated with morbid obesity, 13.2% of the control group versus 2.0% of the BS group (P < .001). BS was associated with favorable 8-year T2D event-free survival estimates of 92.3% in the BS group against 58.2% in the control group. The hazard ratio for the diagnosis of T2D was .18 (95% confidence interval, .17-.19) for the BS group versus controls, after adjustment on age, sex, body mass index, and baseline differences. A significant difference was found between the type of bariatric procedure (P < .001) with more T2D after AGB (4.5%) than after GB (1.2%) or SG (0.9%). T2D complications were more common in controls (P < .001) with multiple T2D complications occurring in 1% of patients in the control group and .1% in the BS group (P < 0.001). GB and SG were more effective than AGB. CONCLUSIONS: This nationwide study shows that BS reduces the new onset of T2D in patients with obesity by 82%. SG and GB give comparable results and both are more effective than AGB.