NRAS Q61R , BRAF V600E immunohistochemistry: a concomitant tool for mutation screening in melanomas

International audienceThe determination of NRAS and BRAF mutation status is a major requirement in the treatment of patients with metastatic melanoma. Mutation specific antibodies against NRAS(Q61R) and BRAF(V600E) proteins could offer additional data on tumor heterogeneity. The specificity and sensitivity of NRAS(Q61R) immunohistochemistry have recently been reported excellent. We aimed to determine the utility of immunohistochemistry using SP174 anti-NRAS(Q61R) and VE1 anti-BRAF(V600E) antibodies in the theranostic mutation screening of melanomas. 142 formalin-fixed paraffin-embedded melanoma samples from 79 patients were analyzed using pyrosequencing and immunohistochemistry. 23 and 26 patients were concluded to have a NRAS-mutated or a BRAF-mutated melanoma respectively. The 23 NRAS (Q61R) and 23 BRAF (V600E) -mutant samples with pyrosequencing were all positive in immunohistochemistry with SP174 antibody and VE1 antibody respectively, without any false negative. Proportions and intensities of staining were varied. Other NRAS (Q61L) , NRAS (Q61K) , BRAF (V600K) and BRAF (V600R) mutants were negative in immunohistochemistry. 6 single cases were immunostained but identified as wild-type using pyrosequencing (1 with SP174 and 5 with VE1). 4/38 patients with multiple samples presented molecular discordant data. Technical limitations are discussed to explain those discrepancies. Anyway we could not rule out real tumor heterogeneity. In our study, we showed that combining immunohistochemistry analysis targeting NRAS(Q61R) and BRAF(V600E) proteins with molecular analysis was a reliable theranostic tool to face challenging samples of melanoma

Screening for Chronic Obstructive Pulmonary Disease in Smoking Cessation ‎Clinic in France

Background: The purpose of this study was to detect chronic obstructive pulmonary disease (COPD) among smokers seeking treatment for the first time in a smoking cessation clinic and to assess the predictors of positive screening. Methods: This study was based on a multicenter survey with questionnaires (Richmond, Fagerstrom, clinical signs) and spirometry miniaturized. Data were analyzed with SAS® by Pearson chi-square test, the test of analysis of variance, Spearman correlation coefficient, and multivariate logistic regression step down. Findings: 1918 patients were assessed for eligibility and only 1737 were included. The report forced expiratory volume in 1 second (FEV1/FEV6) was < 0.8 for 33.2% of smokers and < 0.7 for 7.5% of them. People with likely COPD had more dyspnea (P < 0.010) and chronic bronchitis (CB) (P < 0.010). In multivariate analysis, CB, duration of smoking history since longer than 30 years, and dyspnea significantly increased the risk of being detected as COPD. The odds ratios of the above factors were 2.9, 4.1, and 4.5, respectively. Conclusion: 7.5% of smokers were likely COPD. Patient’s risk factors, such as the presence of CB, smoking addiction for longer than 30 years, or dyspnea, were predictive of a positive screening for COPD

Diagnostic Value of FDG PET-CT Quantitative Parameters and Deauville-Like 5 Point-Scale in Predicting Malignancy of Focal Thyroid Incidentaloma

Objective: To evaluate the diagnostic value of FDG PET-CT metabolic parameters and Deauville-like 5 point-scale to predict malignancy in a population of patients presenting focal thyroid incidentaloma (fTI).Design: This retrospective study included 41 fTI, classified according to cytological and histological data as benign (BL) or malignant lesion (ML). FDG PET-CT semi-quantitative parameters (SUVmax, SUVmean, SUVpeak, MTV, TLG), tumor to liver SUVmean ratio (TLRmax and TLRmean), tumor to blood-pool SUVmean ratio (TBRmax and TBRmean) were calculated. Each fTI was also classified on a Deauville-like 5-point scale (DS) currently used in lymphoma. Comparison between BL and ML was performed for each parameter and a ROC analysis was conducted.Results: All quantitative PET metabolic parameters (SUV parameters, volume based parameters and SUV ratio) were higher in ML compared with BL, yet no significant difference was reported. fTI (uptake) malignancy rate according to DS grades 2, 3, 4, and 5 was, respectively, 25% (1 of 4), 28.6% (2 of 7), 8.3% (1 of 12), and 33.3% (6 of 18) with no significant difference between ML and BL groups. Results of ROC analysis showed that mean TBR had the highest AUC in our cohort (0.66 95%CI [0.41; 0.91]) with a cut-off value of 2.2. Specificity of MTV and TLG was 100% (cut-off values: MTV 9.6 ml, TLG 22.9 g) and their sensitivity was 30 and 40%, respectively.Conclusion: Our study did not highlight any FDG PET/CT parameter predictor of fTI malignancy

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

BACKGROUND: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. METHODS: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. FINDINGS: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. INTERPRETATION: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic. FUNDING: Bill & Melinda Gates Foundation

Long-term safety and efficacy of insulin degludec in the management of type 2 diabetes.

International audienceInsulin degludec (IDeg) is a novel antiglycemic agent belonging to the therapeutic class of ultra-long duration basal insulin analogs. Its half-life and duration of action are 25 hours and 42 hours, respectively. This pharmacodynamic profile leads to a strict dosing schedule, ie, IDeg is injected at the same time each day to ensure optimal biological action and consistent glycemic control. According to the literature, IDeg provides glycemic control and nocturnal hypoglycemia reduction comparable with other long-acting analogs in type 2 diabetes mellitus. The risk of severe hypoglycemic episodes seems also to be reduced when using IDeg therapy; however, long-term follow-up is warranted for monitoring of possible but relatively infrequent adverse events. IDeg is also available in combination with aspart insulin and with liraglutide. The above preparations have been approved by the European Medicines Agency and other national health authorities. In 2012, the US Food and Drug Administration asked for a complementary study on IDeg-associated cardiovascular risk. Future prospective evaluation of large cohorts of patients with type 2 diabetes mellitus treated with IDeg, with long-term follow-up, can provide further relevant information on the safety of IDeg therapy

Traitement de l’information faciale des enfants avec troubles du spectre autistique et enfants au développement typique : un traitement particulier des faces animales ?

National audienceFace processing impairment is associated with social interaction disorders observed in autism spectrum disorders (ASD), such as children with ASD explore human eyes less than do neurotypical (NT) children. In a communicative situation, each partner uses signals emitted by the other (e.g. postures, gestures or gaze directions) to collect information to adjust their behaviour, in both humanhuman or human-animal interactions. Indeed, animals are part of humans’ environment and present numerous benefits. Thus, given the strong bonding between ASD children and animals, we hypothesized that animal face processing by people with ASD would be typical. Our study compared the patterns of fixation of ASD (n=12) and NT (n=18) children recorded while exploring human and animal (horse, dog, and cat) faces in a passive viewing task using an eye tracking technique. Our results, using animal pictures, confirmed that the eyes were the part of the face explored the longest by NT children and, to a lesser extent, by ASD children, but only NT children looked at the eyes of human pictures longer than other parts. Implications for understanding social interaction impairment related to ASD are discussed.Les altérations dans le traitement de l’information faciale peuvent être associées aux difficultés d’interactions sociales observées dans les Troubles du Spectre de l’Autisme (TSA). Les enfants avec TSA (ETSA) accordent peu d’importance à la région des yeux à la différence des enfants au développement typique (EDT). Dans une situation de communication, chaque partenaire utilise les indices émis par l’autre (e.g. posture, geste, direction du regard) pour recueillir des informations afin d’ajuster leurs comportements, aussi bien dans des interactions entre humains qu’entre l’humain et l’animal. En effet, les animaux font partie de l’environnement des êtres humains et présentent de nombreux bénéfices. Ainsi, compte tenu du lien fort pouvant exister entre les ETSA et les animaux, nous posons l’hypothèse que le traitement de l’information faciale des animaux pourrait être typique dans les TSA. Nous avons mis en place une tâche d’exploration visuelle par eye tracking incluant des photographies en noir et blanc représentant des faces d’humains et d’animaux (chat, chien, cheval) qui ont été présentées à 18 EDT et 12 ETSA. Les résultats montrent que sur les photographies de faces d’animaux, la zone des yeux a été la zone la plus regardée tant par les EDT que les ETSA, quel que soit l’espèce animale ; et que sur les photographies de faces d’humains, seuls les EDT ont significativement plus regardé la zone des yeux. Les implications pour la compréhension des altérations des interactions sociales dans les TSA sont discutées

Face Processing of Animal and Human Static Stimuli by Children with Autism Spectrum Disorder: A Pilot Study

International audienceAnimals are part of humans’ social environment and present numerous benefits. Each partner in a human-animal interaction uses signals emitted by the other (e.g. postures, gestures or gaze directions) to collect information to adjust their behaviour. Face processing impairment is associated with social interaction impairment observed in autism spectrum disorders (ASD). For example children with ASD explore human eyes visually less than do neurotypical (NT) children. Given the strong bonding between ASD children and animals, we hypothesized that animal face processing by ASD is normal. Thus, our study compared ASD (n=12) and NT (n=18) childrens’ patterns of fixation of animal (horse, dog, and cat) and human faces in a passive viewing task using an eye tracking technique. Our results, using animal pictures, confirmed that the eyes were the part of the face looked at the longest by NT children and, to a lesser extent, by ASD children, but only NT children looked at the eyes of human pictures longer than other parts. Familiarity with animals seemed to modulate the exploration of animal, especially cat faces. Implications for understanding social interaction impairment related to ASD are discussed

Do children with autistic spectrum disorders look animals in the eyes? A pilot study using eye tracking technique

International audienceAnimals are part of humans’ social environment and present numerous benefits. Each partner in a human-animal interaction uses signals emitted by the other (e.g. postures, gestures or gaze directions) to collect information to adjust their behaviour. Face processing impairment is associated with social interaction impairment observed in autism spectrum disorders (ASD). For example children with ASD explore human eyes visually less than do neurotypical (NT) children. Given the strong bonding between ASD children and animals, we hypothesized that animal face processing by ASD is normal. Thus, our study compared ASD (n=12) and NT (n=18) childrens’ patterns of fixation of animal (horse, dog, and cat) and human faces in a passive viewing task using an eye tracking technique. Our results, using animal pictures, confirmed that the eyes were the part of the face looked at the longest by NT children and, to a lesser extent, by ASD children, but only NT children looked at the eyes of human pictures longer than other parts. Familiarity with animals seemed to modulate the exploration of animal, especially cat faces. Implications for understanding social interaction impairment related to ASD are discussed

Face Processing of Animal and Human Static Stimuli by Children with Autism Spectrum Disorder: A Pilot Study

International audienceAnimals are part of humans’ social environment and present numerous benefits. Each partner in a human-animal interaction uses signals emitted by the other (e.g. postures, gestures or gaze directions) to collect information to adjust their behaviour. Face processing impairment is associated with social interaction impairment observed in autism spectrum disorders (ASD). For example children with ASD explore human eyes visually less than do neurotypical (NT) children. Given the strong bonding between ASD children and animals, we hypothesized that animal face processing by ASD is normal. Thus, our study compared ASD (n=12) and NT (n=18) childrens’ patterns of fixation of animal (horse, dog, and cat) and human faces in a passive viewing task using an eye tracking technique. Our results, using animal pictures, confirmed that the eyes were the part of the face looked at the longest by NT children and, to a lesser extent, by ASD children, but only NT children looked at the eyes of human pictures longer than other parts. Familiarity with animals seemed to modulate the exploration of animal, especially cat faces. Implications for understanding social interaction impairment related to ASD are discussed