The One Health framework endorsed by the quadripartite (World Health Organization, World Organisation for Animal Health, Food and Agriculture Organization, and United Nations Environment Program) is defined, in part, as an "integrated, unifying approach that aims to sustainably balance and optimize the health of people, animals, and ecosystems," and it explicitly refers to the health of plants as part of the whole interrelated system to consider. Although the ultimate issue is the planet's habitability for humans, the definition introduces a shift in perspective-human health is no longer the sole priority but must be balanced and optimized alongside the health of animals, plants, and ecosystems. This raises some practical and ethical questions. Drawing on case studies and the framework of the IPBES (Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services) on the values of nature, this study explores the implications of a global approach to health, with the ethical and practical questions that it raises.

BACKGROUND:Posthepatectomy liver failure remains a potentially life-threatening complication after hepatectomy. Soluble suppression of tumourigenicity 2 is an injury-related biomarker. The aim of the study was to assess soluble suppression of tumourigenicity 2 elevation after hepatectomy and whether it can predict posthepatectomy liver failure. METHODS:This was a single-centre retrospective study including all patients who underwent a liver resection between 2015 and 2019. Plasma concentrations of soluble suppression of tumourigenicity 2 were measured before surgery and at postoperative days 1, 2, 5 and 7. Posthepatectomy liver failure was defined according to the International Study Group of Liver Surgery and the morbidity rate was graded according to the Clavien-Dindo classification. RESULTS:A total of 173 patients were included (75 underwent major and 98 minor resection); plasma levels of soluble suppression of tumourigenicity 2 increased from 43.42 (range 18.69-119.96) pg/ml to 2622.23 (range 1354.18-4178.27) pg/ml on postoperative day 1 (P < 0.001). Postoperative day 1 soluble suppression of tumourigenicity 2 concentration accurately predicted posthepatectomy liver failure ≥ grade B (area under curve = 0.916, P < 0.001) and its outstanding performance was not affected by underlying disease, liver pathological status and extent of resection. The cut-off value, sensitivity, specificity, positive predictive value and negative predictive value of postoperative day 1 soluble suppression of tumourigenicity 2 in predicting posthepatectomy liver failure ≥ grade B were 3700, 92%, 85%, 64% and 97% respectively. Soluble suppression of tumourigenicity 2high patients more frequently experienced posthepatectomy liver failure ≥ grade B (64.3% (n = 36) versus 2.6% (n = 3)) and Clavien-Dindo IIIa higher morbidity rate (23.2% (n = 13) versus 5.1% (n = 6)) compared with soluble suppression of tumourigenicity 2low patients. CONCLUSIONS:Soluble suppression of tumourigenicity 2 may be a reliable predictor of posthepatectomy liver failure ≥ grade B as early as postoperative day 1 for patients undergoing liver resection. Its role in controlling hepatic injury/regeneration needs further investigation. Registration number: ChiCTR-OOC-15007210 (www.chictr.org.cn/).

Immune exhaustion corresponds to a loss of effector function of T cells that associates with cancer or chronic infection. Here, our objective was to decipher the mechanisms involved in the immune suppression of myeloid-derived suppressor cells (MDSCs) and to explore the potential to target these cells for immunotherapy to enhance checkpoint blockade efficacy in a chronic parasite infection. We demonstrated that programmed cell-death-1 (PD-1) expression was significantly upregulated and associated with T-cell dysfunction in advanced alveolar echinococcosis (AE) patients and in Echinococcus multilocularis-infected mice. PD-1 blockade ex vivo failed to reverse AE patients’ peripheral blood T-cell dysfunction. PD-1/PD-L1 blockade or PD-1 deficiency had no significant effects on metacestode in mouse model. This was due to the inhibitory capacities of immunosuppressive granulocytic MDSCs (G-MDSCs), especially in the liver surrounding the parasite pseudotumor. MDSCs suppressed T-cell function in vitro in an indoleamine 2, 3 dioxygenase 1 (IDO1)-dependent manner. Although depleting MDSCs alone restored T-cell effector functions and led to some limitation of disease progression in E. multilocularis-infected mice, combination with PD-1 blockade was better to induce antiparasitic efficacy. Our findings provide preclinical evidence in support of targeting MDSC or combining such an approach with checkpoint blockade in patients with advanced AE. Myeloid-derived suppressor cells play an important role in immune suppression caused by Echinococcus multilocularis infection. This study demonstrates that the removal of this cell type effectively restores T-cell function and potentiates PD-1 blockade therapy in chronic liver infection.

Immune exhaustion corresponds to a loss of effector function of T cells that associates with cancer or chronic infection. Here, our objective was to decipher the mechanisms involved in the immune suppression of myeloid-derived suppressor cells (MDSCs) and to explore the potential to target these cells for immunotherapy to enhance checkpoint blockade efficacy in a chronic parasite infection. We demonstrated that programmed cell-death-1 (PD-1) expression was significantly upregulated and associated with T-cell dysfunction in advanced alveolar echinococcosis (AE) patients and in Echinococcus multilocularis-infected mice. PD-1 blockade ex vivo failed to reverse AE patients' peripheral blood T-cell dysfunction. PD-1/PD-L1 blockade or PD-1 deficiency had no significant effects on metacestode in mouse model. This was due to the inhibitory capacities of immunosuppressive granulocytic MDSCs (G-MDSCs), especially in the liver surrounding the parasite pseudotumor. MDSCs suppressed T-cell function in vitro in an indoleamine 2, 3 dioxygenase 1 (IDO1)-dependent manner. Although depleting MDSCs alone restored T-cell effector functions and led to some limitation of disease progression in E. multilocularis-infected mice, combination with PD-1 blockade was better to induce antiparasitic efficacy. Our findings provide preclinical evidence in support of targeting MDSC or combining such an approach with checkpoint blockade in patients with advanced AE. (200 words) Myeloid-derived suppressor cells play an important role in immune suppression caused by Echinococcus multilocularis infection. This study demonstrates that the removal of this cell type effectively restores T-cell function and potentiates PD-1 blockade therapy in chronic liver infection.

Introduction (contexte de la recherche) Whereas early microbial environment is known as a protective factor for atopic diseases, few studies explored the role of early environment in the development of cough during childhood. Objectif This study aims to assess the association between early environment and childhood trajectories of cough without a cold. Méthodes Early environment was assessed by farm-specific, home, food and infectious exposures during pregnancy and first year of life in the European prospective birth cohort of Protection against Allergy: STUdy in Rural Environment (PASTURE). Multinomial logistic regression was used to evaluate the association between early environment and trajectories of cough without a cold from 1 to 10 years. Résultats Among the 961 children included, apart from the never/infrequent trajectory (59.9%), eight trajectories of cough without a cold were identified: five grouped acute transient classes (24.1%), moderate transient (6.8%), late persistent (4.8%), and early persistent (4.4%). Persistent trajectories were associated with atopic respiratory diseases and food allergy. Any consumption of boiled and raw farm milk in the first year of life were associated with a decreased risk of early persistent cough (OR=0.17 [0.04–0.72] and OR=0.11 [0.01–0.81], respectively), even after adjustment for asthma. Consumption of farm milk was also associated with a decreased risk of acute transient cough. Barn exposure, and dampness at home (with or without moulds) seems to be associated with early persistent cough. Maternal smoking was associated with an increased risk of acute and moderate transient cough. Otitis in the first 4 months and respiratory tract infections for 8 weeks or more during the first year of life were associated with a higher risk of early persistent cough. Conclusions Whereas early otitis and repeated respiratory tract infections are risk factors for early persistent cough, early microbial exposure, especially through farm milk consumption, has a protective effect against persistent cough with an early onset.

Alveolar echinococcosis (AE) is a severe parasitic infection caused by the ingestion of Echinococcus multilocularis eggs. While higher incidence and faster evolution have been reported in immunosuppressed patients, no studies have been performed specifically on AE in transplant patients. We searched for all de novo AE cases diagnosed between January 2008 and August 2018 in solid organ transplant (SOT) recipients included in the Swiss Transplant Cohort Study and the FrancEchino Registry. Eight cases were identified (kidney = 5, lung = 2, heart = 1, liver = 0), half of which were asymptomatic at diagnosis. AE diagnosis was difficult due to the low sensitivity (60%) of the standard screening serology (Em2+) and the frequently atypical radiological presentations. Conversely, Echinococcus Western blot retained good diagnostic performances and was positive in all eight cases. Five patients underwent surgery, but complete resection could only be achieved in one case. Moreover, two patients died of peri-operative complications. Albendazole was initiated in seven patients and was well tolerated. Overall, AE regressed in one, stabilized in three, and progressed in one case, and had an overall mortality of 37.5% (3/8 patients). Our data suggest that AE has a higher mortality and a faster clinical course in SOT recipients; they also suggest that the parasitic disease might be due to the reactivation of latent microscopic liver lesions through immune suppression. Western blot serology should be preferred in this population. Finally, surgery should be considered with caution, because of its low success rate and high mortality, and conservative treatment with albendazole is well tolerated.

This chapter discusses the research on the influence of the environment of a livestock farm in the protection against the occurrence of allergic diseases during the life of an individual. It was the observation of an unprecedented increase in allergic diseases in the European, American and Japanese populations after Second World War that precipitated the implementation of research in these areas. Since the 1990s, a large number of cross-sectional epidemiological studies have supplemented the initial observations of the 1980s. The combination of these epidemiological results gave rise to the explanatory hypothesis of "hygiene", capable of accounting for the observations by resituating them in the immunological concepts of the time. As in the population-based studies, it was the observation of protection by raw milk consumption that was also the most consistent finding in the analyses from the Protection Against Allergy: Study in Rural Environments cohort.

Background: This study aimed to develop and validate a nomogram for individually predicting coronary artery calcium (CAC) progression.Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) cohort with 5486 participants (47.3% male, mean [SD] age 61.9 [10.2] years) were included, who were randomly assigned into the training set, or the internal validation set at a 7:3 ratio. A separate cohort of 2447 participants (44.6% male, a mean [SD] age of 40.4 [3.5] years) from the Coronary Artery Risk Development in Young Adults (CARDIA) study served as the external validation set. Baseline clinical characteristics, findings on physical examination, and laboratory profiles were assessed. CAC progression was the primary outcome measure. A nomogram was established based on the least absolute shrinkage and selection operator (LASSO)-derived Cox regression model. The discrimination and calibration ability of this nomogram was evaluated by Hosmer–Lemeshow test and calibration curves in the training and validation cohorts.Findings: Sixty-one features were reduced to 10, which were age, male gender, smoking status, waist circumference, systolic blood pressure, fasting glucose, lipid abnormalities, antihypertensive medication, and glucose-lowering medication and lipid-lowering medication use. The nomogram model showed a good discrimination in the training set (C-statistics: 0.682; 95% CI, 0.665-0.699), and application in the validation sets also gave good discrimination (C-statistics for the internal validation: 0.664; 95% CI, 0.638-0.690; for the external validation: 0.750; 95% CI, 0.729-0.771), which was better than the Framingham Risk Score model (C-statistics: 0.677; 95% CI, 0.663-0.691 vs. 0.658; 95% CI, 0.644-0.672, P<0.001). Calibration test yielded a high consistency between prediction and observation. Decision curve analysis demonstrated the clinical usefulness of the nomogram for predicting the risk of CAC progression. Interpretation: This study presents a nomogram that may be used to facilitate individualized prediction of CAC progression and should help better focus on primary prevention of cardiovascular disease in clinical practice. Funding: This work was supported by grants from National Natural Science Foundation of China (NSFC) [82170457, 81900379, 81870315, 81970683], Guangdong Basic and Applied Basic Research Foundation [2020A1515110313], and Yat-sen Start-up Foundation [YXQH202014]. The MESA study was supported by contracts N01-HC-95159 through N01-HC-95167 from the National Heart, Lung, and Blood Institute (NHLBI). The CARDIA study is conducted and supported by the NHLBI in collaboration with the University of Alabama at Birmingham (grants HHSN268201800005I and HHSN268201800007I), Northwestern University (grant HHSN268201800003I), University of Minnesota (grant HHSN268201800006I), and Kaiser Foundation Research Institute (grant HHSN268201800004I), of the United States. The authors report no conflicts of interest. (9) Clinical trial registration number: The CARDIA trial was registered at clinicaltrials.gov as NCT00005130. The MESA trial was registered at clinicaltrials.gov as NCT00005487.Declaration of Interest: The authors report no conflicts of interest.Ethical Approval: All participants provided informed consent and the study protocol was approved by the Institutional Review Boards at each participating institution.

L’échinocoque multiloculaire est un parasite provoquant une maladie mortelle pour les humains, l’échinococcose alvéolaire. La combinaison des recherches menées sur les plateaux du Jura, puis en Chine de l’ouest et au Kirgizhistan, permet d’établir, par une approche écoépidémiologique, un tableau des facteurs écologiques et socio-économiques qui favorisent l’émergence de « paysages à risque » et l’enclenchement de processus qui mènent le parasite jusqu’aux personnes.

La santé a, comme le reste de la société, profité des avancées technologiques dès la fin du 20e siècle. La e-santé s’inscrit dans différents domaines, à la fois pour les patients, pour les soignants et pour les institutions. Chaque spécialité médicale s’est impliquée différemment dans chacun des domaines. En allergologie, la téléconsultation s’est particulièrement développée depuis 2020 alors que la téléexpertise est très peu utilisée. Les réseaux sociaux sont pourvoyeurs de beaucoup d’informations sur les allergies mais sans aucun contrôle sur la véracité de celles-ci. Les différentes facettes de l’allergologie peuvent être découvertes et approfondies en ligne grâce à de nombreux sites et applis, aux contenus rédigés ou contrôlés par des médecins. Il reste encore de nombreuses voies à explorer, notamment l’intelligence artificielle et les objets connectés.Health has, like the rest of society, benefited from technological advances since the end of the 20th century. This e-health corresponds to different areas, both for patients, for caregivers and for institutions. Each medical specialty is involved differently in each area. In allergology, teleconsultation has particularly raised since 2020, while tele-expertise is very little used. Social Medias are providers of a lot of information on allergies but without any control on the veracity of these. The different facets of allergology can be discovered and deepened online thanks to numerous sites and apps, with content written or checked by doctors. There are still many ways to explore, including artificial intelligence and connected objects.

BACKGROUND:Although children can frequently experience a cough that affects their quality of life, few epidemiological studies have explored cough without a cold during childhood.OBJECTIVES:The objective of the study was to describe the latent class trajectories of cough from one to 10 years old and analyse their association with wheezing, atopy and allergic diseases.METHODS:Questions about cough, wheeze and allergic diseases were asked at 1, 1.5, 2, 3, 4, 5, 6 and 10 years of age in the European prospective cohort of Protection against Allergy: STUdy in Rural Environment (PASTURE). Specific IgE assays were performed at 10 years of age. Questions regarding a cough without a cold were used to build a latent class model of cough over time.RESULTS:Among the 961 children included in the study, apart from the never/infrequent trajectory (59.9%), eight trajectories of cough without a cold were identified: five grouped acute transient classes (24.1%), moderate transient (6.8%), late persistent (4.8%) and early persistent (4.4%). Compared with the never/infrequent trajectory, the other trajectories were significantly associated with wheezing, asthma and allergic rhinitis. For asthma, the strongest association was with the early persistent trajectory (ORa  = 31.00 [14.03-68.51]), which was inversely associated with farm environment (ORa  = 0.39 [0.19-0.77]) and had a high prevalence of cough triggers and unremitting wheeze. Late and early persistent trajectories were also associated with food allergy. Atopic sensitization was only associated with the late persistent trajectory.CONCLUSION:Late and early persistent coughs without a cold are positively associated with atopic respiratory diseases and food allergy. Children having recurrent cough without a cold with night cough and triggers would benefit from an asthma and allergy assessment. Growing up on a farm is associated with reduced early persistent cough.

L’étude de cohorte PASTURE qui combine depuis 18 ans dans 5 pays européens des études environnementales, microbiologiques, génétiques, et immunologiques chez des enfants vivant ou non dans des fermes d’élevage laitier montre que la biodiversité des milieux de vie traditionnels ruraux est un rempart à l’augmentation sans précédent de la prévalence des maladies allergiques dans la deuxième moitié du XXème siècle.

Background: To investigate whether obesity with or without metabolic syndrome is prospectively associated with coronary artery calcium (CAC) progression and incident cardiovascular disease events. Methods: A total of 1730 participants from the CARDIA study (Coronary Artery Risk Development in Young Adults) were included (age, 40.1±3.6 years; 38.3% men), who completed computed tomography of CAC at baseline (year 15: 2000–2001) and follow-up (year 20 or 25). Metabolically healthy obesity (MHO) was defined as body mass index≥30 kg/m 2 without any metabolic syndrome components in our main analysis. Sensitivity analyses were conducted for several conditions characterizing 4 metabolic phenotypes. Results: During a mean follow-up of 9.1 years, 439 participants had CAC progression. MHO subjects had a significantly higher risk of CAC progression than their metabolically healthy normal weight counterparts (adjusted hazard ratios [95% CIs] from 1.761 [1.369–2.264] to 2.047 [1.380–3.036]) depending on the definition of MHO adopted. Obesity with unhealthy metabolic profile remained the highest significant risk of CAC progression and cardiovascular disease events whatever the definitions adopted for metabolically unhealthy status. Up to 60% of participants with MHO converted to metabolically unhealthy obesity from year 15 to year 20 or year 25. Further sensitivity analysis showed that MHO throughout carried a similar risk of incident cardiovascular disease events compared with metabolically healthy normal weight throughout. Conclusions: Different metabolic phenotypes of obesity beginning at a young age exhibit distinct risks of CAC progression and subsequent cardiovascular disease events in later midlife. MHO represents an intermediate phenotype between metabolically low- to high-risk obese individuals. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00005130.

Objective The study aimed to assess the associations of physical activity (PA) trajectories across a 25-year span with coronary artery calcium (CAC) progression, and subsequent risk of cardiovascular disease (CVD) events. Methods We included 2497 participants from the Coronary Artery Disease Risk Development in Young Adults study who had computed tomography-assessment of CAC at baseline (year 15: 2000-2001) and follow-up (year 20 or 25) and at least three measures of PA from year 0 to year 25. Long-term PA trajectories were determined by latent class modelling using a validated questionnaire. Results Among the included participants, 1120 (44.9%) were men, 1418 (56.8%) were white, and the mean (SD) age was 40.4 (3.6) years. We identified three distinct PA trajectories based on PA average levels and change patterns: low (below PA guidelines, n=1332; 53.3%); moderate (meeting and slightly over PA guidelines, n=919; 36.8%) and high (about three times PA guidelines or more, n=246; 9.9%). During a mean (SD) follow-up of 8.9 (2.1) years, 640 (25.6%) participants had CAC progression. Participants in the high PA trajectory group had a higher risk of CAC progression than those in the low PA trajectory group after adjustment for traditional cardiovascular risk factors (HR 1.51; 95% CI 1.18 to 1.94). However, high PA trajectory was not associated with an increased risk of incident CVD events (HR 1.01; 95% CI 0.44 to 2.31) and the incidence of CVD events in participants with CAC progression was similar across all three PA trajectory groups (p=0.736). Conclusion Long-term PA about three times the guidelines or more is independently associated with CAC progression; however, no additional risk of incident CVD events could be detected.