L’animal : un objet d’étude

Homo animal est : l’être humain appartient lui-même au règne animal, mais il est le seul à projeter sur les autres membres de ce vaste ensemble un regard analytique. Prendre l’animal comme objet d’étude, c’est le propre de l’homme. « Chez absolument tous il y a quelque chose de naturel, c’est-à-dire de beau » : Aristote, s’apprêtant à détailler les Parties des animaux, prévient son lecteur que les animaux les plus répugnants méritent eux aussi l’attention du scientifique, car ils témoignent des règles auxquelles se conforme la nature, que le philosophe a à cœur de percer. Cette longue tradition d’étude du monde animal, renouvelée aujourd’hui par les découvertes sur le génome, a pris de multiples formes au travers des âges ; mais elle a toujours suscité d’amples questionnements, non seulement sur la nature des animaux eux-mêmes, mais aussi, plus largement, sur leur place dans le monde et, en retour, sur celle de l’homme lui-même. Le Congrès national des sociétés historiques et scientifiques rassemble chaque année universitaires, membres de sociétés savantes et jeunes chercheurs. Ce recueil est issu de travaux présentés lors du 141e Congrès sur le thème « L’animal et l’homme »

Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Publisher Copyright: © 2021 The Authors, some rights reserved.Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-alpha and/or IFN-omega are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-alpha and/or IFN-omega (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-beta. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-alpha and/or IFN-omega are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-beta do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases.Peer reviewe

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

SignificanceThere is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged 4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute; The Rockefeller University; the St. Giles Foundation; the NIH (Grants R01AI088364 and R01AI163029); the National Center for Advancing Translational Sciences; NIH Clinical and Translational Science Awards program (Grant UL1 TR001866); a Fast Grant from Emergent Ventures; Mercatus Center at George Mason University; the Yale Center for Mendelian Genomics and the Genome Sequencing Program Coordinating Center funded by the National Human Genome Research Institute (Grants UM1HG006504 and U24HG008956); the Yale High Performance Computing Center (Grant S10OD018521); the Fisher Center for Alzheimer’s Research Foundation; the Meyer Foundation; the JPB Foundation; the French National Research Agency (ANR) under the “Investments for the Future” program (Grant ANR-10-IAHU-01); the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (Grant ANR-10-LABX-62-IBEID); the French Foundation for Medical Research (FRM) (Grant EQU201903007798); the French Agency for Research on AIDS and Viral hepatitis (ANRS) Nord-Sud (Grant ANRS-COV05); the ANR GENVIR (Grant ANR-20-CE93-003), AABIFNCOV (Grant ANR-20-CO11-0001), CNSVIRGEN (Grant ANR-19-CE15-0009-01), and GenMIS-C (Grant ANR-21-COVR-0039) projects; the Square Foundation; Grandir–Fonds de solidarité pour l’Enfance; the Fondation du Souffle; the SCOR Corporate Foundation for Science; The French Ministry of Higher Education, Research, and Innovation (Grant MESRI-COVID-19); Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM; and the University Paris Cité. P. Bastard was supported by the FRM (Award EA20170638020). P. Bastard., J.R., and T.L.V. were supported by the MD-PhD program of the Imagine Institute (with the support of Fondation Bettencourt Schueller). Work at the Neurometabolic Disease lab received funding from Centre for Biomedical Research on Rare Diseases (CIBERER) (Grant ACCI20-767) and the European Union's Horizon 2020 research and innovation program under grant agreement 824110 (EASI Genomics). Work in the Laboratory of Virology and Infectious Disease was supported by the NIH (Grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1), a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Infanta Leonor University Hospital supported the research of the Department of Internal Medicine and Allergology. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (Grant PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (Grant RECOVER WP 6). This work was also partly supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research, NIH (Grants ZIA AI001270 to L.D.N. and 1ZIAAI001265 to H.C.S.). This program is supported by the Agence Nationale de la Recherche (Grant ANR-10-LABX-69-01). K.K.’s group was supported by the Estonian Research Council, through Grants PRG117 and PRG377. R.H. was supported by an Al Jalila Foundation Seed Grant (Grant AJF202019), Dubai, United Arab Emirates, and a COVID-19 research grant (Grant CoV19-0307) from the University of Sharjah, United Arab Emirates. S.G.T. is supported by Investigator and Program Grants awarded by the National Health and Medical Research Council of Australia and a University of New South Wales COVID Rapid Response Initiative Grant. L.I. reports funding from Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e co-morbidità”). This research was partially supported by the Instituto de Salud Carlos III (Grant COV20/0968). J.R.H. reports funding from Biomedical Advanced Research and Development Authority (Grant HHSO10201600031C). S.O. reports funding from Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development (Grant JP20fk0108531). G.G. was supported by the ANR Flash COVID-19 program and SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University iCOVID programs. The 3C Study was conducted under a partnership agreement between INSERM, Victor Segalen Bordeaux 2 University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also supported by the Caisse Nationale d’Assurance Maladie des Travailleurs Salariés, Direction générale de la Santé, Mutuelle Générale de l’Education Nationale, Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Program “Cohortes et collections de données biologiques.” S. Debette was supported by the University of Bordeaux Initiative of Excellence. P.K.G. reports funding from the National Cancer Institute, NIH, under Contract 75N91019D00024, Task Order 75N91021F00001. J.W. is supported by a Research Foundation - Flanders (FWO) Fundamental Clinical Mandate (Grant 1833317N). Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. Work at Vall d’Hebron was also partly supported by research funding from Instituto de Salud Carlos III Grant PI17/00660 cofinanced by the European Regional Development Fund (ERDF/FEDER). C.R.-G. and colleagues from the Canarian Health System Sequencing Hub were supported by the Instituto de Salud Carlos III (Grants COV20_01333 and COV20_01334), the Spanish Ministry for Science and Innovation (RTC-2017-6471-1; AEI/FEDER, European Union), Fundación DISA (Grants OA18/017 and OA20/024), and Cabildo Insular de Tenerife (Grants CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). T.H.M. was supported by grants from the Novo Nordisk Foundation (Grants NNF20OC0064890 and NNF21OC0067157). C.M.B. is supported by a Michael Smith Foundation for Health Research Health Professional-Investigator Award. P.Q.H. and L. Hammarström were funded by the European Union’s Horizon 2020 research and innovation program (Antibody Therapy Against Coronavirus consortium, Grant 101003650). Work at Y.-L.L.’s laboratory in the University of Hong Kong (HKU) was supported by the Society for the Relief of Disabled Children. MBBS/PhD study of D.L. in HKU was supported by the Croucher Foundation. J.L.F. was supported in part by the Evaluation-Orientation de la Coopération Scientifique (ECOS) Nord - Coopération Scientifique France-Colombie (ECOS-Nord/Columbian Administrative department of Science, Technology and Innovation [COLCIENCIAS]/Colombian Ministry of National Education [MEN]/Colombian Institute of Educational Credit and Technical Studies Abroad [ICETEX, Grant 806-2018] and Colciencias Contract 713-2016 [Code 111574455633]). A. Klocperk was, in part, supported by Grants NU20-05-00282 and NV18-05-00162 issued by the Czech Health Research Council and Ministry of Health, Czech Republic. L.P. was funded by Program Project COVID-19 OSR-UniSR and Ministero della Salute (Grant COVID-2020-12371617). I.M. is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies (PID); by the Katholieke Universiteit Leuven C1 Grant C16/18/007; by a Flanders Institute for Biotechnology-Grand Challenges - PID grant; by the FWO Grants G0C8517N, G0B5120N, and G0E8420N; and by the Jeffrey Modell Foundation. I.M. has received funding under the European Union’s Horizon 2020 research and innovation program (Grant Agreement 948959). E.A. received funding from the Hellenic Foundation for Research and Innovation (Grant INTERFLU 1574). M. Vidigal received funding from the São Paulo Research Foundation (Grant 2020/09702-1) and JBS SA (Grant 69004). The NH-COVAIR study group consortium was supported by a grant from the Meath Foundation.Peer reviewe

In vitro analysis of patellar kinematics: validation of an opto-electronic cinematic analysis protocol

Opto-electronic cinematic analysis has already proven useful in the investigation of patients with a knee replacement; however, neither patellar tracking nor the various positional parameters relevant to instability such as patellar tilt and/or patellar shift have ever been specifically evaluated using this type of system. The aim of this research was to validate the relevance of this type of cinematic analysis in order to use it in the evaluation of the main factors underlying patellar instability. Six fresh-frozen anatomical specimens were studied. The data were acquired using the Motion Analysis system. Statistical analysis reveals a good reproducibility of measurements. Our protocol based on an opto-electronic acquisition system has an accuracy of 0.23 mm for shift and of 0.4 for rotation, which is calculated by integrating the various experimental parameters and instrumental features specific to the Motion Analysis system. The results are consistent with published results which further attests to the validity and the efficacy of the protocol and encourages us that this protocol is suitable for the in vitro study of patellar kinematics

Medial patellofemoral ligament anatomy: implications for its surgical reconstruction

The purpose of the present study, based on 23 cadaveric knees, was to perform a detailed anatomical analysis of the medial patellofemoral ligament (MPFL), especially its femoral attachment, its relationships with the vastus medialis obliquus (VMO) and the medial collateral ligament, with the objective of improving its surgical reconstruction. The femoral insertion of the MPFL was defined using an orthonormal frame centered on the middle of the femoral MPFL insertion. The whole measurements were taken using a millimetric compass with a precision of +/-1 mm. The MPFL was always observed, its length was 57.7 +/- 5.8 mm, the junction between the VMO and the MPFL always present measured 25.7 +/- 6.0 mm. When it comes to MPFL reconstruction, the key point is its positioning in the femoral insertion because it is this insertion that is going to restore isometry. By using the orthonormal frame it has to be positioned 10 mm behind the medial epicondyle and 10 mm distal to the adductor tubercle

Pelvic balance in sagittal and Lewinnek reference planes in the standing, supine and sitting positions

INTRODUCTION: Sagittal pelvic balance is a recognized factor influencing targeted acetabular-component anteversion during total hip arthroplasty implantation. However, no studies in the literature have systematically reported pelvic parameters data in the standing, sitting and supine positions. HYPOTHESIS: Variations in acetabular cup orientation can be traced to eventual pelvic balance changes in one of these three usual positions. MATERIALS AND METHODS: In these three positions (supine, standing and sitting), pelvic anatomical parameters and reference planes were radiologically defined from a group of 67 patients (average age: 70.2+/-3.2 years). The complete X-rays individual sets were digitized and measurements were obtained by a single operator using a Spineview software (previously, strictly validated for these kind of measurements). Positioning according to the Lewinnek pelvic coordinate system, which is considered as a possible source of errors when vertically standing or horizontally lying, was also investigated. RESULTS: The average pelvic incidence of 59.6 degrees did not vary in the sitting, supine or standing positions, with no statistically significant difference between sexes. The Legaye equation--pelvic incidence is equals to pelvic version plus sacral slope--was verified. Pelvic version increased by an average 22 degrees from the sitting to the supine or standing positions. Sacral slope varied in a reverse order. Pelvic-femoral angle (PFA) decreased by 20 degrees from the standing to the supine position. The Lewinnek plane was located 4 degrees posterior to the vertical plane. Whatever the position adopted, pelvi-Lewinnek angle appeared constant, averaging 12 degrees. DISCUSSION: The average pelvic incidence in this series was high, most probably associated with advancing patient age and/or pathology. The concept of functional anteversion appeared critical when taking into account pelvic version variations (according to the position, sitting, supine or standing) positions. The Lewinnek plane, commonly accepted as the reference plane for hip navigation, was individualised to each patient and should not be mistaken with the vertical plane; positioning of the femur in relation to the Lewinnek plane was also specific to each patient. Cumulative approximation on these two parameters at surgery resulted in a combined imprecision of 26 degrees when standing and 36 degrees when lying down. We have thus defined crucial parameters to be integrated in computer-assisted hip surgery softwares: positional variations of the pelvic version (functional anteversion), positioning of the Lewinnek plane, and PFA value (both specifically patient's dependant). If integration of these parameters into new sofwares versions appears possible, this would represent a reliable compromise between maximum prosthetic stability, maximum joint amplitudes and elimination of possible prosthetic conflict

Repair of insertional achilles tendinosis with a bone-quadriceps tendon graft

ACKGROUND: While conservative treatment may be successful in most cases, partial rupture at the calcaneal insertion point is a significant concern with insertional Achilles tendinopathy. We report on the outcomes of a surgical technique for Achilles tendon augmentation using a bone-tendon graft harvested from the knee extensor system. MATERIALS AND METHODS: Our retrospective case series includes 25 surgical procedures performed in 24 patients, 19 males and five females, with a mean age of 47 (range, 30 to 59) years, 18 of whom were athletes. The mean followup period was 52 (range, 12 to 156) months. All patients underwent MRI examination prior to surgery which showed partial Achilles tendon rupture. The Achilles tendon was debrided through a posterolateral approach. The bone-quadriceps tendon graft was harvested, then the bone plug of the graft was inserted into a blind tunnel drilled into the calcaneus and fixed with an interference screw. The fibers of the quadriceps tendon were sutured to the residual part of the Achilles tendon with the foot at an angle of 90 degrees. RESULTS: Patients were able to resume their sporting activity after an average of 6.7 months. At last followup examination, physical activity was scored 5.2 on the 10-point Tegner Scale; the mean AOFAS score was 98.4. MRI examination showed good graft integration 1 year postoperatively. CONCLUSION: The bone-quadriceps tendon grafting technique was a good alternative for the insertional Achilles lesions with partial detachment which we felt required augmentation