Maternal and perinatal outcomes following pre-Delta, Delta, and Omicron SARS-CoV-2 variants infection among unvaccinated pregnant women in France and Switzerland: a prospective cohort study using the COVI-PREG registry.

BACKGROUND SARS-CoV-2 positive pregnant women are at higher risk of adverse outcomes, but little evidence is available on how variants impact that risk. We aim to evaluate maternal and perinatal outcomes among unvaccinated pregnant women that tested positive for SARS-CoV-2, stratified by pre-Delta, Delta, and Omicron periods. METHODS This prospective study enrolled women from March 2020 to September 2022. Exposure to the different SARS-CoV-2 variants was defined by their periods of predominance. The primary outcome was severe maternal adverse outcome defined as either intensive care unit admission, acute respiratory distress syndrome, advanced oxygen supplementation, or maternal death. The secondary outcomes were preterm birth and other perinatal outcomes. FINDINGS Overall, 1402, 262, and 391 SARS-CoV-2 positive pregnant women were enrolled during the pre-Delta, Delta, and Omicron periods respectively. Severe maternal adverse outcome was reported in 3.4% (n = 947/1402; 95% confidence intervals (95%CI) 2.5-4.5), 6.5% (n = 7/262; 95%CI 3.8-10.2), and 1.0% (n = 4/391; 95%CI 0.3-2.6) of women during the pre-Delta, Delta, and Omicron periods. The risk of severe maternal adverse outcome was higher during the Delta vs pre-Delta period (adjusted risk ratio (aRR) = 1.8; 95%CI 1.1-3.2) and lower during the Omicron vs pre-Delta period (aRR = 0.3; 95%CI, 0.1-0.8). The risks of hospitalization for COVID-19 were 12.6% (n = 176/1402; 95%CI 10.9-14.4), 17.2% (n = 45/262; 95%CI 12.8-22.3), and 12.5% (n = 49/391; 95%CI 9.4-16.2), during the pre-Delta, Delta, and Omicron period, respectively. Pregnancy complications occurred after SARS-CoV-2 exposure in 30.0% (n = 363/1212; 95%CI 27.4-32.6), 35.2% (n = 83/236; 95%CI 29.1-41.6), and 30.3% (n = 105/347; 95%CI 25.5-35.4) of patients during the pre-Delta, Delta, and Omicron periods, respectively. Stillbirths were reported in 0.5% (n = 6/1159; 95%CI 0.2-1.1), 2.8% (n = 6/210; 95%CI 1.0-6.0), and 0.9% (n = 2/213; 95%CI 0.1-3.4) or patients during the pre-Delta, Delta, and Omicron periods respectively. INTERPRETATION The Delta period was associated with a higher risk of severe maternal adverse outcome and the Omicron period with a lower risk of severe adverse outcome compared to pre-Delta era. The reported risk of hospitalization was high during the Omicron period and should not be trivialized. FUNDING Swiss Federal Office of Public Health, Fondation CHUV

Systematic Review of Active Surveillance for Clinically Localised Prostate Cancer to Develop Recommendations Regarding Inclusion of Intermediate-risk Disease, Biopsy Characteristics at Inclusion and Monitoring, and Surveillance Repeat Biopsy Strategy

none38siContext: There is uncertainty regarding the most appropriate criteria for recruitment, monitoring, and reclassification in active surveillance (AS) protocols for localised prostate cancer (PCa). Objective: To perform a qualitative systematic review (SR) to issue recommendations regarding inclusion of intermediate-risk disease, biopsy characteristics at inclusion and monitoring, and repeat biopsy strategy. Evidence acquisition: A protocol-driven, Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-adhering SR incorporating AS protocols published from January 1990 to October 2020 was performed. The main outcomes were criteria for inclusion of intermediate-risk disease, monitoring, reclassification, and repeat biopsy strategies (per protocol and/or triggered). Clinical effectiveness data were not assessed. Evidence synthesis: Of the 17 011 articles identified, 333 studies incorporating 375 AS protocols, recruiting 264 852 patients, were included. Only a minority of protocols included the use of magnetic resonance imaging (MRI) for recruitment (n = 17), follow-up (n = 47), and reclassification (n = 26). More than 50% of protocols included patients with intermediate or high-risk disease, whilst 44.1% of protocols excluded low-risk patients with more than three positive cores, and 39% of protocols excluded patients with core involvement (CI) >50% per core. Of the protocols, ≥80% mandated a confirmatory transrectal ultrasound biopsy; 72% (n = 189) of protocols mandated per-protocol repeat biopsies, with 20% performing this annually and 25% every 2 yr. Only 27 protocols (10.3%) mandated triggered biopsies, with 74% of these protocols defining progression or changes on MRI as triggers for repeat biopsy. Conclusions: For AS protocols in which the use of MRI is not mandatory or absent, we recommend the following: (1) AS can be considered in patients with low-volume International Society of Urological Pathology (ISUP) grade 2 (three or fewer positive cores and cancer involvement ≤50% CI per core) or another single element of intermediate-risk disease, and patients with ISUP 3 should be excluded; (2) per-protocol confirmatory prostate biopsies should be performed within 2 yr, and per-protocol surveillance repeat biopsies should be performed at least once every 3 yr for the first 10 yr; and (3) for patients with low-volume, low-risk disease at recruitment, if repeat systematic biopsies reveal more than three positive cores or maximum CI >50% per core, they should be monitored closely for evidence of adverse features (eg, upgrading); patients with ISUP 2 disease with increased core positivity and/or CI to similar thresholds should be reclassified. Patient summary: We examined the literature to issue new recommendations on active surveillance (AS) for managing localised prostate cancer. The recommendations include setting criteria for including men with more aggressive disease (intermediate-risk disease), setting thresholds for close monitoring of men with low-risk but more extensive disease, and determining when to perform repeat biopsies (within 2 yr and 3 yearly thereafter).noneWillemse, Peter-Paul M; Davis, Niall F; Grivas, Nikolaos; Zattoni, Fabio; Lardas, Michael; Briers, Erik; Cumberbatch, Marcus G; De Santis, Maria; Dell'Oglio, Paolo; Donaldson, James F; Fossati, Nicola; Gandaglia, Giorgio; Gillessen, Silke; Grummet, Jeremy P; Henry, Ann M; Liew, Matthew; MacLennan, Steven; Mason, Malcolm D; Moris, Lisa; Plass, Karin; O'Hanlon, Shane; Omar, Muhammad Imran; Oprea-Lager, Daniela E; Pang, Karl H; Paterson, Catherine C; Ploussard, Guillaume; Rouvière, Olivier; Schoots, Ivo G; Tilki, Derya; van den Bergh, Roderick C N; Van den Broeck, Thomas; van der Kwast, Theodorus H; van der Poel, Henk G; Wiegel, Thomas; Yuan, Cathy Yuhong; Cornford, Philip; Mottet, Nicolas; Lam, Thomas B LWillemse, Peter-Paul M; Davis, Niall F; Grivas, Nikolaos; Zattoni, Fabio; Lardas, Michael; Briers, Erik; Cumberbatch, Marcus G; De Santis, Maria; Dell'Oglio, Paolo; Donaldson, James F; Fossati, Nicola; Gandaglia, Giorgio; Gillessen, Silke; Grummet, Jeremy P; Henry, Ann M; Liew, Matthew; Maclennan, Steven; Mason, Malcolm D; Moris, Lisa; Plass, Karin; O'Hanlon, Shane; Omar, Muhammad Imran; Oprea-Lager, Daniela E; Pang, Karl H; Paterson, Catherine C; Ploussard, Guillaume; Rouvière, Olivier; Schoots, Ivo G; Tilki, Derya; van den Bergh, Roderick C N; Van den Broeck, Thomas; van der Kwast, Theodorus H; van der Poel, Henk G; Wiegel, Thomas; Yuan, Cathy Yuhong; Cornford, Philip; Mottet, Nicolas; Lam, Thomas B

Maternal outcomes and risk factors for COVID-19 severity among pregnant women.

Pregnant women may be at higher risk of severe complications associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to obstetrical complications. We performed a case control study comparing pregnant women with severe coronavirus disease 19 (cases) to pregnant women with a milder form (controls) enrolled in the COVI-Preg international registry cohort between March 24 and July 26, 2020. Risk factors for severity, obstetrical and immediate neonatal outcomes were assessed. A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented with severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. Pregnant women with severe maternal outcomes were at higher risk of caesarean section [70.7% (n = 53/75)], preterm delivery [62.7% (n = 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n = 31/75)]. In this study, several risk factors for developing severe complications of SARS-CoV-2 infection among pregnant women were identified including pulmonary comorbidities, hypertensive disorders and diabetes. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease

New Strategies in Modeling Electronic Structures and Properties with Applications to Actinides

This chapter discusses contemporary quantum chemical methods and provides general insights into modern electronic structure theory with a focus on heavy-element-containing compounds. We first give a short overview of relativistic Hamiltonians that are frequently applied to account for relativistic effects. Then, we scrutinize various quantum chemistry methods that approximate the $N$-electron wave function. In this respect, we will review the most popular single- and multi-reference approaches that have been developed to model the multi-reference nature of heavy element compounds and their ground- and excited-state electronic structures. Specifically, we introduce various flavors of post-Hartree--Fock methods and optimization schemes like the complete active space self-consistent field method, the configuration interaction approach, the Fock-space coupled cluster model, the pair-coupled cluster doubles ansatz, also known as the antisymmetric product of 1 reference orbital geminal, and the density matrix renormalization group algorithm. Furthermore, we will illustrate how concepts of quantum information theory provide us with a qualitative understanding of complex electronic structures using the picture of interacting orbitals. While modern quantum chemistry facilitates a quantitative description of atoms and molecules as well as their properties, concepts of quantum information theory offer new strategies for a qualitative interpretation that can shed new light onto the chemistry of complex molecular compounds.Comment: 43 pages, 3 figures, Version of Recor

Planck pre-launch status : The Planck mission

Peer reviewe

Conception et réalisation d'un bio-microsystème basé sur la diélectrophorèse et l'électrofusion en vue de l'immunothérapie du cancer

Our subject of research comes from a request of clinicians to obtain in great quantity the hybridomas resulting from fusion between cancer cells and dendritic cells. This work forms part of research against cancer by a process close to vaccination, called immunotherapy of cancer. There exist currently marketed devices, but those do not manage to produce in an important way hybridomas of qualities. The idea was to place itself at the level of the cells, to interact on them in a precise way, while profiting from the miniaturization to control a large number of cells by paralleling the device. Remained to choose which forces to use to act on the cells to move them, to place them and to fusion them, because on a microscopic scale the report of the forces are different from those on our scale. We chose the use of microfluidic for the transport of the cells, the dielectrophoresis to position them and the electrofusion to fusion them. This project is with the conjunction of know-how in the fields of the microtechnology, the interaction field electric-cells and cellular biology.Notre sujet de recherche vient d'une demande de cliniciens pour obtenir en grande quantité des hybridomes issus de la fusion entre cellules cancéreuses et cellules dendritiques. Ces travaux s'insèrent dans la recherche contre le cancer par un procédé proche de la vaccination, appelé immunothérapie du cancer. Il existe actuellement des dispositifs commercialisés, mais ceux-ci ne parviennent pas à produire de façon importante des hybridomes de qualités. L'idée était donc de se placer à l'échelle des cellules, pour interagir sur elles de façon précise, tout en bénéficiant de la miniaturisation pour contrôler un grand nombre de cellules en parallélisant le dispositif. Restait à choisir quelles forces utiliser pour agir sur les cellules pour les déplacer, les placer et les fusionner, car à l'échelle microscopique le rapport des forces sont différents de ceux à notre échelle. Nous avons opté pour l'emploi de la microfluidique pour le transport des cellules, de la diélectrophorèse pour les positionner et de l'électrofusion pour les fusionner. Ce projet est à la conjonction de savoir-faire dans les domaines de la microtechnologie, de l'interaction champs électriques-cellules et de la biologie cellulaire

Conception et réalisation d'un bio-microsystème basé sur la diélectrophorèse et l'électrofusion en vue de l'immunothérapie du cancer

Our subject of research comes from a request of clinicians to obtain in great quantity the hybridomas resulting from fusion between cancer cells and dendritic cells. This work forms part of research against cancer by a process close to vaccination, called immunotherapy of cancer. There exist currently marketed devices, but those do not manage to produce in an important way hybridomas of qualities. The idea was to place itself at the level of the cells, to interact on them in a precise way, while profiting from the miniaturization to control a large number of cells by paralleling the device. Remained to choose which forces to use to act on the cells to move them, to place them and to fusion them, because on a microscopic scale the report of the forces are different from those on our scale. We chose the use of microfluidic for the transport of the cells, the dielectrophoresis to position them and the electrofusion to fusion them. This project is with the conjunction of know-how in the fields of the microtechnology, the interaction field electric-cells and cellular biology.Notre sujet de recherche vient d'une demande de cliniciens pour obtenir en grande quantité des hybridomes issus de la fusion entre cellules cancéreuses et cellules dendritiques. Ces travaux s'insèrent dans la recherche contre le cancer par un procédé proche de la vaccination, appelé immunothérapie du cancer. Il existe actuellement des dispositifs commercialisés, mais ceux-ci ne parviennent pas à produire de façon importante des hybridomes de qualités. L'idée était donc de se placer à l'échelle des cellules, pour interagir sur elles de façon précise, tout en bénéficiant de la miniaturisation pour contrôler un grand nombre de cellules en parallélisant le dispositif. Restait à choisir quelles forces utiliser pour agir sur les cellules pour les déplacer, les placer et les fusionner, car à l'échelle microscopique le rapport des forces sont différents de ceux à notre échelle. Nous avons opté pour l'emploi de la microfluidique pour le transport des cellules, de la diélectrophorèse pour les positionner et de l'électrofusion pour les fusionner. Ce projet est à la conjonction de savoir-faire dans les domaines de la microtechnologie, de l'interaction champs électriques-cellules et de la biologie cellulaire

Conception et réalisation d'un bio-microsystème basé sur la diélectrophorèse et l'électrofusion en vue de l'immunothérapie du cancer

Notre sujet de recherche vient d'une demande de cliniciens pour obtenir en grande quantité des hybridomes issus de la fusion entre cellules cancéreuses et cellules dendritiques. Ces travaux s'insèrent dans la recherche contre le cancer par un procédé proche de la vaccination, appelé immunothérapie du cancer. Il existe actuellement des dispositifs commercialisés, mais ceux-ci ne parviennent pas à produire de façon importante des hybridomes de qualités. L'idée était donc de se placer à l'échelle des cellules, pour interagir sur elles de façon précise, tout en bénéficiant de la miniaturisation pour contrôler un grand nombre de cellules en parallélisant le dispositif. Restait à choisir quelles forces utiliser pour agir sur les cellules pour les déplacer, les placer et les fusionner, car à l'échelle microscopique le rapport des forces sont différents de ceux à notre échelle. Nous avons opté pour l'emploi de la microfluidique pour le transport des cellules, de la diélectrophorèse pour les positionner et de l'électrofusion pour les fusionner. Ce projet est à la conjonction de savoir-faire dans les domaines de la microtechnologie, de l'interaction champs électriques-cellules et de la biologie cellulaire.Our subject of research comes from a request of clinicians to obtain in great quantity the hybridomas resulting from fusion between cancer cells and dendritic cells. This work forms part of research against cancer by a process close to vaccination, called immunotherapy of cancer. There exist currently marketed devices, but those do not manage to produce in an important way hybridomas of qualities. The idea was to place itself at the level of the cells, to interact on them in a precise way, while profiting from the miniaturization to control a large number of cells by paralleling the device. Remained to choose which forces to use to act on the cells to move them, to place them and to fusion them, because on a microscopic scale the report of the forces are different from those on our scale. We chose the use of microfluidic for the transport of the cells, the dielectrophoresis to position them and the electrofusion to fusion them. This project is with the conjunction of know-how in the fields of the microtechnology, the interaction field electric-cells and cellular biology.CACHAN-ENS (940162301) / SudocSudocFranceF

High-resolution analyses of cell fusion dynamics in a biochip

1522-2683In this study, we analyzed the electrofusion of two cells in a biochip that has been developed to perform the capture by dielectrophoresis and the electrofusion of pairs of cells. The good transparency of the microsystem allowed analyzing the details of the fusion events. By staining one of the cells, the mixing of the two cytosols could be observed during the electrofusion experiment. We show for the first time the rapidity of the mixing of the two cytosols: less than 5 s under our experimental conditions. By comparing these experimental results to a numerical simulation, we found that the rate of this phenomenon is compatible with a diffusion-only mechanism, showing that during the fusion, the two cell membranes in contact are affected by very rapid structural changes and do not limit the exchange of the cytosols between the two cells. A point of interest is the use of dielectric structures to concentrate the electric field and of positive dielectrophoresis to capture cells in the area where the electric field is more intense. This technique allows the increase of the cell-to-cell contact and limits cell cytosol leakages during the fusion process