Author: "Dahmani A" / Topic: humans - Searchworks@Jio Institute Digital Library Search Results

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291 results on '"Dahmani A"'

1. Cingulate transcranial direct current stimulation in adults with HIV

Author: Jiang, Xiong, Dahmani, Sophia, Bronshteyn, Margarita, Yang, Fan Nils, Ryan, John Paul, Gallagher, R Craig, Damera, Srikanth R, Kumar, Princy N, Moore, David J, Ellis, Ronald J, and Turkeltaub, Peter E
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Behavioral and Social Science, Clinical Trials and Supportive Activities, Mental Health, Basic Behavioral and Social Science, HIV/AIDS, Neurosciences, Brain Disorders, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Neurological, Mental health, Adult, Aged, Double-Blind Method, Female, Gyrus Cinguli, HIV Infections, Humans, Middle Aged, Pilot Projects, Transcranial Direct Current Stimulation, General Science & Technology
Abstract: BackgroundNeuronal dysfunction plays an important role in the high prevalence of HIV-associated neurocognitive disorders (HAND) in people with HIV (PWH). Transcranial direct current stimulation (tDCS)-with its capability to improve neuronal function-may have the potential to serve as an alternative therapeutic approach for HAND. Brain imaging and neurobehavioral studies provide converging evidence that injury to the anterior cingulate cortex (ACC) is highly prevalent and contributes to HAND in PWH, suggesting that ACC may serve as a potential neuromodulation target for HAND. Here we conducted a randomized, double-blind, placebo-controlled, partial crossover pilot study to test the safety, tolerability, and potential efficacy of anodal tDCS over cingulate cortex in adults with HIV, with a focus on the dorsal ACC (dACC).MethodsEleven PWH (47-69 years old, 2 females, 100% African Americans, disease duration 16-36 years) participated in the study, which had two phases, Phase 1 and Phase 2. During Phase 1, participants were randomized to receive ten sessions of sham (n = 4) or cingulate tDCS (n = 7) over the course of 2-3 weeks. Treatment assignments were unknown to the participants and the technicians. Neuropsychology and MRI data were collected from four additional study visits to assess treatment effects, including one baseline visit (BL, prior to treatment) and three follow-up visits (FU1, FU2, and FU3, approximately 1 week, 3 weeks, and 3 months after treatment, respectively). Treatment assignment was unblinded after FU3. Participants in the sham group repeated the study with open-label cingulate tDCS during Phase 2. Statistical analysis was limited to data from Phase 1.ResultsCompared to sham tDCS, cingulate tDCS led to a decrease in Perseverative Errors in Wisconsin Card Sorting Test (WCST), but not Non-Perseverative Errors, as well as a decrease in the ratio score of Trail Making Test-Part B (TMT-B) to TMT-Part A (TMT-A). Seed-to-voxel analysis with resting state functional MRI data revealed an increase in functional connectivity between the bilateral dACC and a cluster in the right dorsal striatum after cingulate tDCS. There were no differences in self-reported discomfort ratings between sham and cingulate tDCS.ConclusionsCingulate tDCS is safe and well-tolerated in PWH, and may have the potential to improve cognitive performance and brain function. A future study with a larger sample is warranted.
Published: 2022

2. Alterations of Brain Metabolites in Adults With HIV

Author: Dahmani, Sophia, Kaliss, Nicholas, VanMeter, John W, Moore, David J, Ellis, Ronald J, and Jiang, Xiong
Subjects: Medical Biochemistry and Metabolomics, Biomedical and Clinical Sciences, Acquired Cognitive Impairment, Neurosciences, Infectious Diseases, Brain Disorders, HIV/AIDS, Mental Health, Brain, Cognitive Dysfunction, HIV Infections, Humans, Proton Magnetic Resonance Spectroscopy, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract: ObjectiveA meta-analysis of proton magnetic resonance spectroscopy studies to investigate alterations in brain metabolites in people with HIV (PWH), the relationship between metabolite alterations and combination antiretroviral therapy (cART), and the relationship between metabolite alterations and cognitive impairment.MethodsThe PubMed database was searched for studies published from 1997 to 2020. Twenty-seven studies were identified, which included 1255 PWH and 633 controls. Four metabolites (N-acetyl aspartate [NAA], myo-inositol [mI], choline [Cho], and glutamatergic metabolites [Glx]) from 5 brain regions (basal ganglia [BG], frontal gray and white matter [FGM and FWM], and parietal gray and white matter [PGM and PWM]) were pooled separately using random-effects meta-analysis.ResultsDuring early HIV infection, metabolite alterations were largely limited to the BG, including Cho elevation, a marker of inflammation. cART led to global mI and Cho normalization (i.e., less elevations), but improvement in NAA was negligible. In chronic PWH on cART, there were consistent NAA reductions across brain regions, along with Cho and mI elevations in the FWM and BG, and Glx elevations in the FWM. Cognitive impairment was associated with NAA reduction and to a lesser degree mI elevation.ConclusionsThe BG are the primary region affected during early infection. cART is successful in partially controlling neuroinflammation (global mI and Cho normalization). However, neuronal dysfunction (NAA reductions) and neuroinflammation (mI and Cho elevations) persist and contribute to cognitive impairment in chronic PWH. Novel compounds targeting NAA signal pathways, along with better neuroinflammation control, may help to reduce cognitive impairment in PWH.
Published: 2021

3. Combination of high-resolution cone beam computed tomography and metal artefact reduction software: a new image fusion technique for evaluating intracranial stent apposition after aneurysm treatment.

Author: Ishibashi, Toshihiro, Dahmani, Chihebeddine, Kato, Naoki, Ikemura, Ayako, Abe, Yukiko, Otani, Katharina, Kodama, Tomonobu, Kan, Issei, Nishimura, Kengo, Murayama, Yuichi, and Yuki, Ichiro
Subjects: interventional radiology, neuroimaging, neurosurgery, stroke, Adult, Aged, Angiography, Digital Subtraction, Carotid Artery, Internal, Cone-Beam Computed Tomography, Embolization, Therapeutic, Endovascular Procedures, Female, Humans, Imaging, Three-Dimensional, Intracranial Aneurysm, Male, Stents
Abstract: We introduce a new imaging technique to improve visualisation of stent apposition after endovascular treatment of brain aneurysms employing high-resolution cone beam CT and three-dimensional digital subtraction angiography. After performing a stent-assisted coil embolisation of brain aneurysm, the image datasets were processed with a metal artefact reduction software followed by the automated image fusion programmes. Two patients who underwent aneurysm coiling using a Neuroform stent were evaluated. The reconstructed 3D images showed a detailed structure of the stent struts and identified malappositions of the deployed stents. Case 1 showed good apposition on the outer curvature side of the carotid siphon, while the inner curvature side showed prominent malapposition. Case 2, with multiple aneurysms, showed good apposition on both outer and inner curvature sides, although inward prolapse of the struts was observed. This new imaging technique may help evaluate stent apposition after the endovascular aneurysm treatment.
Published: 2019

4. Combination of high-resolution cone beam computed tomography and metal artefact reduction software: a new image fusion technique for evaluating intracranial stent apposition after aneurysm treatment.

Author: Yuki, Ichiro, Ishibashi, Toshihiro, Dahmani, Chihebeddine, Kato, Naoki, Ikemura, Ayako, Abe, Yukiko, Otani, Katharina, Kodama, Tomonobu, Kan, Issei, Nishimura, Kengo, and Murayama, Yuichi
Subjects: Carotid Artery, Internal, Humans, Intracranial Aneurysm, Imaging, Three-Dimensional, Angiography, Digital Subtraction, Embolization, Therapeutic, Stents, Adult, Aged, Female, Male, Cone-Beam Computed Tomography, Endovascular Procedures, interventional radiology, neuroimaging, neurosurgery, stroke, Carotid Artery, Internal, Imaging, Three-Dimensional, Angiography, Digital Subtraction, Embolization, Therapeutic, Clinical Sciences
Abstract: We introduce a new imaging technique to improve visualisation of stent apposition after endovascular treatment of brain aneurysms employing high-resolution cone beam CT and three-dimensional digital subtraction angiography. After performing a stent-assisted coil embolisation of brain aneurysm, the image datasets were processed with a metal artefact reduction software followed by the automated image fusion programmes. Two patients who underwent aneurysm coiling using a Neuroform stent were evaluated. The reconstructed 3D images showed a detailed structure of the stent struts and identified malappositions of the deployed stents. Case 1 showed good apposition on the outer curvature side of the carotid siphon, while the inner curvature side showed prominent malapposition. Case 2, with multiple aneurysms, showed good apposition on both outer and inner curvature sides, although inward prolapse of the struts was observed. This new imaging technique may help evaluate stent apposition after the endovascular aneurysm treatment.
Published: 2019

5. Accuracy of Length of Virtual Stents in Treatment of Intracranial Wide-Necked Aneurysms

Author: Nishimura, Kengo, Otani, Katharina, Mohamed, Ashraf, Dahmani, Chihebeddine, Ishibashi, Toshihiro, Yuki, Ichiro, Kaku, Shogo, Takao, Hiroyuki, and Murayama, Yuichi
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Assistive Technology, Stroke, Bioengineering, Angiography, Digital Subtraction, Cerebral Angiography, Computed Tomography Angiography, Embolization, Therapeutic, Equipment Design, Female, Humans, Imaging, Three-Dimensional, Intracranial Aneurysm, Male, Middle Aged, Reproducibility of Results, Retrospective Studies, Stents, Treatment Outcome, Stent simulation software, Stent-assisted coiling, 3D digital subtraction angiography, Wide-necked aneurysm, Cardiorespiratory Medicine and Haematology, Nuclear Medicine & Medical Imaging, Cardiovascular medicine and haematology
Abstract: Background and purposePrecise stent deployment is important for successful treatment of intracranial aneurysms by stent-assisted coiling (SAC). We evaluated the accuracy of virtual stents generated using commercial stent planning software by comparing the length of virtual and actually deployed intracranial laser cut stents on three-dimensional digital subtraction angiography (3D-DSA) images.MethodsWe retrospectively analyzed the data of 75 consecutive cases of intracranial wide-necked aneurysms treated with the SAC technique using laser cut stents. Based on 3D-DSA images acquired by C-arm CT, stent sizing and placement were intraoperatively simulated by a commercial software application. The difference in length of the stents was estimated by measuring proximal discrepancies between the end points of the virtual and actually deployed stents on fused pre-procedural and post-procedural 3D-DSA images. Discrepancies between distal stent end points were manually minimized. The Kruskal-Wallis test was applied to test whether stent location, type, and length had an effect on difference in length between virtual and real stent.ResultsThe median difference in length between virtual and real stents was 1.58 mm with interquartile range 1.12-2.12 mm. There was no evidence for an effect of stent location (p = 0.23), stent type (p = 0.33), or stent length (p = 0.53) on difference in length between virtual and real stents.ConclusionsStent planning software allows 3D simulation of laser cut stents overlain on 3D-DSA images of vessels and may thus be useful for stent selection and deployment of laser cut stents during stent-assisted coiling of intracranial aneurysms.
Published: 2019

6. Time-resolved magnetic resonance angiography (TR-MRA) for the evaluation of post coiling aneurysms; A quantitative analysis of the residual aneurysm using full-width at half-maximum (FWHM) value.

Author: Suzuki, Hiroaki, Suzuki, Tomoaki, Ishibashi, Toshihiro, Abe, Yukiko, Urashima, Mitsuyoshi, Dahmani, Chihebeddine, Murayama, Yuichi, Ikemura, Ayako, and Yuki, Ichiro
Subjects: Adolescent, Adult, Aged, Aged, 80 and over, Cerebral Angiography, Embolization, Therapeutic, Female, Humans, Image Interpretation, Computer-Assisted, Intracranial Aneurysm, Magnetic Resonance Angiography, Male, Middle Aged, Observer Variation, Postoperative Care, Sensitivity and Specificity, Treatment Outcome, Young Adult
Abstract: Magnetic resonance image (MRI) is now widely used for imaging follow-up for post coiling brain aneurysms. However, the accuracy on the estimation of residual aneurysm, which is crucial for the retreatment planning, remains to be controversial. The purpose of this study is to evaluate a new post-processing technique that provides improved estimation of the residual aneurysm after coil embolization. One hundred aneurysms on 93 patients who underwent coil embolization for brain aneurysm were evaluated using the 1.5 Tesla time-resolved magnetic resonance angiography (TR-MRA) one year after the treatment. To minimize the inter-observer variability caused by the window level adjustment, an automatic post processing protocol using the full-width at half-maximum (FWHM) value was utilized. The result was then compared with that from the conventional cerebral angiography. Of the 97 aneurysms that underwent both TR-MRA and DSA, 23 (23.7%) showed residual neck / dome during follow-up. After window level adjustment, the size of the parent artery in the TR-MRA was consistent with that in the DSA. The reconstructed Volume Rendering images provided clear contours of the residual aneurysms and contributed to the understanding the configuration of residual aneurysm. The largest and the smallest diameter of the residual aneurysms was larger in the TR-MRA than in the DSA (8.05 vs. 7.72 mm, p = 0.0004; 4.99 vs. 4.19 mm, p = 0.007 respectively). The sensitivity, specificity, and positive and negative predictive values of TR-MRA compared to DSA were 100%, 97%, 73%, and 100%, respectively. Using the FWHM value to optimize the window level adjustment, the size of the residual component observed in the TR-MRA was larger compared to that in the DSA whereas the size of neck and the parent artery showed consistency between the two modalities. This image processing technique can be used as an effective screening tool for evaluating residual component in post-coiling brain aneurysms.
Published: 2018

7. Time-resolved magnetic resonance angiography (TR-MRA) for the evaluation of post coiling aneurysms; A quantitative analysis of the residual aneurysm using full-width at half-maximum (FWHM) value.

Author: Ikemura, Ayako, Yuki, Ichiro, Suzuki, Hiroaki, Suzuki, Tomoaki, Ishibashi, Toshihiro, Abe, Yukiko, Urashima, Mitsuyoshi, Dahmani, Chihebeddine, and Murayama, Yuichi
Subjects: Humans, Intracranial Aneurysm, Image Interpretation, Computer-Assisted, Observer Variation, Magnetic Resonance Angiography, Cerebral Angiography, Treatment Outcome, Embolization, Therapeutic, Postoperative Care, Sensitivity and Specificity, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Young Adult, Image Interpretation, Computer-Assisted, Embolization, Therapeutic, and over, General Science & Technology
Abstract: Magnetic resonance image (MRI) is now widely used for imaging follow-up for post coiling brain aneurysms. However, the accuracy on the estimation of residual aneurysm, which is crucial for the retreatment planning, remains to be controversial. The purpose of this study is to evaluate a new post-processing technique that provides improved estimation of the residual aneurysm after coil embolization. One hundred aneurysms on 93 patients who underwent coil embolization for brain aneurysm were evaluated using the 1.5 Tesla time-resolved magnetic resonance angiography (TR-MRA) one year after the treatment. To minimize the inter-observer variability caused by the window level adjustment, an automatic post processing protocol using the full-width at half-maximum (FWHM) value was utilized. The result was then compared with that from the conventional cerebral angiography. Of the 97 aneurysms that underwent both TR-MRA and DSA, 23 (23.7%) showed residual neck / dome during follow-up. After window level adjustment, the size of the parent artery in the TR-MRA was consistent with that in the DSA. The reconstructed Volume Rendering images provided clear contours of the residual aneurysms and contributed to the understanding the configuration of residual aneurysm. The largest and the smallest diameter of the residual aneurysms was larger in the TR-MRA than in the DSA (8.05 vs. 7.72 mm, p = 0.0004; 4.99 vs. 4.19 mm, p = 0.007 respectively). The sensitivity, specificity, and positive and negative predictive values of TR-MRA compared to DSA were 100%, 97%, 73%, and 100%, respectively. Using the FWHM value to optimize the window level adjustment, the size of the residual component observed in the TR-MRA was larger compared to that in the DSA whereas the size of neck and the parent artery showed consistency between the two modalities. This image processing technique can be used as an effective screening tool for evaluating residual component in post-coiling brain aneurysms.
Published: 2018

8. Neonates undergoing pyloric stenosis repair are at increased risk of difficult airway management

Author: Nicola Disma, Thomas Engelhardt, Tom G. Hansen, Jurgen C. de Graaff, Katalin Virag, Walid Habre, Christian Breschan, Rudolf Likar, Manuela Platzer, Isole Edelman, Johanes Eger, Stefan Heschl, Brigitte Messerer, Maria Vittinghof, Ruth Kroess, Martina Stichlberger, David Kahn, Thierry Pirotte, Caroline Pregardien, Francis Veyckemans, France Stevens, Johan Berghmans, Annemie Bauters, Luc De Baerdemaeker, Stefan De Hert, Koen Lapage, Aliaksandra Parashchanka, Jurgen Van Limmen, Piet Wyffels, Julie Lauweryns, Nadia Najafi, Joris Vundelinckx, Diana Butković, Ivana Kerovec Sorić, Sandra Kralik, Ana Markić, Josip Azman, Josko Markic, Daniela Pupacic, Michal Frelich, Petr Reimer, René Urbanec, Petra Cajková, Vladimír Mixa, Yvona Sedláčková, Lenka Knoppová, Alena Zlámalová (neé Květoňová), Martin Vavřina, Jiří Žurek, Tom Hansen, Arash Afshari, Anders Bastholm Bille, Marguerite Ellekvist, Mari-Liis Ilmoja, Reet Moor, Reet Kikas, Merle Väli, Kariantti Kallio, Elisa Reponen, Pertti Suominen, Sami Suvanto, Raisa Vähätalo, Hannu Kokki, Merja Kokki, Jarkko Harju, Miia Kokkonen, Jenni Vieri, Tuula Manner, Amory Catherine, Hugues Ludot, Dina Bert, Juliette Godart, Anne Laffargue, Hervé Dupont, Benjamin Urbina, Catherine Baujard, Philippe Roulleau, Giuseppe Staiti, Maryline Bordes, Karine Nouette Gaulain, Yann Hamonic, François Semjen, Olivier Jacqmarcq, Caroline Lejus-Bourdeau Cécile Magne, Léa Petry, Lilica Ros, Aurélien Zang, Mehdi Bennis, Bernard Coustets, Rose Fesseau, Isabelle Constant, Eliane Khalil, Nada Sabourdin, Noemie Audren, Thomas Descarpentries, Fanny Fabre, Aurélien Legrand, Emilie Druot, Gilles Orliaguet, Lucie Sabau, Lynn Uhrig, François de la Brière, Karin Jonckheer, Jean-Paul Mission, Lucia Scordo, Caroline Couchepin, Christophe Dadure, Pablo De la Arena, Laurent Hertz, Philippe Pirat, Chrystelle Sola, Myriam Bellon, Souhayl Dahmani, Florence Julien-Marsollier, Daphne Michelet, Veronique Depret-Donatien, Anne Lesage, Jost Kaufmann, Michael Laschat, Frank Wappler, Karin Becke, Lena Brunner, Karin Oppenrieder, Gregor Badelt, Karin Hochmuth, Bernhard Koller, Anita Reil, Sebastian Richter, Thomas Fischer, Anja Diers, Clemens Schorer, Andreas Weyland, Ruth Cohausz, Franz-Josef Kretz, Michaela Löffler, Markus Wilbs, Claudia Hoehne, Johanna Ulrici, Christiane Goeters, Armin Flinspach, Matthias Klages, Simone Lindau, Leila Messroghli, Kai Zacharowski, Christoph Eisner, Thomas Mueller, Daniel Richter, Melanie Schäfer, Markus Weigand, Sebastian Weiterer, Miriam Ochsenreiter, Michael Schöler, Tom Terboven, Isabel Eggemann, Sascha Haussmann, Nicolas Leister, Christoph Menzel, Uwe Trieschmann, Sirin Yücetepe, Susanna Keilig, Peter Kranke, Yvonne Jelting, Torsten Baehner, Richard Ellerkmann, Shahab Ghamari, Claudia Neumann, Martin Söhle, Pelagia Chloropoulou, Vagia Ntritsou, Pinelopi Papagiannopoulou, Eleana Garini, Afroditi Karafotia, Panagoula Mammi, Evangelia Bali, Despoina Iordanidou, Anna Malisiova, Artemis Polyzoi, Adelais Tsiotou, Erzsebet Sapi, Edgar Székely, Nandor Kosik, Veronika Maráczi, Janos Schnur, Judit Csillag, János Gál, Gergely Göbl, Balázs Hauser, András Petróczy, Gyula Tövisházi, Stuart Blain, Sarah Gallagher, Sinead Harte, Mandy Jackson, Emma Meehan, Zeenat Nawoor, Brendan O’Hare, Mark Ross, Daniela Lerro, Marinella Astuto, Chiara Grasso, Rita Scalisi, Giulia Frasacco, Elena Lenares, Roberto Leone, Maurizia Grazzini, Carmelo Minardi, Nicola Zadra, Gilda Cinnella, Antonella Cotoia, Dario Galante, Brita De Lorenzo, Beate Kuppers, Giulia Bottazzi, Fabio Caramelli, Maria Cristina Mondardini, Emanuele Rossetti, Sergio Picardo, Alessandro Vittori, Anna Camporesi, Francesca Izzo, Edoardo Calderini, Laura Brigitta Colantonio, Simona Anna Finamore, Giuliana Anna Porro, Rachele Bonfiglio, Svetlana Kotzeva, Girolamo Mattioli, Camilla Micalizzi, Alessia Montaguti, Angela Pistorio, Anna Guddo, Gerald Rogan Neba, Moreno Favarato, Bruno Guido Locatelli, Micol Maffioletti, Valter Sonzogni, Rossella Garra, Maria Sammartino, Fabio Sbaraglia, Andrea Cortegiani, Alessandra Moscarelli, Elena Attanasi, Simonetta Tesoro, Cristina Agapiti, Francesca Pinzoni, Cesare Vezzoli, Bilotta Federico, Arta Barzdina, Zane Straume, Anda Zundane, Laura Lukosiene, Irena Maraulaite, Ilona Razlevice, Bernd Schmitz, Stephanie Mifsud, Carolin Aehling, Celia Allison, Rients De Boer, Dina Emal, Markus Stevens, Marielle Buitenhuis, Jurgen de Graaff, Inge De Liefde, Andreas Machotta, Gail Scoones, Lonneke Staals, Jeremy Tomas, Anouk Van der Knijff-van Dortmont, Marianne Veldhuizen, David Alders, Eva Schafrat, Jan Schreiber, Petronella Mari Vermeulen, Mark Hendriks, Sandra Lako, Marieke Voet-Lindner, Barbe Pieters, Gert-Jan Scheffer, Luc Tielens, Anthony R. Absalom, Margot Bergsma, Joke De Ruiter, Sascha Meier, Martin Volkers, Tjerk Zweers, Anne M. Beukers, Christa Boer, Jurgen Dertinger, Sandra Numan, Bas Van Zaane, Wenche B. Boerke, Nil Ekiz, Kristoffer Stensrud, Inger Marie Drage, Erik Ramon Isern, Alicja Bartkowska-Sniatkowska, Malgorzata Grzeskowiak, Magdalena Juzwa-Sobieraj, Jowita Rosada-Kurasińska, Artur Baranowski, Karina Jakubowska, Dorota Lewandowska, Magdalena Mierzewska-Schmidt, Piotr Sawicki, Magdalena Urban-Lechowicz, Pomianek Przemyslaw, Marzena Zielinska, Teresa Leal, Maria Soares, Pedro Pina, Sílvia Pinho, Maria Domingas Patuleia, Catarina Cruz Esteves, Helena Salgado, Maria João Santos, Rodica Badeti, Iulia Cindea, Loredana Oana, Adriana Gurita, Luminita Ilie, Gabriel Mocioiu, Radu Tabacaru, Irina Trante, Valentin Munteanu, Mihai Morariu, Emese Nyíri, Ivana Budic, Vesna Marjanovic, Biljana Drašković, Marina Pandurov, Jordanka Ilic, Ana Mandras, Zdenka Rados, Nikola Stankovic, Maja Suica, Sladjana Vasiljevic, Mirjana Knezevic, Irina Milojevic, Ivana Petrov, Selena Puric Racic, Dusica Simic, Irena Simic, Marija Stevic, Irena Vulicevic, Banská Bystrica, Barbora Cabanová, Miloslav Hanula, Jelena Berger, Darja Janjatovic, Špela Pirtovšek Štupnik, Dolores Méndez, Gema Pino, Paloma Rubio, Alberto Izquierdo, Silvia López, Cristina González Serrano, Jesús Cebrián, Ana Peleteiro, Pilar Del Rey de Diego, Ernesto Martínez García, Carolina Tormo de las Heras, Pablo Troncoso Montero, Celia Arbona, David Artés, Alicia Chamizo, Silvia Serrano, Montserrat Suarez Comas, Francisco Escribá, Cristina Auli, Osvaldo Pérez Pardo, Natalia Sierra Biddle, Ceferina Suárez Castaño, María Isabel Villalobos Rico, Susana Manrique Muñoz, Irene García Martínez, Nuria Montferrer Estruch, Elena Vilardell Ortíz, Rodrigo Poves-Álvarez, Ivan Kohn, Ulf Lindestam, Jarl Reinhard, Albert Castellheim, Kerstin Sandström, Sporre Bengt, Rainer Dörenberg, Peter Frykholm, Maria Garcia, Ann Kvarnström, Emma Pontén, Thomas Bruelisauer, Gabor Erdoes, Heiko Kaiser, Mathias Marchon, Thomas Riva, Stefan Seiler, Yann Bögli, Mirko Dolci, Carine Marcucci, Isabelle Pichon, Laszlo Vutskits, Mattias Casutt, Martin Hölzle, Thomas Hurni, Martin Jöhr, Anna-Ursina Malär, Jacqueline Mauch, Thomas Erb, Karin Oeinck, Mine Akin, Gulsen Keskin, Yesim Senayli, Guner Kaya, Pinar Kendigelen, Ayse Çiğdem Tutuncu, Zehra Hatipoğlu, Dilek Özcengiz, Hale Aksu Erdost, Elvan Öçmen, Çimen Olguner, Hilmi Ayanoglu, Pelin Corman Dincer, Tumay Umuroglu, Mustafa Azizoglu, Handan Birbiçer, Nurcan Doruk, Aslı Sagun, Sibel Baris, Dmytro Dmytriiev, Sridevi Kuchi, Nuria Masip, Peter Brooks, Alison Hare, Nargis Ahmad, Michelle Casey, Sam De Silva, Nadine Dobby, Prakash Krishnan, L. Amaki Sogbodjor, Ellie Walker, Suellen Walker, Stephanie King, Katy Nicholson, Michelle Quinney, Paul Stevens, Andrew Blevin, Mariangela Giombini, Chulananda Goonasekera, Sadia Adil, Stephanie Bew, Carol Bodlani, Dan Gilpin, Stephanie Jinks, Nalini Malarkkan, Alice Miskovic, Rebecca Pad, Juliet Wolfe Barry, Joy Abbott, James Armstrong, Natalie Cooper, Lindsay Crate, John Emery, Kathryn James, Hannah King, Paul Martin, Stefano Scalia Catenacci, Rob Bomont, Paul Smith, Sara Mele, Alessandra Verzelloni, Philippa Dix, Graham Bell, Elena Gordeva, Lesley McKee, Esther Ngan, Jutta Scheffczik, Li-En Tan, Mark Worrall, Carmel Cassar, Kevin Goddard, Victoria Barlow, Vimmi Oshan, Khairi Shah, Sarah Bell, Lisa Daniels, Monica Gandhi, David Pachter, Chris Perry, Andrew Robertson, Carmen Scott, Lynne Waring, David Barnes, Sophie Childs, Joanne Norman, Robin Sunderland, Dowell Julia, Feijten Prisca, Harlet Pierre, Herbineaux Sarah, Leva Brigitte, Plichon Benoît, Virág Katalin, and Anesthesiology
Subjects: Europe, Anesthesiology and Pain Medicine, Infant, Newborn, Intubation, Intratracheal, Humans, Infant, airway management, complications, difficult airway, neonatal anaesthesia, pyloric stenosis, tracheal intubation, Anesthesia, Pyloric Stenosis, Hypertrophic, Airway Management, Child, Hypoxia
Abstract: Background: Hypertrophic pyloric stenosis in otherwise healthy neonates frequently requires urgent surgical procedure but anaesthesia care may result in respiratory complications, such as hypoxaemia, pulmonary aspiration of gastric contents, and postoperative apnoea. The primary aim was to study whether or not the incidence of difficult airway management and of hypoxaemia in neonates undergoing pyloric stenosis repair was higher than that in neonates undergoing other surgeries. Methods: Data on neonates and infants undergoing anaesthesia and surgery for pyloric stenosis were extracted from the NEonate and Children audiT of Anesthesia pRactice In Europe (NECTARINE) database, for secondary analysis. Results: We identified 310 infants who had anaesthesia for surgery for pyloric stenosis. Difficult airway management (more than two attempts at laryngoscopy) was higher in children with pyloric stenosis when compared with the entire NECTARINE cohort (7.9% [95% confidence interval {CI}, 5.22–11.53] vs 4.4% [95% CI, 1.99–6.58]; relative risk [RR]=1.81 [95% CI, 1.21–2.69]; P=0.004), whereas transient hypoxaemia with oxygen saturation
Published: 2022

9. Defects in Long-Term APC Repopulation Ability of Adult Human Bone Marrow Hematopoietic Stem Cells (HSCs) Compared with Fetal Liver HSCs

Author: Grace Nauman, Nichole M. Danzl, Jaeyop Lee, Chiara Borsotti, Rachel Madley, Jianing Fu, Markus A. Hölzl, Alexander Dahmani, Akaitz Dorronsoro Gonzalez, Éstefania Chavez, Sean R. Campbell, Suxiao Yang, Prakash Satwani, Kang Liu, and Megan Sykes
Subjects: Mice, Liver, Bone Marrow, Immunology, Hematopoietic Stem Cell Transplantation, Animals, Humans, Immunology and Allergy, Bone Marrow Cells, Hematopoietic Stem Cells, Article
Abstract: Immunodeficient mice reconstituted with immune systems from patients, or personalized immune (PI) mice, are powerful tools for understanding human disease. Compared with immunodeficient mice transplanted with human fetal thymus tissue and fetal liver–derived CD34+ cells administered i.v. (Hu/Hu mice), PI mice, which are transplanted with human fetal thymus and adult bone marrow (aBM) CD34+ cells, demonstrate reduced levels of human reconstitution. We characterized APC and APC progenitor repopulation in human immune system mice and detected significant reductions in blood, bone marrow (BM), and splenic APC populations in PI compared with Hu/Hu mice. APC progenitors and hematopoietic stem cells (HSCs) were less abundant in aBM CD34+ cells compared with fetal liver–derived CD34+ cell preparations, and this reduction in APC progenitors was reflected in the BM of PI compared with Hu/Hu mice 14–20 wk posttransplant. The number of HSCs increased in PI mice compared with the originally infused BM cells and maintained functional repopulation potential, because BM from some PI mice 28 wk posttransplant generated human myeloid and lymphoid cells in secondary recipients. Moreover, long-term PI mouse BM contained functional T cell progenitors, evidenced by thymopoiesis in thymic organ cultures. Injection of aBM cells directly into the BM cavity, transgenic expression of hematopoietic cytokines, and coinfusion of human BM-derived mesenchymal stem cells synergized to enhance long-term B cell and monocyte levels in PI mice. These improvements allow a sustained time frame of 18–22 wk where APCs and T cells are present and greater flexibility for modeling immune disease pathogenesis and immunotherapies in PI mice.
Published: 2022
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10. H3K27me3 conditions chemotolerance in triple-negative breast cancer

Author: Justine Marsolier, Pacôme Prompsy, Adeline Durand, Anne-Marie Lyne, Camille Landragin, Amandine Trouchet, Sabrina Tenreira Bento, Almut Eisele, Sophie Foulon, Léa Baudre, Kevin Grosselin, Mylène Bohec, Sylvain Baulande, Ahmed Dahmani, Laura Sourd, Eric Letouzé, Anne-Vincent Salomon, Elisabetta Marangoni, Leïla Perié, Céline Vallot, Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Département de Recherche Translationnelle, Institut Curie [Paris], Laboratoire Physico-Chimie Curie [Institut Curie] (PCC), Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Chimie-Biologie-Innovation (UMR 8231) (CBI), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), HiFiBiO Therapeutics SAS [Paris], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Plateforme de Séquençage ADN haut débit [Institut Curie] (NGS), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Génétique et Biologie du Développement, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the ATIP Avenir program, by Plan Cancer, by the SiRIC-Curie program SiRIC Grants #INCa-DGOS-4654 and #INCa-DGOS-Inserm_12554, and by a starting ERC grant from the H2020 program #948528-ChromTrace (to CV), and by the Fondation de France #00107944 (to JM). The work was supported by an ATIP-Avenir grant from CNRS and Bettencourt-Schueller Foundation, by a starting ERC grant from the H2020 program #758170-Microbar (to LP). And by the SiRIC-Curie program SiRIC Grant #INCa-DGOS- 4654., ANR-11-LABX-0038,CelTisPhyBio,Des cellules aux tissus: au croisement de la Physique et de la Biologie(2011), ANR-10-EQPX-0003,ICGex,Equipement de biologie intégrative du cancer pour une médecine personnalisée(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Perié, Leïla, Des cellules aux tissus: au croisement de la Physique et de la Biologie - - CelTisPhyBio2011 - ANR-11-LABX-0038 - LABX - VALID, Equipements d'excellence - Equipement de biologie intégrative du cancer pour une médecine personnalisée - - ICGex2010 - ANR-10-EQPX-0003 - EQPX - VALID, and Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID
Subjects: Histones, [SDV] Life Sciences [q-bio], Breast cancer, Drug Resistance, Neoplasm, Lysine, [SDV]Life Sciences [q-bio], Genetics, Humans, Triple Negative Breast Neoplasms, Epigenetics, Neoplasm Recurrence, Local, Methylation
Abstract: International audience; The persistence of cancer cells resistant to therapy remains a major clinical challenge. In triple-negative breast cancer, resistance to chemotherapy results in the highest recurrence risk among breast cancer subtypes. The drug-tolerant state seems largely defined by nongenetic features, but the underlying mechanisms are poorly understood. Here, by monitoring epigenomes, transcriptomes and lineages with single-cell resolution, we show that the repressive histone mark H3K27me3 (trimethylation of histone H3 at lysine 27) regulates cell fate at the onset of chemotherapy. We report that a persister expression program is primed with both H3K4me3 (trimethylation of histone H3 at lysine 4) and H3K27me3 in unchallenged cells, with H3K27me3 being the lock to its transcriptional activation. We further demonstrate that depleting H3K27me3 enhances the potential of cancer cells to tolerate chemotherapy. Conversely, preventing H3K27me3 demethylation simultaneously to chemotherapy inhibits the transition to a drug-tolerant state, and delays tumor recurrence in vivo. Our results highlight how chromatin landscapes shape the potential of cancer cells to respond to initial therapy.
Published: 2022
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11. Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE)

Author: Nicola Disma, Katalin Virag, Thomas Riva, Jost Kaufmann, Thomas Engelhardt, Walid Habre, Christian Breschan, Rudolf Likar, Manuela Platzer, Isole Edelman, Johanes Eger, Stefan Heschl, Brigitte Messerer, Maria Vittinghof, Ruth Kroess, Martina Stichlberger, David Kahn, Thierry Pirotte, Caroline Pregardien, Francis Veyckemans, France Stevens, Johan Berghmans, Annemie Bauters, Luc De Baerdemaeker, Stefan De Hert, Koen Lapage, Aliaksandra Parashchanka, Jurgen Van Limmen, Piet Wyffels, Julie Lauweryns, Nadia Najafi, Joris Vundelinckx, Diana Butković, Ivana Kerovec Sorić, Sandra Kralik, Ana Markić, Josip Azman, Josko Markic, Daniela Pupacic, Michal Frelich, Petr Reimer, René Urbanec, Petra Cajková, Vladimír Mixa, Yvona Sedláčková, Lenka Knoppová, Alena Zlámalová (neé Květoňová), Martin Vavřina, Jiří Žurek, Tom Hansen, Arash Afshari, Anders Bastholm Bille, Marguerite Ellekvist, Mari-Liis Ilmoja, Reet Moor, Reet Kikas, Merle Väli, Kariantti Kallio, Elisa Reponen, Pertti Suominen, Sami Suvanto, Raisa Vähätalo, Hannu Kokki, Merja Kokki, Jarkko Harju, Miia Kokkonen, Jenni Vieri, Tuula Manner, Catherine Amory, Hugues Ludot, Dina Bert, Juliette Godart, Anne Laffargue, Hervé Dupont, Benjamin Urbina, Catherine Baujard, Philippe Roulleau, Giuseppe Staiti, Maryline Bordes, Karine Nouette Gaulain, Yann Hamonic, François Semjen, Olivier Jacqmarcq, Caroline Lejus-Bourdeau, Cécile Magne, Léa Petry, Lilica Ros, Aurélien Zang, Mehdi Bennis, Bernard Coustets, Rose Fesseau, Isabelle Constant, Eliane Khalil, Nada Sabourdin, Noemie Audren, Thomas Descarpentries, Fanny Fabre, Aurélien Legrand, Emilie Druot, Gilles Orliaguet, Lucie Sabau, Lynn Uhrig, François de la Brière, Karin Jonckheer, Jean-Paul Mission, Lucia Scordo, Caroline Couchepin, Christophe Dadure, Pablo De la Arena, Laurent Hertz, Philippe Pirat, Chrystelle Sola, Myriam Bellon, Souhayl Dahmani, Florence Julien-Marsollier, Daphne Michelet, Veronique Depret-Donatien, Anne Lesage, Michael Laschat, Frank Wappler, Karin Becke, Lena Brunner, Karin Oppenrieder, Gregor Badelt, Karin Hochmuth, Bernhard Koller, Anita Reil, Sebastian Richter, Thomas Fischer, Anja Diers, Clemens Schorer, Andreas Weyland, Ruth Cohausz, Franz-Josef Kretz, Michaela Löffler, Markus Wilbs, Claudia Hoehne, Johanna Ulrici, Christiane Goeters, Armin Flinspach, Matthias Klages, Simone Lindau, Leila Messroghli, Kai Zacharowski, Christoph Eisner, Thomas Mueller, Daniel Richter, Melanie Schäfer, Markus Weigand, Sebastian Weiterer, Miriam Ochsenreiter, Michael Schöler, Tom Terboven, Isabel Eggemann, Sascha Haussmann, Nicolas Leister, Christoph Menzel, Uwe Trieschmann, Sirin Yücetepe, Susanna Keilig, Peter Kranke, Yvonne Jelting, Torsten Baehner, Richard Ellerkmann, Shahab Ghamari, Claudia Neumann, Martin Söhle, Pelagia Chloropoulou, Vagia Ntritsou, Pinelopi Papagiannopoulou, Eleana Garini, Afroditi Karafotia, Panagoula Mammi, Evangelia Bali, Despoina Iordanidou, Anna Malisiova, Artemis Polyzoi, Adelais Tsiotou, Erzsebet Sapi, Edgar Székely, Nandor Kosik, Veronika Maráczi, Janos Schnur, Judit Csillag, János Gál, Gergely Göbl, Balázs Hauser, András Petróczy, Gyula Tövisházi, Stuart Blain, Sarah Gallagher, Sinead Harte, Mandy Jackson, Emma Meehan, Zeenat Nawoor, Brendan O’Hare, Mark Ross, Daniela Lerro, Marinella Astuto, Chiara Grasso, Rita Scalisi, Giulia Frasacco, Elena Lenares, Roberto Leone, Maurizia Grazzini, Carmelo Minardi, Nicola Zadra, Gilda Cinnella, Antonella Cotoia, Dario Galante, Brita De Lorenzo, Beate Kuppers, Giulia Bottazzi, Fabio Caramelli, Maria Cristina Mondardini, Emanuele Rossetti, Sergio Picardo, Alessandro Vittori, Anna Camporesi, Andrea Wolfler, Edoardo Calderini, Laura Brigitta Colantonio, Simona Anna Finamore, Giuliana Anna Porro, Rachele Bonfiglio, Svetlana Kotzeva, Leila Mameli, Girolamo Mattioli, Camilla Micalizzi, Alessia Montaguti, Angela Pistorio, Clelia Zanaboni, Anna Guddo, Gerald Rogan Neba, Moreno Favarato, Bruno Guido Locatelli, Micol Maffioletti, Valter Sonzogni, Rossella Garra, Maria Sammartino, Fabio Sbaraglia, Andrea Cortegiani, Alessandra Moscarelli, Elena Attanasi, Simonetta Tesoro, Cristina Agapiti, Francesca Pinzoni, Cesare Vezzoli, Federico Bilotta, Arta Barzdina, Zane Straume, Anda Zundane, Laura Lukosiene, Irena Maraulaite, Ilona Razlevice, Bernd Schmitz, Stephanie Mifsud, Carolin Aehling, Celia Allison, Rients De Boer, Dina Emal, Markus Stevens, Marielle Buitenhuis, Jurgen de Graaff, Inge De Liefde, Andreas Machotta, Gail Scoones, Lonneke Staals, Jeremy Tomas, Anouk Van der Knijff-van Dortmont, Marianne Veldhuizen, David Alders, Wolfgang Buhre, Eva Schafrat, Jan Schreiber, Petronella Mari Vermeulen, Mark Hendriks, Sandra Lako, Marieke Voet-Lindner, Barbe Pieters, Gert-Jan Scheffer, Luc Tielens, Anthony R. Absalom, Margot Bergsma, Joke De Ruiter, Sascha Meier, Martin Volkers, Tjerk Zweers, Anne M. Beukers, Christa Boer, Jurgen Dertinger, Sandra Numan, Bas Van Zaane, Wenche B. Boerke, Nil Ekiz, Kristoffer Stensrud, Inger Marie Drage, Erik Ramon Isern, Alicja Bartkowska-Sniatkowska, Malgorzata Grzeskowiak, Magdalena Juzwa-Sobieraj, Jowita Rosada-Kurasińska, Artur Baranowski, Karina Jakubowska, Dorota Lewandowska, Magdalena Mierzewska-Schmidt, Piotr Sawicki, Magdalena Urban-Lechowicz, Pomianek Przemyslaw, Marzena Zielinska, Teresa Leal, Maria Soares, Pedro Pina, Sílvia Pinho, Maria Domingas Patuleia, Catarina Cruz Esteves, Helena Salgado, Maria João Santos, Rodica Badeti, Iulia Cindea, Loredana Oana, Adriana Gurita, Luminita Ilie, Gabriel Mocioiu, Radu Tabacaru, Irina Trante, Valentin Munteanu, Mihai Morariu, Emese Nyíri, Ivana Budic, Vesna Marjanovic, Biljana Drašković, Marina Pandurov, Jordanka Ilic, Ana Mandras, Zdenka Rados, Nikola Stankovic, Maja Suica, Sladjana Vasiljevic, Mirjana Knezevic, Irina Milojevic, Ivana Petrov, Selena Puric Racic, Dusica Simic, Irena Simic, Marija Stevic, Irena Vulicevic, Barbora Cabanová, Miloslav Hanula, Jelena Berger, Darja Janjatovic, Špela Pirtovšek Štupnik, Dolores Méndez, Gema Pino, Paloma Rubio, Alberto Izquierdo, Silvia López, Cristina González Serrano, Jesús Cebrián, Ana Peleteiro, Pilar Del Rey de Diego, Ernesto Martínez García, Carolina Tormo de las Heras, Pablo Troncoso Montero, Celia Arbona, David Artés, Alicia Chamizo, Silvia Serrano, Montserrat Suarez Comas, Francisco Escribá, Cristina Auli, Osvaldo Pérez Pardo, Natalia Sierra Biddle, Ceferina Suárez Castaño, María Isabel Villalobos Rico, Susana Manrique Muñoz, Irene García Martínez, Nuria Montferrer Estruch, Elena Vilardell Ortíz, Rodrigo Poves-Álvarez, Ivan Kohn, Ulf Lindestam, Jarl Reinhard, Albert Castellheim, Kerstin Sandström, Sporre Bengt, Rainer Dörenberg, Peter Frykholm, Maria Garcia, Ann Kvarnström, Emma Pontén, Thomas Bruelisauer, Gabor Erdoes, Heiko Kaiser, Mathias Marchon, Stefan Seiler, Yann Bögli, Mirko Dolci, Carine Marcucci, Isabelle Pichon, Laszlo Vutskits, Mattias Casutt, Martin Hölzle, Thomas Hurni, Martin Jöhr, Anna-Ursina Malär, Jacqueline Mauch, Thomas Erb, Karin Oeinck, Mine Akin, Gulsen Keskin, Yesim Senayli, Guner Kaya, Pinar Kendigelen, Ayse Çiğdem Tutuncu, Zehra Hatipoğlu, Dilek Özcengiz, Hale Aksu Erdost, Elvan Öçmen, Çimen Olguner, Hilmi Ayanoglu, Pelin Corman Dincer, Tumay Umuroglu, Mustafa Azizoglu, Handan Birbiçer, Nurcan Doruk, Aslı Sagun, Sibel Baris, Dmytro Dmytriiev, Sridevi Kuchi, Nuria Masip, Peter Brooks, Alison Hare, Nargis Ahmad, Michelle Casey, Sam De Silva, Nadine Dobby, Prakash Krishnan, L. Amaki Sogbodjor, Ellie Walker, Suellen Walker, Stephanie King, Katy Nicholson, Michelle Quinney, Paul Stevens, Andrew Blevin, Mariangela Giombini, Chulananda Goonasekera, Sadia Adil, Stephanie Bew, Carol Bodlani, Dan Gilpin, Stephanie Jinks, Nalini Malarkkan, Alice Miskovic, Rebecca Pad, Juliet Wolfe Barry, Joy Abbott, James Armstrong, Natalie Cooper, Lindsay Crate, John Emery, Kathryn James, Hannah King, Paul Martin, Stefano Scalia Catenacci, Rob Bomont, Paul Smith, Sara Mele, Alessandra Verzelloni, Philippa Dix, Graham Bell, Elena Gordeva, Lesley McKee, Esther Ngan, Jutta Scheffczik, Li-En Tan, Mark Worrall, Carmel Cassar, Kevin Goddard, Victoria Barlow, Vimmi Oshan, Khairi Shah, Sarah Bell, Lisa Daniels, Monica Gandhi, David Pachter, Chris Perry, Andrew Robertson, Carmen Scott, Lynne Waring, David Barnes, Sophie Childs, Joanne Norman, Robin Sunderland, Dowell Julia, Feijten Prisca, Harlet Pierre, Herbineaux Sarah, Leva Brigitte, Plichon Benoît, Virág Katalin, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Anesthesiology, HUS Children and Adolescents, Children's Hospital, Clinicum, Anestesiologian yksikkö, Disma, Nicola, Virag, Katalin, Riva, Thoma, Kaufmann, Jost, Engelhardt, Thoma, Habre, Walid, Breschan, Christian, Likar, Rudolf, Platzer, Manuela, Edelman, Isole, Eger, Johane, Heschl, Stefan, Messerer, Brigitte, Vittinghof, Maria, Kroess, Ruth, Stichlberger, Martina, Kahn, David, Pirotte, Thierry, Pregardien, Caroline, Veyckemans, Franci, Stevens, France, Berghmans, Johan, Bauters, Annemie, De Baerdemaeker, Luc, De Hert, Stefan, Lapage, Koen, Parashchanka, Aliaksandra, Van Limmen, Jurgen, Wyffels, Piet, Lauweryns, Julie, Najafi, Nadia, Vundelinckx, Jori, Butković, Diana, Kerovec Sorić, Ivana, Kralik, Sandra, Markić, Ana, Azman, Josip, Markic, Josko, Pupacic, Daniela, Frelich, Michal, Reimer, Petr, Urbanec, René, Cajková, Petra, Mixa, Vladimír, Sedláčková, Yvona, Knoppová, Lenka, Zlámalová (neé Květoňová), Alena, Vavřina, Martin, Žurek, Jiří, Hansen, Tom, Afshari, Arash, Bille, Anders Bastholm, Ellekvist, Marguerite, Ilmoja, Mari-Lii, Moor, Reet, Kikas, Reet, Väli, Merle, Kallio, Kariantti, Reponen, Elisa, Suominen, Pertti, Suvanto, Sami, Vähätalo, Raisa, Kokki, Hannu, Kokki, Merja, Harju, Jarkko, Kokkonen, Miia, Vieri, Jenni, Manner, Tuula, Amory, Catherine, Ludot, Hugue, Bert, Dina, Godart, Juliette, Laffargue, Anne, Dupont, Hervé, Urbina, Benjamin, Baujard, Catherine, Roulleau, Philippe, Staiti, Giuseppe, Bordes, Maryline, Nouette Gaulain, Karine, Hamonic, Yann, Semjen, Françoi, Jacqmarcq, Olivier, Lejus-Bourdeau, Caroline, Magne, Cécile, Petry, Léa, Ros, Lilica, Zang, Aurélien, Bennis, Mehdi, Coustets, Bernard, Fesseau, Rose, Constant, Isabelle, Khalil, Eliane, Sabourdin, Nada, Audren, Noemie, Descarpentries, Thoma, Fabre, Fanny, Legrand, Aurélien, Druot, Emilie, Orliaguet, Gille, Sabau, Lucie, Uhrig, Lynn, de la Brière, Françoi, Jonckheer, Karin, Mission, Jean-Paul, Scordo, Lucia, Couchepin, Caroline, Dadure, Christophe, De la Arena, Pablo, Hertz, Laurent, Pirat, Philippe, Sola, Chrystelle, Bellon, Myriam, Dahmani, Souhayl, Julien-Marsollier, Florence, Michelet, Daphne, Depret-Donatien, Veronique, Lesage, Anne, Laschat, Michael, Wappler, Frank, Becke, Karin, Brunner, Lena, Oppenrieder, Karin, Badelt, Gregor, Hochmuth, Karin, Koller, Bernhard, Reil, Anita, Richter, Sebastian, Fischer, Thoma, Diers, Anja, Schorer, Clemen, Weyland, Andrea, Cohausz, Ruth, Kretz, Franz-Josef, Löffler, Michaela, Wilbs, Marku, Hoehne, Claudia, Ulrici, Johanna, Goeters, Christiane, Flinspach, Armin, Klages, Matthia, Lindau, Simone, Messroghli, Leila, Zacharowski, Kai, Eisner, Christoph, Mueller, Thoma, Richter, Daniel, Schäfer, Melanie, Weigand, Marku, Weiterer, Sebastian, Ochsenreiter, Miriam, Schöler, Michael, Terboven, Tom, Eggemann, Isabel, Haussmann, Sascha, Leister, Nicola, Menzel, Christoph, Trieschmann, Uwe, Yücetepe, Sirin, Keilig, Susanna, Kranke, Peter, Jelting, Yvonne, Baehner, Torsten, Ellerkmann, Richard, Ghamari, Shahab, Neumann, Claudia, Söhle, Martin, Chloropoulou, Pelagia, Ntritsou, Vagia, Papagiannopoulou, Pinelopi, Garini, Eleana, Karafotia, Afroditi, Mammi, Panagoula, Bali, Evangelia, Iordanidou, Despoina, Malisiova, Anna, Polyzoi, Artemi, Tsiotou, Adelai, Sapi, Erzsebet, Székely, Edgar, Kosik, Nandor, Maráczi, Veronika, Schnur, Jano, Csillag, Judit, Gál, Jáno, Göbl, Gergely, Hauser, Baláz, Petróczy, Andrá, Tövisházi, Gyula, Blain, Stuart, Gallagher, Sarah, Harte, Sinead, Jackson, Mandy, Meehan, Emma, Nawoor, Zeenat, O’Hare, Brendan, Ross, Mark, Lerro, Daniela, Astuto, Marinella, Grasso, Chiara, Scalisi, Rita, Frasacco, Giulia, Lenares, Elena, Leone, Roberto, Grazzini, Maurizia, Minardi, Carmelo, Zadra, Nicola, Cinnella, Gilda, Cotoia, Antonella, Galante, Dario, De Lorenzo, Brita, Kuppers, Beate, Bottazzi, Giulia, Caramelli, Fabio, Mondardini, Maria Cristina, Rossetti, Emanuele, Picardo, Sergio, Vittori, Alessandro, Camporesi, Anna, Wolfler, Andrea, Calderini, Edoardo, Colantonio, Laura Brigitta, Finamore, Simona Anna, Porro, Giuliana Anna, Bonfiglio, Rachele, Kotzeva, Svetlana, Mameli, Leila, Mattioli, Girolamo, Micalizzi, Camilla, Montaguti, Alessia, Pistorio, Angela, Zanaboni, Clelia, Guddo, Anna, Neba, Gerald Rogan, Favarato, Moreno, Locatelli, Bruno Guido, Maffioletti, Micol, Sonzogni, Valter, Garra, Rossella, Sammartino, Maria, Sbaraglia, Fabio, Cortegiani, Andrea, Moscarelli, Alessandra, Attanasi, Elena, Tesoro, Simonetta, Agapiti, Cristina, Pinzoni, Francesca, Vezzoli, Cesare, Bilotta, Federico, Barzdina, Arta, Straume, Zane, Zundane, Anda, Lukosiene, Laura, Maraulaite, Irena, Razlevice, Ilona, Schmitz, Bernd, Mifsud, Stephanie, Aehling, Carolin, Allison, Celia, De Boer, Rient, Emal, Dina, Stevens, Marku, Buitenhuis, Marielle, de Graaff, Jurgen, De Liefde, Inge, Machotta, Andrea, Scoones, Gail, Staals, Lonneke, Tomas, Jeremy, Van der Knijff-van Dortmont, Anouk, Veldhuizen, Marianne, Alders, David, Buhre, Wolfgang, Schafrat, Eva, Schreiber, Jan, Vermeulen, Petronella Mari, Hendriks, Mark, Lako, Sandra, Voet-Lindner, Marieke, Pieters, Barbe, Scheffer, Gert-Jan, Tielens, Luc, Absalom, Anthony R., Bergsma, Margot, De Ruiter, Joke, Meier, Sascha, Volkers, Martin, Zweers, Tjerk, Beukers, Anne M., Boer, Christa, Dertinger, Jurgen, Numan, Sandra, Van Zaane, Ba, Boerke, Wenche B., Ekiz, Nil, Stensrud, Kristoffer, Drage, Inger Marie, Isern, Erik Ramon, Bartkowska-Sniatkowska, Alicja, Grzeskowiak, Malgorzata, Juzwa-Sobieraj, Magdalena, Rosada-Kurasińska, Jowita, Baranowski, Artur, Jakubowska, Karina, Lewandowska, Dorota, Mierzewska-Schmidt, Magdalena, Sawicki, Piotr, Urban-Lechowicz, Magdalena, Przemyslaw, Pomianek, Zielinska, Marzena, Leal, Teresa, Soares, Maria, Pina, Pedro, Pinho, Sílvia, Patuleia, Maria Dominga, Esteves, Catarina Cruz, Salgado, Helena, Santos, Maria João, Badeti, Rodica, Cindea, Iulia, Oana, Loredana, Gurita, Adriana, Ilie, Luminita, Mocioiu, Gabriel, Tabacaru, Radu, Trante, Irina, Munteanu, Valentin, Morariu, Mihai, Nyíri, Emese, Budic, Ivana, Marjanovic, Vesna, Drašković, Biljana, Pandurov, Marina, Ilic, Jordanka, Mandras, Ana, Rados, Zdenka, Stankovic, Nikola, Suica, Maja, Vasiljevic, Sladjana, Knezevic, Mirjana, Milojevic, Irina, Petrov, Ivana, Puric Racic, Selena, Simic, Dusica, Simic, Irena, Stevic, Marija, Vulicevic, Irena, Cabanová, Barbora, Hanula, Miloslav, Berger, Jelena, Janjatovic, Darja, Pirtovšek Štupnik, Špela, Méndez, Dolore, Pino, Gema, Rubio, Paloma, Izquierdo, Alberto, López, Silvia, González Serrano, Cristina, Cebrián, Jesú, Peleteiro, Ana, Del Rey de Diego, Pilar, Martínez García, Ernesto, Tormo de las Heras, Carolina, Troncoso Montero, Pablo, Arbona, Celia, Artés, David, Chamizo, Alicia, Serrano, Silvia, Suarez Comas, Montserrat, Escribá, Francisco, Auli, Cristina, Pérez Pardo, Osvaldo, Sierra Biddle, Natalia, Suárez Castaño, Ceferina, Villalobos Rico, María Isabel, Manrique Muñoz, Susana, García Martínez, Irene, Montferrer Estruch, Nuria, Vilardell Ortíz, Elena, Poves-Álvarez, Rodrigo, Kohn, Ivan, Lindestam, Ulf, Reinhard, Jarl, Castellheim, Albert, Sandström, Kerstin, Bengt, Sporre, Dörenberg, Rainer, Frykholm, Peter, Garcia, Maria, Kvarnström, Ann, Pontén, Emma, Bruelisauer, Thoma, Erdoes, Gabor, Kaiser, Heiko, Marchon, Mathia, Seiler, Stefan, Bögli, Yann, Dolci, Mirko, Marcucci, Carine, Pichon, Isabelle, Vutskits, Laszlo, Casutt, Mattia, Hölzle, Martin, Hurni, Thoma, Jöhr, Martin, Malär, Anna-Ursina, Mauch, Jacqueline, Erb, Thoma, Oeinck, Karin, Akin, Mine, Keskin, Gulsen, Senayli, Yesim, Kaya, Guner, Kendigelen, Pinar, Tutuncu, Ayse Çiğdem, Hatipoğlu, Zehra, Özcengiz, Dilek, Erdost, Hale Aksu, Öçmen, Elvan, Olguner, Çimen, Ayanoglu, Hilmi, Dincer, Pelin Corman, Umuroglu, Tumay, Azizoglu, Mustafa, Birbiçer, Handan, Doruk, Nurcan, Sagun, Aslı, Baris, Sibel, Dmytriiev, Dmytro, Kuchi, Sridevi, Masip, Nuria, Brooks, Peter, Hare, Alison, Ahmad, Nargi, Casey, Michelle, De Silva, Sam, Dobby, Nadine, Krishnan, Prakash, Sogbodjor, L. Amaki, Walker, Ellie, Walker, Suellen, King, Stephanie, Nicholson, Katy, Quinney, Michelle, Stevens, Paul, Blevin, Andrew, Giombini, Mariangela, Goonasekera, Chulananda, Adil, Sadia, Bew, Stephanie, Bodlani, Carol, Gilpin, Dan, Jinks, Stephanie, Malarkkan, Nalini, Miskovic, Alice, Pad, Rebecca, Wolfe Barry, Juliet, Abbott, Joy, Armstrong, Jame, Cooper, Natalie, Crate, Lindsay, Emery, John, James, Kathryn, King, Hannah, Martin, Paul, Scalia Catenacci, Stefano, Bomont, Rob, Smith, Paul, Mele, Sara, Verzelloni, Alessandra, Dix, Philippa, Bell, Graham, Gordeva, Elena, McKee, Lesley, Ngan, Esther, Scheffczik, Jutta, Tan, Li-En, Worrall, Mark, Cassar, Carmel, Goddard, Kevin, Barlow, Victoria, Oshan, Vimmi, Shah, Khairi, Bell, Sarah, Daniels, Lisa, Gandhi, Monica, Pachter, David, Perry, Chri, Robertson, Andrew, Scott, Carmen, Waring, Lynne, Barnes, David, Childs, Sophie, Norman, Joanne, Sunderland, Robin, Julia, Dowell, Prisca, Feijten, Pierre, Harlet, Sarah, Herbineaux, Brigitte, Leva, Benoît, Plichon, Katalin, Virág, IOO, ACS - Microcirculation, APH - Quality of Care, and ANS - Neuroinfection & -inflammation
Subjects: Male, Time Factors, paediatric, medicine.medical_treatment, morbidity, Severity of Illness Index, 0302 clinical medicine, 030202 anesthesiology, Risk Factors, Clinical endpoint, Anesthesia, Prospective Studies, 610 Medicine & health, Hypoxia, Medical Audit, medicine.diagnostic_test, ddc:617, infants, Incidence (epidemiology), Incidence, Age Factors, anaesthesia, respiratory system, Europe, Treatment Outcome, Cohort, Female, medicine.symptom, Bradycardia, Laryngoscopy, Anesthesia/adverse effects/mortality, Risk Assessment, Europe/epidemiology, 03 medical and health sciences, Laryngoscopy/adverse effects/mortality, Hypoxia/diagnosis/epidemiology/mortality, medicine, Intubation, Intratracheal, Humans, difficult intubation, business.industry, Tracheal intubation, Infant, Newborn, Infant, Perioperative, Newborn, 3126 Surgery, anesthesiology, intensive care, radiology, mortality, neonates, Clinical trial, Intratracheal, Anesthesiology and Pain Medicine, airway, Intubation, Intratracheal/adverse effects/mortality, neonate, Intubation, business, airways
Abstract: Background: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. Methods: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. Results: Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1e6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2
Published: 2021
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12. Contribution of classical complement activation and IgM to the control of Rickettsia infection

Author: Jack H. Cook, Sean P. Riley, Jinyi C. Zhu, and Mustapha Dahmani
Subjects: Complement C1q, Intracellular parasite, Rickettsia Infections, Biology, bacterial infections and mycoses, biology.organism_classification, Antibodies, Bacterial, Microbiology, In vitro, Complement (complexity), Complement system, Mice, Inbred C57BL, Mice, Classical complement pathway, Immune system, Rickettsia, Immunoglobulin M, Immunity, Immunology, Animals, Humans, bacteria, Complement Pathway, Classical, Molecular Biology
Abstract: Pathogenic Rickettsia are obligate intracellular bacteria and the etiologic agents of many life-threatening infectious diseases. Due to the serious nature of these infections, it is imperative to both identify the responsive immune sensory pathways and understand the associated immune mechanisms that restrict Rickettsia proliferation. Previous studies have demonstrated that the mammalian complement system is both activated during Rickettsia infection and contributes to the immune response to infection. To further define this component of the mammalian anti-Rickettsia immune response, we sought to identify the mechanism(s) of complement activation during Rickettsia infection. We have employed a series of in vitro and in vivo models of infection to investigate the role of the classical complement activation pathway during Rickettsia infection. Depletion or elimination of complement activity demonstrates that both C1q and pre-existing IgM contribute to complement activation; thus implicating the classical complement system in Rickettsia-mediated complement activation. Elimination of the classical complement pathway from mice increases susceptibility to R. australis infection with both increased bacterial loads in multiple tissues and decreased immune activation markers. This study highlights the role of the classical complement pathway in immunity against Rickettsia and implicates resident Rickettsia-responsive IgM in the response to infection.
Published: 2021
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13. Effects of opioid-reduced anesthesia during scoliosis surgery in children: a prospective observational study

Author: Rita Assaker, Souhayl Dahmani, Matthieu Camby, Florence Julien-Marsollier, Daphné Michelet, Thomas Vacher, Anne Galland, Lucile Marsac, Anne-Laure Simon, and B. Ilharreborde
Subjects: Pain, Postoperative, Adolescent, Morphine, business.industry, Incidence (epidemiology), Chronic pain, Idiopathic scoliosis, General Medicine, medicine.disease, Scoliosis surgery, Analgesics, Opioid, Spinal Fusion, Scoliosis, Opioid, Anesthesia, Neuropathic pain, medicine, Humans, Observational study, Child, business, Retrospective Studies, medicine.drug
Abstract: Aims: Opioid-reduced anesthesia (ORA) was suggested to decrease morphine consumption after adolescent idiopathic scoliosis (AIS) surgery and incidence of chronic pain. Materials & methods: A prospective analysis using the ORA in AIS surgery was performed. Two cohorts were compared: a control group (opioid-based anesthesia) and the ORA group. The main outcome was morphine consumption at day 1. Results: 33 patients operated for AIS using ORA were compared with 36 with opioid-based anesthesia. Morphine consumption was decreased in the ORA group (1.1 mg.kg-1 [0.2–2] vs 0.8 mg.kg-1 [0.3–2]; p = 0.02) at day 1. Persistent neuropathic pain at 1 year was decreased in the ORA group (p = 0.02). Conclusion: The ORA protocol is efficient to reduce postoperative morphine consumption in AIS surgery and preventing neuropathic pain.
Published: 2021
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14. How concerning is a SARS-CoV-2 variant of concern? Computational predictions and the variants labeling system

Author: Dana Ashoor, Maryam Marzouq, Khaled Trabelsi, Sadok Chlif, Nasser Abotalib, Noureddine Ben Khalaf, Ahmed R. Ramadan, and M-Dahmani Fathallah
Subjects: Microbiology (medical), Infectious Diseases, SARS-CoV-2, Mutation, Immunology, COVID-19, Humans, Pandemics, Microbiology, United States
Abstract: In this study, we evaluated the use of a predictive computational approach for SARS-CoV-2 genetic variations analysis in improving the current variant labeling system. First, we reviewed the basis of the system developed by the World Health Organization (WHO) for the labeling of SARS-CoV-2 genetic variants and the derivative adapted by the United States Centers for Disease Control and Prevention (CDC). Both labeling systems are based on the virus’ major attributes. However, we found that the labeling criteria of the SARS-CoV-2 variants derived from these attributes are not accurately defined and are used differently by the two agencies. Consequently, discrepancies exist between the labels given by WHO and the CDC to the same variants. Our observations suggest that giving the variant of concern (VOC) label to a new variant is premature and might not be appropriate. Therefore, we used a comparative computational approach to predict the effects of the mutations on the virus structure and functions of five VOCs. By linking these data to the criteria used by WHO/CDC for variant labeling, we ascertained that a predictive computational comparative approach of the genetic variations is a good way for rapid and more accurate labeling of SARS-CoV-2 variants. We propose to label all emergent variants, variant under monitoring or variant being monitored (VUM/VBM), and to carry out computational predictive studies with thorough comparison to existing variants, upon which more appropriate and informative labels can be attributed. Furthermore, harmonization of the variant labeling system would be globally beneficial to communicate about and fight the COVID-19 pandemic.
Published: 2022
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15. Preventing the Long-term Effects of General Anesthesia on the Developing Brain: How Translational Research can Contribute

Author: Carine Ali, Souhayl Dahmani, Gilles Orliaguet, Jean-Luc Hanouz, Clément Gakuba, Jean-Louis Gérard, Denis Vivien, Audrey Chagnot, Nicolas Poirel, Jean-Philippe Salaün, Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de psychologie du développement et de l'éducation de l'enfant (LaPsyDÉ - UMR 8240), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Hôpital Robert Debré Paris, Hôpital Robert Debré, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Pharmacologie et évaluations thérapeutiques chez l'enfant et la femme enceinte (URP_7323), Université de Paris (UP), CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, medicine.medical_specialty, Brain development, business.industry, General Neuroscience, Public health, Brain, Translational research, Anesthesia, General, 3. Good health, Translational Research, Biomedical, Food and drug administration, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Anesthesia, Pediatric surgery, medicine, Humans, Neurotoxicity Syndromes, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Child, business, 030217 neurology & neurosurgery, Anesthetics
Abstract: International audience; In 2017, the Food and Drug Administration published a safety recommendation to limit the exposure to general anesthesia as much as possible below the age of three. Indeed, several preclinical and clinical studies have questioned the possible toxicity of general anesthesia on the developing brain. Since then, recent clinical studies tried to mitigate this alarming issue. What is true, what is false? Contrary to some perceptions, the debate is not over yet. Only stronger translational research will allow scientists to provide concrete answers to this public health issue. In this review, we will provide and discuss the more recent data in this field, including the point of view of preclinical researchers, neuropsychologists and pediatric anesthesiologists. Through translational research, preclinical researchers have more than ever a role to play to better understand and identify long-term effects of general anesthesia for pediatric surgery on brain development in order to minimize it.
Published: 2021
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16. Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

Author: Fuchs A., Disma N., Virag K., Ulmer F., Habre W., de Graaff J. C., Riva T., NECTARINE Group of the European Society of Anaesthesiology and Intensive Care Clinical Trial Network: Christian Breschan, Rudolf Likar, Manuela Platzer, Isole Edelman, Johanes Eger, Stefan Heschl, Brigitte Messerer, Maria Vittinghof, Ruth Kroess, Martina Stichlberger, David Kahn, Thierry Pirotte, Caroline Pregardien, Francis Veyckemans, France Stevens, Johan Berghmans, Annemie Bauters, Luc De Baerdemaeker, Stefan De Hert, Koen Lapage, Aliaksandra Parashchanka, Jurgen Van Limmen, Piet Wyffels, Nadia Najafi, Joris Vundelinckx, Diana Butković, Ivana Kerovec Sorić, Sandra Kralik, Ana Markić, Josip Azman, Josko Markic, Daniela Pupacic, Michal Frelich, Petr Reimer, René Urbanec, Petra Cajková, Vladimír Mixa, Yvona Sedláčková, Lenka Knoppová, Alena Zlámalová, Martin Vavřina, Jiří Žurek, Tom Hansen, Arash Afshari, Anders Bastholm Bille, Marguerite Ellekvist, Mari-Liis Ilmoja, Reet Moor, Reet Kikas, Merle Väli, Kariantti Kallio, Elisa Reponen, Pertti Suominen, Sami Suvanto, Raisa Vähätalo, Hannu Kokki, Merja Kokki, Jarkko Harju, Miia Kokkonen, Jenni Vieri, Tuula Manner, Catherine Amory, Hugues Ludot, Dina Bert, Juliette Godart, Anne Laffargue, Hervé Dupont, Benjamin Urbina, Catherine Baujard, Philippe Roulleau, Giuseppe Staiti, Maryline Bordes, Karine Nouette Gaulain, Yann Hamonic, François Semjen, Olivier Jacqmarcq, Caroline Lejus-Bourdeau, Cécile Magne, Léa Petry, Lilica Ros, Aurélien Zang, Mehdi Bennis, Bernard Coustets, Rose Fesseau, Isabelle Constant, Eliane Khalil, Nada Sabourdin, Noemie Audren, Thomas Descarpentries, Fanny Fabre, Aurélien Legrand, Emilie Druot, Gilles Orliaguet, Lucie Sabau, Lynn Uhrig, François de la Brière, Karin Jonckheer, Jean-Paul Mission, Lucia Scordo, Caroline Couchepin, Christophe Dadure, Pablo De la Arena, Laurent Hertz, Philippe Pirat, Chrystelle Sola, Myriam Bellon, Souhayl Dahmani, Florence Julien-Marsollier, Daphne Michelet, Veronique Depret-Donatien, Anne Lesage, Jost Kaufmann, Michael Laschat, Frank Wappler, Karin Becke, Lena Brunner, Karin Oppenrieder, Gregor Badelt, Karin Hochmuth, Bernhard Koller, Anita Reil, Sebastian Richter, Thomas Fischer, Anja Diers, Clemens Schorer, Andreas Weyland, Ruth Cohausz, Franz-Josef Kretz, Michaela Löffler, Markus Wilbs, Claudia Hoehne, Johanna Ulrici, Christiane Goeters, Armin Flinspach, Matthias Klages, Simone Lindau, Leila Messroghli, Kai Zacharowski, Christoph Eisner, Thomas Mueller, Daniel Richter, Melanie Schäfer, Markus Weigand, Sebastian Weiterer, Miriam Ochsenreiter, Michael Schöler, Tom Terboven, Isabel Eggemann, Sascha Haussmann, Nicolas Leister, Christoph Menzel, Uwe Trieschmann, Sirin Yücetepe, Susanna Keilig, Peter Kranke, Yvonne Jelting, Torsten Baehner, Richard Ellerkmann, Shahab Ghamari, Claudia Neumann, Martin Söhle, Pelagia Chloropoulou, Vagia Ntritsou, Pinelopi Papagiannopoulou, Eleana Garini, Afroditi Karafotia, Panagoula Mammi, Evangelia Bali, Despoina Iordanidou, Anna Malisiova, Artemis Polyzoi, Adelais Tsiotou, Erzsebet Sapi, Edgar Székely, Nandor Kosik, Veronika Maráczi, Janos Schnur, Judit Csillag, János Gál, Gergely Göbl, Balázs Hauser, András Petróczy, Gyula Tövisházi, Stuart Blain, Sarah Gallagher, Sinead Harte, Mandy Jackson, Emma Meehan, Zeenat Nawoor, Brendan O'Hare, Mark Ross, Daniela Lerro, Marinella Astuto, Chiara Grasso, Rita Scalisi, Giulia Frasacco, Elena Lenares, Roberto Leone, Maurizia Grazzini, Carmelo Minardi, Nicola Zadra, Gilda Cinnella, Antonella Cotoia, Dario Galante, Brita De Lorenzo, Beate Kuppers, Giulia Bottazzi, Fabio Caramelli, Maria Cristina Mondardini, Emanuele Rossetti, Sergio Picardo, Alessandro Vittori, Anna Camporesi, Andrea Wolfler, Edoardo Calderini, Laura Brigitta Colantonio, Simona Anna Finamore, Giuliana Anna Porro, Rachele Bonfiglio, Svetlana Kotzeva, Leila Mameli, Girolamo Mattioli, Camilla Micalizzi, Alessia Montaguti, Angela Pistorio, Clelia Zanaboni, Anna Guddo, Gerald Rogan Neba, Moreno Favarato, Bruno Guido Locatelli, Micol Maffioletti, Valter Sonzogni, Rossella Garra, Maria Sammartino, Fabio Sbaraglia, Andrea Cortegiani, Alessandra Moscarelli, Elena Attanasi, Simonetta Tesoro, Cristina Agapiti, Francesca Pinzoni, Cesare Vezzoli, Federico Bilotta, Arta Barzdina, Zane Straume, Anda Zundane, Laura Lukosiene, Irena Maraulaite, Ilona Razlevice, Bernd Schmitz, Stephanie Mifsud, Carolin Aehling, Celia Allison, Rients De Boer, Dina Emal, Markus Stevens, Marielle Buitenhuis, Inge De Liefde, Andreas Machotta, Gail Scoones, Lonneke Staals, Jeremy Tomas, Anouk Van der Knijff-van Dortmont, Marianne Veldhuizen, David Alders, Wolfgang Buhre, Eva Schafrat, Jan Schreiber, Petronella Mari Vermeulen, Mark Hendriks, Sandra Lako, Marieke Voet-Lindner, Barbe Pieters, Gert-Jan Scheffer, Luc Tielens, Anthony R Absalom, Margot Bergsma, Joke De Ruiter, Sascha Meier, Martin Volkers, Tjerk Zweers, Anne M Beukers, Christa Boer, Jurgen Dertinger, Sandra Numan, Bas Van Zaane, Wenche B Boerk, Nil Ekiz, Kristoffer Stensrud, Inger Marie Drage, Erik Ramon Isern, Alicja Bartkowska-Sniatkowska, Malgorzata Grzeskowiak, Magdalena Juzwa-Sobieraj, Jowita Rosada-Kurasińska, Artur Baranowski, Karina Jakubowska, Dorota Lewandowska, Magdalena Mierzewska-Schmidt, Piotr Sawicki, Magdalena Urban-Lechowicz, Pomianek Przemyslaw, Marzena Zielinska, Teresa Leal, Maria Soares, Pedro Pina, Sílvia Pinho, Maria Domingas Patuleia, Catarina Cruz Esteves, Helena Salgado, Maria João Santos, Rodica Badeti, Iulia Cindea, Loredana Oana, Adriana Gurita, Luminita Ilie, Gabriel Mocioiu, Radu Tabacaru, Irina Trante, Valentin Munteanu, Mihai Morariu, Emese Nyíri, Ivana Budic, Vesna Marjanovic, Biljana Drašković, Marina Pandurov, Jordanka Ilic, Ana Mandras, Zdenka Rados, Nikola Stankovic, Maja Suica, Sladjana Vasiljevic, Mirjana Knezevic, Irina Milojevic, Ivana Petrov, Selena Puric Racic, Dusica Simic, Irena Simic, Marija Stevic, Irena Vulicevic, Barbora Cabanová, Miloslav Hanula, Jelena Berger, Darja Janjatovic, Špela Pirtovšek Štupnik, Dolores Méndez, Gema Pino, Paloma Rubio, Alberto Izquierdo, Silvia López, Cristina González Serrano, Jesús Cebrián, Ana Peleteiro, Pilar Del Rey de Diego, Ernesto Martínez García, Carolina Tormo de Las Heras, Pablo Troncoso Montero, Celia Arbona, David Artés, Alicia Chamizo, Silvia Serrano, Montserrat Suarez Comas, Francisco Escribá, Cristina Auli, Osvaldo Pérez Pardo, Natalia Sierra Biddle, Ceferina Suárez Castaño, María Isabel Villalobos Rico, Susana Manrique Muñoz, Irene García Martínez, Nuria Montferrer Estruch, Elena Vilardell Ortíz, Rodrigo Poves-Álvarez, Ivan Kohn, Ulf Lindestam, Jarl Reinhard, Albert Castellheim, Kerstin Sandström, Sporre Bengt, Rainer Dörenberg, Peter Frykholm, Maria Garcia, Ann Kvarnström, Emma Pontén, Thomas Bruelisauer, Gabor Erdoes, Heiko Kaiser, Mathias Marchon, Stefan Seiler, Yann Bögli, Mirko Dolci, Carine Marcucci, Isabelle Pichon, Laszlo Vutskits, Mattias Casutt, Martin Hölzle, Thomas Hurni, Martin Jöhr, Anna-Ursina Malär, Jacqueline Mauch, Thomas Erb, Karin Oeinck, Mine Akin, Gulsen Keskin, Yesim Senayli, Guner Kaya, Pinar Kendigelen, Ayse Çiğdem Tutuncu, Zehra Hatipoğlu, Dilek Özcengiz, Hale Aksu Erdost, Elvan Öçmen, Çimen Olguner, Hilmi Ayanoglu, Pelin Corman Dincer, Tumay Umuroglu, Mustafa Azizoglu, Handan Birbiçer, Nurcan Doruk, Aslı Sagun, Sibel Baris, Dmytro Dmytriiev, Sridevi Kuchi, Nuria Masip, Peter Brooks, Alison Hare, Nargis Ahmad, Michelle Casey, Sam De Silva, Nadine Dobby, Prakash Krishnan, L Amaki Sogbodjor, Ellie Walker, Suellen Walker, Stephanie King, Katy Nicholson, Michelle Quinney, Paul Stevens, Andrew Blevin, Mariangela Giombini, Chulananda Goonasekera, Sadia Adil, Stephanie Bew, Carol Bodlani, Dan Gilpin, Stephanie Jinks, Nalini Malarkkan, Alice Miskovic, Rebecca Pad, Juliet Wolfe Barry, Joy Abbott, James Armstrong, Natalie Cooper, Lindsay Crate, John Emery, Kathryn James, Hannah King, Paul Martin, Stefano Scalia Catenacci, Rob Bomont, Paul Smith, Sara Mele, Alessandra Verzelloni, Philippa Dix, Graham Bell, Elena Gordeva, Lesley McKee, Esther Ngan, Jutta Scheffczik, Li-En Tan, Mark Worrall, Carmel Cassar, Kevin Goddard, Victoria Barlow, Vimmi Oshan, Khairi Shah, Sarah Bell, Lisa Daniels, Monica Gandhi, David Pachter, Chris Perry, Andrew Robertson, Carmen Scott, Lynne Waring, David Barnes, Sophie Childs, Joanne Norman, Robin Sunderland, Fuchs A., Disma N., Virag K., Ulmer F., Habre W., de Graaff J.C., Riva T., NECTARINE Group of the European Society of Anaesthesiology and Intensive Care Clinical Trial Network: Christian Breschan, Rudolf Likar, Manuela Platzer, Isole Edelman, Johanes Eger, Stefan Heschl, Brigitte Messerer, Maria Vittinghof, Ruth Kroess, Martina Stichlberger, David Kahn, Thierry Pirotte, Caroline Pregardien, Francis Veyckemans, France Stevens, Johan Berghmans, Annemie Bauters, Luc De Baerdemaeker, Stefan De Hert, Koen Lapage, Aliaksandra Parashchanka, Jurgen Van Limmen, Piet Wyffels, Nadia Najafi, Joris Vundelinckx, Diana Butković, Ivana Kerovec Sorić, Sandra Kralik, Ana Markić, Josip Azman, Josko Markic, Daniela Pupacic, Michal Frelich, Petr Reimer, René Urbanec, Petra Cajková, Vladimír Mixa, Yvona Sedláčková, Lenka Knoppová, Alena Zlámalová, Martin Vavřina, Jiří Žurek, Tom Hansen, Arash Afshari, Anders Bastholm Bille, Marguerite Ellekvist, Mari-Liis Ilmoja, Reet Moor, Reet Kikas, Merle Väli, Kariantti Kallio, Elisa Reponen, Pertti Suominen, Sami Suvanto, Raisa Vähätalo, Hannu Kokki, Merja Kokki, Jarkko Harju, Miia Kokkonen, Jenni Vieri, Tuula Manner, Catherine Amory, Hugues Ludot, Dina Bert, Juliette Godart, Anne Laffargue, Hervé Dupont, Benjamin Urbina, Catherine Baujard, Philippe Roulleau, Giuseppe Staiti, Maryline Bordes, Karine Nouette Gaulain, Yann Hamonic, François Semjen, Olivier Jacqmarcq, Caroline Lejus-Bourdeau, Cécile Magne, Léa Petry, Lilica Ros, Aurélien Zang, Mehdi Bennis, Bernard Coustets, Rose Fesseau, Isabelle Constant, Eliane Khalil, Nada Sabourdin, Noemie Audren, Thomas Descarpentries, Fanny Fabre, Aurélien Legrand, Emilie Druot, Gilles Orliaguet, Lucie Sabau, Lynn Uhrig, François de la Brière, Karin Jonckheer, Jean-Paul Mission, Lucia Scordo, Caroline Couchepin, Christophe Dadure, Pablo De la Arena, Laurent Hertz, Philippe Pirat, Chrystelle Sola, Myriam Bellon, Souhayl Dahmani, Florence Julien-Marsollier, Daphne Michelet, Veronique Depret-Donatien, Anne Lesage, Jost Kaufmann, Michael Laschat, Frank Wappler, Karin Becke, Lena Brunner, Karin Oppenrieder, Gregor Badelt, Karin Hochmuth, Bernhard Koller, Anita Reil, Sebastian Richter, Thomas Fischer, Anja Diers, Clemens Schorer, Andreas Weyland, Ruth Cohausz, Franz-Josef Kretz, Michaela Löffler, Markus Wilbs, Claudia Hoehne, Johanna Ulrici, Christiane Goeters, Armin Flinspach, Matthias Klages, Simone Lindau, Leila Messroghli, Kai Zacharowski, Christoph Eisner, Thomas Mueller, Daniel Richter, Melanie Schäfer, Markus Weigand, Sebastian Weiterer, Miriam Ochsenreiter, Michael Schöler, Tom Terboven, Isabel Eggemann, Sascha Haussmann, Nicolas Leister, Christoph Menzel, Uwe Trieschmann, Sirin Yücetepe, Susanna Keilig, Peter Kranke, Yvonne Jelting, Torsten Baehner, Richard Ellerkmann, Shahab Ghamari, Claudia Neumann, Martin Söhle, Pelagia Chloropoulou, Vagia Ntritsou, Pinelopi Papagiannopoulou, Eleana Garini, Afroditi Karafotia, Panagoula Mammi, Evangelia Bali, Despoina Iordanidou, Anna Malisiova, Artemis Polyzoi, Adelais Tsiotou, Erzsebet Sapi, Edgar Székely, Nandor Kosik, Veronika Maráczi, Janos Schnur, Judit Csillag, János Gál, Gergely Göbl, Balázs Hauser, András Petróczy, Gyula Tövisházi, Stuart Blain, Sarah Gallagher, Sinead Harte, Mandy Jackson, Emma Meehan, Zeenat Nawoor, Brendan O'Hare, Mark Ross, Daniela Lerro, Marinella Astuto, Chiara Grasso, Rita Scalisi, Giulia Frasacco, Elena Lenares, Roberto Leone, Maurizia Grazzini, Carmelo Minardi, Nicola Zadra, Gilda Cinnella, Antonella Cotoia, Dario Galante, Brita De Lorenzo, Beate Kuppers, Giulia Bottazzi, Fabio Caramelli, Maria Cristina Mondardini, Emanuele Rossetti, Sergio Picardo, Alessandro Vittori, Anna Camporesi, Andrea Wolfler, Edoardo Calderini, Laura Brigitta Colantonio, Simona Anna Finamore, Giuliana Anna Porro, Rachele Bonfiglio, Svetlana Kotzeva, Leila Mameli, Girolamo Mattioli, Camilla Micalizzi, Alessia Montaguti, Angela Pistorio, Clelia Zanaboni, Anna Guddo, Gerald Rogan Neba, Moreno Favarato, Bruno Guido Locatelli, Micol Maffioletti, Valter Sonzogni, Rossella Garra, Maria Sammartino, Fabio Sbaraglia, Andrea Cortegiani, Alessandra Moscarelli, Elena Attanasi, Simonetta Tesoro, Cristina Agapiti, Francesca Pinzoni, Cesare Vezzoli, Federico Bilotta, Arta Barzdina, Zane Straume, Anda Zundane, Laura Lukosiene, Irena Maraulaite, Ilona Razlevice, Bernd Schmitz, Stephanie Mifsud, Carolin Aehling, Celia Allison, Rients De Boer, Dina Emal, Markus Stevens, Marielle Buitenhuis, Inge De Liefde, Andreas Machotta, Gail Scoones, Lonneke Staals, Jeremy Tomas, Anouk Van der Knijff-van Dortmont, Marianne Veldhuizen, David Alders, Wolfgang Buhre, Eva Schafrat, Jan Schreiber, Petronella Mari Vermeulen, Mark Hendriks, Sandra Lako, Marieke Voet-Lindner, Barbe Pieters, Gert-Jan Scheffer, Luc Tielens, Anthony R Absalom, Margot Bergsma, Joke De Ruiter, Sascha Meier, Martin Volkers, Tjerk Zweers, Anne M Beukers, Christa Boer, Jurgen Dertinger, Sandra Numan, Bas Van Zaane, Wenche B Boerk, Nil Ekiz, Kristoffer Stensrud, Inger Marie Drage, Erik Ramon Isern, Alicja Bartkowska-Sniatkowska, Malgorzata Grzeskowiak, Magdalena Juzwa-Sobieraj, Jowita Rosada-Kurasińska, Artur Baranowski, Karina Jakubowska, Dorota Lewandowska, Magdalena Mierzewska-Schmidt, Piotr Sawicki, Magdalena Urban-Lechowicz, Pomianek Przemyslaw, Marzena Zielinska, Teresa Leal, Maria Soares, Pedro Pina, Sílvia Pinho, Maria Domingas Patuleia, Catarina Cruz Esteves, Helena Salgado, Maria João Santos, Rodica Badeti, Iulia Cindea, Loredana Oana, Adriana Gurita, Luminita Ilie, Gabriel Mocioiu, Radu Tabacaru, Irina Trante, Valentin Munteanu, Mihai Morariu, Emese Nyíri, Ivana Budic, Vesna Marjanovic, Biljana Drašković, Marina Pandurov, Jordanka Ilic, Ana Mandras, Zdenka Rados, Nikola Stankovic, Maja Suica, Sladjana Vasiljevic, Mirjana Knezevic, Irina Milojevic, Ivana Petrov, Selena Puric Racic, Dusica Simic, Irena Simic, Marija Stevic, Irena Vulicevic, Barbora Cabanová, Miloslav Hanula, Jelena Berger, Darja Janjatovic, Špela Pirtovšek Štupnik, Dolores Méndez, Gema Pino, Paloma Rubio, Alberto Izquierdo, Silvia López, Cristina González Serrano, Jesús Cebrián, Ana Peleteiro, Pilar Del Rey de Diego, Ernesto Martínez García, Carolina Tormo de Las Heras, Pablo Troncoso Montero, Celia Arbona, David Artés, Alicia Chamizo, Silvia Serrano, Montserrat Suarez Comas, Francisco Escribá, Cristina Auli, Osvaldo Pérez Pardo, Natalia Sierra Biddle, Ceferina Suárez Castaño, María Isabel Villalobos Rico, Susana Manrique Muñoz, Irene García Martínez, Nuria Montferrer Estruch, Elena Vilardell Ortíz, Rodrigo Poves-Álvarez, Ivan Kohn, Ulf Lindestam, Jarl Reinhard, Albert Castellheim, Kerstin Sandström, Sporre Bengt, Rainer Dörenberg, Peter Frykholm, Maria Garcia, Ann Kvarnström, Emma Pontén, Thomas Bruelisauer, Gabor Erdoes, Heiko Kaiser, Mathias Marchon, Stefan Seiler, Yann Bögli, Mirko Dolci, Carine Marcucci, Isabelle Pichon, Laszlo Vutskits, Mattias Casutt, Martin Hölzle, Thomas Hurni, Martin Jöhr, Anna-Ursina Malär, Jacqueline Mauch, Thomas Erb, Karin Oeinck, Mine Akin, Gulsen Keskin, Yesim Senayli, Guner Kaya, Pinar Kendigelen, Ayse Çiğdem Tutuncu, Zehra Hatipoğlu, Dilek Özcengiz, Hale Aksu Erdost, Elvan Öçmen, Çimen Olguner, Hilmi Ayanoglu, Pelin Corman Dincer, Tumay Umuroglu, Mustafa Azizoglu, Handan Birbiçer, Nurcan Doruk, Aslı Sagun, Sibel Baris, Dmytro Dmytriiev, Sridevi Kuchi, Nuria Masip, Peter Brooks, Alison Hare, Nargis Ahmad, Michelle Casey, Sam De Silva, Nadine Dobby, Prakash Krishnan, L Amaki Sogbodjor, Ellie Walker, Suellen Walker, Stephanie King, Katy Nicholson, Michelle Quinney, Paul Stevens, Andrew Blevin, Mariangela Giombini, Chulananda Goonasekera, Sadia Adil, Stephanie Bew, Carol Bodlani, Dan Gilpin, Stephanie Jinks, Nalini Malarkkan, Alice Miskovic, Rebecca Pad, Juliet Wolfe Barry, Joy Abbott, James Armstrong, Natalie Cooper, Lindsay Crate, John Emery, Kathryn James, Hannah King, Paul Martin, Stefano Scalia Catenacci, Rob Bomont, Paul Smith, Sara Mele, Alessandra Verzelloni, Philippa Dix, Graham Bell, Elena Gordeva, Lesley McKee, Esther Ngan, Jutta Scheffczik, Li-En Tan, Mark Worrall, Carmel Cassar, Kevin Goddard, Victoria Barlow, Vimmi Oshan, Khairi Shah, Sarah Bell, Lisa Daniels, Monica Gandhi, David Pachter, Chris Perry, Andrew Robertson, Carmen Scott, Lynne Waring, David Barnes, Sophie Childs, Joanne Norman, Robin Sunderland, and Anesthesiology
Subjects: Red Blood Cell Transfusion, NEONATE, Haemoglobin levels, 610 Medicine & health, Peri-operative, red blood cell transfusion, neonates, infants, High morbidity, Hemoglobins, TRANSFUSION, medicine, Clinical endpoint, Humans, Anesthesia, Prospective Studies, business.industry, Postmenstrual Age, Infant, Newborn, Perioperative, Europe, Red blood cell, Anesthesiology and Pain Medicine, medicine.anatomical_structure, Observational study, business, 610 Medizin und Gesundheit, Erythrocyte Transfusion
Abstract: BACKGROUND Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12��g��dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (��week 3) onwards. OBJECTIVE To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN A multicentre observational study. SETTING The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g��dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g��dl-1 in week 2 and 8.0 [7.3 to 9.0] g��dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml��kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g��dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION ClinicalTrials.gov, identifier: NCT02350348.
Published: 2021
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17. A computer-aided approach to identify novel Leishmania major protein disulfide isomerase inhibitors for treatment of leishmaniasis

Author: Giuseppe Romeo, Noureddine Ben Khalaf, Ivy Hurwitz, Douglas J Perkins, Loredana Salerno, Peter Sedillo, Susie Pham, Jessica Gonzales, Dahmani M. Fathallah, Sebastiano Intagliata, Valeria Pittalà, and Sara Abdelghany
Subjects: Protein Conformation, Hexachlorophene, Protein Disulfide-Isomerases, Virulence, 01 natural sciences, Drug design, Small Molecule Libraries, Structure-Activity Relationship, Anti-Infective Agents, Catalytic Domain, 0103 physical sciences, Drug Discovery, medicine, Humans, Leishmania major, Enzyme Inhibitors, Physical and Theoretical Chemistry, Protein disulfide-isomerase, Leishmaniasis, Pathogen, Leishmania, Virtual screening, 010304 chemical physics, biology, Chemistry, Cheminformatics, Protein disulfide isomerase, medicine.disease, biology.organism_classification, In vitro, 0104 chemical sciences, Computer Science Applications, Molecular Docking Simulation, 010404 medicinal & biomolecular chemistry, Biochemistry, Computer-Aided Design, Protein Binding
Abstract: Leishmaniasis is an infectious disease caused by parasites of the genus Leishmania and transmitted by the bite of a sand fly. To date, most available drugs for treatment are toxic and beyond the economic means of those affected by the disease. Protein disulfide isomerase (PDI) is a chaperone protein that plays a major role in the folding of newly synthesized proteins, specifically assisting in disulfide bond formation, breakage, or rearrangement in all non-native proteins. In previous work, we demonstrated that Leishmania major PDI (LmPDI) has an essential role in pathogen virulence. Furthermore, inhibition of LmPDI further blocked parasite infection in macrophages. In this study, we utilized a computer-aided approach to design a series of LmPDI inhibitors. Fragment-based virtual screening allowed for the understanding of the inhibitors' modes of action on LmPDI active sites. The generated compounds obtained after multiple rounds of virtual screening were synthesized and significantly inhibited target LmPDI reductase activity and were shown to decrease in vitro parasite growth in human monocyte-derived macrophages. This novel cheminformatics and synthetic approach led to the identification of a new series of compounds that might be optimized into novel drugs, likely more specific and less toxic for the treatment of leishmaniasis.
Published: 2021
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18. Reducing the time to successful intravenous cannulation in anaesthetised children with poor vein visibility using a near-infrared device

Author: Souhayl Dahmani, Fabian Roy-Gash, Anne-Emmanuelle Colas, Jean-Michel Devys, Béatrice Bruneau, Severine Gras, Nadège Salvi, Gilles Orliaguet, and Alia Skhiri
Subjects: Paris, Intravenous cannulation, Vascular imaging, business.industry, Hazard ratio, Anesthesia, General, Clinical trial, Anesthesiology and Pain Medicine, medicine.anatomical_structure, Child, Preschool, Anesthesia, Catheterization, Peripheral, Humans, Medicine, General anaesthesia, France, Prospective Studies, Child, business, Vein, Inhalational anesthesia, Venous cannulation
Abstract: Background During inhalational induction of anaesthesia for children, severe respiratory events can occur but can be rapidly treated once intravenous access is in place. Reducing the time to successful cannulation during inhalational induction for children with poor vein visibility would improve safety. Objective To study the effectiveness of a near-infrared (NIR) vascular imaging device (Veinviewer) to facilitate intravenous cannulation. Design A prospective, multicentre, randomised, open clinical trial. Setting The operating rooms of three paediatric hospitals in Paris, France, from 1 October 2012 to 31 March 2016. Patients Children up to the age of 7 years, with poor vein visibility requiring general anaesthesia. Intervention Inhalational anaesthesia was initiated and intravenous cannulation was performed with the standard approach or with the Veinviewer Vision. Main outcome measures The primary outcome was the time to successful intravenous cannulation. A secondary outcome was the proportion of successful first attempts. Results The mean time to successful intravenous cannulation was 200 (95% CI, 143 to 295) seconds in the Veinviewer and 252 (95% CI, 194 to 328) seconds for the control group: hazard ratio 1.28 (1.02 to 1.60) (P = 0.03). The adjusted hazard ratio for known predictive factors was 1.25 (0.99 to 1.56) (P = 0.06). Success at the first attempt was 64.6% (102/158) in the 'Veinviewer' group vs. 55.6% (85/153) in the 'control' group (P = 0.10). Conclusion The Veinviewer has limited value in reducing the time to successful intravenous cannulation during inhalational anaesthesia for young children with poor vein visibility. However, there is a strong trend to reducing the delay in some cases and, given its absence of side effects, it could be part of a rescue option for a difficult venous-access strategy. Clinical trial registration NCT01685866 (http://www.clinicaltrials.gov).
Published: 2021
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19. Determinants of Work-Related Quality of Life in French Anesthesiologists

Author: Benjamin Gafsou, Florence Julien-Marsollier, Marie-Christine Becq, Souhayl Dahmani, Daphné Michelet, and Christopher Brasher
Subjects: Adult, Male, Gerontology, Attitude of Health Personnel, Workload, Family income, Work related, Job Satisfaction, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), 030202 anesthesiology, Surveys and Questionnaires, Humans, Medicine, Interpersonal Relations, Big Five personality traits, Workplace, Extraversion and introversion, business.industry, Conscientiousness, Middle Aged, Neuroticism, Anesthesiologists, Anesthesiology and Pain Medicine, Income, Quality of Life, Female, Job satisfaction, France, business, 030217 neurology & neurosurgery, Personality
Abstract: Background Little evidence is available regarding work-related quality of life (WRQoL) for anesthesiologists. We aimed to explore factors associated with WRQoL among French anesthesiologists. Methods The study surveyed French anesthesiologists qualified for more than 2 years. The primary objective was the determination of factors associated with WRQoL. Factors analyzed included demographic characteristics, lifestyle, financial status, personality traits, professional relations, management and organization, and occupational tasks when at work. Statistical analyses were performed using a multivariable quantile regression model. Results Overall, 2040 anesthesiologists responded to the survey and 1922 responses were analyzed. The latter represents 19% of practicing French anesthesiologists. The following factors were independently associated with increased WRQoL: family income, long-term employment, organizational and managerial factors (lesser weekly workload, the belief of providing high quality, safe health care services, team management, and operating theatre organization), human relations (satisfaction with workplace ambiance and relations with hospital management and colleagues), and occupational tasks (participation in team activities). Three personality traits were found to be significantly associated with increased WRQoL: extraversion, conscientiousness, and openness. Neuroticism was associated with reduced WRQoL. Conclusions The current study demonstrates exogenous and endogenous factors associated with increased WRQoL in anesthesiologists. Results should be considered as explorative and provide hypotheses for further research in this domain.
Published: 2021
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20. Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts

Author: Woo, X.Y., Giordano, J., Srivastava, A., Zhao, Z.-., Lloyd, M.W., de Bruijn, R., Suh, Y.-., Patidar, R., Chen, L., Scherer, S., Bailey, M.H., Yang, C.-., Cortes-Sanchez, E., Xi, Y., Wang, J., Wickramasinghe, J., Kossenkov, A.V., Rebecca, V.W., Sun, H., Mashl, R.J., Davies, S.R., Jeon, R., Frech, C., Randjelovic, J., Rosains, J., Galimi, F., Bertotti, A., Lafferty, A., O'Farrell, A.C., Modave, E., Lambrechts, D., ter Brugge, P., Marangoni, E., El Botty, R., Kim, H., Kim, J.-., Yang, H.-., Lee, C., Dean, D.A., Davis-Dusenbery, B., Evrard, Y.A., Doroshow, J.H., Welm, A.L., Welm, B.E., Lewis, M.T., Fang, B., Roth, J.A., Meric-Bernstam, F., Herlyn, M., Davies, M.A., Ding, L., Li, S., Govindan, R., Isella, C., Moscow, J.A., Trusolino, L., Byrne, A.T., Jonkers, J., Bult, C.J., Medico, E., Chuang, J.H., Robinson, P.N., Sanderson, B.J., Neuhauser, S.B., Dobrolecki, L.E., Zheng, X., Majidi, M., Zhang, R., Zhang, X., Akcakanat, A., Evans, K.W., Yap, T.A., Li, D., Yucan, E., Lanier, C.D., Saridogan, T., Kirby, B.P., M. J., H., Chen, H., Kopetz, S., Menter, D.G., Zhang, J., Westin, S.N., Kim, M.P., Dai, B., Gibbons, D.L., Tapia, C., Jensen, V.B., Boning, G., Minna, J.D., Park, H., Timmons, B.C., Girard, L., Fingerman, D., Liu, Q., Somasundaram, R., Xiao, M., Yennu-Nanda, V.G., Tetzlaff, M.T., Xu, X., Nathanson, K.L., Cao, S., Chen, F., Dipersio, J.F., Lim, K.H., C. X., M., Rodriguez, F.M., Van Tine, B.A., Wang-Gillam, A., Wendl, M.C., Wu, Y., Wyczalkowski, M.A., Yao, L., Jayasinghe, R., Aft, R.L., Fields, R.C., Luo, J., Fuh, K.C., Chin, V., Digiovanna, J., Grover, J., Koc, S., Seepo, S., Wallace, T., Pan, C.-., Chen, M.S., Carvajal-Carmona, L.G., Kirane, A.R., Cho, M., Gandara, D.R., Riess, J.W., Le, T., deVere White, R.W., Tepper, C.G., Zhang, H., Coggins, N.B., Lott, P., Estrada, A., Toal, T., Arana, A.M., Polanco-Echeverry, G., Rocha, S., A. -H., M., Mitsiades, N., Kaochar, S., O'Malley, B.W., Ellis, M.J., Hilsenbeck, S.G., Ittmann, M., Corso, S., Fiori, A., Giordano, S., van de Ven, M., Peeper, D.S., Miller, I., Bernado, C., Morancho, B., Ramirez, L., Arribas, J., Palmer, H.G., Piris-Gimenez, A., Soucek, L., Dahmani, A., Montaudon, E., Nemati, F., Dangles-Marie, V., Decaudin, D., Roman-Roman, S., Alferez, D.G., Spence, K., Clarke, R.B., Bentires-Alj, M., Chang, D.K., Biankin, A.V., Bruna, A., O'Reilly, M., Caldas, C., Casanovas, O., Gonzalez-Suarez, E., Munoz, P., Villanueva, A., Conte, N., Mason, J., Thorne, R., Meehan, T.F., Parkinson, H., Dudova, Z., Krenek, A., Stuchlik, D., Elemento, O., Inghirami, G., Golebiewska, A., Niclou, S.P., Wisman, G.B.A., de Jong, S., Kralova, P., Sedlacek, R., Claeys, E., Leucci, E., Borsani, M., Lanfrancone, L., Pelicci, P.G., Maelandsmo, G.M., Norum, J.H., Vinolo, E., Serra, V., and Leucci, Eleonora
Subjects: endocrine system diseases, Microarray, gene amplification, Whole Exome Sequencing, Mice, 0302 clinical medicine, Gene expression, Databases, Genetic, Gene duplication, Neoplasm Metastasis, Exome sequencing, Cancer, Regulation of gene expression, 0303 health sciences, Manchester Cancer Research Centre, adult, adult, animal experiment, animal model, animal tissue, breast cancer, microarray, DNA sequencing engraftment, gene amplification, tumor, xenograft, tumor-related gene, Polymorphism, Single Nucleotide/genetics, 3. Good health, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, microarray, hormones, hormone substitutes, and hormone antagonists, tumor, endocrine system, DNA sequencing engraftment, animal experiment, DNA Copy Number Variations/genetics, Biology, digestive system, DNA sequencing, Article, animal tissue, 03 medical and health sciences, breast cancer, Breast cancer, Genetics, medicine, Animals, Humans, xenograft, Gene, 030304 developmental biology, Settore MED/04 - Patologia Generale, Microarray analysis techniques, animal model, ResearchInstitutes_Networks_Beacons/mcrc, tumor-related gene, medicine.disease, Xenograft Model Antitumor Assays, Computational biology and bioinformatics, Cancer research, Human cancer
Abstract: Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment and propagation, affecting the accuracy of PDX modeling of human cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 PDX and matched patient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing and microarray data displayed substantially higher resolution and dynamic range than gene expression-based inferences, and they also showed strong CNA conservation from PTs through late-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-late trios confirmed high-resolution CNA retention. We observed no significant enrichment of cancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between patient and PDX tumors were comparable to variations in multiregion samples within patients. Our study demonstrates the lack of systematic copy number evolution driven by the PDX mouse host., Analysis of copy number alterations in 1,451 patient-derived xenografts (PDXs) and matched patient tumor samples shows strong conservation from patient tumors through late-passage PDXs and a lack of systematic copy number evolution driven by the mouse host.
Published: 2021
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21. [Resistance to BRAF inhibitors: A lesson from clinical observations]

Author: Cylia, Dahmani, Eulalie, Corre, Sarah, Dandou, Alain, Mangé, Ovidiu, Radulescu, Peter J, Coopman, Pierre, Cuq, and Romain M, Larive
Subjects: Proto-Oncogene Proteins B-raf, Drug Resistance, Neoplasm, MAP Kinase Signaling System, Cell Line, Tumor, Neoplasms, Mutation, Humans, Protein Kinase Inhibitors
Abstract: The MAPK/ERK pathway is an essential intracellular signaling pathway. Its deregulation is involved in tumor transformation and progression. The discovery of activating mutations of BRAF in various cancers has opened new therapeutic avenues with BRAF protein kinase inhibitors. Depending on the type of cancers, these inhibitors have shown either insufficient efficacy due to primary resistance of tumor cells or transient efficacy due to the development of acquired resistance. In this review, we revisit the discoveries that led to the development of BRAF inhibitors and detail the molecular and cellular mechanisms of resistance in cancers treated with these inhibitors. Understanding these mechanisms is crucial for developing more efficient therapeutic strategies.La résistance aux inhibiteurs de BRAF - Les leçons de la clinique.La voie de signalisation MAPK/ERK est une voie centrale de la signalisation intracellulaire. Sa dérégulation participe à la transformation et la progression tumorales. Dans plusieurs cancers, la découverte de mutations activatrices de BRAF, à l’origine de l’activation de cette voie, a ouvert de nouvelles perspectives thérapeutiques avec le développement d’inhibiteurs spécifiques de la protéine. Selon les cancers, ces inhibiteurs ont cependant montré soit une efficacité insuffisante, due à la résistance primaire des cellules tumorales, soit une efficacité transitoire, due à l’apparition d’une résistance acquise. Dans cette revue, nous revenons sur les découvertes qui ont conduit au développement de ces inhibiteurs de BRAF. Nous détaillons également les mécanismes moléculaires et cellulaires de la résistance à ces inhibiteurs observée dans différents types de cancers. Comprendre ces mécanismes est en effet primordial pour développer des stratégies thérapeutiques qui soient plus efficaces.
Published: 2022

22. Sharing Rewards Undermines Coordinated Hunting

Author: Minglu Zhao, Ning Tang, Annya L. Dahmani, Yixin Zhu, Federico Rossano, and Tao Gao
Subjects: Computational Mathematics, Computational Theory and Mathematics, Reward, Artificial Intelligence, Modeling and Simulation, Genetics, Animals, Humans, Hunting, Learning, Molecular Biology, Algorithms
Abstract: Coordinated hunting is widely observed in animals, and sharing rewards is often considered a major incentive for its success. While current theories about the role played by sharing in coordinated hunting are based on correlational evidence, we reveal the causal roles of sharing rewards through computational modeling with a state-of-the-art Multi-agent Reinforcement Learning (MARL) algorithm. We show that counterintuitively, while selfish agents reach robust coordination, sharing rewards undermines coordination. Hunting coordination modeled through sharing rewards (1) suffers from the free-rider problem, (2) plateaus at a small group size, and (3) is not a Nash equilibrium. Moreover, individually rewarded predators outperform predators that share rewards, especially when the hunting is difficult, the group size is large, and the action cost is high. Our results shed new light on the actual importance of prosocial motives for successful coordination in nonhuman animals and suggest that sharing rewards might simply be a byproduct of hunting, instead of a design strategy aimed at facilitating group coordination. This also highlights that current artificial intelligence modeling of human-like coordination in a group setting that assumes rewards sharing as a motivator (e.g., MARL) might not be adequately capturing what is truly necessary for successful coordination.
Published: 2022

23. TMPRSS6 gene mutations in six Saudi families with iron refractory iron deficiency anemia

Author: Lamiaa H. Al-Jamea, Alexander Woodman, Nihal M. Heiba, Shereen A. Elshazly, Noureddine Ben Khalaf, Fatimah S. Al-Yami, Khawaja Bilal Waheed, Abbas Al Mutair, Ahmad Alsedi, Jenifer V. Quiambao, Faisal M. Alzahrani, Walaa F. Albaqami, Faisal H. Al Qahtani, Nasser Mohammed Aljarah, Dahmani M. Fathallah, and Abdel Halim Deifalla
Subjects: Iron, Serine Endopeptidases, Mutation, Genetics, Serine, Saudi Arabia, Humans, Membrane Proteins, General Medicine, Iron Deficiencies, Peptide Hydrolases, Genome-Wide Association Study
Abstract: Iron-refractory iron deficiency anemia (IRIDA) is considered an autosomal recessive iron deficiency anemia due to mutations in the transmembrane protease serine 6 (TMPRSS6) gene. Variations in iron parameters and a higher risk of iron deficiency have been linked to the TMPRSS6 mutations. Furthermore, human genome-wide association studies (GWAS) identified a common mutation (rs855791) linked to abnormal hematological parameters, highlighting the importance of the TMPRSS6 gene in the regulation of iron homeostasis. This is the first study to investigate TMPRSS6 gene mutation in six Saudi families of probands with iron deficiency anemia unresponsive to oral iron and partially responsive to parenteral iron administration. Each participant provided a vacutainer tube with three blood samples (2.5 ml each) and analyzed based on hematological, biochemical iron profiles, and followed by genotyping by PCR. The TMPRSS6 gene was amplified, sequenced, and analyzed in all probands and family members. Statistical analysis was done using SPSS and SHEsis software. Few functional mutations in these families were suggested (p.W73X, p.E523K and p.V736A). The proband of family 6 presented numerous hematological abnormalities upon initial consultation, including normocytic anemia accompanied by low Hb, normal MCV, low serum iron, low serum ferritin, and normal TIBC. While the p.W73X variant was only found in 2 families, the p.V736A variant was found in all examined Saudi families with IRIDA. Given the evidence outlined for these six cases, future genotype-phenotype correlation studies in a large number of IRIDA patients in Saudi Arabia may be very informative for patient management, in addition to increasing knowledge of TMPRSS6 function during development as well as factors in the regulation of TMPRSS6 and its effect on iron levels in the body.
Published: 2022

24. Investigating pharmacy students’ therapeutic decision-making with respect to antimicrobial stewardship cases

Author: Ziad G. Nasr, Diala Alhaj Moustafa, Sara Dahmani, and Kyle J. Wilby
Subjects: Antimicrobial Stewardship, Anti-Infective Agents, Students, Pharmacy, Humans, General Medicine, Pharmacists, Qualitative Research, Education
Abstract: Background Antimicrobial stewardship programs (ASPs) play a big role in minimizing antimicrobial resistance. Pharmacists are essential members of the health care team and in order for them to fulfill roles on ASP teams and become antimicrobial stewards, they must be prepared adequately by pharmacy schools prior to entry into actual practice. Although programming has been implemented into entry-to-practice programs worldwide, little is known about how students interpret antimicrobial stewardship (AMS) data and arrive at clinical decisions. We aimed to explore students’ cognitive processes and determine how they formulate therapeutic decisions when presented with AMS cases. Methods This was a qualitative study conducted using a case study approach, in which a sample (n=20) of pharmacy students was recruited to interpret AMS cases. Semi-structured 1-on-1 interviews were arranged with each participant. A think-aloud procedure with verbal protocol analysis was adopted to determine students’ decision-making processes. Thematic analysis was used to interpret themes from the interview data. Results Two themes were interpreted from the data: students’ focus and students’ approach to case interpretation. Students’ focus relates to external factors students consider when interpreting AMS case data and use to make and justify therapeutic decisions including patient-centered factors, drug-related factors, AMS interventions, and pharmacist’s role. Students’ clinical reasoning describes the approach that students use to interpret the data and the decision-making processes they employ to arrive at a clinical decision including a systematic approach versus non-systematic approach. Conclusions Students vary in their focus and the cognitive strategies used to interpret AMS cases. Findings support the notion that clinical reasoning and decision-making should be explicitly taught in pharmacy curricula, in order to help students become aware of their own cognitive processes and decision-making abilities.
Published: 2022
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25. GATA3 and MDM2 are synthetic lethal in estrogen receptor-positive breast cancers

Author: Gaia Bianco, Mairene Coto-Llerena, John Gallon, Venkatesh Kancherla, Stephanie Taha-Mehlitz, Mattia Marinucci, Martina Konantz, Sumana Srivatsa, Hesam Montazeri, Federica Panebianco, Vijaya G. Tirunagaru, Marta De Menna, Viola Paradiso, Caner Ercan, Ahmed Dahmani, Elodie Montaudon, Niko Beerenwinkel, Marianna Kruithof-de Julio, Luigi M. Terracciano, Claudia Lengerke, Rinath M. Jeselsohn, Robert C. Doebele, François-Clément Bidard, Elisabetta Marangoni, Charlotte K. Y. Ng, and Salvatore Piscuoglio
Subjects: Phosphatidylinositol 3-Kinases, Receptors, Estrogen, Medicine (miscellaneous), Humans, Antineoplastic Agents, Breast Neoplasms, Female, Proto-Oncogene Proteins c-mdm2, 610 Medicine & health, GATA3 Transcription Factor, General Agricultural and Biological Sciences, 610 Medizin und Gesundheit, General Biochemistry, Genetics and Molecular Biology
Abstract: Synthetic lethal interactions, where the simultaneous but not individual inactivation of two genes is lethal to the cell, have been successfully exploited to treat cancer. GATA3 is frequently mutated in estrogen receptor (ER)-positive breast cancers and its deficiency defines a subset of patients with poor response to hormonal therapy and poor prognosis. However, GATA3 is not yet targetable. Here we show that GATA3 and MDM2 are synthetically lethal in ER-positive breast cancer. Depletion and pharmacological inhibition of MDM2 significantly impaired tumor growth in GATA3-deficient models in vitro, in vivo and in patient-derived organoids/xenograft (PDOs/PDX) harboring GATA3 somatic mutations. The synthetic lethality requires p53 and acts via the PI3K/Akt/mTOR pathway. Our results present MDM2 as a therapeutic target in the substantial cohort of ER-positive, GATA3-mutant breast cancer patients. With MDM2 inhibitors widely available, our findings can be rapidly translated into clinical trials to evaluate in-patient efficacy., Communications Biology, 5, ISSN:2399-3642
Published: 2022
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26. The impact of psychological factors on the management of intraoperative haemodynamic events in children

Author: Daphné Michelet, Souhayl Dahmani, Abdellouahabe Berdji, Charlotte Du Fayet De La Tour, Honorine Delivet, Florence Julien-Marsollier, Candy Benichou, Pierre-François Ceccaldi, Patrick Plaisance, Jennifer Truchot, Hôpital Robert Debré, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Lariboisière-Fernand-Widal [APHP], Laboratoire Universitaire Médical d’Enseignement basé sur les technologies Numériques et de Simulation (iLumens - site Paris 7), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Physiopathologie, conséquences fonctionnelles et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-IFR2-Institut National de la Santé et de la Recherche Médicale (INSERM), CCSD, Accord Elsevier, and Université Sorbonne Paris Cité (USPC)-Université de Paris (UP)
Subjects: Agreeableness, [SDV]Life Sciences [q-bio], media_common.quotation_subject, Context (language use), Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology, 030202 anesthesiology, Surveys and Questionnaires, Humans, Learning, Medicine, Personality, Big Five personality traits, Child, Children, media_common, Paediatric anaesthesia, Intraoperative, business.industry, Hemodynamics, 030208 emergency & critical care medicine, Conscientiousness, General Medicine, Cardiac arrest, Management algorithm, [SDV] Life Sciences [q-bio], Anesthesiology and Pain Medicine, Personality type, business, Simulation, Clinical psychology
Abstract: International audience; Introduction: Paediatric anaesthesia requires specific theoretical knowledge and practical training. Non-technical skills and psychological factors might influence learning and practice. The aim of this study was to assess personality type and decision-making styles of paediatric anaesthesiology residents during the management of simulated intraoperative life-threatening cases.Method: Residents in anaesthesiology (between 4 and 5 years of training) participated in a simulated hypoxic cardiac arrest in the operating theatre. Their performance was evaluated using a score derived from international recommended management algorithm. They were asked to answer self-assessment questionnaires regarding both their personality (the five personality factors) and their decision-making style. Correlations between performance and personality were investigated.Results: Thirty-eight residents participated in the simulation session and 36 accepted to answer the questionnaires. Good management scoring was positively correlated with agreeableness and conscientiousness personality traits but was negatively correlated with avoidance and spontaneous decision-making styles.Discussion: The current study identified personality traits and decision-making styles that might influence the management of critical situations during paediatric anaesthesia. The proper identification of these factors might allow targeted personalised training to improve knowledge mobilisation and translation in the clinical context.
Published: 2020
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27. Subthalamic Nucleus Deep Brain Stimulation Modulates 2 Distinct Neurocircuits

Author: Fangang Meng, Louisa Dahmani, Yi Guo, Shujun Xu, Changqing Jiang, Hesheng Liu, Catherine S Hubbard, Lunhao Shen, Yiming Liu, Jianguo Zhang, Luming Li, Jianxun Ren, Danhong Wang, and Changgeng He
Subjects: Male, 0301 basic medicine, Cerebellum, Deep brain stimulation, Deep Brain Stimulation, medicine.medical_treatment, Thalamus, Stimulation, Globus Pallidus, Deep cerebellar nuclei, Article, 03 medical and health sciences, 0302 clinical medicine, Subthalamic Nucleus, Neural Pathways, medicine, Humans, business.industry, Putamen, Motor Cortex, Parkinson Disease, Middle Aged, Magnetic Resonance Imaging, nervous system diseases, Subthalamic nucleus, surgical procedures, operative, 030104 developmental biology, medicine.anatomical_structure, Cerebellar Nuclei, nervous system, Neurology, Female, Neurology (clinical), Primary motor cortex, business, therapeutics, Neuroscience, 030217 neurology & neurosurgery
Abstract: Objective Current understanding of the neuromodulatory effects of deep brain stimulation (DBS) on large-scale brain networks remains elusive, largely due to the lack of techniques that can reveal DBS-induced activity at the whole-brain level. Using a novel 3T magnetic resonance imaging (MRI)-compatible stimulator, we investigated whole-brain effects of subthalamic nucleus (STN) stimulation in patients with Parkinson disease. Methods Fourteen patients received STN-DBS treatment and participated in a block-design functional MRI (fMRI) experiment, wherein stimulations were delivered during "ON" blocks interleaved with "OFF" blocks. fMRI responses to low-frequency (60Hz) and high-frequency(130Hz) STN-DBS were measured 1, 3, 6, and 12 months postsurgery. To ensure reliability, multiple runs (48 minutes) of fMRI data were acquired at each postsurgical visit. Presurgical resting-state fMRI (30 minutes) data were also acquired. Results Two neurocircuits showed highly replicable, but distinct responses to STN-DBS. A circuit involving the globus pallidus internus (GPi), thalamus, and deep cerebellar nuclei was significantly activated, whereas another circuit involving the primary motor cortex (M1), putamen, and cerebellum showed DBS-induced deactivation. These 2 circuits were dissociable in terms of their DBS-induced responses and resting-state functional connectivity. The GPi circuit was frequency-dependent, selectively responding to high-frequency stimulation, whereas the M1 circuit was responsive in a time-dependent manner, showing enhanced deactivation over time. Finally, activation of the GPi circuit was associated with overall motor improvement, whereas M1 circuit deactivation was related to reduced bradykinesia. Interpretation Concurrent DBS-fMRI using 3T revealed 2 distinct circuits that responded differentially to STN-DBS and were related to divergent symptoms, a finding that may provide novel insights into the neural mechanisms underlying DBS. ANN NEUROL 2020;88:1178-1193.
Published: 2020
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28. Reconstructing lost BOLD signal in individual participants using deep machine learning

Author: Louisa Dahmani, Yuanxiang Lin, Chen Gong, Jianxun Ren, Changgeng He, Shijun Li, Yuxiang Yan, Meiyun Wang, Lunhao Shen, Luming Li, Hesheng Liu, Ye Tian, Xiaolong Peng, Yi Guo, Ruiqi Wang, Changqing Jiang, Jianguo Zhang, and Bo Hong
Subjects: 0301 basic medicine, Male, genetic structures, Computer science, Deep Brain Stimulation, General Physics and Astronomy, Datasets as Topic, computer.software_genre, Brain mapping, Signal, 0302 clinical medicine, Image Processing, Computer-Assisted, lcsh:Science, Cerebral Cortex, Brain Mapping, Multidisciplinary, Parkinson Disease, Magnetic Resonance Imaging, Healthy Volunteers, Female, psychological phenomena and processes, Adult, Adolescent, Science, Models, Neurological, Image processing, Machine learning, Neural circuits, behavioral disciplines and activities, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Young Adult, Deep Learning, Functional neuroimaging, Bold fmri, Humans, business.industry, Deep learning, Frame (networking), General Chemistry, Oxygen, 030104 developmental biology, nervous system, Computational neuroscience, lcsh:Q, Artificial intelligence, business, computer, 030217 neurology & neurosurgery
Abstract: Signal loss in blood oxygen level-dependent (BOLD) functional neuroimaging is common and can lead to misinterpretation of findings. Here, we reconstructed compromised fMRI signal using deep machine learning. We trained a model to learn principles governing BOLD activity in one dataset and reconstruct artificially compromised regions in an independent dataset, frame by frame. Intriguingly, BOLD time series extracted from reconstructed frames are correlated with the original time series, even though the frames do not independently carry any temporal information. Moreover, reconstructed functional connectivity maps exhibit good correspondence with the original connectivity maps, indicating that the model recovers functional relationships among brain regions. We replicated this result in two healthy datasets and in patients whose scans suffered signal loss due to intracortical electrodes. Critically, the reconstructions capture individual-specific information. Deep machine learning thus presents a unique opportunity to reconstruct compromised BOLD signal while capturing features of an individual’s own functional brain organization., Signal loss in blood oxygen level‐dependent (BOLD) fMRI can lead to misinterpretation of findings. The authors trained a deep learning model to reconstruct compromised BOLD signal in datasets from healthy participants and in patients whose scans suffered signal loss due to intracortical electrodes.
Published: 2020

29. The 14-3-3ζ–c-Src–integrin-β3 complex is vital for platelet activation

Author: Ren Lai, June Li, Runjia Xu, Pingguo Chen, Zilei Duan, Heyu Ni, James Mwangi, Daniel Thomas Mackeigan, Fatima Zohra Dahmani, Gan Wang, Wenjing Ma, Ming Liu, Chuanbin Shen, Qiumin Lu, and Zhiye Zhang
Subjects: Adult, Male, 0301 basic medicine, Proto-Oncogene Proteins pp60(c-src), Immunology, Integrin, Mice, Transgenic, 030204 cardiovascular system & hematology, Biochemistry, Mice, 03 medical and health sciences, 0302 clinical medicine, Antithrombotic, Animals, Humans, Platelet, Platelet activation, biology, Chemistry, HEK 293 cells, Integrin beta3, Cell Biology, Hematology, Platelet Activation, Cell biology, Mice, Inbred C57BL, HEK293 Cells, 030104 developmental biology, 14-3-3 Proteins, Multiprotein Complexes, Hemostasis, biology.protein, Female, Signal transduction, Signal Transduction, Proto-oncogene tyrosine-protein kinase Src
Abstract: Several adaptor molecules bind to cytoplasmic tails of β-integrins and facilitate bidirectional signaling, which is critical in thrombosis and hemostasis. Interfering with integrin-adaptor interactions spatially or temporally to inhibit thrombosis without affecting hemostasis is an attractive strategy for the development of safe antithrombotic drugs. We show for the first time that the 14-3-3ζ–c-Src–integrin-β3 complex is formed during platelet activation. 14-3-3ζ–c-Src interaction is mediated by the -PIRLGLALNFSVFYYE- fragment (PE16) on the 14-3-3ζ and SH2-domain on c-Src, whereas the 14-3-3ζ–integrin-β3 interaction is mediated by the -ESKVFYLKMKGDYYRYL- fragment (EL17) on the 14-3-3ζ and -KEATSTF- fragment (KF7) on the β3-integrin cytoplasmic tail. The EL17-motif inhibitor, or KF7 peptide, interferes with the formation of the 14-3-3ζ–c-Src–integrin-β3 complex and selectively inhibits β3 outside-in signaling without affecting the integrin-fibrinogen interaction, which suppresses thrombosis without causing significant bleeding. This study characterized a previously unidentified 14-3-3ζ–c-Src–integrin-β3 complex in platelets and provided a novel strategy for the development of safe and effective antithrombotic treatments.
Published: 2020
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30. COVID-19 pneumonia: relationship between inflammation assessed by whole-body FDG PET/CT and short-term clinical outcome

Author: Dietz, Matthieu, Chironi, Gilles, Claessens, Yann-Erick, Farhad, Ryan Lukas, Rouquette, Isabelle, Serrano, Benjamin, Nataf, Valérie, Hugonnet, Florent, Paulmier, Benoît, Berthier, Frédéric, Keita-Perse, Olivia, Giammarile, Francesco, Perrin, Christophe, Faraggi, Marc, Fissore-Magdelein, C., Gabriel-Solean, S., Dahmani, B., Riss, I., Sorlin, P., Dupasquier, V., Pathak, A., Dugourd, C., Nicolai, M., Rijo, N., Beau, N., Magdelein, X., Olyve, F., Chaillou-Orpitz, S., Lépine, J., Lorillou, M., Maincent, C., Bertrand, S., Brunner, P., Dittlot, C., Fuerxer, F., Liberatore, M., Armando, G., Bouregba, M., Catineau, J., Garcia, P., and Tran, D.
Subjects: Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Glucose uptake, Inflammation, Gastroenterology, Fluorodeoxyglucose F18, Positron Emission Tomography Computed Tomography, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Lung, Aged, Aged, 80 and over, business.industry, COVID-19, Heart, General Medicine, Middle Aged, medicine.disease, FDG PET/CT, Pneumonia, Treatment Outcome, medicine.anatomical_structure, Radiology Nuclear Medicine and imaging, Anaerobic glycolysis, Original Article, Female, Lymph Nodes, Lymph, Bone marrow, Radiopharmaceuticals, medicine.symptom, business
Abstract: Purpose [18F]-2-Fluoro-2-deoxy-D-glucose PET/CT (FDG PET/CT) is a sensitive and quantitative technic for detecting inflammatory process. Glucose uptake is correlated with an increased anaerobic glycolysis seen in activated inflammatory cells such as monocytes, lymphocytes, and granulocytes. The aim of the study was to assess the inflammatory status at the presumed peak of the inflammatory phase in non-critically ill patients requiring admission for COVID-19. Methods Patients admitted with COVID-19 were prospectively enrolled. FDG PET/CT was performed from day 6 to day 14 of the onset of symptoms. Depending on FDG PET/CT findings, patients’ profiles were classified as “inflammatory” or “low inflammatory.” FDG PET/CT data were compared with chest CT evolution and short-term clinical outcome. All inflammatory sites were reported to screen potential extra-pulmonary tropism. Results Thirteen patients were included. Maximum standardized uptake values ranged from 4.7 to 16.3 in lungs. All patients demonstrated increased mediastinal lymph nodes glucose uptake. Three patients (23%) presented mild nasopharyngeal, two patients (15%) bone marrow, and five patients (38%) splenic mild increase in glucose uptake. No patient had significant digestive focal or segmental glucose uptake. There was no significant physiological myocardial glucose uptake in all patients except one. There was no correlation between PET lung inflammatory status and chest CT evolution or short-term clinical outcome. Conclusion Inflammatory process at the presumed peak of the inflammatory phase in COVID-19 patients is obvious in FDG PET/CT scans. Glucose uptake is heterogeneous and typically focused on lungs. Trial registration NCT04441489. Registered 22 June 2020 (retrospectively registered). Electronic supplementary material The online version of this article (10.1007/s00259-020-04968-8) contains supplementary material, which is available to authorized users.
Published: 2020
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31. Habitual use of GPS negatively impacts spatial memory during self-guided navigation

Author: Louisa Dahmani and Véronique D. Bohbot
Subjects: 0301 basic medicine, Adult, Male, Geographic information system, Computer science, lcsh:Medicine, Context (language use), Hippocampus, Session (web analytics), Article, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Spatial memory, Encoding (memory), Human behaviour, Humans, Longitudinal Studies, lcsh:Science, Memory Disorders, Multidisciplinary, Landmark, Cognitive map, business.industry, lcsh:R, Navigation system, 030104 developmental biology, Cross-Sectional Studies, Global Positioning System, Geographic Information Systems, Female, lcsh:Q, business, 030217 neurology & neurosurgery, Cognitive psychology, Follow-Up Studies, Spatial Navigation
Abstract: Global Positioning System (GPS) navigation devices and applications have become ubiquitous over the last decade. However, it is unclear whether using GPS affects our own internal navigation system, or spatial memory, which critically relies on the hippocampus. We assessed the lifetime GPS experience of 50 regular drivers as well as various facets of spatial memory, including spatial memory strategy use, cognitive mapping, and landmark encoding using virtual navigation tasks. We first present cross-sectional results that show that people with greater lifetime GPS experience have worse spatial memory during self-guided navigation, i.e. when they are required to navigate without GPS. In a follow-up session, 13 participants were retested three years after initial testing. Although the longitudinal sample was small, we observed an important effect of GPS use over time, whereby greater GPS use since initial testing was associated with a steeper decline in hippocampal-dependent spatial memory. Importantly, we found that those who used GPS more did not do so because they felt they had a poor sense of direction, suggesting that extensive GPS use led to a decline in spatial memory rather than the other way around. These findings are significant in the context of society’s increasing reliance on GPS.
Published: 2020
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32. Predictive Model for Designing Soft-Tissue Mimicking Ultrasound Phantoms With Adjustable Elasticity

Author: Yvan Petit, Daniel Pereira, Jawad Dahmani, Catherine Laporte, and Pierre Belanger
Subjects: Time Factors, Materials science, Acoustics and Ultrasonics, Image registration, Models, Biological, 01 natural sciences, Imaging phantom, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Elastic Modulus, Materials Testing, 0103 physical sciences, medicine, Humans, Electrical and Electronic Engineering, 010301 acoustics, Instrumentation, Elastic modulus, Ultrasonography, medicine.diagnostic_test, Phantoms, Imaging, business.industry, Attenuation, Ultrasound, Echogenicity, Equipment Design, 3. Good health, Gelatin, Elastography, Acoustic impedance, business, Biomedical engineering
Abstract: The use of mechanically representative phantoms is important for experimental validation in ultrasound (US) imaging, elastography, and image registration. This article proposes a model to predict the elastic modulus of a soft tissue-mimicking phantom based on two very easily controllable parameters: gelatin concentration and refrigeration duration. The model has been validated on small- and large-scale phantoms; it provides a good prediction of the elastic modulus in both cases (error < 16.2%). The tissue-mimicking phantom is made following a low-cost and simple fabrication procedure using commercial household gelatin with psyllium hydrophilic mucilloid fiber to obtain echogenicity. A large range of elastic properties was obtained (15–100kPa) by adjusting the gelatin concentration between 5% and 20% (g/mL) and the refrigeration time of the sample between 2 and 168 h, allowing to mimic normal and pathological human soft tissues. The phantom’s acoustic properties (velocity, attenuation, and acoustic impedance) are also assessed using the American Institute of Ultrasound in Medicine (AIUM) standard.
Published: 2020
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33. Perioperative management of surgical correction of ureteropelvic junction obstruction in children: A comparison of robotic-assisted versus conventional minimally invasive techniques

Author: Florence Julien‐Marsollier, Maud Loiselle, Kelly Brouns, Christopher Brasher, and Souhayl Dahmani
Subjects: Anesthesiology and Pain Medicine, Treatment Outcome, Robotic Surgical Procedures, Pediatrics, Perinatology and Child Health, Humans, Minimally Invasive Surgical Procedures, Urologic Surgical Procedures, Laparoscopy, Child, Ureteral Obstruction
Published: 2022

34. Proportion and predictors of Hypogonadism Recovery in Men with Macroprolactinomas treated with dopamine agonists

Author: Khaled M, Al Dahmani, Mussa H, Almalki, Aishah, Ekhzaimy, Faisal, Aziz, Alaaeldin, Bashier, Moeber M, Mahzari, and Salem A, Beshyah
Subjects: Adult, Male, Hypothyroidism, Hypogonadism, Dopamine Agonists, Humans, Pituitary Neoplasms, Prolactinoma, Testosterone, Ergolines, Prolactin, Retrospective Studies
Abstract: Hypogonadism is the most common form of hypopituitarism in men with macroprolactinoma. However, evidence on factors related to hypogonadism recovery is limited.We estimated the proportion of hypogonadism in men with macroprolactinoma exclusively treated with dopamine agonists, and we assessed the factors predicting hypogonadism recovery.This was a multicenter retrospective study of men with macroprolactinoma identified using ICD 9 and 10 codes and treated between 2009 and 2019 in five centers in the United Arab Emirates and Saudi Arabia. We evaluated hypogonadism, defined as low total testosterone (TT) level with normal or low gonadotropins on presentation and during the last clinic visit.A total of 79 patients (median age 32 years) were included in the study. The most common symptoms at presentation were headache (73.7%), erectile dysfunction (55.4%), and low libido (54.3%). The median tumor size was 2.9 cm (1.0-9.7) at diagnosis. Sixty-three patients (79.7%) had hypogonadism at baseline. Growth hormone deficiency (GHD) and hypothyroidism were present in 34.4% and 32.9% of patients, respectively. The median serum prolactin (PRL) level was 20,175 (min-max 2254 - 500,000) mIU/l with a median serum TT of 4.5 (min-max 0.4-28.2) nmol/l. Most patients were treated with cabergoline (n = 77, 97.5%) with a median of 6 (min-max 0.6-22) years. At follow-up, 65% of patients recovered their pituitary-testicular axis. Patients with recovered hypogonadism had smaller median tumor size (2.4 [1-5.4] vs. 4.3 [1.6-9.7], p = 0.003), lower PRL level (18, 277 [2254 - 274, 250] vs. 63,703 [ 3,365-500,000], p = 0.008 ), higher TT level (4.6 [0.6-9.2] vs. 2.3 [0.5-7.3], p = 0.008), lower PRL normalization time on medical therapy (8 months (0.7-72) vs. 24 (3-120), p = 0.009) as well as lower frequency of GHD (17.1% vs. 60%, p = 0.006) and secondary hypothyroidism (17.9% vs. 57.1%, p = 0.003) compared with those with persistent hypogonadism respectively. Age at diagnosis, presenting symptoms and duration of medical therapy did not predict hypogonadism recovery.About two-thirds of men with macroprolactinoma recover from hypogonadism, mostly with 24 months of therapy. Smaller adenoma size, lower prolactin level, earlier prolactin normalization, and higher testosterone patients were related to testosterone normalization.
Published: 2022

35. Morbidity and mortality after anaesthesia in early life:results of the European prospective multicentre observational study, neonate and children audit of anaesthesia practice in Europe (NECTARINE)

Author: Nicola Disma, Francis Veyckemans, Katalin Virag, Tom G. Hansen, Karin Becke, Pierre Harlet, Laszlo Vutskits, Suellen M. Walker, Jurgen C. de Graaff, Marzena Zielinska, Dusica Simic, Thomas Engelhardt, Walid Habre, Christian Breschan, Rudolf Likar, Manuela Platzer, Isole Edelman, Johanes Eger, Stefan Heschl, Brigitte Messerer, Maria Vittinghof, Ruth Kroess, Martina Stichlberger, David Kahn, Thierry Pirotte, Caroline Pregardien, France Stevens, Johan Berghmans, Annemie Bauters, Luc De Baerdemaeker, Stefan De Hert, Koen Lapage, Aliaksandra Parashchanka, Jurgen Van Limmen, Piet Wyffels, Julie Lauweryns, Nadia Najafi, Joris Vundelinckx, Diana Butković, Ivana Kerovec Sorić, Sandra Kralik, Ana Markić, Josip Azman, Josko Markic, Daniela Pupacic, Michal Frelich, Petr Reimer, Rene Urbanec, Petra Cajkova, Vladimir Mixa, Yvona Sedlačkova, Lenka Knoppova, Alena Zlamalova (nee Květoňova), Martin Vavřina, Jiři Žurek, Tom Hansen, Arash Afshari, Anders B. Bille, Marguerite Ellekvist, Mari-Liis Ilmoja, Reet Moor, Reet Kikas, Merle Vali, Kariantti Kallio, Elisa Reponen, Pertti Suominen, Sami Suvanto, Raisa Vahatalo, Hannu Kokki, Merja Kokki, Jarkko Harju, Miia Kokkonen, Jenni Vieri, Tuula Manner, Catherine Amory, Hugues Ludot, Dina Bert, Juliette Godart, Anne Laffargue, Herve Dupont, Benjamin Urbina, Catherine Baujard, Philippe Roulleau, Giuseppe Staiti, Maryline Bordes, Karine Nouette Gaulain, Yann Hamonic, Francois Semjen, Olivier Jacqmarcq, Caroline Lejus-Bourdeau, Cecile Magne, Lea Petry, Lilica Ros, Aurelien Zang, Mehdi Bennis, Bernard Coustets, Rose Fesseau, Isabelle Constant, Eliane Khalil, Nada Sabourdin, Noemie Audren, Thomas Descarpentries, Fanny Fabre, Aurelien Legrand, Emilie Druot, Gilles Orliaguet, Lucie Sabau, Lynn Uhrig, Francois de la Briere, Karin Jonckheer, Jean-Paul Mission, Lucia Scordo, Caroline Couchepin, Christophe Dadure, Pablo De la Arena, Laurent Hertz, Philippe Pirat, Chrystelle Sola, Myriam Bellon, Souhayl Dahmani, Florence Julien-Marsollier, Daphne Michelet, Veronique Depret-Donatien, Anne Lesage, Jost Kaufmann, Michael Laschat, Frank Wappler, Lena Brunner, Karin Oppenrieder, Gregor Badelt, Karin Hochmuth, Bernhard Koller, Anita Reil, Sebastian Richter, Thomas Fischer, Anja Diers, Clemens Schorer, Andreas Weyland, Ruth Cohausz, Franz-Josef Kretz, Michaela Loffler, Markus Wilbs, Claudia Hoehne, Johanna Ulrici, Christiane Goeters, Armin Flinspach, Matthias Klages, Simone Lindau, Leila Messroghli, Kai Zacharowski, Christoph Eisner, Thomas Mueller, Daniel Richter, Melanie Schafer, Markus Weigand, Sebastian Weiterer, Miriam Ochsenreiter, Michael Scholer, Tom Terboven, Isabel Eggemann, Sascha Haussmann, Nicolas Leister, Christoph Menzel, Uwe Trieschmann, Sirin Yucetepe, Susanna Keilig, Peter Kranke, Yvonne Jelting, Torsten Baehner, Richard Ellerkmann, Shahab Ghamari, Claudia Neumann, Martin Sohle, Pelagia Chloropoulou, Vagia Ntritsou, Pinelopi Papagiannopoulou, Eleana Garini, Afroditi Karafotia, Panagoula Mammi, Evangelia Bali, Despoina Iordanidou, Anna Malisiova, Artemis Polyzoi, Adelais Tsiotou, Erzsebet Sapi, Edgar Szekely, Nandor Kosik, Veronika Maraczi, Janos Schnur, Judit Csillag, Janos Gal, Gergely Gobl, Balazs Hauser, Andras Petroczy, Gyula Tovishazi, Stuart Blain, Sarah Gallagher, Sinead Harte, Mandy Jackson, Emma Meehan, Zeenat Nawoor, Brendan O’Hare, Mark Ross, Daniela Lerro, Marinella Astuto, Chiara Grasso, Rita Scalisi, Giulia Frasacco, Elena Lenares, Roberto Leone, Maurizia Grazzini, Carmelo Minardi, Nicola Zadra, Gilda Cinnella, Antonella Cotoia, Dario Galante, Brita De Lorenzo, Beate Kuppers, Giulia Bottazzi, Fabio Caramelli, Maria C. Mondardini, Emanuele Rossetti, Sergio Picardo, Alessandro Vittori, Anna Camporesi, Andrea Wolfler, Edoardo Calderini, Laura B. Colantonio, Simona A. Finamore, Giuliana A. Porro, Rachele Bonfiglio, Svetlana Kotzeva, Leila Mameli, Girolamo Mattioli, Camilla Micalizzi, Alessia Montaguti, Angela Pistorio, Clelia Zanaboni, Anna Guddo, Gerald R. Neba, Moreno Favarato, Bruno G. Locatelli, Micol Maffioletti, Valter Sonzogni, Rossella Garra, Maria Sammartino, Fabio Sbaraglia, Andrea Cortegiani, Alessandra Moscarelli, Elena Attanasi, Simonetta Tesoro, Cristina Agapiti, Francesca Pinzoni, Cesare Vezzoli, Federico Bilotta, Arta Barzdina, Zane Straume, Anda Zundane, Laura Lukosiene, Irena Maraulaite, Ilona Razlevice, Bernd Schmitz, Stephanie Mifsud, Carolin Aehling, Celia Allison, Rients De Boer, Dina Emal, Markus Stevens, Marielle Buitenhuis, Jurgen de Graaff, Inge De Liefde, Andreas Machotta, Gail Scoones, Lonneke Staals, Jeremy Tomas, Anouk Van der, Knijff-van Dortmont, Marianne Veldhuizen, David Alders, Wolfgang Buhre, Eva Schafrat, Jan Schreiber, Petronella M. Vermeulen, Mark Hendriks, Sandra Lako, Marieke Voet-Lindner, Barbe Pieters, Gert-Jan Scheffer, Luc Tielens, Anthony R. Absalom, Margot Bergsma, Joke De Ruiter, Sascha Meier, Martin Volkers, Tjerk Zweers, Anne M. Beukers, Christa Boer, Jurgen Dertinger, Sandra Numan, Bas Van Zaane, Wenche B. Boerke, Nil Ekiz, Kristoffer Stensrud, Inger M. Drage, Erik R. Isern, Alicja Bartkowska-Sniatkowska, Malgorzata Grzeskowiak, Magdalena Juzwa-Sobieraj, Jowita Rosada-Kurasińska, Artur Baranowski, Karina Jakubowska, Dorota Lewandowska, Magdalena Mierzewska-Schmidt, Piotr Sawicki, Magdalena Urban-Lechowicz, Pomianek Przemyslaw, Teresa Leal, Maria Soares, Pedro Pina, Silvia Pinho, Maria Domingas Patuleia, Catarina C. Esteves, Helena Salgado, Maria J. Santos, Rodica Badeti, Iulia Cindea, Loredana Oana, Adriana Gurita, Luminita Ilie, Gabriel Mocioiu, Radu Tabacaru, Irina Trante, Valentin Munteanu, Mihai Morariu, Emese Nyiri, Ivana Budic, Vesna Marjanovic, Biljana Drašković, Marina Pandurov, Jordanka Ilic, Ana Mandras, Zdenka Rados, Nikola Stankovic, Maja Suica, Sladjana Vasiljevic, Mirjana Knezevic, Irina Milojevic, Ivana Petrov, Selena Puric Racic, Irena Simic, Marija Stevic, Irena Vulicevic, Barbora Cabanova, Miloslav Hanula, Jelena Berger, Darja Janjatovic, Špela P. Štupnik, Ivan Kohn, Ulf Lindestam, Jarl Reinhard, Albert Castellheim, Kerstin Sandstrom, Sporre Bengt, Rainer Dorenberg, Peter Frykholm, Maria Garcia, Ann Kvarnstrom, Emma Ponten, Thomas Bruelisauer, Gabor Erdoes, Heiko Kaiser, Mathias Marchon, Thomas Riva, Stefan Seiler, Yann Bogli, Mirko Dolci, Carine Marcucci, Isabelle Pichon, Mattias Casutt, Martin Holzle, Thomas Hurni, Martin Johr, null Anna-Ursina, null Malar, Jacqueline Mauch, Thomas Erb, Karin Oeinck, Mine Akin, Gulsen Keskin, Yesim Senayli, Guner Kaya, Pinar Kendigelen, Ayse C. Tutuncu, Zehra Hatipoğlu, Dilek Ozcengiz, Hale Aksu Erdost, Elvan Ocmen, Cimen Olguner, Hilmi Ayanoglu, Pelin C. Dincer, Tumay Umuroglu, Mustafa Azizoglu, Handan Birbicer, Nurcan Doruk, Aslı Sagun, Sibel Baris, Dmytro Dmytriiev, Sridevi Kuchi, Nuria Masip, Peter Brooks, Alison Hare, Nargis Ahmad, Michelle Casey, Sam De Silva, Nadine Dobby, Prakash Krishnan, L. Amaki Sogbodjor, Ellie Walker, Suellen Walker, Stephanie King, Katy Nicholson, Michelle Quinney, Paul Stevens, Andrew Blevin, Mariangela Giombini, Chulananda Goonasekera, Sadia Adil, Stephanie Bew, Carol Bodlani, Dan Gilpin, Stephanie Jinks, Nalini Malarkkan, Alice Miskovic, Rebecca Pad, Juliet W. Barry, Joy Abbott, James Armstrong, Natalie Cooper, Lindsay Crate, John Emery, Kathryn James, Hannah King, Paul Martin, Stefano S. Catenacci, Rob Bomont, Paul Smith, Sara Mele, Alessandra Verzelloni, Philippa Dix, Graham Bell, Elena Gordeva, Lesley McKee, Esther Ngan, Jutta Scheffczik, Li-En Tan, Mark Worrall, Carmel Cassar, Kevin Goddard, Victoria Barlow, Vimmi Oshan, Khairi Shah, Sarah Bell, Lisa Daniels, Monica Gandhi, David Pachter, Chris Perry, Andrew Robertson, Carmen Scott, Lynne Waring, David Barnes, Sophie Childs, Joanne Norman, Robin Sunderland, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'anesthésiologie, Tampere University, Department of Prehospital Emergency Care, Pain Management and Anaesthesiology, Anesthesiology, APH - Quality of Care, ANS - Neuroinfection & -inflammation, Disma, Nicola, Veyckemans, Franci, Virag, Katalin, Hansen, Tom G., Becke, Karin, Harlet, Pierre, Vutskits, Laszlo, Walker, Suellen M., de Graaff, Jurgen C., Zielinska, Marzena, Simic, Dusica, Engelhardt, Thoma, Habre, Walid, Breschan, Christian, Likar, Rudolf, Platzer, Manuela, Edelman, Isole, Eger, Johane, Heschl, Stefan, Messerer, Brigitte, Vittinghof, Maria, Kroess, Ruth, Stichlberger, Martina, Kahn, David, Pirotte, Thierry, Pregardien, Caroline, Stevens, France, Berghmans, Johan, Bauters, Annemie, De Baerdemaeker, Luc, De Hert, Stefan, Lapage, Koen, Parashchanka, Aliaksandra, Van Limmen, Jurgen, Wyffels, Piet, Lauweryns, Julie, Najafi, Nadia, Vundelinckx, Jori, Butković, Diana, Sorić, Ivana Kerovec, Kralik, Sandra, Markić, Ana, Azman, Josip, Markic, Josko, Pupacic, Daniela, Frelich, Michal, Reimer, Petr, Urbanec, Rene, Cajkova, Petra, Mixa, Vladimir, Sedlačkova, Yvona, Knoppova, Lenka, Zlamalova (nee Květoňova), Alena, Vavřina, Martin, Žurek, Jiři, Hansen, Tom, Afshari, Arash, Bille, Anders B., Ellekvist, Marguerite, Ilmoja, Mari-Lii, Moor, Reet, Kikas, Reet, Vali, Merle, Kallio, Kariantti, Reponen, Elisa, Suominen, Pertti, Suvanto, Sami, Vahatalo, Raisa, Kokki, Hannu, Kokki, Merja, Harju, Jarkko, Kokkonen, Miia, Vieri, Jenni, Manner, Tuula, Amory, Catherine, Ludot, Hugue, Bert, Dina, Godart, Juliette, Laffargue, Anne, Dupont, Herve, Urbina, Benjamin, Baujard, Catherine, Roulleau, Philippe, Staiti, Giuseppe, Bordes, Maryline, Gaulain, Karine Nouette, Hamonic, Yann, Semjen, Francoi, Jacqmarcq, Olivier, Lejus-Bourdeau, Caroline, Magne, Cecile, Petry, Lea, Ros, Lilica, Zang, Aurelien, Bennis, Mehdi, Coustets, Bernard, Fesseau, Rose, Constant, Isabelle, Khalil, Eliane, Sabourdin, Nada, Audren, Noemie, Descarpentries, Thoma, Fabre, Fanny, Legrand, Aurelien, Druot, Emilie, Orliaguet, Gille, Sabau, Lucie, Uhrig, Lynn, de la Briere, Francoi, Jonckheer, Karin, Mission, Jean-Paul, Scordo, Lucia, Couchepin, Caroline, Dadure, Christophe, De la Arena, Pablo, Hertz, Laurent, Pirat, Philippe, Sola, Chrystelle, Bellon, Myriam, Dahmani, Souhayl, Julien-Marsollier, Florence, Michelet, Daphne, Depret-Donatien, Veronique, Lesage, Anne, Kaufmann, Jost, Laschat, Michael, Wappler, Frank, Brunner, Lena, Oppenrieder, Karin, Badelt, Gregor, Hochmuth, Karin, Koller, Bernhard, Reil, Anita, Richter, Sebastian, Fischer, Thoma, Diers, Anja, Schorer, Clemen, Weyland, Andrea, Cohausz, Ruth, Kretz, Franz-Josef, Loffler, Michaela, Wilbs, Marku, Hoehne, Claudia, Ulrici, Johanna, Goeters, Christiane, Flinspach, Armin, Klages, Matthia, Lindau, Simone, Messroghli, Leila, Zacharowski, Kai, Eisner, Christoph, Mueller, Thoma, Richter, Daniel, Schafer, Melanie, Weigand, Marku, Weiterer, Sebastian, Ochsenreiter, Miriam, Scholer, Michael, Terboven, Tom, Eggemann, Isabel, Haussmann, Sascha, Leister, Nicola, Menzel, Christoph, Trieschmann, Uwe, Yucetepe, Sirin, Keilig, Susanna, Kranke, Peter, Jelting, Yvonne, Baehner, Torsten, Ellerkmann, Richard, Ghamari, Shahab, Neumann, Claudia, Sohle, Martin, Chloropoulou, Pelagia, Ntritsou, Vagia, Papagiannopoulou, Pinelopi, Garini, Eleana, Karafotia, Afroditi, Mammi, Panagoula, Bali, Evangelia, Iordanidou, Despoina, Malisiova, Anna, Polyzoi, Artemi, Tsiotou, Adelai, Sapi, Erzsebet, Szekely, Edgar, Kosik, Nandor, Maraczi, Veronika, Schnur, Jano, Csillag, Judit, Gal, Jano, Gobl, Gergely, Hauser, Balaz, Petroczy, Andra, Tovishazi, Gyula, Blain, Stuart, Gallagher, Sarah, Harte, Sinead, Jackson, Mandy, Meehan, Emma, Nawoor, Zeenat, O’Hare, Brendan, Ross, Mark, Lerro, Daniela, Astuto, Marinella, Grasso, Chiara, Scalisi, Rita, Frasacco, Giulia, Lenares, Elena, Leone, Roberto, Grazzini, Maurizia, Minardi, Carmelo, Zadra, Nicola, Cinnella, Gilda, Cotoia, Antonella, Galante, Dario, De Lorenzo, Brita, Kuppers, Beate, Bottazzi, Giulia, Caramelli, Fabio, Mondardini, Maria C., Rossetti, Emanuele, Picardo, Sergio, Vittori, Alessandro, Camporesi, Anna, Wolfler, Andrea, Calderini, Edoardo, Colantonio, Laura B., Finamore, Simona A., Porro, Giuliana A., Bonfiglio, Rachele, Kotzeva, Svetlana, Mameli, Leila, Mattioli, Girolamo, Micalizzi, Camilla, Montaguti, Alessia, Pistorio, Angela, Zanaboni, Clelia, Guddo, Anna, Neba, Gerald R., Favarato, Moreno, Locatelli, Bruno G., Maffioletti, Micol, Sonzogni, Valter, Garra, Rossella, Sammartino, Maria, Sbaraglia, Fabio, Cortegiani, Andrea, Moscarelli, Alessandra, Attanasi, Elena, Tesoro, Simonetta, Agapiti, Cristina, Pinzoni, Francesca, Vezzoli, Cesare, Bilotta, Federico, Barzdina, Arta, Straume, Zane, Zundane, Anda, Lukosiene, Laura, Maraulaite, Irena, Razlevice, Ilona, Schmitz, Bernd, Mifsud, Stephanie, Aehling, Carolin, Allison, Celia, De Boer, Rient, Emal, Dina, Stevens, Marku, Buitenhuis, Marielle, de Graaff, Jurgen, De Liefde, Inge, Machotta, Andrea, Scoones, Gail, Staals, Lonneke, Tomas, Jeremy, Van der, Anouk, Dortmont, Knijff-van, Veldhuizen, Marianne, Alders, David, Buhre, Wolfgang, Schafrat, Eva, Schreiber, Jan, Vermeulen, Petronella M., Hendriks, Mark, Lako, Sandra, Voet-Lindner, Marieke, Pieters, Barbe, Scheffer, Gert-Jan, Tielens, Luc, Absalom, Anthony R., Bergsma, Margot, De Ruiter, Joke, Meier, Sascha, Volkers, Martin, Zweers, Tjerk, Beukers, Anne M., Boer, Christa, Dertinger, Jurgen, Numan, Sandra, Van Zaane, Ba, Boerke, Wenche B., Ekiz, Nil, Stensrud, Kristoffer, Drage, Inger M., Isern, Erik R., Bartkowska-Sniatkowska, Alicja, Grzeskowiak, Malgorzata, Juzwa-Sobieraj, Magdalena, Rosada-Kurasińska, Jowita, Baranowski, Artur, Jakubowska, Karina, Lewandowska, Dorota, Mierzewska-Schmidt, Magdalena, Sawicki, Piotr, Urban-Lechowicz, Magdalena, Przemyslaw, Pomianek, Leal, Teresa, Soares, Maria, Pina, Pedro, Pinho, Silvia, Patuleia, Maria Dominga, Esteves, Catarina C., Salgado, Helena, Santos, Maria J., Badeti, Rodica, Cindea, Iulia, Oana, Loredana, Gurita, Adriana, Ilie, Luminita, Mocioiu, Gabriel, Tabacaru, Radu, Trante, Irina, Munteanu, Valentin, Morariu, Mihai, Nyiri, Emese, Budic, Ivana, Marjanovic, Vesna, Drašković, Biljana, Pandurov, Marina, Ilic, Jordanka, Mandras, Ana, Rados, Zdenka, Stankovic, Nikola, Suica, Maja, Vasiljevic, Sladjana, Knezevic, Mirjana, Milojevic, Irina, Petrov, Ivana, Racic, Selena Puric, Simic, Irena, Stevic, Marija, Vulicevic, Irena, Cabanova, Barbora, Hanula, Miloslav, Berger, Jelena, Janjatovic, Darja, Štupnik, Špela P., Kohn, Ivan, Lindestam, Ulf, Reinhard, Jarl, Castellheim, Albert, Sandstrom, Kerstin, Bengt, Sporre, Dorenberg, Rainer, Frykholm, Peter, Garcia, Maria, Kvarnstrom, Ann, Ponten, Emma, Bruelisauer, Thoma, Erdoes, Gabor, Kaiser, Heiko, Marchon, Mathia, Riva, Thoma, Seiler, Stefan, Bogli, Yann, Dolci, Mirko, Marcucci, Carine, Pichon, Isabelle, Casutt, Mattia, Holzle, Martin, Hurni, Thoma, Johr, Martin, Anna-Ursina, null, Malar, null, Mauch, Jacqueline, Erb, Thoma, Oeinck, Karin, Akin, Mine, Keskin, Gulsen, Senayli, Yesim, Kaya, Guner, Kendigelen, Pinar, Tutuncu, Ayse C., Hatipoğlu, Zehra, Ozcengiz, Dilek, Erdost, Hale Aksu, Ocmen, Elvan, Olguner, Cimen, Ayanoglu, Hilmi, Dincer, Pelin C., Umuroglu, Tumay, Azizoglu, Mustafa, Birbicer, Handan, Doruk, Nurcan, Sagun, Aslı, Baris, Sibel, Dmytriiev, Dmytro, Kuchi, Sridevi, Masip, Nuria, Brooks, Peter, Hare, Alison, Ahmad, Nargi, Casey, Michelle, De Silva, Sam, Dobby, Nadine, Krishnan, Prakash, Sogbodjor, L. Amaki, Walker, Ellie, Walker, Suellen, King, Stephanie, Nicholson, Katy, Quinney, Michelle, Stevens, Paul, Blevin, Andrew, Giombini, Mariangela, Goonasekera, Chulananda, Adil, Sadia, Bew, Stephanie, Bodlani, Carol, Gilpin, Dan, Jinks, Stephanie, Malarkkan, Nalini, Miskovic, Alice, Pad, Rebecca, Barry, Juliet W., Abbott, Joy, Armstrong, Jame, Cooper, Natalie, Crate, Lindsay, Emery, John, James, Kathryn, King, Hannah, Martin, Paul, Catenacci, Stefano S., Bomont, Rob, Smith, Paul, Mele, Sara, Verzelloni, Alessandra, Dix, Philippa, Bell, Graham, Gordeva, Elena, McKee, Lesley, Ngan, Esther, Scheffczik, Jutta, Tan, Li-En, Worrall, Mark, Cassar, Carmel, Goddard, Kevin, Barlow, Victoria, Oshan, Vimmi, Shah, Khairi, Bell, Sarah, Daniels, Lisa, Gandhi, Monica, Pachter, David, Perry, Chri, Robertson, Andrew, Scott, Carmen, Waring, Lynne, Barnes, David, Childs, Sophie, Norman, Joanne, Sunderland, Robin, HUS Children and Adolescents, Children's Hospital, and Clinicum
Subjects: Male, Time Factors, Health Status, Comorbidity, Intraoperative Complications/diagnosis/epidemiology/mortality/therapy, 0302 clinical medicine, Postoperative Complications, 030202 anesthesiology, Risk Factors, patient safety, Medicine, Anesthesia, Prospective Studies, Prospective cohort study, Intraoperative Complications, Medical Audit, ddc:617, Incidence (epidemiology), Incidence, Age Factors, Gestational age, critical events, Europe, Anesthetics/adverse effects, quality, Surgical Procedures, Operative, outcome, Female, Infant, Premature, Gestational Age, Anesthesia/adverse effects/mortality, Risk Assessment, Europe/epidemiology, 03 medical and health sciences, Humans, Anesthetics, business.industry, Postoperative Complications/diagnosis/epidemiology/mortality/therapy, Postmenstrual Age, Infant, Newborn, Infant, medicine.disease, 3126 Surgery, anesthesiology, intensive care, radiology, neonates, Clinical trial, Surgical Procedures, Operative/adverse effects/mortality, Anesthesiology and Pain Medicine, Blood pressure, Observational study, critical event, neonate, business
Abstract: Background: Neonates and infants requiring anaesthesia are at risk of physiological instability and complications, but triggers for peri-anaesthetic interventions and associations with subsequent outcome are unknown. Methods: This prospective, observational study recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. The primary aim was to identify thresholds of pre-determined physiological variables that triggered a medical intervention. The secondary aims were to evaluate morbidities, mortality at 30 and 90 days, or both, and associations with critical events. Results: Infants (n=5609) born at mean (standard deviation [SD]) 36.2 (4.4) weeks postmenstrual age (35.7% preterm) underwent 6542 procedures within 63 (48) days of birth. Critical event(s) requiring intervention occurred in 35.2% of cases, mainly hypotension (>30% decrease in blood pressure) or reduced oxygenation (SpO2
Published: 2021
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36. Intraoperative cerebral oxygen saturation and neurological outcomes following surgical management of necrotizing enterocolitis: Predictive factors of neurological complications following neonatal necrotizing enterocolitis: Predictive factors of neurological complications following neonatal necrotizing enterocolitis

Author: Florence, Julien-Marsollier, Clementine, Cholet, Adrien, Coeffic, Thibault, Dupont, Thibault, Gauthier, Maud, Loiselle, Kelly, Brouns, Arnaud, Bonnard, Valerie, Biran, Christopher, Brasher, and Souhayl, Dahmani
Subjects: Fetal Diseases, Enterocolitis, Necrotizing, Oxygen Saturation, Infant, Newborn, Humans, Female, Cerebral Hemorrhage, Retrospective Studies
Abstract: The goal of the present study was to investigate intraoperative factors associated with major neurological complications at 1 year following surgery for necrotizing enterocolitis.The study consisted of a retrospective review of medical charts of patients operated for over one calendar year in one institution. Data collected included demographic data, cardiac resuscitation at birth, Bell classification, antibiotics usage, time of day of surgery, surgical technique, surgical duration, type of ventilation, intraoperative vasoactive agents, and albumin use, nadir cerebral saturation, the decrease in cerebral saturation from baseline, the time period when cerebral saturation was at least 20% below baseline, and the mean arterial pressure at nadir cerebral saturation. Reported follow-up complications were assessed during formal neonatologist consultation and additional imaging exploration as needed. Analyses included descriptive statistics, and univariable and multivariable statistics.The study included 32 patients with no prior clinical neurological complications, of which 25 had normal cerebral imaging. Severe neurological complications occurred in nine patients at 1 year: Intraventricular hemorrhage (N = 2) and Periventricular leukomalacia (N = 7). However, preoperative cerebral imaging was lacking in seven patients. Consequently, the observed neurological complications at 1 year might be present before the surgery. Multivariable analysis found the decrease in cerebral saturation ≥36% from baseline as the only factor associated with the occurrence of those complications.Intraoperative decrease of cerebral oxygen saturation below ≥36% from baseline is associated with severe neurological complications in neonates undergoing surgery for necrotizing enterocolitis.
Published: 2021

37. Understanding Patients' and Living Donors' Kidney Paired Donation Educational Experiences and Recommendations for Improvement

Author: Rachyl Pines, Yaquelin Arevalo Iraheta, Katia A. Dahmani, Matthew Cooper, and Amy D. Waterman
Subjects: Transplantation, Decision Making, Living Donors, Tissue and Organ Harvesting, Humans, Kidney, Kidney Transplantation
Abstract: Introduction Educating potential kidney patients and living donors about the risks and benefits of kidney paired donation to ensure they make informed decisions is complex. This study aimed to increase understanding of patients’ and donors’ decision-making about donation, the educational content they received, and their recommendations for educational improvements. Method We conducted a mixed methods study, including semistructured interviews and quantitative surveys, with 43 participants (25 living donors; 18 kidney recipients). Findings Participants reported that the benefits of paired donation motivated them to participate (ie, helping multiple people, receiving a transplant sooner, flexible timing of donation). Although deciding to participate in paired donation was a systematic, logical, and carefully considered process for some. For most, it was a quickly made, often emotion-based decision. Paired donation educational content on different topics varied, with recipients reporting receiving less information than donors about donor protections and processes to ameliorate the challenges faced, such as broken swaps and chains, and delays in matching. Those who faced challenges requested more information about donor protections and support during and after paired donation. Although many acknowledged their transplant coordinators’ helpfulness, participants also recommended being more proactive in learning about kidney paired donation and speaking to former donors and recipients beforehand. Discussion Standardized, health literate educational content addressing the gaps and variability in education received may help increase paired donation informed decision-making.
Published: 2021

38. Melatonin for prevention of postoperative delirium after lower limb fracture surgery in elderly patients (DELIRLESS): study protocol for a multicentre randomised controlled trial

Author: Stéphanie Sigaut, Camille Couffignal, Marina Esposito-Farèse, Vincent Degos, Serge Molliex, Jacques Boddaert, Agathe Raynaud-Simon, Isabelle Durand-Zaleski, Estelle Marcault, Madalina Jacota, Souhayl Dahmani, Catherine Paugam-Burtz, Emmanuel Weiss, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service de Médecine Gériatrique [CHU Pitié-Salpêtrière], Hôpital Hôtel-Dieu [Paris], Hôpital Ambroise Paré [AP-HP], Hôpital Robert Debré Paris, Hôpital Robert Debré, HAL-SU, Gestionnaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de gériatrie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, hip, Hip Fractures, geriatric medicine, anaesthesia in orthopaedics, delirium & cognitive disorders, Delirium, General Medicine, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Lower Extremity, Humans, Multicenter Studies as Topic, Prospective Studies, 030212 general & internal medicine, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Aged, Melatonin, Randomized Controlled Trials as Topic
Abstract: IntroductionPostoperative delirium (POD) is one of the most frequent complication after surgery in elderly patients, and is associated with increased morbidity and mortality, prolonged length of stay, cognitive and functional decline leading to loss of autonomy, and important additional healthcare costs. Perioperative inflammatory stress is a key element in POD genesis. Melatonin exhibits antioxidative and immune-modulatory proprieties that are promising concerning delirium prevention, but in perioperative context literature are scarce and conflicting. We hypothesise that perioperative melatonin can reduce the incidence of POD.Methods and analysisThe DELIRLESS trial is a prospective, national multicentric, phase III, superiority, comparative randomised (1:1) double-blind clinical trial. Among patients aged 70 or older, hospitalised and scheduled for surgery of a severe fracture of a lower limb, 718 will be randomly allocated to receive either melatonin 4 mg per os or placebo, every night from anaesthesiologist preoperative consultation and up to 5 days after surgery. The primary outcome is POD incidence measured by either the French validated translation of the Confusion Assessment Method (CAM) score for patients hospitalised in surgery, or CAM-ICU score for patients hospitalised in ICU (Intensive Care Unit). Daily delirium assessment will take place during 10 days after surgery, or until the end of hospital stay if it is shorter. POD cumulative incidence function will be compared at day 10 between the two randomised arms in a competing risks framework, using the Fine and Grey model with death as a competing risk of delirium.Ethics and disseminationThe DELIRLESS trial has been approved by an independent ethics committee the Comité de Protection des Personnes (CPP) Sud-Est (ref CPP2020-18-99 2019-003210-14) for all study centres. Participant recruitment begins in December 2020. Results will be published in international peer-reviewed medical journals.Trial registration numberNCT04335968, first posted 7 April 2020.Protocol version identifierN°3–0, 3 May 2021.
Published: 2021
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39. Cingulate transcranial direct current stimulation in adults with HIV

Author: Xiong Jiang, Sophia Dahmani, Margarita Bronshteyn, Fan Nils Yang, John Paul Ryan, R. Craig Gallagher, Srikanth R. Damera, Princy N. Kumar, David J. Moore, Ronald J. Ellis, Peter E. Turkeltaub, and Schwenkreis, Peter
Subjects: Adult, Multidisciplinary, General Science & Technology, Clinical Trials and Supportive Activities, Neurosciences, Evaluation of treatments and therapeutic interventions, HIV Infections, Pilot Projects, Middle Aged, Transcranial Direct Current Stimulation, Basic Behavioral and Social Science, Gyrus Cinguli, Brain Disorders, Mental Health, Double-Blind Method, Clinical Research, 6.1 Pharmaceuticals, Behavioral and Social Science, Neurological, HIV/AIDS, Humans, Female, Aged
Abstract: Background Neuronal dysfunction plays an important role in the high prevalence of HIV-associated neurocognitive disorders (HAND) in people with HIV (PWH). Transcranial direct current stimulation (tDCS)—with its capability to improve neuronal function—may have the potential to serve as an alternative therapeutic approach for HAND. Brain imaging and neurobehavioral studies provide converging evidence that injury to the anterior cingulate cortex (ACC) is highly prevalent and contributes to HAND in PWH, suggesting that ACC may serve as a potential neuromodulation target for HAND. Here we conducted a randomized, double-blind, placebo-controlled, partial crossover pilot study to test the safety, tolerability, and potential efficacy of anodal tDCS over cingulate cortex in adults with HIV, with a focus on the dorsal ACC (dACC). Methods Eleven PWH (47–69 years old, 2 females, 100% African Americans, disease duration 16–36 years) participated in the study, which had two phases, Phase 1 and Phase 2. During Phase 1, participants were randomized to receive ten sessions of sham (n = 4) or cingulate tDCS (n = 7) over the course of 2–3 weeks. Treatment assignments were unknown to the participants and the technicians. Neuropsychology and MRI data were collected from four additional study visits to assess treatment effects, including one baseline visit (BL, prior to treatment) and three follow-up visits (FU1, FU2, and FU3, approximately 1 week, 3 weeks, and 3 months after treatment, respectively). Treatment assignment was unblinded after FU3. Participants in the sham group repeated the study with open-label cingulate tDCS during Phase 2. Statistical analysis was limited to data from Phase 1. Results Compared to sham tDCS, cingulate tDCS led to a decrease in Perseverative Errors in Wisconsin Card Sorting Test (WCST), but not Non-Perseverative Errors, as well as a decrease in the ratio score of Trail Making Test—Part B (TMT-B) to TMT—Part A (TMT-A). Seed-to-voxel analysis with resting state functional MRI data revealed an increase in functional connectivity between the bilateral dACC and a cluster in the right dorsal striatum after cingulate tDCS. There were no differences in self-reported discomfort ratings between sham and cingulate tDCS. Conclusions Cingulate tDCS is safe and well-tolerated in PWH, and may have the potential to improve cognitive performance and brain function. A future study with a larger sample is warranted.
Published: 2021

40. Spectrum of acute hepatitis and its clinical outcome in a central region in Tunisia

Author: Elleuch, Nour, Moalla, Manel, Mahmoud, Sana, Hammami, Aya, Jaziri, Hanen, Ameur, Wafa Ben, Dahmani, Wafa, Slama, Aida Ben, Brahem, Ahlem, Ajmi, Salem, Ksiaa, Mehdi, and Jmaa, Ali
Subjects: Adult, Male, Acute hepatitis, etiology, epidemiology, prognosis, Sousse, Tunisia, Adolescent, Hepatitis, Viral, Human, viruses, Budd-Chiari Syndrome, Severity of Illness Index, Young Adult, Age Distribution, Humans, Aged, Retrospective Studies, Aged, 80 and over, Research, Middle Aged, Hospitalization, Hepatitis, Autoimmune, Acute Disease, Female
Abstract: Introduction:given the lack of studies on acute hepatitis (AH) in Tunisia, we carried out this study to find the etiological spectrum and clinical profile of AH and to investigate the impact of viral etiology on the outcomes of AH. Methods:retrospective descriptive study collecting all patients with AH from 2010 to 2017. The data were compared between two groups (viral AH and non-viral AH). Results:one hundred and three patient´s files were included. The average age of our patients was 30.15 years. An etiology was found in 92 patients (89.3%). The viral etiology was found in 70 patients (76.1%). Hepatitis A virus (HAV), Hepatitis A virus (HBV), Hepatitis A virus (HCV) and cytomegalovirus (CMV) were in the cause in 52, 16, 1 and 1 patient respectively. Elsewhere, it was toxic hepatitis in 10 patients (10.9%) including 7 of drug-related AH. Budd-Chiari syndrome and autoimmune hepatitis with acute onset were reported in 3 (3.3%) and 7 (7.6%) patients, respectively. Patients with viral AH were younger than those with non-viral AH (p = 10-³). There was more recourse to hospitalization for non-viral AH. Patients with viral AH had a higher mean ALT level than those with non-viral AH. The liver damage was more severe in the non-viral AH group with lower PT. There was more severe form, more transition to chronicity and more deaths in the non-viral AH group. Conclusion:the results found in our study concerning the distribution of the etiologies of AH as well as their evolutionary aspects are consistent with the data in the literature.
Published: 2021

41. Alterations of Brain Metabolites in Adults With HIV: A Systematic Meta-analysis of Magnetic Resonance Spectroscopy Studies

Author: David J. Moore, Nicholas Kaliss, Xiong Jiang, Sophia Dahmani, Ronald J. Ellis, and John W. VanMeter
Subjects: Cart, medicine.medical_specialty, Metabolite, Proton Magnetic Resonance Spectroscopy, Clinical Sciences, Inflammation, HIV Infections, White matter, chemistry.chemical_compound, Glutamatergic, Internal medicine, Basal ganglia, medicine, Acquired Cognitive Impairment, Choline, Humans, Cognitive Dysfunction, Neuroinflammation, Neurology & Neurosurgery, business.industry, Neurosciences, Brain, Brain Disorders, Endocrinology, medicine.anatomical_structure, Infectious Diseases, Mental Health, chemistry, HIV/AIDS, Cognitive Sciences, Neurology (clinical), medicine.symptom, business, Research Article
Abstract: ObjectiveA meta-analysis of proton magnetic resonance spectroscopy studies to investigate alterations in brain metabolites in people with HIV (PWH), the relationship between metabolite alterations and combination antiretroviral therapy (cART), and the relationship between metabolite alterations and cognitive impairment.MethodsThe PubMed database was searched for studies published from 1997 to 2020. Twenty-seven studies were identified, which included 1255 PWH and 633 controls. Four metabolites (N-acetyl aspartate [NAA], myo-inositol [mI], choline [Cho], and glutamatergic metabolites [Glx]) from 5 brain regions (basal ganglia [BG], frontal gray and white matter [FGM and FWM], and parietal gray and white matter [PGM and PWM]) were pooled separately using random-effects meta-analysis.ResultsDuring early HIV infection, metabolite alterations were largely limited to the BG, including Cho elevation, a marker of inflammation. cART led to global mI and Cho normalization (i.e., less elevations), but improvement in NAA was negligible. In chronic PWH on cART, there were consistent NAA reductions across brain regions, along with Cho and mI elevations in the FWM and BG, and Glx elevations in the FWM. Cognitive impairment was associated with NAA reduction and to a lesser degree mI elevation.ConclusionsThe BG are the primary region affected during early infection. cART is successful in partially controlling neuroinflammation (global mI and Cho normalization). However, neuronal dysfunction (NAA reductions) and neuroinflammation (mI and Cho elevations) persist and contribute to cognitive impairment in chronic PWH. Novel compounds targeting NAA signal pathways, along with better neuroinflammation control, may help to reduce cognitive impairment in PWH.
Published: 2021

42. HRAS is a therapeutic target in malignant chemo-resistant adenomyoepithelioma of the breast

Author: Cécile Reyes, David Gentien, Francesco Ricci, André Nicolas, Sophie Vacher, Elisabetta Marangoni, Florence Coussy, Fabien Reyal, Sophie Château-Joubert, Rania El-Botty, Caterina Marchiò, Anne Vincent-Salomon, Ahmed Dahmani, Elodie Montaudon, Ivan Bièche, and Marick Laé
Subjects: Cancer Research, medicine.medical_specialty, Pyridones, medicine.medical_treatment, Antineoplastic Agents, Breast Neoplasms, Pyrimidinones, Proto-Oncogene Proteins p21(ras), Breast cancer, Internal medicine, Oximes, medicine, Humans, Point Mutation, Diseases of the blood and blood-forming organs, HRAS, Breast, Molecular Biology, Letter to the Editor, Protein Kinase Inhibitors, RC254-282, PDX, Aged, Trametinib, Aged, 80 and over, Chemotherapy, MEK inhibitor, Hematology, Adenomyoepithelioma, business.industry, Imidazoles, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Dabrafenib, Middle Aged, medicine.disease, Oncology, Drug Resistance, Neoplasm, Cancer research, Female, RC633-647.5, business, medicine.drug
Abstract: Malignant adenomyoepithelioma (AME) of the breast is an exceptionally rare form of breast cancer, with a significant metastatic potential. Chemotherapy has been used in the management of advanced AME patients, however the majority of treatments are not effective. Recent studies report recurrent mutations in the HRAS Q61 hotspot in small series of AMEs, but there are no preclinical or clinical data showing H-Ras protein as a potential therapeutic target in malignant AMEs. We performed targeted sequencing of tumours’ samples from new series of 13 AMEs, including 9 benign and 4 malignant forms. Samples from the breast tumour and the matched axillary metastasis of one malignant HRAS mutated AME were engrafted and two patient-derived xenografts (PDX) were established that reproduced the typical AME morphology. The metastasis-derived PDX was treated in vivo by different chemotherapies and a combination of MEK and BRAF inhibitors (trametinib and dabrafenib). All malignant AMEs presented a recurrent mutation in the HRAS G13R or G12S hotspot. Mutation of PIK3CA were found in both benign and malignant AMEs, while AKT1 mutations were restricted to benign AMEs. Treatment of the PDX by the MEK inhibitor trametinib, resulted in a marked anti-tumor activity, in contrast to the BRAF inhibitor and the different chemotherapies that were ineffective. Overall, these findings further expand on the genetic features of AMEs and suggest that patients carrying advanced HRAS-mutated AMEs could potentially be treated with MEK inhibitors.
Published: 2021

43. mTOR Repression in Response to Amino Acid Starvation Promotes ECM Degradation Through MT1‐MMP Endocytosis Arrest

Author: Sandra Antoine, Nadia Elkhatib, Philippe Chavrier, David Remy, Elisabetta Marangoni, Ahmed Dahmani, Cecilia Colombero, Elodie Montaudon, Guillaume Montagnac, Pedro Monteiro, Anne-Sophie Macé, Margot Fournier, Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), BioImaging Cell and Tissue Core Facility (PICT-IBiSA), and Institut Curie [Paris]
Subjects: clathrin‐mediated endocytosis, [SDV]Life Sciences [q-bio], General Chemical Engineering, medicine.medical_treatment, extracellular matrix, Science, General Physics and Astronomy, Medicine (miscellaneous), Breast Neoplasms, Matrix metalloproteinase, Endocytosis, Biochemistry, Genetics and Molecular Biology (miscellaneous), MT1‐MMP, Extracellular matrix, Mice, 03 medical and health sciences, 0302 clinical medicine, breast cancer, Cell Line, Tumor, Matrix Metalloproteinase 14, medicine, Extracellular, Animals, Humans, General Materials Science, Amino Acids, Psychological repression, Research Articles, ComputingMilieux_MISCELLANEOUS, PI3K/AKT/mTOR pathway, 030304 developmental biology, invadopodia, Metalloproteinase, 0303 health sciences, Chemistry, TOR Serine-Threonine Kinases, Growth factor, starvation, General Engineering, Receptor-mediated endocytosis, Cell biology, 030220 oncology & carcinogenesis, Invadopodia, mTOR, Female, Research Article
Abstract: Under conditions of starvation, normal and tumor epithelial cells can rewire their metabolism toward the consumption of extracellular proteins, including extracellular matrix‐derived components as nutrient sources. The mechanism of pericellular matrix degradation by starved cells has been largely overlooked. Here it is shown that matrix degradation by breast and pancreatic tumor cells and patient‐derived xenograft explants increases by one order of magnitude upon amino acid and growth factor deprivation. In addition, it is found that collagenolysis requires the invadopodia components, TKS5, and the transmembrane metalloproteinase, MT1‐MMP, which are key to the tumor invasion program. Increased collagenolysis is controlled by mTOR repression upon nutrient depletion or pharmacological inhibition by rapamycin. The results reveal that starvation hampers clathrin‐mediated endocytosis, resulting in MT1‐MMP accumulation in arrested clathrin‐coated pits. The study uncovers a new mechanism whereby mTOR repression in starved cells leads to the repurposing of abundant plasma membrane clathrin‐coated pits into robust ECM‐degradative assemblies., Cancer cells catabolize extracellular matrix (ECM) components to maintain growth when nutrients are depleted. This study reports that tumor cells repurpose the invadopodia‐, protease‐dependent program to elicit a massive ECM degradation mechanism, under regulation by mechanistic target of rapamycin complex 1. Nutrient scarcity blocks endocytosis of membrane type 1‐matrix metalloproteinase converting arrested clathrin‐coated pits into powerful matrix degradation units.
Published: 2021
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44. A Computational Approach to Evaluate the Combined Effect of SARS-CoV-2 RBD Mutations and ACE2 Receptor Genetic Variants on Infectivity: The COVID-19 Host-Pathogen Nexus

Author: M. Dahmani Fathallah, Dana Ashoor, Sadok Chlif, Maryam Marzouq, Noureddine Ben Khalaf, and Hamdi Al Jarjanazi
Subjects: Microbiology (medical), Immunology, Protein Data Bank (RCSB PDB), Plasma protein binding, Biology, Molecular Dynamics Simulation, Peptidyl-Dipeptidase A, medicine.disease_cause, Microbiology, Virus, Cellular and Infection Microbiology, Polymorphism (computer science), medicine, Ensembl, Humans, Receptor, Pathogen, Original Research, Infectivity, Genetics, Mutation, receptor binding domain, virus-host interaction, SARS-CoV-2, Point mutation, angiotensin converting enzyme 2 receptor, COVID-19, spike, QR1-502, Infectious Diseases, SARS-CoV-2 mutations, Spike Glycoprotein, Coronavirus, hormones, hormone substitutes, and hormone antagonists, Protein Binding
Abstract: SARS-CoV-2 infectivity is largely determined by the virus Spike protein binding to the ACE2 receptor. Meanwhile, marked infection rate differences were reported between populations and individuals. To understand the disease dynamic, we developed a computational approach to study the implications of both SARS-CoV-2 RBD mutations and ACE2 polymorphism on the stability of the virus-receptor complex. We used the 6LZG PDB RBD/ACE2 3D model, the mCSM platform, the LigPlot+ and PyMol software to analyze the data on SARS-CoV-2 mutations and ACE variants retrieved from GISAID and Ensembl/GnomAD repository. We observed that out of 351 RBD point mutations, 83% destabilizes the complex according to free energy (ΔΔG) differences. We also spotted variations in the patterns of polar and hydrophobic interactions between the mutations occurring in 15 out of 18 contact residues. Similarly, comparison of the effect on the complex stability of different ACE2 variants showed that the pattern of molecular interactions and the complex stability varies also according to ACE2 polymorphism. We infer that it is important to consider both ACE2 variants and circulating SARS-CoV-2 RBD mutations to assess the stability of the virus-receptor association and evaluate infectivity. This approach might offers a good molecular ground to mitigate the virus spreading.
Published: 2021

45. Synthetic Peptides That Antagonize the Angiotensin-Converting Enzyme-2 (ACE-2) Interaction with SARS-CoV-2 Receptor Binding Spike Protein

Author: Taha Azad, Alexander Dömling, Jørgen de Jonge, Harry van Goor, Marco A. Velasco-Velázquez, Angel J Ruiz-Moreno, Matthew Groves, John C. Bell, Alessandra Monti, Afsaneh Sadremomtaz, Zayana M Al-Dahmani, Jolanda M. Smit, Nunzianna Doti, Chao Wang, Debora de Jong, Drug Design, Microbes in Health and Disease (MHD), Medicinal Chemistry and Bioanalysis (MCB), Groningen Institute for Organ Transplantation (GIOT), and Groningen Kidney Center (GKC)
Subjects: Models, Molecular, Binding Sites, Chemistry, Microscale thermophoresis, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Genome, Article, Molecular dynamics, HEK293 Cells, Drug Discovery, Angiotensin-converting enzyme 2, Spike Glycoprotein, Coronavirus, Biophysics, Molecular Medicine, Bioluminescence, Humans, Angiotensin-Converting Enzyme 2, Peptides, Protein secondary structure, Intracellular, Cells, Cultured
Abstract: The SARS-CoV-2 viral spike protein S receptor-binding domain (S-RBD) binds ACE2 on host cells to initiate molecular events, resulting in intracellular release of the viral genome. Therefore, antagonists of this interaction could allow a modality for therapeutic intervention. Peptides can inhibit the S-RBD:ACE2 interaction by interacting with the protein-protein interface. In this study, protein contact atlas data and molecular dynamics simulations were used to locate interaction hotspots on the secondary structure elements α1, α2, α3, β3, and β4 of ACE2. We designed a library of discontinuous peptides based upon a combination of the hotspot interactions, which were synthesized and screened in a bioluminescence-based assay. The peptides demonstrated high efficacy in antagonizing the SARS-CoV-2 S-RBD:ACE2 interaction and were validated by microscale thermophoresis which demonstrated strong binding affinity (∼10 nM) of these peptides to S-RBD. We anticipate that such discontinuous peptides may hold the potential for an efficient therapeutic treatment for COVID-19.
Published: 2021

46. Rupture Risk of Small Unruptured Intracranial Aneurysms in Japanese Adults

Author: Puneet Sharma, Chihebeddine Dahmani, Yuichi Murayama, Cosmin Nita, Hiroshi Ohno, Saikiran Rapaka, Yuya Uchiyama, Katharina Otani, Soichiro Fujimura, Takashi Suzuki, Ashraf Mohamed, Hiroyuki Takao, Makoto Yamamoto, Thomas Redel, Toshihiro Ishibashi, and Viorel Mihalef
Subjects: Adult, Male, medicine.medical_specialty, Younger age, Hemodynamics, Aneurysm, Ruptured, Logistic regression, symbols.namesake, Japan, Risk Factors, Internal medicine, medicine, Humans, Rupture risk, Fisher's exact test, Aged, Retrospective Studies, Advanced and Specialized Nursing, business.industry, Age Factors, Area under the curve, Intracranial Aneurysm, Odds ratio, Therapeutic decision making, Middle Aged, Cerebral Angiography, ROC Curve, symbols, Cardiology, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business
Abstract: Background and Purpose— Therapeutic decision making for small unruptured intracranial aneurysms ( Methods— We analyzed 338 small unruptured aneurysms; 35 ruptured during the observation period, and 303 remained stable. Clinical, morphological, and hemodynamic parameters were considered. Computational fluid dynamics was used to calculate hemodynamic parameters based on computed tomography images of all aneurysms in their unruptured state. Differences between the ruptured and unruptured groups were tested by the Mann-Whitney U or Fisher exact tests. Multivariate logistic regression was applied to obtain a rupture risk model. Its predictive ability was investigated by receiver operating characteristic analysis. Results— The risk model revealed that rupture may be more likely to in younger patients (odds ratio [OR], 0.92 for each age increase of 1 year [95% CI, 0.88−0.96] P P =0.03), located at a bifurcation (OR, 5.45 [95% CI, 1.87−15.85] P =0.002), with a bleb (OR, 4.09 [95% CI, 1.42−11.79] P =0.009), larger length (OR, 1.91 for each increase of 1 mm [95% CI, 1.42−2.57] P P =0.01). The sensitivity, specificity, and area under the curve were 0.800, 0.752, and 0.826 (95% CI, 0.739−0.914) respectively. Conclusions— Younger age, presence of multiple aneurysms, location at a bifurcation, presence of a bleb, larger length, and lower pressure loss coefficient were identified as risk factors for rupture of small intracranial aneurysms. The risk model should be validated in further studies.
Published: 2020
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47. Anaesthesiologist workload during intra-operative paediatric anaesthesia

Author: Florence Julien-Marsollier, Souhayl Dahmani, Mehdi Azale, and Christopher Brasher
Subjects: Anesthesiology and Pain Medicine, Intra operative, business.industry, Anesthesia, Humans, Medicine, Workload, Child, business, Anesthesiologists, Paediatric anaesthesia
Published: 2022
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48. Accuracy of the sleep-related breathing disorder scale to diagnose obstructive sleep apnea in children: a meta-analysis

Author: Béatrice Bruneau, Julien Fournier, Florence Julien-Marsollier, Christopher Brasher, Virginie Luce, Thomas Vacher, Thierno Diallo, Alia Skhiri, Myriam Bellon, Souhayl Dahmani, and Daphné Michelet
Subjects: Sleep Apnea, Obstructive, medicine.medical_specialty, education.field_of_study, medicine.diagnostic_test, Receiver operating characteristic, business.industry, Polysomnography, medicine.medical_treatment, Population, Sleep apnea, General Medicine, medicine.disease, Sensitivity and Specificity, Confidence interval, Tonsillectomy, Obstructive sleep apnea, Surveys and Questionnaires, Internal medicine, Meta-analysis, medicine, Humans, Child, business, education
Abstract: Objectives The main objective of this meta-analysis was to assess the accuracy of the Sleep-Related Breathing Disorder (SRBD) Scale in the diagnosis of obstructive sleep apnea syndrome (OSAS) in children. Patients/methods A literature search of studies comparing SRBD to polysomnography for the diagnosis of OSAS in children was performed. Risks of biases were quantified using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Analyses determined the summary receiver operator characteristic area under the curve (SROC), the pooled sensitivity (Se), the specificity (Sp), and the positive and negative likelihood ratios (LR+ and LR–). Results were graded and are expressed as means [95% confidence interval]. Post-test probabilities were computed for various populations. Results Eleven studies were included; and two were considered to have high risk of bias. The SROC was 0.73 [CI: 0.63; 0.82]. The combined Se, Sp, LR+ and LR– were: 0.72 [CI: 0.68; 0.77], 0.59 [CI: 0.56; 0.63], 1.74 [CI: 1.32; 2.30], 0.53 [CI: 0.39; 0.71], respectively. Sub-group analyses displayed similar results in comparison to overall results. GRADE evidence for the overall analysis was low to moderate. Finally, pre-test to post-test probabilities were estimated to be: 3.5%–1%, 50%–30% and 75%–30%, for the general population, the obese patients and the patients assigned for surgical treatment of OSAS, respectively. Conclusions The current meta-analysis indicates that the SRBD scale has acceptable accuracy in detecting patients with OSAS. It may be useful when evaluating patients with suspected OSAS before surgery. Study registration PROSPERO database (CRD42018088216).
Published: 2019
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49. Epidemiology and complications of anaesthesia in the French centres that participated to NECTARINE: A secondary analysis

Author: Souhayl Dahmani, Anne Laffargue, Christophe Dadure, Mathilde De Queiroz, Florence Julien-Marsollier, Daphné Michelet, Francis Veyckemans, Catherine Amory, Hugues Ludot, Dina Bert, Juliette Godart, Hervé Dupont, Benjamin Urbina, Catherine Baujard, Philippe Roulleau, Giuseppe Staiti, Maryline Bordes, Karine Nouette Gaulain, Yann Hamonic, François Semjen, Olivier Jacqmarcq, Caroline Lejus-Bourdeau, Cécile Magne, Léa Petry, Lilica Ros, Aurélien Zang, Mehdi Bennis, Bernard Coustets, Rose Fesseau, Isabelle Constant, Eliane Khalil, Nada Sabourdin, Noémie Audren, Thomas Descarpentries, Fanny Fabre, Aurélien Legrand, Emilie Druot, Gilles Orliaguet, Lucie Sabau, Lynn Uhrig, François De La Briere, Karin Jonckheer, Jean-Paul Mission, Lucia Scordo, Caroline Couchepin, Pablo De La Arena, Laurent Hertz, Philippe Pirat, Chrystelle Sola, Myriam Bellon, Véronique Depret-Donatien, and Anne Lesage
Subjects: Cohort Studies, Anesthesiology and Pain Medicine, Postoperative Complications, Infant, Newborn, Humans, Infant, Anesthesia, General Medicine, France, Prospective Studies, Critical Care and Intensive Care Medicine
Abstract: Neonatal and infant anaesthesia are associated with a high risk of perioperative complications. The aim of the current study was to describe those risks in France using the French data from the NECTARINE study.Data from the French centres that participated to the NECTARINE study were analysed. The primary goal of the study was the description of patients' characteristics, procedures and perioperative management and their comparison with the results of the European NECTARINE study. Secondary outcomes were the description of major perioperative complications and death.Overall, 926 procedures collected in 15 centres (all teaching hospitals) were analysed. Comparison between the French and European NECTARINE cohorts found few differences related to patients' characteristics and procedures. The rate of interventions for critical events (respiratory, haemodynamic, and metabolic) was similar between the two cohorts. Near-infrared spectroscopy monitoring was used in 12% of procedures. Nearly none of the thresholds for these interventions met the published standards. By day 30, complications (respiratory, haemodynamic, metabolic, renal, and liver failure) and death were observed in 14.4% [95% CI 11.6-16.4]% and 1.8% [95% CI 1.1-2.9] of cases, respectively.Although the health status of the patients in the French cohort was less severe, procedures, management and postoperative complications and mortality rates were similar to the European cohort. However, thresholds for interventions were often inadequate in both cohorts. Efforts should be undertaken to improve the knowledge and use of new monitoring devices in this population.
Published: 2021

50. Analysis of genomic and non-genomic signaling of estrogen receptor in PDX models of breast cancer treated with a combination of the PI3K inhibitor alpelisib (BYL719) and fulvestrant

Author: Muriel Le Romancer, Ahmed Dahmani, Ludivine Morisset, Coralie Poulard, Ivan Bièche, Loay Kassem, Isabelle Treilleux, Julien Jacquemetton, Sophie Vacher, Laura Sourd, Rania El Botty, Olivier Tredan, Ludmilla de Plater, Elodie Montaudon, Elisabetta Marangoni, Sophie Chateau-Joubert, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cairo University - Faculty of Medicine, Centre de recherche de l'Institut Curie [Paris], Institut Curie [Paris], Ecole Nationale Vétérinaire d'Alfort, École nationale vétérinaire - Alfort (ENVA), Centre Léon Bérard [Lyon], and Manship, Brigitte
Subjects: medicine.drug_class, Resistance, Proto-Oncogene Proteins pp60(c-src), Estrogen receptor, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Proximity ligation assay, Biology, PI3K, 03 medical and health sciences, Mice, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Surgical oncology, Antineoplastic Combined Chemotherapy Protocols, medicine, Biomarkers, Tumor, PTEN, Animals, Humans, Fulvestrant, RC254-282, PI3K/AKT/mTOR pathway, 030304 developmental biology, PDX, Phosphoinositide-3 Kinase Inhibitors, 0303 health sciences, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Biomarker, Genomics, Middle Aged, Prognosis, Xenograft Model Antitumor Assays, Thiazoles, Receptors, Estrogen, Estrogen, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Female, Tamoxifen, Estrogen signaling, medicine.drug, Research Article, Signal Transduction
Abstract: Background Endocrine therapies targeting estrogen signaling have significantly improved breast cancer (BC) patient survival, although 40% of ERα-positive BCs do not respond to those therapies. Aside from genomic signaling, estrogen triggers non-genomic pathways by forming a complex containing methylERα/Src/PI3K, a hallmark of aggressiveness and resistance to tamoxifen. We aimed to confirm the prognostic value of this complex and investigated whether its targeting could improve tumor response in vivo. Methods The interaction of ERα/Src and ERα/PI3K was studied by proximity ligation assay (PLA) in a cohort of 440 BC patients. We then treated patient-derived BC xenografts (PDXs) with fulvestrant or the PI3K inhibitor alpelisib (BYL719) alone or in combination. We analyzed their anti-proliferative effects on 6 ERα+ and 3 ERα− PDX models. Genomic and non-genomic estrogen signaling were assessed by measuring ERα/PI3K interaction by PLA and the expression of estrogen target genes by RT-QPCR, respectively. Results We confirmed that ERα/Src and ERα/PI3K interactions were associated with a trend to poorer survival, the latter displaying the most significant effects. In ERα+ tumors, the combination of BYL719 and fulvestrant was more effective than fulvestrant alone in 3 models, irrespective of PI3K, PTEN status, or ERα/PI3K targeting. Remarkably, resistance to fulvestrant was associated with non-genomic ERα signaling, since genomic degradation of ERα was unaltered in these tumors, whereas the treatment did not diminish the level of ERα/PI3K interaction. Interestingly, in 2 ERα− models, fulvestrant alone impacted tumor growth, and this was associated with a decrease in ERα/PI3K interaction. Conclusions Our results demonstrate that ERα/PI3K may constitute a new prognostic marker, as well as a new target in BC. Indeed, resistance to fulvestrant in ERα+ tumors was associated with a lack of impairment of ERα/PI3K interaction in the cytoplasm. In addition, an efficient targeting of ERα/PI3K in ERα− tumors could constitute a promising therapeutic option.
Published: 2021
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