Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Motivation et énergisation du comportement : une exploration du cerveau motivationnel dans le compromis récompense/effort

Choisir entre l'action ou l'inaction est peut-être le type de décision le plus critique auquel un animal peut faire face. Une formalisation simple de ces choix consiste à évaluer les bénéfices attendus (nourriture, argent par exemple) ainsi que les coûts (punitions, pertes de temps ou d'argent) associés à chaque action et d'optimiser le rapport entre récompenses reçues et coûts assumés. Notre motivation à s'engager dans une action donnée dépend donc de la valeur de ce rapport. Dans le domaine de l'économie comportementale, l’optimisation de ce rapport bénéfices/coûts constitue le principe fondamental qui régule et explique le comportement des individus. Dans mes travaux de thèse, j'ai réalisé une implémentation de ces concepts venant de l'économie comportementale en utilisant une forme expérimentalement quantifiable de coûts: l'effort physique. Dans notre vie de tous les jours, si l'on nous demande de choisir entre deux options rapportant les même bénéfices mais demandant différents efforts (par exemple, travailler 3 ou 7 jours par semaine pour le même salaire), nous choisissons habituellement l'option qui nécessite la plus petite dépense d'énergie, en optant donc pour le moindre effort. Néanmoins, l'effort physique a été beaucoup moins étudié en comparaison à d'autres formes de coûts comme le fait de différer la récompense ou d'en augmenter l'incertitude. Le présent travail de recherche a donc pour but de mettre en lumière les bases neurales de la balance récompense / effort dans la prise de décision. Comprendre comment l'effort affecte la dévaluation des potentielles récompenses a un intérêt particulier pour la prise de décisions économiques mais aussi pour la clinique, étant donné que la diminution de la capacité à accepter d'avoir à exercer un effort est un symptôme-clé de nombreuses pathologies comme l'apathie ou la dépression. Nous faisons l’hypothèse que de tels désordres pourraient résulter de deux différents processus comportementaux: (a) une diminution de la sensibilité aux bénéfices futurs et/ou (b) une sensibilité excessive aux coûts potentiels. Ainsi, lorsqu'interrogés sur les raisons pour lesquelles ils ne veulent pas aller au cinéma regarder un film qu'ils apprécient, les patients apathiques peuvent déclarer que (a) le film n'est pas assez bon (soit une plus faible réponse à la valeur attendue), (b) le cinéma est trop loin (soit une plus forte sensibilité à l'effort anticipé). Afin de tester ces hypothèses, nous avons enregistré l'activité de neurones chez le singe pendant des tâches comportementales. Nous avons trouvé que d'une part, la dopamine encode la valeur de l'action future et oriente le comportement vers l'option demandant le moindre effort. D'autre part, la noradrénaline permet à l'individu de faire face à l'effort à venir en réduisant la sensibilité à l'anticipation de l'effort. En utilisant une approche pharmacologique, nous avons démontré que lorsque le niveau de noradrénaline est augmenté, les singes exercent d'avantage d'effort. En outre, nous avons montré que les potentiels locaux de champ dans le cortex pré-frontal ventro-médian, enregistrés dans une tâche comportementale identique, sont modulés par la valeur attendue et prédisent le choix du singe. En résumé, ce travail permet de départager en partie les circuits neuronaux impliqués dans le calcul de la balance récompense / effort, principalement encodée par les neurones dopaminergiques et dans les potentiels locaux de champ au niveau du cortex pré-frontal ventro-médian. Enfin, ce travail souligne le rôle de la noradrénaline dans la mobilisation de l'énergie d'un individu afin de faire face au défi que représente l'effort physique.There is perhaps no more critical factor for the behaviour of an animal than the way it chooses between action and inaction. A simple way to formalise such choices is to evaluate the predicted benefit (e.g. food, money) and costs (e.g. punishments, losses, delays) associated with each action and optimise the rates at which rewards are received and costs avoided. Our motivation to perform a given action depends upon such value ratio. In the current behavioural economics literature, the optimisation of the benefits/costs ratio stands as the fundamental principle that regulates and explains agents’ behaviour. In my Ph.D. studies, I implement a realistic model of such concepts from behavioural economics by using an empirical type of cost: physical effort. In our everyday life, if we are asked to choose between two options that imply the same reward but different efforts (e.g., working 3 or 7 days per week for the same salary), we usually opt for the alternative that requires the slightest energy expenditure, thus the least effort. However, physical effort has been far less studied compared to other decision costs such as delay or uncertainty. The present Ph.D. work aims at highlighting the neuronal bases of such reward/effort tradeoff. Understanding how effort cost affects the discounting of potential rewards has a clear significance for economic decisions and clinics, since the reduced willingness to exert effort is a key signature of several clinical disorders such as apathy and depression We suggest that disorders such as apathy could result from two different behavioural processes: (a) a decreased responsiveness to future benefits and/or (b) an excessive sensitivity to potential costs. For instance, when asked why they would not go see a movie they like, patients may say that (a) the movie is not good enough (i.e. low responsiveness to expected value) or that (b) the theatre is too far away (i.e. high sensitivity to anticipated effort). To test our hypothesis, we combined behavioural tasks and pharmacological approach with neuron recordings in monkeys, targeting specifically two majors actors of the rewarding and effort system, dopamine and noradrenaline. We found that dopamine and noradrenaline have distinct but complementary roles. On the one hand, dopamine tracks the reward value of future outcomes and orient the behaviour towards the least effortful options. On the other hand, noradrenaline enables subjects to face the effort at hand, reducing the sensitivity to anticipated effort. Using a pharmacological approach, we found that, when we increase noradrenaline, monkeys exerted significantly more effort. Moreover, we have found that local field potentials in the ventromedial prefrontal cortex recorded in the same task encode the expected value and predict action selection. In summary, this Ph.D. work allows to disentangle some of the neuronal circuits implicated in the computation of the reward/effort tradeoff, mainly encoded by dopaminergic neurons and in the local field potential of the ventromedial prefrontal cortex. On the other hand, this work highlights the role of noradrenaline in the energization of behaviour to face the challenge represented by the physical effort

Noradrenergic But Not Dopaminergic Neurons Signal Task State Changes and Predict Reengagement After a Failure

International audienceThe two catecholamines, noradrenaline and dopamine, have been shown to play comparable roles in behavior. Both noradrenergic and dopaminergic neurons respond to cues predicting reward availability and novelty. However, even though both are thought to be involved in motivating actions, their roles in motivation have seldom been directly compared. We therefore examined the activity of putative noradrenergic neurons in the locus coeruleus and putative midbrain dopaminergic neurons in monkeys cued to perform effortful actions for rewards. The activity in both regions correlated with engagement with a presented option. By contrast, only noradrenaline neurons were also (i) predictive of engagement in a subsequent trial following a failure to engage and (ii) more strongly activated in nonrepeated trials, when cues indicated a new task condition. This suggests that while both catecholaminergic neurons are involved in promoting action, noradrenergic neurons are sensitive to task state changes, and their influence on behavior extends beyond the immediately rewarded action

Bases cérébrales de la motivation chez le singe rhésus : études pharmacologiques et neurophysiologiques

La motivation regroupe l’ensemble des processus qui sous-tendent le comportement, en bref, pourquoi on fait ce que l’on fait ? Que ce soit en termes de choix entre plusieurs actions ou de quantité d’énergie dépensée pour une action donnée, les comportements du rapport entre les bénéfices attendus et les coûts escomptés. Au niveau cérébral, la motivation implique un certain nombre de structures clefs, comme les systèmes neuromodulateurs et le cortex préfrontal. En effet, ces structures sont atteintes dans de nombreuses maladies neurologiques (Parkinson) ou psychiatriques (dépression). Mais la contribution spécifique de ces structures aux processus motivationnels précis reste mal comprise. Par ailleurs, la régulation des comportements en fonction du rapport entre les apports et les dépenses énergétiques est essentielle pour appréhender le comportement des primates dans leur milieu naturel. Mieux comprendre les bases cérébrales de la motivation devrait donc nous aider à mieux comprendre le comportement de l’ensemble des primates. Notre travail de recherche vise à identifier les processus cérébraux impliqués dans la gestion du compromis entre la récompense (le but de l’action) et l’effort physique nécessaire à son obtention. Nous entrainons des singes (Macaca mulatta) dans des tâches simples où ils doivent produire un effort physique (serrer une pince) pour obtenir une récompense hydrique. Nous mesurons plusieurs variables comportementales (choix, temps de réaction, force exercée, expressions faciales) et végétatives (diamètre pupillaire). Une fois les singes entrainés, nous mesurons l’activité des neurones du cortex préfrontal, ainsi que celle des neurones à dopamine (DA) de la substance noire (SN) et des neurones à noradrénaline (NA) du locus coeruleus (LC). Nous évaluons par ailleurs le rôle des systèmes dopaminergiques (DA) et noradrénergiques (NA) en utilisant des traitements pharmacologiques (L-DOPA et Atomoxetine). Nous avons ainsi identifié les rôles spécifiques de plusieurs éléments clefs dans le contrôle de la motivation en fonction du compromis effort/récompense. Tout d’abord, nous montrons que les deux systèmes neuromodulateurs régulent l’engagement des singes en fonction d’informations sur la récompense et la difficulté. Nous confirmons le rôle de la DA dans les processus incitatifs, c’est-à-dire l’énergisation en fonction de la valeur du but. La NA aurait un rôle complémentaire, en favorisant la production d’effort en fonction de la difficulté attendue. Par ailleurs, nous montrons que le cortex préfrontal ventro-médian joue un rôle spécifique dans les processus d’évaluation en fonction de paramètres internes. Nos expériences futures viseront à comprendre les interactions fonctionnelles entre ces différentes structures cérébrales, et ainsi à mieux comprendre le comportement des primates

Dual contributions of noradrenaline to behavioural flexibility and motivation

International audienceINTRODUCTION: While several theories have highlighted the importance of the noradrenergic system for behavioral flexibility, a number of recent studies have also shown a role for noradrenaline in motivation, particularly in effort processing. Here, we designed a novel sequential cost/benefit decision task to test the causal influence of noradrenaline on these two functions in rhesus monkeys.METHODS: We manipulated noradrenaline using clonidine, an alpha-2 noradrenergic receptor agonist, which reduces central noradrenaline levels and examined how this manipulation influenced performance on the task.RESULTS: Clonidine had two specific and distinct effects: first, it decreased choice variability, without affecting the cost/benefit trade-off; and second, it reduced force production, without modulating the willingness to work.CONCLUSIONS: Together, these results support an overarching role for noradrenaline in facing challenging situations in two complementary ways: by modulating behavioral volatility, which would facilitate adaptation depending on the lability of the environment, and by modulating the mobilization of resources to face immediate challenges

A multicenter survey on computer‐aided design and computer‐aided manufacturing mandibular reconstruction from Italian community

Computer-aided design and computer-aided manufacturing (CAD/CAM) technology has revolutionized mandibular reconstructive surgery. The possibilities of planning margins of bone resection, flap segmentation, and plate design allow highly precise reconstructions with great improve- ment of functional and esthetic results (Rana et al., 2012). Despite some initial concerns limiting the application of these systems, daily practice and several reports in the literature have resolved many of these issues (Wilde, Cornelius, & Schramm, 2014). In particular, the accuracy of plan- ning transfer from virtual planning into the operating room, precision of reconstructive plates, and reliability of cutting guides have been largely documented in the international literature (Tarsitano, Ciocca, Scotti, & Marchetti, 2016; Wilde et al., 2015). Cost is the greatest factor limiting the adoption of such technologies, but recent studies have suggested that sparing of surgical time and increasingly accurate results minimize this problem, and several reports indicate that the costs are comparable to those of freehand procedures (Bolzoni et al., 2019)

Accuracy of Fibula Reconstruction Using Patient‐Specific Cad/Cam Plates: A Multicenter Study on 47 Patients

Objectives: This prospective study evaluated the accuracy of mandibular reconstruction using free fibular flaps (by comparing virtual plans to the three-dimensional postoperative results), and the extent of bone-to-bone contact after computer-assisted surgery.Methods: We included 65 patients who underwent partial-continuity mandibular resections from February 2013 to January 2017, and evaluated virtual planning, surgical techniques, and accuracy.Results: Forty-seven patients were analysed. A total of 112 fibular segments received 54 implants. We measured 227 distances between landmarks to assess the accuracy of reconstruction. Postoperative reconstruction accuracy ranged from 0.5 to 3 mm.Conclusion: Virtual surgical planning very accurately translated simulation into reality, particularly in patients requiring large, complex mandibular reconstructions using multiple fibular segments.Level of evidence:

Behavioural and social sciences are critical for pandemic prevention, preparedness, and response. WHO Technical Advisory Group on Behavioural Insights and Sciences for Health [Open Letter]

Open letter to the Bureau of the Intergovernmental Negotiating Body to strengthen pandemic prevention, preparedness and respons

Accuracy of Fibula Reconstruction Using Patient-Specific Cad/Cam Plates: A Multicenter Study on 47 Patients

Objectives: This prospective study evaluated the accuracy of mandibular reconstruction using free fibular flaps (by comparing virtual plans to the three-dimensional postoperative results), and the extent of bone-to-bone contact after computer-assisted surgery.Methods: We included 65 patients who underwent partial-continuity mandibular resections from February 2013 to January 2017, and evaluated virtual planning, surgical techniques, and accuracy.Results: Forty-seven patients were analysed. A total of 112 fibular segments received 54 implants. We measured 227 distances between landmarks to assess the accuracy of reconstruction. Postoperative reconstruction accuracy ranged from 0.5 to 3 mm.Conclusion: Virtual surgical planning very accurately translated simulation into reality, particularly in patients requiring large, complex mandibular reconstructions using multiple fibular segments.Level of evidence: