Shifting towards Antifragile Critical Infrastructure Systems

Antifragility, which is an evolutionary understanding of resilience, has become a predominant concept in academic and industrial fields as the criticality of vital infrastructures (like healthcare and transportation) has become more flexible and varying due the impact of digitization and adverse circumstances, such as changing the prioritization of industrial services while accelerating IoT (Internet of Things) deployment during the COVID-19 pandemic. The crucial role of antifragility is to enable critical infrastructures to gain from disorder to foster their adaptability to real unexpected environmental changes. Thus, this paper aims to provide a comprehensive survey on the antifragility concept while clarifying the difference with the resilience concept. Moreover, it highlights how the COVID-19 crisis has revealed the fragility of critical infrastructures and unintentionally promoted the antifragility concept. To showcase the main concepts, we adopt the blockchain as an example of an antifragile system. Copyright © 2022 by SCITEPRESS – Science and Technology Publications, Lda. All rights reserved.

Virtual sarcoma disease multidisciplinary team: A jump into the future?

Background: Sarcomas are rare cancers with complex diagnoses, requiring multimodal management in referral Centers with a dedicated Disease Multidisciplinary Team (DMT). COVID-19 pandemic imposed a sudden revolution in care management leading to activation of digital health tools such as virtual DMT meetings. We investigated how transition from face-to-face (FTF) to virtual meetings (VM) impacted clinical practice in a Sarcoma referral Center in Italy. Method(s): An online survey was administered to the participants of the Sarcoma DMT meetings held between 2020 and 2022 at Regina Elena National Cancer Institute of Rome. The survey consisted of 40 questions inquiring the experience of professionals in DMT meetings, opinions about FTF/VM, future perspectives. Moreover, we retrospectively analyzed the registries of DMT meetings held from March 9th 2019 to March 8th 2022 and we defined three 12-months periods by using the date of National lockdown beginning in Italy (March 9th 2020) as cutoff: a pre-covid, a covid, a post-covid phase. Result(s): A total of 22 healthcare professionals answered the survey: 18 medical doctors, 1 psychologist and 3 data/case managers. The most important changes in VM were better quality of clinical approach and research (22%), technological innovation (50%), and better logistical setting (95%). Between participants, 90% were highly/moderately satisfied with the depth of discussion, 100% declared that attendance was similar (68%) or increased (32%) compared to FTF, 86% thought that decision-making process was not affected, and 95% were still able to interact adequately and access relevant patients' data. 91% thought that VM could be approved hereafter and 100% that would facilitate DMT expansion globally. The median participation rate in Institutional Sarcoma DMT meetings was 58% (95% confidence interval (CI) 55%-60%), 62% (95% CI 48%-71%), and 64% (95% CI 61%-68%) respectively in the pre-covid, covid, and post-covid periods (p 0.0159). Compared to the re-discussed cases, the new ones rose from 30.1% in the pre-covid to 37.9% in the covid and 42.3% in the post-covid period (p<0.0001). Conclusion(s): VM guarantees a great standard of effectiveness in health assistance and should be a suitable or additional tool for the management of patients in clinical practice. Legal entity responsible for the study: IRCCS Regina Elena National Cancer Institute (IRE). Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest.Copyright © 2023 European Society for Medical Oncology

Intérêt d'une dose unique de Tocilizumab 400 mg sur les formes sévères d'infection respiratoire à COVID-19

Introduction Afin d'éviter le transfert en réanimation, des patients atteints de formes sévères de COVID-19 ont bénéficié hors AMM d'un traitement par tocilizumab, un médicament ciblant l'interleukine-6. Cette étude cherche à évaluer l'impact de cette thérapeutique. Patients et méthodes Tous les patients atteints de formes respiratoires sévères du COVID-19 hospitalisés dans les unités COVID à Robert Ballanger entre le 28 février et le 31 mai 2020 ont été inclus. La forme sévère est définie par une SpO2 ≤ 96 % malgré une oxygénothérapie ≥ 6 L/min pendant plus de 6 heures. Ont été exclus les patients admis en service de réanimation ou ceux restés aux portes. À partir de cette cohorte une étude cas-témoins rétrospective a cherché à comparer la survie sans intubation des patients n'ayant pas reçu le tocilizumab versus ceux qui l'ont reçu (posologie de 400 mg dose unique) à l'aide de trois méthodes statistiques : appariement sur le score de propension, survie en multivariée de Cox et analyses de pondération du score de probabilité inverse. Le critère de jugement principal était la survie sans intubation à 28 jours. Résultats 246 patients ont été inclus (106 traités par tocilizumab). Ils étaient âgés de 67,6 ± 15,3 ans, dont 95 (38,5 %) de femmes. Le délai entre les premiers symptômes et l'inclusion était de 8,4 ± 4,5 jours. 105 (42,7 %) patients n'ont pas survécu sans intubation dans les 28 jours dont 71 (28,9 %) décès. Parmi cette cohorte nous avons obtenus 84 paires de patients comparables. Dans la cohorte appariée (n = 168), le tocilizumab était associé à une meilleure survie sans incubation (hazard ratio (HR) = 0,49 (intervalle de confiance à 95 % (95CI) = 0,3–0,81), p = 0,005). Ces résultats étaient similaires dans la cohorte globale (n = 246), et l'analyse multivariée de Cox confirme un effet protecteur du tocilizumab sur l'apparition du critère de jugement principal (HR ajusté = 0,26 (95CI = 0,135–0,51, p = 0,0001), tout comme l'analyse IPSW (p < 0,0001). Des analyses sur la mortalité seule avec un suivi de 28 jours ont donné des résultats similaires. Conclusion Dans cette étude rétrospective, le tocilizumab à dose unique a été associé à une amélioration de la survie sans ventilation mécanique chez les patients atteints de COVID-19 sévère.

Effects of Covid19 Pandemic on Quality of Life in Patients with Newly Diagnosed Sarcoma in a Referral Centre in Italy: Results from the Sarcord Study (Cometa Project)

Background: Sarcomas are extremely rare and disabling tumours causing physical impairments as well as psychological issues. The Health-related quality of life (HRQoL) in these patients (pts) is impaired as a consequence of their illness and its treatments. It is widely demonstrated the harmful impact of covid19 pandemic and its effects on the HRQoL of the general population and especially on cancer pts. We investigated this important aspect in sarcoma pts. Material (patients) and Methods: We performed a retrospective observational study including pts with diagnosis of soft tissue (STS) and bone sarcoma (BS) referred to Regina Elena National Cancer Institute in Rome and with histological diagnosis obtained during the year preceding (Control group-Ctg) or following (Covid group-Covg) the start of covid19 lockdown in Italy (March 9th 2020). Patients were evaluated with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), with scores analysed as continuous scales, and with the Distress Thermometer (DT), where the pts were accounted for as having low/ absent (score 0-4) or high distress (5-10). Result(s): We enrolled a total of 115 pts, 76 in the Ctg and 39 in the Covg;43 women and 72 men. Median age was 55 years (range 94-21). In the Ctg and in the Covg respectively, the most common diagnosis was STS (N=52 vs 27) followed by BS (N=24 vs 12). Most pts had a localized disease at diagnosis (N=64 vs 34) and only 17 (N=12 vs 5) had distant metastasis. The first treatment received was surgery in 75 pts (N=52 vs 23), chemotherapy in 30 pts (N=18 vs 12), concomitant chemo-radiotherapy in 4 pts (N=3 vs 1), and 6 pts (N=3 vs 3) had a follow-up strategy. In the Covg, compared with the Ctg, we found a decline in Social functioning (average score (mu)=81,64;SD=30,54 vs 91,38;SD=16,24 respectively;p=0,027) as well as an increase in financial difficulties (mu=11,95;SD=22,31 vs 3,93;SD=13,29;p=0,017) and increased nausea (mu=5,13;SD=13,31 vs 1,12;SD=4,24;p=0,018). We also found a higher rate of patients with emotional distress in the Covg (50% vs 71,8% p=0,025). Worsening, although not statistically significant, was observed in almost all questionnaire domains. Conclusion(s): Our study suggests that the covid19 pandemic had a detrimental effect on HRQoL in sarcoma patients. This study makes an effort on the strong need of improvement psychological support for both emotional and physical effects in our pts.

Shifting towards Antifragile Critical Infrastructure Systems

Antifragility, which is an evolutionary understanding of resilience, has become a predominant concept in academic and industrial fields as the criticality of vital infrastructures (like healthcare and transportation) has become more flexible and varying due the impact of digitization and adverse circumstances, such as changing the prioritization of industrial services while accelerating IoT (Internet of Things) deployment during the COVID-19 pandemic. The crucial role of antifragility is to enable critical infrastructures to gain from disorder to foster their adaptability to real unexpected environmental changes. Thus, this paper aims to provide a comprehensive survey on the antifragility concept while clarifying the difference with the resilience concept. Moreover, it highlights how the COVID-19 crisis has revealed the fragility of critical infrastructures and unintentionally promoted the antifragility concept. To showcase the main concepts, we adopt the blockchain as an example of an antifragile system.

Caractéristiques des patients présentant des infections sévères à SARS-CoV-2 avec des auto-anticorps neutralisant les Interférons de type I et étude de l'impact des anti-IL6

Les interférons (IFN) de type I jouent un rôle important dans l'immunité protectrice contre le SARS-CoV-2. La présence d'auto-anticorps (auto-Ac) neutralisant les IFN de type I est significativement associée à des atteintes de COVID-19 critiques ou sévères. Nous avons cherché à évaluer la prévalence et l'impact clinique des auto-Ac anti IFN de type I et du tocilizumab en Seine-Saint-Denis sur le pronostic des patients. Nous avons testé la présence d'auto-Ac neutralisants contre les IFN de type I chez des patients préalablement identifiés pour une pneumonie sévère au COVID-19 hospitalisés au printemps 2020 dans les services de médecine de l'hôpital Robert Ballanger d'Aulnay sous-bois. Il s'agissait d'une cohorte comprenant tous les patients hospitalisés entre début mars et fin avril 2020 ayant nécessité 6 litres ou plus d'oxygène pour une infection SARS CoV-2. Au sein de cette cohorte, les patients ayant encore des prélèvements sériques disponibles en sérothèque ont été testés pour rechercher les auto-Ac et nous avons étudié en parallèle leurs caractéristiques cliniques et pronostiques. Parmi les 246 patients, seuls 139 avaient encore un prélèvement sérique disponible en sérothèque lors de la réalisation de l'étude. Nous avons trouvé des auto-anticorps circulants présentant une activité neutralisante vis-à-vis des IFN de type I chez 7,9 % des patients (11 sur 139). La présence d'auto-Ac neutralisants était associée à un risque accru de mortalité et ces auto-Ac ont été détectés chez 21 % des patients décédés d'une pneumonie au COVID-19. La technique Gyros a trouvé que 107/139 (77 %) des patients présentaient des anticorps anti IFN. Cette méthode n'était donc pas performante pour identifier une activité neutralisante des anticorps. Un kit ELISA commercial a également été évalué pour la détection des auto-Ac anti-IFN-alpha et des titres élevés d'anticorps par cette technique étaient bien corrélés à l'activité neutralisante. De façon intéressante, le taux de mortalité parmi les patients présentant des auto-Ac est de 100 % (5/5) chez les patients n'ayant pas reçu de tocilizumab versus 17 % 1/6) chez les patients traités par tocilizumab (p < 0,001). Parmi les 128 patients n'ayant pas d'anticorps neutralisants, le taux de mortalité entre les patients traités par tocilizumab 16 % (12/74) versus ceux non traités 20 % (11/54) ne présentait pas de différence significative (p = 0,64). Ces résultats confirment l'importance de la voie IFN-I dans la défense contre l'infection par le SARS-CoV-2. La détection des auto-Ac neutralisants contre les IFN de type I est associée à une plus grande mortalité. Le tocilizumab pourrait avoir une efficacité chez ces patients. Ces résultats nécessitent néanmoins d'être confirmés sur des échantillons de patients plus importants. (French) [ FROM AUTHOR] Copyright of Revue de Médecine Interne is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Effect of hydroxychloroquine on endothelial function in older adults with moderate-severe sleep apnea: A randomized clinical trial

Introduction: Obstructive sleep apnea (OSA) is considered a low-grade chronic inflammatory disease. OSA impairs endothelial function and increases cardiovascular mortality. Hydroxychloroquine (HCQ), an antiinflammatory drug, seems to reduce cardiovascular mortality. In animal and in vitro models, HCQ improved endothelial function. Its effects on endothelial function of patients with OSA is unknown. Hypothesis: Hydroxychloroquine can improve endothelial function in patients with OSA. Methods: Adults older than 65 years with an apnea-hypopnea index (AHI) greater than 15 events/hour were allocated to receive either 400mg of HCQ or placebo daily for eight-weeks. The randomization was computer-generated and pharmacycontrolled. Participants and outcome evaluators were blinded to the group allocation. Home sleep apnea test and measurements of flow-mediated dilation of brachial artery (FMD) and peripheral artery tonometry (PAT) were performed at baseline and follow-up in a research facility. The primary outcomes were the change in FMD (Δ%FMD) and change in PAT reactive-hyperemia index (ΔRHI). Change in AHI (ΔAHI) was a secondary outcome. Generalized estimating equations were used to verify time∗group interaction. Results: Fourteen patients were assigned to the HCQ group and fifteen patients to the placebo group between April 2019 and May 2020 with no losses to follow-up. The recruitment was interrupted due to COVID-19 pandemic. Mean Δ%FMD was 0.35 (95% CI -4.26 to 4.97) in placebo group and 0.48 (95% CI -4.08 to 5.04) in HCQ group. Mean ΔRHI was 0.02 (95% CI -0.11 to 0.07) in placebo group and 0.05 (95% CI -0.24 to 0.13) in HCQ group. Mean ΔAHI was 7 (95% CI -1 to 15) in placebo group and -4 (95% CI -11 to 2) in HCQ group. P values for time∗group interaction were 0.97, 0.74 and 0.04, respectively. No important adverse events have occurred. Conclusions: In this trial, HCQ did not improve endothelial function measured by FMD and PAT in older adults with OSA. A slight but significant reduction in AHI was observed in HCQ group, suggesting that some specific inflammatory mechanisms participate in OSA causation that could become a future therapeutic approach.