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CONTEXT: Endocrine therapy combined with CDK4/6 inhibitor is the standard frontline treatment for the vast majority of HR+/HER2- metastatic breast cancer (MBC) patients. Despite an overall survival benefit, patients eventually progress and mechanisms of resistance to this combination are not well identified. Non-invasive monitoring of the efficacy of treatment could help into tailoring therapeutic regimen. Extracellular vesicles (EVs) are a group of heterogeneous nanosized bioparticles (30-1000nm), released by almost all cell types - including tumor, platelets, and immune cells – carrying informative biological material emanating from the mother cell and circulating in the blood stream. In this project, we ambition to assess whether the vesiclemia, i.e. plasmatic extracellular vesicle concentration can be used as a clinic-biological parameter to assist in the monitoring of patients. METHODS: EPICURE is an ongoing pilot prospective cohort study of heterogeneous and massive data integration, i.e. multi-omics approaches in MBC patients. The present study focused on patients with HR+/HER2- MBC receiving frontline endocrine therapy+iCDK4/6. Plasma samples were drawn every 3 months during the treatment until progression. The workflow for the enrichment of circulating EVs was developed from frozen plasma. A semi-automatized isolation procedure using size exclusion chromatography combined with the newly developed interference light microscopy apparatus Videodrop allowed to routinely separate plasmatic EVs and quantify vesiclemia in a fast and reliable manner for a large number of samples (longitudinal follow-up of MBC patients). RESULTS: 26 patients were included and monitored for vesiclemia. Median age was 58.5y (±13.7). Metastatic disease sites were distributed as follows: bone metastases (21; 84%), liver (21; 84%), thoracic (10; 40%), node (2; 8%), brain (1; 4%), others (2; 8%). Endocrine therapy included aromatase inhibitors (20; 77%), fulvestrant (6; 29%), GnRH agonists (5; 19%) and CDK4/6 inhibitors palbocilib (15; 57%), abemaciclib (8; 31%) and ribociclib (3; 11%). With a median follow-up time of 22.1 months (95%CI 21.2 - not reached), median progression free survival was 21.8 months (95%CI 18.1 - not reached). Median time on treatment was 19.4 months (IQR 11.6 - 22.1). Objective response rate was confirmed in 12 patients (6 with complete response). Out of the 26 patients, 12 stopped the frontline treatment due to disease progression. 135 longitudinal follow-up samples were analyzed for EVs. All patients who progressed rapidly after treatment initiation (i.e median PFS< 6 months) had an increased vesiclemia at the months 2 and 6 after inclusion. Conversely, patients who had a median PFS >18m had a stable vesiclemia during this period. CONCLUSION This study aims to use circulating EVs as a therapeutic companion to anticipate treatment resistance and tumor progression in MBC patients. Our preliminary data suggest that the vesiclemia could be used as a predictive tool to anticipate treatment failure, and thus might be used to tailor treatments in time. Citation Format: Mathilde Richard, Jean Sebastien FRENEL, Laurent Mathiot, Mario Campone, Mathilde Colombie, Marie Robert, Anne Patsouris, Frederic Bigot, Julie Gavard, Gwennan André-Grégoire, Laetitia Guevel. Extracellular vesicle-based biomarker assay for the monitoring of the efficacy of frontline endocrine therapy + CDK4-6 inhibitors in metastatic breast cancer. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-11-09.

Plant cell culture technology serves as an effective alternative system for in vitro production of bioactive molecules, as it allows for the exploration of valuable compounds under a controlled environment. The present study was conducted to evaluate the effect of plant growth regulator (PGR); 2,4-dichlorophenoxyacetic acid (2,4-D) on the expression of compounds in coloured callus of Capsicum frutescens, a vital spice in various cuisines worldwide. The differential accumulation of compounds in the callus was analysed using liquid chromatography-mass spectrometry (LCMS) and the PGR concentration that resulted in the highest accumulation of the valuable compounds was identified. In this study, calli of various colours (cream, yellow and green) were successfully produced from C. frutescens through plant tissue culture. The increase in 2,4-D concentrations was found to increase callus growth index (GI) and specific growth rate (Sg), where the highest GI (0.5690) and Sg (0.6348 mg/week) were observed in callus produced in media supplemented with 0.5 mg/L 2,4-D. LCMS data analyses showed that 19 compounds were detected in the callus, with 8 compounds (fatty acids and phenolics) were successfully identified, while the remaining 11 compounds were reported as unknowns. Yellow-coloured callus was observed to contain the highest number of compounds (18 compounds), while green callus contained the least (14 compounds). This analysis provides valuable information on the application of biotechnological tools such as plant tissue culture as an alternative for sustainable production of compounds with high bioactivity in Capsicum frutescens.

Identification of tumours harbouring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. Our objective was to develop a reliable and stable scoring system to identify those immunologically active tumours.Using gene expression profiles of 421 HNSCC, we developed a score to identify immunologically active tumours. Validation of the 'HOT' score was done in 40 HNSCC and 992 NSCLC. Stability of the 'HOT' score was tested in paired HNSCC samples from diagnostic biopsies versus surgically resected specimens, untreated versus recurrent samples, and pre-versus post-cetuximab samples in a total of 76 patients. The association between the 'HOT' score with overall survival (OS) and progression-free survival (PFS) was tested in 184 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors.A 27-gene expression based 'HOT' score was correlated with: (i) PD-L1 and IDO1 expression, (ii) TCD8 infiltrate and (iii) activation of the IFN-γ pathway. The HOT score concordance when comparing diagnostic biopsies and surgically resected specimens was higher than in untreated samples versus recurrent or pre-versus post-cetuximab samples. In 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors, the HOT score was associated with an improved OS and PFS in multivariate analysis.The 'HOT' score is a simple and robust approach to identify real-world patients with HNSCC and NSCLC immunologically active tumours who may benefit from PD-1/PD-L1 inhibitors.

Approximately a third of Malaysian adult has been diagnosed with hypertension. This study aimed to investigate the prevalence and key risk factors of hypertension in a community living in a rural area of Kudat, Sabah. Methods: The study included participants of at least 18 years old, able to communicate in the local dialect, no mental disability, not pregnant or lactating and no known cause of secondary hypertension. Sociodemographic data were recorded in addition to assessment of depression, anxiety, stress, and dietary salt of the participants using standard DASS-21 questionnaire (Depression Anxiety Stress Scales standard questionnaire) questionnaire. Multiple logistic regression analyses were used to assess the association of hypertension and health-related variables predicted to be a risk factor. Results: Out of 111 participants, 30% were diagnosed with hypertension of which 60.6% were not aware of their health condition. Among the variables analyzed, higher age (at least 40 years old) and excess BMI (≥23.0) highly contributed to the predisposition of hypertension (p0.05). Conclusion: The community in Kudat, as a representation of the rural population in Sabah, has a high prevalence of hypertension, implying that lifestyle changes and regular health checks are effective interventions to minimise the risk of hypertension.

Epithelial-to-mesenchymal transition (EMT) is associated with tumor aggressiveness, drug resistance, and poor survival in non-small cell lung cancer (NSCLC) and other cancers. The identification of immune-checkpoint ligands (ICPLs) associated with NSCLCs that display a mesenchymal phenotype (mNSCLC) could help to define subgroups of patients who may benefit from treatment strategies using immunotherapy.We evaluated ICPL expression in silico in 130 NSCLC cell lines. In vitro, CRISPR/Cas9-mediated knockdown and lentiviral expression were used to assess the impact of ZEB1 expression on CD70. Gene expression profiles of lung cancer samples from the TCGA (n = 1018) and a dataset from MD Anderson Cancer Center (n = 275) were analyzed. Independent validation was performed by immunohistochemistry and targeted-RNA sequencing in 154 NSCLC whole sections, including a large cohort of pulmonary sarcomatoid carcinomas (SC, n = 55).We uncover that the expression of CD70, a regulatory ligand from the tumor necrosis factor ligand family, is enriched in mNSCLC in vitro models. Mechanistically, the EMT-inducer ZEB1 impacted CD70 expression and fostered increased activity of the CD70 promoter. CD70 overexpression was also evidenced in mNSCLC patient tumor samples and was particularly enriched in SC, a lung cancer subtype associated with poor prognosis. In these tumors, CD70 expression was associated with decreased CD3Our results provide evidence on the pivotal roles of CD70 and ZEB1 in immune escape in mNSCLC, suggesting that EMT might promote cancer progression and metastasis by not only increasing cancer cell plasticity but also reprogramming the immune response in the local tumor microenvironment.

Background Hypofractionated stereotactic radiotherapy (hFSRT) is a salvage option for recurrent glioblastoma (GB) which may synergize anti-PDL1 treatment. This phase I study evaluated the safety and the recommended phase II dose of anti-PDL1 durvalumab combined with hFSRT in patients with recurrent GB. Methods Patients were treated with 24 Gy, 8 Gy per fraction on days 1, 3, and 5 combined with the first 1500 mg Durvalumab dose on day 5, followed by infusions q4weeks until progression or for a maximum of 12 months. A standard 3 + 3 Durvalumab dose de-escalation design was used. Longitudinal lymphocytes count, cytokines analyses on plasma samples, and magnetic resonance imaging (MRI) were collected. Results Six patients were included. One dose limiting toxicity, an immune-related grade 3 vestibular neuritis related to Durvalumab, was reported. Median progression-free interval (PFI) and overall survival (OS) were 2.3 and 16.7 months, respectively. Multi-modal deep learning-based analysis including MRI, cytokines, and lymphocytes/neutrophil ratio isolated the patients presenting pseudoprogression, the longest PFI and those with the longest OS, but statistical significance cannot be established considering phase I data only. Conclusion Combination of hFSRT and Durvalumab in recurrent GB was well tolerated in this phase I study. These encouraging results led to an ongoing randomized phase II. (ClinicalTrials.gov Identifier: NCT02866747).

Within the biodiversity hotspot of the West Indies, Guadeloupe presents a remarkable plant biodiversity. The strong urbanization along its rivers leads to the alarming degradation of their banks through artificialization and proliferation of invasive alien species.Since 2015, the "PROTEGER" project, led by the Guadeloupe National Park and involving INRAE and the University of the West Indies, and funded by the European Union and the French Biodiversity Agency, has been promoting and developing the use of native species and copying natural models to restore riparian ecosystems using soil bioengineering techniques. The first phase of the project (2016-2018) characterized 12 types of Guadeloupe's riparian forests and identified 80 native species potentially suitable for riparian restoration. The second phase of the project (2019-2022) focused on the control of the multiplication of 26 of these species, and their use on bank protection and restoration sites. An experiment on cuttings was conducted on 21 native species (9 tree 4 shrub species; and 8 herbaceous species), another on the germination and growth of seedlings of 5 species of tree legumes. The first soil water bioengineering demonstration projects was implemented along a riverbank through a training course. The third phase to come aims to disseminate the knowledge to local stakeholders and the development of a local economic sector of nurseries and specialized companies.This project allows the improvement of scientific knowledge of Guadeloupean riparian environments and the development of innovative techniques for the restoration and protection of these environments using local plant species. This project associates managers and researchers in a global approach for the development of a sustainable sector of ecological engineering on the Guadeloupean territory.

The coastal environment is meeting numerous anthropogenic changes especially with the increased implementation of bottom-fixed Offshore Wind Farms. Few feedbacks are available for these recent infrastructures facing a complex turbulent marine environment made of combined waves and currents. In the presence of a pile, strong hydrodynamical eddies structures form that are responsible for the scour process which may lead to the failure of the wind turbine. Former two-phase flow simulations of this problem [1] have been performed using the Reynolds-Averaged Navier-Stokes approach for turbulence modelling and they have shown some limitations to reproduce the main features of the scour process. Turbulence modelling was argued to be the major bottleneck. In order to further investigate this problem, an extensive study of the numerical simulation of the flow hydrodynamic around a wall-mounted cylinder has been carried out using a hierarchy of turbulence models including RANS, hybrid RANS-LES and LES. The range of Reynolds numbers is too large to allow for a well-resolved LES and therefore hybrid RANS-LES is essential to reproduce main hydrodynamical features at an affordable cost. In this study we evaluated the k-omega SST model coupled with the Improved Delayed Detached Eddy Simulation [2] and the Scale-Adaptative Simulation [3]. All the simulations have been performed using OpenFOAM an open-source Computational Fluid Dynamics toolbox. Our simulations suggest that the k-ω SST SAS is the best model for this configuration. It has been adapted for the two-phase flow Eulerian-Eulerian approach and implemented in sedFOAM [4]. Preliminary results of the two-phase simulation of Roulund and co-worker experiments [5] shows very encouraging results in terms of morphological features at short-time scales. These results will be presented during the conference together with in-depth analysis of the sediment transport fluxes.References[1] Nagel T., Chauchat J., Bonamy C., Liu X., Cheng Z. and Hsu T. - J., Three-dimensional scour simulations with a two-phase flow model, Advances in Water Resources (2020).[2] M. S. Gritskevich, A. V. Garbaruk, J. Schütze and F. R. Menter, Development of DDES and IDDES Formulations for the k-ω SST Model, Flow Turbulence Combust (2012).[3] F. R. Menter and Y. Egorov, A scale-adaptative simulation model using two-equation models, American Institute of Aeronautics and Astronautics Paper (2005).[4] J. Chauchat, Z. Cheng, T. Nagel, C. Bonamy, and T.-J. Hsu, Sedfoam-2.0: a 3-d two-phase flow numerical model for sediment transport, Geoscientific Model Development (2017).[5] Roulund A., Sumer B. M., Fredsøe J. and Michelsen J., Numerical and experimental investigation of flow and scour around a circular pile, Journal of Fluid Mechanics (2005).

Introduction: Endoxifen exposure, the most active metabolite of tamoxifen, may be a better predictor of tamoxifen efficacy, than CYP2D6 genotypes. However, conflicting results have been reported so far. We evaluated prospectively the impact of 5 weeks of pre-operative tamoxifen on Ki-67 levels in early-stage breast cancer (EBC) patients. We correlated CYP2D6 genotype, exposure of tamoxifen and its metabolites with long-term outcome. Patients and methods: TAM pre-op was an open-label, multicentre, phase 2 trial in which pre and postmenopausal women with WHO performance status 0-1 and HR+ HER2-, operable breast cancer were given tamoxifen (20mg per day orally) for 5 weeks before surgery. Adjuvant treatments were given as standard practice. CYP2D6 genotype was determined at initiation. Plasma concentrations of tamoxifen and its main metabolites (N-desmethyltamoxifen, Z-endoxifen, and Z-4-hydroxytamoxifen) were assessed at baseline (b), week 2 (w2) and week 5 (w5) of treatment, using a validated performed LC-MS/MS method. AUCs, used as marker of exposure, were computed with Monolix© (Lixoft, Antony, France). Tumour Ki-67 variations between baseline (Ki-67b) and w5 (Ki-67w5) were determined to assess the sensitivity to tamoxifen. We used a pre-defined 10% cut-off to dichotomize low versus high Ki-67. All these parameters were associated with disease free survival by Cox regression analyses. Results: Out of the 136 patients enrolled, 98 pts had paired Ki-67 values evaluable. With a median follow up of 78 months (IQR 58-95), 14/136 women had cancer recurrence (12 distant and 2 contralateral) with the proportion free from cancer recurrence at 5 years of 90% (95% CI 83-94). Ki-67b, Ki-67w5 and variations between baseline and week 5 were not associated with DFS. Endoxifen AUC was correlated with CYP2D6 genotype (normal/hyper metabolizer versus low metabolizer) but CYP2D6 genotype was not predictive for DFS (adjusted hazard ratio, 2.24; 95% CI, 0.29 to 17.37; P = 0.44). Endoxifen AUCs at w2 and w5 were similar in patients with low Ki67b and low Ki67w5 (low-low) (n=36), low Ki67b and high Ki67w5 (n=12), high Ki67b and low Ki67w5 (n=14) and high Ki67b and high Ki67w5 (n=30). However, low endoxifen AUC at w5 was a pejorative factor of disease free survival: 5 years PFS 81.8% vs 90.3% (HR 2.70, CI 95% [1.04-7.06], p=0.04). Conclusion: This prospective clinical study shows that endoxifen exposure at w5 of pre-operative tamoxifen is associated with DFS in patients with HR+/HER2- EBC. Translationnal studies are ongoing. N°EUDRACT 2008-007652-10. Citation Format: Jean-Sebastien Frenel, Loic Campion, Antonin Schmitt, Patricia De Cremoux, Elsa Rossignol, Celine Renaudeau, Marie Robert, Jean-Marie Bard, Christine Bobin-Dubigeon, Mario Campone. Endoxifen exposure after 5 weeks of preoperative tamoxifen is predictive of long-term outcome of operable hormone receptor positive (HR+) HER2 - early breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-07-06.

Background: The management of HER2+ BC has changed dramatically with the introduction and widespread use of HER2-targeted therapies, especially in the adjuvant setting. It is well-known that de novo metastatic HER2+ breast cancer patients have better outcomes that women with metastatic relapse. This could be related both to a lead time bias, as well as to an ATRESS (adjuvant therapy-related shortening of survival) phenomenon [1]. Indeed, cancer treatments induce increased both clonal selection, as well as globally tumor resistance and agressivity [2]. However, there is relatively limited real-world information on the impact of adjuvant and neoadjuvant anti-HER2 targeted treatments on patterns of recurrence and outcomes of HER2+ MBC. Thus, the purpose of this study was to determine how and how long anti-HER2 targeted treatment in early setting impact outcomes of patients with HER2+ recurring BC. Methods: Since 2014, the 18 French Cancer Centers launched the Epidemiological Strategy and Medical Economics (ESME) program to provide real-world data on MBC patients (pts). All pts who started a 1st-line treatment for MBC between 01-Jan-2008 and 31-Dec-2017 were included. We examined clinical characteristics and outcomes (overall survival [OS] and time to 1st metastasis [TTM]) in patients with HER2+ MBC pretreated with trastuzumab in the (neo)adjuvant setting (aT) compared with trastuzumab-naïve patients and patients with de novo HER2+ MBC. Multivariate analyses adjusted for baseline demographic, prognostic factors, adjuvant treatment received and time to MBC. Results: Among the 23698 pts of the ESME database, 4145 were women treated in 1st line of a HER2+ MBC: 1716 pts (41%) had de novo and 2429 pts (59%) recurrent and 65% had Hormone Receptor (HR) + MBC; 53%, 26% and 21% had respectively 1, 2, or > 2 metastatic sites (64% visceral and 11% brain). With a median follow-up of 60.7 m, median OS is 42.4 m (95% CI: 40.1-45.0) for patients who relapsed. OS is significantly longer in de novo MBC: 64.7 m (95% CI: 60.2-73) (HRadjusted=0.68, 95% CI: 0.62-0.76, p < 0.0001). Among pts with recurrent MBC, 56% (1343) had received adjuvant trastuzumab (aT). As 1st-line therapy for MBC, 86 % of pts received HER2-targeted agents (74% T-based, 24% T-pertuzumab-based). Median TTM was 46.9 months (m): 57.6 m in HR+ and 30.2 m in HR-. Among pts with HR- diseases, 38% relapsed during the first 2 years of follow-up and 30% after 4 years (14.8%% and 56.9% in HR+ respectively). Among pts with recurrent MBC, crude median OS is inferior in pts who received aT, as compared to those who did not: 37.2 m (95% CI: 34.4-40.3) vs. 53.5 m (95% CI: 47.6-60.1), but this difference does not persist after adjustment for age, performans status, disease-free interval and number and type of metastatic sites in the multivariate model (HR=1.05, 95% CI: 0.91-1.22). A short disease-free interval (6-24 months compared to >48) remains, however, a strong adverse prognostic factor (HR=2.1, 95% CI: 1.82-2.50). Conclusions: The receipt of adjuvant trastuzumab does not predict for worse outcomes when adjusted to the other prognostic factors, among patients who relapsed during the 2008-2017 period. An ATRESS phenomenon is not suggested, although we cannot rule it out for those who relapsed within the initial 2 years. The much better prognosis of de novo MBC may be largely linked to lead time biases. Citation Format: Fanny Le Du, Matthieu Carton, Mahasti Saghatchian, David Perol, Barbara Pistilli, Etienne Brain, Delphine Loirat, Laurence Vanlemmens, Thomas Vermeulin, Christelle Levy, Anthony Goncalves, Mony Ung, Marie Robert, Anne Jaffre, Mathieu Robain, Suzette Delaloge, Véronique Dieras. Impact of prior adjuvant trastuzumab (aT) on clinical characteristics, patterns of recurrence and outcomes in 4145 patients with Her2 positive (HER2+) metastatic breast cancer (MBC)- Results from the French ESME UNICANCER program [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-09.

Resume Les maladies multisystemiques, dont la plupart sont en France prises en charge en medecine interne, touchent par definition plusieurs organes ou tissus. Si les atteintes cutanees ou articulaires sont frequentes, les atteintes neurologiques sont souvent synonymes de gravite. Parmi ces dernieres, les atteintes du systeme nerveux peripherique (par exemple : neuropathies) ou du systeme nerveux central (par exemple : myelites) sont generalement de diagnostic aise, a l’aide de l’expertise clinique et d’examens complementaires adaptes. Les atteintes neuropsychologiques, c’est-a-dire touchant le fonctionnement cognitif, et notamment la memoire, l’attention, les fonctions executives ou les capacites de raisonnement, sont de diagnostic plus difficile, parfois banalisees par les cliniciens. Leurs causes sont souvent multiples et intriquees. Pourtant, ces manifestations cognitives sont cruciales dans le retentissement fonctionnel et le ressenti des patients, et sont etroitement liees a leur qualite de vie. Elles affectent ainsi l’insertion sociale, familiale et professionnelle des patients, et peuvent avoir des retentissements sur le suivi medical ou l’observance medicamenteuse. L’objectif de cette mise au point, sur les troubles cognitifs associes au lupus systemique, de leur physiopathologie a leur prise en charge, est de sensibiliser les medecins internistes aux manifestations cognitives des maladies multisystemiques, a leur prise en charge diagnostique et therapeutique, ainsi que de catalyser les futurs efforts de recherche et de mise en place de parcours de soins pour les patients suivis en medecine interne presentant des difficultes cognitives.

Since the outbreak of COVID-19, numerous studies from around the world have reported declines in mental health. However, most of these studies were of low-to-moderate quality and many were based on convenience samples or used mental health measures with low validity, or both. Consequently, it has been difficult to draw conclusions.Both the 2020 Survey on COVID-19 and Mental Health (SCMH) and the Canadian Community Health Survey (CCHS) (2015-2019) used the Patient Health Questionnaire-9 to screen for major depressive disorder (MDD) in adults aged 18 or older. The prevalence of MDD was compared between the SCMH and the CCHS. Risk and protective factors for MDD in the SCMH were examined using bivariate and logistic regression analyses.Based on SCMH data, 15.2% (95% CI: 14.2-16.2) of Canadians screened positive for MDD. The prevalence of MDD was more than two times higher in the SCMH (during COVID-19) than in the CCHS (predating COVID-19). In bivariate analysis, Canadians reporting five or more COVID-19-related risk factors were close to 30 times more likely to have MDD than those reporting no risk factors. Mastery and a sense of community belonging were protective factors for MDD.After remaining stable for two decades, the prevalence of depression among Canadians increased substantially with the onset of COVID-19. Ongoing monitoring of this common condition associated with major morbidity is vital to determine if elevated levels of MDD persist as we progress through and beyond future waves of COVID-19.Depuis le début de la pandémie de COVID 19, de nombreuses études à l’échelle mondiale ont fait état d’une détérioration de la santé mentale. Toutefois, la plupart de ces études sont de qualité faible ou moyenne, et bon nombre d’entre elles s’appuient sur des échantillons de commodité ou utilisent des mesures de la santé mentale à faible validité, voire les deux. Par conséquent, il est difficile d’en tirer des conclusions.L’Enquête sur la COVID 19 et la santé mentale (ECSM) de 2020 et l’Enquête sur la santé dans les collectivités canadiennes (ESCC) (2015-2019) ont toutes les deux utilisé le Questionnaire en 9 points sur la santé du patient pour dépister le trouble dépressif majeur (TDM) chez les adultes de 18 ans et plus. On a comparé la prévalence du TDM dans l’ECSM et dans l’ESCC. Dans l’ECSM, on a étudié les facteurs de risque de TDM et les facteurs de protection par analyses bivariées à l’aide de régressions logistiques.Selon les données de l’ECSM, 15,2 % (IC à 95 % : 14,2 à 16,2 %) des Canadiens ont obtenu un résultat positif au dépistage du TDM. La prévalence du TDM était plus de deux fois plus élevée dans l’ECSM (durant la COVID 19) que dans l’ESCC (avant la COVID 19). Dans l’analyse bivariée, les Canadiens ayant déclaré avoir au moins cinq facteurs de risque liés à la COVID 19 étaient environ 30 fois plus susceptibles d’avoir un TDM que ceux ayant déclaré n’avoir aucun facteur de risque. Le sentiment de maîtrise et le sentiment d’appartenance à la communauté se sont révélés des facteurs de protection contre le TDM.Après être demeurée stable pendant 20 ans, la prévalence de la dépression chez les Canadiens a considérablement augmenté depuis le début de la pandémie de COVID 19. Il est essentiel de surveiller de façon continue ce trouble courant qui est associé à une morbidité importante, afin de déterminer si les taux élevés de TDM vont persister pendant et après les différentes vagues de COVID 19.During the second wave of COVID-19 in the fall of 2020, the prevalence of major depressive disorder (MDD) among Canadians aged 18 or older (defined as the proportion screening positive for MDD using the Patient Health Questionnaire-9) was 15% (13% for males and 18% for females). Based on data from eight Canadian provinces, the prevalence of MDD during the fall of 2020 was more than double what it had been in pre-COVID times (16% vs. 7%). A dose-response relationship was observed between MDD and COVID-19-related risk factors for poor mental health. Each increase in the number of COVID-19-related risk factors was associated with an increase the prevalence of MDD, ranging from 2% among those reporting no risk factors to 62% among those reporting five or more risk factors. Mastery, the extent to which individuals perceive they have control over their life circumstances, was strongly associated with MDD. Those with low levels of mastery were 17 times more likely to screen positive for MDD than those with high mastery. Individuals reporting a very weak sense of community belonging were 10 times more likely to screen positive for MDD than those with a very strong sense of belonging.Au cours de la deuxième vague de COVID 19 à l’automne 2020, la prévalence du trouble dépressif majeur (TDM), défini comme la proportion des répondants ayant un résultat positif au dépistage du TDM à l’aide du questionnaire sur la santé du patient (PHQ-9) chez les Canadiens de 18 ans et plus, était de 15 % (13 % chez les hommes et 18 % chez les femmes). D’après les données de huit provinces canadiennes, la prévalence du TDM à l’automne 2020 avait plus que doublé par rapport à la prévalence observée avant la pandémie de COVID (16 % contre 7 %). Une relation dose réponse a été observée entre le TDM et les facteurs de risque liés à la COVID 19 susceptibles d’entraîner une mauvaise santé mentale. Il est à noter que plus le nombre de facteurs de risque liés à la COVID 19 augmente, plus la prévalence du TDM augmente : ainsi, la prévalence du TDM passe de 2 % chez les personnes ne déclarant aucun facteur de risque lié à la COVID 19 à 62 % chez les personnes déclarant avoir cinq facteurs de risque ou plus. Le sentiment de maîtrise, c’est à dire la mesure dans laquelle une personne a l’impression d’exercer un contrôle sur ses conditions de vie, est fortement associé au TDM. Les personnes ayant l’impression d’avoir peu de maîtrise sur leur vie étaient 17 fois plus susceptibles d’obtenir un résultat positif au dépistage du TDM que celles ayant un fort sentiment de maîtrise de leur vie. Par ailleurs, les personnes déclarant avoir un très faible sentiment d’appartenance à la communauté étaient 10 fois plus susceptibles d’obtenir un résultat positif au dépistage du TDM que celles ayant un très fort sentiment d’appartenance.

Introduction Depuis le début de la pandémie de COVID 19, de nombreuses études à l’échelle mondiale ont fait état d’une détérioration de la santé mentale. Toutefois, la plupart de ces études sont de qualité faible ou moyenne, et bon nombre d’entre elles s’appuient sur des échantillons de commodité ou utilisent des mesures de la santé mentale à faible validité, voire les deux. Par conséquent, il est difficile d’en tirer des conclusions. Méthodologie L’Enquête sur la COVID 19 et la santé mentale (ECSM) de 2020 et l’Enquête sur la santé dans les collectivités canadiennes (ESCC) (2015-2019) ont toutes les deux utilisé le Questionnaire en 9 points sur la santé du patient pour dépister le trouble dépressif majeur (TDM) chez les adultes de 18 ans et plus. On a comparé la prévalence du TDM dans l’ECSM et dans l’ESCC. Dans l’ECSM, on a étudié les facteurs de risque de TDM et les facteurs de protection par analyses bivariées à l’aide de régressions logistiques. Résultats Selon les données de l’ECSM, 15,2 % (IC à 95 % : 14,2 à 16,2 %) des Canadiens ont obtenu un résultat positif au dépistage du TDM. La prévalence du TDM était plus de deux fois plus élevée dans l’ECSM (durant la COVID 19) que dans l’ESCC (avant la COVID 19). Dans l’analyse bivariée, les Canadiens ayant déclaré avoir au moins cinq facteurs de risque liés à la COVID 19 étaient environ 30 fois plus susceptibles d’avoir un TDM que ceux ayant déclaré n’avoir aucun facteur de risque. Le sentiment de maîtrise et le sentiment d’appartenance à la communauté se sont révélés des facteurs de protection contre le TDM. Conclusion Après être demeurée stable pendant 20 ans, la prévalence de la dépression chez les Canadiens a considérablement augmenté depuis le début de la pandémie de COVID 19. Il est essentiel de surveiller de façon continue ce trouble courant qui est associé à une morbidité importante, afin de déterminer si les taux élevés de TDM vont persister pendant et après les différentes vagues de COVID 19.

BackgroundIdiopathic inflammatory myopathies (IIMs) are a group of rare acquired muscular diseases. In healthy muscle, myofibers do not express major histocompatibility complex (MHC) class I and II. It was established that MHC-I positive immunostaining, although non-specific, is a marker for IIM diagnosis, while the significance of MHC-II immunostaining remains unclear. The present study investigates the expression of MCH-II in myofibers and capillaries of IIM muscles, taking into account the current IIM classification.Patients & MethodsA historical cohort was designed, including dermatomyositis (DM), inclusion body myositis (IBM), anti-synthetase syndrome (ASyS), immune-mediated necrotizing myopathy (IMNM), or overlap myositis (OM). MHC-II immunostaining was performed on patient muscle sections and was analyzed in a standardized and blind manner.ResultsMuscle sections from biopsies of 72 IIM patients were included: 23 DM, 17 IBM, 12 IMNM, 9 ASyS, and 11 OM. Overall, abnormal MHC-II immunostaining was found in myofibers and/or capillaries in 67 (93%) patients. Myofiber MHC-II immunostaining patterns differed according to the IIM subgroup: the immunostaining was diffuse in IBM (100%), negative in IMNM (75%), perifascicular in ASyS (67%), and either diffuse heterogeneous, clustered, or perifascicular in OM (27%, 27%, and 18%, respectively). MHC-II expression was found in 50% of DM (n=11/22).While all IIM subgroups presented quantitative and qualitative abnormalities of MHC-II immunostaining in capillaries, some subgroups displayed specificities. Most IBM and IMNM muscles presented frequent dilated capillaries (88% and 67%, respectively). DM, ASyS, and OM exhibited high frequencies of capillary lesions, including capillary dropout, leaky capillaries, and dilated capillaries.ConclusionWhile recent expert opinion (EURO-NMD pathology working group) recommended that MHC-II immunostaining of muscle biopsy remains optional, the present work demonstrates that the expression pattern of MHC-II allows to distinguish between several IIM subgroups. Our data argue for the inclusion of MHC-II immunostaining in the routine histological diagnosis for IIMs.

Objectives Idiopathic inflammatory myopathies are mainly defined by inflammatory infiltrates within the muscle (lymphocytes and macrophages). Eosinophil muscle infiltration has been described in idiopathic eosinophilic myositis (IEM) and rarely in EF. This study aimed to further delineate the nosological frame of idiopathic eosinophil muscle infiltration through the exhaustive analysis of IEM and EF patients. Methods This multicentre retrospective case series included IEM patients diagnosed between 2000 and 2022. IEM inclusion criteria were eosinophilic muscle infiltration with myositis pathological features, after the exclusion of differential diagnoses. An additional group of EF patients diagnosed between 2016 and 2022 was constituted. Inclusion criteria were an EF diagnosis and fascia thickening with inflammatory infiltrate. Results A total of 20 IEM cases and 10 EF cases were included. The median (interquartile range) age at diagnosis was 65 (49–70) years; there were 18 males. Data analysis delineated four subgroups: focal EM (FEM, n = 3), diffuse EM (DEM, n = 6), eosinophilic myofasciitis (EMF, n = 11) and EF (n = 10). FEM represented a limited and benign form of myositis. DEM cases presented objective muscle impairment with eosinophilic muscle infiltration. EMF patients presented subjective muscle impairment (myalgia, 55%), fasciitis (on histology and/or imaging), eosinophilic muscle infiltration and frequent hypereosinophilia (55%). EF patients presented myalgia (50%), muscle lesions on histology with fascia-restricted inflammatory infiltrates with (60%) or without (40%) eosinophils. Conclusions The analysis of IEM and EF patient characteristics delineates four subgroups (FEM, DEM, EMF and EF) in terms of clinical, laboratory, imaging, pathological and outcome specificities, and proposes an adapted diagnostic and care management approach.

Background: Atrophic papulosis (AP) is a rare obliterating vasculopathy characterized by specific skin lesions. The etiology and the pathophysiology of the disease remain unclear. The treatment is still empirical, while the malignant form of the disease is associated with a poor prognosis. Summary: The underlying pathogenesis of AP includes three mechanisms with vasculopathy, coagulopathy, and endothelial dysfunction. Benign and malignant forms of AP are described. The benign form is confined to the skin. The pathognomonic skin lesions evolve over time and are large papules with an atrophic porcelain-white center and an erythematous rim. However, systemic involvement can occur months or years after the initial skin features. In this latter case, the associated mortality is very high with a mortality rate of over 65% in some series. Gastrointestinal involvement and central nervous system infarctions are the most frequent causes of death. Treatment is empirical with the use of antiplatelet therapy, anticoagulants, steroids, intravenous immunoglobulins, and immunosuppressive agents. Recent evidence shows that eculizumab, a complement inhibitor, is the most effective therapy in malignant AP with gastrointestinal involvement of the disease and should be combined with treprostinil to prevent relapse.

Introduction During administration of chemotherapies, disconnection presents risks for nurses. Thus, it is recommended to flush the infusion line with solvent to reduce this risk and ensure that the entire dose is administered. Objectives of this study were to evaluate flushing practices and to investigate the efficiency of flushing, according to the type of hospitalization, in hospitalization (HU) or day-care unit (DCU), for three drugs. Methods Twenty secondary infusion lines were collected in five HU and 20 in two DCU. Flushing volumes were estimated by weighing solvent bags. The amount of residual drug was measured for secondary lines by mass spectrometry coupled with high-performance liquid chromatography. Results Chemotherapies were administered by 26 nurses. All of infusion lines contained chemotherapy after flushing. Flushing volumes, residual concentrations and flushing efficiencies were significantly different between these two types of units. In contrast, flushing volumes administrated did not differ between chemotherapy drugs. Conclusions Local recommendations are fully implemented in HU and partially in DCU. The use of small volumes in DCU is related to the patient length of stay, it may, also, be due to omitting the average tubing volume. All infusion lines still contained chemotherapy, including those with a flush volume much higher than recommended, showing that the risk of exposure persists. To achieve a rinse volume greater than 50 mL, it is necessary to use at least 100 mL. It is also important to insist on personal protective equipment and to consider closed safety system for administration.

Background: Immune checkpoint inhibition is an increasingly popular strategy for the management of numerous malignancies. Unfortunately, severe inflammatory toxicities affect up to 60% of patients, often leading to treatment discontinuation in settings where few alternative therapies are available to control disease. Checkpoint inhibitor induced colitis is a common toxicity for which the underlying mechanisms are poorly defined. Methods: To better understand the changing colon-specific and peripheral immune environments over the course of disease progression and treatment, we collected blood and colon tissue from a Merkel Cell carcinoma patient who developed colitis after treatment with pembrolizumab. We performed 10X Genomics single cell RNA sequencing on samples collected before, during and after checkpoint inhibition and various interventions to mitigate toxicity. Results: We identified both shared and colon-exclusive clonal expansion of T cells defined by distinct transcriptional programs, including cytotoxicity, memory, and proliferation markers, at various stages of the disease process. These clones decreased dramatically in the colon after infliximab and vedolizumab therapies. Conclusions: We identified several distinct T cell subsets as potential drivers of colitis in the colon. T cell clones that potentially recognize colonic tissue with a high degree of specificity can be harnessed for therapeutic intervention. Our findings emphasize the need for a more detailed understanding of the immune environment in the colon and suggest the potential for peripheral blood as a readout for immune activity during CPI treatment. Citation Format: Jacqueline E. Mann, Liliana Lucca, Matthew Austin, Ross D. Merkin, Lilach Aizenbud, Kevan Herold, Marie Robert, Harriet M. Kluger. Single cell RNA sequencing defines dynamic immune cell subsets in serial colon and peripheral blood samples in a patient with checkpoint inhibitor-induced colitis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2268.