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Because Systemic Lupus Erythematosus (SLE) is a rare disease, and due to the significant prognostic impact of early management, a diagnosis confirmed by a physician with experience in SLE is recommended, for example from an expert center. Once the diagnosis is confirmed, existing manifestations should be identified in particular, renal involvement by an assessment of proteinuria, disease activity and severity should be determined, potential complications anticipated, associated diseases searched for, and the patient's socioprofessional and family context noted. Therapeutic management of SLE includes patient education on recognizing symptoms, understanding disease progression as well as when they should seek medical advice. Patients are informed about routine checkups, treatment side effects, and the need for regular vaccinations, especially if they are receiving immunosuppressive treatment. They are also advised on lifestyle factors such as the risks of smoking, sun exposure, and dietary adjustments, especially when they are receiving corticosteroids. The importance of contraception, particularly when teratogenic medications are being used, and regular cancer screening are emphasized. Support networks can help relieve a patient's isolation. The first-line medical treatment of SLE is hydroxychloroquine (HCQ), possibly combined with an immunosuppressant and/or low-dose corticosteroid therapy. The treatment of flares depends on their severity, and typically involves HCQ and NSAIDs, but may be escalated to corticosteroid therapy with immunosuppressants or biologic therapies in moderate to severe cases. Because there is no curative treatment, the goals of therapy are patient comfort, preventing progression and flares, and preserving overall long-term health and fertility. The frequency of follow-up visits depends on disease severity and any new symptoms. Regular specialized assessments are necessary, especially when treatment changes, but a frequency of every 3 to 6 months is recommended during periods of remission and monthly during active or severe disease, especially in children. These assessments include both clinical and laboratory tests to monitor complications and disease activity, with specific attention to proteinuria., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: The definition of Takayasu arteritis (TAK) remission and disease activity is still unclear. Vascular imaging is an essential tool for following-up patients. Herein, we aimed to compare the evolution of vascular lesions (ie vessel wall thickening and stenosis) under conventional disease-modifying anti-rheumatic drugs (cDMARDs) relatively to biological DMARDs (bDMARDs) in TAK patients followed with the same CT angiography modalities., Method: We compared 75 lines of therapy in TAK patients who received cDMARDs (n = 40 lines) and bDMARDs (n = 35 lines) using CT angiography. We established 1-3 main target vessels with vessel wall thickening and/or stenosis. Every targeted vessel had its thickness and its lumen diameter measured at the initiation of immunosuppressive treatment and at 12 months., Results: We observed an overall reduction of arterial wall thickness in 73% of cases and 31% had >25% of wall thickness relative decrease. Using a linear mixed effects model, first line immunosuppressive therapy (p= 0.012) and bDMARDs relatively to cDMARDs (p= 0.026) were independently associated with vessel wall thickness reduction in TAK. Thirty-eight percent of the stenotic vessels had a > 25% relative increase in lumen diameter under immunosuppressive therapy. The relative increase >25% in lumen diameter was noted in 56% vs 17% with bDMARDs compared with cDMARDs., Conclusion: Immunosuppressive treatments can reduce arterial wall thickness and widen lumen diameter in TAK. bDMARDs seems to be more effective than cDMARDs to improve arterial lesions in TAK., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In the field of complex autoimmune diseases such as systemic lupus erythematosus (SLE), systems immunology approaches have proven invaluable in translational research settings. Large-scale datasets of transcriptome profiling have been collected and made available to the research community in public repositories, but remain poorly accessible and usable by mainstream researchers. Enabling tools and technologies facilitating investigators' interaction with large-scale datasets such as user-friendly web applications could promote data reuse and foster knowledge discovery. Microarray blood transcriptomic data from the LUPUCE cohort (publicly available on Gene Expression Omnibus, GSE49454), which comprised 157 samples from 62 adult SLE patients, were analyzed with the third-generation (BloodGen3) module repertoire framework, which comprises modules and module aggregates. These well-characterized samples corresponded to different levels of disease activity, different types of flares (including biopsy-proven lupus nephritis), different auto-antibody profiles and different levels of interferon signatures. A web application was deployed to present the aggregate-level, module-level and gene-level analysis results from LUPUCE dataset. Users can explore the similarities and heterogeneity of SLE samples, navigate through different levels of analysis, test hypotheses and generate custom fingerprint grids and heatmaps, which may be used in reports or manuscripts. This resource is available via this link: https://immunology-research.shinyapps.io/LUPUCE/. This web application can be employed as a stand-alone resource to explore changes in blood transcript profiles in SLE, and their relation to clinical and immunological parameters, to generate new research hypotheses., (© The Author(s) 2024. Published by Oxford University Press.)

Objective: The C reactive protein polymyalgia rheumatica activity score (CRP-PMR-AS) is a composite index that includes CRP levels and was developed specifically for PMR. As treatments such as interleukin-6 antagonists can normalise CRP levels, the erythrocyte sedimentation rate (ESR) of PMR-AS, the clinical (clin)-PMR-AS and the imputed-CRP (imp-CRP)-PMR-AS have been developed to avoid such bias. Our primary objective was to measure the correlation of these activity scores. Our secondary objective was to evaluate the concordance between different cutoffs of the PMR-ASs., Method: Data from the Safety and Efficacy of tocilizumab versus Placebo in Polymyalgia rHeumatica With glucocORticoid dEpendence (SEMAPHORE) trial, a superiority randomised double-blind placebo-controlled trial, were subjected to post hoc analysis to compare the efficacy of tocilizumab versus placebo in patients with active PMR. The CRP-PMR-AS, ESR-PMR-AS, clin-PMR-AS and imp-CRP-PMR-AS were measured at every visit. The concordance and correlation between these scores were evaluated using kappa correlation coefficients, Bland-Altman correlations, intraclass correlation coefficients (ICCs) and scatter plots., Results: A total of 101 patients were included in the SEMAPHORE trial, and 100 were analysed in this study. The correlation between the PMR-ASs was excellent, as the ICC and kappa were >0.85 from week 4 until week 24 (CRP-PMR-AS ≤10 or >10). Bland-Altman plots revealed that the differences between the CRP-PMR-AS and the other threescores were low. The cut-off values for the clin-PMR-AS were similar to those for the CRP-PMR-AS 86% of the time., Conclusion: The correlation between all the PMR-ASs was excellent, reflecting the low weight of CRP. In clinical trials using drugs that have an impact on CRP, the derived activity scores can be used., Trial Registration Number: NTC02908217., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: NJ-C declares personal consulting fees from Otsuka and AstraZeneca, personal speaking fees from GSK and Otsuka, and personal payment for expert testimony from Otsuka. LC declares research grants paid to his institution from AstraZeneca and GSK, personal consulting fees from Novartis and AstraZeneca, and personal speaking fees from GSK and Novartis.

Objectives: To estimate prevalence, incidence and mortality rates, and annual healthcare costs of primary Sjögren's syndrome (pSS) and SS associated with other autoimmune disorders (SS+AID) in France., Methods: French national healthcare claims-based study within the prospective Système National des Données de Santé database that includes the majority of the French population. An algorithm was developed to identify patients with SS and SS-related healthcare claims were analysed between 2011 and 2018., Results: Overall, 23 848 patients with pSS and 14 809 with SS+AID were identified. From 2011 to 2018, the prevalence rate increased slightly for pSS (23-32 per 100000) and SS+AID (16-20 per 100 000), with females comprising 90%-91% and 92%-93% of cases, respectively. The incidence rate of SS per 100 000 persons decreased from 2012 (pSS: 4.3; SS+AID: 2.0) to 2017 (pSS: 0.7; SS+AID: 0.3). Mortality rates per 100 000 persons increased from 2012 to 2018 in patients with pSS (0.2-0.8) or SS+AID (0.1-0.5); mean age of death also increased. Artificial tears and hydroxychloroquine were the most common drug reimbursements. Less than half of patients received annual specialist care from a dentist or ophthalmologist. Healthcare costs associated with SS increased from 2011 to 2018 and exceeded the national estimate of expected costs for chronic diseases., Conclusion: In this large French population database study, the low prevalence of pSS confirms that it is an orphan disease. SS is clinically and economically burdensome; these findings may help clinicians better understand routine healthcare received by patients., Competing Interests: Competing interests: RS is a consultant for Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Fresenius Kabi, GlaxoSmithKline, Janssen, Pfizer and Roche. LC is a consultant for Bristol Myers Squibb. GD is a consultant for Bristol Myers Squibb and a consultant with no fees for Roche. JZ and VV-M are employees of and shareholders in Bristol Myers Squibb. VD-P is a consultant for AbbVie, Bristol Myers Squibb and Novartis, and has received grant/research support from Bristol Myers Squibb, Eli Lilly and Roche-Chugai. MB declares no conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Fungal prosthetic vascular graft infections are rare and mainly supra-inguinal. Current guidelines are based on the few studies that have specifically investigated this population, with few risk factors described. The objective of this study is to compare fungal and non-fungal supra-inguinal prosthetic vascular graft infections (PVGI), describing their specificities, identifying risk factors, and evaluating outcomes., Patients and Methods: This is a single-center retrospective cohort study carried out at the Pitié-Salpêtrière Hospital in Paris, including all patients who were treated for a supra-inguinal PVGI between January 1st, 2009 and February 28th, 2021. Preoperative, intraoperative and postoperative data were compared between fungal and non-fungal PVGI., Results: Out of the 475 patients screened, 148 developed a supra-inguinal PVGI: 32 fungal and 116 non-fungal. Factors independently associated with fungal PVGI were presence of a prostheto-digestive fistula (OR 5.98; 95% CI 2.29-15.62) and preoperative antibiotic therapy of seven days or more (OR 2.87; 95% CI 1.12-7.38). Mortality rate at 180 days was significantly higher for fungal as compared to non-fungal PVGIs (38% vs. 16% p = 0.009) and for fungal PVGI with prostheto-digestive fistula. However, there was no statistically significant relation between mortality due to prostheto-digestive fistula in contrast with fungal PVGI alone (p = 0.21)., Conclusion: Prostheto-digestive fistula was strongly associated with fungal PVGI, which leads us to suggest that in such cases, an anti-fungal agent should be prescribed., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The optimal surgical treatment for extended thoracoabdominal aortic aneurysms (TAAAs) is still a matter of debate. The historical treatment is open repair (OR), but over the past fifteen years, endovascular strategies have gained widespread acceptance. Although several endovascular techniques have been described for the treatment of TAAAs, fenestrated and branched stent grafts (F/BEVARs) are the most frequently used and best documented. They have become the first-line treatment for both high- and moderate-risk surgical patients in most vascular centers. However, no randomized study comparing OR and F/BEVAR has been published, and decision-making is mainly based on the physician's preference and/or hospital expertise. The objective of this manuscript is to provide an overview of current comparative data for OR and F/BEVAR.

Background: Feature selection is a critical step for translating advances afforded by systems-scale molecular profiling into actionable clinical insights. While data-driven methods are commonly utilized for selecting candidate genes, knowledge-driven methods must contend with the challenge of efficiently sifting through extensive volumes of biomedical information. This work aimed to assess the utility of large language models (LLMs) for knowledge-driven gene prioritization and selection., Methods: In this proof of concept, we focused on 11 blood transcriptional modules associated with an Erythroid cells signature. We evaluated four leading LLMs across multiple tasks. Next, we established a workflow leveraging LLMs. The steps consisted of: (1) Selecting one of the 11 modules; (2) Identifying functional convergences among constituent genes using the LLMs; (3) Scoring candidate genes across six criteria capturing the gene's biological and clinical relevance; (4) Prioritizing candidate genes and summarizing justifications; (5) Fact-checking justifications and identifying supporting references; (6) Selecting a top candidate gene based on validated scoring justifications; and (7) Factoring in transcriptome profiling data to finalize the selection of the top candidate gene., Results: Of the four LLMs evaluated, OpenAI's GPT-4 and Anthropic's Claude demonstrated the best performance and were chosen for the implementation of the candidate gene prioritization and selection workflow. This workflow was run in parallel for each of the 11 erythroid cell modules by participants in a data mining workshop. Module M9.2 served as an illustrative use case. The 30 candidate genes forming this module were assessed, and the top five scoring genes were identified as BCL2L1, ALAS2, SLC4A1, CA1, and FECH. Researchers carefully fact-checked the summarized scoring justifications, after which the LLMs were prompted to select a top candidate based on this information. GPT-4 initially chose BCL2L1, while Claude selected ALAS2. When transcriptional profiling data from three reference datasets were provided for additional context, GPT-4 revised its initial choice to ALAS2, whereas Claude reaffirmed its original selection for this module., Conclusions: Taken together, our findings highlight the ability of LLMs to prioritize candidate genes with minimal human intervention. This suggests the potential of this technology to boost productivity, especially for tasks that require leveraging extensive biomedical knowledge., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Aortitis is a group of disorders characterized by the inflammation of the aorta. The large-vessel vasculitides are the most common causes of aortitis. Aortitis long-term outcomes are not well known., Objectives: The purpose of this study was to assess the long-term outcome and prognosis of noninfectious surgical thoracic aortitis., Methods: This was a retrospective multicenter study of 5,666 patients with thoracic aorta surgery including 217 (3.8%) with noninfectious thoracic aortitis (118 clinically isolated aortitis, 57 giant cells arteritis, 21 Takayasu arteritis, and 21 with various systemic autoimmune disorders). Factors associated with vascular complications and a second vascular procedure were assessed by multivariable analysis., Results: Indications for aortic surgery were asymptomatic aneurysm with a critical size (n = 152 [70%]), aortic dissection (n = 28 [13%]), and symptomatic aortic aneurysm (n = 30 [14%]). The 10-year cumulative incidence of vascular complication and second vascular procedure was 82.1% (95% CI: 67.6%-90.6%), and 42.6% (95% CI: 28.4%-56.1%), respectively. Aortic arch aortitis (HR: 2.08; 95% CI: 1.26-3.44; P = 0.005) was independently associated with vascular complications. Descending thoracic aortitis (HR: 2.35; 95% CI: 1.11-4.96; P = 0.031) and aortic dissection (HR: 3.08; 95% CI: 1.61-5.90; P = 0.002) were independently associated with a second vascular procedure, while treatment with statins after aortitis diagnosis (HR: 0.47; 95% CI: 0.24-0.90; P = 0.028) decreased it. After a median follow-up of 3.9 years, 19 (16.1%) clinically isolated aortitis patients developed features of a systemic inflammatory disease and 35 (16%) patients had died., Conclusions: This multicenter study shows that 82% of noninfectious surgical thoracic aortitis patients will experience a vascular complication within 10 years. We pointed out specific characteristics that identified those at highest risk for subsequent vascular complications and second vascular procedures., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Recent studies have highlighted that systemic lupus erythematosus (SLE) is characterized by different types of symptoms: type 1 symptoms related to inflammation and disease activity and type 2 symptoms such as fatigue, anxiety-depression, and pain. Our aim was to investigate the relation between type 1 and type 2 symptoms, and their impact on health-related quality of life (HRQoL) in SLE., Methods: A literature review was conducted about disease activity/type1 and type 2 symptoms. Articles in English published after 2000 were located on Medline via Pubmed. The articles chosen evaluated at least one type 2 symptom or HRQoL using a validated scale in adult patients., Results: Overall, 182 articles were analyzed and 115 were retained including 21 randomized, controlled trials and corresponding to 36 831 patients. We found that in SLE, inflammatory activity/type 1 symptoms were mostly uncorrelated with type 2 symptoms and/or HRQoL. Several studies even showing an inverse relationship. No or weak correlation was observed in 85, 3% (92, 6%), 76, 7% (74, 4%) and 37, 5% (73, 1%) of studies (patients) for fatigue, anxiety-depression, and pain, respectively. For HRQoL, no or weak correlation was observed in 77, 5% of studies (88% of patients)., Conclusion: Type 2 symptoms are poorly correlated with inflammatory activity/type 1 symptoms in SLE. Possible explanations and implications for clinical care and therapeutic evaluation are discussed.

Objective: Patients with systemic lupus erythematosus (SLE) display symptoms that are not always related to disease activity and may distort clinical trial results. Recently, a clinical categorization based on the presence of type 1 (inflammatory manifestations) and/or type 2 (widespread pain, fatigue, depression) symptoms has been proposed in SLE. Our aim was to develop a type 2 score derived from the Short-Form health survey (SF-36) to categorize SLE patients and to compare immunological and transcriptomic profiles between groups., Method: Seventeen items from the SF-36 were selected to build a type 2 score for 50 SLE patients (100 visits; LUPUCE cohort), and the SLEDAI was used to define type 1 symptoms. Patients were categorized into four groups: minimal (no symptoms), type 1, type 2, and mixed (both type 1 and type 2 symptoms). Clinical, immunological, and transcriptomic profiles were compared between the groups., Results: Type 2 scores ranged from 0 to 31, with a cutoff value of 14 (75th percentile). The sample categorization was minimal in 39%, type 1 in 37%, and type 2 in 9%, and mixed in 15%. Type 2 patients were older than minimal patients and had a longer disease duration than type 1 and mixed patients. Immunological data and modular interferon signatures did not differ between the groups., Conclusion: Patients with SLE can be categorized into four clinical groups using the SLEDAI score and our SF-36-derived type 2 score. This categorization is non-redundant with immunological or transcriptomic profiles and could prove useful to stratify patients in clinical trials. Key Points • A score derived from selected items of the SF-36 can be used to identify SLE patients with type 2 symptoms according to the Duke University categorization. • Using the SLEDAI and this type 2 score, SLE patients can be categorized into four clinical groups. • This categorization is not related to immunological activity or blood transcriptome profiles (and not to the interferon signature in particular). • This categorization could be useful in the daily care of patients as well as in clinical trials, for upstream patient stratification or for the interpretation of results., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Lupus nephritis (LN) is one of the main determinants of the severity of systemic lupus erythematosus (SLE). LN flares can lead to organ damage with chronic kidney disease (CKD) or even end-stage kidney disease (ESKD) and impair patients' survival. The "treat-to-target" strategy, which aims at obtaining and maintaining remission or low disease activity of SLE to alleviate symptoms and prevent organ damage, also refers to the control of residual activity in the kidney. But damage in SLE can also come from treatments, and toxicities related to long-term use of treatments should be prevented. This may contribute to the frequent nonadherence in patients with SLE. The de-escalation or even weaning of treatments whenever possible, or "think-to-untreat" (T2U) strategy, is to be considered in patients with LN. This possibility of treatment weaning in LN was explored in retrospective cohorts, on the basis of long-term clinical remission. It was also proposed prospectively with a kidney-biopsy-based approach, combining clinical and pathologic remission to secure treatment weaning. The WIN-Lupus trial was the first randomized controlled trial comparing the continuation to the discontinuation of maintenance immunosuppressive therapy (IST) after 2 to 3 years in patients with LN in remission. It showed a higher risk of severe SLE flares in patients who discontinued treatment, but also a possibility of weaning without flare in some patients, who need to be better identified. We propose here a narrative review of the available literature on the weaning of treatment in LN and discuss how to secure a T2U strategy., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Background: Identifying a specific threshold level of SARS-CoV-2 antibodies that confers protection in immunocompromised patients has been very challenging. The aim was to assess the threshold of 264 binding antibody units (BAU)/ml using four different SARS-CoV-2 antibody assays (Abbott, Beckman, Roche, and Siemens) and to establish a new optimal threshold of protection for each of the four antibody assays., Methods: This study was performed on data retrieved from 69 individuals, who received at least one dose of the Pfizer/BioNTech BNT162b2 or Moderna COVID-19 vaccine (Spikevax) at the Alphabio Laboratory in Marseille, France (European Hospital, Alphabio-Biogroup). The results were compared to the percent inhibition calculated using a functional surrogate of a standardized virus neutralization test (Genscript)., Results: Samples from 69 patients were analyzed. For a reference cutoff of 264 BAU/ml, assays showed moderate to good overall concordance with Genscript: 87% concordance for Abbott, 78% for Beckman, 75% for Roche, and 88% for Siemens. Overall concordance increased consistently after applying new thresholds, i.e., 148 BAU/ml (Abbott), 48 (Beckman), 559 (Roche), and 270 (Siemens)., Conclusion: We suggest specific adjusted thresholds (BAU/ml) for the four commercial antibody assays that are used to assess pre-exposure prophylaxis in immunocompromised patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Halfon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To evaluate the impact of local therapeutic recommendation updates made by the COVID multidisciplinary consultation meeting (RCP) at the Hôpital Européen Marseille (HEM) through the description of the drug prescriptions for COVID-19 during the first two waves of the epidemic., Methods: This retrospective observational study analysed data from the hospital's pharmaceutical file. We included all patients hospitalized for COVID-19 between February 1, 2020 and January 21, 2021 and extracted specific anti-COVID-19 therapies (ST) from computerized patient record, as well as patients' demographic characteristics, comorbidities and outcome. The evolution of ST prescriptions during the study period was described and put into perspective with the updates of local recommendations made during the first (V1, from 2/24/2020 to 7/27/2020), and second (V2, from 7/28/2020 to 1/21/2021) epidemic waves., Results: A total of 607 COVID-19 hospitalized patients, 197 during V1 and 410 during V2. Their mean age was 65 years-old, and they presented frequent comorbidities. In total, 93% of hospitalized patients received ST: anticoagulants (90%), glucocorticoids (39%) mainly during V2 (49% vs 17%, P<0.001), and azithromycin (30%) mainly during V1 (71% vs 10%, P<0.001). Lopinavir/ritonavir and hydroxychloroquine were prescribed to 17 and 7 inpatients, respectively, and only during V1. Remdesivir was never administered. A total of 22 inpatients were enrolled into clinical trials., Conclusions: The effective dissemination of evidence-based and concerted recommendations seems to have allowed an optimized management of COVID-19 drug therapies in the context of this emerging infection with rapidly evolving therapeutic questions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Peretti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease driven by complex interactions between genetics and environmental factors. SLE is characterised by breaking self-immune tolerance and autoantibody production that triggers inflammation and damage of multiple organs. Given the highly heterogeneous nature of SLE, the treatments currently used are still not satisfactory with considerable side effects, and the development of new therapies is a major health issue for better patient management. In this context, mouse models significantly contribute to our knowledge of the pathogenesis of SLE and are an invaluable tool for testing novel therapeutic targets. Here, we discuss the role of the most used SLE mouse models and their contribution to therapeutic improvement. Considering the complexity of developing targeted therapies for SLE, adjuvant therapies are also increasingly proposed. Indeed, murine and human studies have recently revealed that gut microbiota is a potential target and holds great promises for successful new SLE therapies. However, the mechanisms of gut microbiota dysbiosis in SLE remain unclear to date. In this review, we propose an inventory of existing studies investigating the relationship between gut microbiota dysbiosis and SLE to establish microbiome signature that may serve as a potential biomarker of the disease and its severity as well as a new potential therapy target. This approach may open new possibilities for early diagnosis, prevention and therapeutic perspectives of SLE based on gut microbiome., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Immune-checkpoint inhibitors (ICIs) have dramatically changed the management of advanced cancers. Designed to enhance the antitumour immune response, they can also cause off-target immune-related adverse events (irAEs), which are sometimes severe. Although the efficacy of ICIs suggests that they could have wide-ranging benefits, clinical trials of the drugs have so far excluded patients with pre-existing autoimmune disease. However, evidence is accumulating with regard to the use of ICIs in this 'at-risk' population, with retrospective data suggesting that they have an acceptable safety profile, but that there is a risk of disease flare or other irAE occurrence. The management of immunosuppressive drugs at ICI initiation in patients with autoimmune disease (or later in instances of disease flare or irAE) remains a question of particular interest in clinical practice, in which there is always a search for the balance between protecting against autoimmunity and ensuring a good tumour response. Although temporary use of immunosuppressants seems safe, prolonged use or use at ICI initiation might hamper the antitumour immune response, prompting clinicians to use the minimal efficient immunosuppressive regimen. However, a new paradigm is emerging, in which inhibitors of TNF or IL-6 could have synergistic effects with ICIs on tumour response, while also preventing severe irAEs. If confirmed, this 'decoupling' effect on toxicity and efficacy could change therapeutic practice in this field. Knowledge of the current use of ICIs in patients with pre-existing autoimmune disease, particularly with regard to the use of immunosuppressive drugs and/or biologic DMARDs, can help to guide clinical practice., (© 2022. Springer Nature Limited.)

Objective: Life habits (LH) encompass an individual's engagement in daily activities such as nutrition, fitness, personal care, communication, housing, and mobility, along with his/her social role (responsibility, interpersonal relationships, community life, education, employment, and recreation). This qualitative study explores the nature and context of LH restrictions in systemic lupus erythematosus (SLE) individuals across their SLE journey., Methods: Narrative interviews were conducted with adult SLE patients. Interview transcripts were subjected to a thematic content analysis, using the Disability Creation Process model as a framework., Results: Forty participants were interviewed. Three major themes were highlighted: (1) Temporality, capabilities, and environmental contexts: although all participants experienced LH restrictions at some point, the expression of these limitations depended on the individual's and SLE disease characteristics as well as on temporal (time of life and lupus course) and environmental (material, social, and societal) contexts. (2) Identity issues, illness stigma, and (fear of) discriminations: LH were discussed through the lens of participants' social roles and identities. While illness stigma can influence social relations, it is also expressed at a societal level. (3) Masking and minimizing strategies: due to illness stigma and fear of discrimination, participants developed strategies to manage their relationships, including masking and minimization. Their use was both advantageous and disadvantageous regarding LH., Conclusions: For individuals with SLE, LH restrictions must be considered as an ongoing process that takes place within specific contexts. Our findings provide many opportunities for interventions that can benefit patients and their families, as well as healthcare providers.

Background: COVID-19 infection is associated not only with venous thromboses but also with arterial thromboses (COV-ATs) in relation with an endothelial dysfunction, a coagulopathy and rhythm disorders. The incidence, the topography, and the prognosis of COV-ATs remain poorly known. The objective of this study was to report the overall experience of the Greater Paris University Hospitals (Assistance Publique - Hopitaux de Paris, AP-HP) during the first pandemic wave of COVID-19 infection., Methods: After approval by the ethics committee, a study using the AP-HP clinical data warehouse was carried out between March and May 2020. Overall, 124,609 patients had a polymerase chain reaction for COVID-19 in our hospitals, of which 25,345 were positive. From 20,710 exploitable stays, patients tested positive for COVID who presented an episode of acute COV-AT (except coronary and intracranial arteries) were selected on the basis of the French medical classification for clinical procedures codes. The data are presented as absolute values with percentages and/or means with standard deviation., Results: Over the studied period, 60 patients (aged 71±14 years, 42 men) presented a COV-AT at the time of their hospitalization, an incidence of 0.2%. The arterial complication occurred 3±7 days after the COVID infection and was inaugural in 30% of the cases (n = 18). The sites of COV-AT were the lower extremities (n = 35%, 58%), the abdominal aorta (n = 10%, 17%), the thoracic aorta (n = 7%, 12%), the upper limbs (n = 7%, 12%), the cerebral arteries (n = 7%, 12%), the digestive arteries (n = 6%, 10%), the renal arteries (n = 2%, 3%), and the ophthalmic artery (n = 1%, 2%). Multiple COV-ATs were observed in 13 patients (22%). At the time of diagnosis, 20 (33%) patients were in intensive care, including six (10%) patients who were intubated. On computed tomography angiography, COVID lesions were classified as moderate and severe in 25 (42%) and 21 (35%) cases, respectively. Revascularization was attempted in 27 patients (45%), by open surgery in 16 cases, using endovascular techniques in 8 cases and with a hybrid approach in three cases. Six patients (22%) required reinterventions. The duration of hospitalization was 12±9 days. Early mortality (in-hospital or at 30 days) was 30% (n = 18). Nine (15%) patients presented severe nonlethal ischemic complications., Conclusions: Arterial involvement is rare during COVID-19 infection. The aorta and the arteries of the limbs are the privileged sites. The morbi-mortality of these patients is high. Future studies will have to determine if the systematization of anticoagulation therapy decreases the incidence and the severity of the condition., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Lupus nephritis (LN) is a frequent complication of systemic lupus erythematosus (SLE). Severe (proliferative) forms of LN are treated with induction immunosuppressive therapy (IST), followed by maintenance IST, to target remission and avoid relapses. The optimal duration of maintenance IST is unknown. The WIN-Lupus trial tested whether IST discontinuation after 2‒3 years was non-inferior to IST continuation for two more years in proliferative LN., Methods: WIN-Lupus was an investigator-initiated multicentre randomised controlled trial. Patients receiving maintenance IST with azathioprine or mycophenolate mofetil for 2-3 years, and hydroxychloroquine, were randomised (1:1) into two groups: (1) IST continuation and (2) IST discontinuation. The primary endpoint was the relapse rate of proliferative LN at 24 months. Main secondary endpoints were the rate of severe SLE flares, survival without renal relapse or severe flare, adverse events., Results: Between 2011 and 2016, 96 patients (out of 200 planned) were randomised in WIN-Lupus: IST continuation group (n=48), IST discontinuation group (n=48). Relapse of proliferative LN occurred in 5/40 (12.5%) patients with IST continuation and in 12/44 (27.3%) patients with IST discontinuation (difference 14.8% (95% CI -1.9 to 31.5)). Non-inferiority was not demonstrated for relapse rate; time to relapse did not differ between the groups. Severe SLE flares (renal or extrarenal) were less frequent in patients with IST continuation (5/40 vs 14/44 patients; p=0.035). Adverse events did not differ between the groups., Conclusions: Non-inferiority of maintenance IST discontinuation after 2‒3 years was not demonstrated for renal relapse. IST discontinuation was associated with a higher risk of severe SLE flares., Trial Registration Number: NCT01284725., Competing Interests: Competing interests: NJ-C reports receiving non-financial support from Sanofi-Genzyme and Vifor; speaking and consulting fees from Vifor and Otsuka; research grant from Fresenius Medical Care; outside the submitted work. NC-C reports research grant from Roche; outside the submitted work. LB reports speaking fees from GSK, Novartis, Biocryst, Takeda, Behring and Blueprint; research grants from Takeda, GSK, Sanofi, Biocryst, Novartis; outside the submitted work. LCh reports speaking fees from BMS and non-financial support from AstraZeneca; outside the submitted work. LCo reports speaking fees from Astellas, Chiesi, Novartis, Sandoz, Otsuka, GSK, Biotest; consultancy fees from Biotest, Hansa, Novartis; research grants from Novartis, Astellas; travel funding from Astellas, Chiesi, Novartis, Sandoz, Vifor; outside the submitted work. LD reports speaking fees from AstraZeneca and Janssen. BD reports speaking fees from Genzyme and Novonordisk; consultancy fees from Amicus; research grant from Shire; outside the submitted work. SF reports speaking fees from Asahi, Vifor and Sanofi; consultancy fees from Abyonyx Pharma; outside the submitted work. GG reports speaking fees from Genzyme, Pfizer and Novartis; non-financial support from Novartis, Amgen, Addmedicca, Lilly, Abbvie, Amicus therapeutics, Shire, Pfizer and LFB medicaments; outside the submitted work. AH reports speaking fees from Janssen and Pfizer; outside the submitted work. AK reports speaking fees from Vifor, GSK, AstraZeneca, Roche; consultancy fees from Novartis, GSK, Bohringer-Ingelheim; non-financial support from Vifor, Sanofi and Alexion; outside the submitted work. ML reports speaking fees from Chugai-Roche, Bayer, Pfizer, Leopharma; grant from Chugai-Roche; outside the submitted work. VQ reports consultancy fees from Boehringer Ingelheim and GSK; outside the submitted work. EH reports consulting fees from Johnson&Johnson, Boehringer Ingelheim, Bayer, GSK, Roche-Chugai, Sanofi-Genzyme; speaking fees from Johnson&Johnson, GSK, Roche-Chugai; research grants from CSL Behring, Johnson&Johnson, GSK, Roche-Chugai; outside the submitted work. ZA reports speaking and consultancy fees from GSK. ED reports speaking fees from GSK, Amgen, AstraZeneca; consultancy fees from GSK, AstraZeneca, Amgen; research grant from Roche; outside the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Few treatments are available for patients with glucocorticoid-dependent polymyalgia rheumatica. IL-6 antagonists may reduce disease activity in patients with active glucocorticoid-dependent polymyalgia rheumatica., Objective: To compare the efficacy of tocilizumab vs placebo in patients with glucocorticoid-dependent polymyalgia rheumatica., Design, Setting, and Participants: This double-blind, parallel-group, placebo-controlled randomized clinical trial enrolled 101 patients with polymyalgia rheumatica at 17 hospitals in France from February 2017 to October 2019. Final follow-up occurred in November 2020. Inclusion criteria were persistent disease activity (polymyalgia rheumatica activity score computed using the C-reactive protein level [CRP PMR-AS] >10) and prednisone dose greater than or equal to 10 mg per day., Interventions: Patients were randomly assigned to receive intravenous tocilizumab (8 mg/kg; n = 51) or placebo (n = 50) every 4 weeks for 24 weeks, combined with predefined standardized tapering of oral prednisone., Main Outcomes and Measures: The primary efficacy end point was CRP PMR-AS less than 10 (range, 0-100; higher values indicate greater activity; no minimal clinically important difference defined) combined with either prednisone dose less than or equal to 5 mg per day or a decrease in prednisone dose greater than or equal to 10 mg from baseline at week 24. There were 11 secondary outcomes assessed at week 24 included in this report, including disease activity (measured by CRP PMR-AS) and the proportion of patients no longer taking prednisone., Results: Of the 101 randomized patients (mean age, 67.2 years; 68 [67.3%] women), 100 (99%) received at least 1 infusion and 100 completed the trial. The primary end point was achieved in 67.3% of patients in the tocilizumab group and 31.4% of patients in the placebo group (adjusted difference, 36.0% [95% CI, 19.4%-52.6%]; adjusted relative risk, 2.3 [95% CI, 1.5-3.6]; P < .001). Of 11 reported secondary end points at 24 weeks, 7 showed significant differences favoring tocilizumab, including mean CRP PMR-AS score (7.5 [95% CI, 5.4-9.6] vs 14.9 [95% CI, 11.4-18.4]; adjusted difference, -7.5 [95% CI, -11.2 to -3.8]; P < .001) and the percentage of patients no longer receiving prednisone (49.0% vs 19.6%; adjusted difference, 29.3% [95% CI, 18.9%-39.7%]; adjusted relative risk, 2.5 [95% CI, 1.8-3.5]; P < .001). The most frequent adverse events were infections, experienced by 23 patients (46.9%) in the tocilizumab group and 20 (39.2%) in the placebo group., Conclusions and Relevance: Among patients with active polymyalgia rheumatica despite prednisone therapy, tocilizumab, compared with placebo, resulted in a significantly greater percentage of patients with a CRP PMR-AS less than 10 with reduced prednisone requirements at week 24. Further research is needed to confirm efficacy and to determine the balance of potential benefits and harms., Trial Registration: ClinicalTrials.gov Identifier: NCT02908217.

An increasing number of studies have provided strong evidence that gut microbiota interact with the immune system and stimulate various mechanisms involved in the pathogenesis of auto-immune diseases such as Systemic Lupus Erythematosus (SLE). Indeed, gut microbiota could be a source of diagnostic and prognostic biomarkers but also hold the promise to discover novel therapeutic strategies. Thus far, specific SLE microbial signatures have not yet been clearly identified with alteration patterns that may vary between human and animal studies. In this study, a comparative analysis of a clinically well-characterized cohort of adult patients with SLE showed reduced biodiversity, a lower Firmicutes/Bacteroidetes ( F/B ) ratio, and six differentially abundant taxa compared with healthy controls. An unsupervised clustering of patients with SLE patients identified a subgroup of patients with a stronger alteration of their gut microbiota. Interestingly, this clustering was strongly correlated with the disease activity assessed with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score ( p = 0.03 , odd ratio = 15) and the identification of specific alterations involving the F/B ratio and some different taxa. Then, the gut microbiota of pristane-induced lupus and control mice were analyzed for comparison with our human data. Among the six differentially abundant taxa of the human disease signature, five were common with our murine model. Finally, an exhaustive cross-species comparison between our data and previous human and murine SLE studies revealed a core-set of gut microbiome species that might constitute biomarker panels relevant for future validation studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Toumi, Goutorbe, Plauzolles, Bonnet, Mezouar, Militello, Mege, Chiche and Halfon.)

Aortitis is a classic manifestation of large vessel vasculitis. Antiphospholipid syndrome (APS), sometimes known as Hughes syndrome, is an acquired autoimmune disorder that manifests clinically as recurrent venous or arterial thrombosis. Patients with APS may also suffer from various underlying diseases, most frequently systemic lupus erythematosus (SLE). Catastrophic antiphospholipid syndrome (CAPS) is a rare but serious complication of APS characterized by failure of several organs due to diffuse microcirculatory thrombi. Its main manifestations involve the kidneys, lungs, heart and central nervous system, and require early diagnosis and rapid therapeutic management. While APS can affect virtually any blood vessel, aortitis is not a known symptom of APS. We report the case of a 36-year-old patient with APS and SLE who presented with CAPS during pregnancy, with no concomitant SLE flare. The first manifestation of CAPS was aortitis, preceding renal, cardiac and haematological manifestations. The outcome was favourable with combined treatment including corticosteroids, anticoagulants, plasma exchange and rituximab. We then carried out a literature search for papers describing the presence of aortitis in APS and/or SLE. In the cases of aortic involvement identified in the literature, including another case of CAPS, the occurrence of aortitis in SLE, often associated with the presence of antiphospholipid antibodies/APS, suggests that aortitis should be considered as an under-recognized manifestation and potential non-criterion feature of APS.

Background: Takayasu arteritis (TA) is a large vessel vasculitis that may complicate with cerebrovascular ischemic events. The objective was to describe clinical and vascular features of TA patients with cerebrovascular ischemic events and to identify risk factors for these events., Methods: We analyzed the prevalence and type of stroke/transient ischemic attack (TIA), factors associated with cerebrovascular ischemic events, and stroke-free survival in a large cohort fulfilling the American College of Rheumatology or Ishikawa criteria of TA., Results: Among 320 patients with TA (median age at diagnosis, 36 [25-47] years; 261 [86%] women), 63 (20%) had a stroke (n=41; 65%) or TIA (n=22; 35%). Ischemic event localized in the carotid territory for 55 (87%) patients and the vertebral artery territory in 8 (13%) patients. Multiple stenosis were observed in 33 (52%) patients with a median number of stenosis of 2 (minimum, 0 to maximum, 11), and aneurysms were observed in 10 (16%) patients. A history of stroke or TIA before TA diagnosis (hazard ratio [HR], 4.50 [2.45-8.17]; P <0.0001), smoking (HR, 1.75 [1.01-3.02]; P =0.05), myocardial infarction history (HR, 0.21 [0.05-0.89]; P =0.039), thoracic aorta involvement (HR, 2.05 [1.30-3.75]; P =0.023), time from first symptoms to diagnosis >1 year (HR, 2.22 [1.30-3.80]; P =0.005), and aspirin treatment (HR, 1.82 [1.04-3.19]; P =0.035) were associated with cerebrovascular ischemic event. In multivariate analysis, time from first symptoms to TA diagnosis >1 year (HR, 2.16 [1.27-3.70]; P =0.007) was independently associated with cerebrovascular ischemic events in patients with TA. The HR for cerebrovascular ischemic event in patients who already experienced a stroke/TIA was 5.11 (2.91-8.99; P <0.0001), compared with those who had not., Conclusions: Carotid stroke/TIA is frequent in TA. We identified factors associated with cerebrovascular ischemic events.

Introduction: Tertiary centers recruit a large proportion of locally advanced or recurrent soft tissue sarcomas (STSs) that may have been preoperatively irradiated. The objective of this study was to evaluate the results of oncoplastic surgery (OPS) for patients affected by extremities or parietal trunk STS., Materials and Methods: This retrospective study includes patients who underwent a flap reconstruction after sarcoma resection between January 2018 and December 2020 at Institut Curie. The primary endpoint was the evaluation of the impact of OPS on the quality of surgical margins. The secondary endpoint was to quantify the morbidity of OPS and identify predictive factors for wound complications., Results: Of 211 patients, 89 (42.2%) had a flap reconstruction. Surgery was realized on an irradiated field in 56 (62.9%) patients. Without OPS, all patients were candidates either for amputation (n = 9,10.1%) due to vessels/nerve infiltration, or R1/R2 resection (n = 80,89.9%). Seventy-two (80.0%) pedicle flaps and 18 (20.0%) free flaps were used. No R2 resections were performed. R0 and R1 margins were achieved in 82 (92.1%) and 7 (7.9%), respectively. The median closest margin was 3 mm (IQR 1-6 mm). Among R1 patients, 5 had positive margins along a preserved critical structure, 2 patients had well-differentiated liposarcomas. The surgical morbidity rate was 33.3% (30/90 flaps). The reoperation rate was 15.7% (14/89 patients)., Conclusions: In a referral sarcoma center, the collaboration between the surgical oncologist and the plastic surgery team should be considered upfront in the surgical plan, allowing the most adequate wide oncological resection with acceptable postoperative morbidity., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: Mycotic/infective native aortic aneurysms (INAA) are managed heterogeneously. In the context of disparate literature, this study aimed to assess the outcomes of INAA surgical management and provide comprehensive data in alignment with recent suggestions for reporting standards., Methods: A retrospective review of patients presenting with INAA from September 2002 to March 2020 at two institutions was conducted. In hospital mortality, 90 day mortality, overall mortality, and infection related complications (IRCs) were the study endpoints. Overall survival and IRC free survival were estimated, and predictors of mortality tested using uni- and multivariable analyses., Results: Seventy patients (60 men [86%], median age 68 years [range 59 - 76 years]) were included. Twenty (29%) were ruptured at presentation. INAA location was thoracic in 11 (16%) cases, thoraco-abdominal in seven (10%), and abdominal in 50 (71%). Half of the abdominal INAAs were suprarenal. Two INAAs were concomitantly abdominal and thoracic. Pathogens were identified in 83%. The bacterial spectrum was scattered, with rare Salmonella species (n = 6; 9%). Open surgical repair was performed in 66 (94%) patients, including five conversions of initially attempted endovascular grafts (EVAR), three hybrid procedures, and one palliative EVAR. Vascular substitutes were cryopreserved arterial allografts (n = 67; 96%), prosthesis (n = 2), or femoral veins (n = 1). Kaplan-Meier estimates of overall survival at 30 and 90 days were 87% (95% confidence interval [CI] 76.6 - 93.0) and 71.7% (95% CI 59.2 - 80.9), respectively. The overall in hospital mortality rate was 27.9% (95% CI 1.8 - 66.5). IRCs occurred in seven (10%) patients. The median follow up period was 26.5 months (range 13.0-66.0 months). Chronic kidney disease (CKD) was independently related to in hospital mortality (odds ratio [OR] 20.7, 95% CI 1.8 - 232.7). American Society of Anesthesiologists score of 3 (OR 6.0, 95% CI 1.1 - 33.9), 4 (OR 14.9, 95% CI 1.7 - 129.3), and CKD (OR 32.0, 95% CI 1.2 - 821.5) were related to 90 day mortality., Conclusion: Surgical INAA management has significant mortality and a low re-infection rate. EVAR necessitated secondary open repair, but its limited use in this report did not allow conclusions to be drawn., (Copyright © 2021 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Microbiotas play critical roles in human health, yet in most cases scientists lack standardized and reproducible methods from collection and preservation of samples, as well as the choice of omic analysis, up to the data processing. To date, stool sample preservation remains a source of technological bias in metagenomic sequencing, despite newly developed storage solutions. Here, we conducted a comparative study of 10 storage methods for human stool over a 14-day period of storage at fluctuating temperatures. We first compared the performance of each stabilizer with observed bacterial composition variation within the same specimen. Then, we identified the nature of the observed variations to determine which bacterial populations were more impacted by the stabilizer. We found that DNA stabilizers display various stabilizing efficacies and affect the recovered bacterial profiles thus highlighting that some solutions are more performant in preserving the true gut microbial community. Furthermore, our results showed that the bias associated with the stabilizers can be linked to the phenotypical traits of the bacterial populations present in the studied samples. Although newly developed storage solutions have improved our capacity to stabilize stool microbial content over time, they are nevertheless not devoid of biases hence requiring the implantation of standard operating procedures. Acknowledging the biases and limitations of the implemented method is key to better interpret and support true associated microbiome patterns that will then lead us towards personalized medicine, in which the microbiota profile could constitute a reliable tool for clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Plauzolles, Toumi, Bonnet, Pénaranda, Bidaut, Chiche, Allardet-Servent, Retornaz, Goutorbe and Halfon.)

Background: During thyroid surgery, preservation of parathyroid gland (PG) feeding vessels is often impossible. The aim of the Fluogreen study was to determine the feasibility of using indocyanine green (ICG)-based intraoperative mapping angiograms of the PG (iMAP) to improve vascular preservation., Study Design: This prospective study enrolled all patients undergoing thyroid lobectomy or total thyroidectomy at the Hôpital Européen Marseille between September and December 2018. After exploring the thyroid lobe by autofluorescence to locate the PGs, ICG solution was injected intravenously to locate the PG feeding vessels and guide dissection. A second ICG injection was administered at the end of the lobectomy to assess perfusion of the PGs. The primary outcome was the quality of the angiogram, scaled as iMAP 0 (not informative), iMAP 1 (general vascular pattern visible but no clear vascular pedicle flowing into the PG), or iMAP 2 (clear vascular pedicle flowing into the PG). The secondary outcome was the PG perfusion score at the end of surgery, scaled from ICG 0 (no perfusion) to ICG 2 (intense uptake)., Results: A total of 47 adult patients were analyzed, including 34 total thyroidectomies and 13 lobectomies. ICG angiography assessed 76 PGs, which were scored as iMAP 2 in 24 cases (31.6%), iMAP 1 in 46 (60.5%) and iMAP 0 in six (7.9%). At the end of dissection, the ICG perfusion score was significantly better for the PGs with informative angiography (iMAP 1 or 2), than for the PGs with uninformative angiography (iMAP 0), or the PGs not evaluated by vascular angiography (p < 0.05)., Conclusion: iMAP is feasible and provides direct vascular information in one-third of the cases. Further improvements to this technology are necessary, and the influence of this technique on patient outcomes during thyroidectomy will need to be further evaluated., (© 2021. Société Internationale de Chirurgie.)

Background: Takayasu arteritis (TAK) is a large vessel vasculitis resulting in artery wall remodeling with segmental stenosis and/or aneurysm formation. Mast cells (MCs) are instrumental in bridging cell injury and inflammatory response., Objectives: This study sought to investigate the contribution of MCs on vessel permeability, angiogenesis, and fibrosis in patients with TAK., Methods: MC activation and their tissue expression were assessed in sera and in aorta from patients with TAK and from healthy donors (HDs). In vivo permeability was assessed using a modified Miles assay. Subconfluent cultured human umbilic vein endothelial cells and fibroblasts were used in vitro to investigate the effects of MC mediators on angiogenesis and fibrogenesis., Results: This study found increased levels of MC activation markers (histamine and indoleamine 2,3-dioxygenase) in sera of patients with TAK compared with in sera of HDs. Marked expression of MCs was shown in aortic lesions of patients with TAK compared with in those of noninflammatory aorta controls. Using Miles assay, this study showed that sera of patients with TAK significantly increased vascular permeability in vivo as compared with that of HDs. Vessel permeability was abrogated in MC-deficient mice. MCs stimulated by sera of patients with TAK supported neoangiogenesis (increased human umbilic vein endothelial cell proliferation and branches) and fibrosis by inducing increased production of fibronectin, type 1 collagen, and α-smooth muscle actin by fibroblasts as compared to MCs stimulated by sera of HD., Conclusions: MCs are a key regulator of vascular lesions in patients with TAK and may represent a new therapeutic target in large vessel vasculitis., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: FLNA Loss-of-Function (LoF) causes periventricular nodular heterotopia type 1 (PVNH1), an acknowledged cause of seizures of various types. Neurological symptoms are inconstant, and cardiovascular (CV) defects or connective tissue disorders (CTD) have regularly been associated. We aimed at refining the description of CV and CTD features in patients with FLNA LoF and depicting the multisystemic nature of this condition., Methods: We retrospectively evaluated FLNA variants and clinical presentations in FLNA LoF patient with at least one CV or CTD feature, from three cohorts: ten patients from the French Reference Center for Rare Vascular Diseases, 23 patients from the national reference diagnostic lab for filaminopathies-A, and 59 patients from literature review., Results: Half of patients did not present neurological symptoms. Most patients presented a syndromic association combining CV and CTD features. CV anomalies, mostly aortic aneurysm and/or dilation were present in 75% of patients. CTD features were present in 75%. Variants analysis demonstrated an enrichment of coding variants in the CH1 domain of FLNA protein., Conclusion: In FLNA LoF patients, the absence of seizures should not be overlooked. When considering a diagnosis of PVNH1, the assessment for CV and CTD anomalies is of major interest as they represent interlinked features. We recommend systematic study of FLNA within CTD genes panels, regardless of the presence of neurological symptoms., (© 2021. The Author(s).)

Background & Aim: Screening for genital infection (GI) such as bacterial vaginosis (BV) and yeast infection, for sexually transmitted infection (STI), and for asymptomatic carriage of group B streptococcus (GBS) in pregnant women are common reason for medical appointments. The diagnosis and control of GIs, STIs, and GBS are major issues, for fertility and overall well-being of affected women. Conventional testing is performed using vaginal/cervical classical sampling (VCS); this procedure requires pelvic examination performed by health care professionals which raises concerns among women. Vaginal-self-sampling (VSS), as an alternative to VCS, might capture more women. The aim was first to show non-inferiority of VSS compared with VCS to screen for GIs, STIs, and GBS; second to determine the feasibility of VSS., Methods: VSS and VCS from 1027 women were collected by health care professionals and simultaneously carried out on each patient. GIs, STIs, and GBS were systematically screened in both paired VSS and VCS samples. Non-inferiority of VSS compared with VCS was assessed using z statistic for binomial proportions., Results: Prevalence of GIs were 39.7% using VSS and 38.1% using VCS (p = 0.0016). Prevalence of STIs was 8.5% (VSS) vs 8.1% (VCS) (p = 0.0087). Prevalence of GBS was 13.4% (VSS) and 11.5% (VCS) (p = 0.0001). Most participants (84%) recommended the use of VSS., Conclusions: This study shows that VSS was not inferior to VCS for the detection of GIs, STIs, and GBS. This study provides evidence that VSS can be used as a universal specimen for detection of lower genital tract infections in women., Study Identification Number: ID-RCB 2014-A01250-4., Competing Interests: Roche Molecular Systems, Inc., supported Claire Camus for the preliminary presentation at the ECCMID congress 2017. All authors declared no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: Lupus is a chronic complex autoimmune disease. Non-adherence to treatment can affect patient outcomes. Considering patients' preferences into medical decisions may increase acceptance to their medication. The PREFERLUP study used unsupervised clustering analysis to identify profiles of patients with similar treatment preferences in an online community of French lupus patients., Methods: An online survey was conducted in adult lupus patients from the Carenity community between August 2018 and April 2019. Multiple Correspondence Analysis (MCA) was used with three unsupervised clustering methods (hierarchical, kmeans and partitioning around medoids). Several indicators (measure of connectivity, Dunn index and Silhouette width) were used to select the best clustering algorithm and choose the number of clusters., Results: The 268 participants were mostly female (96%), with a mean age of 44.3 years 83% fulfilled the American College of Rheumatology (ACR) self-reported diagnostic criteria for systemic lupus erythematosus. Overall, the preferred route of administration was oral (62%) and the most important feature of an ideal drug was a low risk of side-effects (32%). Hierarchical clustering identified three clusters. Cluster 1 (59%) comprised patients with few comorbidities and a poor ability to identify oncoming flares; 84% of these patients desired oral treatments with limited side-effects. Cluster 2 (13%) comprised younger patients, who had already participated in a clinical trial, were willing to use implants and valued the compatibility of treatments with pregnancy. Cluster 3 (28%) comprised patients with a longer lupus duration, poorer control of the disease and more comorbidities; these patients mainly valued implants and injections and expected a reduction of corticosteroid intake., Conclusions: Different profiles of lupus patients were identified according to their drug preferences. These clusters could help physicians tailor their therapeutic proposals to take into account individual patient preferences, which could have a positive impact on treatment acceptance and then adherence. The study highlights the value of data acquired directly from patient communities.

Mastocytosis is an orphan disease associated with many systemic symptoms, chronic handicap, and potentially marked social consequences despite improved therapies. In this study, the authors aimed to measure the effect of 2 hypnosis sessions on mastocytosis symptoms in a clinical setting. Questionnaires (pain, flushes, energy, digestive symptoms, quality of life, perceived symptom severity, and global impression of change) were completed pre- and posthypnosis intervention. Data from 20 patients were analyzed (mean age: 53.3 years, 75% female). Compared to baseline assessment, patients exhibited a significant improvement immediately after the first and second hypnosis sessions with regard to the number of days with abdominal pain, abdominal pain intensity and fatigue ( p = .03 and p = .005; p = .05 and p = .02; p = .034, and p = .039, respectively). Perceived severity of symptoms was significantly improved throughout the study ( p = .0075). Long-term improvement in global impression of change was observed in half the responders (8/16). Patients with mastocytosis had an improvement in disabling symptoms with the impact of hypnotic intervention persisting at 1 month. Several patients experienced long-term improvement.

Liver transection is the most challenging part of hepatectomy due to the risk of hemorrhage which is associated with postoperative morbidity and mortality and reduced long-term survival. Parenchymal ultrasonic dissection (UD) with bipolar coagulation (BPC) has been widely recognized as a safe, effective, and standard technique during open and laparoscopic hepatectomy. We here introduce our technique of robotic liver transection using UD with BPC and report on short-term perioperative outcomes. From a single-institution prospective liver surgery database, we identified patients who underwent robotic liver resection. Demographic, anesthetic, perioperative, and oncologic data were analyzed. Fifty patients underwent robotic liver resection using UD and BPC for liver malignancies (n = 42) and benign lesions (n = 8). The median age of the patients was 67 years and 28 were male. According to the difficulty scoring system, 60% (n = 30) of liver resection were considered difficult. Three cases (6%) were converted to open surgery. The median operative time was 240 min, and the median estimated blood loss was 200 ml; 2 patients required operative transfusions. The overall complication rate was 38% (grade I, 29; grade II, 15; grade III, 3; grade IV, 1). Seven patients (14%) experienced biliary leakage. The median length of hospital stay post-surgery was 7 (range 3-20) days. The R0 resection rate was 92%. Robotic parenchymal transection using UD and irrigated BPC appears a simple, safe, and effective technique. However, our results must be confirmed in larger series or in randomized controlled trials., (© 2020. Springer-Verlag London Ltd., part of Springer Nature.)

Background & Aim: Liver fibrosis screening in primary care population is a major public health issue. The FIB-4 index is a simple non-invasive fibrosis test combining age, transaminases, platelets count, developed for the diagnosis of advanced fibrosis. The aim of our study was to evaluate the interest of liver fibrosis screening using systematic calculation of FIB-4 in routine blood analysis., Methods: Between December 2018 and May 2019, we conducted a prospective screening of liver fibrosis in 134 158 patients during a medical check-up including routine blood analysis. Among these patients, 29 707 had transaminases and platelets counts available and benefited from an automatic calculation of FIB-4. Results were obtained from 21 French clinical laboratories in the Bouches du Rhône region., Results: Among the 29 707 patients, 2161 (7.3%) had a high risk of advanced fibrosis (FIB-4>2.67). Individual investigation of patients with FIB-4>2.67 allowed to screen 1268 (1268/2161: 58.7%) patients who were not managed for any liver disease., Conclusions: This work demonstrates the interest of FIB-4 for the screening of liver fibrosis in primary care population. Although additional clinical validation study is required to determine the utility and applicability of Fib-4 to daily practice, our study strongly supports this easy-to-implement strategy using a simple Fib-4 measure resulting from the use of available routine test results., Competing Interests: The authors have declared that no competing interests exist.

As the capacity for generating large-scale molecular profiling data continues to grow, the ability to extract meaningful biological knowledge from it remains a limitation. Here, we describe the development of a new fixed repertoire of transcriptional modules, BloodGen3, that is designed to serve as a stable reusable framework for the analysis and interpretation of blood transcriptome data. The construction of this repertoire is based on co-clustering patterns observed across sixteen immunological and physiological states encompassing 985 blood transcriptome profiles. Interpretation is supported by customized resources, including module-level analysis workflows, fingerprint grid plot visualizations, interactive web applications and an extensive annotation framework comprising functional profiling reports and reference transcriptional profiles. Taken together, this well-characterized and well-supported transcriptional module repertoire can be employed for the interpretation and benchmarking of blood transcriptome profiles within and across patient cohorts. Blood transcriptome fingerprints for the 16 reference cohorts can be accessed interactively via:  https://drinchai.shinyapps.io/BloodGen3Module/ ., (© 2021. The Author(s).)

Objective: To investigate the use of cryopreserved arterial allografts (CAA) as a substitute for infected infrarenal aortic prostheses, and its outcomes., Methods: A single centre retrospective study of consecutive patients receiving an abdominal aortic CAA after removal of an infected graft was conducted between January 1997 and December 2013. The primary outcome was the rate of allograft related revision surgery. Secondary outcomes were the 30 day mortality rate, survival, primary patency, limb salvage, and infection recurrence. Allograft ruptures secondary to infection and risk factors for allograft failure were also investigated., Results: Two hundred patients (mean age 64.2 ± 9.4 years) were included. In 56 (28%) cases, infection was related to an enteric fistula. The mean follow up duration was 4.1 years. The 30 day mortality rate was 11%. Early revision surgery was needed in 59 patients (29.5%). Among them, 15 (7.5%) were allograft related and led to the death of three patients (1.5%), corresponding to a 7.5% 30 day allograft related revision surgery rate. During the first six months, 17 (8.5%) patients experienced 21 events with complete or partial rupture (pseudo-aneurysm) of the allograft responsible for five (2.5%) deaths, corresponding to a re-infection rate of 8.5%. The multivariable analysis showed that diabetes and pseudo-aneurysm of the native aorta on presentation were predictive factors for short term allograft rupture. After six months, 25 (12.5%) patients experienced long term allograft complications (rupture, n = 2, 1%; pseudo-aneurysm, n = 6, 3%; aneurysm, n = 2, 1%; thrombosis, n = 11, 5.5%; stenosis, n = 4, 2%;) requiring revision surgery resulting in one death. The five year rates of survival, allograft related revision surgery, limb salvage, primary patency, and infection recurrence were 56%, 30%, 89%, 80%, and 12%, respectively., Conclusion: CAAs provide acceptable results to treat aortic graft infection with few early graft related fatal complications. Long term allograft related complications are quite common but are associated with low mortality and amputation rates., (Copyright © 2021 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Aim: To assess the efficacy and tolerance of programmed death-1 (PD-1) and PD-ligand 1 (PD-L1) inhibitors and the impact of a standardised management-based protocol in a real-world setting., Patients and Methods: Data from patients who had received anti-PD-(L)1 were collected from our pharmacy database. Clinical response and toxicity were assessed using RECIST criteria and CTCAE version 5.0, respectively. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan-Meier method. Potential prognostic factors were identified using Cox's model., Results: A total of 196 patients and 201 lines of treatment were included (median age: 66 (range: 38-89) years). Types of cancer included non-small cell lung cancer (73%), transitional cell carcinoma (10%), renal cell carcinoma (6%), small cell lung cancer (5%), head and neck squamous cell carcinoma (4%) and classical Hodgkin's lymphoma (1%). Twenty-five (12%) patients had pre-existing autoimmune conditions. Our standardised management-based protocol included 129 (64%) patients. Objective response rate was 29%, median OS was 10 months (IQR: 7-15) and median PFS was 5 months (IQR: 1-22). Patients with an abnormal baseline complete blood count had a worse OS (HR=2.48 [95% CI: 1.24-4.96]; p=0.0103). Thirty-three (16%) patients experienced severe (grade 3 or 4) immune-related adverse event (irAE). There were three (1%) irAE-related deaths. AEs resolved faster when patients were assessed by an internist before anti-PD-(L)1 initiation (p=0.0205)., Conclusion: PD-1 and PD-L1 inhibitors are effective and safe in a real-world setting. Implementation of a standardised management-based protocol with internal medicine specialists is an effective way to optimise irAE management., Competing Interests: The authors reported no conflicts of interest for this work., (© 2021 Grimaud et al.)

Background : Lupus nephritis (LN) is a severe manifestation of Systemic Lupus Erythematosus (SLE). The therapeutic strategy relies on kidney biopsy (KB) results. We tested whether urinary peptidome analysis could non-invasively differentiate active from non-active LN. Design : Urinary samples were collected from 93 patients (55 with active LN and 38 with non-active LN), forming a discovery ( n = 42) and an independent validation ( n = 51) cohort. Clinical characteristics were collected at inclusion and prospectively for 24 months. The urinary peptidome was analyzed by capillary-electrophoresis coupled to mass-spectrometry, comparing active LN to non-active LN, and assessing chronic lesions and response to therapy. The value of previously validated prognostic (CKD273) and differential diagnostic (LN172) signatures was evaluated. Results: Urinary peptides could not discriminate between active and non-active LN or predict early response to therapy. Tubulo-interstitial fibrosis was correlated to the CKD273. The LN172 score identified 92.5% of samples as LN. Few patients developed new-onset CKD. Conclusions: We validated the CKD273 and LN172 classifiers but did not identify a robust signature that could predict active LN and replace KB. The value of urinary peptidome to predict long-term CKD, or renal flares in SLE, remains to be evaluated.

Background: The objective of this study was to better understand the factors associated with the heterogeneity of in-hospital COVID-19 morbidity and mortality across France, one of the countries most affected by COVID-19 in the early months of the pandemic., Methods: This geo-epidemiological analysis was based on data publicly available on government and administration websites for the 96 administrative departments of metropolitan France between March 19 and May 11, 2020, including Public Health France, the Regional Health Agencies, the French national statistics institute, and the Ministry of Health. Using hierarchical ascendant classification on principal component analysis of multidimensional variables, and multivariate analyses with generalised additive models, we assessed the associations between several factors (spatiotemporal spread of the epidemic between Feb 7 and March 17, 2020, the national lockdown, demographic population structure, baseline intensive care capacities, baseline population health and health-care services, new chloroquine and hydroxychloroquine dispensations, economic indicators, degree of urbanisation, and climate profile) and in-hospital COVID-19 incidence, mortality, and case fatality rates. Incidence rate was defined as the cumulative number of in-hospital COVID-19 cases per 100 000 inhabitants, mortality rate as the cumulative number of in-hospital COVID-19 deaths per 100 000, and case fatality rate as the cumulative number of in-hospital COVID-19 deaths per cumulative number of in-hospital COVID-19 cases., Findings: From March 19 to May 11, 2020, hospitals in metropolitan France notified a total of 100 988 COVID-19 cases, including 16 597 people who were admitted to intensive care and 17 062 deaths. There was an overall cumulative in-hospital incidence rate of 155·6 cases per 100 000 inhabitants (range 19·4-489·5), in-hospital mortality rate of 26·3 deaths per 100 000 (1·1-119·2), and in-hospital case fatality rate of 16·9% (4·8-26·2). We found clear spatial heterogeneity of in-hospital COVID-19 incidence and mortality rates, following the spread of the epidemic. After multivariate adjustment, the delay between the first COVID-19-associated death and the onset of the national lockdown was positively associated with in-hospital incidence (adjusted standardised incidence ratio 1·02, 95% CI 1·01-1·04), mortality (adjusted standardised mortality ratio 1·04, 1·02-1·06), and case fatality rates (adjusted standardised fatality ratio 1·01, 1·01-1·02). Mortality and case fatality rates were higher in departments with older populations (adjusted standardised ratio for populations with a high proportion older than aged >85 years 2·17 [95% CI 1·20-3·90] for mortality and 1·43 [1·08-1·88] for case fatality rate). Mortality rate was also associated with incidence rate (1·0004, 1·0002-1·001), but mortality and case fatality rates did not appear to be associated with baseline intensive care capacities. We found no association between climate and in-hospital COVID-19 incidence, or between economic indicators and in-hospital COVID-19 incidence or mortality rates., Interpretation: This ecological study highlights the impact of the epidemic spread, national lockdown, and reactive adaptation of intensive care capacities on the spatial distribution of COVID-19 morbidity and mortality. It provides information for future geo-epidemiological analyses and has implications for preparedness and response policies to current and future epidemic waves in France and elsewhere., Funding: None., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)