In inflammatory myopathies, dropped head/bent spine syndrome is associated with scleromyositis: an international case–control study

Dermatomyositis; Polymyositis; Systemic sclerosisDermatomiositis; Polimiositis; Esclerosis sistémicaDermatomiositis; Polimiositis; Esclerosi sistèmicaBackground Some myopathies can lead to dropped head or bent spine syndrome (DH/BS). The significance of this symptom has not been studied in inflammatory myopathies (IM). Objectives To assess the significance of DH/BS in patients with IM. Methods Practitioners from five IM networks were invited to report patients with IM suffering from DH/BS (without other known cause than IM). IM patients without DH/BS, randomly selected in each participating centre, were included as controls at a ratio of 2 to 1. Results 49 DH/BS-IM patients (DH: 57.1%, BS: 42.9%) were compared with 98 control-IM patients. DH/BS-IM patients were older (65 years vs 53 years, p<0.0001) and the diagnosis of IM was delayed (6 months vs 3 months, p=0.009). Weakness prevailing in the upper limbs (42.9% vs 15.3%), dysphagia (57.1% vs 25.5%), muscle atrophy (65.3% vs 34.7%), weight loss (61.2% vs 23.5%) and loss of the ability to walk (24.5% vs 5.1%) were hallmarks of DH/BS-IM (p≤0.0005), for which the patients more frequently received intravenous immunoglobulins (65.3% vs 34.7%, p=0.0004). Moreover, DH/BS-IM patients frequently featured signs and/or complications of systemic sclerosis (SSc), fulfilling the American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for this disease in 40.8% of the cases (vs 5.1%, p<0.0001). Distribution of the myopathy, its severity and its association with SSc were independently associated with DH/BS (p<0.05). Mortality was higher in the DH/BS-IM patients and loss of walking ability was independently associated with survival (p<0.05). Conclusion In IM patients, DH/BS is a marker of severity and is associated with SSc (scleromyositis)

Fibrillation auriculaire chez les patients traités par bisphosphonates intraveineux : une analyse systématique de la base de données VigiBase de l’Organisation Mondiale de la Santé

Médecine. RhumatologieIntroduction : la fibrillation auriculaire (FA) est une pathologie potentiellement grave dont la survenue pourrait être associée à la perfusion intraveineuse de bisphosphonates (BPIV), tel que le zolédronate (ZOL) ou le pamidronate (PAM). L’objectif de cette étude était de confirmer l'existence d'une association entre FA et BPIV, puis de comparer les caractéristiques et la sévérité des FA associées à l’administration de ZOL ou de PAM. Méthode : nous avons utilisé VigiBase, la base de recueil des effets indésirables médicamenteux de l’Organisation Mondiale de la Santé (OMS), qui répertorie ces effets indésirables sous forme de rapports individuels (Individual Case Safety Reports, ICSRs). Nous avons procédé à l’analyse des ICSRs rapportant l’administration de ZOL ou PAM associé à "Atrial Fibrillation" (Preferred term, [PT] level) selon les termes du Medical Dictionary for Drug Regulatory Activities (MedDRA), entre 1967 et mars 2018. La force de l’association entre FA et BPIV a été déterminée par l’IC025, qui correspond à la borne inférieure de l’intervalle de confiance à 95% de l'Information Component (IC), un indicateur de disproportionnalité par méthode d’inférence bayésienne ; sa positivité est le seuil habituel de détection d’un signal statistique significatif dans VigiBase. Résultats : au total, nous avons analysé 530 ICSRs de FA associées aux BPIV (501 avec le ZOL et 105 avec le PAM). Une analyse de disproportionnalité bayésienne a permis de détecter une association significative entre la FA et le ZOL (IC025=1.83) ainsi qu’entre la FA et le PAM (IC025=2.16). Après avoir exclu 76 ICSRs concernant une exposition aux deux molécules, nous avons analysé les 454 cas restants. Les FA étaient sévères dans 85% des cas, et le décès est survenu dans 17.7% des cas. D’après cette base de données, le risque de FA sévère était plus important avec le ZOL qu’avec le PAM (OR : 2.98 [IC95 : 1.17-7.57]) après ajustement sur l’âge et le sexe. Conclusion : il s’agit de la première étude de pharmacovigilance montrant qu'il existe une association significative entre FA et BPIV (ZOL ou PAM). Les FA rapportées étaient majoritairement sévères avec un taux de mortalité important. Le risque de FA sévères était plus important avec le ZOL qu’avec le PAM. Ces données suggèrent que l'utilisation des BPIV doit être prudente.Objective : Atrial Fibrillation (AF) may be triggered by intravenous bisphosphonates (IVBP) such as zoledronic acid (ZOL) or pamidronic acid (PAM). Our objective was to confirm the association between AF and IVBP in a real-life large pharmacovigilance database. Methods: Analysis of adverse events reported as “Atrial Fibrillation” (according to the Medical Dictionary for Drug Regulatory Activities) associated with the use of ZOL or PAM, in VigiBase, the World Health Organization global Individual Case Safety Report (ICSR) database. All ICSRs reporting AF associated with ZOL or PAM were analysed in a disproportionality analysis determining the lower end of the 95% credibility interval for the Information Component (IC025), showing a statistical association when -0. Results: 530 ICSRs reporting on the association between AF and IVBP were extracted (501 with ZOL and 105 with PAM). Bayesian disproportionality analysis detected a significant association between AF and use of ZOL (IC025=1.83) and PAM (IC025=2.16). After excluding 76 ICSRs reporting on both drugs, 454 ICSRs were further analyzed. AF was severe in 85.0% of cases and death occurred in 17.7%. The risk of severe AF was increased (OR: 2.98 [95%CI: 1.17-7.57], p=0.02) following ZOL versus PAM, after adjustment for age and gender. Conclusions: This study is the first pharmacovigilance analysis to confirm the association between IVBP and AF. Most AF were severe, with a high frequency of lethal outcomes. The risk of severe AF was increased following ZOL use compared to PAM, advocating for a cautious use of IVB

Atrial fibrillation in patients treated with intravenous zoledronic or pamidronic acid: a pharmacoepidemiological study

International audienceObjective Atrial fibrillation (AF) may be triggered by intravenous bisphosphonates (IVBPs) such as zoledronic acid or pamidronic acid. Our objective was to confirm the association between AF and IVBPs in a real-life large pharmacovigilance database. Design A systematic analysis of VigiBase, the World Health Organization's pharmacovigilance database. Methods Analysis of adverse events reported as ‘atrial fibrillation’ (according to the Medical Dictionary for Drug Regulatory Activities) associated with the use of zoledronic acid or pamidronic acid, in VigiBase, the World Health Organization's global Individual Case Safety Report (ICSR) database. All ICSRs reporting AF associated with zoledronic acid or pamidronic acid were included in a disproportionality analysis determining the lower end of the 95% credibility interval for the information component (IC 025 ), showing a statistical association when >0. Results 530 ICSRs reporting on the association between AF and IVBPs were extracted. Bayesian disproportionality analysis detected a significant association between AF and use of zoledronic acid (IC 025 = 1.83) and pamidronic acid (IC 025 = 2.16). Further analysis of these ICSRs determined that AF was severe in 85.0% of cases and with a mortality of 17.7%. The risk of severe AF was increased (OR: 2.98 (95% CI: 1.17–7.57), P = 0.02) following zoledronic acid vs pamidronic acid, after adjustment for age and gender. Conclusions This is the first VigiBase pharmacoepidemiological study confirming the association between IVBPs and AF. Most AF were severe, with a high frequency of lethal outcome. The risk of severe AF was increased following zoledronic acid use compared to pamidronic acid, advocating for a cautious use of IVBPs

Effect of SARS-CoV-2 Vaccination on Symptoms from Post-Acute Sequelae of COVID-19: Results from the Nationwide VAXILONG Study

Introduction: Few data are available concerning the effect of SARS-CoV-2 vaccination on the persistent symptoms associated with COVID-19, also called long-COVID or post-acute sequelae of COVID-19 (PASC). Patients and methods: We conducted a nationwide online study among adult patients with PASC as defined by symptoms persisting over 4 weeks following a confirmed or probable COVID-19, without any identified alternative diagnosis. Information concerning PASC symptoms, vaccine type and scheme and its effect on PASC symptoms were studied. Results: 620 questionnaires were completed and 567 satisfied the inclusion criteria and were analyzed. The respondents’ median age was 44 (IQR 25–75: 37–50) and 83.4% were women. The initial infection was proven in 365 patients (64%) and 5.1% had been hospitalized to receive oxygen. A total of 396 patients had received at least one injection of SARS-CoV-2 vaccine at the time of the survey, after a median of 357 (198–431) days following the initially-reported SARS-CoV-2 infection. Among the 380 patients who reported persistent symptoms at the time of SARS-CoV-2 vaccination, 201 (52.8%) reported a global effect on symptoms following the injection, corresponding to an improvement in 21.8% and a worsening in 31%. There were no differences based on the type of vaccine used. After a complete vaccination scheme, 93.3% (28/30) of initially seronegative patients reported a positive anti-SARS-CoV-2 IgG. A total of 170 PASC patients had not been vaccinated. The most common reasons for postponing the SARS-CoV-2 vaccine were fear of worsening PASC symptoms (55.9%) and the belief that vaccination was contraindicated because of PASC (15.6%). Conclusion: Our study suggests that SARS-CoV-2 vaccination is well tolerated in the majority of PASC patients and has good immunogenicity. Disseminating these reassuring data might prove crucial to increasing vaccine coverage in patients with PASC

Preclinical safety study of a combined therapeutic bone wound dressing for osteoarticular regeneration

Arthroplasty is the main clinical option for the treatment of osteoarticular lesions, but has limited efficacy. Here, the authors use a wound dressing with autologous mesenchymal stromal cells, functionalised for local BMP2 delivery, and show feasibility and safety in standardised preclinical tests in animal models, suggesting suitability for use in clinical trials

Preclinical and clinical evaluation of a new method to assess cardiac insulin resistance using nuclear imaging

International audienceAbstract Ki67 has potential clinical importance in breast cancer but has yet to see broad acceptance due to inter-laboratory variability. Here we tested an open source and calibrated automated digital image analysis (DIA) platform to: (i) investigate the comparability of Ki67 measurement across corresponding core biopsy and resection specimen cases, and (ii) assess section to section differences in Ki67 scoring. Two sets of 60 previously stained slides containing 30 core-cut biopsy and 30 corresponding resection specimens from 30 estrogen receptor-positive breast cancer patients were sent to 17 participating labs for automated assessment of average Ki67 expression. The blocks were centrally cut and immunohistochemically (IHC) stained for Ki67 (MIB-1 antibody). The QuPath platform was used to evaluate tumoral Ki67 expression. Calibration of the DIA method was performed as in published studies. A guideline for building an automated Ki67 scoring algorithm was sent to participating labs. Very high correlation and no systematic error ( p = 0.08) was found between consecutive Ki67 IHC sections. Ki67 scores were higher for core biopsy slides compared to paired whole sections from resections ( p ≤ 0.001; median difference: 5.31%). The systematic discrepancy between core biopsy and corresponding whole sections was likely due to pre-analytical factors (tissue handling, fixation). Therefore, Ki67 IHC should be tested on core biopsy samples to best reflect the biological status of the tumor

B-cell targeted therapy is associated with severe COVID-19 among patients with inflammatory arthritides: a 1-year multicentre study in 1116 successive patients receiving intravenous biologics

No abstract availabl