OBJECTIVE: Flares of autoimmune rheumatic diseases (AIRDs) following COVID-19 vaccination are a particular concern in vaccine-hesitant individuals. Therefore, we investigated the incidence, predictors and patterns of flares following vaccination in individuals living with AIRDs, using global COVID-19 Vaccination in Autoimmune Diseases (COVAD) surveys.

METHODS: The COVAD surveys were used to extract data on flare demographics, comorbidities, COVID-19 history, and vaccination details for patients with AIRDs. Flares following vaccination were identified as patient-reported (a), increased immunosuppression (b), clinical exacerbations (c) and worsening of PROMIS scores (d). We studied flare characteristics and used regression models to differentiate flares among various AIRDs.

RESULTS: Of 15 165 total responses, the incidence of flares in 3453 patients with AIRDs was 11.3%, 14.8%, 9.5% and 26.7% by definitions a-d, respectively. There was moderate agreement between patient-reported and immunosuppression-defined flares (K = 0.403, P = 0.022). Arthritis (61.6%) and fatigue (58.8%) were the most commonly reported symptoms. Self-reported flares were associated with higher comorbidities (P = 0.013), mental health disorders (MHDs) (P < 0.001) and autoimmune disease multimorbidity (AIDm) (P < 0.001).In regression analysis, the presence of AIDm [odds ratio (OR) = 1.4; 95% CI: 1.1, 1.7; P = 0.003), or a MHD (OR = 1.7; 95% CI: 1.1, 2.6; P = 0.007), or being a Moderna vaccine recipient (OR = 1.5; 95% CI: 1.09, 2.2; P = 0.014) were predictors of flares. Use of MMF (OR = 0.5; 95% CI: 0.3, 0.8; P = 0.009) and glucocorticoids (OR = 0.6; 95% CI: 0.5, 0.8; P = 0.003) were protective.A higher frequency of patients with AIRDs reported overall active disease post-vaccination compared with before vaccination (OR = 1.3; 95% CI: 1.1, 1.5; P < 0.001).

CONCLUSION: Flares occur in nearly 1 in 10 individuals with AIRDs after COVID vaccination; people with comorbidities (especially AIDm), MHDs and those receiving the Moderna vaccine are particularly vulnerable. Future avenues include exploring flare profiles and optimizing vaccine strategies for this group.

OBJECTIVES: We aimed to investigate gender-based differences in idiopathic inflammatory myopathies (IIMs), with a particular focus on patient-reported outcomes, utilizing data obtained through the international COVID-19 vaccination in autoimmune disease (COVAD) e-survey.

METHODS: Patient-reported outcomes including fatigue, pain, and physical function were extracted from the COVAD database and compared between genders, adjusting for demographics and IIM subgroups by multivariable analysis. Inclusion body myositis (IBM) was analysed separately because of substantial differences in outcomes.

RESULTS: 1197 complete responses from patients with IIMs as of 31 August 2021 were analysed. Seventy percent were women. Women were younger (58 [48-68] vs. 69 [58-75] years old, median [IQR], p < 0.001) and more likely to suffer from autoimmune multimorbidity, defined as three or more autoimmune diseases in an individual patient (11.4% vs. 2.8%, p < 0.001). In non-IBM IIMs, fatigue visual analogue scale scores were higher in women (5 [3-7] vs. 4 [2-6], median [IQR], p = 0.004), whereas no significant gender-based differences were noted in IBM. Multivariable analysis in non-IBM IIMs revealed women, residence in high-income countries, overlap myositis, and autoimmune multimorbidity were independently associated with increased fatigue.

CONCLUSIONS: Women with IIMs suffer from autoimmune multimorbidity and experience increased fatigue compared to men.

Atrial fibrillation (AF) is the most common chronic arrhythmia presenting a heavy disease burden. We report a new approach for generating cardiomyocytes (CMs) resembling atrial cells from human-induced pluripotent stem cells (hiPSCs) using a combination of Gremlin 2 and retinoic acid treatment. More than 40% of myocytes showed rod-shaped morphology, expression of CM proteins (including ryanodine receptor 2, -actinin-2 and F-actin) and striated appearance, all of which were broadly similar to the characteristics of adult atrial myocytes (AMs). Isolated myocytes were electrically quiescent until stimulated to fire action potentials with an AM profile and an amplitude of approximately 100 mV, arising from a resting potential of approximately -70 mV. Single-cell RNA sequence analysis showed a high level of expression of several atrial-specific transcripts including , , , , , and . Amplitudes of calcium transients recorded from spontaneously beating cultures were increased by the stimulation of -adrenoceptors (activated by phenylephrine and blocked by prazosin) or -adrenoceptors (activated by isoproterenol and blocked by CGP20712A). Our new approach provides human AMs with mature characteristics from hiPSCs which will facilitate drug discovery by enabling the study of human atrial cell signalling pathways and AF. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'.

Real-world data and real-world evidence (RWE) are becoming more important for healthcare decision making and health technology assessment. We aimed to propose solutions to overcome barriers preventing Central and Eastern European (CEE) countries from using RWE generated in Western Europe. To achieve this, following a scoping review and a webinar, the most important barriers were selected through a survey. A workshop was held with CEE experts to discuss proposed solutions. Based on survey results, we selected the nine most important barriers. Multiple solutions were proposed, for example, the need for a European consensus, and building trust in using RWE. Through collaboration with regional stakeholders, we proposed a list of solutions to overcome barriers on transferring RWE from Western Europe to CEE countries.

Idiopathic inflammatory myopathies (IIMs) confer a significant risk of disability and poor quality of life, though fatigue, an important contributing factor, remains under-reported in these individuals. We aimed to compare and analyze differences in visual analog scale (VAS) scores (0-10 cm) for fatigue (VAS-F) in patients with IIMs, non-IIM systemic autoimmune diseases (SAIDs), and healthy controls (HCs). We performed a cross-sectional analysis of the data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) international patient self-reported e-survey. The COVAD survey was circulated from December 2020 to August 2021, and details including demographics, COVID-19 history, vaccination details, SAID details, global health, and functional status were collected from adult patients having received at least one COVID-19 vaccine dose. Fatigue experienced 1 week prior to survey completion was assessed using a single-item 10 cm VAS. Determinants of fatigue were analyzed in regression models. Six thousand nine hundred and eighty-eight respondents (mean age 43.8 years, 72% female; 55% White) were included in the analysis. The overall VAS-F score was 3 (IQR 1-6). Patients with IIMs had similar fatigue scores (5, IQR 3-7) to non-IIM SAIDs [5 (IQR 2-7)], but higher compared to HCs (2, IQR 1-5; P < 0.001), regardless of disease activity. In adjusted analysis, higher VAS-F scores were seen in females (reference female; coefficient -0.17; 95%CI -0.21 to -13; P < 0.001) and Caucasians (reference Caucasians; coefficient -0.22; 95%CI -0.30 to -0.14; P < 0.001 for Asians and coefficient -0.08; 95%CI -0.13 to 0.30; P = 0.003 for Hispanics) in our cohort. Our study found that patients with IIMs exhibit considerable fatigue, similar to other SAIDs and higher than healthy individuals. Women and Caucasians experience greater fatigue scores, allowing identification of stratified groups for optimized multidisciplinary care and improve outcomes such as quality of life.

INTRODUCTION: Postcardiotomy veno-arterial extracorporeal membrane oxygenation (V-A-ECMO) is associated with significant mortality. Identification of patients at very high risk for death is elusive and the decision to initiate V-A-ECMO is based on clinical judgment. The prognostic impact of pre-V-A-ECMO arterial lactate level in these critically ill patients has been herein evaluated.

METHODS: A systematic review was conducted to identify studies on postcardiotomy VA-ECMO for the present individual patient data meta-analysis.

RESULTS: Overall, 1269 patients selected from 10 studies were included in this analysis. Arterial lactate level at V-A-ECMO initiation was increased in patients who died during the index hospitalization compared to those who survived (9.3 vs 6.6 mmol/L, < 0.0001). Accordingly, in hospital mortality increased along quintiles of pre-V-A-ECMO arterial lactate level (quintiles: 1, 54.9%; 2, 54.9%; 3, 67.3%; 4, 74.2%; 5, 82.2%, < 0.0001). The best cut-off for arterial lactate was 6.8 mmol/L (in-hospital mortality, 76.7% vs. 55.7%, < 0.0001). Multivariable multilevel mixed-effect logistic regression model including arterial lactate level significantly increased the area under the receiver operating characteristics curve (0.731, 95% CI 0.702-0.760 vs 0.679, 95% CI 0.648-0.711, DeLong test < 0.0001). Classification and regression tree analysis showed the in-hospital mortality was 85.2% in patients aged more than 70 years with pre-V-A-ECMO arterial lactate level ≥6.8 mmol/L.

CONCLUSIONS: Among patients requiring postcardiotomy V-A-ECMO, hyperlactatemia was associated with a marked increase of in-hospital mortality. Arterial lactate may be useful in guiding the decision-making process and the timing of initiation of postcardiotomy V-A-ECMO.

OBJECTIVES: The assessment of physical function is fundamental in the management of patients with idiopathic inflammatory myopathies (IIMs). We aimed to investigate the physical function of patients with IIMs compared with those with non-IIM autoimmune rheumatic diseases (AIRDs) utilizing Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function (PF) data obtained in the COVAD study, an international self-reported e-survey assessing the safety of COVID-19 vaccines in AIRDs.

METHODS: Demographics, AIRD diagnosis, disease activity, and PROMIS PF short form-10a data were extracted from the COVAD database. PROMIS PF-10a scores were compared between disease categories and stratified by disease activity. Factors affecting PROMIS PF-10a scores other than disease activity were identified by multivariable regression analysis in patients with inactive disease.

RESULTS: A total of 1057 IIM patients, 3635 non-IIM AIRD patients and 3981 healthy controls (HCs) responded to the COVAD e-survey from April to August 2021. Using a binomial regression model, the predicted mean of PROMIS PF-10a scores was significantly lower in IIM patients compared with non-IIM AIRD patients or HCs [36.3 (95% CI 35.5, 37.1) vs 41.3 (95% CI 40.2, 42.5) vs 46.2 (95% CI 45.8, 46.6), P < 0.001], irrespective of disease activity. The independent factors for lower PROMIS PF-10a scores in patients with inactive disease were older age, female, longer disease duration, and a diagnosis of inclusion body myositis or polymyositis.

CONCLUSION: Physical function is significantly impaired in IIMs compared with non-IIM AIRDs or HCs, even in patients with inactive disease. Our study highlights a critical need for better strategies to minimize functional disability in patients with IIMs.

Rainfall erosivity is a key factor that influences soil erosion by water. Rain-gauge measurements are commonly used to estimate rainfall erosivity. However, long-term gauge records with sub-hourly resolutions are lacking in large parts of the world. Satellite observations provide spatially continuous estimates of rainfall, but they are subject to biases that affect estimates of rainfall erosivity. We employed a novel approach to map global rainfall erosivity based on a high-temporal-resolution (30-min), long-term (2001–2020) satellite-based precipitation product—the Integrated Multi-satellitE Retrievals for Global Precipitation Measurement (GPM-IMERG)—and mean annual rainfall erosivity from the Global Rainfall Erosivity Database (GloREDa) stations (n = 3286). We used a residual-based merging scheme to integrate GPM-IMERG-based rainfall erosivity with GloREDa using Geographically Weighted Regression (GWR). The accuracy of the GWR-based merging scheme was evaluated with a 10-fold cross-validation against GloREDa stations. Based on GPM-IMERG-only, the global mean annual rainfall erosivity was estimated to be 1173 MJ mm ha−1 h−1 yr−1 with a standard deviation of 1736 MJ mm ha−1 h−1 yr−1. The mean value estimated via GPM-IMERG merged with GloREDa was 2020 MJ mm ha−1 h−1 yr−1 with a standard deviation of 3415 MJ mm ha−1 h−1 yr−1. Overall, GPM-IMERG-only estimates underestimated rainfall erosivity. The underestimations were greatest in areas of high rainfall erosivity. The accuracy of rainfall erosivity estimates from GPM-IMERG merged with GloREDa substantially improved (Nash-Sutcliffe efficiency = 0.83, percent bias = −2.4%, and root mean square error = 1122 MJ mm ha−1 h−1 yr−1) compared to estimates by GPM-IMERG-only (Nash-Sutcliffe efficiency = 0.51, percent bias = 27.8%, and root mean square error = 1730 MJ mm ha−1 h−1 yr−1). Improving satellite-based global rainfall erosivity estimates through integrating with gauge data is relevant as it can contribute to enhancing soil erosion modeling and, in turn, support land degradation neutrality programs.

Multi-omic analyses are necessary to understand the complex biological processes taking place at the tissue and cell level, but also to make reliable predictions about, for example, disease outcome. Several linear methods exist that create a joint embedding using paired information per sample, but recently there has been a rise in the popularity of neural architectures that embed paired -omics into the same non-linear manifold. This work describes a head-to-head comparison of linear and non-linear joint embedding methods using both bulk and single-cell multi-modal datasets. We found that non-linear methods have a clear advantage with respect to linear ones for missing modality imputation. Performance comparisons in the downstream tasks of survival analysis for bulk tumor data and cell type classification for single-cell data lead to the following insights: First, concatenating the principal components of each modality is a competitive baseline and hard to beat if all modalities are available at test time. However, if we only have one modality available at test time, training a predictive model on the joint space of that modality can lead to performance improvements with respect to just using the unimodal principal components. Second, -omic profiles imputed by neural joint embedding methods are realistic enough to be used by a classifier trained on real data with limited performance drops. Taken together, our comparisons give hints to which joint embedding to use for which downstream task. Overall, product-of-experts performed well in most tasks and was reasonably fast, while early integration (concatenation) of modalities did quite poorly.

OBJECTIVES: To analyse how the key components at the time of diagnosis of the Sjögren's phenotype (epidemiological profile, sicca symptoms, and systemic disease) can be influenced by the potential exposure to climate-related natural hazards.

METHODS: For the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Climate-related hazards per country were defined according to the OECD and included seven climate-related hazard types: extreme temperature, extreme precipitation, drought, wildfire, wind threats, river flooding, and coastal flooding. Climatic variables were defined as dichotomous variables according to whether each country is ranked among the ten countries with the most significant exposure.

RESULTS: After applying data-cleaning techniques and excluding people from countries not included in the OECD climate rankings, the database study analysed 16,042 patients from 23 countries. The disease was diagnosed between 1 and 3 years earlier in people living in countries included among the top 10 worst exposed to extreme precipitation, wildfire, wind threats, river flooding, and coastal flooding. A lower frequency of dry eyes was observed in people living in countries exposed to wind threats, river flooding, and coastal flooding, with a level of statistical association being classified as strong (p<0.0001 for the three variables). The frequency of dry mouth was significantly lower in people living in countries exposed to river flooding (p<0.0001) and coastal flooding (p<0.0001). People living in countries included in the worse climate scenarios for extreme temperature (p<0.0001) and river flooding (p<0.0001) showed a higher mean ESSDAI score in comparison with people living in no-risk countries. In contrast, those living in countries exposed to worse climate scenarios for wind threats (p<0.0001) and coastal flooding (p<0.0001) showed a lower mean ESSDAI score in comparison with people living in no-risk countries.

CONCLUSIONS: Local exposure to extreme climate-related hazards plays a role in modulating the presentation of Sjögren across countries concerning the age at which the disease is diagnosed, the frequency of dryness, and the degree of systemic activity.

OBJECTIVES: To explore current management practices for PMR by general practitioners (GPs) and rheumatologists including implications for clinical trial recruitment.

METHODS: An English language questionnaire was constructed by a working group of rheumatologists and GPs from six countries. The questionnaire focused on: 1: Respondent characteristics; 2: Referral practices; 3: Treatment with glucocorticoids; 4: Diagnostics; 5: Comorbidities; and 6: Barriers to research. The questionnaire was distributed to rheumatologists and GPs worldwide via members of the International PMR/Giant Cell Arteritis Study Group.

RESULTS: In total, 394 GPs and 937 rheumatologists responded to the survey. GPs referred a median of 25% of their suspected PMR patients for diagnosis and 50% of these were returned to their GP for management. In general, 39% of rheumatologists evaluated patients with suspected PMR >2 weeks after referral, and a median of 50% of patients had started prednisolone before rheumatologist evaluation. Direct comparison of initial treatment showed that the percentage prescribing >25 mg prednisolone daily for patients was 30% for GPs and 12% for rheumatologists. Diagnostic imaging was rarely used. More than half (56%) of rheumatologists experienced difficulties recruiting people with PMR to clinical trials.

CONCLUSION: This large international survey indicates that a large proportion of people with PMR are not referred for diagnosis, and that the proportion of treatment-naive patients declined with increasing time from referral to assessment. Strategies are needed to change referral and management of people with PMR, to improve clinical practice and facilitate recruitment to clinical trials.