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Summary Background Preliminary criteria for the very early diagnosis of systemic sclerosis (VEDOSS) have been previously proposed to identify signs and symptoms in patients with Raynaud's phenomenon. Patients with all signs or symptoms of the VEDOSS criteria already fulfil the 2013 American College of Rheumatology–European League Against Rheumatism (ACR–EULAR) classification criteria for systemic sclerosis. However, prospective data for the evolution to fulfilling these criteria do not exist. We therefore aimed to determine the clinical value of the VEDOSS criteria to identify patients with Raynaud's phenomenon who progress to systemic sclerosis within 5 years. Methods The VEDOSS project was a multicentre, longitudinal registry study done in 42 European Scleroderma Trial and Research group centres located in 20 countries in Europe, North America, and South America. Patients with Raynaud's phenomenon were eligible for enrolment. Those who had fulfilled the 1980 ACR or the 2013 ACR–EULAR classification criteria for systemic sclerosis, as well as of any other ACR or EULAR classification criteria for other definite connective tissue diseases at enrolment were excluded. Data were recorded each year during follow-up visits and included the four VEDOSS criteria (ie, positivity for antinuclear antibodies [ANAs], puffy fingers, systemic sclerosis-specific autoantibodies, and abnormal nailfold capillaroscopy). The primary endpoint was the fulfilment of the 2013 ACR–EULAR classification criteria for systemic sclerosis (ie, progression from enrolment to follow-up). Proportion of progressors and VEDOSS criteria interaction were reported descriptively. Predictors of progression of the distinct VEDOSS criteria interactions were determined based on the point prevalence at 5 years. To investigate the intermediate course of progression of the distinct VEDOSS criteria and their combinations, Kaplan-Meier analysis was done. Results Between March 1, 2010, and Oct 4, 2018, we enrolled 1150 patients with Raynaud's phenomenon in the VEDOSS database. 764 (66·4%) of 1150 patients met the VEDOSS criteria for study inclusion. Of the 764 patients, 553 (72·4%) had at least one available follow-up visit and the median duration of follow-up was 3·6 years (IQR 1·7–5·8). The mean age was 45·9 years (SD 15·0), 507 (91·7%) of 553 participants were female, and the median time since the onset of Raynaud's phenomenon was 4·0 years (IQR 1·7–10·0). At baseline, 401 (73·7%) of 544 patients with Raynaud's phenomenon had detectable ANA, with 208 (39·5%) of 527 patients positive for systemic sclerosis-specific autoantibodies. Nailfold capillaroscopy abnormalities were present in 182 (36·0%) of 505 patients and puffy fingers were detected in 96 (17·8%) of 540 at baseline. 1885 follow-up visits were recorded. 254 (45·9%) of 553 patients completed the study with progression or a 5-year follow-up; of whom, 133 reached the primary endpoint, resulting in an overall progression rate of 52·4%. The absence of ANA at baseline was the factor most strongly associated with a lack of progression within 5 years, with only four (10·8%) of 37 ANA-negative patients progressing. Conversely, positivity at baseline for systemic sclerosis-specific autoantibodies and puffy fingers was the combination having the highest risk of progression (16 [94·1%] of 17). Interpretation Our results from the VEDOSS project offers a useful tool for a stratified risk approach to patients with Raynaud's phenomenon. The absence of ANA is a strong protective factor that identifies patients with very low risk of developing systemic sclerosis whereas the presence of one or two VEDOSS criteria in patients with Raynaud's phenomenon confers a progressively higher risk for systemic sclerosis over time. This stratification tool can be used both for clinical management and to inform early interventional trials. Funding European Scleroderma Trial And Research and World Scleroderma Foundation.

Background Pulmonary hypertension (PH) in COPD is a poorly investigated clinical condition. Research Question Which factors determine the outcome of PH in COPD? Study Design and Methods We analyzed the characteristics and outcome of patients enrolled in the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) with moderate or severe PH in COPD as defined during the 6th PH World Symposium who received medical therapy for PH and compared them with patients with idiopathic pulmonary arterial hypertension (IPAH). Results The population included incident patients with moderate PH in COPD (n = 68), with severe PH in COPD (n = 307), and with IPAH (n = 489). Patients with PH in COPD were older, predominantly male, and treated mainly with phosphodiesterase-5 inhibitors. Despite similar hemodynamic impairment, patients with PH in COPD achieved a worse 6-min walking distance (6MWD) and showed a more advanced World Health Organization functional class (WHO FC). Transplant-free survival rates at 1, 3, and 5 years were higher in the IPAH group than in the PH in COPD group (IPAH: 94%, 75%, and 55% vs PH in COPD: 86%, 55%, and 38%; P = .004). Risk factors for poor outcomes in PH in COPD were male sex, low 6MWD, and high pulmonary vascular resistance (PVR). In patients with severe PH in COPD, improvements in 6MWD by ≥ 30 m or improvements in WHO FC after initiation of medical therapy were associated with better outcomes. Interpretation Patients with PH in COPD were functionally more impaired and had a poorer outcome than patients with IPAH. Predictors of death in the PH in COPD group were sex, 6MWD, and PVR. Our data raise the hypothesis that some patients with severe PH in COPD may benefit from PH treatment. Randomized controlled studies are necessary to explore this hypothesis further. Trial Registry ClinicalTrials.gov; No.: NCT01347216 ; URL: www.clinicaltrials.gov

Summary Background Interstitial lung disease (ILD) is the most common cause of death in systemic sclerosis. To date, the progression of systemic sclerosis-associated ILD is judged by the accrual of lung damage on CT and pulmonary function tests. However, diagnostic tools to assess disease activity are not available. Here, we tested the hypothesis that quantification of fibroblast activation by PET-CT using a 68Ga-labelled selective inhibitor of prolyl endopeptidase FAP (68Ga-FAPI-04) would correlate with ILD activity and disease progression in patients with systemic sclerosis-associated ILD. Methods Between Sept 10, 2018, and April 8, 2020, 21 patients with systemic sclerosis-associated ILD confirmed by high-resolution CT (HRCT) within 12 months of inclusion and with onset of systemic sclerosis-associated ILD within 5 years or signs of progressive ILD and 21 controls without ILD were consecutively enrolled. All participants underwent 68Ga-FAPI-04 PET-CT imaging and standard-of-care procedures, including HRCT and pulmonary function tests at baseline. Patients with systemic sclerosis-associated ILD were followed for 6 months with HRCT and pulmonary function tests. We compared baseline 68Ga-FAPI-04 PET-CT uptake with standard diagnostic tools and predictors of ILD progression. The association of 68Ga-FAPI-04 uptake with changes in forced vital capacity was analysed using mixed-effects models. Follow-up 68Ga-FAPI-04 PET-CT scans were obtained in a subset of patients treated with nintedanib (follow-up between 6–10 months) to assess change over time. Findings 68Ga-FAPI-04 accumulated in fibrotic areas of the lungs in patients with systemic sclerosis-associated ILD compared with controls, with a median standardised uptake value (SUV) mean over the whole lung of 0·80 (IQR 0·60–2·10) in the systemic sclerosis-ILD group and 0·50 (0·40–0·50) in the control group (p Interpretation Our study presents the first in-human evidence that fibroblast activation correlates with fibrotic activity and disease progression in the lungs of patients with systemic sclerosis-associated ILD and that 68Ga-FAPI-04 PET-CT might improve risk assessment of systemic sclerosis-associated ILD. Funding German Research Foundation, Erlangen Anschubs-und Nachwuchsfinanzierung, Interdisziplinares Zentrum fur Klinische Forschung Erlangen, Bundesministerium fur Bildung und Forschung, Deutsche Stiftung Systemische Sklerose, Wilhelm-Sander-Foundation, Else-Kroner-Fresenius-Foundation, European Research Council, Ernst-Jung-Foundation, and Clinician Scientist Program Erlangen.

Summary Background Extracellular matrix remodelling is a hallmark of systemic sclerosis. We evaluated extracellular matrix neo-epitopes as potential serum biomarkers for progression of fibrosis in systemic sclerosis. Methods We included patients meeting the 2013 American College of Rheumatology and European League Against Rheumatism criteria and healthy controls from a derivation and validation cohort. The primary outcome was progression of fibrosis at follow-up, defined as decline in percentage of predicted forced vital capacity of 10% or more in patients with interstitial lung disease or increase in modified Rodnan skin score of 25% or more and more than 5 points at a 1-year follow-up visit. Longitudinal assessment and biobanking followed European Scleroderma Trials and Research standards. Extracellular matrix-degradation (BGM, C3M, C4M, and C6M) and extracellular matrix-formation neo-epitopes (PRO-C1, PRO-C3, PRO-C4, PRO-C5, and PRO-C6) were measured in serum using validated ELISAs. Findings Between Aug 18, 2011, and Jan 19, 2015, 149 patients with systemic sclerosis (27 [18%] progressors and 122 [82%] non-progressors) and 29 healthy controls were included in the derivation cohort. Concentrations of type III and IV collagen neo-epitopes were higher in patients with systemic sclerosis compared with healthy controls and were significantly associated with systemic sclerosis in univariable logistic regression. Concentrations of degradation neo-epitopes of type III and IV collagens and their turnover ratios distinguished between progressors and non-progressors (C3M area under the curve 0·77 [95% CI 0·67–0·86], p Interpretation These data suggest that neo-epitopes of type III and IV collagens are promising biomarkers for the assessment and prediction of extracellular matrix remodelling in systemic sclerosis. They could be used in clinical practice to risk stratify patients at risk of progression of fibrosis. Funding None.

To analyze the safety and effectiveness of abatacept (ABA) given in routine care to patients with systemic sclerosis (SSc).Retrospective multicenter observational study that enrolled patients with SSc treated with ABA. We collected epidemiological data and clinical outcomes. First, we analyzed the frequency of adverse effects. Secondly, we compared the evolution of different organ manifestations during ABA treatment. We collected data from 6 months before start of therapy to the last follow-up the following parameters: modified Rodnan Skin Score (mRSS), joints, lung and gastrointestinal involvement, concomitant medications, and laboratory tests.Data on twenty-seven patients with SSc were collected (93% females; 67% limited SSc). Rheumatoid arthritis was the most frequent concomitant autoimmune disease. ILD was present in 15 patients. Anti-Scl 70 antibodies were present in 13 patients and rheumatoid factor and ACPA antibodies were present in eight and seven patients respectively. The main indication to use abatacept was joint involvement (59%) followed by myositis (26%). A total of 16 adverse effects were reported in 28 months of abatacept treatment including five that required hospitalization. Most of them occurred in the first 3 months after starting abatacept. After 12 months, the number of tender and swollen joints decreased compared to baseline (p0.03 and p0.02 respectively). Moreover, a beneficial effect of abatacept on HAQ-DI at 3 and 6 months (p0.05) and on morning stiffness at 6 and 12 months (p0.03) was observed. We also observed a decrease in the modified Rodnan skin score (p0.05). No changes in lung or gastrointestinal involvement were found.ABA demonstrated a good safety profile and seems to have some effectiveness on joint involvement and related disability in SSc patients treated in routine care.

Summary Background Systemic sclerosis-associated interstitial lung disease (ILD) carries a high mortality risk; expert guidance is required to aid early recognition and treatment. We aimed to develop the first expert consensus and define an algorithm for the identification and management of the condition through application of well established methods. Methods Evidence-based consensus statements for systemic sclerosis-associated ILD management were established for six domains (ie, risk factors, screening, diagnosis and severity assessment, treatment initiation and options, disease progression, and treatment escalation) using a modified Delphi process based on a systematic literature analysis. A panel of 27 Europe-based pulmonologists, rheumatologists, and internists with expertise in systemic sclerosis-associated ILD participated in three rounds of online surveys, a face-to-face discussion, and a WebEx meeting, followed by two supplemental Delphi rounds, to establish consensus and define a management algorithm. Consensus was considered achieved if at least 80% of panellists indicated agreement or disagreement. Findings Between July 1, 2018, and Aug 27, 2019, consensus agreement was reached for 52 primary statements and six supplemental statements across six domains of management, and an algorithm was defined for clinical practice use. The agreed statements most important for clinical use included: all patients with systemic sclerosis should be screened for systemic sclerosis-associated ILD using high-resolution CT; high-resolution CT is the primary tool for diagnosing ILD in systemic sclerosis; pulmonary function tests support screening and diagnosis; systemic sclerosis-associated ILD severity should be measured with more than one indicator; it is appropriate to treat all severe cases; no pharmacological treatment is an option for some patients; follow-up assessments enable identification of disease progression; progression pace, alongside disease severity, drives decisions to escalate treatment. Interpretation Through a robust modified Delphi process developed by a diverse panel of experts, the first evidence-based consensus statements were established on guidance for the identification and medical management of systemic sclerosis-associated ILD. Funding An unrestricted grant from Boehringer Ingelheim International.

Movement control tests (MCTs) are clinical tests to evaluate impairment of movement and associated neuromuscular control and are commonly used to evaluate people with neck pain or headache conditions. The aim of this study was to establish inter-rater reliability as well as discriminatory and predictive validity for seven MCTs of the upper (UCS) and lower cervical spine (LCS) in office workers with headache or neck pain.Seven MCTs of the UCS (3) and LCS (4) were performed at baseline on 140 office workers which were included in a cluster randomized controlled trial. The occurrences of headache and neck pain were established at baseline (discriminatory validity) and at a 15-month follow-up (predictive validity). Inter-rater-reliability was established in a separate cross-sectional study.MCTs showed slight to almost perfect inter-rater reliability but limited discriminatory (baseline) and limited to small predictive validity (15-month follow up) for different subgroups of office workers with headache and/or neck pain. MCTs of the UCS showed limited discriminatory validity, especially for rotation in participants with headache and neck pain compared to those with headache only (Negative Likelihood-ratio: 0.82, 95% CI: 0.69-0.98). Participants with neck pain only and ≥1/4 positive MCTs for the sagittal plane had an increased risk for future neck pain (Relative risk: 3.33, 95% CI: 1.05-10.56).MCTs of the UCS and LCS are reliable but have only limited to small validity to predict future headache events in office workers. Insufficient sagittal plane movement control may predict neck pain relapses in the future.

Systemic sclerosis (SSc) is associated with increased mortality mostly due to cardiovascular or pulmonary causes [(1,2)][1]. Diagnosis of cardiac involvement remains challenging, especially at an early stage because standard echocardiography lacks sensitivity to detect subtle myocardial dysfunction

Background: Interstitial lung disease (ILD) is the most common cause of death in systemic sclerosis (SSc). However, the course of ILD in this population is highly variable. Effective diagnostic tools to assess activity and to predict the individual course of the disease are lacking. Here, we tested the hypothesis that in vivo quantification of fibroblast activation may correlate with ILD activity and improve risk stratification in SSc patients. Methods: Fibroblast activation was visualized by positron emission tomography/computed tomography (PET/CT) using the 68Gallium-labeled selective inhibitor of fibroblast activation protein (68Ga-FAPI-04). We correlated 68Ga-FAPI-04 uptake with changes in lung function parameters, high resolution CT scan (HRCT) and patient reported outcomes. 68Ga-FAPI-04 PET/CTs, HRCTs and lung function tests were evaluated in a blinded manner. Findings: In this single center study, we enrolled 21 patients with SSc-ILD, five patients with dermatomyositis-associated-ILD, ten non-SSc/non-ILD control patients and ten non-diseased control individuals. 68Ga-FAPI-04 accumulated in fibrotic areas of the lungs in SSc-ILD with significantly higher wlSUVmean (p 1.0 or a wlTL-FAPI > 500 cm3 demonstrated radiologic progression and decline of FVC after 6 months, but none of the patients with less 68Ga-FAPI-04 accumulation. In consecutive 68Ga-FAPI-04-PET/CTs, changes in 68Ga-FAPI-04 uptake correlated with response to the fibroblast-targeting antifibrotic agent nintedanib. Interpretation: Our study presents first in human evidence that fibroblast activation correlates with fibrotic activity and disease progression in the lungs of SSc-ILD patients and that 68Ga-FAPI-04-PET/CT may improve risk stratification. Funding: German Research Foundation, ELAN-Foundation-Erlangen and Bundesministerium fur Bildung und Forschung. Conflict of Interest: O.D. has consulted for, or has received research funding from, 4D Science, Actelion, Active Biotech, Bayer-Schering, Biogen, Biovitrium, BMS, Boehringer, EpiPharm, Ergonex, GSK, Inventiva, Medac, Novartis, Pfizer, Roche/Genentech, Sanofi/Genzyme, Serodapharm, Sinoxa and United BioSource Corporation; JHWD has consultancy relationships and/or has received research funding from Actelion, BMS, Celgene, Bayer Pharma, Boehringer Ingelheim, JBTherapeutics, Sanofi-Aventis, Novartis, UCB, GSK, Array Biopharma, Galapagos, Inventiva and Active Biotech in the area of potential treatments of SSc and is stock owner of 4D Science. Ethical Approval: File number 30_19B, Ethics Committee Friedrich-Alexander-University Erlangen.

The facial tissue of 9 healthy volunteers (m/f; age: 23-60y) is characterized at three different locations using a procedure combining suction measurements and 18MHz ultrasound imaging. The time-dependent and multilayered nature of skin is accounted for by adopting multiple loading protocols which differ with respect to suction probe opening size and rate of tissue deformation. Over 700 suction measurements were conducted and analyzed according to location-specific mechanical and morphological characteristics. All corresponding data are reported and made available for facial tissue analysis and biomechanical modeling. Higher skin stiffness is measured at the forehead in comparison to jaw and parotid; these two regions are further characterized by lower creep deformation. Thicker tissue regions display a tendency towards a more compliant and less dissipative response. Comparison of superficial layer thickness and corresponding mechanical measurements suggests that connective tissue density determines the resistance to deformation in suction experiments.

Introduction Dans l’etude INBUILD sur 52 semaines de traitement, le nintedanib versus placebo a ralenti le taux de declin de la capacite vitale forcee (CVF) sur la population totale atteinte de PID fibrosantes progressives autres qu’une fibrose pulmonaire idiopathique [n = 663] incluant le sous-groupe des patients avec une PID fibrosante progressive (PID-FP) associee a une maladie auto-immune [n = 170]. Nous avons evalue dans ce sous-groupe le delai de survenue : – du deces ; – de la premiere exacerbation aigue de la PID ou du deces ; – jusqu’a progression de la maladie (declin absolu de la CVF≥ 10 % de la valeur predite) ou deces sur l’ensemble de l’etude. Patients et methodes Les patients ont ete randomises pour recevoir le nintedanib 150 mg bid ou le placebo et ont poursuivi le traitement randomise en aveugle jusqu’a la fin de l’etude. Les taux d’incidence des evenements indesirables pour 100 patient–annees ont ete calcules sur la base des evenements survenus entre la premiere prise du medicament a l’etude et la derniere prise plus 28 jours. Les analyses etaient descriptives. Resultats 89 PID-PR, 39 PID-ScS, 19 PID-CM, 23 autres PID auto-immunes dont PID associee a un syndrome de Gougerot-Sjogren [n = 7], PID avec manifestations auto-immunes [n = 5] et PID associee a une connectivite indifferenciee [n = 3]. Respectivement dans les groupes nintedanib et placebo, 9,8 % et 12,5 % des patients sont decedes, 12,2 % et 20,5 % ont developpe ≥ 1 exacerbation aigue de PID ou sont decedes et 40,2 % et 53,4 % une progression de la maladie ou sont decedes. La diarrhee a ete l’evenement indesirable le plus frequent, avec des taux d’incidence de 139,2 et 26,3 evenements pour 100 patient–annees dans les groupes respectivement nintedanib et placebo. Les evenements indesirables ont entraine l’arret du traitement chez 20,7 % des patients (nintedanib) et 13,6 % des patients (placebo). Conclusion Les donnees de l’etude INBUILD suggerent que le nintedanib a un effet cliniquement significatif sur le ralentissement de la progression de la PID chez les patients atteints d’une PID associee a une maladie auto-immune fibrosante progressive, avec des evenements indesirables pouvant etre toleres par la majorite des patients.

The factors that determine how people eat when they are healthy or have disease have not been defined. We used high resolution manometry (HRM) to assess pharyngeal swallowing and oesophageal motility during ingestion of a solid test meal (STM) in healthy volunteers and patients with motility disorders.This study was based at University Hospital Zurich (Zürich, Switzerland). Healthy volunteers who responded to an advertisement completed HRM with ten single water swallows (SWS) in recumbent and upright positions followed by a 200 g rice STM in the upright position. Healthy volunteers were stratified for age and sex to ensure a representative population. For comparison, consecutive patients with major motility disorders on SWS and patients with dysphagia but no major motility disorders on SWS (disease controls) were selected from a database that was assembled prospectively; the rice meal data were analysed retrospectively. During STM, pharyngeal swallows were timed and oesophageal contractions were classified as representing normal motility or different types of abnormal motility in accordance with established metrics. Factors that could potentially be associated with eating speed were investigated, including age, sex, body-mass index, and presence of motility disorder. We compared diagnoses based on SWS findings, assessed with the Chicago Classification v3.0, with those based on STM findings, assessed with the Chicago Classification adapted for solids. These studies are registered with ClinicalTrials.gov, numbers NCT02407938 and NCT02397616.Between April 2, 2014, and May 13, 2015, 72 healthy volunteers were recruited and underwent HRM. Additionally, we analysed data from 54 consecutive patients with major motility disorders and 53 with dysphagia but no major motility disorders recruited between April 2, 2013, and Dec 18, 2014. We found important variations in oesophageal motility and eating speed during meal ingestion in healthy volunteers and patients. Increased time between swallows was accompanied by more effective oesophageal contractions (in healthy volunteers, 20/389 [5%] effective swallows at4 s between swallows vs 586/900 [65%] effective swallows at11 s between swallows, p0·0001). Obstructive, spastic, or hypercontractile swallows were rare in healthy volunteers (total1%). Patients with motility disorders ate slower than healthy volunteers (14·95 g [IQR 11-25] per min vs 32·9 g [25-40] per min, p0·0001) and pathological oesophageal motility were reproduced when patients consumed the STM. In healthy volunteers, eating speed was associated only with frequency of swallows (slope 2·5 g per min per pharyngeal swallow per min [95% CI 1·1-4·0], p=0·0009), whereas in patients with dysphagia, it was correlated with frequency of effective oesophageal contractions (6·4 g per min per effective contraction per min [4·3-8·5], p0·0001). Diagnostic agreement was good between the HRM with SWS and rice STM (intra-class correlation coefficient r=0·81, 95% CI 0·74-0·87, p0·0001).Our results show normative values for pharyngeal swallowing and oesophageal motility in healthy volunteers. Detailed analysis of HRM data acquired during an STM shows that the rate-limiting factor for intake of solids in health is the frequency of pharyngeal swallowing and not oesophageal contractility. The reverse is true in patients with oesophageal motility disorders, in whom the frequency of effective oesophageal contractions determines eating speed.University Hospital Zurich.

Introduction Dans l’essai SENSCIS, le nintedanib a reduit la progression de la pneumopathie interstitielle diffuse associee a la sclerodermie systemique (ScS-PID) par rapport au placebo, comme demontre par un taux significativement plus faible du declin de la capacite vitale forcee (CVF) sur une periode de 52 semaines (critere principal d’evaluation). L’objectif etait d’evaluer l’effet du nintedanib sur le taux de declin de la CVF dans l’essai SENSCIS dans des sous-groupes predefinis suivant leurs caracteristiques a l’inclusion. Methodes Les patients atteints d’une ScS-PID avec une apparition du premier symptome autre que le phenomene de Raynaud ≤ 7 ans a compter de la selection et avec une fibrose pulmonaire etendue de ≥ 10 % au scanner thoracique ont ete randomises en double aveugle pour recevoir du nintedanib 150 mg 2 fois par jour ou un placebo. Le taux annuel de declin de la CVF (mL/an) evalue sur 52 semaines (critere principal) a ete analyse dans la population globale en utilisant un modele a coefficient de regression aleatoire (avec pentes et interceptes aleatoires) incluant comme covariables le statut des anticorps anti-topo-isomerase I (ATI), l’âge, la taille, le sexe, et la CVF a l’inclusion. Les analyses en sous-groupes selon les caracteristiques a l’inclusion ont inclus des termes supplementaires pour l’interaction entre traitement et sous-groupes, et pour l’interaction entre traitement et sous-groupes en fonction du temps. Resultats Au total, 576 patients ont ete traites (288 dans chaque groupe). La plupart des patients etaient des femmes, 51,9 % avaient une ScS cutanee diffuse et 48,4 % recevaient du mycophenolate a l’inclusion. L’âge moyen (± DS) etait de 54,0 ± 12,2 ans et 21,4 % des patients avaient au moins 65 ans. Le nintedanib a montre une efficacite homogene en reduisant le taux de declin de la CVF dans les differents sous-groupes predefinis suivant leurs caracteristiques a l’inclusion (p > 0,05 d’interaction pour tous les traitements par sous-groupe et selon le temps) ( Fig. 1 ). Conclusion Le nintedanib est efficace pour reduire la progression de la PID chez un large eventail de patients atteints de ScS-PID.

Introduction: During March and April 2020, the COVID-19 pandemic forced around50 % of employees of Switzerland into a working from home setting. Working from home appears to have considerably changed the work experience of office workers. Newspapers reported an increase in non-specific neck pain as a negative consequence of working from home. Therefore, the main driver for this abstract was to confirm these observations with higher levels of evidence. Purpose of the study: The aim of this analysis was to investigate the effect of the first COVID-19 lockdown on neck pain. We hypothesised that the COVID-19 lockdown would increase neck pain. Methods: This longitudinal analysis is based on control group data from an ongoing stepped-wedge cluster randomised controlled trial. Office workers from two Swiss organisations, aged 18-65 years, were included. Baseline data collected in January 2020 before the COVID-19 pandemic were compared with follow-up data collected during the fourth and fifth week of the first lockdown in April 2020. Neck pain was assessed with a measure of intensity (numeric rating scale NRS from 0 = no pain to 10 = maximum pain), frequency (number of days within the last 28 days), and disability (neck disability index from 0 % = no disability to 100 % = maximum disability). Paired Wilcoxon signed rank tests were performed for statistical analysis as the normality assumption was not met. Results: Data from 76 participants were analysed. The mean age was 42.7 years (ranging from 21.8 to 62.7) at baseline and fifty-four participants (71.1 %) were female. At baseline, the meanintensity of neck pain was NRS 2.3 (± 1.9), mean frequency of neck pain 4.5 / 28 days (± 8.3), and mean neck disability 11.7 % (± 10.0). At follow-up, the mean intensity of neck pain was NRS 2.2 (± 2.2), mean frequency of neck pain 6.8 / 28 days (± 7.4), and mean neck disability 11.1 % (± 10.9). We found no evidence for a difference in the intensity of neck pain (estimate = 2.59*10-5, 95 % CI from -0.50 to 0.50, p-value = 0.607), frequency of neck pain (estimate = 3.26*10-5, 95 % CI from -2.00 to 2.50, p-value = 0.964), or neck disability index (estimate = 4.43*10-6, 95 % CI from -2.00 to 3.00, p-value = 0.794) between both measurement time points. Conclusion: The first COVID-19 lockdown did not result in a difference of neck pain among our sample of office workers, neither in intensity nor in frequency nor in disability. Therefore, our hypothesis and the findings of the newspapers could not be confirmed. A higher number of work breaks taken as well as improved working times and work-life balance may have contributed to this result. To enable more comprehensive statements, further dimensions of pain (i.e., duration) and the effect of psychosocial factors (i.e., mental health) would need to be investigated.

Objective Systemic sclerosis (SSc) is systemic autoimmune disease that is characterized by microangiopathy with progressive loss of capillaries, sparse inflammation and an overproduction of extracellular matrix proteins by SSc fibroblasts leading to tissue fibrosis. IM is a tyrosine kinase inhibitor that is widely used for the treatment of CML and GIST tumors and that targets selectively abl and PDGF receptor. We have demonstrated recently, the IM inhibits potently the productions of extracellular matrix by SSc fibroblasts and prevents experimental dermal fibrosis. The aim of the present study was to exclude that the antifibrotic effects of SSc are accompanied by antiangiogenic side-effects, which might augment vascular disease in SSc. Methods and results EC were incubated with IM in concentrations from 0.01 to 1.0 μg/ml IM, which corresponds to physiologically relevant doses. The expression of VEGF was analyzed in microvascular EC after incubation with IM. IM did not alter the expression of mRNA of VEGF as analyzed by real-time PCR. Cell viability was analyzed by caspase3 assays and by annexin V/ propidium iodide staining. IM did not increase the percentage of PI-positive and annexin V–positive cells. Consistently, the activity of caspase3 did not increase upon incubation of EC with IM. IM also did not alter the rate of proliferating cells or metabolic capacity of EC as assessed with the MTT assay neither after 24 h nor after long term incubation for 4 d. Cell migration was analyzed by scratch and migration assay. IM did not reduce the migratory capacity of EC. IM did also not alter the ability of endothelial cells to form tubes upon stimulation with VEGF as analyzed by capillary morphogenesis assay. The mouse model of bleomycin-induced dermal fibrosis was used to assess the effect of IM on markers of endothelial apoptosis in vivo. Consistent with the in vitro data, no differences in the number of apoptotic endothelial cells was observed in vivo with TUNEL assay. Conclusion IM does not inhibit proliferation, migration or tube forming in endothelial cells or induce apoptosis in vitro or in vivo, suggesting that IM has no direct inhibitory effects on endothelial cells.