The first EULAR provisional recommendations on the management of rheumatic and musculoskeletal diseases (RMDs) in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), largely based on expert opinion, were published in June 2020. Since then, an unprecedented number of clinical studies have accrued in the literature. Several SARS-CoV-2 vaccines have been approved for population-wide vaccination programmes in EULAR-affiliated countries. Studies regarding vaccination of patients with (inflammatory) RMDs have released their first results or are underway.EULAR found it opportune to carefully review to what extent the initially consensus expert recommendations stood the test of time, by challenging them with the recently accumulated body of scientific evidence, and by incorporating evidence-based advice on SARS-CoV-2 vaccination. EULAR started a formal (first) update in January 2021, performed a systematic literature review according to EULAR’s standard operating procedures and completed a set of updated overarching principles and recommendations in July 2021. Two points to consider were added in November 2021, because of recent developments pertaining to additional vaccination doses.

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Background & aimsHypothyroidism has recently been proposed as predisposing factor for HCC development. However, the role of thyroid hormones (TH) in established HCC is largely unclear. We investigated the impact of TH on clinical characteristics and prognosis of HCC patients.MethodsOf 838 patients diagnosed with nonsurgical HCC at the Division of Gastroenterology and Hepatology/Medical University of Vienna between 1992 and 2012, 667 patients fulfilled the inclusion criteria. The associations of thyroid function tests with patient, liver, and tumor characteristics as well as their impact on overall survival (OS) were investigated.ResultsThyroid hormone substitution was more often observed in patients with low thyroid-stimulating hormone (TSH) concentration and in patients with elevated free tetraiodthyronine (fT4). Patients with high TSH (>3.77uU/ml) concentrations had larger tumors, while the opposite was true for patients with low TSH (<0.44uU/ml) concentrations. Subjects with elevated fT4 (>1.66ng/dl) were more likely to have elevated CRP. While TSH was only associated with OS in univariate analysis (≤1.7 vs. >1.7uU/ml, median OS (95%CI), 12.3 (8.9–15.7 months) vs. 7.3 months (5.4–9.2 months); p = 0.003), fT4 (≤1.66 vs. >1.66ng/dl, median OS (95%CI), 10.6 (7.5–13.6 months) vs. 3.3 months (2.2–4.3 months); p = 0.007) remained an independent prognostic factor for OS (HR (95%CI) for fT4>1.66ng/dl, 2.1 (1.3–3.3); p = 0.002) in multivariate analysis.ConclusionsTSH and fT4 were associated with prognostic factors of HCC (i.e., tumor size, CRP level). Elevated fT4 concentrations were independently associated with poor prognosis in HCC. Further studies are needed to characterize the role of TH in HCC in detail.

BackgroundIt is an ongoing matter of research, whether the natural course of rheumatoid arthritis (RA) can be altered by an early intervention, a concept historically referred to as the “window of opportunity” (1). So far, only short-term disease activity outcomes have been investigated (e.g. “remission off drugs”), which are, however, inherently affected by the unknown rate of underlying rate self-limiting disease. It is unclear, whether among those, who eventually develop RA, the disease course is really affected by the timing of their initial treatment.ObjectivesTo explore whether the long-term course of RA is different according to the delay of initial treatment.MethodsBased on a longitudinal observational dataset, we initially identified a group of patients with an observed refractory disease, we defined presenting with ongoing moderate or high disease activity (by the Simplified Disease Activity Index, SDAI), despite at least three courses of DMARDs, of which at least on course was a biological compound. To ensure that sufficient time had been allowed for the previous treatments to be exert their non-effects, we also required these patients to have total treatment time of at least 18 months in accordance with treat to target strategy (3 x 6 months).We identified 399 patients with a treatment time of at least 18 months. 48 patients were excluded despite fulfilling the disease activity criteria, because they haven't experienced enough treatment courses, or had received a biological compound yet, to claim refractory disease as per our criteria above. We could include 69 refractory and 282 non-refractory patients in our analyses and then performed logistic regression analysis to assess the effects of different characteristics at baseline, including disease duration, on becoming refractory.ResultsBy comparing patient characteristics (Table 1), more of the patients, who later will become refractory, are female (94.2% Vs 73.4%, p>0.001), have higher baseline disease activity (SDAI of 25.5 vs 17.7, p<0.001), and longer delay of the initial treatment from symptom onset (3.17 Vs 1.34 years, p=0.001).The multivariable logistic regression model confirmed that a longer delay of first treatment is independently afflicted with a higher probability of a refractory disease course at a later stage. This model was adjusted for disease activity at baseline and gender (p<0.001, Figure 1). With increasing treatment delay, the chance of a dire disease course rises by approximately 1% every 6 months.Table 1.Baseline characteristics in refractory and non-refractory patientsBaseline DescriptiveReRA (n=69)non-ReRA (n=282)Sig. % Female94.273.4<0.001% RF +56.562.10.398% ACPA +60.961.00.985Time to Treatment*3.17 (4.10)1.34 (2.70)0.001SDAI25.54 (12.24)17.70 (12.17)<0.001CRP†2.02 (2.30)1.80 (2.02)0.435SJC 286.42 (5.35)4.64 (4.72)0.009TJC 289.22 (6.98)4.35 (5.40)<0.001EGA‡37.78 (20.49)28.77 (21.40)0.002PGA‡55.19 (26.67)41.42 (26.67)<0.001*years; †mg/dl; ‡100mm VAS scale.ConclusionsOur data suggest that delay to initial treatment in RA affe...