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Background and Purpose: The biallelic repeat expansion (AAGGG)exp in the replication factor C subunit 1 gene (RFC1) is a frequent cause of cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) as well as late-onset ataxia. The clinical spectrum of RFC1 disease has expanded since the first identification of biallelic (AAGGG)exp and includes now various nonclassical phenotypes. Biallelic (AAGGG)exp in RFC1 in patients with clinically confirmed Parkinson's disease (PD) has recently been found. Methods: A nationwide cohort of 273 Finnish patients with early-onset PD was examined for the biallelic intronic expansion in RFC1. The expansion (AAGGG)exp was first screened using extra long polymerase chain reactions (Extra Large-PCRs) and flanking multiplex PCR. The presence of biallelic (AAGGG)exp was then confirmed by repeat-primed PCR and, finally, the repeat length was determined by long-read sequencing. Results: Three patients were found with the biallelic (AAGGG)exp in RFC1 giving a frequency of 1.10% (0.23%–3.18%; 95% confidence interval). The three patients fulfilled the diagnostic criteria of PD, none of them had ataxia or neuropathy, and only one patient had a mild vestibular dysfunction. The age at onset of PD symptoms was 40–48 years and their disease course had been unremarkable apart from the early onset. Conclusions: Our results suggest that (AAGGG)exp in RFC1 is a rare cause of early-onset PD. Other populations should be examined in order to determine whether our findings are specific to the Finnish population. publishedVersion

Background The ten-joint juvenile arthritis disease activity score (JADAS10) is designed to measure the level of disease activity in non-systemic juvenile idiopathic arthritis by providing a single numeric score. The clinical JADAS10 (cJADAS10) is a modification of the JADAS10 that excludes erythrocyte sedimentation rate (ESR). Three different sets of JADAS10/cJADAS10 cut-offs for disease activity states have been published, i.e., the Backström, Consolaro, and Trincianti cut-offs. The objective of this study was to investigate the performance of existing JADAS10 cut-offs in real-life settings using patient data from The Finnish Rheumatology Quality Register (FinRheuma). Methods Data were collected from the FinRheuma register. The proportion of patients with an active joint count (AJC) above zero when classified as being in clinically inactive disease (CID) or low disease activity (LDA) groups according to existing JADAS10/cJADAS10 cut-off levels were analyzed. Results A significantly larger proportion of the patients classified as being in CID had an AJC > 0 when using the JADAS10/cJADAS10 cut-offs by Trincianti et al. compared to those for the other cut-offs. In the LDA group, a significantly larger proportion of the polyarticular patients (35%/29%) had an AJC of two when Trincianti JADAS10/cJADAS10 cut-offs were used compared with when Backström (11%/10%) and Consolaro (7%/3%) JADAS10/cJADAS10 cut-offs were used. Conclusions We found the cut-offs proposed by Consolaro et al. to be the most feasible, since these cut-off levels for CID do not result in the misclassification of active disease as remission, and the proportion of patients with AJC > 1 in the LDA group is lowest using these cut-offs.

Background: Our aim is to describe and compare the profile and outcome of patients attending the ED with a confirmed COVID-19 infection with patients with a suspected COVID-19 infection. Methods: We conducted a multicentric retrospective study including adults who were seen in 21 European emergency departments (ED) with suspected COVID-19 between 9 March and 8 April 2020. Patients with either a clinical suspicion of COVID-19 or confirmed COVID-19, detected using either a RT-PCR or a chest CT scan, formed the C+ group. Patients with non-confirmed COVID-19 (C− group) were defined as patients with a clinical presentation in the ED suggestive of COVID-19, but if tests were performed, they showed a negative RT-PCR and/or a negative chest CT scan. Results: A total of 7432 patients were included in the analysis: 1764 (23.7%) in the C+ group and 5668 (76.3%) in the C− group. The population was older (63.8 y.o. ±17.5 vs. 51.8 y.o. +/− 21.1, p < 0.01), with more males (54.6% vs. 46.1%, p < 0.01) in the C+ group. Patients in the C+ group had more chronic diseases. Half of the patients (n = 998, 56.6%) in the C+ group needed oxygen, compared to only 15% in the C− group (n = 877). Two-thirds of patients from the C+ group were hospitalized in ward (n = 1128, 63.9%), whereas two-thirds of patients in the C− group were discharged after their ED visit (n = 3883, 68.5%). Conclusion: Our study was the first in Europe to examine the emergency department’s perspective on the management of patients with a suspected COVID-19 infection. We showed an overall more critical clinical situation group of patients with a confirmed COVID-19 infection.

Background Dysbiotic intestinal and oral microbiota have been implicated in the pathogenesis of rheumatoid arthritis (RA), but the mechanisms how microbiota could impact disease activity have remained elusive. The aim of this study was to assess the association of the biological activity of serum lipopolysaccharides (LPS) with disease activity and likelihood of achieving remission in RA patients. Methods We measured Toll-like receptor (TLR) 4-stimulating activity of sera of 58 RA patients with a reporter cell line engineered to produce secreted alkaline phosphatase in response to TLR4 stimulation. Levels of LPS-binding protein, CD14, and CD163 were determined by ELISA assays. Results The patient serum-induced TLR4 activation (biological activity of LPS) was significantly associated with inflammatory parameters and body mass index at baseline and at 12 months and with disease activity (DAS28-CRP, pp=0.031) and, in 28 early RA patients, the likelihood of achieving remission at 12 months (p=0.009). The level of LPS bioactivity was similar at baseline and 12-month visits, suggesting that LPS bioactivity is an independent patient-related factor. Neutralization of LPS in serum by polymyxin B abrogated the TLR4 signaling, suggesting that LPS was the major contributor to TLR4 activation. Conclusion We describe a novel approach to study the biological activity of serum LPS and their impact in diseases. The results suggest that LPS contribute to the inflammatory burden and disease activity on patients with RA and that serum-induced TLR4 activation assays can serve as an independent prognostic factor. Graphical Abstract A graphical summary of the conclusions of the study.

Background Previous research on parastomal hernia repair following ileal conduit urinary diversion is limited. This nationwide cohort study aims to present the results of keyhole and Sugarbaker techniques in parastomal hernia repair in the setting of ileal conduit urinary diversion. Method All patients in this cohort underwent primary elective parastomal hernia repair following ileal conduit urinary diversion in four university hospitals and one central hospital in Finland in 2007–2017. Retrospective clinical data were collected from patient registries to compare keyhole and Sugarbaker parastomal hernia repair techniques. The primary outcome was parastomal hernia recurrence during the follow-up from primary surgery to the last confirmed follow-up date of the patient. The secondary outcomes were reoperations during the follow-up and complication rate at 30 days’ follow-up. Results The results of 28 hernioplasties were evaluated. The overall parastomal hernia recurrence rate was 18%, the re-operation rate was 14%, and the complication rate was 14% during the median follow-up time of 30 (21–64) months. Recurrence rates were 22% (4/18) after keyhole repair and 10% (1/10) after Sugarbaker repair. Re-operation rates referred to keyhole repair were 22% and Sugarbaker repair 0% during follow-up. The majority of reoperations were indicated by recurrence. Complication rates were 17% after keyhole and 10% after Sugarbaker repair during the 30 days’ follow-up. Conclusion The results of parastomal hernia repair in the setting of ileal conduits are below optimal in this nationwide cohort comparing keyhole to Sugarbaker repair in elective parastomal hernia repair. Nonetheless, the Sugarbaker technique should be further studied to confirm the encouraging results of this cohort in terms of recurrence.

Julkaisua ei hallinnoi Genomibiologian yksikkö, mutta en saanut yksikköä vaihdettua. Päätekijöiden affiliaatio: Department of Rheumatology, University of Helsinki and Helsinki University Hospital , Helsinki, Finland. Oma julkaisuun liittyvä affiliaationi: University of Helsinki, Faculty of Medicine, Clinicum. Objectives: To study whether female patients with active rheumatoid arthritis (RA) have myocardial abnormalities and whether progression of myocardial involvement can be attenuated by disease-modifying anti-rheumatic drugs (DMARDs). Method: Cardiac magnetic resonance (cMR; 1.5 or 3.0 T), including late gadolinium enhancement (LGE), T1 relaxation time, and ventricular functions, was performed in 30 patients with untreated active early RA starting first DMARDs, and 28 patients with chronic RA with inadequate response to conventional synthetic DMARDs starting biological DMARDs. cMR was repeated in RA patients 1 year later. cMR was conducted once in 22 fibromyalgia (FM) subjects and in 35 healthy volunteers serving as controls. All subjects were non-smoking females without coronary heart disease, heart failure, or diabetes. Results: Compared with controls, 58 RA patients had slightly lower ventricular function, although in the normal range, and longer T1 time at baseline. None of the FM subjects had LGE, but it was frequent in RA (67%). During the 1 year DMARD treatment, Disease Activity Score based on 28-joint count-C-reactive protein declined, ventricular functions tended to improve, but the number of patients with LGE remained unchanged. However, the number of LGE-positive heart segments either decreased or stayed the same in 91% of RA patients. In early RA patients, achieving tight remission was associated with LGE stabilization, after adjustment for age, metabolic syndrome, baseline inflammatory activity, and leisure-time physical activity. Conclusion: Treatment targeted to tight remission in early stages of RA seems to be important to prevent not only joint damage but also myocardial abnormalities.