The TBLR1/TBL1 Co-Factor Complex Acts as a Transcriptional Checkpoint in the Brown Adipose Tissue Response to Prolonged Cold Exposure.

Brown adipose tissue (BAT) is a key thermogenic organ, whose activation in response to cold environmental temperatures and β-adrenergic stimulation requires the proper function of the NCOR/HDAC3 corepressor complex in brown adipocytes. The NCOR/HDAC3 complex is large and multi-component, including the transducin beta-like 1 (TBL1) and TBL1-related 1 (TBLR1) proteins. Loss of TBL1 in the hepatocytes and TBLR1 in the white adipocytes has been shown to impair fasting- and β-adrenergic-induced lipolysis.

Functional liver genomics identifies hepatokines promoting wasting in cancer cachexia.

In cancer cachexia, the presence of a tumor triggers systemic metabolic disruption that leads to involuntary body weight loss and accelerated mortality in affected patients. Here, we conducted transcriptomic and epigenomic profiling of the liver in various weight-stable cancer and cancer cachexia models. An integrative multilevel analysis approach identified a distinct gene expression signature that included hepatocyte-secreted factors and the circadian clock component REV-ERBα as key modulator of hepatic transcriptional reprogramming in cancer cachexia.

Interchangeability of patient pain, fatigue and global scores in patients with spondyloarthritis - a registry-based simulation study.

Background: To investigate a patient-level single imputation approach for patient reported outcomes (PROs) that express similar contents or associated PROs, where a PRO whose value is missing at a particular timepoint is substituted by another PRO whose value is available at the same timepoint.

Methods: We performed a simulation study on registry-based spondyloarthritis data to explore the potential interchangeability between the patient pain (PPA) and fatigue (PFA) assessment scores and relevant Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) individual questions, and between PPA, PFA and patient global assessment (PGA). Performance was assessed per imputation method in terms of relative bias and coverage.

Exploring associations of single nucleotide polymorphisms in ERAP1 and ERAP2 with susceptibility to multiple immune-mediated inflammatory diseases.

Single nucleotide polymorphisms (SNPs) in the endoplasmic reticulum aminopeptidase 1 (ERAP1) and ERAP2 genes have been associated with susceptibility to various immune-mediated inflammatory diseases (IMIDs). We utilized a unique cohort from the National Centre for Autoimmune Diseases (NCAS) to investigate whether specific SNPs in ERAP1 and ERAP2 act as a shared genetic susceptibility factor across various IMIDs. The study population comprised 171 patients from the NCAS cohort with two or more IMIDs and 57 healthy controls.

Towards a consensus atlas of human and mouse adipose tissue at single-cell resolution.

Adipose tissue (AT) is a complex connective tissue with a high relative proportion of adipocytes, which are specialized cells with the ability to store lipids in large droplets. AT is found in multiple discrete depots throughout the body, where it serves as the primary repository for excess calories. In addition, AT has an important role in functions as diverse as insulation, immunity and regulation of metabolic homeostasis.

Disparities in the organisation of national healthcare systems for treatment of patients with psoriatic arthritis and axial spondyloarthritis across Europe.

Background: Studies on national policies for biologics are warranted.

Objectives: To map and compare national healthcare set-ups for prescription, start, switch, tapering, and discontinuation of biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) in patients with psoriatic arthritis and axial spondyloarthritis across Europe, and assess the healthcare set-ups in relation to countries' socio-economic status.

Methods: An electronic survey was developed to collect and compare information on national healthcare systems.

Handling of missing component information for common composite score outcomes used in axial spondyloarthritis research when complete-case analysis is unbiased.

Background: Observational data on composite scores often comes with missing component information. When a complete-case (CC) analysis of composite scores is unbiased, preferable approaches of dealing with missing component information should also be unbiased and provide a more precise estimate. We assessed the performance of several methods compared to CC analysis in estimating the means of common composite scores used in axial spondyloarthritis research.

Challenge of missing data in observational studies: investigating cross-sectional imputation methods for assessing disease activity in axial spondyloarthritis.

Objectives: We aimed to compare various methods for imputing disease activity in longitudinally collected observational data of patients with axial spondyloarthritis (axSpA).

Methods: We conducted a simulation study on data from 8583 axSpA patients from ten European registries. Disease activity was assessed by the Axial Spondyloarthritis Disease Activity Score (ASDAS) and the corresponding low disease activity (LDA; ASDAS<2.

Complement proteins in axial spondyloarthritis: associations with disease activity and TNFi treatment response in a multicentre RCT.

Objectives: To investigate lectin pathway proteins (LPPs) and complement activation marker C3dg as biomarkers for disease activity and treatment response in a multicentre, randomized controlled trial of axial spondyloarthritis (axSpA) patients initiating TNF inhibitor (TNFi) therapy.

Methods: Serum samples from 108 patients with active radiographic axSpA from the CONSUL study, collected before and after 12 weeks of TNFi therapy, were measured using immunoassays for LPPs (MBL, CL-L1, M-, L-, and H-ficolin, MASP-1, -2, and -3, MAp44) and the complement activation marker C3dg.

Results: After 12 weeks of TNFi therapy, serum levels of LPPs L-ficolin, M-ficolin, and MASP-2 decreased, while MASP-3 increased after adjustment for baseline CRP.

Predictors of Secukinumab Treatment Response and Continuation in Axial Spondyloarthritis: Results From the EuroSpA Research Collaboration Network.

Objective: In patients with axial spondyloarthritis (axSpA) initiating secukinumab (SEC), we aimed to identify baseline (treatment start) predictors of achieving low disease activity (LDA) after 6 months, as measured by the Axial Spondyloarthritis Disease Activity Score using C-reactive protein (ASDAS-CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), as well as treatment continuation after 12 months.

Methods: From 11 European registries, patients with axSpA who initiated SEC treatment in routine care, with available data on 6-month ASDAS-CRP and BASDAI assessments were included. Logistic regression analyses on multiply imputed baseline data were performed; potential baseline predictors included demographic, diagnosis, lifestyle, clinical, and patient-reported variables.

Differences in the response to TNF inhibitors at distinct joint locations in patients with psoriatic arthritis: results from nine European registries.

Background: Efficacy of tumour necrosis factor inhibitors (TNFi) for peripheral arthritis in patients with psoriatic arthritis (PsA) has been established in randomized clinical trials that have used improvement in summated joint counts as an outcome. Whether joints at different anatomical locations might respond differentially to TNFi remains unknown. The aim of the study was to investigate potential variations in the responsiveness to a first tumour necrosis factor inhibitor (TNFi) among joints at distinct locations in patients with psoriatic arthritis (PsA) treated in routine clinical care.

Impact of patient characteristics on ASDAS disease activity state cut-offs in axial spondyloarthritis: results from nine European rheumatology registries.

Objectives: To re-evaluate cut-offs for disease activity states according to the Axial Spondyloarthritis Disease Activity Score (ASDAS), and study the impact of sex, age, calendar time, disease and symptom duration on ASDAS and ASDAS cut-offs in a large contemporary cohort.

Methods: Data from 2939 patients with axial spondyloarthritis (axSpA) starting their first tumour necrosis factor inhibitor in nine European registries were pooled and analysed. Receiver operating characteristic analyses were performed to identify cut-offs against external criteria.

Effectiveness of secukinumab in radiographic and non-radiographic axial spondyloarthritis: a European routine-care observational study.

Objectives: To compare the treatment effectiveness of secukinumab in radiographic (r) versus non-radiographic (nr) axial spondyloarthritis (axSpA) patients treated in routine care across Europe.

Methods: Prospectively collected data on secukinumab-treated axSpA patients with known radiographic status were pooled from nine countries.Remission rates based on patient-reported outcomes (PROs; Numeric Rating Scale (0-10), for example, pain ≤2/Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≤2 and Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease (ID) <1.

Exploring TNFi drug-levels and anti-drug antibodies during tapering among patients with inflammatory arthritis: secondary analyses from the randomised BIODOPT trial.

To evaluate tumour necrosis factor inhibitor (TNFi) drug-levels and presence of anti-drug antibodies (ADAb) in patients with inflammatory arthritis who taper TNFi compared to TNFi continuation. Patients with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis on stable TNFi dose and in low disease activity ≥ 12 months were randomised (2:1) to disease activity-guided tapering or control. Blood samples at baseline, 12- and 18-months were evaluated for TNFi drug-levels and ADAb.

Patient-reported outcomes in axial spondyloarthritis and psoriatic arthritis patients treated with secukinumab for 24 months in daily clinical practice.

Objectives: In patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) initiating secukinumab, we aimed to assess and compare the proportion of patients achieving 6-, 12- and 24-month patient-reported outcomes (PRO) remission and the 24-month retention rates.

Patients And Methods: Patients with axSpA or PsA from 16 European registries, who initiated secukinumab in routine care were included. PRO remission rates were defined as pain, fatigue, Patient Global Assessment (PGA) ≤2 (Numeric Rating Scale (NRS) 0-10) and Health Assessment Questionnaire (HAQ) ≤0.

Patient-Reported Outcomes (PROs) and PRO Remission Rates in 12,262 Biologic-Naïve Patients With Psoriatic Arthritis Treated With Tumor Necrosis Factor Inhibitors in Routine Care.

Objective: To evaluate patient-reported outcomes (PROs) after initiation of tumor necrosis factor inhibitor (TNFi) treatment in European real-world patients with psoriatic arthritis (PsA). Further, to investigate PRO remission rates across treatment courses, registries, disease duration, sex, and age at disease onset.

Methods: Visual analog scale or numerical rating scale scores for pain, fatigue, patient global assessment (PtGA), and the Health Assessment Questionnaire-Disability Index (HAQ-DI) from 12,262 patients with PsA initiating a TNFi in 13 registries were pooled.

Sex Differences in the Effectiveness of First-Line Tumor Necrosis Factor Inhibitors in Psoriatic Arthritis: Results From the European Spondyloarthritis Research Collaboration Network.

Objective: Women with psoriatic arthritis (PsA) may have reduced tumor necrosis factor inhibitor (TNFi) effectiveness compared to men. We examined sex differences in treatment response and retention rates during 24 months of follow-up among patients with PsA initiating their first TNFi.

Methods: Data from patients with PsA across 13 European Spondyloarthritis Research Collaboration Network registries starting their first TNFi were pooled.

Endometrial preparation protocols prior to frozen embryo transfer - convenience or safety?

The number of frozen embryo transfer (FET) cycles is increasing rapidly worldwide. Different endometrial preparations for FET result in comparable live birth rates. However, several recent publications have reported higher maternal risks for hypertensive disorders of pregnancy (HDP), pre-eclampsia and postpartum haemorrhage (PPH) in programmed cycles (PC-FET) compared with natural cycles and modified natural cycles with an intact corpus luteum.