A retrospective study of people with familial hypercholesterolaemia in a Belgian lipid clinic.

BACKGROUND: Familial hypercholesterolaemia (FH) is a genetic disease characterised by hypercholesterolaemia and premature cardiovascular events. Early diagnosis and treatment can reduce the cardiovascular burden. We describe the characteristics of patients with heterozygous FH followed in a tertiary hospital in Belgium. METHODS: We retrospectively studied a population of 321 patients with definite heterozygous FH who visited the UZ Leuven lipid clinic at least once between 1 January 2016 and 31 December 2020. Data are represented as mean ± SD. RESULTS: The age at time of diagnosis of FH was 39 ± 18 years. Patients with atherosclerotic disease (secondary prevention) were older (p < .001), more often male (p < .001), had a higher body mass index (p < .001), prevalence of (pre)diabetes (p < .001) and hypertension (p < .001) and had lower levels of low-density lipoprotein-cholesterol (LDL-C) (p < .001) than individuals without atherosclerotic disease (primary prevention). The average LDL-C in both primary (109 ± 53 mg/dL) and secondary (81 ± 63 mg/dL) prevention did not meet the targets of LDL-C as proposed by the 2019 ESC/EAS guidelines for the management of dyslipidaemias. However, LDL-C levels in the subgroup of patients treated with PCSK9 inhibition therapy, and especially in the triple therapy group (combination of statin, ezetimibe and PCSK9 inhibitor), were markedly lower (p < .001). CONCLUSIONS: In this Belgian population, people with heterozygous FH remain undertreated. Reaching treatment targets in FH seems possible, although this requires combination treatment (with PCSK9-targeted therapy) in most patients. Earlier diagnosis of FH, more extensive lipid-lowering treatment and reimbursement options and a more holistic approach are needed to lower LDL-C and cardiovascular risk in patients with FH.

Hypoxia and Wnt signaling inversely regulate expression of chondroprotective molecule ANP32A in articular cartilage.

OBJECTIVES: ANP32A is a key protector of cartilage health, via preventing oxidative stress and Wnt hyper-activation. We aimed to unravel how ANP32A is regulated in cartilage. METHODS: A bioinformatics pipeline was applied to identify regulators of ANP32A. Pathways of interest were targeted to study their impact on ANP32A in in vitro cultures of the human chondrocyte C28/I2 cell-line and primary human articular chondrocytes (hACs) from up to five different donors, using Wnt-activator CHIR99021, hypoxia-mimetic IOX2 and a hypoxia chamber. ANP32A was evaluated using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. In vivo, the effect of hypoxia was examined by immunohistochemistry in mice injected intra-articularly with IOX2 after destabilization of the medial meniscus. Effects of Wnt hyper-activation were investigated using Frzb-knockout mice and wild-type mice treated intra-articularly with CHIR99021. Wnt inhibition effects were assessed upon intra-articular injection of XAV939. RESULTS: The hypoxia and Wnt signaling pathways were identified as networks controlling ANP32A expression. In vitro and in vivo experiments demonstrated increases in ANP32A upon hypoxic conditions (1.3-fold in hypoxia in C28/I2 cells with 95% confidence interval (CI) [1.11-1.54] and 1.90-fold in hACs [95% CI: 1.56-2] and 1.67-fold in ANP32A protein levels after DMM surgery with IOX2 injections [95% CI: 1.33-2.08]). Wnt hyper-activation decreased ANP32A in chondrocytes in vitro (1.23-fold decrease [95% CI: 1.02-1.49]) and in mice (1.45-fold decrease after CHIR99021 injection [95% CI: 1.22-1.72] and 1.41-fold decrease in Frzb-knockout mice [95% CI: 1.00-1.96]). Hypoxia and Wnt modulated ataxia-telangiectasia mutated serine/threonine kinase (ATM), an ANP32A target gene, in hACs (1.89-fold increase [95% CI: 1.38-2.60] and 1.41-fold decrease [95% CI: 1.02-1.96]). CONCLUSIONS: Maintaining hypoxia and limiting Wnt activation sustain ANP32A and protect against osteoarthritis.

Belgian rheumatologists' preferences regarding measures of disease activity in patients with rheumatoid arthritis: results from a mixed-methods study.

The reliability and clinical usefulness of the different composite disease activity scores and their individual components in Rheumatoid Arthritis (RA) are still debated. This study investigated which measures of disease activity were preferred by rheumatologists. A mixed-method study was performed. First, ten Belgian rheumatologists were invited for individual interviews on their current practice and preferences for measurement of RA disease activity. Results of this qualitative study and evidence from literature served as input for developing a survey. This survey asked rheumatologists to rate preferred standard disease activity score(s), their individual components, ultrasound and related patient-reported outcomes (PROs), by maximum difference scaling. The relative importance score (RIS) for each indicator was calculated using hierarchical Bayes modeling. The qualitative study included 6/10 invited rheumatologists. Composite scores and components were perceived as useful, while PROs were found subjective. Interestingly, ultrasound was used to mediate discrepancies between physician and patient. The survey based on this was sent to 244 Belgian rheumatologists, 83/244 (34%) responded, including 66/83 (80%) complete and 17/83 (20%) incomplete surveys (two missing essential information). Most rheumatologists (75/81, 93%) used a disease activity score and 68/81 (84%) preferred the DAS28-CRP. Swollen joint count obtained the highest mean ± SD RIS (22.54 ± 2.64), followed by DAS28 ESR/CRP (20.61 ± 4.06), ultrasound (16.47 ± 7.97), CRP (13.34 ± 6.11) and physician's global assessment (12.59 ± 7.83). PROs including fatigue, pain, and patient's global assessment, and Health Assessment Questionnaire, obtained the lowest mean RIS (0.34-2.54). Rheumatologists place more faith in self-assessed disease activity components or in laboratory tests. Trust in PROs to evaluate disease activity is low in clinical practice.

Tapering of Etanercept is feasible in patients with Rheumatoid Arthritis in sustained remission: a pragmatic randomized controlled trial.

OBJECTIVE: In patients with rheumatoid arthritis (RA) in sustained remission, tapering of biological disease-modifying anti-rheumatic drugs can be considered. Tapering has already been investigated, but its feasibility remains to be determined. Therefore, we explored the feasibility of tapering etanercept in RA in a setting close to practice. METHOD: Patients with RA in 28-joint Disease Activity Score (DAS28) remission (≥ 6 months) and treated with etanercept 50 mg weekly (≥ 1 year) were included in the pragmatic 1 year open-label multicentre randomized controlled TapERA (Tapering Etanercept in Rheumatoid Arthritis) trial. Patients were assigned to continue etanercept weekly or to taper to every other week (EOW). Patients who lost remission [DAS28-C-reactive protein (CRP) ≥ 2.6] were re-escalated to etanercept weekly. The primary outcome was the proportion of patients maintaining DAS28-CRP remission for 6 months. RESULTS: Sixty-six patients were randomized to etanercept weekly (n = 34) or EOW (n = 32). After 6 months, 26/34 patients (76%) in the weekly and 19/32 (59%) in the EOW group maintained disease control (p = 0.136). In the EOW group, 20/32 patients (63%) remained on their tapered treatment during the trial. Two patients reintroduced weekly etanercept themselves. Ten patients were re-escalated to etanercept weekly by the rheumatologist, after a median (interquartile range) interval of 3.0 (2.0-6.0) months. Among these patients, 7/10 regained remission after re-escalation, four of them at the next study visit. CONCLUSIONS: Although non-inferiority could not be demonstrated, tapering of etanercept to EOW appeared feasible in patients in sustained remission.

A systematic review on the effect of DMARDs on fertility in rheumatoid arthritis.

INTRODUCTION: Drug therapy could alter fertility in patients with rheumatoid arthritis (RA). We aimed to perform a systematic review to evaluate if Disease-modifying antirheumatic drug (DMARD) therapy influences fertility as this is an important point to consider in shared decision making on RA therapy. METHODS: A search was conducted at 18/10/2019 in EMBASE, PubMed (including MEDLINE) and the Web of Science Core Collection. Our inclusion criteria were studies involving women or men diagnosed with RA, older than 18 years and on DMARD therapy, with as outcome a fertility parameter. Systematic reviews, meta-analyses, case reports, case series and animal studies were excluded. Studies not in English or Dutch or published before 2004 were excluded. Quality appraisal was performed by the CASP systematic review checklist. RESULTS: After duplicate removal, 9030 references were identified. After title/abstract screening, 82 articles remained. After full text screening, 4 articles could be retained. No studies were found through backward snowballing. Only studies involving women could be retained. The included studies investigated the effect of methotrexate, certolizumab pegol, etanercept and sulfasalazine on fertility. No detrimental effects of these DMARDs on time-to-pregnancy, anti-Müllerian hormone serum level or presence of a history of infertility, were reported. CONCLUSION: This systematic review underlines the gap in knowledge regarding the effect of DMARDs on fertility in women and especially men with RA. DMARD treatment, contrary to general belief, seemed to have no harmful effect on fertility, possibly because it resulted in better controlled disease activity. More research is needed to improve guidance for patients with RA with a child wish.

Lupus miliar diseminado facial (LDMF) / Facial disseminated Miliar Lupus (FDML)

Se presenta un paciente con lupuis vulgar diseminado facial; se comentan algunos rasgos de esta patología y se plantean diagnósticos diferencxiales por su similitud clínica e histológica con otras entidades. Con respecto al tratamiento se utilizó prednisona a dosis decrecientes manteniendo dosis bajas por cuatro meses, obteniendo buenos resultados(AU)

Lupus miliar diseminado facial (LDMF) / Facial disseminated Miliar Lupus (FDML)

Se presenta un paciente con lupuis vulgar diseminado facial; se comentan algunos rasgos de esta patología y se plantean diagnósticos diferencxiales por su similitud clínica e histológica con otras entidades. Con respecto al tratamiento se utilizó prednisona a dosis decrecientes manteniendo dosis bajas por cuatro meses, obteniendo buenos resultados