Remission and low disease activity are associated with lower healthcare costs: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.

OBJECTIVES: This study aims to determine the independent impact of definitions of remission/low disease activity (LDA) on direct/indirect costs (DCs, ICs) in a multicentre inception cohort. METHODS: Patients from 31 centres in 10 countries were enrolled within 15 months of diagnosis and assessed annually. Five mutually exclusive disease activity states (DAS) were defined as (1) remission off-treatment: clinical (c) SLEDAI-2K=0, without prednisone/immunosuppressants; (2) remission on-treatment: cSLEDAI-2K=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; (3) LDA-Toronto Cohort (TC): cSLEDAI-2K≤2, without prednisone/immunosuppressants; (4) modified lupus LDA state (mLLDAS): SLEDAI-2K≤4, no activity in major organs/systems, no new activity, prednisone ≤7.5 mg/day and/or maintenance immunosuppressants and (5) active: all remaining assessments.At each assessment, patients were stratified into the most stringent DAS fulfilled and the proportion of time in a DAS since cohort entry was determined. Annual DCs/ICs (2021 Canadian dollars) were based on healthcare use and lost workforce/non-workforce productivity over the preceding year.The association between the proportion of time in a DAS and annual DC/IC was examined through multivariable random-effects linear regressions. RESULTS: 1692 patients were followed a mean of 9.7 years; 49.0% of assessments were active. Remission/LDA (per 25% increase in time in a remission/LDA state vs active) were associated with lower annual DC/IC: remission off-treatment (DC -$C1372; IC -$C2507), remission on-treatment (DC -$C973; IC -$C2604,) LDA-TC (DC -$C1158) and mLLDAS (DC -$C1040). There were no cost differences between remission/LDA states. CONCLUSIONS: Our data suggest that systemic lupus erythematosus patients who achieve remission, both off and on-therapy, and reductions in disease activity incur lower costs than those experiencing persistent disease activity.

Coronary Artery Calcification Progression in Patients With Systemic Lupus Erythematosus.

OBJECTIVE: To evaluate the progression of coronary artery calcification (CAC) and associated risk factors in a systemic lupus erythematosus (SLE) cohort. METHODS: We reassessed the presence of CAC in patients with SLE who were screened 9 years before, using multidetector computed tomography. Clinical variables (cumulated disease activity and damage accrual), antiphospholipid syndrome and SLE serology, and cardiovascular (CV) risk factors (hypertension, BMI [kg/m2], modified Framingham risk score, lipid profile, menopausal status) were assessed longitudinally. RESULTS: We included 104 patients from the parent study. Most of them were women (94.2%), with a mean age of 41.0 (SD 8.3) years and mean disease duration of 14.8 (SD 2.9) years. We documented CAC in 17 patients (16.3%). Seven cases were from the parent study and 10 were incident cases. The cumulative incidence of CAC was 9% and the incidence density was 1 per 100 person-years. CAC occurred more frequently in the age groups 30-39 years and 40-44 years. All patients with previous CAC had worsening of their calcium indexes, and none developed clinical CV events. When comparing prevalent CAC cases (n = 17) vs patients without calcification (n = 87), both groups were similar in traditional CV risk factors, disease duration, Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) area under the curve (AUC), and Systemic Lupus International Collaborating Clinics (SLICC) score, but were more likely to be postmenopausal and have higher apolipoprotein B (apoB) levels. Patients with previous CAC had higher apoB levels, SLEDAI-2K AUC scores, and anticardiolipin IgG antibodies than incident cases. CONCLUSION: CAC in patients with SLE progressed over time but was not associated with adverse CV events during the first 9 years of follow-up. ApoB levels and postmenopausal status might be associated with this progression.

Anti-KIF20B autoantibodies are associated with cranial neuropathy in systemic lupus erythematosus.

BACKGROUND: Cranial neuropathies (CN) are a rare neuropsychiatric SLE (NPSLE) manifestation. Previous studies reported that antibodies to the kinesin family member 20B (KIF20B) (anti-KIF20B) protein were associated with idiopathic ataxia and CN. We assessed anti-KIF20B as a potential biomarker for NPSLE in an international SLE inception cohort. METHODS: Individuals fulfilling the revised 1997 American College of Rheumatology (ACR) SLE classification criteria were enrolled from 31 centres from 1999 to 2011 and followed annually in the Systemic Lupus Erythematosus International Collaborating Clinics inception cohort. Anti-KIF20B testing was performed on baseline (within 15 months of diagnosis or first annual visit) samples using an addressable laser bead immunoassay. Logistic regression (penalised maximum likelihood and adjusting for confounding variables) examined the association between anti-KIF20B and NPSLE manifestations (1999 ACR case definitions), including CN, occurring over the first 5 years of follow-up. RESULTS: Of the 1827 enrolled cohort members, baseline serum and 5 years of follow-up data were available on 795 patients who were included in this study: 29.8% were anti-KIF20B-positive, 88.7% female, and 52.1% White. The frequency of anti-KIF20B positivity differed only for those with CN (n=10) versus without CN (n=785) (70.0% vs 29.3%; OR 5.2, 95% CI 1.4, 18.5). Compared with patients without CN, patients with CN were more likely to fulfil the ACR haematological (90.0% vs 66.1%; difference 23.9%, 95% CI 5.0%, 42.8%) and ANA (100% vs 95.7%; difference 4.3%, 95% CI 2.9%, 5.8%) criteria. In the multivariate analysis adjusting for age at baseline, female, White race and ethnicity, and ACR haematological and ANA criteria, anti-KIF20B positivity remained associated with CN (OR 5.2, 95% CI 1.4, 19.1). CONCLUSION: Anti-KIF20B is a potential biomarker for SLE-related CN. Further studies are needed to examine how autoantibodies against KIF20B, which is variably expressed in a variety of neurological cells, contribute to disease pathogenesis.

Mutaciones del genoma mitocondrial y su expresión clínica en cardiología / Mitochondrial genoma mutations and their clinical expression in cardiology

Uno de los mayores retos de la biología molecular es comprender los mecanismos por los cuales un defecto genético particular origina una determinada enfermedad. El DNA mitocondrial es más vulnerable a sufrir mutaciones que el DNA nuclear. Las mutaciones del DNA mitocondrial han sido asociadas a diversa gama de trastornos caracterizados por un fenotipo complejo y que actualmente se conocen como citopatías mitocondriales o enfermedades de fosforilación oxidativa. El objetivo de este trabajo es revisar los conceptos genéticos, clínicos y morfológicos más relevantes de la afección cardíaca en este heterogéneo pero fascinante grupo de enfermedades. La afección cardíaca en las citopatías mitocondriales es diferente en cada subgrupo de estos trastornos y mutaciones mitocondriales puntuales son capaces de originar trastornos cardiacos característicos.

El otro genoma: El concepto clínico de las citopatías mitocondriales o enfermedades de la fosforilación oxidativa / The other genome: clinical spectrum of mitochondrial cytopathies or oxidative phosphorylation diseases

El estudio de las anormalidades del DNA mitocondrial y de su relaicón con trastornos a nivel de la fosforilación oxidativa y cadena de transporte de electrones ha permitido la descripción de una gama de síndromes denominados enfermedades o citopatías mitocondriales. El objetivo del presente trabajo es hacer una revisión de los aspectos clínicos más relevantes de este diverso grupo de enfermedades, y proponer un algoritmo diagnóstico, con la finalidad de que los médicos que atienden a estos pacientes puedan considerarlas dentro del espectro de diagnósticos diferenciales en los casos pertinentes