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OBJECTIVE: To investigate the risk of DM and evaluate the impact of SLE therapies on the risk of developing DM in patients with SLE. METHODS: Electronic database searches of PubMed, Embase, Cochrane Library and Web of Science were performed from inception to February 2023. Cohort and cross-sectional studies that analysed the risk of DM in patients with SLE were included. The associations between diabetes and antirheumatic agents, such as antimalarials and glucocorticoids, were analysed in cohort studies. Data were pooled using fixed- or random-effects meta-analysis to estimate pooled odd ratios (OR), relative risks (RR) and 95% confidence intervals (CIs). This study was registered with PROSPERO (CRD42023402774). RESULTS: A total of 37 studies (23 cross-sectional and 14 cohort studies) involving 266 537 patients with SLE were included. The pooled analyses from cross-sectional studies and cohort studies did not show an increased risk of DM in SLE patients (OR = 1.05, 95% CI 0.87-1.27; P = 0.63 and RR = 1.32, 95% CI 0.93-1.87; P = 0.12, respectively). However, several cohort studies consistently demonstrated a reduced risk of diabetes with antimalarials, while glucocorticoid use has been associated with an increased risk of developing diabetes. Age, sex, hypertension and immunosuppressants have not been identified as risk factors for DM in SLE patients. CONCLUSION: Although there was no increased risk of DM in patients with SLE compared with controls, HCQ users or adherents had a decreased risk, whereas glucocorticoid users had an increased risk.

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OBJECTIVE: This study aimed to describe the disease burden and trends of musculoskeletal (MSK) disorders in Mexico from 1990 to 2019. METHOD: A cross-sectional study using systematic analysis from the Global Burden of Disease Study 2019 (GBD study 2019) was performed to analyze data on MSK disorders and estimate crude and age-standardized rates per 100,000 population concerning disease prevalence, incidence, mortality, disability-adjusted life-years (DALY), and years lived with disability (YLD). The average annual percentage change (AAPC) was calculated using the joinpoint regression. RESULTS: In 2019, there were 4.8 million (95% UI 4.3, 5.4) new cases and 3,312 (95% UI 2201, 4,790) deaths attributable to MSK disorders. In 2019, MSK disorders ranked first, increasing from 1990 (second rank) for the YLD in Mexico. Subnational variations were identified, with the state of Oaxaca having the highest age-standardized incidence rate (ASIR) per 100,000 population in 2019. Joinpoint analysis revealed a significant increase in prevalence in Mexico from 1990 to 2019 (AAPC: 0.14%; 95%CI 0.09-0.19), incidence (AAPC: 0.05%; 95%CI 0.03-0.07), DALY (AAPC: 0.13%; 95%CI 0.04-0.22), and YLD (AAPC: 0.13%; 95%CI 0.02-0.24). Among the risk factors, occupational ergonomic factors and high body mass index (BMI) had the largest influence on MSK disorders. CONCLUSIONS: In Mexico, we observed an increase the national burden of MSK disorders from 1990 to 2019. Specific determinants, such as occupational ergonomic factors and high BMI, contribute to the MSK disorder burden. The burden of MSK disorders requires an improved and prompt assessment to plan valuable diagnostic and management approaches. Key Points • In Mexico, the burden of musculoskeletal (MSK) disorders increased from 1990 to 2019. • Specific risk factors, such as occupational ergonomic factors and high body mass index, contribute to the MSK disorder burden.

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BACKGROUND: Low disease activity state (LDAS) has been linked to a significant reduction in flares and damage accrual in patients with systemic lupus erythematosus (SLE); however, the effect of LDAS on the risk of vertebral fractures (VFs) in subjects with SLE is unknown, considering that low bone mineral density (BMD) and VF are frequent in SLE. OBJECTIVE: to evaluate whether achieving LDAS ≥50% of the observation time prevents new VF and BMD changes in Mestizo women. METHODS: We carried out a longitudinal, observational, and retrospective study. Mestizo women with SLE were included for a median of an 8-year follow-up. LDAS was described as Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≤4, prednisone ≤7.5 mg/day, and stable immunosuppressive therapies. BMD measurements and lateral thoracic and lumbar radiographs for a semiquantitative analysis for VF were assessed at baseline and during the follow-up. Uni- and multivariable interval-censored survival regression models were carried out. RESULTS: We included 110 patients: 35 (31.8%) had new VF. A total of 56 patients (50.1%) achieved LDAS ≥50% of the time during the follow-up and achieved a significantly lesser risk of incident VF (HR = 0.16; 95% CI, 0.06-0.49). After adjusting by age, BMI, menopause, prevalent VF, baseline BMD, cumulative glucocorticoid use, and anti-osteoporotic therapy, LDAS-50 was significantly related to a decrease in the risk of a new VF (HR = 0.39; 95% CI, 0.16-0.98). There was no association between LDAS and BMD measurement changes. When only patients on LDAS but not in remission (n = 43) were evaluated for the risk of incident VF, both uni- and multivariate analyses were significant (HR = 0.12; 95 CI, 0.04-47; p = 0.001, and HR = 0.26; 95% CI, 0.7-0.88; p = 0.03). CONCLUSIONS: LDAS ≥50% of the time was significantly associated with a diminished risk of new VF in Mestizo women with SLE, even in patients not in remission. However, LDAS did not help modify BMD changes over time.

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The Systemic Lupus International Clinics (SLICC)-Frailty Index (FI) is associated with adverse outcomes in systemic lupus erythematosus (SLE). However, to our knowledge, its association with bone mineral density (BMD) and vertebral fractures (VF), has not been investigated using a standardized methods. Our aim was to evaluate the relationship between frailty assessed by SLICC-FI, and BMD and VF in Mestizo women with SLE. Adult women were included in this cross-sectional study. Information concerning the risk factors for VF and BMD in the lumbar spine and total hip was acquired. SLICC-FI was assessed at baseline. A semi-quantitative method was utilized to evaluate the prevalence of VF on lateral thoracolumbar radiographs. Univariate and multivariate regression analyses were performed adjusting for age, body mass index (BMI), SLE duration, cumulative glucocorticoid dose, bisphosphonate use, and BMD measurements. We included 202 women with SLE (mean age [SD] = 43.3 [13.6] years). The mean (SD) SLICC-FI value was 0.14 (0.09). Eleven (5.4%) patients were categorized as robust, 62 (30.7%) as relatively less fit, 84 (41.6%) as least fit, and 45 (22.3%) as frail. Both univariate and multivariate models showed associations between frailty (defined as SLICC-FI > 0.21) and prevalent VF in the entire population (OR 5.76, 95% CI 2.53-13.12; P < 0.001) and in the premenopausal group (OR 4.29, 95% CI; P = 0.047). We also found an association between the SLICC-FI and low BMD. In conclusion, frailty assessed by SLICC-FI might be associated with VF and low BMD in mestizo females with SLE.

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The study aimed to analyze the influence of the COVID-19 pandemic on mortality rates in patients with systemic autoimmune rheumatic diseases (SARD) in Mexico. We selected SARD-related deaths using National Open Data and Information from the Ministry of Health, Mexico, and ICD-10 codes. We assessed the observed compared to the predicted mortality values for 2020 and 2021, employing trends from 2010 to 2019 with joinpoint and prediction modelling analyses. Among 12,742 deaths due to SARD between 2010 and 2021, the age-standardized mortality rate (ASMR) increased significantly between 2010 and 2019 (pre-pandemic) (annual percentage change [APC] 1.1%; 95% CI 0.2-2.1), followed by a non-significant decrease during the pandemic period (APC 13.9%; 95% CI 13.9-5.3). In addition, the observed ASMR of 1.19 for 2020 for SARD and of 1.14 for 2021 were lower than the predicted values of 1.25 (95% CI 1.22-1.28) for 2020 and 1.25 (95% CI 1.20-1.30) for 2021. Similar findings were identified for specific SARD, mainly systemic lupus erythematosus (SLE), or by sex or age group. Interestingly, the observed mortality rates for SLE in the Southern region of 1.00 in 2020 and 1.01 in 2021 were both significantly greater than the predicted values of 0.71 (95% CI 0.65-0.77) in 2020 and 0.71 (95% CI 0.63-0.79). In Mexico, the observed SARD mortality rates were not higher than the expected values during the pandemic, except for SLE in the Southern region. No differences by sex or age group were identified.

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Type 2 Diabetes Mellitus (T2DM) is a rapidly rising disease with cardiovascular complications constituting the most common cause of death among diabetic patients. Chronic hyperglycemia can induce vascular dysfunction through damage of the components of the vascular wall, such as vascular smooth muscle cells (VSMCs), which regulate vascular tone and contribute to vascular repair and remodeling. These functions are dependent on intracellular Ca2+ changes. The mechanisms by which T2DM affects Ca2+ handling in VSMCs still remain poorly understood. Therefore, the objective of this study was to determine whether and how T2DM affects Ca2+ homeostasis in VSMCs. We evaluated intracellular Ca2+ signaling in VSMCs from Zucker Diabetic Fatty rats using Ca2+ imaging with Fura-2/AM. Our results indicate that T2DM decreases Ca2+ release from the sarcoplasmic reticulum (SR) and increases the activity of store-operated channels (SOCs). Moreover, we were able to identify an enhancement of the activity of the main Ca2+ extrusion mechanisms (SERCA, PMCA and NCX) during the early stage of the decay of the ATP-induced Ca2+ transient. In addition, we found an increase in Ca2+ entry through the reverse mode of NCX and a decrease in SERCA and PMCA activity during the late stage of the signal decay. These effects were appreciated as a shortening of ATP-induced Ca2+ transient during the early stage of the decay, as well as an increase in the amplitude of the following plateau. Enhanced cytosolic Ca2+ activity in VSMCs could contribute to vascular dysfunction associated with T2DM.

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The aims of this study were in systemic lupus erythematosus (SLE) patients: 1) to compare the metabolomic profile of insulin resistance (IR) with controls and 2) to correlate the metabolomic profile with other IR surrogates and SLE disease variables and vitamin levels. In this cross-sectional study, serum samples were collected from women with SLE (n=64) and gender- and age-matched controls (n=71), which were not diabetic. Serum metabolomic profiling was performed using UPLC-MS-MS (Quantse score). HOMA and QUICKI were carried out. Serum 25(OH)D concentrations were measured by chemiluminescent immunoassay. In women with SLE, the metabolomic Quantose score significantly correlated with HOMA-IR, HOMA2-IR, and QUICKI. Although concentrations of IR metabolites were not different between SLE patients and controls, fasting plasma insulin levels were higher and insulin sensitivity lower in SLE women. Interestingly, the Quantose IR score was significantly correlated with complement C3 levels (r=0.7; p=0.001). 25 (OH)D did not correlate with any metabolite or the Quantose IR index. Quantose IR may be a useful tool for IR assessment. There was a possible correlation between the metabolomic profile and complement C3 levels. The implementation of this metabolic strategy may help develop biochemical insight into metabolic disorders in SLE.

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OBJECTIVE: We carried out a systematic review (SR) of adherence in diagnostic and prognostic applications of ML in SLE using the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) Statement. METHODS: A SR employing five databases was conducted from its inception until December 2021. We identified articles that evaluated the utilization of ML for prognostic and/or diagnostic purposes. This SR was reported based on the PRISMA guidelines. The TRIPOD statement assessed adherence to reporting standards. Assessment for risk of bias was done using PROBAST tool. RESULTS: We included 45 studies: 29 (64.4%) diagnostic and 16 (35.5%) prognostic prediction- model studies. Overall, articles adhered by between 17% and 67% (median 43%, IQR 37-49%) to TRIPOD items. Only few articles reported the model's predictive performance (2.3%, 95% CI 0.06-12.0), testing of interaction terms (2.3%, 95% CI 0.06-12.0), flow of participants (50%, 95% CI; 34.6-65.4), blinding of predictors (2.3%, 95% CI 0.06-12.0), handling of missing data (36.4%, 95% CI 22.4-52.2), and appropriate title (20.5%, 95% CI 9.8-35.3). Some items were almost completely reported: the source of data (88.6%, 95% CI 75.4-96.2), eligibility criteria (86.4%, 95% CI 76.2-96.5), and interpretation of findings (88.6%, 95% CI 75.4-96.2). In addition, most of model studies had high risk of bias. CONCLUSIONS: The reporting adherence of ML-based model developed for SLE, is currently inadequate. Several items deemed crucial for transparent reporting were not fully reported in studies on ML-based prediction models. REVIEW REGISTRATION: PROSPERO ID# CRD42021284881. (Amended to limit the scope).

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