Association between adipophilin expression and risk of dyslipidaemia in patients with granuloma annulare.

BACKGROUND: An association between granuloma annulare (GA) and dyslipidaemia has been reported. Adipophilin expression may play a plausible role as a cutaneous biomarker for dyslipidaemia in patients with GA; however, this potential link remains to be explored. METHODS: Patients with GA were identified at our hospital between January 1, 1990, and December 31, 2021, with a thorough review of their clinical and histological characteristics. Adipophilin staining was assessed in biopsies of GA lesions. RESULTS: A total of 107 patients with GA were included. The prevalence of dyslipidaemia in patients with positive adipophilin staining was clearly higher than in those with negative labelling (62.3% vs 13.3%). Relative to the dyslipidaemia risk for patients with negative adipophilin expression, the odds for patients with positive adipophilin expression were increased 10-fold (OR: 10.8; p-value<.01). We identified 23 incident cases of dyslipidaemia over a median follow-up period of 91 months among 54 patients with no history of dyslipidaemia. The patients with positive adipophilin expression showed a higher risk of developing dyslipidaemia (HR: 8.9; p-value<.01). CONCLUSIONS: Patients with positive adipophilin staining in their GA biopsies were found to be associated with a higher risk for both baseline and incident dyslipidaemia.

Phase II multicenter randomized controlled clinical trial on the efficacy of intra-articular injection of autologous bone marrow mesenchymal stem cells with platelet rich plasma for the treatment of knee osteoarthritis.

BACKGROUND: Mesenchymal stromal cells are a safe and promising option to treat knee osteoarthritis as previously demonstrated in different clinical trials. However, their efficacy, optimal dose and addition of adjuvants must be determined. Here, we evaluated the clinical effects of a dose of 100 × 106 bone marrow mesenchymal stromal cells (BM-MSCs) in combination with Platelet Rich Plasma (PRGF®) as adjuvant in a randomized clinical trial. METHODS: A phase II, multicenter, randomized clinical trial with active control was conducted. Sixty patients diagnosed with knee OA were randomly assigned to 3 weekly doses of PRGF® or intraarticular administration of 100 × 106 cultured autologous BM-MSCs plus PRGF®. Patients were followed up for 12 months, and pain and function were assessed using VAS and WOMAC and by measuring the knee range of motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage. RESULTS: No adverse effects were reported after BM-MSC administration or during follow-up. According to VAS, the mean value (SD) for PRGF® and BM-MSC with PRGF® went from 5 (1.8) to 4.5 (2.2) (p = 0.389) and from 5.3 (1.9) to 3.5 (2.5) (p = 0.01), respectively at 12 months. In WOMAC, the mean (SD) baseline and 12-month overall WOMAC scores in patients treated with PRGF® was 31.9 (16.2) and 22.3 (15.8) respectively (p = 0.002) while that for patients treated with BM-MSC plus PRGF® was 33.4 (18.7) and 23.0 (16.6) (p = 0.053). Although statistical significances between groups have been not detected, only patients being treated with BM-MSC plus PRGF® could be considered as a OA treatment responders following OARSI criteria. X-ray and MRI (WORMS protocol) revealed no changes in knee joint space width or joint damage. CONCLUSIONS: Treatment with BM-MSC associated with PRGF® was shown to be a viable therapeutic option for osteoarthritis of the knee, with clinical improvement at the end of follow-up. Further phase III clinical trials would be necessary to confirm the efficacy. Trial registration Clinical Trials.gov identifier NCT02365142. Nº EudraCT: 2011-006036-23.

Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: long-term follow up of a multicenter randomized controlled clinical trial (phase I/II).

BACKGROUND: Mesenchymal stromal cells (MSCs) are a promising option to treat knee osteoarthritis (OA). Their safety and usefulness have been reported in several short-term clinical trials but less information is available on the long-term effects of MSC in patients with osteoarthritis. We have evaluated patients included in our previous randomized clinical trial (CMM-ART, NCT02123368) to determine their long-term clinical effect. MATERIALS: A phase I/II multicenter randomized clinical trial with active control was conducted between 2012 and 2014. Thirty patients diagnosed with knee OA were randomly assigned to Control group, intraarticularly administered hyaluronic acid alone, or to two treatment groups, hyaluronic acid together with 10 × 106 or 100 × 106 cultured autologous bone marrow-derived MSCs (BM-MSCs), and followed up for 12 months. After a follow up of 4 years adverse effects and clinical evolution, assessed using VAS and WOMAC scorings are reported. RESULTS: No adverse effects were reported after BM-MSCs administration or during the follow-up. BM-MSCs-administered patients improved according to VAS, median value (IQR) for Control, Low-dose and High-dose groups changed from 5 (3, 7), 7 (5, 8) and 6 (4, 8) to 7 (6, 7), 2 (2, 5) and 3 (3, 4), respectively at the end of follow up (Low-dose vs Control group, p = 0.01; High-dose vs Control group, p = 0.004). Patients receiving BM-MSCs also improved clinically according to WOMAC. Control group showed an increase median value of 4 points (- 11;10) while Low-dose and High-dose groups exhibited values of - 18 (- 28;- 9) and - 10 (- 21;- 3) points, respectively (Low-dose vs Control group p = 0.043). No clinical differences between the BM-MSCs receiving groups were found. CONCLUSIONS: Single intraarticular injection of in vitro expanded autologous BM-MSCs is a safe and feasible procedure that results in long-term clinical and functional improvement of knee OA.

Television viewing, computer use, time driving and all-cause mortality: the SUN cohort.

BACKGROUND: Sedentary behaviors have been directly associated with all-cause mortality. However, little is known about different types of sedentary behaviors in relation to overall mortality. Our objective was to assess the association between different sedentary behaviors and all-cause mortality. METHODS AND RESULTS: In this prospective, dynamic cohort study (the SUN Project) 13 284 Spanish university graduates with a mean age of 37 years were followed-up for a median of 8.2 years. Television, computer, and driving time were assessed at baseline. Poisson regression models were fitted to examine the association between each sedentary behavior and total mortality. All-cause mortality incidence rate ratios (IRRs) per 2 hours per day were 1.40 (95% confidence interval (CI): 1.06 to 1.84) for television viewing, 0.96 (95% CI: 0.79 to 1.18) for computer use, and 1.14 (95% CI: 0.90 to 1.44) for driving, after adjustment for age, sex, smoking status, total energy intake, Mediterranean diet adherence, body mass index, and physical activity. The risk of mortality was twofold higher for participants reporting ≥ 3 h/day of television viewing than for those reporting <1 h/d (IRR: 2.04 [95% CI 1.16 to 3.57]). CONCLUSIONS: Television viewing was directly associated with all-cause mortality. However, computer use and time spent driving were not significantly associated with higher mortality. Further cohort studies and trials designed to assess whether reductions in television viewing are able to reduce mortality are warranted. The lack of association between computer use or time spent driving and mortality needs further confirmation.

Aspirin, non-aspirin analgesics and the risk of hypertension in the SUN cohort.

INTRODUCTION AND OBJECTIVES: The use of aspirin and non-aspirin analgesics has been associated with changes in blood pressure. The aim of this study was to investigate prospectively the association between the regular use of aspirin and non-aspirin analgesics and the incidence of hypertension. METHODS: The SUN project is an ongoing, continuously expanding, prospective cohort of Spanish university graduates initially free of hypertension, cardiovascular disease, diabetes and cancer; 9986 (mean age 36 years) were recruited during 1999-2005 and followed up for a mean of 51 months. Regular aspirin and non-aspirin analgesic use and the presence of other risk factors for hypertension were assessed by questionnaire at baseline, and the incidence of hypertension was assessed using biennial follow-up questionnaires. RESULTS: In total, 543 new cases of hypertension were identified during follow-up. Regular aspirin use (i.e. 2 or more days/week) was associated with a higher risk of hypertension (hazard ratio=1.45; 95% confidence interval, 1.02-2.04) after adjustment for various confounding factors. Regular use of non-aspirin analgesic drugs was also associated with a higher risk of hypertension (hazard ratio=1.69; 95% confidence interval, 1.28-2.23). CONCLUSIONS: The regular use of aspirin and non-aspirin analgesics were both associated with an increased risk of developing hypertension, independently of other risk factors.

Aspirina, analgésicos y riesgo de hipertensión arterial en la Cohorte SUN / Aspirin, non-aspirin analgesics and the risk of hypertension in the SUN cohort

Introducción y objetivos. Se ha relacionado el consumo de aspirina y de otros analgésicos con cambios en la presión arterial. El objetivo de nuestro estudio fue valorar prospectivamente la asociación del uso habitual de aspirina y otros analgésicos con la incidencia de hipertensión arterial. Métodos. El proyecto SUN es una cohorte prospectiva y dinámica que incluyó a 9.986 graduados universitarios españoles inicialmente libres de hipertensión, enfermedad cardiovascular, diabetes o cáncer (media de edad, 36 años). Fueron reclutados durante el periodo 1999- 2005 y se los siguió prospectivamente durante una media de 51 meses. El uso habitual de aspirina y otros analgésicos, así como la presencia de otros factores de riesgo de hipertensión arterial, se valoró mediante un cuestionario basal. La incidencia de hipertensión se valoró con cuestionarios de seguimiento bienales. Resultados. Durante el seguimiento se identificaron 543 casos nuevos de hipertensión arterial. El uso habitual de aspirina (2 o más días/semana) se asoció con un mayor riesgo de hipertensión (hazard ratio [HR] = 1,45; intervalo de confianza [IC] del 95%, 1,02-2,04) tras ajustar por diversos factores de confusión. El uso habitual de otros analgésicos diferentes de la aspirina también se asoció a un mayor riesgo de hipertensión arterial (HR = 1,69; IC del 95%, 1,28-2,23). Conclusiones. El uso habitual tanto de aspirina como de otros analgésicos diferentes a la aspirina parece asociarse a mayor riesgo de hipertensión arterial, independientemente de otros factores de riesgo (AU)

Introduction and objectives. The use of aspirin and non-aspirin analgesics has been associated with changes in blood pressure. The aim of this study was to investigate prospectively the association between the regular use of aspirin and non-aspirin analgesics and the incidence of hypertension. Methods. The SUN project is an ongoing, continuously expanding, prospective cohort of Spanish university graduates initially free of hypertension, cardiovascular disease, diabetes and cancer; 9986 (mean age 36 years) were recruited during 1999-2005 and followed up for a mean of 51 months. Regular aspirin and non-aspirin analgesic use and the presence of other risk factors for hypertension were assessed by questionnaire at baseline, and the incidence of hypertension was assessed using biennial follow-up questionnaires. Results. In total, 543 new cases of hypertension were identified during follow-up. Regular aspirin use (i.e. 2 or more days/week) was associated with a higher risk of hypertension (hazard ratio=1.45; 95% confidence interval, 1.02-2.04) after adjustment for various confounding factors. Regular use of non-aspirin analgesic drugs was also associated with a higher risk of hypertension (hazard ratio=1.69; 95% confidence interval, 1.28-2.23). Conclusions. The regular use of aspirin and non-aspirin analgesics were both associated with an increased risk of developing hypertension, independently of other risk factors (AU)