Immunogenicity and safety of primary fractional-dose yellow fever vaccine in autoimmune rheumatic diseases.

BACKGROUND: Brazil faced a yellow fever(YF) outbreak in 2016-2018 and vaccination was considered for autoimmune rheumatic disease patients(ARD) with low immunosuppression due to YF high mortality. OBJECTIVE: This study aimed to evaluate, prospectively for the first time, the short-term immunogenicity of the fractional YF vaccine(YFV) immunization in ARD patients with low immunossupression. METHODS AND RESULTS: A total of 318 participants(159 ARD and 159 age- and sex-matched healthy controls) were vaccinated with the fractional-dose(one fifth) of 17DD-YFV. All subjects were evaluated at entry(D0), D5, D10, and D30 post-vaccination for clinical/laboratory and disease activity parameters for ARD patients. Post-vaccination seroconversion rate(83.7%vs.96.6%, p = 0.0006) and geometric mean titers(GMT) of neutralizing antibodies[1143.7 (95%CI 1012.3-1292.2) vs.731 (95%CI 593.6-900.2), p<0.001] were significantly lower in ARD compared to controls. A lower positivity rate of viremia was also identified for ARD patients compared to controls at D5 (53%vs.70%, p = 0.005) and the levels persisted in D10 for patients and reduced for controls(51%vs.19%, p = 0.0001). The viremia was the only variable associated with seroconvertion. No serious adverse events were reported. ARD disease activity parameters remained stable at D30(p>0.05). CONCLUSION: Fractional-dose 17DD-YF vaccine in ARD patients resulted in a high rate of seroconversion rate(>80%) but lower than controls, with a longer but less intense viremia. This vaccine was immunogenic, safe and did not induce flares in ARD under low immunosuppression and may be indicated in YF outbreak situations and for patients who live or travel to endemic areas. TRIAL REGISTRATION: This clinical trial was registered with Clinicaltrials.gov (#NCT03430388).

A High-Intensity Exercise Intervention Improves Older Women Lumbar Spine and Distal Tibia Bone Microstructure and Function: A 20-Week Randomized Controlled Trial.

Introduction: The effects of ageing on bone can be mitigated with different types of physical training, such as power training. However, stimuli that combine increasing external and internal loads concomitantly may improve bone quality. The goal of this study was to assess the efficacy of a combined power and plyometric training on lumbar spine and distal tibia microstructure and function. Methods: 38 sedentary elderly women between 60 and 70 years were randomly allocated in experimental (N = 21) and control group (N = 17). The effects of the 20-week protocol on lumbar spine microstructure and tibia microstructure and function were assessed by trabecular bone score (TBS), high resolution peripheral quantitative computed tomography (HR-pQCT) and microfinite element analysis. Results: when compared to the effects found in the control group, the experimental group showed significant improvements in lumbar spine TBS (Hedges' g = 0.77); and in distal tibia trabecular thickness (g = 0.82) and trabecular bone mineral density (g=0.63). Conclusion: our findings underscore the effectiveness of the proposed intervention, suggesting it as a new strategy to slow down and even reverse the structural and functional losses in the skeletal system due to ageing.

Creatine Supplementation (3 g/d) and Bone Health in Older Women: A 2-Year, Randomized, Placebo-Controlled Trial.

BACKGROUND: Creatine supplementation could be a nonexpensive, safe, and effective dietary intervention to counteract bone loss. The aim of this study was to investigate whether long-term creatine supplementation can improve bone health in older, postmenopausal women. METHODS: A double-blind, placebo-controlled, parallel-group, randomized trial was conducted between November 2011 and December 2017 in Sao Paulo, Brazil. Two hundred postmenopausal women with osteopenia were randomly allocated to receive either creatine monohydrate (3 g/d) or placebo for 2 years. At baseline and after 12 and 24 months, we assessed areal bone mineral density (aBMD; primary outcome), lean and fat mass (through dual X-ray absorptiometry), volumetric BMD and bone microarchitecture parameters, biochemical bone markers, physical function and strength, and the number of falls and fractures. Possible adverse effects were self-reported. RESULTS: Lumbar spine (p < .001), femoral neck (p < .001), and total femur aBMD (p = .032) decreased across time; however, no interaction effect was observed (all p > .050). Bone markers, microarchitecture parameters, and the number of falls/fractures were not changed with creatine (all p > .050). Lean mass and appendicular skeletal muscle mass increased throughout the intervention (p < .001), with no additive effect of creatine (p = .731 and p = .397, respectively). Creatine did not affect health-related laboratory parameters. CONCLUSION: Creatine supplementation more than 2 years did not improve bone health in older, postmenopausal women with osteopenia, nor did it affect lean mass or muscle function in this population. This refutes the long-lasting notion that this dietary supplement alone has osteogenic or anabolic properties in the long run. CLINICAL TRIAL REGISTRY: Clinicaltrials.gov: NCT: 01472393.

Discriminating sarcopenia in overweight/obese male patients with heart failure: the influence of body mass index.

AIMS: The definition of sarcopenia based on appendicular lean mass/height (2) (ALM/height (2) ) is often used, although it can underestimate the prevalence of sarcopenia in overweight/obese patients with heart failure. Therefore, new methods have been proposed to overcome this limitation. We aimed to evaluate the prevalence of sarcopenia by three methods and compare body composition in this population. METHODS AND RESULTS: We enrolled 168 male patients with heart failure (left ventricular ejection fraction <40%). Sixty-six patients (39.3%) were identified with sarcopenia by at least one method. The lower 20th percentile defined as the cut-off point for sarcopenia was 7.03 kg/m2 , -2.32 and 0.76 for Baumgartner's (20.8%), Newman's (21.4%), and Studenski's methods (21.4%), respectively. Patients with body mass index (BMI) <25 kg/m2 were more likely to be identified by Baumgartner's than Studenski's method (P < 0.001). However, in patients with BMI ≥ 25 kg/m2 , Studenski's and Newman's methods were more likely to detect sarcopenia than Baumgartner's method (both P < 0.005). Patients were further divided into three subgroups: (i) patients classified in all indexes (n = 8), (ii) patients classified in Baumgartner's (sarcopenic; n = 27), and (iii) patients classified in both Newman's and Studenski's methods (sarcopenic obesity; n = 31). Comparing body composition among groups, all sarcopenic groups presented lower total lean mass compared with non-sarcopenic patients, whereas sarcopenic obese patients had higher total lean mass than lean sarcopenic patients. CONCLUSIONS: Our results demonstrate that the prevalence of sarcopenia in overweight/obese patients is similar to lean sarcopenic patients when other methods are considered. In patients with higher BMI, Studenski's method seems to be more feasible to detect sarcopenia.

Telmisartan use in rats with preexisting osteoporotics bone disorders increases bone microarchitecture alterations via PPARγ.

AIMS: Telmisartan (TEL), an angiotensin II type I receptor blocker and PPARγ partial agonist, has been used for to treat hypertension. It is known that PPARγ activation induces bone loss. Therefore, we evaluate the effects of telmisartan on PPARγ protein expression, biomechanics, density and bone microarchitecture of femurs and lumbar vertebrae in SHR ovariectomized animals, a model of hypertension in which preexisting bone impairment has been demonstrated. MAIN METHODS: SHR females (3 months old) were distributed into four groups: sham (S), sham + TEL (ST), OVX (C) and OVX + TEL (CT). TEL (5 mg/kg/day) or vehicle were administered according to the groups. After the protocol, blood pressure was measured and density, microarchitecture and biomechanics of bone were analyzed. Western blotting analysis was performed to evaluate PPARγ protein expression in the bones. KEY FINDINGS: Castration induced a deleterious effect on mineral density and trabecular parameters, with telmisartan enhancing such effects. Telmisartan increased PPARγ levels, which were at their highest when the treatment was combined with castration. As to biomechanical properties, telmisartan reduced the stiffness in the castration group (CT vs. S or C group), as well as resilience and failure load in ST group (vs. all others groups). SIGNIFICANCE: These results demonstrated that telmisartan compromised bone density and microarchitecture in animals that shows preexisting osteoporotic bone disorders, probably via mechanisms associated with increased PPARγ. If this translates to humans, a need for greater caution in the use of telmisartan by patients that have preexisting bone problems, as in the postmenopausal period, may be in order.

Severe loss of clinical attachment level: an independent association with low hip bone mineral density in postmenopausal females.

BACKGROUND: Bone loss is a feature of both periodontitis and osteoporosis, and several studies have analyzed whether the periodontal destruction could have been influenced by systemic bone loss. The aim of this study is to assess the association between clinical attachment level (CAL) and bone mineral density (BMD) at the lumbar spine and hip, lifestyle, smoking, sociodemographic factors, and dental clinical variables in postmenopausal women. METHODS: One hundred forty-eight women were interviewed using a structured written questionnaire and clinically examined. The periodontal examination, which was performed by calibrated investigators, included CAL, probing depth, gingival recession, bleeding on probing (BOP), visible plaque, supragingival calculus, and mean tooth loss. The sample was stratified into two groups: moderate and severe CAL. The moderate group had all sites with CAL ≤5 mm. The severe group had ≥1 site with CAL >5 mm. BMD, measured using dual-energy x-ray absorptiometry, was assessed at the lumbar spine, femoral neck, and total femur (grams per square centimeters). RESULTS: Severe CAL was identified in 86 women (58.1%). The multiple linear regression analysis using CAL (dependent variable), adjusted by menopause, education, and family income, demonstrated an inverse relationship of severe CAL with the BMD of the femoral neck (P = 0.015), as well as a positive association of severe CAL with tooth loss (P = 0.000), BOP (P = 0.004), and heavy smokers (P = 0.001). CONCLUSIONS: Our study demonstrated that severe CAL was associated with low BMD of the femoral neck and deleterious clinical dental parameters and smoking. Our findings suggest that, in addition to appropriate oral care, individuals with severe CAL may also require additional attention to their systemic bone health.

Exercise training in juvenile dermatomyositis.

OBJECTIVE: To investigate the effects of a supervised exercise training program on health parameters, physical capacity, and health-related quality of life in patients with mild and chronic juvenile dermatomyositis (DM). METHODS: This was a prospective longitudinal study following 10 children with mild and chronic juvenile DM (disease duration >1 year). The exercise program consisted of twice-a-week aerobic and resistance training. At baseline and after the 12-week intervention, we assessed muscle strength and function, aerobic conditioning, body composition, juvenile DM scores, and health-related quality of life. RESULTS: Child self-report and parent proxy-report Pediatric Quality of Life Inventory scores were improved after the intervention (-40.3%; P = 0.001 and -48.2%; P = 0.049, respectively). Importantly, after exercise, the Disease Activity Score was reduced (-26.9%; P = 0.026) and the Childhood Muscle Assessment Scale was improved (+2.5%; P = 0.009), whereas the Manual Muscle Test presented a trend toward statistical significance (+2.2%; P = 0.081). The peak oxygen consumption and time-to-exhaustion were increased by 13.3% (P = 0.001) and 18.2% (P = 0.003), respectively, whereas resting heart rate was decreased by 14.7% (P = 0.006), indicating important cardiovascular adaptations to the exercise program. Upper and lower extremity muscle strength and muscle function were also significantly improved after the exercise training (P < 0.05). Both the whole-body and the lumbar spine bone mineral apparent density were significantly increased after training (1.44%; P = 0.044 and 2.85%; P = 0.008, respectively). CONCLUSION: We showed for the first time that a 12-week supervised exercise program is safe and can improve muscle strength and function, aerobic conditioning, bone mass, disease activity, and health-related quality of life in patients with active and nonactive mild and chronic juvenile DM with near normal physical function and quality of life.