46 research outputs found
Fracture Risk Reduction by Bisphosphonates in Mastocytosis?
BACKGROUND: Fragility fractures (FFxs) and osteoporosis are frequent manifestations of indolent systemic mastocytosis (ISM). So far, the effect of antiosteoporotic therapy on FFxs has scarcely been investigated. OBJECTIVE: This study evaluates the long-term effect of bisphosphonate treatment on FFxs, bone mineral density (BMD), and bone resorption in patients with ISM in daily clinical practice. METHODS: Patients with ISM who received bisphosphonates because of osteoporosis and/or FFxs were retrospectively analyzed (n = 58). Fractures were recorded by vertebral fracture assessment, X-rays of the thoracolumbar spine, medical records, and a questionnaire. Five-year analysis (n = 30) was made by comparing observed 5-year FFx risk with MastFx-predicted FFx risk for patients with ISM not treated with antiosteoporotic drugs and analyzing 5-year change in BMD and serum collagen C telopeptide (sCTx) Z-scores. RESULTS: During the median follow-up of 7.3 years, 14 of 58 patients suffered 40 FFxs. Five- and 10-year FFx-free survival were 81.9% (standard error [SE], 5.5%) and 67.0% (SE, 7.7%), respectively. FFx risk was significantly higher in patients with previous vertebral FFxs (P = .004), lower femoral BMD at baseline (P = .042), and history of anaphylaxis (P = .028). No 5-year FFx risk reduction could be proven, possibly due to the small sample size. The lumbar BMD Z-score significantly increased from median (interquartile range [IQR]) -2.20 (-2.80 to -1.50) to -1.50 ( -2.30 to -0.60) (P<.001, n = 27). The sCTx Z-score decreased from median 0.71 (IQR, -0.59 to 2.39) to -0.95 (-1.30 to -0.16) (P = .008, n = 15). CONCLUSION: Bisphosphonates significantly increase BMD and decrease sCTx in patients with ISM. However, FFxs still frequently occur. Especially patients with previous FFxs remain at high risk of new FFxs. (C) 2020 American Academy of Allergy, Asthma & Immunolog
Small artery elasticity is decreased in patients with systemic lupus erythematosus without increased intima media thickness
Introduction: The objectives of this study were to determine small arterial elasticity (SAE) in systemic lupus erythematosus (SLE) and to investigate its relationship with intima media thickness (IMT), accumulation of advanced glycation end products (AGEs), endothelial activation and inflammation. Methods: Thirty SLE patients with inactive disease and 30 age- and sex-matched healthy controls were included. Twenty patients with essential hypertension (EH) served as positive control. SAE was assessed by pulse-wave analysis using tonometric recordings of the radial artery. IMT of the carotid arteries was measured by ultrasound. AGE accumulation was assessed with an AGE-reader. Endothelial activation markers and C-reactive protein (CRP) were determined by enzyme-linked immunosorbent assay (ELISA). Results: SAE was decreased in SLE (P = 0.01) and further decreased in EH (P <0.01) compared to healthy controls. IMT was increased in EH (P <0.05), but not in SLE. AGE accumulation was increased in SLE (P <0.05) and further increased in EH (P <0.01) compared to healthy controls. Endothelial activation markers and CRP were increased in SLE but not in EH. SAE related to AGE accumulation (r = -0.370, P <0.05), CRP (r = -0.429, P <0.05) and creatinine clearance (r = 0.440, P <0.05), but not to IMT and endothelial activation markers. In multivariate analysis SLE was an independent predictor of SAE. Conclusions: SAE is decreased in SLE patients without increased IMT, independently of traditional cardiovascular risk factors. Longitudinal studies are needed to investigate whether SAE, endothelial activation and AGE accumulation are early markers for cardiovascular disease in SLE
Positive effects of a chicken eggshell powder-enriched vitamin-mineral supplement on femoral neck bone mineral density in healthy late post-menopausal Dutch women
Although bone metabolism is largely under genetic control, the role of nutrition is considerable. The present study evaluates the effects of chicken eggshell powder, a new source of dietary Ca, and purified CaCO3 on bone mineral density (BMD) of the lumbar spine and hip. Besides BMD we also looked at biochemical markers of bone and Ca metabolism. Both Ca sources were provided in combination with minerals and vitamins including Mg, cholecalciferol and phylloquinone. We designed a randomised, double-blind, placebo-controlled study to take place over 12 months. Healthy Caucasian women (n 85), selected by age (greater than or equal to50 and - 2.5. At baseline, their mean habitual daily Ca intake was adequate. The women were randomly allocated to: eggshell powder-enriched (group A; n 24), purified CaCO3-enriched (group B; n 22), or a placebo product (group C; n 27). BMD was measured at baseline and then after 6 and 12 months of supplementation as were the biochemical markers bone-specific alkaline phosphatase, amino-terminal propeptide extension of type I collagen, deoxypyridinoline, calcitonin, intact parathyroid hormone, calcidiol, and urinary Ca. After 12 months of supplementation, only mean BMD of the femoral neck in group A was significantly increased (P=0.014) by 1.75% (95% CI 0.18, 332) compared with a decrease of -0.60 % (95% CI -1.92, 0.72) in group C. This increase coincided with significant decreases in markers of bone resorption and formation. No significant changes were seen in BMD at other sites, including lumbar spine, nor in groups B and C. No differences were found between groups A and B, or B and C. The present study indicates that healthy late post-menopausal women with an adequate Ca intake at baseline may increase BMD of the hip within 12 months following supplementation with the chicken eggshell powder-enriched supplement
Changes in vitamin-D metabolites and parathyroid hormone in plasma following cholecalciferol administration to pre- and postmenopausal women in the Netherlands in early spring and to postmenopausal women in Curacao
To study the effect on plasma 25-hydroxycholecalciferol (25(OH)D), 1, 25-dihydroxycholecalciferol (1, 25(OH)(2)D) and parathyroid hormone (PTH) we supplemented premenopausal (aged 30 (so 7) years) and postmenopausal (aged 61 (so 2) years) white women living in The Netherlands in late winter/early spring, and elderly black and white women (aged 75 (so 6) years) living in Curacao (Dutch Antilles) with either 10 or 20 mu g cholecalciferol/d for 4, 5 and 9 weeks respectively, Baseline plasma 25(OH)D concentration of Dutch women was lower than that of Curacao women, Postmenopausal Dutch women had a higher PTH concentration in plasma than premenopausal Dutch and postmenopausal Curacao women, There were no differences in plasma 1,25(OH),D, Cholecalciferol administration increased 25(OH)D in all groups, 1, 25(OH),D in postmenopausal Curacao women and PTH in postmenopausal Curacao women and premenopausal Dutch women, Serum and urinary Ca and phosphate concentrations did not change, There were no response differences between 10 and 20 mu g doses, Oral cholecalciferol administration (either 10 or 20 mu g/d) to women living at northern latitudes in late winter/early spring increased 25(OH)D levels to the baseline levels of elderly people living in the tropics
The Effect of Aggressive Versus Conventional Lipid-lowering Therapy on Markers of Inflammatory and Oxidative Stress
Purpose Recent trial results are in favor of aggressive lipid lowering using high dose statins in patients needing secondary prevention. It is unclear whether these effects are solely due to more extensive lipid lowering or the result of the potentially anti-inflammatory properties of statins. We aimed to determine whether aggressive compared with conventional statin therapy is more effective in reducing systemic markers of inflammation and oxidative stress. Materials and methods This was a multi-centre, double-blind, placebo-controlled trial. Patients with previous cardiovascular disease, who did not achieve low density lipoprotein (LDL) cholesterol levels <2.6 mmol/l on conventional statin therapy (simvastatin 40 mg) were randomized to continue with simvastatin 40 mg or to receive atorvastatin 40 mg for 8 weeks and thereafter atorvastatin 80 mg for the final 8 weeks (aggressive treatment). Lipids, C-reactive protein, soluble cellular adhesion molecules, neopterin, von Willebrand Factor, and antibodies against oxidized LDL were measured at baseline and after 16 weeks. Results Lipid levels decreased significantly in the aggressive treatment group (LDL-C reduction 20.8%; P <0.001), whereas a slight increase was observed in the conventional group (LDL-C increase 3.7%; P = 0.037). A significant reduction in antibodies against oxidized LDL was seen in the aggressive (13.4%; P <0.001) and the conventional (26.8%; P <0.001) group, but there was no difference between groups (P = 0.25). Furthermore, no significant differences in change in other biomarkers was observed between both groups. Conclusions This study does not support the hypothesis that a more profound reduction in inflammatory and oxidative stress contributes to the benefits of aggressive statin therapy
Acute Endovascular Treatment of Patients With lschemic Stroke From Intracranial Large Vessel Occlusion and Extracranial Carotid Dissection
Introduction: Carotid artery dissection (CAD) and atherosclerotic carotid artery occlusion (ACAO) are major causes of a tandem occlusion in patients with intracranial large vessel occlusion (LVO). Presence of tandem occlusions may hamper intracranial access and potentially increases the risk of procedural complications of endovascular treatment (EVT). Our aim was to assess neurological, functional and technical outcome and complications of EVT for intracranial LVO in patients with CAD in comparison to patients with ACAO and to patients without CAD or ACAO. Methods: We analyzed data of the MR CLEAN trial intervention arm and MR CLEAN Registry, acquired in 16 Dutch EVT-centers. Primary outcome was the change in stroke severity by comparing the National Institute of Health Stroke Scale (NIHSS) score at 24-48 h after treatment vs. baseline. Secondary outcomes included reperfusion rate and symptomatic intracranial hemorrhage (sICH). We compared outcomes and complications between patients with CAD vs. patients with ACAO and patients without CAD or ACAO. Results: In total, we identified 74 (4.7%) patients with CAD, 92 (5.9%) patients with ACAO and 1398 (89.4%) patients without CAD or ACAO. Neurological improvement at short-term after EVT in patients with CAD was significantly better compared to ACAO (raw mean -5 vs. mean -1 NIHSS point; p = 0.03) and did not differ compared to patients without CAD or ACAO (-4 NIHSS points; p = 0.62). Rates of successful reperfusion in patients with CAD (47%) was comparable to patients with ACAO (47%; p = 1.00), but was less often achieved compared to patients without CAD or ACAO (58%; p = 0.08). Occurrence of sICH did not differ significantly between CAD patients (5%) and ACAO (11%; p = 0.33) or without CAD/ACAO (6%; p = 1.00). Conclusion: EVT in patients with intracranial LVO due to CAD results in neurological improvement comparable to patients without tandem occlusions. Therefore, carotid artery dissection by itself should not be a contraindication for endovascular treatment in stroke patients with intracranial large vessel occlusion. Although more challenging endovascular procedures are to be suspected in both patients with CAD or ACAO, accurate distinction between CAD and ACAO might influence clinical decision making as better clinical outcome can be expected in patients with CAD
Fatal Anaphylaxis to Yellow Jacket Stings in Mastocytosis:Options for Identification and Treatment of At-Risk Patients
BACKGROUND: Patients with indolent systemic mastocytosis (ISM) are at risk for severe anaphylactic reactions to yellow jacket (YJ) stings while demonstration of sensitization can be challenging because specific IgE (sIgE) levels are regularly below 0.35 kU(A)/L. The implication of missing YJ allergy is illustrated by a case of fatal anaphylaxis. OBJECTIVE: To explore the natural course of YJ venom allergy and the diagnostic accuracy and therapeutic consequence of YJ venom sIgE in patients with ISM. METHODS: All patients with ISM seen from 1981 to 2015 (n = 243) were evaluated on the number of YJ stings, reaction severity, and sensitivity and specificity of YJ venom sIgE. YJ venom allergic patients without mastocytosis served as control (n = 313). RESULTS: A total of 153 patients with ISM were stung during adult life. The first systemic reaction was more often severe in patients with ISM than in patients without mastocytosis (69.9% vs 22.0%) and reactions recurred in 40 of 41 re-stung patients with ISM. ISM reactors showed lower YJ venom sIgE levels than nonmastocytosis reactors (0.61 vs 4.83 kU(A)/L; P <.001) and asymptomatic sensitization was exceedingly rare. In ISM the current clinical threshold of 0.35 kU(A)/L yields a sensitivity and specificity of 77.6% and 87.5%, respectively. The optimal diagnostic accuracy is achieved at 0.17 kU(A)/L (sensitivity, 83.6%; specificity, 85.0%). CONCLUSIONS: The high rate of severe reactions and the fatal case underscore the importance of adequate diagnostic sensitivity of sIgE in patients with ISM. The sensitivity of sIgE can be ameliorated by lowering the threshold to 0.17 kU(A)/L, retaining good specificity. We recommend sIgE screening in all patients with ISM and discussing immunotherapy when YJ venom sIgE exceeds 0.17 kU(A)/L