Vertebroplasty versus sham procedure for painful acute osteoporotic vertebral compression fractures (VERTOS IV):Randomised sham controlled clinical trial

Objective To assess whether percutaneous vertebroplasty results in more pain relief than a sham procedure in patients with acute osteoporotic compression fractures of the vertebral body. Design Randomised, double blind, sham controlled clinical trial. Setting Four community hospitals in the Netherlands, 2011-15. Participants 180 participants requiring treatment for acute osteoporotic vertebral compression fractures were randomised to either vertebroplasty (n=91) or a sham procedure (n=89). Interventions Participants received local subcutaneous lidocaine (lignocaine) and bupivacaine at each pedicle. The vertebroplasty group also received cementation, which was simulated in the sham procedure group. Main outcome measures Main outcome measure was mean reduction in visual analogue scale (VAS) scores at one day, one week, and one, three, six, and 12 months. Clinically significant pain relief was defined as a decrease of 1.5 points in VAS scores from baseline. Secondary outcome measures were the differences between groups for changes in the quality of life for osteoporosis and Roland-Morris disability questionnaire scores during 12 months’ follow-up. Results The mean reduction in VAS score was statistically significant in the vertebroplasty and sham procedure groups at all follow-up points after the procedure compared with baseline. The mean difference in VAS scores between groups was 0.20 (95% confidence interval −0.53 to 0.94) at baseline, −0.43 (−1.17 to 0.31) at one day, −0.11 (−0.85 to 0.63) at one week, 0.41 (−0.33 to 1.15) at one month, 0.21 (−0.54 to 0.96) at three months, 0.39 (−0.37 to 1.15) at six months, and 0.45 (−0.37 to 1.24) at 12 months. These changes in VAS scores did not, however, differ statistically significantly between the groups during 12 months’ follow-up. The results for secondary outcomes were not statistically significant. Use of analgesics (non-opioids, weak opioids, strong opioids) decreased statistically significantly in both groups at all time points, with no statistically significant differences between groups. Two adverse events occurred in the vertebroplasty group: one respiratory insufficiency and one vasovagal reaction. Conclusions Percutaneous vertebroplasty did not result in statistically significantly greater pain relief than a sham procedure during 12 months’ follow-up among patients with acute osteoporotic vertebral compression fractures

Uterine Artery Embolization in Patients with a Large Fibroid Burden: Long-Term Clinical and MR Follow-up

Uterine artery embolization (UAE) in patients with a large fibroid burden is controversial. Anecdotal reports describe serious complications and limited clinical results. We report the long-term clinical and magnetic resonance (MR) results in a large series of women with a dominant fibroid of >10 cm and/or an uterine volume of >700 cm3. Seventy-one consecutive patients (mean age, 42.5 years; median, 40 years; range, 25–52 years) with a large fibroid burden were treated by UAE between August 2000 and April 2005. Volume reduction and infarction rate of dominant fibroid and uterus were assessed by comparing the baseline and latest follow-up MRIs. Patients were clinically followed at various time intervals after UAE with standardized questionnaires. There were no serious complications of UAE. During a mean follow-up of 48 months (median, 59 months; range, 6–106 months), 10 of 71 patients (14%) had a hysterectomy. Mean volume reduction of the fibroid and uterus was 44 and 43%. Mean infarction rate of the fibroid and overall fibroid infarction rate was 86 and 87%. In the vast majority of patients there was a substantial improvement of symptoms. Clinical results were similar in patients with a dominant fibroid >10 cm and in patients with large uterine volumes by diffuse fibroid disease. In conclusion, our results indicate that the risk of serious complications after UAE in patients with a large fibroid burden is not increased. Moreover, clinical long-term results are as good as in other patients who are treated with UAE. Therefore, a large fibroid burden should not be considered a contraindication for UAE

Oxidative stress in the developing brain: effects of postnatal glucocorticoid therapy and antioxidants in the rat.

In premature infants, glucocorticoids ameliorate chronic lung disease, but have adverse effects on long-term neurological function. Glucocorticoid excess promotes free radical overproduction. We hypothesised that the adverse effects of postnatal glucocorticoid therapy on the developing brain are secondary to oxidative stress and that antioxidant treatment would diminish unwanted effects. Male rat pups received a clinically-relevant tapering course of dexamethasone (DEX; 0.5, 0.3, and 0.1 mg x kg(-1) x day(-1)), with or without antioxidant vitamins C and E (DEXCE; 200 mg x kg(-1) x day(-1) and 100 mg x kg(-1) x day(-1), respectively), on postnatal days 1-6 (P1-6). Controls received saline or saline with vitamins. At weaning, relative to controls, DEX decreased total brain volume (704.4±34.7 mm(3) vs. 564.0±20.0 mm(3)), the soma volume of neurons in the CA1 (1172.6±30.4 µm(3) vs. 1002.4±11.8 µm(3)) and in the dentate gyrus (525.9±27.2 µm(3) vs. 421.5±24.6 µm(3)) of the hippocampus, and induced oxidative stress in the cortex (protein expression: heat shock protein 70 [Hsp70]: +68%; 4-hydroxynonenal [4-HNE]: +118% and nitrotyrosine [NT]: +20%). Dexamethasone in combination with vitamins resulted in improvements in total brain volume (637.5±43.1 mm(3)), and soma volume of neurons in the CA1 (1157.5±42.4 µm(3)) and the dentate gyrus (536.1±27.2 µm(3)). Hsp70 protein expression was unaltered in the cortex (+9%), however, 4-HNE (+95%) and NT (+24%) protein expression remained upregulated. Treatment of neonates with vitamins alone induced oxidative stress in the cortex (Hsp70: +67%; 4-HNE: +73%; NT: +22%) and in the hippocampus (NT: +35%). Combined glucocorticoid and antioxidant therapy in premature infants may be safer for the developing brain than glucocorticoids alone in the treatment of chronic lung disease. However, antioxidant therapy in healthy offspring is not recommended

Comparison of Human Primary with Human iPS Cell-Derived Dopaminergic Neuron Grafts in the Rat Model for Parkinson's Disease

Neuronal degeneration within the substantia nigra and the loss of the dopaminergic nigro-striatal pathway are the major hallmarks of Parkinson’s disease (PD). Grafts of foetal ventral mesencephalic (VM) dopaminergic (DA) neurons into the striatum have been shown to be able to restore striatal dopamine levels and to improve overall PD symptoms. However, human foetus-derived cell grafts are not feasible for clinical application. Autologous induced pluripotent stem cell (iPS cell)-derived DA neurons are emerging as an unprecedented alternative. In this review, we summarize and compare the efficacy of human iPS cell-derived DA neuron grafts to restore normal behaviour in a rat model for PD with that of human foetal primary DA neurons. The differences we observed in the efficacy to restore normal function between the 2 types of DA neuron grafts could be ascribed to intrinsic properties of the iPS cell-derived DA neurons that critically affected survival and proper neurite extension in the striatum after implantation

Uterine artery embolization versus hysterectomy in the treatment of symptomatic adenomyosis: Protocol for the randomized QUESTA trial

Background: Adenomyosis is a benign uterine disease characterized by invasion of endometrium into the myometrium resulting in heavy menstrual bleeding and pain (dysmenorrhea). Hysterectomy is established as the final treatment option when conservative treatment fails. Uterine artery embolization (UAE) in patients with symptomatic adenomyosis has demonstrated to reduce symptoms and improve quality of life. However, randomized controlled trials are lacking. Objective: With this study, we aim to evaluate the impact of UAE on Health-Related Quality of Life (HRQOL) in a randomized comparison to hysterectomy in patients with symptomatic adenomyosis. Methods: This is a multicenter non-blinded randomized controlled trial comparing UAE and hysterectomy. Eligible patients are symptomatic premenopausal women without the desire to conceive and who have symptomatic magnetic resonance imaging (MRI)–confirmed pure adenomyosis or dominant adenomyosis accompanied by fibroids. After obtaining informed consent, patients will be randomly allocated to treatment in a 2:1 UAE versus hysterectomy ratio. The primary objective is HRQOL at 6 months following the assigned intervention. Secondary outcomes are technical results, pain management, clinical outcomes, HRQOL, and cost effectiveness during 2 years of follow-up. In addition, transvaginal ultrasound (TVUS) and MRI will be performed at regular intervals after UAE. Results: Patient enrollment started November 2015. The follow-up period will be completed two years after inclusion of the last patient. At the time of submission of this article, data cleaning and analyses have not yet started. Conclusions: This trial will provide insight for caretakers and future patients about the effect of UAE compared to the gold standard hysterectomy in the treatment of symptomatic adenomyosis and is therefore expected to improve patients’ wellbeing and quality of life

Uterine Artery Embolization in Women with Symptomatic Cervical Leiomyomata: Efficacy and Safety

Purpose: To perform an evaluation on safety and efficacy of uterine artery embolization (UAE) in the patients with symptomatic cervical leiomyomata. Methods: Patients with symptomatic cervical leiomyomata who underwent UAE in one specialized hospital were retrospectively analyzed, both clinically and with MR imaging. The 3-month outcomes were assessed with MR imaging and a validated questionnaire. Long-term follow-up was assessed by direct contact or file review. To determine the efficacy of UAE for cervical leiomyomata, the primary objective was to assess the clinical outcome with the UFS-QOL questionnaire, containing the health-related quality of life (HRQOL) and symptom severity score (SSS). To assess safety, the secondary objective included leiomyomata volume reduction, the infarction/complication rate and secondary interventions were needed. Results: Between 2006 and 2017, eight of 1180 patients underwent UAE and were eligible for inclusion. All embolizations were technically successful (n = 8). At 3 months, all patients showed cervical leiomyomata volume reduction with a median reduction of 41.5% (38.8 cm3) compared to baseline (p = 0.012). No complications occurred. At a median follow-up of 3 months (range 1–7, n = 7), the HRQOL and SSS improved with a median difference of 13 points (range − 5 to 60, p = 0.063) and − 13 points (range − 79 to 3, p = 0.046), respectively. Long-term follow-up showed two secondary interventions (median of 43.5 months). Six patients reported no symptom recurrence. Conclusion: UAE in women with symptomatic cervical leiomyomata is effective and safe with significant improvement in symptoms and quality of life. UAE is a valuable option for women seeking a non-surgical solution