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All-trans retinoic acid plus high-dose dexamethasone as first-line treatment for patients with newly diagnosed immune thrombocytopenia: a multicentre, open-label, randomised, controlled, phase 2 trial.
Huang, QS, Liu, Y, Wang, JB, Peng, J, Hou, M, Liu, H, Feng, R, Wang, JW, Xu, LP, Wang, Y, et al
The Lancet. Haematology. 2021;(10):e688-e699
Abstract
BACKGROUND High-dose dexamethasone is the standard initial treatment for patients with immune thrombocytopenia, but many patients still relapse and require further treatments. All-trans retinoic acid has been shown to exert immunomodulatory effects and promote thrombopoiesis, and so we aimed to assess the activity and safety of all-trans retinoic acid plus high-dose dexamethasone as a first-line treatment for newly diagnosed patients with immune thrombocytopenia. METHODS This multicentre, open-label, randomised, controlled, phase 2 trial was done at six different tertiary medical centres in China. Eligible participants were adults (aged >18 years) with treatment-naive, newly diagnosed, primary immune thrombocytopenia who had either a platelet count of less than 30 × 109 platelets per L or a platelet count of less than 50 × 109 platelets per L and clinically significant bleeding. We randomly assigned (1:1) participants to receive either all-trans retinoic acid (10 mg orally twice daily for 12 weeks) plus high-dose dexamethasone (40 mg/day intravenously for 4 consecutive days) or high-dose dexamethasone alone using a central, web-based randomisation system. If patients did not respond by day 14, the 4-day course of dexamethasone was repeated. The primary endpoint was 6-month sustained response, defined as the maintenance of a platelet count of at least 30 × 109 platelets per L and at least 2-times higher than the baseline count and the absence of bleeding, with no need for rescue medication at this time. The primary endpoint was analysed by intention-to-treat and safety was assessed in all participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov, NCT04217148, and is now completed. FINDINGS Between Jan 1, 2020, and June 30, 2020, 132 patients were randomly assigned to either all-trans retinoic acid plus high-dose dexamethasone (n=66) or high-dose dexamethasone alone (n=66). Three patients did not receive their allocated treatment, leaving 129 in the safety analysis set. At 6 months, a significantly higher proportion of participants in the all-trans retinoic acid plus high-dose dexamethasone group (45 [68%] of 66) than in the high-dose dexamethasone monotherapy group (27 [41%] of 66) had a sustained response (OR 3·095, 95% CI 1·516-6·318; p=0·0017). The most common adverse events were dry skin (31 [48%] of 64 patients), headaches (12 [19%]), and insomnia (12 [19%]) in the combination group, and insomnia (ten [15%] of 65 patients) and anxiety or mood disorders (eight [12%]) in the monotherapy group. Both treatments were well tolerated and no grade 4 or worse adverse events occurred. There were no treatment-related deaths. INTERPRETATION The combination of all-trans retinoic acid and high-dose dexamethasone was safe and active in newly diagnosed patients with primary immune thrombocytopenia, providing a sustained response. This regimen represents a potential first-line treatment in this setting, but further studies are needed to validate its efficacy and safety. FUNDING The Beijing Municipal Science and Technology Commission, the National Natural Science Foundation of China, the Beijing Natural Science Foundation, the National Key Research and Development Program of China, and the Foundation for Innovative Research Groups of the National Natural Science Foundation of China.
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Immune-Mediated Fetal Complete Atrioventricular Block: Can Dexamethasone Therapy Revert the Process?
Perles, Z, Ishay, Y, Nir, A, Gavri, S, Golender, J, Ta-Shma, A, Abu-Zahira, I, Natsheh, J, Elchalal, U, Mevorach, D, et al
The Israel Medical Association journal : IMAJ. 2020;(22):711-716
Abstract
Fetal complete atrioventricular block (CAVB) is usually autoimmune mediated. The risk of developing CAVB is 2% to 3% in anti-Ro/SS-A seropositive pregnancies and it increases 10 times after previous CAVB in siblings. Despite being a rare complication, CAVB carries a 20% mortality rate and substantial morbidity, as about 65% of newborns will eventually need life-long pacing. Once found, fetal CAVB is almost always irreversible, despite aggressive immunotherapy. This poor outcome prompted some research groups to address this situation. All groups followed anti-Ro/SS-A seropositive pregnancies on a weekly basis during the second trimester of pregnancy and tried to detect first degree atrioventricular block (AVB) using accurate echocardiographic tools, assuming they may characterize the initiation of the immune damage to the A-V conduction system, at which point the process might still be reversible. Some of the groups treated fetuses with first degree AVB with maternal oral fluorinated steroids. We summarized the results of all groups, including our group. We describe a case of a fetus that developed CAVB 6 days after normal sinus rhythm (NSR), who under aggressive dexamethasone therapy gradually reverted to NSR. This fetus had a previous sibling with CAVB. We assumed the immune damage to the conduction system in this small group of fetuses with a previous CAVB sibling may have occurred more quickly than usual. We therefore recommend a twice-weekly follow-up with these fetuses.
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Dexamethasone for the prevention of recurrent laryngeal nerve palsy and other complications after thyroid surgery: a randomized double-blind placebo-controlled trial.
Schietroma, M, Cecilia, EM, Carlei, F, Sista, F, De Santis, G, Lancione, L, Amicucci, G
JAMA otolaryngology-- head & neck surgery. 2013;(5):471-8
Abstract
IMPORTANCE Recurrent laryngeal nerve dysfunction and hypoparathyroidism are well-recognized, important complications of thyroid surgery. The duration of convalescence after noncomplicated thyroid operation may depend on several factors, of which pain and fatigue are the most important. Nausea and vomiting occur mainly on the day of operation. Glucocorticoids are well known for their analgesic, anti-inflammatory, immune-modulating and antiemetic effects. However, there is little information in the literature on the use of steroids in thyroid surgery, and the information that is available is conflicting. OBJECTIVE To investigate whether preoperative dexamethasone could improve surgical outcome in patients undergoing thyroid surgery. DESIGN A randomized double-blind placebo-controlled trial. A 30-day follow-up for morbidity was performed in all cases. SETTING All patients were hospitalized in a public hospital. PARTICIPANTS From June 2008 through August 2011, 328 patients were randomized to receive either intravenous dexamethasone, 8 mg, administered 90 minutes before skin incision, or saline solution (placebo). INTERVENTIONS Intravenous dexamethasone, 8 mg. MAIN OUTCOMES AND MEASURES The primary end points were temporary or permanent recurrent laryngeal nerve palsy. Transient and definitive hypoparathyroidism, pain and fatigue scores, nausea, and the number of vomiting episodes were also registered. Preoperatively and at several times during the first 24 postoperative hours, we measured C-reactive protein, interleukin 6, and interleukin 1β levels. RESULTS In the dexamethasone group, the rate of temporary recurrent laryngeal nerve palsy (4.9%) was significantly lower compared with the placebo group (8.4%) (P = .04). Also, postoperative transient biochemical hypoparathyroidism occurred more frequently in the placebo group (37.0%) than in the dexamethasone group (12.8%). Dexamethasone use significantly reduced postoperative levels of C-reactive protein (P = .01) and interleukin 6 and interleukin 1β (P = .02), fatigue (P = .01), and overall pain during the first 24 postoperative hours (P = .04), as well as the total analgesic (ketorolac tromethamine) requirement (P = .04). Dexamethasone use also reduced nausea and vomiting on the day of operation (P = .045). CONCLUSIONS AND RELEVANCE Preoperative administration of dexamethasone, 8 mg, reduced postoperative temporary recurrent laryngeal nerve palsy and hypoparathyroidism rates and reduced pain, fatigue, nausea, and vomiting after thyroid surgery. However, these data require further analysis in randomized prospective studies. TRIAL REGISTRATION clinicaltrials.gov Identifier:NCT01690806.
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Effects of 20-hydroxyecdysone, Leuzea carthamoides extracts, dexamethasone and their combinations on the NF-κB activation in HeLa cells.
Peschel, W, Kump, A, Prieto, JM
The Journal of pharmacy and pharmacology. 2011;(11):1483-95
Abstract
OBJECTIVES The plant steroid 20-hydroxyecdysterone (20E) and 20E-containing extracts from Leuzea carthamoides (Willd.) DC are sold with claims of anabolic and immunomodulatory effects. Yet their effect on the activation of nuclear factor kappa B (NF-κB), a key player in immune response and cell fate, and their influence on the NF-κB-inhibiting activity of steroidal anti-inflammatory drugs is still unknown. METHODS The ability of 20E, Leuzea extracts and selected steroidal/non-steroidal anti-inflammatory drugs to influence the activation of NF-κB was explored using, as the experimental model, human cervical cancer HeLa-IL-6 cells stably transfected with an IL-6-bound reporter gene. Effects on cell viability and proliferation were monitored (MTT assay). HPLC-DAD was used to establish links between chemical patterns of Leuzea extracts and their bioactivities. KEY FINDINGS 20E inhibited NF-κB activation (IC50 31.8 µm) but was less active than other plant metabolites (xanthohumol 3.8 µm, withaferin A 1.4 µm). Leuzea extracts with high content in 20E had a fair activating effect, but in contrast, some extracts with low 20E content significantly inhibited NF-κB activation at IC50s ranging from 3.5 to 6.2 µg/ml. Combination tests confirmed that 20E does not explain the NF-κB modulation achieved by Leuzea extracts. The extracts but not 20E itself showed a significant modulation of the NF-κB inhibitory effect of dexamethasone. CONCLUSIONS 20E is unlikely a major player in the NF-κB inhibitory effects displayed by some Leuzea extracts in vitro. If confirmed in vivo, caution should prevail towards marketed Leuzea extracts that are non-standardised or standardised on 20E only, since different starting materials and extracts may even cause opposite effects. More importantly, our results indicate the interaction potential of Leuzea with steroidal anti-inflammatory drugs.
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How does dexamethasone influence surgical outcome after laparoscopic Nissen fundoplication? A randomized double-blind placebo-controlled trial.
Schietroma, M, Giuliani, M, Zoccali, G, Carlei, F, Bianchi, Z, Amiccucci, G, Daniloiu, AG
Updates in surgery. 2010;(1):47-54
Abstract
Laparoscopic floppy Nissen fundoplication (LFNF) is an effective treatment for gastroesophageal reflux disease. The duration of convalescence, after noncomplicated LFNF, may depend on several factors of which pain, fatigue and sociocultural factors are the most important. Nausea and vomiting occur mainly on the day of operation. Glucocorticoids are well known for their analgesic, anti-inflammatory, immune-modulating and antiemetic effects. We therefore undertook the present study to investigate whether preoperative dexamethasone could improve surgical outcome in patients undergoing uncomplicated laparoscopic floppy Nissen fundoplication. From March 2005 to April 2008, 82 patients were randomized to receive dexamethasone (8 mg) intravenously, 90 min before skin incision or saline (placebo). Patients received a similar standardized anesthetic, surgical and multimodal analgesic treatment. The primary end points were pain and fatigue. Preoperatively and at several times during the first 24 postoperative hours, we measured C-reactive protein (CRP), interleukin-6 and 1 (IL-6, IL-1), pain scores and nausea, and the number of vomiting episodes were registered. Dexamethasone significantly reduced postoperative levels of CRP (p = 0.01), IL-6 and IL-1 (p < 0.05), fatigue (p = 0.01) and overall pain during the first 24 postoperative hours (p < 0.05) and the total requirement of analgesic (ketorolac) (p < 0.05). Dexamethasone also reduced nausea and vomiting on the day of operation (p < 0.05). Preoperative dexamethasone (8 mg) reduced pain, fatigue, nausea and vomiting in patients undergoing uncomplicated LNF when compared with placebo.
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[Clinical control trial of methylprednisolone and dexamethasone in treatment of intracranial tumor edema].
Ding, X, Mao, B, Ju, Y, Liu, Y
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition. 2003;(2):327-9
Abstract
OBJECTIVE This study was designed to evaluate the therapeutic effect and side effect of methylprednisolone on brain tumor edema. METHODS Fifty-eight patients with brain tumor edema revealed by CT/MRI were randomly divided into two groups. 30 patients of trial group were treated with methylprednisolone, and 28 patients of the control group received dexamethasone for 3-5 days before and after operation. The patients' clinical neurological symptoms and signs were observed at the beginning and end of treatment before operation, and Karnofsky Performance Scores, were given to the case. Furthermore, the patients' cell immunity, electrolytes, blood sugar that might be affected, by methylprednisolone and dexamethasone were investigated concerned. RESULTS Nineteen of 30 patients taking methylprednisolone and seventeen of 28 patients taking dexamethasone showed improvement in their clinical neurological symptoms, total effective rates for methylprednisolone and dexamethasone groups were 63.0% and 60.7% respectively, there was no obvious difference between the two groups in this regard rate (P > 0.05). Furthermore nine patients (30.0%) in trial group show significant improvement, whereas only four patients (14.3%) in the control group show significant improvement, the difference here was statistically significant (P < 0.05). There was no obvious side effect in both groups during treatment. CONCLUSION Vasogenic edema associated with brain tumor and its induced symptoms was effectively treated by methylprednisolone without adverse effects, Current findings suggest that further study of methylprednisolone in the management of control nervous system tumors is warranted.