Treatment with Thalidomide and Cyclophosphamide (TCID) is Superior to Vincristine (VID) and to Vinorelbine (VRID) Regimens in Patients with Refractory or Recurrent Multiple Myeloma

Treatment of relapsed or refractory multiple myeloma remains a challenge and novel treatment regimen are required. Here, a matched pair analysis was performed comparing TCID (thalidomide, cyclophosphamide, idarubicin, dexamethasone) treatment to the treatment of patients with VID (vincristine, idarubicin, dexamethasone) or with VRID (vinorelbine, idarubicin, dexamethasone) for relapsed or refractory multiple myeloma. In total, 197 patients were enrolled in multicenter trials. After matching for important prognostic variables 46 matched-pairs (total of 138 patients) could be analysed with regard to survival, toxicity and efficacy. Interestingly, a significant improvement of overall response rate (ORR) for TCID treatment compared to VID and VRID was found. In addition, TCID treatment also led to a significantly higher overall survival (OS) as well as progression-free survival (PFS) compared to VID and VRID. In conclusion, TCID treatment appears to be superior to VRID and VID treatment in patients with progressive or refractory myeloma.     

Postoperative nausea and vomiting prophylaxis: The efficacy of a novel antiemetic drug (palonosetron) combined with dexamethasone

BackgroundPalonosetron is a new, potent, and long-acting 5HT3-receptors antagonist that had been approved by the FDA for use in postoperative nausea and vomiting (PONV) prophylaxis. This study is designed to evaluate its efficacy combined with dexamethasone in PONV prophylaxis in highrisk patients scheduled for laparoscopic surgeries.MethodsIn this double-blind, active-controlled study, 150 patients aged 20–55 years, ASA I–II, and with Apfel’s PONV score 2–4 were equally randomized to receive dexamethasone 8 mg before anesthesia induction and saline 30 min before the end of surgery (group D + S), dexamethasone 8 mg before anesthesia induction and metoclopramide 25 mg 30 min before the end of surgery (group D + M), or dexamethasone 8 mg combined with palonosetron 0.075 mg before anesthesia induction and saline 30 min before the end of surgery (group D + P). Incidences of early and late PONV, complete response, adverse events from antiemetics used, and overall patients’ satisfaction were recorded.ResultsThe incidence of PONV was comparable in the three groups 0–6 h postoperatively. Palonosetron–dexamethasone and dexamethasone–metoclopramide combination therapies significantly reduced the incidence of PONV at 6–12 h postoperatively compared to dexamethasone monotherapy (12% and 16%, vs. 36%, respectively, with P < 0.05). Moreover, palonosetron–dexamethasone combination therapy significantly reduced the incidence of PONV at 12–24 h postoperatively compared to both dexamethasone monotherapy (16% vs. 48%, P < 0.01), and dexamethasone–metoclopramide combination therapy (16% vs. 40%, P < 0.05). The incidence of adverse drug effects was comparable in the three groups. The overall patients’ satisfaction was significantly higher in palonosetron–dexamethasone combination therapy compared to other groups.ConclusionPalonosetron–dexamethasone combination is effective and safe in PONV (early and late) prophylaxis in high-risk patients undergoing laparoscopic surgeries with known high-risk of PONV.     

Dexamethasone treatment modulates aquaporin-4 expression after intracerebral hemorrhage in rats

This study investigated whether dexamethasone (DEX) treatment could regulate the expression of aquaporin-4 (AQP4) in rats with intracerebral hemorrhage (ICH). The results demonstrated that DEX significantly reduced AQP4 mRNA level in the perihematomal area compared with control group, but it increased the level in the brain area surrounding the third ventricle at day 1 post-ICH. There was no difference in AQP4 protein levels between DEX group and control group at the two above-mentioned brain regions at day 1 after ICH. The changes in AQP4 protein induced by DEX were marked at day 3 following surgery and still lasted at day 5 post-ICH, which were accompanied by a reduction of brain edema. Our results demonstrated that the expression of AQP4 protein after ICH was region-specific, time-dependent, and also indicated that DEX-induced cerebral edema clearance was correlated with the regulation of AQP4 expression in different brain regions.     

Sudden sensorineural hearing loss – A contemporary review of management issues

Sudden sensorineural hearing loss (SSNHL) is an enigmatic entity, with obscure pathophysiology and debatable efficacy of the treatment agents used. An underlying cause is identified in only 10–15% of cases. The management of the remaining patients, classified as ‘idiopathic’, is empirical, and is conventionally with systemic steroids, vasodilator therapy, rheological agents, and antioxidants, to list a few amongst the host of the agents employed for the treatment. The availability of conflicting outcomes and lack of conclusive evidence has resulted in the propagation of consensus-based treatment protocols. In the present review, we discuss the various controversial issues and newer developments in the management of idiopathic SSNHL. The current review aims to present a narrative outlook of the updated evidence base available from PUBMED, augmented with relevant designated publications.     

Comparative Safety,Bioavailability, and Pharmacokinetics of Oral Dexamethasone, 4-mg and 20-mg Tablets,in Healthy Volunteers Under Fasting and Fed Conditions: A Randomized Open-label, 3-way Crossover Study

BackgroundGlucocorticoids, particularly dexamethasone, are often used in combination with novel agents in multiple myeloma. This study compared the safety, rate, and extent of absorption of a single dose of an orally administered 20-mg dexamethasone tablet to five 4-mg tablets (total, 20 mg).Patients and MethodsThis was a single-center, open-label, randomized, 3-way crossover comparative study. Thirty-six volunteers received at least 1 dose of either a single 20-mg dexamethasone tablet, under fasting or fed conditions, or five 4-mg dexamethasone tablets (total, 20 mg). Blood samples were collected before study drug administration and at 21 time points for up to 36 hours after drug administration.ResultsMean area under the concentration-time curve from time zero to the time of last non-zero concentration (AUC_0–t), mean area under the concentration-time curve from time zero to infinity (extrapolated) (AUC_0–∞), and maximum observed concentration (C_max) were 1314.38 ng × h/mL, 1329.24 ng × h/mL, and 257.22 ng/mL, respectively for fasting test formulation (single dexamethasone 20-mg tablet), 1339.74 ng × h/mL, 1358.07 ng × h/mL, and 194.56 ng/mL, respectively, for the fed test formulation (single dexamethasone 20-mg tablet), and 1325.12 ng × h/mL, 1342.12 ng × h/mL, and 244.12 ng/mL, respectively, for the reference formulation (5 dexamethasone 4-mg tablets). The median time of observed C_max was 0.997 hours for the fasting and 2.502 hours for the fed test formulation, compared with 1.495 hours for the reference. Mean plasma elimination half-lives (t_1/2) were 4.0 hours (test fasting), 4.03 hours (test fed), and 3.96 hours (reference). The point estimates and 90% confidence intervals (CIs) for AUC_0-t, AUC_0-∞, and C_max were 99.37% (90% CI, 95.65%-103.24%), 99.24% (90% CI, 95.47%-103.16%), and 106.28% (90% CI, 97.69%-115.62%), respectively, satisfying the bioequivalence criteria of the United States Food and Drug Administration guidelines.ConclusionThe 2 formulations were well-tolerated, and one 20-mg tablet or five 4-mg tablets of dexamethasone are bioequivalent under fasting conditions and thus may be prescribed interchangeably.     

来曲唑联合地塞米松对多囊卵巢综合征患者血清Galectin-3及HSP70的影响

目的 探讨来曲唑联合地塞米松对多囊卵巢综合征(PCOS)患者血清半乳糖凝集素-3(Galectin-3)及热休克蛋白(HSP70)表达的影响。方法 选择2019年6月—2021年6月在我院治疗的PCOS患者220例为研究对象,按随机数表法分为对照组(n=110)和观察组(n=110),对照组常规给予来曲唑治疗。观察组在对照组的基础上加用地塞米松联合治疗。观察并比较两组患者的激素水平,促排卵情况,血清抗苗勒管激素(AMH)、Galectin-3、HSP70及单核细胞趋化蛋白-1(MCP-1)水平及不良反应发生率。结果 治疗后两组患者的性激素水平均改善,且观察组变化幅度高于对照组(P<0.05)。观察组患者雌二醇(E₂)用量低于对照组,成熟卵泡数量和最大卵泡直径均高于对照组(均P<0.05)。两组患者的早期流产率差异无统计学意义(P>0.05);观察组患者的妊娠率高于对照组(P<0.05)。治疗前两组患者AMH、Galectin-3、HSP70、MCP-1水平差异无统计学意义(P>0.05),治疗后两组患者的AMH、Galectin-3、...     

地塞米松的抗氧化作用及其对实验性大鼠急性肝损伤的保护效果

目的　探讨地塞米松（Ｄｅｘ）在急性肝损伤中的作用及机制。方法　用Ｄ－ 半乳糖胺（Ｄ－ ＧａｌＮ）加内毒素脂多糖（ＬＰＳ） 制成大鼠急性肝损伤模型,并用Ｄｅｘ 预处理。结果　Ｄｅｘ 组肝损伤明显减轻,伴有血中一氧化氮（ＮＯ） 含量、肝组织中ＭＤＡ及铁含量降低,ＳＯＤ活性及锌含量增高。结论　Ｄｅｘ 对此种肝损伤有保护作用,这种保护作用可能与其抑制ＮＯ 过量产生,抑制脂质过氧化反应,增加组织抗氧化活性有关。     

麻醉穿刺时地塞米松对神经根损伤的疗效

目的探讨麻醉穿刺时地塞米松对神经根损伤的临床效果。方法腰硬联合麻醉穿刺过程中神经根损伤的剖腹产手术56患者随机分为观察组和对照组。观察组在手术结束前硬膜外注射地塞米松5mg加0.9%氯化钠注射液19mL。对照组注射0.9%氯化钠注射液10mL。比较2组患者的手术、麻醉时间和治疗效果。结果 2组患者手术时间和麻醉时间差异无统计学意义(P>0.05)。观察组有效率100%,无并发症发生,对照组有效率71.4%,并发症发生率为28.6%,差异有统计学意义(P<0.05)。结论地塞米松对腰硬联合麻醉穿刺时造成的神经根损伤作用效果明显,并发症发生率较低,疗效确切。     

地塞米松对成纤维细胞核仁组成区相关嗜银蛋白增生的抑制作用

目的和方法：应用核仁组成区相关嗜银蛋白（ＡｇＮＯＲｓ）染色结合图像分析技术,观察皮质类固醇激素地塞米松对体外培养的ＮＩＨ／３Ｔ３成纤维细胞ＡｇＮＯＲｓ增生的抑制作用。结果：（１）地塞米松对正常和不同因子刺激的成纤维细胞ＡｇＮＯＲｓ的增生均显示不同程度的抑制作用,其抑制强弱的顺序为：正常〉５－羟色胺〉ＩＬ－１和肝素;（２）地塞米松的抑制作用与其浓度密切相关,对正常５－羟色胺和肝素、ＩＬ－１刺激的成纤     

Targeted IL‐4 therapy synergizes with dexamethasone to induce a state of tolerance by promoting Treg cells and macrophages in mice with arthritis

F8‐IL‐4 is a recently developed immunocytokine that delivers IL‐4 to sites of inflammation by targeting the neovasculature. We previously reported that F8‐IL‐4, in combination with dexamethasone (DXM), provides a durable therapy in mice with collagen‐induced arthritis (CIA). Therefore, the objective of this study was to identify the mechanism by which IL‐4 and DXM combination therapy provides long‐lasting disease remission. F8‐IL‐4 alone attenuated inflammation in CIA and this was associated with increased T_H2 and decreased T_H17 cell numbers in the joints. Similarly, DXM alone had an antiinflammatory effect associated with lower T_H17 cell numbers. In both cases, these therapeutic benefits were reversed once treatment was stopped. On the other hand, combination therapy with F8‐IL‐4 plus DXM led to a synergistic increase in the percentage of regulatory T (Treg) cells and antiinflammatory macrophages in the arthritic joint and spleen as well as IL‐10 levels in serum and spleen. The net result of this was a more pronounced attenuation of inflammation and, more importantly, protection from arthritis relapse post therapy retraction. In conclusion, F8‐IL‐4 plus DXM is a durable treatment for arthritis that acts by promoting Treg cells in a synergistic manner, and by producing a sustained increase in antiinflammatory macrophages.