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1.
《Molecular therapy》2022,30(5):1952-1965
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Neuro-inflammation may be important in the pathogenesis of postoperative delirium following hip fracture surgery. Studies have suggested a potential role for steroids in reducing postoperative delirium; however, the potential efficacy and safety of pre-operative high-dose dexamethasone in this specific population is largely unknown. Conducting such a study could be challenging, considering the multidisciplinary team involvement and the emergency nature of the surgery. The aim of this study was to assess feasibility and effectiveness of dexamethasone given as early as possible following hospital admission for hip fracture, to inform whether a full-scale trial is warranted. This single-centre, randomised, double-blind, placebo-controlled study randomly allocated 79 participants undergoing hip fracture surgery to dexamethasone 20 mg or placebo pre-operatively. Eligibility and recruitment rates, timing of the intervention and adverse events were recorded. Incidence and severity of postoperative delirium were assessed using the 4AT delirium screening tool and the Memorial Delirium Assessment Scale. Postoperative pain, length of stay and mortality were also assessed. The eligibility rate for inclusion was 178/527 (34%), and 57/178 (32%) of eligible patients presented to hospital when no researcher was available (e.g. after-hours, weekends, public holidays). Recruitment was limited mainly by ethical limitations (not including patients with impaired cognition) and lack of weekend staffing. Median (IQR [range]) time from emergency department admission to drug administration was 13.3 (5.9–17.6 [1.8–139.6]) hours. There was a significant difference in delirium severity scores, favouring the dexamethasone group: median (IQR [range]) 5 (3–6 [3–7]) vs. 9 (6–13 [5–14]) in the placebo group, with the probability of superiority effect size being 0.89, p = 0.010. Delirium incidence did not differ between groups: 6/40 (15%) in the dexamethasone group vs. 9/39 (23%) in the placebo group, relative risk (95%CI) 0.65 (0.22–1.65), p = 0.360). A larger randomised controlled trial is feasible and ideally this should include people with existing cognitive impairment, seven days-a-week cover and a multicentre design.  相似文献   
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目的: 探讨地塞米松及其拮抗剂维生素B12干预妊娠关键期孕鼠后,小鼠胚胎腭突上Shh信号通路重要因子、细胞周期调控因子及初级纤毛解聚相关因子的调控及三者间的变化关系。方法: 予特定孕期C57BL/6J孕鼠腹腔注射一定剂量的生理盐水(空白对照组)、地塞米松(地塞米松组)、维生素B12(维生素B12组)、地塞米松+维生素B12(地塞米松+维生素B12组),观察妊娠17.5 d和13.5 d各组小鼠胚胎腭突融合情况;Western blot检测妊娠13.5 d各组小鼠胚胎腭突中Smo、Ptch1、Cyclin D1、Aurora A的表达变化并进行统计学分析。结果: 地塞米松延缓胚胎腭突发育而导致腭裂发生,而维生素B12干预后,可部分恢复胚胎腭突发育。Western blot结果显示,与对照组相比,Ptch 1、Aurora A、Cyclin D1的表达在地塞米松组中明显降低(均P=0.000),Smo无明显改变(P=0.695);地塞米松+维生素B12组中Ptch 1、Aurora A、Cyclin D1的表达与地塞米松组相比,均不同程度上调(均P=0.000),Smo无明显改变(P=0.818);维生素B12组中各目的蛋白表达与对照组无统计学差异(P=0.879、0.399、0.645、0.168)。结论: 地塞米松影响小鼠胚胎腭突Shh下游信号传递和初级纤毛解聚,从而抑制Cyclin D1表达使小鼠胚胎腭突细胞增殖降低,维生素B12可通过上调相关因子蛋白含量拮抗这一抑制效果。  相似文献   
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Bortezomib in combination with cyclophosphamide and dexamethasone (CyBorD, is a well-established frontline chemotherapy regimen for patients with multiple myeloma, but prospective data on elderly non-transplant eligible patients is limited. A total of 155 patients aged 70 years or older with newly diagnosed multiple myeloma who received at least one cycle of CyBorD chemotherapy in three centres across New Zealand were evaluated. Partial response or better was achieved in 79·4%, of whom 52·9% achieved at least a very good partial response. After a median follow-up of 31·9 months, the median event-free survival (EFS) was 17·0 months (age 70–80 years, 17·7 months; age above 80 years, 8·6 months; P = 0·002). The median overall survival was 45·1 months (age 70–80, 49·8 months; above 80, 33·3 months; P = 0·003). Amongst those who had seven or more cycles of treatment, those who had a pre-planned switch to bortezomib-thalidomide-dexamethasone (VTD) consolidation had a superior median EFS of 25·4 months, compared with 20·3 months in the CyBorD only group (P = 0·028). This is the largest real-world dataset on the efficacy of CyBorD in the elderly population, and pre-planned switch to VTD was associated with better outcomes.  相似文献   
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The aim of this systematic review and meta-analysis was to determine whether there are clinically effective reductions in postoperative pain, oedema, and trismus following submucosal dexamethasone administration during impacted mandibular third molar surgery. An electronic database search was conducted up to and including June 2018. Randomized and quasi-randomized trials assessing the effects of submucosal dexamethasone in adult patients undergoing mandibular third molar surgery were included. The mean differences or standardized mean differences were extracted and pooled using the fixed-effects or random-effects model. Seventeen trials were included and independently assessed for risk of bias. There was low quality evidence that submucosal dexamethasone reduces early postoperative pain, early and late postoperative trismus, and late postoperative oedema after mandibular third molar extraction. Moderate quality evidence was found for the reduction of late postoperative pain and early postoperative oedema. The greatest clinical effect of submucosal dexamethasone injection during impacted mandibular third molar surgery was a reduction of early postoperative pain (number needed to treat (NNT) = 4) and early postoperative oedema (NNT = 5). The reduction in trismus was not clinically significant (<5 mm). Further research focusing on strengthening the quality of evidence, investigating potential harms and a definitive protocol for submucosal administration during mandibular third molar surgery is required.  相似文献   
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BackgroundDexamethasone has been shown to reduce postoperative pain and opioid consumption for total joint arthroplasty patients; however, its impact on patients who received neuraxial anesthesia (NA) is not well described. We examined the impact of perioperative dexamethasone on outcomes for patients undergoing direct anterior approach total hip arthroplasty (THA) under NA.MethodsA retrospective review was conducted for 376 THA patients from a single institution. Univariate analysis was used to compare postoperative outcomes for 164 THA patients receiving dexamethasone compared to 212 who did not receive dexamethasone.ResultsNo differences in age, gender, body mass index, or American Society of Anesthesiologists (ASA) Score were observed between the groups. Patients receiving perioperative dexamethasone reported statistically significantly lower postanesthesia care unit (PACU) pain numeric rating scale (Dexamethasone 1.6 vs No dexamethasone 2.3, P = .014) and received lower PACU morphine milligram equivalents (MME) (Dexamethasone 8.57 vs No dexamethasone 11.44, P < .001). Patients receiving dexamethasone had significantly shorter LOS (Dexamethasone 29.40 vs No dexamethasone 35.26 hrs., P < .001).ConclusionPerioperative dexamethasone is associated with decreased postoperative pain and narcotic consumption, and shorter length of stay for patients undergoing primary direct anterior approach THA with NA.  相似文献   
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