结核性胸膜炎患者化疗时是否加用糖皮质激素对肺功能动态变化的对比研究

目的 探讨结核性胸膜炎患者化疗时是否加用糖皮质激素对肺功能的动态变化。方法 回顾性分析首都医科大学附属北京胸科医院2015年5月至2018年5月收治的结核性胸膜炎患者172例,对患者的肺通气、容积、弥散功能和呼吸肌力学指标在化疗前,以及化疗第1、6、12个月末进行4次检测;根据在抗结核药品化疗方案的基础上是否加用糖皮质激素分为两组,即加用组60例(醋酸泼尼松+2H-R-Z-E/10H-R-E)和未加用组112例(2H-R-Z-E/10H-R-E)。肺通气功能的检测指标为患者用力肺活量检测值占正常预计值的百分比(FVC)、第1秒用力呼气容积检测值占正常预计值的百分比(FEV₁% pred)、第1秒钟用力呼气容积/用力肺活量比值占正常预计值的百分比(FEV₁/FVC% pred)、用力呼出75%肺总量时瞬间呼气流量检测值占正常预计值的百分比(FEF₇₅)、最大分钟通气量检测值占正常预计值的百分比(MVV% pred);肺容积功能的检测指标为残气量检测值占正常预计值的百分比(RV% pred)、肺总量检测值占正常预计值的百分比(TLC% pred)、残气量/肺总量比值占正常预计值的百分比(RV/TLC% pred);弥散功能的检测指标为肺弥散量检测值占正常预计值的百分比(D_LCO)和肺泡容量校正的肺弥散率检测值占正常预计值的百分比(D_LCO/VA% pred);呼吸肌力学的检测指标为气道阻力检测值占正常预计值的百分比(Rtot% pred、呼气峰流量检测值占正常预计值的百分比(PEF% pred)、吸气峰值流量实测值(PIF),通过对检测指标的观察,了解肺功能的变化。肺功能测定结果按“测定值/正常预计值×100%”表示(除PIF为实测值),符合正态分布的计量资料采用“$\overline{x}$±s”进行统计描述,统计学处理采用t检验;不符合正态分布的计量资料采用中位数(四分位数)[M(Q₁,Q₃)] 表示,统计学处理采用Z检验,P<0.05为差异有统计学意义。结果 (1)结核性胸膜炎患者化疗前,以限制性通气功能障碍为主,FVC% pred为(62.1±13.4)%,FEV₁% pred为(64.4±15.5)%,FEV₁/FVC% pred为(87.0±11.1)%,MVV% pred (65.7±21.1)%,FEF₇₅% pred为61.6(41.6,83.0)%,RV% pred为111.3(89.8,131.4)%, TLC% pred为 (77.0±16.9)%,RV/TLC% pred为(146.9±35.9)%, D_LCO% pred为(62.6±18.3)%,D_LCO/VA% pred为(92.3±16.6)%,PEF% pred为(64.1±18.13)%,PIF为 3.2(2.3,4.1)L/s,Rtot% pred为96.0(69.3,118.9)%]。(2)化疗过程中,第1、6、12个月末 FVC<80%的患者分别为80.2%(138/172)、75.0%(129/172)、0.0%(0/0);化疗第6个月末D_LCO<80%的患者为44.2%(76/172)); (3)加用组和未加用组患者在化疗前、化疗第1、6、12个月末FEF₇₅% pred[分别为(68.7(49.8,84.1)%和60.7(39.4,80.7)%);87.1(70.5,94.4)%和73.1(51.9,87.0)%;80.1(66.5,111.9)%和66.8(59.9,87.2)%;90.4(55.3,102.9)%和78.4(54.6,87.3)%],两组比较差异均无统计学意义值分别为-1.091、-0.111、-1.609、-1.171,P值均>0.05); MVV% pred[分别为(65.8±19.4)%和(65.5±18.6)%);(86.9±18.6)%和(79.5±18.7)%;(90.3±16.0)%和(86.3±16.0)%;(96.8±11.1)%和(87.3±19.8)],两组比较差异均无统计学意义(t值分别为1.043、0.444、0.708、1.113,P值均>0.05)。结论 结核性胸膜炎患者治疗前、治疗第1个月末肺功能减退主要表现为限制性通气功能障碍和弥散功能减退,治疗第6个月末仅通气功能恢复正常,而弥散功能在治疗第12个月末恢复正常;早期糖皮质激素辅助治疗对结核性胸膜炎患者的肺功能无明显影响。     

特布他林联合糖皮质激素治疗慢性阻塞性肺疾病急性加重期的疗效研究

目的：探讨特布他林联合糖皮质激素治疗慢性阻塞性肺疾病（ COPD）急性加重期的疗效。方法选取2011—2012年安新县医院收治的COPD急性加重期患者112例,随机分为观察组与对照组,各56例。对照组患者予以特布他林治疗,观察组患者在对照组基础上加用糖皮质激素治疗。观察两组患者动脉血气指标、临床疗效及呼吸困难分级。结果治疗前两组患者PaO2、PaCO2和pH值比较,差异无统计学意义（ P>0.05）,治疗后观察组患者PaO2和pH值高于对照组,PaCO2低于对照组,差异有统计学意义（P<0.05）;观察组患者临床疗效优于对照组（P<0.05）;治疗前两组患者呼吸困难分级比较,差异无统计学意义（ P>0.05）,治疗后观察组患者呼吸困难分级优于对照组（ P<0.05）。结论特布他林联合糖皮质激素治疗COPD急性加重期的疗效显著,可改善患者临床症状,提高生活质量。     

Risk for osteoporosis and fracture with glucocorticoids

Glucocorticoid use is ubiquitous and is associated with multiple adverse reactions. Among them, osteoporosis and bone fractures are of our concern. In this review, we present current evidence on the effect of glucocorticoids on bone mineral density and the risk of fractures, the mechanisms underlying those effects, and the recommendations for monitoring and treating patients who take them.The bone mineral density of the lumbar spine and total hip is lower, and the risk of fractures is higher in glucocorticoid users than non-users. These effects have a rapid onset, are dose-dependent, and improve soon after discontinuation of glucocorticoids. They also appear to occur even with non-systemic routes of administration and with low doses.Glucocorticoids reduce bone mineral density by increasing osteoclast activity and decreasing osteoblast and osteocyte activity. Calcium metabolism and parathyroid hormone activity are less important than was initially thought.Treatment decisions are on risk stratification using clinical, radiographic, and prediction tools. Our armamentarium for the treatment and prevention of glucocorticoid-induced osteoporosis includes calcium and vitamin D, bisphosphonates, recombinant parathyroid hormone, monoclonal antibodies against receptor activator of nuclear factor kappa-B ligand, and hormone treatments.     

Unmet need in the treatment of polymyalgia rheumatica and giant cell arteritis

For decades, aside from prednisone and the occasional use of immune suppressive drugs such as methotrexate, there was little to offer patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). However, there is a great interest in various steroid sparing treatments in both these conditions. This paper aims to provide an overview of our current knowledge of PMR and GCA, examining their similarities and distinctions in terms of clinical presentation, diagnosis, and treatment, with emphasis placed on reviewing recent and ongoing research efforts on emerging treatment. Multiple recent and ongoing clinical trials are demonstrating new therapeutics that will provide benefit and contribute to the evolution of clinical guidelines and standard of care for patients with GCA and/or PMR.     

儿童肾移植术后激素撤除对生长曲线的影响CSCD

目的探究儿童肾移植术后生长趋势以及激素撤除对于生长曲线的影响。方法回顾性分析2013年5月至2021年3月于郑州大学第一附属医院肾移植科接受肾移植手术的儿童受者临床资料,术后采用他克莫司+霉酚酸+糖皮质激素(glucocorticoid,GC)三联免疫治疗方案,根据术后3个月内是否撤除激素分为撤激素组和未撤激素组,观察两组各时间段内生长发育变化情况,比较两组在撤除激素前后各时间段生长变化速率的差异。结果共214例患儿纳入研究,其中未撤激素组142例,撤激素组72例;两组术前身高年龄别评分(height for age Z-score,HAZ评分)分别为(-1.60±1.48)分和(-1.44±1.38)分,差异无统计学意义(P=0.539);术后1年时两组HAZ评分分别为(-0.95±1.31)分和(-0.51±1.10)分,差异具有统计学意义(P=0.046)。两组术前、术后3个月、术后6个月的HAZ评分差异均无统计学意义(P>0.05)。两组手术后前3个月、手术后3~6个月HAZ评分的变化速率差异均无统计学意义(P>0.05),而手术后6~12个月的差异具有统计学意义(P=0.016)。结论慢性终末期肾病(end-stage renal disease,ESRD)患儿术前存在不同程度的发育迟缓,接受肾移植后患儿生长缺陷有所弥补,术后不同时间段身高发育速率有所不同,在术后追赶性生长的高峰期到来之前撤除激素对于儿童手术后远期发育有积极的影响。     

Churg‐Strauss syndrome with poor‐prognosis factors: A prospective multicenter trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in forty‐eight patients

Objective

To compare long and short durations of adjunctive cyclophosphamide for the treatment of severe Churg‐Strauss syndrome (CSS).

Methods

In this prospective multicenter therapeutic trial, 48 patients with CSS with at least 1 poor‐prognosis factor at baseline were treated with glucocorticoids and either 12 or 6 intravenous cyclophosphamide pulses.

Results

At 8 years, complete remission rates and severe side effects of therapy were comparable for both groups. The overall difference in relapses was not significant between the 12‐pulse and the 6‐pulse regimens (P = 0.07), but when considering only the number of mild relapses this difference became statistically significant (P < 0.02). Although the total number of inclusions was not reached, the study was stopped prematurely in response to the superiority of the 12‐pulse regimen.

Conclusion

We concluded that 12 cyclophosphamide pulses were better able to control severe CSS than a 6‐pulse regimen. The optimal duration of therapy remains to be determined.     

Osteoporosis in children and young adults

Osteoporosis is a major public health problem with serious long-term complications. In children, the definition of osteoporosis is not only based on densitometric criteria but also takes into account vertebral and long bone fragility fractures. Several factors, such as long-term high-dose steroids, chronic inflammation, malnutrition, immobility, lack of sex steroids, and medication can reduce bone density and increase the risk for fragility fractures when left untreated. Also, genetic conditions can predispose to primary bone fragility disorders, with osteogenesis imperfecta being the most common. Furthermore, since the growing skeleton is at an increased rate of bone remodeling, the ability to heal long bone fractures and reshape vertebral fractures differentiates children from adults. The scope of this chapter is to review the risk factors of osteoporosis and fragility fractures and describe the commonest causes of primary and secondary osteoporosis and their management in children and young adults.     

Eosinophilic gastroenteritis with severe protein-losing enteropathy: Successful treatment with budesonide

We report the clinical, laboratory, endoscopic and histopathological findings in a 40-year-old woman with watery diarrhoea and hypoproteinaemia. Elevated alpha(1)-antitrypsin clearance confirmed massive protein-losing enteropathy. Gastroscopic and colonoscopic biopsies showed abundant infiltration of the small bowel wall with eosinophils in proximal duodenum and terminal ileum, respectively. These findings established the diagnosis of eosinophilic gastroenteritis. Both the inflammatory alterations and the severe intestinal protein loss were successfully treated with budesonide, a topically active corticosteroid preparation with controlled small bowel release. The case report illustrates that remission of protein-losing enteropathy secondary to eosinophilic gastroenteritis can be achieved with budesonide, thus supporting its use for this uncommon disease characterised by inflammatory intestinal lesions.     

siRNA沉默MIF基因对糖皮质激素抑制脂质炎症介质释放的影响及其机制

 目的： 研究小干扰RNA（siRNA）阻断巨噬细胞移动抑制因子（macrophage migration-inhibitory factor,MIF）基因表达对糖皮质激素抑制脂质炎症介质释放的影响及其细胞内机制。方法：体外培养小鼠巨噬细胞系RAW2647,采用免疫荧光法观测siRNA转染效率,RT-PCR检测MIF mRNA的表达,Western blotting检测MIF蛋白的表达;RAW2647细胞转染MIF siRNA后观察地塞米松（Dex）抗炎作用的变化,用ELISA检测细胞上清中前列腺素E2(PGE2)和白三烯B4(LTB4)的含量,Western blotting检测胞浆膜联蛋白Annexin 1和下游胞浆磷酸酯酶A2α（cPLA2α）的蛋白表达变化。结果：与阴性对照相比,MIF siRNA能有效阻断细胞内源性MIF蛋白的表达,增强RAW2647细胞对Dex作用的敏感性;明显增强Dex抑制PGE2和LTB4产生的效应,增加胞浆蛋白Annexin 1的表达,抑制cPLA2α的磷酸化。结论：MIF siRNA能增强糖皮质激素抑制脂质炎症介质PGE2和LTB4的释放,且可能是通过影响Annexin 1-cPLA2α信号通路实现的。阻断内源性MIF蛋白的表达可显著增强RAW2647细胞对糖皮质激素抗炎作用的敏感性。     

Restraint stress and ethanol consumption in two mouse strains

Background: This study examined the interaction between restraint stress and ethanol drinking in mice that consume low and high amounts of ethanol. Methods: Two strains of mice (129SVEV and C57BL/6J) underwent 1 hour of restraint stress twice per day for 4 days in the presence of a CRF‐1 receptor antagonist, a glucocorticoid receptor antagonist or vehicle. Ethanol preference and consumption were assessed using a two bottle choice design. In another study, mice were implanted with pellets containing corticosterone; ethanol preference and consumption were assessed using a two bottle choice design. Results: Restraint stress significantly increased ethanol preference and consumption in 129SVEV mice but not in C57BL/6J mice. Then 129SVEV mice underwent the identical stress procedure; however, mice received either the CRF‐1 receptor antagonist, R121919 (15 or 20 mg/kg, ip) or vehicle 30 minutes prior to stress. R121919 did not block the stress‐induced change in ethanol preference despite causing a significant blunting in the HPA axis. Negative results were also obtained using the CRF‐1 receptor antagonist, Antalarmin (20 mg/kg, ip). In another study, 129SVEV mice were administered either the glucocorticoid receptor antagonist Mifepristone (25, 50 or 100 μg/kg, ip) or vehicle under the same procedure. Mifepristone did not alter ethanol preference. Moreover, the three receptor antagonist did not alter nonstress ethanol consumption either. In the last study, both mouse strains underwent active or sham adrenalectomy, then pellets containing corticosterone or placebo were implanted and preference for ethanol versus water was tested. Corticosterone administration decreased ethanol consumption in a strain‐dependent manner. Conclusion: These data show the restraint model for stress can modestly increase ethanol consumption in 129SVEV mice but not in C57BL/6J mice. Pharmacologic manipulation of CRF and corticosterone did not blunt baseline or stress‐induced change in ethanol preference nor did administration of corticosterone mimic the effects of restraint stress on ethanol consumption. These findings suggest the mechanism responsible for increasing ethanol consumption in this model is independent of the HPA axis and extra‐hypothalamic CRF.