Acute Migraine Treatment in Adults

There are many options for acute migraine attack treatment, but none is ideal for all patients. This study aims to review current medical office‐based acute migraine therapy in adults and provides readers with an organized approach to this important facet of migraine treatment. A general literature review includes a review of several recent published guidelines. Acetaminophen, 4 nonsteroidal anti‐inflammatory drugs (NSAIDs) (ibuprofen, acetylsalicylic acid [ASA], naproxen sodium, and diclofenac potassium), and 7 triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan) have good evidence for efficacy and form the core of acute migraine treatment. NSAID–triptan combinations, dihydroergotamine, non‐opioid combination analgesics (acetaminophen, ASA, and caffeine), and several anti‐emetics (metoclopramide, domperidone, and prochlorperazine) are additional evidence‐based options. Opioid containing combination analgesics may be helpful in specific patients, but should not be used routinely. Clinical features to be considered when choosing an acute migraine medication include usual headache intensity, usual rapidity of pain intensity increase, nausea, vomiting, degree of disability, patient response to previously used medications, history of headache recurrence with previous attacks, and the presence of contraindications to specific acute medications. Available acute medications can be organized into 4 treatment strategies, including a strategy for attacks of mild to moderate severity (strategy one: acetaminophen and/or NSAIDs), a triptan strategy for patients with severe attacks and for attacks not responding to strategy one, a refractory attack strategy, and a strategy for patients with contraindications to vasoconstricting drugs. Acute treatment of migraine attacks during pregnancy, lactation, and for patients with chronic migraine is also discussed. In chronic migraine, it is particularly important that medication overuse is eliminated or avoided. Migraine treatment is complex, and treatment must be individualized and tailored to the patient's clinical features. Clinicians should make full use of available medications and formulations in an organized approach.     

ω-3鱼油脂肪乳剂对脓毒症患者炎症反应和免疫功能的影响

目的探讨ω-3鱼油脂肪乳剂对脓毒症患者炎症反应和免疫功能的影响。方法选择70例脓毒症患者并随机分为中长链脂肪乳组和鱼油组,肠外营养支持方案中长链脂肪乳组给予中长链脂肪乳剂1.2 g·kg-1·d-1静脉滴注,每日一次;鱼油组加用ω-3鱼油脂肪乳剂0.24 g·kg-1·d-1静脉滴注,每日一次,余与中长链脂肪乳组肠外营养治疗方案成分相同,共7 d,其他治疗措施相同。检测两组患者治疗第1天和第7天外周血中炎症反应指标[C反应蛋白（CRP）、白介素1β（IL-1β）、白介素6（IL-6）、肿瘤坏死子-α（TNF-α）]和T 细胞亚群的变化（CD3+、CD4+、CD8+、CD4+/CD8+）。结果治疗后第7天,鱼油组患者的炎症反应指标中的CRP、IL-1β、IL-6均较第1天有所下降,差异均有统计学意义（t分别=190.78、72.26、115.08,P均＜0.05）;中长链脂肪乳组与治疗第1天相比,CRP和IL-6明显下降、IL-1β和TNF-α明显上升,差异均有统计学意义（t分别=138.36、64.85、77.13、59.56, P均＜0.05）。鱼油组第7天各项炎症反应指标均低于中长链脂肪乳组,差异均有统计学意义（t分别=28.56、134.72、56.85、42.18, P均＜0.05）。鱼油组第7天CD3+、CD4+、CD4+/CD8+较第1天明显升高,CD8+较第1天明显降低,差异均有统计学意义（t分别=43.03、71.62、-29.37、35.04, P均＜0.05）。中长链脂肪乳组第7天CD3+、CD4+、CD4+/CD8+较第1天明显升高,CD8+较第1天明显降低,差异均有统计学意义（t分别=38.24、65.73、-25.68、30.17, P均＜0.05）。且第7天时,两组间CD3+、CD4+、CD8+、CD4+/CD8+比较,差异均有统计学意义（t分别=22.73、10.60、-15.38、7.25, P均＜0.05）。结论ω-3鱼油脂肪乳剂可能会减轻脓毒症患者的炎症反应,改善患者的细胞免疫功能。     

手足口病患儿皮质醇β-内啡肽和部分细胞因子监测价值

目的明确手足口病患儿皮质醇、β-内啡肽和部分细胞因子监测的临床价值。方法选取2011年1~6月该院收治的手足口病患儿(普通组30例、重型组30例)及健康儿童(对照组30例),比较皮质醇、β-内啡肽、白细胞介素10(IL-10)、白细胞介素13(IL-13)、γ干扰素(IFN-γ)及肿瘤坏死因子-α(TNF-α)水平,并对其治疗前后各项指标水平进行对比。结果与对照组比较,普通组与重型组的皮质醇、β-内啡肽、IL-10、IL-13、IFN-γ及TNF-α水平均有所升高,组间比较,差异有统计学意义(P0.05)。随着病情的加重,皮质醇、β-内啡肽及细胞因子水平逐渐增加,且重型组与普通组的各项指标差异有统计学意义(P0.05)。普通组患儿治疗后,皮质醇、β-内啡肽、IL-10、IL-13、IFN-γ及TNF-α水平下降,接近对照组。重型组患儿治疗后,皮质醇、β-内啡肽、IL-10、IL-13、IFN-γ及TNF-α水平升高。两组患儿治疗前后皮质醇、β-内啡肽及细胞因子水平组内比较,差异有统计学意义(P0.05)。结论血清皮质醇、β-内啡肽及部分细胞因子水平对手足口病的病情判断及治疗具有重要的临床价值。     

全身型幼年特发性关节炎患儿自身抗体和炎性细胞因子研究

目的探讨自身抗体和炎性细胞因子在全身型幼年特发性关节炎(So-JIA)中的变化。方法分别采用间接免疫荧光法和酶联免疫吸附法检测活动期、缓解期So-JIA患儿血清抗角蛋白抗体(AKA)、抗环瓜氨酸肽抗体(抗CCP抗体)、白细胞介素-17(IL-17)和白细胞介素-6(IL-6)的表达水平。以健康儿童作为健康对照组进行比较。结果活动期组血清AKA、抗CCP抗体阳性率分别为29.4%、47.1%,缓解期组分别为17.2%、27.6%,活动期组均高于缓解期组(P0.05)。So-JIA组AKA的灵敏度和特异度分别为21.1%和97.2%,抗CCP抗体的灵敏度和特异度分别为41.3%和91.9%,抗CCP抗体的灵敏度高于AKA。活动期组抗CCP抗体、IL-17、IL-6水平均高于健康对照组和缓解期组(P0.05);缓解期组抗CCP抗体、IL-17、IL-6水平高于健康对照组,但比较差异无统计学意义(P0.05)。结论自身抗体AKA和抗CCP抗体对So-JIA具有较高的特异度,但灵敏度欠佳,二者联合检测对提高So-JIA诊断特异度,尤其对提高活动期So-JIA诊断阳性率有一定的临床价值。     

PEG hydrogel degradation and the role of the surrounding tissue environment

Poly(ethylene glycol) (PEG)‐based hydrogels are extensively used in a variety of biomedical applications, due to ease of synthesis and tissue‐like properties. Recently there have been varied reports regarding PEG hydrogel's degradation kinetics and in vivo host response. In particular, these studies suggest that the surrounding tissue environment could play a critical role in defining the inflammatory response and degradation kinetics of PEG implants. In the present study we demonstrated a potential mechanism of PEG hydrogel degradation, and in addition we show potential evidence of the role of the surrounding tissue environment on producing variable inflammatory responses. Copyright © 2013 John Wiley & Sons, Ltd.     

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery

Inflammation has an integral role in the pathophysiology of AKI. We investigated the associations of two biomarkers of inflammation, plasma IL-6 and IL-10, with AKI and mortality in adults undergoing cardiac surgery. Patients were enrolled at six academic centers (n=960). AKI was defined as a ≥50% or ≥0.3-mg/dl increase in serum creatinine from baseline. Pre- and postoperative IL-6 and IL-10 concentrations were categorized into tertiles and evaluated for associations with outcomes of in-hospital AKI or postdischarge all-cause mortality at a median of 3 years after surgery. Preoperative concentrations of IL-6 and IL-10 were not significantly associated with AKI or mortality. Elevated first postoperative IL-6 concentration was significantly associated with higher risk of AKI, and the risk increased in a dose-dependent manner (second tertile adjusted odds ratio [OR], 1.61 [95% confidence interval (95% CI), 1.10 to 2.36]; third tertile adjusted OR, 2.13 [95% CI, 1.45 to 3.13]). First postoperative IL-6 concentration was not associated with risk of mortality; however, the second tertile of peak IL-6 concentration was significantly associated with lower risk of mortality (adjusted hazard ratio, 0.75 [95% CI, 0.57 to 0.99]). Elevated first postoperative IL-10 concentration was significantly associated with higher risk of AKI (adjusted OR, 1.57 [95% CI, 1.04 to 2.38]) and lower risk of mortality (adjusted HR, 0.72 [95% CI, 0.56 to 0.93]). There was a significant interaction between the concentration of neutrophil gelatinase-associated lipocalin, an established AKI biomarker, and the association of IL-10 concentration with mortality (P=0.01). These findings suggest plasma IL-6 and IL-10 may serve as biomarkers for perioperative outcomes.     

Deficiency of Fibroblast Growth Factor-Inducible 14 (Fn14) Preserves the Filtration Barrier and Ameliorates Lupus Nephritis

TNF ligand superfamily member 12, also known as TNF-related weak inducer of apoptosis (TWEAK), acts through its receptor, fibroblast growth factor-inducible 14 (Fn14), to mediate several key pathologic processes involved in tissue injury relating to lupus nephritis. To explore the potential for renal protection in lupus nephritis by targeting this pathway, we introduced the Fn14 null allele into the MRL-lpr/lpr lupus mouse strain. At 26–38 weeks of age, female Fn14-knockout MRL-lpr/lpr mice had significantly lower levels of proteinuria compared with female wild-type MRL-lpr/lpr mice. Furthermore, Fn14-knockout mice had significantly improved renal histopathology accompanied by attenuated glomerular and tubulointerstitial inflammation. There was a significant reduction in glomerular Ig deposition in Fn14-knockout mice, despite no detectable differences in either serum levels of antibodies or splenic immune cell subsets. Notably, we found that the Fn14-knockout mice displayed substantial preservation of podocytes in glomeruli and that TWEAK signaling directly damaged barrier function and increased filtration through podocyte and glomerular endothelial cell monolayers. Our results show that deficiency of the Fn14 receptor significantly improves renal disease in a spontaneous lupus nephritis model through prevention of the direct injurious effects of TWEAK on the filtration barrier and/or modulation of cytokine production by resident kidney cells. Thus, blocking the TWEAK/Fn14 axis may be a novel therapeutic intervention in immune-mediated proliferative GN.     

IL‐17 Deficiency Attenuates Allograft Injury and Prolongs Survival in a Murine Model of Fully MHC‐Mismatched Renal Allograft Transplantation

IL‐17 is a pro‐inflammatory cytokine implicated in the pathogenesis of inflammatory and autoimmune diseases. However the role of IL‐17 in renal allograft rejection has not been fully explored. Here, we investigate the impact of IL‐17 in a fully MHC‐mismatched, life‐sustaining, murine model of kidney allograft rejection using IL‐17 deficient donors and recipients (IL‐17^?/? allografts). IL‐17^?/? allografts exhibited prolonged survival which was associated with reduced expression of the Th1 cytokine IFN‐γ and histological attenuation of acute and chronic allograft rejection, as compared to wild‐type allograft recipients. Results were confirmed in WT allograft recipients treated with an IL‐17 blocking antibody. Subsequent experiments using either donors or recipients deficient in IL‐17 showed a trend towards prolongation of survival only when recipients were IL‐17^?/?. Administration of a depleting anti‐CD25 antibody to IL‐17^?/? recipients abrogated the survival advantage conferred by IL‐17 deficiency, suggesting the involvement of a CD4⁺CD25⁺ T cell regulatory mechanism. Therefore, IL‐17 deficiency or neutralization was protective against the development of kidney allograft rejection, which may be mediated by impairment of Th1 responses and/or enhanced protection by Tregs.