- 作者列表："Garrahy A","Cuesta M","Murphy B","O'Reilly MW","Tormey WP","Sherlock M","Thompson CJ
Objective:Severe hyponatraemia (plasma sodium concentration, pNa <120 mmol/L) is reported to be associated with mortality rates as high as 50%. Although there are several international guidelines for the management of severe hyponatraemia, there are few data on the impact of treatment. Design and methods:We have longitudinally reviewed rates of specialist input, active management of hyponatraemia, treatment outcomes and mortality rates in patients with severe hyponatraemia (pNa <120 mmol/L) in 2005, 2010 and 2015, and compared the recent mortality rate with that of patients with pNa 120-125 mmol/L. Results:Between 2005 and 2010 there was a doubling in the rate of specialist referral (32 to 68%, P = 0.003) and an increase in the use of active management of hyponatraemia in patients with pNa <120 mmol/L (63 to 88%, P = 0.02), associated with a reduction in mortality from 51 to 15% (P < 0.001). The improved rates of intervention were maintained between 2010 and 2015, but there was no further reduction in mortality. When data from all three reviews were pooled, specialist consultation in patients with pNa <120 mmol/L was associated with a 91% reduction in mortality risk, RR 0.09 (95% CI: 0.03-0.26), P < 0.001. Log-rank testing on in-hospital survival in 2015 found no significant difference between patients with pNa <120 mmol/L and pNa 120-125 mmol/L (P = 0.56). Conclusion:Dedicated specialist input and active management of severe hyponatraemia are associated with a reduction in mortality, to rates comparable with moderate hyponatraemia.
目的: 据报道，严重低钠血症 (血浆钠浓度，pNa <120 mmol/L) 与高达50% 的死亡率相关。虽然有几个国际指南用于严重低钠血症的管理，但关于治疗影响的数据很少。 设计和方法: 我们纵向回顾了2005年、120年和2010年严重低钠血症 (pNa <2015 mmol/L) 患者的专家投入、低钠血症的积极管理、治疗结果和死亡率，比较pNa 120 ~ 125 mmol/L患者的近期死亡率。 结果: 在2005至2010之间，pNa <68% mmol/L患者的专科转诊率增加了一倍 (32至0.003，P = 120)，低钠血症积极管理的使用增加 (63至88%，P = 0.02)，与死亡率从51下降到15%(P <0.001)。在2010年至2015年期间，干预率有所提高，但死亡率没有进一步降低。当合并所有三个综述的数据时，pNa <120 mmol/L患者的专家咨询与死亡风险降低91% 相关，RR 0.09 (95% CI: 0.03-0.26)，P <0.001。2015年住院生存率的时序检验发现，pNa <120 mmol/L和pNa 120-125 mmol/L患者之间无显著差异 (P = 0.56)。 结论: 专门的专家投入和积极管理重度低钠血症与死亡率降低相关，与中度低钠血症相当。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.