- 作者列表："Volpicelli G","Gargani L","Perlini S","Spinelli S","Barbieri G","Lanotte A","Casasola GG","Nogué-Bou R","Lamorte A","Agricola E","Villén T","Deol PS","Nazerian P","Corradi F","Stefanone V","Fraga DN","Navalesi P","Ferre R","Boero E","Martinelli G","Cristoni L","Perani C","Vetrugno L","McDermott C","Miralles-Aguiar F","Secco G","Zattera C","Salinaro F","Grignaschi A","Boccatonda A","Giostra F","Infante MN","Covella M","Ingallina G","Burkert J","Frumento P","Forfori F","Ghiadoni L","on behalf of the International Multicenter Study Group on LUS in COVID-19.
PURPOSE:To analyze the application of a lung ultrasound (LUS)-based diagnostic approach to patients suspected of COVID-19, combining the LUS likelihood of COVID-19 pneumonia with patient's symptoms and clinical history. METHODS:This is an international multicenter observational study in 20 US and European hospitals. Patients suspected of COVID-19 were tested with reverse transcription-polymerase chain reaction (RT-PCR) swab test and had an LUS examination. We identified three clinical phenotypes based on pre-existing chronic diseases (mixed phenotype), and on the presence (severe phenotype) or absence (mild phenotype) of signs and/or symptoms of respiratory failure at presentation. We defined the LUS likelihood of COVID-19 pneumonia according to four different patterns: high (HighLUS), intermediate (IntLUS), alternative (AltLUS), and low (LowLUS) probability. The combination of patterns and phenotypes with RT-PCR results was described and analyzed. RESULTS:We studied 1462 patients, classified in mild (n = 400), severe (n = 727), and mixed (n = 335) phenotypes. HighLUS and IntLUS showed an overall sensitivity of 90.2% (95% CI 88.23-91.97%) in identifying patients with positive RT-PCR, with higher values in the mixed (94.7%) and severe phenotype (97.1%), and even higher in those patients with objective respiratory failure (99.3%). The HighLUS showed a specificity of 88.8% (CI 85.55-91.65%) that was higher in the mild phenotype (94.4%; CI 90.0-97.0%). At multivariate analysis, the HighLUS was a strong independent predictor of RT-PCR positivity (odds ratio 4.2, confidence interval 2.6-6.7, p < 0.0001). CONCLUSION:Combining LUS patterns of probability with clinical phenotypes at presentation can rapidly identify those patients with or without COVID-19 pneumonia at bedside. This approach could support and expedite patients' management during a pandemic surge.
目的: 结合新型冠状病毒肺炎例肺炎患者的症状和临床病史，分析肺部超声 (LUS) 诊断方法在新型冠状病毒肺炎例疑似肺炎患者中的应用。 方法: 这是一项在20家美国和欧洲医院进行的国际多中心观察性研究。对疑似新型冠状病毒肺炎的患者进行逆转录-聚合酶链反应 (rt-pcr) 拭子检测，并进行LUS检查。我们基于预先存在的慢性疾病 (混合表型) 以及就诊时呼吸衰竭的体征和/或症状的存在 (严重表型) 或不存在 (轻度表型)，确定了三种临床表型。我们根据四种不同的模式定义了新型冠状病毒肺炎肺炎的LUS可能性: 高 (HighLUS) 、中 (IntLUS) 、备选 (AltLUS) 和低 (LowLUS) 概率。描述和分析了模式和表型与rt-pcr结果的组合。 结果: 我们研究了1462例患者，分为轻度 (n = 400) 、重度 (n = 727) 和混合 (n = 335) 表型。HighLUS和IntLUS在识别rt-pcr阳性患者方面显示出90.2% 的总体灵敏度 (95% CI 88.23-91.97%)，在混合 (94.7%) 和严重表型 (97.1%) 中具有更高的值，在那些有客观呼吸衰竭的患者中甚至更高 (99.3%)。HighLUS显示88.8% 的特异性 (CI 85.55-91.65%)，在轻度表型中更高 (94.4%; CI 90.0-97.0%)。在多变量分析中，HighLUS是rt-pcr阳性的强独立预测因子 (比值比4.2，置信区间2.6-6.7，p <0.0001)。 结论: 将LUS概率模式与临床表型相结合，可以快速识别床边有或没有新型冠状病毒肺炎肺炎的患者。这种方法可以在大流行期间支持和加快患者的管理。
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.