- 作者列表："Birati EY","Najjar SS","Tedford RJ","Houston BA","Shore S","Vorovich E","Atluri P","Urgo K","Molina M","Chambers S","Escobar N","Hsich E","Estep JD","Alexander KM","Teuteberg JJ","Chaudhry SP","Ravichandran A","DeVore AD","Margulies KB","Hanff TC","Zimmer R","Kilic A","Wald JW","Vidula H","Martens J","Blumberg EA","Mazurek JA","Owens AT","Goldberg LR","Alvarez-Garcia J","Mancini DM","Moss N","Genuardi MV
BACKGROUND:The coronavirus disease 2019 (COVID-19) pandemic continues to afflict millions of people worldwide. Patients with end-stage heart failure and left ventricular assist devices (LVADs) may be at risk for severe COVID-19 given a high prevalence of complex comorbidities and functional impaired immunity. The objective of this study is to describe the clinical characteristics and outcomes of COVID-19 in patients with end-stage heart failure and durable LVADs. METHODS:The Trans-CoV-VAD registry is a multi-center registry of LVAD and cardiac transplant patients in the United States with confirmed COVID-19. Patient characteristics, exposure history, presentation, laboratory data, course, and clinical outcomes were collected by participating institutions and reviewed by a central data repository. This report represents the participation of the first 9 centers to report LVAD data into the registry. RESULTS:A total of 40 patients were included in this cohort. The median age was 56 years (interquartile range, 46-68), 14 (35%) were women, and 21 (52%) were Black. Among the most common presenting symptoms were cough (41%), fever, and fatigue (both 38%). A total of 18% were asymptomatic at diagnosis. Only 43% of the patients reported either subjective or measured fever during the entire course of illness. Over half (60%) required hospitalization, and 8 patients (20%) died, often after lengthy hospitalizations. CONCLUSIONS:We present the largest case series of LVAD patients with COVID-19 to date. Understanding these characteristics is essential in an effort to improve the outcome of this complex patient population.
背景: 冠状病毒疾病2019 (新型冠状病毒肺炎) 大流行继续困扰着全球数百万人。患有终末期心力衰竭和左心室辅助装置 (lvad) 的患者可能处于严重新型冠状病毒肺炎的风险中，因为复杂合并症和功能性免疫受损的患病率很高。本研究的目的是描述新型冠状病毒肺炎例终末期心力衰竭和持久lvad患者的临床特征和预后。 方法: Trans-CoV-VAD注册登记是美国LVAD和心脏移植患者的多中心注册登记，确认新型冠状病毒肺炎。参与机构收集患者特征、暴露史、表现、实验室数据、病程和临床结局，并通过中央数据储存库进行审查。该报告代表前9个中心参与将LVAD数据报告到注册表中。 结果: 本队列共纳入40例患者。中位年龄为56岁 (四分位距46-68岁)，14名 (35%) 为女性，21名 (52%) 为黑人。最常见的症状是咳嗽 (41%)，发热乏力均为38%)。共有18% 例在诊断时无症状。只有43% 的患者在整个病程中报告了主观或测量的发热。超过一半 (60%) 的患者需要住院治疗，8名患者 (20%) 在长期住院治疗后死亡。 结论: 我们提出了迄今为止最大的LVAD患者病例系列，新型冠状病毒肺炎。了解这些特征对于改善这种复杂患者群体的结果至关重要。
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.