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1.
Whitney S. Brandt Wanpu Yan Jian Zhou Kay See Tan Joseph Montecalvo Bernard J. Park Prasad S. Adusumilli James Huang Matthew J. Bott Valerie W. Rusch Daniela Molena William D. Travis Mark G. Kris Jamie E. Chaft David R. Jones 《The Journal of thoracic and cardiovascular surgery》2019,157(2):743-753.e3
Objective
Comparative survival between neoadjuvant chemotherapy and adjuvant chemotherapy for patients with cT2-4N0-1M0 non–small cell lung cancer has not been extensively studied.Methods
Patients with cT2-4N0-1M0 non–small cell lung cancer who received platinum-based chemotherapy were retrospectively identified. Exclusion criteria included stage IV disease, induction radiotherapy, and targeted therapy. The primary end point was disease-free survival. Secondary end points were overall survival, chemotherapy tolerance, and ability of Response Evaluation Criteria In Solid Tumors response to predict survival. Survival was estimated using the Kaplan–Meier method, compared using the log-rank test and Cox proportional hazards models, and stratified using matched pairs after propensity score matching.Results
In total, 330 patients met the inclusion criteria (n = 92/group after propensity-score matching; median follow-up, 42 months). Five-year disease-free survival was 49% (95% confidence interval, 39-61) for neoadjuvant chemotherapy versus 48% (95% confidence interval, 38-61) for adjuvant chemotherapy (P = .70). On multivariable analysis, disease-free survival was not associated with neoadjuvant chemotherapy or adjuvant chemotherapy (hazard ratio, 1.1; 95% confidence interval, 0.64-1.90; P = .737), nor was overall survival (hazard ratio, 1.21; 95% confidence interval, 0.63-2.30; P = .572). The neoadjuvant chemotherapy group was more likely to receive full doses and cycles of chemotherapy (P = .014/0.005) and had fewer grade 3 or greater toxicities (P = .001). Response Evaluation Criteria In Solid Tumors response to neoadjuvant chemotherapy was associated with disease-free survival (P = .035); 15% of patients receiving neoadjuvant chemotherapy (14/92) had a major pathologic response.Conclusions
Timing of chemotherapy, before or after surgery, is not associated with an improvement in overall or disease-free survival among patients with cT2-4N0-1M0 non–small cell lung cancer who undergo complete surgical resection. 相似文献2.
《Drug metabolism and pharmacokinetics》2020,35(1):56-70
Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CLh) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CLh involving OATP1B-mediated hepatic uptake. CLh can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CLh and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction. 相似文献
3.
《ALTER. European Journal of Disability research, Journal europeen de recherche sur le handicap》2019,13(2):113-125
The aim of this article is to examine how different ideological perspectives on Swedish disability policy, are reflected in the experiences of disabled people and their families personal assistants. Personal assistance provided within the family can be seen as a hybridization between publicly regulated and paid work performed in the private family sphere, and thus conflicting norms and practices may coexist. In Sweden, family members of the assistant user can be employed as paid personal assistants. Many users combine personal assistance from family members with non-family assistance. Approximately 20–25% of the employed personal assistants are relatives of the assistance users. The empirical data consists of qualitative interviews with seventeen adult users and twenty-three family members employed as PAs with different types of family ties; parent-child relationships, sibling relationships and partner relationships. The findings show that family assistance could entail advantages such as personalised services, to combine instrumental and emotional assistance as well as achieving a power-balance between the parties. But there were also disadvantages, such as unwanted or enforced dependency, with a risk for both parties to be ‘locked up’ in the family. In an overall analysis, we distinguished three broad approaches towards family assistance, family as a substitute, family as a supplement and family first. 相似文献
4.
Matthew D. Li Katrina F. Chu Allegra DePietro Vincent Wu Eric Wehrenberg-Klee Omar Zurkiya Raymond W. Liu Suvranu Ganguli 《Journal of vascular and interventional radiology : JVIR》2019,30(3):314-319
Purpose
To evaluate the feasibility of a same-day yttrium-90 (90Y) radioembolization protocol with resin microspheres (including pretreatment angiography, lung shunt fraction [LSF] determination, and radioembolization) for the treatment of hepatocellular carcinoma (HCC) and liver metastases.Materials and Methods
All same-day radioembolization procedures performed over 1 y (February 2017 to January 2018) were included in this single-institutional retrospective analysis, in which 34 procedures were performed in 26 patients (median age, 63 y; 13 women), 19 with liver metastases and 7 with HCC. Yttrium-90 treatment activities were calculated by body surface area method. Tumor imaging response was assessed by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for liver metastases and modified RECIST for HCC. Clinical side effects and adverse events were graded per Common Terminology Criteria for Adverse Events version 4.0.Results
All planned cases were technically successful, and no cases were canceled for elevated LSF or vascular anatomic reasons. Pretreatment angiography modified the planned 90Y treatment activity in 1 case in which vascular anatomy required a lobar-dose split into 2 for segmental infusions. In 18% of cases, patients were briefly admitted after the procedure for observation or symptom management. Imaging evaluation of initial efficacy at 1 month demonstrated partial response in 25% and stable disease in 67% of patients with liver metastases and partial/complete response in 43% and stable disease in 14% of patients with HCC. Grade ≥ 3 adverse events occurred in 6% of cases, with no systemic therapy–limiting toxicities. The mean total procedure time was 4.2 hours.Conclusions
A same-day 90Y radioembolization protocol with resin microspheres is feasible in select patients, which can expedite cancer therapy. 相似文献5.
6.
目的:应用原位PCR技术检测B细胞系恶性淋巴瘤。方法:采用免疫球蛋白重链(IgH)基因第三互补决定区(CDR-Ⅲ)的引物,dig-11-dUTP标记物,应用直接原位PCR技术检测Ⅲ-Ⅳ级恶性淋巴瘤的间期淋巴细胞,结果:在初诊的15例恶性淋巴瘤患中,12例检测到IgH基因重排;4例临床表现呈现淋巴瘤性白血病患,治疗后骨髓完全缓解,2例间期细胞原位PCR仍显示有IgH基因重排,6个月复发,结论:间期细胞原位PCR技术能敏感、准确地检测Ⅲ级以上的恶性淋巴瘤,并帮助预测复发,为一有效的基因诊断方法。 相似文献
7.
The localization of CGRP mRNA in neurons of the rat brain and spinal cord was assessed by in situ hybridization histochemistry (ISH) using a radiolabeled synthetic 57-mer oiigodeoxynucleotide probe complementary to the rat prepro CGRP mRNA. Results were compared with previously published findings of CGRP-immunoreactive (CGRP-IR) cell bodies revealed by an indirect immunofluorescence technique. The highest numbers of CGRP mRNA expressing neurons as well as the greatest intensity of staining were found in the lateral hypothalamic area, the parabrachial nuclei, and among the cranial motor nuclei, especially in the nuclei of the 7th and 12th nerve and the ambiguus nucleus, which is generally in good agreement with findings assessed by immunocytochemistry (ICH). However, some mismatches between the localizaton of the peptide by ICH and the localization of the CGRP mRNA were also observed. Thus, ISH was not able to confirm CGRP-IR in cells of the amygdaloid complex and parts of the medial hypothalamus, the central gray, and the inferior colliculus, but ISH revealed considerably more CGRP mRNA expressing cells in the lateral hypothalamic area, arcuate nucleus, posterior and peripeduncular thalamic nuclei, and all cranial motor nuclei than CGRP-IR containing cells found by ICH. Moreover, ISH also revealed CGRP mRNA synthesis in the nucleus of the lateral olfactory tract and in the perihypoglossal nuclei that were devoid of CGRP-IR. The reasons for the observed mismatches still remain to be elucidated; however, intracerebroventricular colchicine pretreatment used to increase immunocytochemical signals also might have induced or suppressed gene expression in certain brain regions in an unpredictable matter. On the other hand, detection of only the mRNA in a certain region does not necessarily mean that also the active peptide is synthesized there. 相似文献
8.
目的:研究大黄乙醇提取物的抗新城疫病毒(NDV)作用。方法:采用体外细胞培养的方法研究大黄乙醇提取物对NDV感染的拮抗作用。结果:20g/L剂量大黄乙醇提取物对BHK21细胞未有任何毒性作用;0.5g/L大黄对NDV所致CPE有明显的抑制作用;大黄可预防NDV感染,并对NDV的复制动力学有明显影响。结论:大黄乙醇提取物具有明显的抗NDV作用。 相似文献
9.
目的快速鉴定血培养中的金黄色葡萄球菌和凝固酶阴性葡萄球菌(CoNS),结合临床快速判定是否为污染菌。方法采用荧光原位杂交法鉴定血培养中的金黄色葡萄球菌和CoNS,杂交结果若为CoNS,根据临床资料进行判断,并与文献推荐的污染判断法进行结果比较。结果探针的特异性经由标准菌株和临床分离菌株证实。金黄色葡萄球菌探针的特异性和敏感性均为100%,GoNS探针的特异性和敏感性分别为100%和95.5%。179株CoNS中117株判断为污染菌,污染率为68%,与文献推荐的污染判断方法一致。结论荧光原位杂交法适用于血培养中的金黄色葡萄球菌和CoNS的快速鉴定,以排除CoNS污染。 相似文献
10.
The recent development of brain atlases with computer graphics templates, and of huge databases of neurohistochemical data on the internet, has forced a systematic re-examination of errors associated with comparing histological features between adjacent sections of the same brain, between brains treated in the same way, and between brains from groups treated in different ways. The long-term goal is to compare as accurately as possible a broad array of data from experimental brains within the framework of reference atlases. Main sources of error, each of which ideally should be measured and minimized, include intrinsic biological variation, linear and nonlinear distortion of histological sections, plane of section differences between each brain, section alignment problems, and sampling errors. These variables are discussed, along with approaches to error estimation and minimization in terms of a specific example—the distribution of neuroendocrine neurons in the rat paraventricular nucleus. Based on the strategy developed here, the main conclusion is that the best long-term solution is a high-resolution 3D computer graphics model of the brain that can be sliced in any plane and used as the framework for quantitative neuroanatomy, databases, knowledge management systems, and structure–function modeling. However, any approach to the automatic annotation of neuroanatomical data—relating its spatial distribution to a reference atlas—should deal systematically with these sources of error, which reduce localization reliability. 相似文献