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1.
Fabrice Barlesi Edward B. Garon Dong-Wan Kim Enriqueta Felip Ji-Youn Han Joo-Hang Kim Myung-Ju Ahn Mary Jo Fidler Matthew A. Gubens Gilberto de Castro Veerle Surmont Qiao Li Anne C. Deitz Gregory M. Lubiniecki Roy S. Herbst 《Journal of thoracic oncology》2019,14(5):793-801
Introduction
In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1–expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.Methods
Patients were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks or docetaxel 75 mg/m2 every 3 weeks. HRQoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLC) Core 30 (C30), EORTC QLQ–Lung Cancer 13 (LC13), and EuroQoL-5D. Key analyses included mean baseline-to-week-12 change in global health status (GHS)/quality of life (QoL) score, functioning and symptom domains, and time to deterioration in a QLQ-LC13 composite endpoint of cough, dyspnea, and chest pain.Results
Patient reported outcomes compliance was high across all three instruments. Pembrolizumab was associated with better QLQ-C30 GHS/QoL scores from baseline to 12 weeks than docetaxel, regardless of pembrolizumab dose or tumor proportion score status (not significant). Compared with docetaxel, fewer pembrolizumab-treated patients had “deteriorated” status and more had “improved” status in GHS/QoL. Nominally significant improvement was reported in many EORTC symptom domains with pembrolizumab, and nominally significant worsening was reported with docetaxel. Significant prolongation in true time to deterioration for the QLQ-LC13 composite endpoint emerged for pembrolizumab 10 mg/kg compared to docetaxel (nominal two-sided p = 0.03), but not for the 2-mg/kg dose.Conclusions
These findings suggest that HRQoL and symptoms are maintained or improved to a greater degree with pembrolizumab than with docetaxel in this NSCLC patient population. 相似文献2.
OBJECTIVE: This article 1) provides an overview of formal Health Sciences Teaching Scholars Programs as presented in medical education literature and 2) presents information about an innovative multidiscipline Teaching Scholars Program. METHOD: Health Sciences Teaching Scholars Programs and similar programs were reviewed in the medical education literature to identify similar and dissimilar characteristics. The WVU Teaching Scholars Program highlighted in this article is presented with a discussion of goals, objectives, target audiences, course length, session frequency, program topics, learning methods, and assessments of the programs. A summary of the WVU Teaching Scholars Program and two Teaching Scholars Programs at McGill University and the University of Toronto were presented at the Association for American Medical Colleges (AAMC) annual meeting in 2006 for input from the general medical education audience. RESULTS: Comparisons of Health Sciences Teaching Scholars Programs reveal that successful programs are uniquely shaped by their educational environments. Scholars report that they value learning new teaching methods and improving their educational careers. CONCLUSION: Teaching Scholars Programs are valuable for the development of enhancing both teaching and scholarship in Health Sciences Programs and must adapt to the uniqueness of their respective educational environments and must continue to nurture scholars beyond graduation. 相似文献
3.
M. Myslak H. Amer P. Morales M. E. Fidler J. M. Gloor T. S. Larson M. D. Stegall F. G. Cosio 《American journal of transplantation》2006,6(7):1660-1665
Increasing numbers of patients receive kidney transplants before initiation of dialysis or shortly thereafter. Some of these patients have significant proteinuria pre-transplant making the interpretation of post-transplant proteinuria problematic. In this study, we evaluated post-transplant proteinuria in 115 patients who had urine protein measured within 3 months of transplant and assessed the association of proteinuria with allograft pathology. Proteinuria declined rapidly from 3650 +/- 3702 mg/day pre-transplant to 550 + 918 at 3 weeks (p < 0.0001) and continued to decline until 1 year post-transplant (472 +/- 1116, p < 0.0001 vs. 3 weeks). Proteinuria greater than 3000 mg/day was present in 48 patients (42%) pre-transplant, in 1 patient (1%) at 3 weeks and in 4 patients (4%) at 1 year. Surveillance graft biopsies were done at 1 year in 93% of patients. Proteinuria > or = 1500 mg/day and/or an absolute increase in proteinuria > 500 mg/day after 3 weeks post-transplant was associated with allograft glomerular pathology. In conclusion, pre-transplant proteinuria, even when high grade, declines rapidly after transplantation. Failure to decline or persistence of proteinuria greater than 1500 mg/day is indicative of allograft pathology. 相似文献
4.
Twenty-two adult patients with uncontrolled epilepsy and severe learning difficulties were included in an open study of vigabatrin. Patients were all in residential care and had experienced at least 12 seizures during the previous 12 months despite all attempts to optimize antiepileptic drug (AED) treatment. Following a 4 month baseline period, vigabatrin 500 mg twice daily was added to the current AED treatment and the dose increased according to response, up to a maximum of 4 g/day. Ten patients achieved a reduction in seizure frequency of more than 50% during this 4 month dose titration phase. Two patients had no seizures during the baseline period. For the 30 patients with seizures during the baseline period the median improvement in seizure frequency with the addition of vigabatrin was 49% (P = 0.014). The response rate was higher for patients with partial seizures than for those with generalized seizures. Ten patients continued with vigabatrin while the dose of one of their other AEDs was gradually reduced and successfully withdrawn in three patients. Adverse events were reported in 20 patients during the 64 week study period. The most frequently reported events were sedation (8 patients), aggression (4 patients), agitation (3 patients) and ataxia (3 patients). No patients were withdrawn from the study as a consequence of adverse events. Vigabatrin was therefore an effective add-on therapy in 45% of these difficult-to-treat patients and allowed reduction of other AED treatment in a small number. 相似文献
5.
6.
J P Waymack J Fidler G D Warden 《Burns : journal of the International Society for Burn Injuries》1988,14(2):156-160
The results of reconstructive procedures for the treatment of burn scar contractures of the feet in 55 children undergoing 90 operations were reviewed. The patients were treated in all but one case by release of the contracture band with placement of a skin graft in the resulting defect. There was an overall recurrence rate of 15 per cent that was not affected by the use of split-thickness versus full-thickness grafts. The time delay from the thermal injury to the reconstructive procedure was also found not to affect the outcome. Postoperative immobilization by the use of either a dynamic or an adynamic splint was found to be important both for preventing graft loss and for decreasing the rate of contracture recurrence. 相似文献
7.
Joint custody: historical, legal, and clinical perspectives with emphasis on the situation in Canada
The search for ways to mitigate the effects of family breakdown on parents and children includes legislative and clinical efforts which to some extent influence each other. In the past year much public interest has been aroused in Canada, and particularly in Ontario, in the issue of legislative changes which would make joint custody the usual or "preferred" legal disposition of custody cases. This paper provides a discussion of the legislated preference, or "rebutable presumption" of joint custody from a historical, legal and clinical point of view. Definition and elaboration of what joint custody is from the legal and practical perspectives is provided with an emphasis on Canadian laws and practice. The legal rights of the non-custodial parent are explained, and relevant case law is highlighted. The relationship between joint custody, support orders and relitigation rates are elaborated. Following this is a critical overview of the empirical research on joint custody as it relates to the adjustment of children and parent satisfaction is included. It is concluded that while there is little question that shared parenting can be beneficial to children, the enthusiasm of legislators for joint custody has not been supported by empirical data. It is necessary to examine under what circumstances and for which kinds of parents and children joint custody might be beneficial since it is unlikely that one solution will fit the needs of all families and all stages of family life. 相似文献
8.
Expression of interleukin-8 correlates with vascularity in human gastric carcinomas. 总被引:16,自引:3,他引:16
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Y. Kitadai K. Haruma K. Sumii S. Yamamoto T. Ue H. Yokozaki W. Yasui Y. Ohmoto G. Kajiyama I. J. Fidler E. Tahara 《The American journal of pathology》1998,152(1):93-100
Interleukin (IL)-8 is a multifunctional cytokine that can stimulate the division of endothelial cells. We examined the expression of IL-8 mRNA using Northern blot analysis and in situ mRNA hybridization (ISH) and protein production using enzyme-linked immunosorbent assay and immunohistochemistry in 8 human gastric carcinoma cell lines and 39 gastric carcinomas and corresponding normal mucosa (34 surgical specimens and 5 biopsy specimens). Of the 8 human gastric carcinoma cell lines, 6 expressed 1.8-kb IL-8 mRNA and secreted various levels of IL-8 protein. The expression of IL-8 by TMK-1 cells was induced by exposure to IL-1 alpha, epidermal growth factor, and transforming growth factor-alpha, shown previously to be autocrine growth stimulators for human gastric carcinoma cells. In tumor tissues, most of the tumors (28 of 34 surgical specimens and 4 of 5 biopsy specimens) expressed IL-8 at higher levels than the corresponding normal mucosa. ISH and immunohistochemical analyses revealed that IL-8 mRNA and protein were localized in the cytoplasm of tumor cells. The number of blood vessels in the gastric carcinomas was determined by using antibodies against CD34. The level of IL-8 mRNA in the neoplasms strongly correlated with vascularization (Spearman correlation, r = 0.812; P = 0.001). The data suggest that IL-8 produced by tumor cells may regulate neovascularization and, hence, the growth and spread of human gastric carcinoma. 相似文献
9.
Kuniyasu H Yasui W Shinohara H Yano S Ellis LM Wilson MR Bucana CD Rikita T Tahara E Fidler IJ 《The American journal of pathology》2000,157(5):1523-1535
We determined whether hyperplastic mucosa adjacent to colon cancer contributes to neoplastic angiogenesis. Surgical specimens of human colon cancer (40 Dukes' stage B and 34 Dukes' stage C) were analyzed by immunohistochemistry for expression of proliferative and angiogenic molecules. The mucosa adjacent to Dukes' stage C tumors (but not Dukes' stage B tumors) had a higher Ki-67 labeling index and a higher expression of epidermal growth factor receptor and transforming growth factor-alpha than distant mucosa. The expression levels of vascular endothelial growth factor, basic fibroblast growth factor, interleukin-8, and the vascular density in the adjacent mucosa were similar to those in the tumor lesions and significantly higher than those in the distant mucosa. The expression of interferon-beta inversely correlated with the level of pro-angiogenic molecules and the vascular density. The injection of metastatic human colon cancer cells and murine colon cancer cells into the cecal wall of mice induced hyperplastic changes in the adjacent mucosa which expressed higher levels of epidermal growth factor receptor, basic fibroblast growth factor, and vascular endothelial growth factor, and lower levels of interferon-beta than did the control mucosa, which directly correlated with the degree of hyperplasia. These data suggest that metastatic human colon cancer cells can induce hyperplasia in the adjacent mucosa, which in turn produces angiogenic molecules that contribute to neoplastic angiogenesis. 相似文献
10.
McCarty MF Bielenberg D Donawho C Bucana CD Fidler IJ 《Clinical & experimental metastasis》2002,19(7):609-615
Primary tumor growth and metastasis depend on angiogenesis, which is determined by the balance between proangiogenic and antiangiogenic
molecules. Interferon (IFN)-α and -β inhibit angiogenesis through downregulation of interleukin-8, matrix metalloproteinase-9,
and basic fibroblast growth factor. To provide evidence for the causal role of IFN-α/β in the induction of neoplasms, their
angiogenesis, and hence, progressive growth, we carried out experiments using 129S6 IFN-α/β receptor −/− mice back-crossed
to BALB/c nude mice. Subcutaneous angiogenesis was determined following implantation of gelfoam sponges containing 0.4% agarose
and several proangiogenic molecules. Tumorigenicity and production of lung metastasis were determined subsequent to subcutaneous
and intravenous injections, respectively, of highly metastatic A375SM human melanoma cells. Carcinogenesis was induced by
chronic exposure of mice to UVB radiation (5 kJ/m2, 3 times/week). Angiogenesis, tumorigenicity, and production of metastasis, as well as development of autochthonous skin
tumors, were all accelerated in IFN-α/β receptor −/− mice as compared to control mice. Collectively, the data show that inability
to respond to endogenous IFN-α/β (through a mutation in the IFN-α/β receptor) leads to increased susceptibility to carcinogenesis,
enhanced angiogenesis, tumorigenicity, and metastasis.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献