Age is an independent predictor of outcome in endometrial cancer patients: An Israeli Gynecology Oncology Group cohort study.
- 作者列表："Hag-Yahia N","Gemer O","Eitan R","Raban O","Vaknin Z","Levy T","Leytes S","Lavie O","Ben-Arie A","Amit A","Namazov A","Volodarsky M","Ben-Shachar I","Atlas I","Bruchim I","Kadan Y","Helpman L
INTRODUCTION:Advanced age is considered an adverse factor in endometrial cancers but may be a surrogate for other conditions that impact outcomes. The study objective was to assess the association of age with endometrial cancer features, treatment and prognosis. MATERIAL AND METHODS:In this multicenter cohort study, consecutive women with endometrial cancer treated at 10 Israeli institutions between 2000 and 2014 were accrued in an assimilated database. Postmenopausal women were stratified into age groups with a cut-off of 80. Clinical, pathological and treatment data were compared using t test or Mann-Whitney test for continuous variables, and Chi-square Test or Fisher's Exact test for categorical variables. Main outcome measures included disease recurrence and disease-specific and overall survival; these were plotted using the Kaplan-Meier method and compared using the log-rank test. The association between age and recurrence and survival, adjusted for other clinical and pathological factors, was assessed using multivariable Cox regression modeling. RESULTS:A total of 1764 postmenopausal women with endometrial cancer were identified. Adverse pathological features were more prevalent in older women, including high-risk histologies (35% vs 27%, P = .025), deep myoinvasion (44% vs 29%, P = .001) and lymphovascular involvement (22% vs 15%, P = .024). Surgical staging was performed less frequently among older women (33% vs 56%; P < .001). Chemotherapy was less often prescribed, even for non-endometrioid histologies (72% vs 45%; P < .001). On multivariable analysis, age remained a significant predictor for recurrence (HR = 1.75, P = .007), death of disease (HR = 1.89, P = .003) and death (HR = 2.4, P < .001). CONCLUSIONS:Older age in women with endometrial cancer is associated with more adverse disease features, limited surgery and adjuvant treatment, and worse outcomes. On multivariable analysis, age remains an independent prognosticator in this population.
引言: 高龄被认为是子宫内膜癌的不良因素，但可能是影响结局的其他疾病的替代因素。本研究的目的是评估年龄与子宫内膜癌特征、治疗和预后的关系。 材料和方法: 在这项多中心队列研究中，在2000年至2014年期间，在10家以色列机构接受子宫内膜癌治疗的连续妇女被纳入同化数据库。将绝经后妇女分为年龄组，截止值为80。对连续变量采用t检验或Mann-Whitney检验，对分类变量采用卡方检验或Fisher精确检验，比较临床、病理和治疗数据。主要结果指标包括疾病复发和疾病特异性及总体生存率; 这些指标使用Kaplan-Meier方法绘制，并使用时序检验进行比较。使用多变量Cox回归模型评估年龄与复发和生存之间的关系，并校正其他临床和病理因素。 结果: 共发现1764例绝经后妇女子宫内膜癌。不良病理特征在老年女性中更常见，包括高危组织学 (35% vs 27%，P = .025)，深部肌层浸润 (44% vs 29%，P = .001) 和淋巴管受累 (22% vs 15%，P = .024)。手术分期在老年女性中进行的频率较低 (33% vs 56%; P <.001)。即使对于非子宫内膜样组织，也不经常使用化疗 (72% vs 45%; P <.001)。在多变量分析中，年龄仍然是复发 (HR = 1.75，P = .007) 、疾病死亡 (HR = 1.89，P = .003) 和死亡 (HR = 2.4，P <.001) 的显著预测因子。 结论: 子宫内膜癌患者的年龄较大与更多的不良疾病特征、有限的手术和辅助治疗以及更差的预后相关。在多变量分析中，年龄仍然是该人群的独立预测因素。
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.