Clinical characteristics and outcomes of extranodal stage I diffuse large B-cell lymphoma in the rituximab era.
- 作者列表："Bobillo S","Joffe E","Lavery JA","Sermer D","Ghione P","Noy A","Caron PC","Hamilton A","Hamlin PA","Horwitz SM","Kumar A","Matasar MJ","Moskowitz A","Owens CN","Palomba ML","Batlevi CL","Straus D","von Keudell G","Zelenetz AD","Yahalom J","Dogan A","Seshan VE","Younes A
:This retrospective study aimed to better define the characteristics and outcomes of extranodal stage I diffuse large B-cell lymphoma (DLBCL) in the rituximab era. Patients diagnosed with stage I DLBCL from 2001 to 2015 treated with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) or R-CHOP-like regimens with or without radiation (RT) were included. We identified 1955 patients with newly diagnosed DLBCL, of whom 341 had stage I and were eligible for this analysis. Extranodal presentation was observed in 224 (66%) patients, whereas 117 (34%) had nodal involvement. The most common extranodal sites were as follows: bone, 21%; stomach, 19%; testis, 9%; intestine, 8%; breast, 8%. Overall, 69% extranodal patients and 68% nodal patients received RT. Median follow-up was 5.5 years (interquartile range, 4.3-8.2). Ten-year overall survival (OS) and disease-free survival were 77% (95% confidence interval [CI], 67%-83%) and 77% (95% CI, 68%-85%). In the multivariable analyses, extranodal involvement was associated with worse OS (hazard ratio [HR], 3.44; 95% CI, 1.05-11.30) and progression-free survival (PFS; HR, 3.25; 95% CI, 1.08-9.72) compared with nodal involvement. Consolidation RT was associated with better OS (HR, 0.26; 95% CI, 0.12-0.49) and PFS (HR, 0.35; 95% CI, 0.18-0.69) in the extranodal population; however, the benefit was no longer observed in patients that were positron emission tomography (PET) negative at the end of immunochemotherapy. Relapses occurred usually late (median, 37 months), and the most common sites were the lymph nodes (31%) and the central nervous system (27%). Extranodal stage I DLBCL had a worse outcome than nodal stage 1 DLBCL. End of immunochemotherapy PET results may help select extranodal patients for consolidation RT.
: 这项回顾性研究旨在更好地确定利妥昔单抗时代结外I期弥漫性大b细胞淋巴瘤 (DLBCL) 的特征和结局。包括2001年至2015年诊断为I期DLBCL的患者，接受利妥昔单抗、环磷酰胺、多柔比星、长春新碱、泼尼松 (r-chop) 或r-chop样方案 (伴或不伴放疗 (RT)) 治疗。我们确定了1955例新诊断的DLBCL患者，其中341例为I期，符合该分析的条件.在224 (66%) 例患者中观察到结外表现，而117 (34%) 有淋巴结受累。最常见的结外部位如下: 骨，21%; 胃，19%; 睾丸，9%; 肠，8%; 乳腺，8%。总体上，69% 名结外患者和68% 名结外患者接受了RT。中位随访时间为5.5年 (四分位距，4.3-8.2).10年总生存率 (OS) 和无病生存率分别为77% (95% 可信区间 [CI]，67%-83%) 和77% (95% CI，68%-85%)。在多变量分析中，与淋巴结受累相比，结外受累与较差的OS (风险比 [HR]，3.44; 95% CI，1.05-11.30) 和无进展生存期 (PFS; HR，3.25; 95% CI，1.08-9.72) 相关。在结外人群中，巩固RT与更好的OS (HR，0.26; 95% CI，0.12-0.49) 和PFS (HR，0.35; 95% CI，0.18-0.69) 相关; 然而，在正电子发射断层扫描 (PET) 的患者中不再观察到益处。免疫化疗结束时阴性。复发通常发生在晚期 (中位数，37个月)，最常见的部位是淋巴结 (31%) 和中枢神经系统 (27%)。结外I期DLBCL的预后比淋巴结1期DLBCL差。免疫化疗结束PET结果可能有助于选择结外患者进行巩固RT。
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.