The prognostic role of epigenetic dysregulation in bladder cancer: A systematic review

BackgroundDespite adequate treatment and follow-up, around one fifth of patients with localized bladder cancer will present with disease progression. Adequate prognostic biomarkers are lacking to define patients who are at risk. Mutations in chromatin remodeling genes are more frequently found in bladder cancer than in any other solid tumor. However, the prognostic relevance of epigenetic dysregulation has not been established and may offer an opportunity for biomarker discovery.MethodsLooking for prognostic epigenetic factors, we performed a comprehensive PubMed search using keywords such as “bladder cancer”, “chromatin remodeling”, “gene methylation” and “epigenetics”. We only included studies reporting on the association of epigenetic markers with prognostic outcomes such as recurrence, progression or survival.ResultsOf 1113 results, 87 studies met the inclusion criteria, which represented a total of 85 epigenetic markers with potential prognostic relevance. No prospective studies were identified. Seventy-three percent (64/87) of the studies involved mixed cohorts of muscle invasive and non-muscle invasive bladder cancer. Promoter methylation of genes with putative prognostic value affected cellular processes such as cell cycle, apoptosis, cell-adhesion or migration, as well as critical pathways such as MAP-kinase or Wnt. Alteration of chromatin regulatory elements suggest a prognostic relevance alterations leading to a predominantly silenced chromatin state.ConclusionsThe prognostic impact of epigenetic alterations in bladder cancer is still unclear. Prospective evaluation of methylation marks and chromatin remodeling gene alterations using consistent methods and criteria is warranted.     

血清HBVDNA水平及抗病毒治疗对HBV相关性肝细胞癌患者术后预后的影响

目的探讨血清乙型肝炎病毒脱氧核糖核苷酸（HBVDNA）水平及术后抗病毒治疗对HBV相关性肝细胞癌（HCC）患者行根治性切除术后预后的影响。方法回顾性分析行肿瘤根治性切除术的701例HBV相关性HCC患者，分析患者临床病理资料与术后预后的关系。结果平均随访64.5个月后，肿瘤复发450例（64.2%），死亡217例（35.3%）。单因素分析发现HBeAg阳性、AST＞37U/L、HBVDNA≥2000U/ml、γ-谷氨酰转肽酶（γ-GT）＞61U/L、碱性磷酸酶（AKP）＞129U/L、PT＞13s、甲胎蛋白（AFP）＞20滋g/L、肿瘤个数≥2、肿瘤直径较大、肿瘤切距＜1cm、肿瘤无包膜、门静脉癌栓、微血管癌栓、肝硬化、肿瘤pTNM分期越高，患者术后肿瘤复发的风险较大。多因素分析发现HBeAg阳性、γ-GT＞61U/L、PT＞13s、肿瘤个数≥2、肿瘤直径较大、门静脉癌栓及肿瘤切距＜1cm均为患者术后复发的独立危险因素。术前HBVDNA≥2000U/ml的患者，抗病毒组患者复发率低于未抗病毒组患者（P＜0.01）。结论HBVDNA水平较高与HCC患者行根治性切除术后复发的高风险相关，抗病毒治疗能减少HCC患者根治性切除术后复发。     

急性白血病遗传学改变的预后分析及微小残留病检测

随着化疗、靶向治疗等技术的进展,白血病的治疗效果日益改善,但复发仍是一大难题。白血病微小残留病(MRD)是指患者达血液学完全缓解后体内仍残留106¹09/L白血病细胞计数的状态,为白血病复发的主要原因。因此,监测MRD具有重要的临床意义。近年来发现越来越多的异常表达基因有望用于MRD的检测,从而监测复发,提示预后。该文选取WT1(Wilms's tumor-1 gene)、尾型同源盒基因2和表皮生长因子受体通路底物8基因的临床意义予以综述。     

Posicionamiento postoperatorio de la cabecera tras drenaje de hematomas subdurales crónicos por trepanación: Revisión sistemática y metaanálisis de estudios controlados aleatorizados

IntroductionSeveral studies have suggested the possible influence of postoperative bed header position on the risk of symptomatic recurrences and medical complications in patients who have been intervened due chronic subdural haematomas. Nevertheless, this hypothesis has not been assessed by a meta-analysis.MethodsAll randomised controlled trials analysing symptomatic recurrence rates in patients who underwent burr-hole drainage of chronic subdural haematomas, describing postoperative bed header positioning, were included.The primary outcome was risk of recurrence and the secondary outcome were the risks of reoperation and medical complications. Results were presented as pooled relative risks, with 95% confidence intervals.ResultsA total of 4 controlled studies were included. Pooled relative risks were: symptomatic recurrences 0.51 ([95% CI: 0.22-1.16]; P=.11), reoperations, 1.07 ([95% CI: 0.42-2.69]; P=.89) and medical complications, 1.15 ([95% CI: 0.7-1.91]; P=.58). No statistically significant heterogeneity was found in any of the analyses.ConclusionThere were no differences regarding frequency of symptomatic recurrences, reoperations or medical complications in patients who were maintained in a flat position compared with those whose bed header was elevated during the postoperative course. Despite there being consistency between the results, there is a potential risk of bias; thus proscribing definitive recommendations until studies with higher methodological quality are available.     

结核病复发的流行病学研究进展

结核病是我国重点控制的传染病之一.在短程督导治疗(DOTs)下,绝大多数肺结核患者可治愈,但仍有部分肺结核患者治愈后复发.由于复发结核病患者的耐药率较高、病情复杂,往往难以治愈,造成疾病的迁延不愈和进一步传播.同时,复发结核病患者往往需用二线抗结核药物治疗,而这些药物副反应发生率较高,且费用昂贵,给患者带来沉重的生理和心理负担.为此就近年来国内外学者在结核病复发水平、复发原因和复发危险因素等方面的流行病学研究进展进行综述.     

Prediction Tests for Recurrent Hypertensive Disease in Pregnancy,A Systematic Review

Objective. To summarize reported evidence on the performance and clinical usefulness of prediction tests for recurrent hypertensive disease in pregnancy. Methods. A literature search was conducted in MEDLINE/PubMed and EMBASE. Test characteristics were extracted for relevant reports. Results. Thirty-three of 4,311 articles found met the inclusion criteria. Twenty-four potential predictors were identified. Pre-pregnant plasma volume, uterine-artery blood flow velocity profiles, and combined longitudinal patterns of in-pregnancy laboratory variables had reasonable predictive capacity, but also some practical shortcomings. Confidence intervals were often wide. Conclusions. Although evidence points to promising predictive accuracy of some tests, immediate applicability is hampered by statistical imprecision and clinical drawbacks.     

Estimating fall risk with inertial sensors using gait stability measures that do not require step detection

Falls have major consequences both at societal (health-care and economy) and individual (physical and psychological) levels. Questionnaires to assess fall risk are commonly used in the clinic, but their predictive value is limited. Objective methods, suitable for clinical application, are hence needed to obtain a quantitative assessment of individual fall risk. Falls in older adults often occur during walking and trunk position is known to play a critical role in balance control. Therefore, analysis of trunk kinematics during gait could present a viable approach to the development of such methods. In this study, nonlinear measures such as harmonic ratio (HR), index of harmonicity (IH), multiscale entropy (MSE) and recurrence quantification analysis (RQA) of trunk accelerations were calculated. These measures are not dependent on step detection, a potentially critical source of error. The aim of the present study was to investigate the association between the aforementioned measures and fall history in a large sample of subjects (42 fallers and 89 non-fallers) aged 50 or older. Univariate associations with fall history were found for MSE and RQA parameters in the AP direction; the best classification results were obtained for MSE with scale factor τ = 2 and for maximum length of diagonals in RQA (72.5% and 71% correct classifications, respectively). MSE and RQA were found to be positively associated with fall history and could hence represent useful tools in the identification of subjects for fall prevention programs.     

Prognosis impact of posttreatment pelvic MRI in patients treated for stage IB2-IIB cervical cancer with chemoradiation therapy

ObjectivesTo evaluate the performances of systematic posttreatment pelvic magnetic resonance imaging (PPMRI) in predicting prognosis of patients treated with chemoradiation therapy (CRT) for locally advanced cervical cancer (LACC).Materials and methodsMulti-institutional data from 216 patients presenting FIGO IB2-IIB cervical cancer for which PPMRI was performed following CRT were retrospectively reviewed. Incomplete response was defined as the identification of persistent lesion on PPMRI. Primary endpoints were patients’ 5-year recurrence free (RFS) and overall (OS) survivals. Secondary endpoint was the identification of residual histologic disease on hysterectomy specimens when completion surgery was performed.ResultsPPMRI identified an incomplete response in 102 (47.2%) cases. A 70% or more reduction in tumor size on PPMRI was identified as the best predictive cut-off for recurrence (37.7% sensitivity and 78.7% specificity) and death (50% sensitivity and 77.9% specificity) with significant impact on those risks (HRa: 0.42; 95%CI: 0.23–0.77 and HRa: 0.18; 95%CI: 0.06–0.50, respectively). Completion hysterectomy was performed in 117 (54.4%) cases, with histologic residual disease in 55 (47.4%). PPMRI demonstrated 74.5% sensitivity and 50.8% specificity in predicting residual disease. Although survival of patients with complete response at PPMRI was not impacted by completion hysterectomy, it significantly increased 5-year RFS and OS of those with incomplete response: 38.7% vs. 65.3% (p < 0.001) and 63% vs. 82.9% (p = 0.038), respectively.ConclusionA 70% or more reduction of in tumor size on PPMRI following CRT in patients with LACC is predictive of RFS and OS. PPMRI could help triaging patients who could benefit from completion hysterectomy.     

Prediction of Oncotype Dx recurrence score using clinical parameters: A comparison of available tools and a simple predictor based on grade and progesterone receptor

Objective/BackgroundThe Oncotype Dx test is a genomic test currently used in clinical practice to predict the risk of disease recurrence in estrogen receptor (ER)-positive, HER2-negative breast cancer patients with axillary lymph node-negative or micrometastatic disease. The test is one of several similar genomically based tests available. Although it has a good predictive value, it is expensive and thus constitutes a significant financial burden for health systems. Thus, several attempts have been made to devise low-cost tools that could predict the recurrence score derived from the genomic evaluation using easily obtainable clinical parameters.MethodsTwo previously proposed predictive tools were evaluated in a cohort of 201 patients that had undergone the Oncotype Dx test for their efficacy in predicting the Oncotype Dx Recurrence Score (RS). A simple predictor, named GR-PR, based on two available pathologic parameters, grade and progesterone receptor status was devised and also evaluated.ResultsThe sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of all three tools were compared and found to be similar for all cutoff points of Oncotype Dx RS. The accuracy of GR-PR was comparable to the best performing of the two other prediction tools for all four cutoff points.ConclusionThe simple GR-PR predictor proposed in this study seems to be at least as accurate as more complex tools and should be the preferred tool for the prediction of Oncotype Dx RS from clinicopathologic parameters when the Oncotype Dx test is not available.