Evaluation of <i>MGMT</i> Gene Methylation in Neuroendocrine Neoplasms

Unresectable neuroendocrine neoplasms (NENs) often poorly respond to standard therapeutic approaches. Alkylating agents, in particular temozolomide, commonly used to treat high-grade brain tumors including glioblastomas, have recently been tested in advanced or metastatic NENs, where they showed promising response rates. In glioblastomas, prediction of response to temozolomide is based on the assessment of the methylation status of the MGMT gene, as its product, O6 -methylguanine-DNA methyltransferase, may counteract the damaging effects of the alkylating agent. However, in NENs, such a biomarker has not been validated yet. Thus, we have investigated MGMT methylation in 42 NENs of different grades and from various sites of origin by two different approaches: in contrast to methylation-specific PCR (MSP), which is commonly used in glioblastoma management, amplicon bisulfite sequencing (ABS) is based on high-resolution, next-generation sequencing and interrogates several additional CpG sites compared to those covered by MSP. Overall, we found MGMT methylation in 74% (31/42) of the NENs investigated. A higher methylation degree was observed in welldifferentiated tumors and in tumors originating in the gastrointestinal tract. Comparing MSP and ABS results, we demonstrate that the region analyzed by the MSP test is sufficiently informative of the MGMT methylation status in NENs, suggesting that this predictive parameter could routinely be interrogated also in NENs.     

Claims in total hip arthroplasty: analysis of the instigating factors,costs and possible solution

Over the years, the number of total hip replacements has been steadily increasing. Despite the improvement in surgical results, the number of claims for malpractice is higher. The primary endpoint of this work is to provide an analysis of litigation after hip replacement, to outline what are the instigating causes and costs. The secondary endpoint is to propose a possible preventive strategy for an improved care and a reduction in legal proceedings. The data of this study were collected from medical and legal files and from professional liability insurance of our institution from January 2005 to December 2016. Out of a total of 4770 THA, 40 claims were received. Peripheral nerve injuries represent the first cause of litigation (37%), followed by infectious complications, leg length discrepancy, metallosis, dislocations of the implant and a case of deep vein thrombosis. From the analysis of the past trial judgment, complications such as nerve lesions and infections are almost always recognized, as a medical error, with a high percentage of claims settled. This study shows the necessity of preventive strategies to reduce the higher number of claims for malpractice in total hip arthroplasty. Some complications such as nerve injuries and infection are frequently considered directly dependent on physician’s errors. Litigations can be reduced providing evidence of a diligent execution of the surgical procedure and of a proper postoperative management: the correct compilation of a specific informed consent and adequate doctor–patient communication.     

SWIM技术治疗后循环大血管闭塞所致急性缺血性卒中的有效性和安全性观察

目的 观察SWIM技术治疗后循环大血管闭塞所致急性缺血性卒中的有效性及安全性。 方法 回顾性分析2017年2月-2018年11月于大连市中心医院采用SWIM技术治疗的后循环大血管闭 塞所致急性缺血性卒中患者的临床资料，评价该技术的疗效和安全性，并分析影响患者预后的因素。 观察指标为术后即刻成功再通（mTICI≥2b）、90 d良好预后（mRS评分≤2分），以及术后24 h任何颅内 出血、90 d全因死亡。 结果 共纳入35例患者，平均年龄66.1±12.1岁，男性26例（74.3%），基线NIHSS评分22（15～34）分。 术后即刻成功再通率为94.3%（33/35），90 d良好预后率为45.7%（16/35），24 h颅内出血率为17.1% （6/35），90 d全因死亡率为37.1%（13/35）。单因素分析显示，基线NIHSS评分较低（P =0.001）、基 线后循环ASPECTS评分较高（P =0.016）、发病至到院时间较短（P =0.039）、发病至再通时间较短 （P =0.047）、血管成功再通率较高（P =0.036）以及饮酒比例较低（P =0.042）与良好预后相关。 结论 使用SWIM技术治疗后循环急性缺血性卒中相对安全、有效。     

Classification and cyclic fatigue evaluation of new kinematics for endodontic instruments

This study evaluated the effect of new motions of the motor TriAuto ZX2 on the cyclic fatigue of endodontic instruments. Vortex Blue 35.06 instruments were divided into four groups (n = 10) and tested for fatigue in a curved artificial canal (90° and 2 mm radius) using the following motions: continuous rotation (CR), Optimum Torque Reverse (OTR) set at 180° and the Optimum Glide Path (OGP), which was tested at 90° and 240°. The time to fracture (TTF) and the lengths of the fractured fragments were recorded. The mean TTF was significantly different among the groups (anova , P < 0.05): OGP 90° (213.39 ± 27.45), OTR 180° (121.24 ± 17.03), OGP 240° (45.24 ± 5.61) and CR (8.43 ± 1.27). Weibull analysis confirmed the shortest life expectancy for CR and the longest survival for OGP at 90°. The resistance to fatigue was affected by motions and pre‐set angles. The proprietary movements that are currently available for endodontic instruments were classified according to their kinematics.     

金莲花提取物代谢产物研究

目的:研究金莲花化学成分的体内代谢产物及代谢规律。方法:静脉注射方式给予大鼠金莲花提取物并在各时间段采血,利用高效液相色谱-电喷雾电离-串联质谱技术(LC-ESI-MS)对血清中的代谢产物进行研究。结果:根据LC-ESI-MS结果发现了23种原型成分及45种代谢产物。原型成分中有3种酚酸类物质、19种黄酮类物质、1种生物碱类物质。通过准分子离子峰及二级碎片得到了代谢产物可能的化学结构,分析了这些代谢产物的裂解途径,推测19种来源于酚酸类物质、20种来源于黄酮类物质、6种来源于生物碱类物质。结论:本研究探讨了金莲花提取物中化学成分的代谢规律,为其血液移行成分及药理作用的进一步研究奠定基础。     

后Pilon骨折的诊治现状与进展

后Pilon骨折是一种新近报道的Pilon骨折的特殊模式,其特征是累及后外踝和后内踝.在过去由于后Pilon骨折没有得到充分的认识,常被误诊为后踝骨折,也导致这类患者功能恢复不良.因此是否能作出正确诊断至关重要,只有熟悉后Pilon骨折的各种影像学特征并了解合并损伤的机制,才能及时、准确地诊断后Pilon骨折,并改进这种具有挑战性骨折的术前计划和临床结果.本文着重介绍了后Pilon骨折的损伤机制,现有的分类方案,并讨论了目前使用的各种手术方法.     

Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high‐risk Chinese individuals

Identification of deleterious variants in hereditary breast and ovarian cancer (HBOC) susceptibility genes allows for increased clinical surveillance and early detection, and could predict the response to poly (ADP‐ribose) polymerase (PARP) inhibitor in patients with advanced ovarian carcinomas. To determine the prevalence and clinical prediction factors for HBOC syndrome, 882 selected individuals underwent multigene panel testing for HBOC risk assessment during the period from January 2015 to March 2018. Overall, 176 deleterious mutations were observed in 19.50% (n = 172) of individuals. Twenty‐six of 176 mutations could not be retrieved in related public databases and were considered to be novel. Among patients with ovarian cancer, 115 deleterious mutations were identified in 429 patients (48.6%) with significant enrichment for a family history of breast or ovarian cancer syndrome (P < .05). In the breast cancer subgroup, 31 deleterious mutations were identified in 261 patients. Besides BRCA1 (8; 25.8%) and BRCA2 (11; 35.5%), the most frequently occurring genes, an additional 12 deleterious mutations (38.7%) were found in seven other susceptibility genes. Higher mutation incidence (57.9%) was observed in subjects with histories of breast and ovarian cancer. Our results highlighted the genetic heterogeneity of HBOC and the efficiency of a multigene panel in carrying out risk assessment.     

颗粒松质骨压紧植骨全髋关节置换术治疗创伤性髋关节炎的疗效

目的探讨颗粒松质骨压紧植骨全髋关节置换术(THA)治疗髋臼骨折继发创伤性髋关节炎的疗效。方法1998年12月-2005年5月,对15例髋臼骨折继发创伤性髋关节炎患者行颗粒松质骨压紧植骨THA,所有患者髋臼假体均采用骨水泥固定,颗粒骨均取自体骨,术后24h后开始被动活动,3个月后开始全负重锻炼。临床随访采用Harris髋关节评分(HSS)系统评分,对任何原因引起髋臼假体翻修均视为临床失败。根据Conn等影像学评价法观察颗粒骨长人情况,根据DeLee的三区法测量臼杯、骨水泥与移植骨间的界面宽度,臼杯的移位程度则依据其相对于泪点间线的距离而定。结果14例患者获得平均4．3年(1．0-7．5年)随访,HHS评分由术前平均42分(10-62分)提高到随访结束时平均84分(58-98分)。1例髋部有轻度疼痛,无患者行翻修手术。大部分髋部恢复了其正常的旋转中心,仅有2例高出对侧0．8 mm。大多数患者影像学表现稳定,2例在Ⅰ区和Ⅲ区出现进行性增宽的透亮带,1例在Ⅲ区出现非进行性增宽的透亮带。1例臼杯假体在术后7年出现明显移位(6 mm),但并没有行翻修手术。结论颗粒骨压紧植骨技术作为一种生物学髋臼重建方法,其联合THA治疗髋臼骨折后继发创伤性关节炎伴髋臼缺损的疗效令人满意,能够恢复髋关节的正常解剖和功能活动。