Assessing the Effects of Geniculate Artery Embolization in a Nonsurgical Animal Model of Osteoarthritis

PurposeTo create a nonsurgical animal model of osteoarthritis (OA) to evaluate the effects of embolotherapy during geniculate artery embolization (GAE).Materials and MethodsFluoroscopy-guided injections of 700 mg of sodium monoiodoacetate were performed into the left stifle in 6 rams. Kinematic data were collected before and after induction. At 10 weeks after induction, Subjects 1 and 4–6 underwent magnetic resonance (MR) imaging with dynamic contrast enhancement (DCE) and Subjects 1, 3, and 4–6 underwent angiography with angiographic scoring to identify regions with greatest disease severity for superselective embolization (75–250-μm microspheres). Target vessel size was measured. At 24 weeks after angiography, DCE-MR imaging, angiography, and euthanasia were performed, and bilateral stifles were harvested. Medial/lateral tibial and femoral condylar, patellar, and synovial samples were cut, preserved, decalcified, and scored using the Osteoarthritis Research Society International criteria. The stifle and synovium Whole-Organ Magnetic Resonance Imaging Score and Multicenter Osteoarthritis Study score were determined. The volume transfer constant (K_trans) and extracellular volume fraction (v_e) were calculated from DCE-MR imaging along the lateral synovial regions of interest.ResultsThe mean gross and microscopic pathological scores were elevated at 38 and 61, respectively. Mean synovitis score was elevated at 9.2. Mean pre-embolization and postembolization angiographic scores were 5 and 3.8, respectively. Mean superior, transverse, and inferior geniculate artery diameters were 3.1 mm ± 1.21, 2.0 mm ± 0.50, and 1.6 mm ± 0.41 mm, respectively. Mean pre-embolization and postembolization cartilage and synovitis scores were elevated at 35.13 and 73.3 and 5.5 and 9.2, respectively. The K_trans/v_e values of Subjects 4, 5, and 6 were elevated at 0.049/0.38, 0.074/0.53, and 0.065/0.51, respectively. Altered gait of the hind limb was observed in all subjects after induction, with reduced joint mobility. No skin necrosis or osteonecrosis was observed.ConclusionsA nonsurgical ovine animal knee OA model was created, which allowed the collection of angiographic, histopathological, MR imaging, and kinematic data to study the effects of GAE.     

Dual-target inhibitors of bromodomain-containing protein 4 (BRD4) in cancer therapy: Current situation and future directions

Bromodomain-containing protein 4 (BRD4) is emerging as a therapeutic target that acts synergistically with other targets of small-molecule drugs in cancer. Therefore, the discovery of potential new dual-target inhibitors of BRD4 may be a promising strategy for cancer therapy. In this review, we highlight a series of strategies to design therapeutic dual-target inhibitors of BRD4 that focus on the synergistic functions of this protein. Drug combinations that exploit synthetic lethality, protein–protein interactions, functional complementarity, and blocking of resistance mechanisms could ultimately overcome the barriers inherent to the development of BRD4 inhibitors as future cancer drugs.     

胸段食管鳞癌术后复发模式及术后放疗靶区的研究北大核心

目的:研究胸段食管鳞癌术后复发模式,为术后放疗靶区勾画提供参考。方法:回顾分析我院2012年7月至2017年5月收治术后复发的81例胸段食管鳞癌患者的临床资料,参照AJCC第八版食管癌分期,将第1-8M站定义为上中纵隔淋巴结区,8Lo、9、15站定义为下纵隔淋巴结区,16-20站定义为上腹部淋巴结区。标记患者的复发部位,并分析局部复发、区域复发和远处转移的模式。结果:中位复发时间为12个月(2~103个月)。6例(7.4%)患者发生单纯局部复发,64例(79.0%)患者发生区域复发,11例(13.6%)患者发生远处转移。区域淋巴结复发中最高危的复发区域为上中纵隔淋巴引流区,此区域包含了82.8%的复发淋巴结,其次为上腹部淋巴结引流区(13.6%)。11例患者发生上腹部淋巴结复发,其中10(90.9%)例为胸下段,7例(63.6%)患者术后分期≥Ⅲ_(b)期。结论:胸段食管鳞癌术后复发模式以区域淋巴结复发为主,上中纵隔淋巴引流区为最高危复发区域,术后放疗靶区应重点包含。对于术后分期较晚的胸下段食管鳞癌,上腹部淋巴结引流区可能需要涵盖在放疗靶区内。吻合口、瘤床和下纵隔复发风险低,可不必常规涵盖在放疗靶区内。     

短期非融合固定治疗枢椎齿状突Ⅱ型骨折后的颈椎活动度

[目的]探讨短期寰枢椎椎弓根螺钉非融合固定治疗枢椎齿状突Ⅱ型骨折后颈椎活动功能。[方法]2012年2月~2017年12月,选取枢椎齿状突II型骨折后接受后路寰枢椎椎弓根螺钉非融合内固定术,并二次手术取出内固定物的患者32例。对比患者自身前后两次手术后颈椎过伸过屈、左右旋转角度,同时参考正常人群颈椎活动度进行比较。[结果]32例患者均顺利完成C1/2椎弓根螺钉非融合内固定术,经影像学确认内固定位置良好,无血管、神经损伤等并发症的发生。于初次内固定术后4~15个月,平均(9.55±2.72)个月,32例患者再次入院行内固定取出术。取内固定术后平均随访(16.41±4.25)个月。末次随访时32例患者前屈、后伸、左旋转和右旋转ROM均显著大于取内固定之前角度(P<0.05),但仍显著不及正常人。[结论]短期寰枢椎椎弓根螺钉非融合内固定治疗枢椎齿状突骨折,可有效保留颈椎活动功能,值得临床推广应用。     

Synthetic MRI is not yet ready for morphologic and functional assessment of patellar cartilage at 1.5 Tesla

PurposeThe purpose of this study was to compare morphologic assessment and relaxometry of patellar hyaline cartilage between conventional sequences (fast spin-echo [FSE] T2-weighted fat-saturated and T2-mapping) and synthetic T2 short-TI inversion recovery (STIR) and T2 maps at 1.5 T magnetic resonance imaging (MRI).MethodThe MRI examinations of the knee obtained at 1.5 T in 49 consecutive patients were retrospectively studied. There were 21 men and 28 women with a mean age of 45 ± 17.7 (SD) years (range: 18–88 years). Conventional and synthetic acquisitions were performed, including T2-weighted fat-saturated and T2-mapping sequences. Two radiologists independently compared patellar cartilage T2-relaxation time on conventional T2-mapping and synthetic T2-mapping images. A third radiologist evaluated the patellar cartilage morphology on conventional and synthetic T2-weighted images. The presence of artifacts was also assessed. Interobserver agreement for quantitative variables was assessed using intraclass correlation coefficient (ICC).ResultsIn vitro, conventional and synthetic T2 maps yielded similar mean T2 values 58.5 ± 2.3 (SD) ms and 58.8 ± 2.6 (SD) ms, respectively (P = 0.414) and 6% lower than the expected experimental values (P = 0.038). Synthetic images allowed for a 15% reduction in examination time compared to conventional images. On conventional sequences, patellar chondropathy was identified in 35 patients (35/49; 71%) with a mean chondropathy grade of 4.8 ± 4.8 (SD). On synthetic images, 28 patients (28/49; 57%) were diagnosed with patellar chondropathy, with a significant 14% difference (P = 0.009) and lower chondropathy scores (3.7 ± 4.9 [SD]) compared to conventional images. Motion artifacts were more frequently observed on synthetic images (18%) than on conventional ones (6%). The interobserver agreement was excellent for both conventional and synthetic T2 maps (ICC > 0.83). Mean cartilage T2 values were significantly greater on synthetic images (36.2 ± 3.8 [SD] ms; range: 29-46 ms) relative to conventional T2 maps (31.8 ± 4.1 [SD] ms; range: 26-49 ms) (P < 0.0001).ConclusionDespite a decrease in examination duration, synthetic images convey lower diagnostic performance for chondropathy, greater prevalence of motion artifacts, and an overestimation of T2 values compared to conventional MRI sequences.     

Dual-Energy Computed Tomography as an Adjunct in the Evaluation of Peripheral Chronic Total Occlusions: A Feasibility Study

This study investigated the role of dual-energy computed tomography (CT) for lesion characterization in patients with peripheral arterial disease manifesting with chronic total occlusions (CTOs). Forty-one symptomatic patients with CTOs underwent dual-energy CT angiography before endovascular treatment. The lesions were subsequently analyzed in a dedicated workstation, and 2 indexes—dual-energy index (DEI) and effective Z (Z_eff)—were calculated, ranging from 0.0027 to 0.321 and from 6.89 to 13.02, respectively. Statistical analysis showed a significant correlation between the DEI and Z_eff values (P < .001). The interobserver intraclass correlation coefficient was 0.91 for the mean Z_eff values and 0.86 for the mean DEI values. This technique could potentially provide useful information regarding the composition of a CTO.     

一种新型撑开钳及其在寰枢椎脱位撑开复位中的应用研究

目的研究一种专用于颅颈交界区手术的新型撑开钳,及其在寰枢椎脱位(AAD)撑开复位中的应用效果。方法设计制作新型撑开钳,用于30例寰枢椎脱位患者的撑开复位手术操作中。术后对患者进行随访,观察患者症状变化。对术前术后的寰齿间距(ADI)、日本骨科协会(JOA)评分进行比较分析,评估改善率。结果本组患者在手术过程中均未出现撑开钳滑脱。术后平均随访时间13.4(6~25)个月,患者术后神经功能均恢复良好,症状得到明显改善,均未出现并发症。ADI由术前的(6.31±0.89)mm复位到(2.74±0.91)mm(P<0.001);JOA评分由术前的(12.67±2.70)分改善至(15.80±1.06)分(P<0.001),平均改善率为69.1%。结论新型撑开钳在寰枢椎脱位撑开复位中的使用效果良好,有一定的临床使用价值。     

枕下三角的超声解剖学研究

目的探讨枕下三角境界及内容物的检查方法与超声解剖学特点,为临床检查枕下三角提供超声影像学资料。方法对100例健康成年人枕下区进行超声检查,描述枕下三角境界的超声判定及解剖关系;阐述枕大神经的走行特点,测量头下斜肌表面枕大神经的横截面积;记录椎动脉V3段管腔内径(D)、收缩期峰值流速(PSV)、舒张期末流速(EDV)、阻力指数(PI)。结果 (1)寰椎后结节左侧约1 cm处纵切声像图显示寰椎后弓呈"短弧形"强回声,其后上方为头后大直肌、后下方为头下斜肌,三者分别构成枕下三角的底、内上界和外下界。(2)寰椎侧块处纵切声像图显示侧块为"平台样"强回声结构,其后方为椎动脉V3段、下方紧接寰椎后弓;后弓后方为头下斜肌、后上方为头上斜肌,头上斜肌构成三角的外上界,后弓与椎动脉V3段之间为枕下神经所在区域。(3)枕大神经长轴声像图显示神经从头下斜肌下缘发出后向内上走行于头下斜肌及头后大直肌与头半棘肌之间;不同性别头下斜肌表面枕大神经横截面积两侧比较,差异均无统计学意义(P>0.05)。(4)寰椎侧块处横切声像图显示椎动脉V3段呈"倒U形"绕侧块进入枕骨大孔,排除发育不良者,测V3段D为(3.52±0.39)mm、PSV及EDV分别为(43.33±9.05)、(21.87±5.86)cm/s、RI为(0.49±0.11)。结论超声是检查枕下三角及其内容物的理想方法。