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。     

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.     

Lingual lymph nodes: Anatomy,clinical considerations,and oncological significance

Lingual lymph nodes are an inconstant group of in-transit nodes, which are located on the route of lymph drainage from the tongue mucosa to the regional nodes in neck levels I and II. There is growing academic data on the metastatic spread of oral cancer, particularly regarding the spreading of oral tongue squamous cell carcinoma to lingual nodes. These nodes are not currently included in diagnostic and treatment protocols for oral tongue cancer. Combined information on surgical anatomy, clinical observations, means of detection, and prognostic value is presented. Anatomically obtained incidence of lingual nodes ranges from 8.6% to 30.2%. Incidence of lingual lymph node metastasis ranges from 1.3% to 17.1%. It is clear that lymph nodes that bear intervening tissues from the floor of the mouth should be removed to improve loco-regional control. Extended resection volume, which is required for the surgical treatment of lingual node metastasis, cannot be implied to every tongue cancer patient. As these lesions significantly influence prognosis, special efforts of their detection must be made. Reasonably, every tongue cancer patient must be investigated for the existence of lingual lymph node metastasis. Lymphographic tracing methods, which are currently implied for sentinel lymph node biopsies, may improve the detection of lingual lymph nodes.