Comparison of Cancer Detection Rates Between TRUS-Guided Biopsy and MRI-Targeted Biopsy According to PSA Level in Biopsy-Naive Patients: A Propensity Score Matching Analysis

Background

The purpose of the study was to compare cancer detection rates between 12-core transrectal ultrasound-guided prostate biopsy (TRUS-Bx) and multiparametric magnetic resonance imaging (mpMRI)-guided target prostate biopsy (MRI-TBx) according to prostate-specific antigen (PSA) level in biopsy-naive patients.

Colitis following the use of immune checkpoint inhibitors: A real-world analysis of spontaneous reports submitted to the FDA adverse event reporting system

BackgroundAlthough colitis has been reported in patients treated with immune checkpoint inhibitors (ICIs), associations between colitis and ICIs had not been thoroughly assessed in real-world studies. Here, we identified and characterized significant colitis-associated with ICIs.MethodsBased on the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to December 2019, the disproportionality analysis and Bayesian analysis, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN) and the multi-item gamma Poisson shrinker (MGPS) algorithms were adopted to data mining of the suspected adverse events of colitis after ICIs administrating. Clinical characteristics of patients with ICIs-associated colitis and the time to onset of colitis following different ICI regimens were collected.ResultsA total of 3786 reports of colitis adverse events were identified with ICIs. Seven ICI monotherapies were associated with the reporting of colitis. Statistically significant ROR, PRR, information component (IC), and empirical Bayesian geometric mean (EBGM) emerged for all ICI monotherapies and combination therapies. ICIs-associated colitis affected mostly male (53.51%), with a wide mean age range (60.65 to 72 years). Colitis adverse events were commonly reported in patients with melanoma and lung cancer. Adverse outcomes of colitis concerning ICI were mainly outcomes of hospitalization-initiated or prolonged and other serious. Among colitis cases, 17.43% cases of colitis concerning ICI lead to death. The adverse event of colitis occurred earliest in ipilimumab monotherapy with a median time to onset of 64.21 days (IQR: 27–69 days) among all monotherapies.ConclusionsICI may lead to severe and disabling ICIs-associated colitis during therapy. Analysis of FAERS data identified signals for adverse events of colitis with ICI regimens. Practitioners should consider the factors that may increase the likelihood of colitis. The findings support a continued surveillance and risk factor identification studies.     

超声造影联合血清CEA、CA72-4对卵巢良恶性肿瘤鉴别诊断的价值

目的:探讨超声造影联合血清癌胚抗原（CEA）、糖类抗原72-4（CA72-4）对卵巢良恶性肿瘤鉴别诊断的价值。方法:选取2017年1月至2018年6月本院肿瘤科收治的128例卵巢肿瘤患者进行研究，进行超声造影和血清CEA、CA72-4水平检测，观察超声造影、CEA、CA72-4及联合检测对卵巢良恶性肿瘤鉴别诊断的价值。结果:在良性肿瘤组中超声造影符合率为72.92%，恶性肿瘤组中超声造影符合率为75.00%，两组比较差异无统计学意义（P>0.05）；恶性肿瘤组患者血清CEA、CA72-4水平高于良性肿瘤组，两组比较差异有统计学意义（P<0.05）；恶性肿瘤组超声造影、CA72-4检测阳性率均高于良性肿瘤组（P<0.05），两组血清CEA检测阳性率比较差异无统计学意义（P>0.05），三者联合检测阳性率高于单项指标检测（P<0.05）；通过ROC曲线分析显示，CEA的AUC为0.644，诊断灵敏度为31.25%，特异性为82.29%，CA72-4的AUC为0.702，诊断灵敏度为40.63%，特异性为79.17%，二者联合检测的AUC为0.785，诊断敏感性为56.25%，特异性为73.96%；三项指标单独检测，超声造影检测的灵敏度、阳性预测率、阴性预测率、诊断准确度及误诊率最高，CEA检测的特异性、漏诊率最高，三者联合检测的灵敏度、特异性、阳性预测率、阴性预测率、诊断准确度最高，漏诊率、误诊率最低。结论:超声造影联合血清CEA、CA72-4检测较单独检测诊断效能高，对卵巢良恶性肿瘤鉴别诊断有较高参考价值。     

血清学检测联合前列腺超声造影对老年患者前列腺癌的诊断价值分析

目的分析血清前列腺特异性抗原(PSA)检查联合超声造影诊断老年前列腺癌的价值。方法选取2016年4月至2018年12月湖北钟祥市中医院诊治的50例前列腺癌患者作为研究对象。将这50例患者设为前列腺癌组,另将50例非前列腺癌患者设为非前列腺癌组。所有患者均行超声造影检查和血清PSA检查。对比前列腺癌组与非前列腺癌组年龄、前列腺体积、超声造影参数(强度减半时间、绝对增强强度、峰值强度、基础强度、加速时间、达峰时间、显影时间);对比两组血清游离PSA(f-PSA)、血清总PSA(T-PSA)、游离前列腺特异抗原/前列腺特异抗原比值(f/T-PSA)、PSA密度(PSAD);分析不同病理类型患者血清PSA水平分布情况;经ROC曲线评估血清PSA、超声造影在该病中的诊断价值。结果①与非前列腺癌组相比,前列腺癌组强度减半时间、加速时间、达峰时间、显影时间均更短,且差异具有统计学意义(P<0.05)。②前列腺癌组患者T-PSA、PSAD组水平均较非前列腺癌组高,差异具有统计学意义(P<0.05)。③结节型和隐匿性血清PSA<4ng/mL率最高,弥散浸润伴结节型>100ng/mL最高,不同病理分型的前列腺癌患者血清PSA水平分布差异具有统计学意义(P<0.05)。④超声造影参数中仅达峰值时间、显影时间的ROC曲线下面积超过0.5。血清PSAD、T-PSA联合达峰值时间、显影时间诊断该病的ROC曲线下面积为0.924。结论血清PSAD、T-PSA联合超声造影能提高老年前列腺癌诊断价值,其中血清PSA能辅助疾病类型鉴别。     

1,8-桉叶油素自微乳给药系统的制备及质量评价和细胞摄取研究

目的优化1,8-桉叶油素(1,8-cineole,1,8-Cin)自微乳给药系统(1,8-cineole self-microemulsion drug delivery system,1,8-Cin-SMEDDS)处方,对其进行表征并进行细胞摄取考察。方法通过绘制伪三元相图,确定1,8-Cin-SMEDDS有效自乳化区域,进行初步处方筛选。以粒径和载药量为指标,采用星点设计-效应面法对1,8-Cin-SMEDDS处方进行优化并验证。荧光显微镜观察高糖损伤的人脐静脉内皮细胞(HUVEC)对1,8-Cin-SMEDDS的摄取情况。结果 1,8-Cin-SMEDDS的最佳处方是大豆油(7.5%)与1,8-Cin(22.5%)为混合油相,HS15(56%)为乳化剂,乙醇(14%)为助乳化剂,滴加纯水至8m L得半透明略带蓝色乳光液体。透射电镜观察其外观呈球形液滴,激光粒度Zeta电位测定仪测得平均粒径为(131.68±1.44)nm,Zeta电位为(-10.03±1.63)m V;HPLC法测得包封率为(99.890±0.012)%,载药量为(224.750±0.028)mg/g。HUVEC细胞摄取实验结果表明,细胞对1,8-Cin-SMEDDS的摄取高于游离1,8-Cin。结论 1,8-Cin-SMEDDS制备方法简便,重复性好,所得1,8-Cin-SMEDDS外观良好,包封率高,理化性质稳定,且能促进细胞摄取。     

CD20 和CD19 双靶点CAR-T细胞对B淋巴细胞肿瘤的杀伤作用

目的：设计同时靶向B淋巴细胞表面CD20 和CD19 两个抗原蛋白的双特异嵌合抗原受体（chimeric antigen receptor,CAR）并制备BiCAR-T 细胞，检测其对B淋巴细胞肿瘤细胞的杀伤作用以及对免疫缺陷B-NSG 小鼠白血病模型的治疗效果。方法：构建基于鼠源CD19 和人源化CD20 scFv 的双靶点CAR分子，将CAR基因装载于慢病毒载体中，在293T细胞中包装慢病毒，感染健康人T 细胞制备BiCAR-T 细胞。构建表达CD19 和CD20 的K562-CD19-GFP、K562-CD20-GFP 以及表达Luciferase 的Nalm6-Luc-GFP 细胞作为靶细胞，将BiCAR-T 细胞与靶细胞共同孵育，检测其对靶细胞杀伤能力及释放IFN-γ 水平。使用Nalm6-Luc-GFP 细胞构建白血病小鼠模型，尾静脉注射BiCAR-T细胞，通过小动物成像方法观察BiCAR-T细胞对荷瘤小鼠的治疗作用。结果：健康人来源的BiCAR-T 细胞经7 d 培养后扩增良好，扩增倍数为20~50 倍，阳性率为10%~92%，显示成功制备BiCAR-T细胞。在效靶比为10∶1 时，BiCAR-T细胞对Nalm-6、K562-CD19-GFP 和K562-CD20-GFP 的杀伤率显著高于对照组细胞[ （76.7±7.4）% vs（8.7±2.4）%、（93.3±5.2）% vs（46.7±6.2）、（51.0±0.8）vs（30.7±0.5）%，均P<0.01]；与对照组相比，与Nalm-6细胞共孵育后BiCAR-T 细胞分泌IFN- γ 量显著增加[（872.7±7.7）vs（101.0±5.3）pg/ml ，P<0.01]。动物实验表明，BiCAR-T细胞对B-NSG小鼠白血病模型治疗效果明显，注射BiCAR-T细胞后白血病细胞逐渐减少，第50 天时基本消失，小鼠全部存活至第70 天被安乐死；PBS和对照T细胞组小鼠分别在（19±3）和（20±1）d 全部死亡。结论：成功设计了表达CD19 和CD20 的双靶点CAR分子后成功制备了BiCAR-T 细胞，该细胞能够有效杀伤表达CD19 和/或CD20 的B淋巴细胞肿瘤细胞，与靶细胞共同孵育后能够分泌大量IFN-γ，对B-NSG免疫缺陷小鼠白血病模型具有明显的治疗效果。