Five-year clinical outcomes using the bioresorbable vascular scaffold: Insights from the FRANCE ABSORB registry

Central illustration: cumulative major adverse cardiac events (MACE) and bioresorbable vascular scaffold (BVS) thrombosis rates after 1, 2, 3, 4 and 5 years.

     

Platelets in Early Antibody-Mediated Rejection of Renal Transplants

Antibody-mediated rejection is a major complication in renal transplantation. The pathologic manifestations of acute antibody-mediated rejection that has progressed to functional impairment of a renal transplant have been defined in clinical biopsy specimens. However, the initial stages of the process are difficult to resolve with the unavoidable variables of clinical studies. We devised a model of renal transplantation to elucidate the initial stages of humoral rejection. Kidneys were orthotopically allografted to immunodeficient mice. After perioperative inflammation subsided, donor-specific alloantibodies were passively transferred to the recipient. Within 1 hour after a single transfer of antibodies, C4d was deposited diffusely on capillaries, and von Willebrand factor released from endothelial cells coated intravascular platelet aggregates. Platelet-transported inflammatory mediators platelet factor 4 and serotonin accumulated in the graft at 100- to 1000-fold higher concentrations compared with other platelet-transported chemokines. Activated platelets that expressed P-selectin attached to vascular endothelium and macrophages. These intragraft inflammatory changes were accompanied by evidence of acute endothelial injury. Repeated transfers of alloantibodies over 1 week sustained high levels of platelet factor 4 and serotonin. Platelet depletion decreased platelet mediators and altered the accumulation of macrophages. These data indicate that platelets augment early inflammation in response to donor-specific antibodies and that platelet-derived mediators may be markers of evolving alloantibody responses.     

A new approach to prevent HIV transmission: Project Protect intervention for recently infected individuals

Past research suggests that as many as 50% of onward human immunodeficiency virus (HIV) transmissions occur during acute and recent HIV infection. It is clearly important to develop interventions which focus on this highly infectious stage of HIV infection to prevent further transmission in the risk networks of acutely and recently infected individuals. Project Protect tries to find recently and acutely infected individuals and prevents HIV transmission in their risk networks. Participants are recruited by community health outreach workers at community-based HIV testing sites and drug users' community venues, by coupon referrals and through referrals from AIDS clinics. When a network with acute/recent infection is identified, network members are interviewed about their risky behaviors, network information is collected, and blood is drawn for HIV testing. Participants are also educated and given prevention materials (condoms, syringes, educational materials); HIV-infected participants are referred to AIDS clinics and are assisted with access to care. Community alerts about elevated risk of HIV transmission are distributed within the risk networks of recently infected. Overall, 342 people were recruited to the project and screened for acute/recent HIV infection. Only six index cases of recent infection (2.3% of all people screened) were found through primary screening at voluntary counseling and testing (VCT) sites, but six cases of recent infection were found through contact tracing of these recently infected participants (7% of network members who came to the interview). Combining screening at VCT sites and contact tracing the number of recently infected people we located as compared to VCT screening alone. No adverse events were encountered. These first results provide evidence for the theory behind the intervention, i.e., in the risk networks of recently infected people there are other people with recent HIV infection and they can be successfully located without increasing stigma for project participants.     

Differentiating autoimmune pancreatitis from pancreatic ductal adenocarcinoma with CT radiomics features

PurposeThe purpose of this study was to determine whether computed tomography (CT)-based machine learning of radiomics features could help distinguish autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC).Materials and MethodsEighty-nine patients with AIP (65 men, 24 women; mean age, 59.7 ± 13.9 [SD] years; range: 21–83 years) and 93 patients with PDAC (68 men, 25 women; mean age, 60.1 ± 12.3 [SD] years; range: 36–86 years) were retrospectively included. All patients had dedicated dual-phase pancreatic protocol CT between 2004 and 2018. Thin-slice images (0.75/0.5 mm thickness/increment) were compared with thick-slices images (3 or 5 mm thickness/increment). Pancreatic regions involved by PDAC or AIP (areas of enlargement, altered enhancement, effacement of pancreatic duct) as well as uninvolved parenchyma were segmented as three-dimensional volumes. Four hundred and thirty-one radiomics features were extracted and a random forest was used to distinguish AIP from PDAC. CT data of 60 AIP and 60 PDAC patients were used for training and those of 29 AIP and 33 PDAC independent patients were used for testing.ResultsThe pancreas was diffusely involved in 37 (37/89; 41.6%) patients with AIP and not diffusely in 52 (52/89; 58.4%) patients. Using machine learning, 95.2% (59/62; 95% confidence interval [CI]: 89.8–100%), 83.9% (52:67; 95% CI: 74.7–93.0%) and 77.4% (48/62; 95% CI: 67.0–87.8%) of the 62 test patients were correctly classified as either having PDAC or AIP with thin-slice venous phase, thin-slice arterial phase, and thick-slice venous phase CT, respectively. Three of the 29 patients with AIP (3/29; 10.3%) were incorrectly classified as having PDAC but all 33 patients with PDAC (33/33; 100%) were correctly classified with thin-slice venous phase with 89.7% sensitivity (26/29; 95% CI: 78.6–100%) and 100% specificity (33/33; 95% CI: 93–100%) for the diagnosis of AIP, 95.2% accuracy (59/62; 95% CI: 89.8–100%) and area under the curve of 0.975 (95% CI: 0.936–1.0).ConclusionsRadiomic features help differentiate AIP from PDAC with an overall accuracy of 95.2%.     

Acute toxicity of chlorpyrifos to the non-target organism Cnesterodon decemmaculatus

Chlorpyrifos is the most used insecticide in Argentina. Cnesterodon decemmaculatus is a widely distributed, endemic fish from Neotropical America. It attains high densities in the shallow water assemblages of Argentina and Brazil. The aim of this study was to assess the acute toxicity of chlorpyrifos to C. decemmaculatus. The mean 96-h LC₅₀ of three independent determinations was 105.3 (±?3.1) μg/L. Sublethal effects were observed. Swimming behavioral changes at each chlorpyrifos exposure concentration were reported. C. decemmaculatus represents a good model for ecotoxicological risk assessment.     

经鼻导管高流量吸氧与经鼻气道正压通气在重症毛细支气管炎呼吸支持中的应用价值比较

目的：比较经鼻导管高流量吸氧（HFNC）与经鼻气道正压通气（nCPAP）在重症毛细支气管炎呼吸支持中的应用价值，为临床治疗方案的选择提供参考。方法：选取2016年12月至2018年12月我院儿科收治的重症毛细支气管炎患儿90例，采用随机数字表法分为观察组和对照组各45例。两组患儿入院后均给予常规综合治疗以保证呼吸道通畅，在此基础上观察组采用HFNC治疗，对照组采用nCPAP治疗，比较两组患儿治疗前和治疗24 h后呼吸频率、经皮血氧饱和度（TcSO2）、呼吸窘迫评分体系（CSS）评分、动脉血氧分压（PaO2）等呼吸相关指标及治疗前后临床症状体征改善情况。结果：两组患儿治疗24 h后呼吸频率、CSS评分均降低，且观察组降低程度更大，TcSO2、PaO2于治疗24 h后升高，观察组升高幅度较对照组明显；治疗后两组患儿咳嗽及肺部湿啰音、肺部炎症情况均改善，观察组症状体征消失时间早于对照组，差异均有统计学意义（P<0.05）。结论：重症毛细支气管炎患儿采用HFNC治疗可明显改善通气功能和临床症状，治疗效果优于nCPAP治疗，可扩大样本量进一步观察。     

鼻塞式同步间歇正压通气(NIPPV)联合布地奈德雾化治疗新生儿急性呼吸窘迫综合征疾病的临床应用研究

目的:分析鼻塞式同步间歇正压通气(NIPPV)联合布地奈德雾化治疗ARDS(新生儿急性呼吸窘迫综合征)疾病的临床应用效果。方法:纳入病例是2017年5月—2019年11月收治的104例ARDS新生儿,随机平均分为两组。参照组52例采纳CPAP(持续气道正压通气通气)治疗,实验组52例采纳NIPPV+布地奈德雾化治疗,对比两组呼吸机通气时间、用氧时间、住院时间、血气指标以及并发症发生情况。结果:实验组呼吸机通气时间、用氧时间、住院时间均明显短于参照组,差异有统计学意义P<0.05;实验组治疗3 d后PaCO2明显低于参照组,实验组治疗3 d后PH以及PaO2明显高于参照组,差异有统计学意义P<0.05;实验组并发症发生率(3.85%,2/52)明显低于参照组(21.15%,11/52),差异有统计学意义P<0.05。结论:NIPPV+布地奈德雾化可有效缩短ARDS患者机械通气时间,改善血气指标,降低并发症发生率,值得借鉴。     

依维莫司联合全反式维甲酸逆转急性早幼粒细胞白血病细胞耐药的研究

目的探讨依维莫司联合全反式维甲酸(简称维甲酸)逆转急性早幼粒细胞白血病(APL)细胞株NB4-R1耐药的作用。方法应用CD11b染色流式细胞术及硝基四唑氮蓝(NBT)还原实验检测两药联合应用对细胞分化的影响, 流式细胞术检测细胞周期情况, Annexin V/PI双染色检测细胞凋亡情况, 蛋白质印迹法检测自噬相关蛋白微管结合蛋白轻链3(LC3)、Beclin 1及早幼粒白血病-维甲酸受体融合蛋白(PML-RARα)、磷酸化核糖体S6激酶(P-P70S6K)、磷酸化4E结合蛋白1(P-4E-BP1) 等表达水平。结果与维甲酸组比较, 联用组能诱导耐药细胞株NB4-R1细胞的分化, 并将细胞增殖阻止在G ₁期而对细胞凋亡无明显影响。100 nmol/L依维莫司组、1μmol/L维甲酸组、联用组、对照组NB4-R1细胞培养48 h后分化百分率分别为(2.29±0.57)%、(17.06±2.65)%、(54.47±4.91)%、(2.54±0.53)%; 处于G ₁期的细胞百分率分别为(35.20±11.97)%、(33.54±6.25)%、(53.70±8.73)%、(27.40±6.01)%; 四组细胞凋亡细胞百分率分别为(2.30±0.14)%、(2.25±0.21)%、(2.40±0.28)%、(1.95±0.07)%。与维甲酸组比较, 联用组mTOR信号通路下游的P70S6K、4E-BP1分子磷酸化水平下降, LC3-II和Beclin 1的表达上调, 且能部分降解融合蛋白PML-RARα。 结论依维莫司联合维甲酸能诱导NB4-R1细胞分化, 且能阻滞细胞周期而不致细胞凋亡, 其机制可能与依维莫司联合维甲酸抑制mTOR信号通路激活自噬作用从而降解PML-RARα蛋白有关。