International Hand Function Study Following Distal Radial Access: The RATATOUILLE Study

BackgroundDistal radial access (DRA) has been proposed to improve procedure ergonomics and favor radial artery patency. Although promising data, nothing is known on evolving hand function after DRA.ObjectivesThis study sought to comprehensively evaluate hand function in patients undergoing DRA.MethodsReal-world patients undergoing DRA undertook a thorough multimodality assessment of hand function implementing multidomain questionnaires (Disabilities of the Arm, Shoulder and Hand and Levine-Katz), and motor (pinch grip test) and sensory (Semmes-Weinstein monofilaments test) examinations of both hands. All assessments were performed at preprocedural baseline and planned at 1-, 6-, and 12-month follow-up (FU). Adverse clinical and procedural events were documented too.ResultsData of 313 patients (220 men, age 66 ± 10 years) from 9 international centers were analyzed. The Disabilities of the Arm, Shoulder and Hand and the Levine-Katz scores slightly improved from baseline to FU (P = 0.008 and P = 0.029, respectively). Pinch strength mildly improved from baseline to FU (P < 0.001 for both the left and right hands). Similarly, touch pressure threshold appeared to faintly improve in both the left and right hands (P < 0.012 for all the sites). For both motor and sensory function tests, comparable findings were found for the DRA hand and the contralateral one, with no significant differences between them. Repeated assessment of all tests over all FU time points similarly showed lack of worsening hand function. Access-related adverse events included 19 harmless bleedings and 3 forearm radial artery and 3 distal radial artery occlusions. None affected hand function at FU.ConclusionsIn a systematic multidimensional assessment, DRA was not associated with hand function impairment. Moreover, DRA emerges as a safe alternative vascular access.     

胫前动脉踝上穿支皮瓣修复足踝部软组织缺损19例

目的探讨胫前动脉踝上穿支皮瓣修复足踝部软组织缺损的临床疗效。方法回顾性研究2018年4月至2019年6月采用胫前动脉踝上穿支皮瓣修复足踝部软组织缺损19例的资料,其中男11例,女8例;年龄为21~75岁,平均39岁。根据前踝上穿支皮瓣解剖学基础,按照足踝部软组织缺损大小和形状,在小腿下端前外侧设计并切取皮瓣转位修复创面。切取胫前动脉踝上穿支皮瓣面积为6.0 cm×5.0 cm^14.0 cm×8.0 cm,均为带蒂皮瓣转位。根据皮瓣成活、感染控制、弹性色泽、外观形态、供区瘢痕、皮肤感觉、患者认可等情况,对患者足踝部软组织缺损的修复情况进行综合评价。结果本组19例皮瓣全部成活,软组织缺损、肌腱、骨质及钢板外露均得以修复。供区均I期愈合。术后门诊随访2~16个月,皮瓣血运良好,颜色接近周围正常皮肤,臃肿不明显,患者对外观表示满意;供区皮片愈合良好,无明显增生、挛缩及溃疡,踝关节功能良好。结论胫前动脉踝上穿支皮瓣是修复足踝部软组织缺损较为理想的方法之一,手术操作简便,穿支较恒定,血供可靠,具有一定的临床应用价值。     

Carboxylesterase catalyzed 18O-labeling of carboxylic acid and its potential application in LC-MS/MS based quantification of drug metabolites

LC-MS quantification of drug metabolites is sometimes impeded by the availability of internal standards that often requires customized synthesis and/or extensive purification. Although isotopically labeled internal standards are considered ideal for LC-MS/MS based quantification, de novo synthesis using costly isotope-enriched starting materials makes it impractical for early stage of drug discovery. Therefore, quick access to these isotope-enriched compounds without chemical derivatization and purification will greatly facilitate LC-MS/MS based quantification. Herein, we report a novel ¹⁸O-labeling technique using metabolizing enzyme carboxylesterase (CES) and its potential application in metabolites quantification study. Substrates of CES typically undergo a two-step oxygen exchange with H₂¹⁸O in the presence of the enzyme, generating singly- and doubly-¹⁸O-labeled carboxylic acids; however, unexpected hydrolytic behavior was observed for three of the test compounds – indomethacin, piperacillin and clopidogrel. These unusual observations led to the discovery of several novel hydrolytic mechanisms. Finally, when used as internal standard for LC-MS/MS based quantification, these in situ labeled compounds generated accurate quantitation comparable to the conventional standard curve method. The preliminary results suggest that this method has potential to eliminate laborious chemical synthesis of isotope-labeled internal standards for carboxylic acid-containing compounds, and can be developed to facilitate quantitative analysis in early-stage drug discovery.     

Association between de novo lipogenesis susceptibility genes and coronary artery disease

Background and aimsCoronary artery disease (CAD) is the principal cause of death in individuals with non-alcoholic fatty liver disease (NAFLD). The aim of this study was to use genetic epidemiology to study the association between de novo lipogenesis (DNL), one of the major pathways leading to NAFLD, and CAD risk.Methods and resultsDNL susceptibility genes were used as instruments and selected using three approaches: 1) genes that are associated with both high serum triglycerides and low sex hormone-binding globulin, both downstream consequences of DNL (unbiased approach), 2) genes that have a known role in DNL (biased approach), and 3) genes that have been associated with serum fatty acids, used as a proxy of DNL. Gene-CAD effect estimates were retrieved from the meta-analysis of CARDIoGRAM and the UK Biobank (～76014 cases and ～264785 controls). Effect estimates were clustered using a fixed-effects meta-analysis. Twenty-two DNL susceptibility genes were identified by the unbiased approach, nine genes by the biased approach and seven genes were associated with plasma fatty acids. Clustering of genes selected in the unbiased and biased approach showed a statistically significant association with CAD (OR:1.016, 95%CI:1.012; 1.020 and OR:1.013, 95%CI:1.007; 1.020, respectively), while clustering of fatty acid genes did not (OR:1.004, 95%CI:0.996–1.011). Subsequent exclusion of potential influential outliers did reveal a statistically significant association (OR:1.009, 95%CI:1.000; 1.018).ConclusionsDNL susceptibility genes are associated with an increased risk of CAD. These findings suggest that DNL may be involved in the pathogenesis of CAD and favor further development of strategies that target NAFLD through DNL.     

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。     

Factors Affecting Recurrent Deep Vein Thrombosis after Pharmacomechanical Thrombolysis and Left Iliac Vein Stent Placement in Patients with Iliac Vein Compression Syndrome

PurposeThis study evaluated the factors affecting contralateral and ipsilateral recurrent deep vein thrombosis (DVT) after iliac vein stent placement in patients with iliac vein compression syndrome (IVCS).Materials and MethodsData from 130 patients (95 female patients) who underwent catheter-directed thrombolysis and stent placement for IVCS with left lower leg thrombosis at a single institution were retrospectively analyzed. Mean patient age was 69.0 ± 14.0 years old. Median follow-up was 14 months (range, 3–164 months). Anticoagulation therapy was prescribed for 6 months, followed by lifelong antiplatelet therapy. Multivariate logistic regression analysis was performed to evaluate the factors affecting the development of contralateral and ipsilateral recurrent DVT.ResultsSeven patients (5.4%) developed contralateral DVT (median, 26 months; range, 2–61 months), and 11 patients (8.5%) developed ipsilateral DVT (median, 1 month; range, 0–53 months). Stent location (odds ratio [OR], 11.564; 95% confidence interval [CI], 1.159–115.417) and in-stent thrombosis during follow-up (OR, 15.142; 95% CI, 1.406–163.119) were predictors of recurrent contralateral DVT. Thrombophilia (OR, 47.560; 95% CI, 2.369–954.711), remaining inferior vena cava filter (OR, 30.552; 95% CI, 3.495–267.122), and in-stent thrombosis during follow-up (OR, 82.057; 95% CI, 2.915–2309.848) were predictors of ipsilateral DVT.ConclusionsContralateral DVT occurs late and is associated with extension of the iliac vein stent to the inferior vena cava and in-stent thrombosis. Ipsilateral DVT occurs relatively early and is associated with thrombophilia, remaining inferior vena cava filter, and in-stent thrombosis.     

Inactivated influenza vaccine formulated with single-stranded RNA-based adjuvant confers mucosal immunity and cross-protection against influenza virus infection

Influenza vaccination is considered the most valuable means to prevent and control seasonal influenza infections, which causes various clinical symptoms, ranging from mild cough and fever to even death. Among various influenza vaccine types, the inactivated subunit type is known to provide improved safety with reduced reactogenicity. However, there are some drawbacks associated with inactivated subunit type vaccines, with the main ones being its low immunogenicity and the induction of Th2-biased immune responses. In this study, we investigated the role of a single-stranded RNA (ssRNA) derived from the intergenic region in the internal ribosome entry site of the Cricket paralysis virus as an adjuvant rather than the universal vaccine for a seasonal inactivated subunit influenza vaccine. The ssRNA adjuvant stimulated not only well-balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and IL-4) immune responses but also a mucosal immune response (indicated by IgA), a key protector against respiratory virus infections. It also increases the HI titer, the surrogate marker of influenza vaccine efficacy. Furthermore, ssRNA adjuvant confers cross-protective immune responses against heterologous influenza virus infection while promoting enhanced viral clearance. Moreover, ssRNA adjuvant increases the number of memory CD4⁺ and CD8⁺ T cells, which can be expected to induce long-term immune responses. Therefore, this ssRNA-adjuvanted seasonal inactivated subunit influenza vaccine might be the best influenza vaccine generating robust humoral and cellular immune responses and conferring cross-protective and long-term immunity.