China/Asia On Demand (CAOD)

Modern Rehabilitation. Year 2019 Issue 27 is now available on CAOD. In this issue: guan yu ju ban...

Modern Rehabilitation. Year 2019 Issue 27 is now available on CAOD.In this issue:guan yu ju ban 2019 di san jie zhong guo kang fu yi xue hui zong he xue shu nian hui zuo guo ji kang fu she bei zhan lan hui de tong zhi (关于举办2019第三届中国康复医学会综合学术年会暨国际康复设备展览会的通知)...... page:4260kuo da lun wen ji qi yan jiu de xue shu ying xiang li : zuo zhe chu ban hou wen zhang zen yang cai neng gou bei guo nei wai xiao tong xing zhuan jia he geng duo de zhuan ye qi kan bian ji kan jian (2) (扩大论文及其研究的学术影响力:作者出版后文章怎样才能够被国内外小同行专家和更多的专业期刊编辑看见(2))ZHAO...

Αλέξανδρος Γ. Σφακιανάκης

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Stomatology. Year 2019Issue 06 is now available on CAOD. In this issue: Performance study of two new...

Stomatology. Year 2019Issue 06 is now available on CAOD.In this issue:Performance study of two new collagen membranes for guiding bone tissue regeneration in vivo and in vitro (两种新型胶原膜引导骨组织再生的体内外性能研究)WANG Lili, ,YAN Jia, ,LI Dongsheng, ,MO Xiumei, ,HU Xiaokun, ,ZHANG Feimin, ,LIU Mei, ,Jiangsu Key Laboratory of Oral Diseases,Nanjing Medical University, ,Department of Prosthodontics,Affiliated Hospital of Stomatology,Nanjing Medical University, ,...... page:481-487kou qiang yi xue za zhi tou gao xu...

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Clinical Radiology. Year 2019 Issue 06 is now available on CAOD. In this issue: jing wai jing mai...

Clinical Radiology. Year 2019 Issue 06 is now available on CAOD.In this issue:jing wai jing mai fen cha bian yi ban jia xing jing mai liu yi li (颈外静脉分叉变异伴假性静脉瘤一例)WANG Zuo, ,HU Tianyi, ,...... page:946lin chuang fang she xue za zhi gao yue (《临床放射学杂志》稿约)...... page:951-952zuo qian sui xi tuan kuai zhuang yi chang xin hao qing zhen duan fen xi (骶前髓系团块状异常信号——请诊断分析)HUANG Zuoyu, ,ZHANG Yong, ,CHENG Jingliang, ,WEN Mengmeng, ,...... page:953+1153Abnormal Topological Attribute of Functional Brain Network...

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Dermatology. Year 2019 Issue 06 is now available on CAOD. In this issue: Bullous pilomatricoma (水疱型毛母质瘤)...

Dermatology. Year 2019 Issue 06 is now available on CAOD.In this issue:Bullous pilomatricoma (水疱型毛母质瘤)MA Guo-an, ,WANG Bao-juan, ,...... page:335-336+333-334Dermoscopic features of molluscum contagiosum (传染性软疣皮肤镜观察1例)XU Chen-chen, ,WANG Jun-hui, ,ZENG Xue, ,LIU Nan, ,...... page:338+337Free androgen index and expression levels of androgen receptor mRNA in patients with androgenetic alopecia (雄激素性秃发患者游离睾酮及毛囊中雄激素受体mRNA表达的临床研究)XU Yu-xuan, ,DING Qi, ,SUN Wei-ling, ,CAO Chun-yu, ,LIU Jing-jing, ,ZHOU...

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Shanghai Journal of Stomatology. Year 2019 Issue 03 is now available on CAOD. In this issue: shang...

Shanghai Journal of Stomatology. Year 2019 Issue 03 is now available on CAOD.In this issue:shang hai bai bo kou qiang yi yuan jian jie (上海拜博口腔医院简介)...... page:216Instructions for Authors by Shanghai Journal of Stomatology (《上海口腔医学》杂志投稿须知)...... page:218-219shang hai shi zuo xing qu ya bing fang zhi suo jian jie (上海市闵行区牙病防治所简介)...... page:220The effect and mechanism of ANXA1 on TPF chemosensitivity in oral squamous cell carcinoma (ANXA1对口腔鳞癌TPF化疗敏感性的影响及作用机制探讨)ZHU Dong-wang, ,SUN Wen-wen, ,ZHAO Tong-chao, ,ZHONG...

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Chinese Nursing Research. Year 2019 Issue 12 is now available on CAOD. In this issue: Correlation...

Chinese Nursing Research. Year 2019 Issue 12 is now available on CAOD.In this issue:Correlation between core self-evaluation,positive coping and work engagement of clinical nurses (临床护士核心自我评价、积极应对与工作投入的相关性)YANG Yan, ,YAN Xiaofei, ,HAO Fu, ,ZHANG Hui, ,DANG Limei, ,GU Yong, ,The First Hospital of the Air Force Military Medical University, ,...... page:2003-2006Bibliometric analysis of nursing research on tuberculosis in China (我国结核病护理研究的文献计量分析)CHANG Leilei, ,SU Yanbing, ,YU Qi, ,WANG Chen, ,LIU Chao, ,DUAN...

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Modern Oncology. Year 2019 Issue 13 is now available on CAOD. In this issue: ji yu sheng wu xin xi...

Modern Oncology. Year 2019 Issue 13 is now available on CAOD.In this issue:ji yu sheng wu xin xi xue fen xi de jie chang ai shu niu ji yin shai xuan ji diao kong wang luo gou jian (基于生物信息学分析的结肠癌枢纽基因筛选及调控网络构建)ZHAO Zuohui, ,LIU Jun, ,HE Fenfei, ,YU Yanping, ,WANG Zuo, ,ZHANG Xiang, ,ZHANG Rui, ,LI Jipeng, ,...... page:2227-2231sirna chen mo ifitm1 dui luan chao ai xi bao xi cp70 sheng wu xue xiao ying de ying xiang ji ji zhi yan jiu (siRNA沉默IFITM1对卵巢癌细胞系CP70生物学效应的影响及机制研究)YANG Rong, ,zhang , ,WANG Jian, ,CHEN...

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Rehabilitative Tissue Engineering Research. Year 2019 Issue 27 is now available on CAOD. In this issue:...

Rehabilitative Tissue Engineering Research. Year 2019 Issue 27 is now available on CAOD.In this issue:guan yu ju ban 2019 di san jie zhong guo kang fu yi xue hui zong he xue shu nian hui zuo guo ji kang fu she bei zhan lan hui de tong zhi (关于举办2019第三届中国康复医学会综合学术年会暨国际康复设备展览会的通知)...... page:4260kuo da lun wen ji qi yan jiu de xue shu ying xiang li : zuo zhe chu ban hou wen zhang zen yang cai neng gou bei guo nei wai xiao tong xing zhuan jia he geng duo de zhuan ye qi kan bian ji kan jian (2) (扩大论文及其研究的学术影响力:作者出版后文章怎样才能够被国内外小同行专家和更多的专业期刊编辑看见(2))ZHAO...

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Pharmaceutical & Engineering Design. Year 2019 Issue 03 is now available on CAOD. In this issue:...

Pharmaceutical & Engineering Design. Year 2019 Issue 03 is now available on CAOD.In this issue:Application Discussion of Analytical Hierarchy Process in the Location Selection Assessment of Underground Water Sealed Rock Caverns (层次分析法在地下水封洞库选址评价中的应用探讨)Liu Shikun, ,He Guofu, ,Dai Jie, ,SINOPEC Shanghai Engineering Co.Ltd, ,...... page:1-8zhong shi hua shang hai gong cheng you xian gong si rong zuo shang hai shi wen ming dan wei jiu lian guan (中石化上海工程有限公司荣膺"上海市文明单位"九连冠)WEI Yongzhong, ,...... page:8zhong...

Αλέξανδρος Γ. Σφακιανάκης

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Medical Biomechanics. Year 2019 Issue 03 is now available on CAOD. In this issue: ddh huan zhe quan...

Medical Biomechanics. Year 2019 Issue 03 is now available on CAOD.In this issue:ddh huan zhe quan zuo guan jie zhi huan zhong gu gu pian xin ju dui gu ji duo ti dong li xue he jie chu li xue de ying xiang (DDH患者全髋关节置换中股骨偏心距对骨肌多体动力学和接触力学的影响)CHEN Xihui, ,CHAI Wei, ,GAO Yongchang, ,ZHANG Zhifeng, ,JIN Zhongmin, ,...... page:225-231xiao tui can zhi yu jie shou qiang de fei xian xing you xian yuan fen xi (小腿残肢与接受腔的非线性有限元分析)YANG Haiyan, ,WU Xiao, ,FENG Xiaohua, ,...... page:232-236ji yu any body gu zuo...

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Apoplexy and Nervous Diseases. Year 2019 Issue 06 is now available on CAOD. In this issue: The associations...

Apoplexy and Nervous Diseases. Year 2019 Issue 06 is now available on CAOD.In this issue:The associations of DWI infarct volume with FLAIR hyperintensities-DWI mismatch and functional outcome (DWI梗死体积与FLAIR血管高信号-DWI不匹配及预后的相关性研究)CHEN Guanghao, ,QIU Jianbo, ,MIAO Zhengfei, ,Department of Radiology,Nanjing First Hospital,Nanjing Medical University, ,...... page:484-487Association study of COX-1、COX-2 gene polymorphism and aspirin resistance in ischemic stroke patients (脑梗死患者COX-1及COX-2基因多态性与阿司匹林抵抗的相关性分析)LI...

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Clinical Anatomy. Year 2019 Issue 03 is now available on CAOD. In this issue: kuang shang wai ce -...

Clinical Anatomy. Year 2019 Issue 03 is now available on CAOD.In this issue:kuang shang wai ce - zong lie ru lu chu li qian jiao tong dong mai liu de lin chuang ying yong jie po (眶上外侧-纵裂入路处理前交通动脉瘤的临床应用解剖)ZHANG Guanghui, ,HAN Ruizuo, ,JIN Hua, ,WANG Yuhai, ,...... page:241-244gang yu qie ji de jie po xing tai xue ce liang ji lin chuang yi yi (冈盂切迹的解剖形态学测量及临床意义)ZHAO Hongzuo, ,LIU Yang, ,LI Jing, ,ZHANG Lei, ,...... page:245-248tai er wei bu dong mai de jie po jie gou ji qi san wei zhong jian fen ge...

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Clinical Pharmacology. Year 2019 Issue 12 is now available on CAOD. In this issue: kang jun yao wu...

Clinical Pharmacology. Year 2019 Issue 12 is now available on CAOD.In this issue:kang jun yao wu xun zheng yong yao lun tan (抗菌药物循证用药论坛)...... page:1224Pemetrexed versus docetaxel in non-small cell lung cancer (培美曲塞注射剂与多西他赛注射剂治疗非小细胞肺癌患者的临床研究)LI Ya-fang, ,WANG Yong, ,Department of Respiratory Medicine,Shangyu People's Hospital, ,Clinical Laboratory,Shangyu People's Hospital, ,...... page:1227-1229Expression of human antigen R and androgen aeceptor in prostate cancer and the relation with clinical...

Αλέξανδρος Γ. Σφακιανάκης

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Natural Medicines. Year 2019 Issue 06 is now available on CAOD. In this issue: The mechanisms of traditional...

Natural Medicines. Year 2019 Issue 06 is now available on CAOD.In this issue:The mechanisms of traditional Chinese medicine underlying the prevention and treatment of atherosclerosis LI Ting-Ting, ,WANG Zhi-Bin, ,LI Yang, ,CAO Feng, ,YANG Bing-You, ,KUANG Hai-Xue, ,Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, ,...... page:401-4123'-Methoxydaidzein exerts analgesic activity by inhibiting voltage-gated sodium channels XU Run-Jia, ,FEI...

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New Drugs and Clinical Remedies. Year 2019 Issue 06 is now available on CAOD. In this issue: Advances...

New Drugs and Clinical Remedies. Year 2019 Issue 06 is now available on CAOD.In this issue:Advances in anti-tumor research of vorinostat complex substance and its analogues (伏立诺他复合物及其类似物的抗肿瘤研究进展)LI Jia-xin, ,ZHAI Hong-ju, ,SUN De-wu, ,GUAN Ren-quan, ,WANG Yan, ,QI Yun-feng, ,Key Laboratory of Preparation and Applications of Environmental Friendly Materials of the Ministry of Education,Jilin Normal University, ,College of Chemistry,Jilin Normal University, ,College of Life Science,Jilin Normal University, ,...... page:321-327zhong...

Αλέξανδρος Γ. Σφακιανάκης

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China Pharmacy. Year 2019 Issue 12 is now available on CAOD. In this issue: Study on the R&D Contribution...

China Pharmacy. Year 2019 Issue 12 is now available on CAOD.In this issue:Study on the R&D Contribution Rate of Listed Pharmaceutical Enterprises in Southwest China Based on Super-efficiency DEA Model (基于超效率DEA模型的西南地区上市药企研发贡献度研究)ZHANG Dan, ,ZHOU Geyao, ,TIAN Haiyu, ,CHEN Wenjiao, ,MENG Xiaoxia, ,School of Medical and Health Management,Guizhou Medical University, ,...... page:1585-1590Determination of Plasma Concentration of Harmine Derivative DH-330 by UPLC-MS and Its Pharmacokinetics Evaluation...

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Medicinal Chemistry. Year 2019 Issue 03 is now available on CAOD. In this issue: Concise elucidation...

Medicinal Chemistry. Year 2019 Issue 03 is now available on CAOD.In this issue:Concise elucidation of coordinating PD and PK based upon biological principles (生物学导向协调药效和药代的药物设计)GUO Zong-ru, ,Institute of Material Medica,Chinese Academy of Medical Sciences and Peking Medical College, ,...... page:167-174Synthesis and antitumor activity in vitro of novel PARP-1 inhibitors (新型PARP-1抑制剂的合成及体外抗肿瘤活性研究)KUANG Yuan-jie, ,BAO Gang, ,WANG Xiao-long, ,XUE Xin, ,School of Pharmacy,Nanjing University of Chinese...

Αλέξανδρος Γ. Σφακιανάκης

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Drug Dependence. Year 2019 Issue 03 is now available on CAOD. In this issue: ben er dan zuo zhuo lei...

Drug Dependence. Year 2019 Issue 03 is now available on CAOD.In this issue:ben er dan zuo zhuo lei yao wu : huo yi feng xian he li shi yong (苯二氮艹卓类药物:获益、风险、合理使用)SUO Lin, ,WANG Jia, ,SUN Lili, ,LIU Jianfeng, ,LI Jing, ,...... page:163-171zu sai xing shui mian hu xi zan ting yu jiao lv de guan xi (阻塞性睡眠呼吸暂停与焦虑的关系)JI Yanbin, ,CHEN Xiaomin, ,WANG Zhong, ,CHEN Wenhao, ,XIE Zuo, ,...... page:172-177jing shen huo xing chu fang yao wu lan yong xian zhuang (精神活性处方药物滥用现状)WANG Wenzhe, ,JIANG Haifeng, ,ZHAO...

Αλέξανδρος Γ. Σφακιανάκης

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Pharmaceuticals. Year 2019 Issue 06 is now available on CAOD. In this issue: zhong liu de mian yi...

Pharmaceuticals. Year 2019 Issue 06 is now available on CAOD.In this issue:zhong liu de mian yi ji yin zhi liao tu po yu tiao zhan (肿瘤的免疫基因治疗——突破与挑战)HU Yang, ,WEI Gang, ,LU Weiyue, ,...... page:579-588kang ni zhuan lu bing du yao wu zhi ji de yan jiu jin zhan (抗逆转录病毒药物制剂的研究进展)ZHONG Yan, ,CHAI Xuzuo, ,WANG Jian, ,...... page:589-595xin xing kang ru xian ai yao rui bo xi ni de he cheng yan jiu jin zhan (新型抗乳腺癌药瑞博西尼的合成研究进展)WENG Zhibing, ,TIAN Miao, ,...... page:596-603rui ge fei ni he cheng yan jiu...

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Cancer Biotherapy. Year 2019 Issue 06 is now available on CAOD. In this issue: mir-1269a zai shi guan...

Cancer Biotherapy. Year 2019 Issue 06 is now available on CAOD.In this issue:mir-1269a zai shi guan ai zu zhi zhong de biao da ji qi dui kyse30 xi bao e xing sheng wu xue xing wei de ying xiang (miR-1269a在食管癌组织中的表达及其对KYSE30细胞恶性生物学行为的影响)WEI Sisi, ,LI Xiaoya, ,DONG Pei, ,DAI Suli, ,ZHANG Zuo, ,ZHAO Lianmei, ,DAN Baoen, ,...... page:623-631xiong guo suan dui wei ai xi bao zhu mgc-803 diao wang he zi shi de diao kong ji qi zuo yong ji zhi (熊果酸对胃癌细胞株MGC-803凋亡和自噬的调控及其作用机制)CHEN Weizuo, ,LIU Chunying, ,...... page:638-643tet1-cd...

Αλέξανδρος Γ. Σφακιανάκης

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Chinese Ophthalmology. Year 2019 Issue 03 is now available on CAOD. In this issue: zhen ci zhi liao...

Chinese Ophthalmology. Year 2019 Issue 03 is now available on CAOD.In this issue:zhen ci zhi liao ma bi xing xie shi de lin chuang ti hui (针刺治疗麻痹性斜视的临床体会)LIANG Fengming, ,...... page:171-174shi jue guang xue huan jing dui zuo shu yan qu guang fa yu de ying xiang (视觉光学环境对豚鼠眼屈光发育的影响)LV Meng, ,KANG Zefeng, ,...... page:175-179yang xue bu shen fang dui xing jue bao duo xing gao du jin shi mo xing gong mo chao wei jie gou de ying xiang (养血补肾方对形觉剥夺性高度近视模型巩膜超微结构的影响)MA Xiaobing, ,GAO Jun, ,KANG Zefeng, ,WU...

Αλέξανδρος Γ. Σφακιανάκης

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Pharmaceutical Affairs. Year 2019 Issue 06 is now available on CAOD. In this issue: wo guo xue ye...

Pharmaceutical Affairs. Year 2019 Issue 06 is now available on CAOD.In this issue:wo guo xue ye zhi pin qi ye gmp jian cha que xian fen xi ji jian guan si lu tan suo (我国血液制品企业GMP检查缺陷分析及监管思路探索)YANG Jingpeng, ,XU Xiaozuo, ,WANG Yuan, ,...... page:605-608yun nan sheng ji ceng yi liao wei sheng ji gou shi shi ji ben yao wu zhi du xiao guo ping jia ji fen xi (云南省基层医疗卫生机构实施基本药物制度效果评价及分析)SHI Xiuyuan, ,HUANG Runqing, ,li , ,...... page:609-615chu xiong yi yi yao fa zhan xian zhuang cun zai wen ti ji dui...

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Biomedical and Environmental Sciences. Year 2019 Issue 05 is now available on CAOD. In this issue:...

Biomedical and Environmental Sciences. Year 2019 Issue 05 is now available on CAOD.In this issue:Relationship between Maternal PBMC HBV cccDNA and HBV Serological Markers and its Effect on HBV Intrauterine Transmission WANG Dan Dan, ,YI Lin Zhu, ,WU Li Na, ,YANG Zhi Qing, ,HAO Hai Yun, ,SHI Xiao Hong, ,WANG Bo, ,FENG Shu Ying, ,FENG Yong Liang, ,WANG Su Ping...... page:315-323Inactivation of Poliovirus by Ozone and the Impact of Ozone on the Viral Genome JIANG Han Ji, ,CHEN Na, ,SHEN Zhi Qiang, ,YIN...

Αλέξανδρος Γ. Σφακιανάκης

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Labeled Immunoassays and Clinical Medicine. Year 2019 Issue 05 is now available on CAOD. In this issue:...

Labeled Immunoassays and Clinical Medicine. Year 2019 Issue 05 is now available on CAOD.In this issue:ru he zai gong zuo zhong fa xian ke yan wen ti (如何在工作中发现科研问题)ZHANG Man...... page:721The Clinical Features of Breast Cancer Patients with Type-2 Diabetes Mellitus (乳腺癌伴2型糖尿病的临床特征分析)FENG Yu, ,LEI Ting, ,LI Yan-ping, ,ZHAO Xia, ,ZHANG Man...... page:722-725Differential Expression of Transthyretin in the Serum of Colorectal Cancer Patients (转甲状腺素蛋白在结直肠肿瘤患者血清中的差异表达)HU Hui-hui, ,ZHANG Man...... page:726-728,733The...

Αλέξανδρος Γ. Σφακιανάκης

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Radiologic Practice. Year 2019 Issue 04 is now available on CAOD. In this issue: rsna2018 fu bu ying...

Radiologic Practice. Year 2019 Issue 04 is now available on CAOD.In this issue:rsna2018 fu bu ying xiang xue (RSNA2018腹部影像学)LUO Yan, ,MENG Xiaoyan, ,LI Jiali, ,CHEN Xiao, ,HU Yao, ,ZUO Di, ,LIANG Ping, ,YANG Yang, ,ZHOU Ziling, ,LI Anqin, ,ZOU Xianlun, ,LV Yinzhang, ,WANG Zuo, ,FAN Zuozuo, ,XIE Jinzuo, ,KE Zan, ,YOU Huijuan, ,LI Zhen, ,WANG Liang, ,HU Daoyu...... page:357-361rsna2018 er ke ying xiang xue (RSNA2018儿科影像学)TIAN Zuoyao, ,ZHU Xiaohu, ,ZENG Guang, ,YAO Jing, ,SHAO Jianbo...... page:362-373MR...

Αλέξανδρος Γ. Σφακιανάκης

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Immunology. Year 2019 Issue 03 is now available on CAOD. In this issue: Molecular cloning,expression...

Immunology. Year 2019 Issue 03 is now available on CAOD.In this issue:Molecular cloning,expression and purification of hyper-variable region in the hexon protein of human adenovirus (人腺病毒六邻体高变区蛋白的亚克隆表达及纯化)Li Ye, ,Qu Lixin, ,Dong Tuo, ,Wang Yingchen, ,Zhang Zhe, ,Du Xiqiao, ,Lu Bing, ,Gao Hong, ,Shang Lei, ,Li Yu, ,O.N.Reva, ,V.I.Zlobin, ,Qu Zhangyi...... page:229-234Sulforaphane inhibits apoptosis of heat-killed E. coli-induced HeLa cell (Sulforaphane抑制热灭活大肠杆菌诱导的HeLa细胞凋亡)Zhang Jian, ,Dong Yanyan, ,Qu...

Αλέξανδρος Γ. Σφακιανάκης

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Cerebrovascular Diseases. Year 2019 Issue 04 is now available on CAOD. In this issue: Should we wait...

Cerebrovascular Diseases. Year 2019 Issue 04 is now available on CAOD.In this issue:Should we wait for routine laboratory findings before intravenous thrombolysis for ischemic stroke? (缺血性卒中静脉溶栓治疗前应该等待化验结果吗?)Huang Qiang, ,Xu Wendeng, ,Wei Chenming, ,Zhang Xiaofeng, ,Song Xiaowei, ,Wu Jian...... page:241-245P-wave dispersion parameters predict paroxysmal atrial fibrillation in patients with embolic stroke of undetermined source (P波离散参数预测栓子源不明的栓塞性卒中患者阵发性心房颤动)Tao Jingzhi, ,Tang Tieyu, ,Duan Zuowei, ,Zhang...

Αλέξανδρος Γ. Σφακιανάκης

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Biomedical Engineering. Year 2019 Issue 02 is now available on CAOD. In this issue: ji guang zhi liao...

Biomedical Engineering. Year 2019 Issue 02 is now available on CAOD.In this issue:ji guang zhi liao xiong ji su xing tuo fa he ban tu de ji shu zhi nan (激光治疗雄激素性脱发和斑秃的技术指南)ZHONG Guozhongyiyaoxinxixuehuikangshuailaofenhui...... page:95-99wu li ji shu fu zhu nao zu zhong kang fu de lin chuang zhi nan (物理技术辅助脑卒中康复的临床指南)ZHONG Guozhongyiyaoxinxixuehuikangshuailaofenhui...... page:100-108Molecular epidemiological and genotypic analysis of human adenovirus infection in children with acute diarrhea in Tianjin...

Αλέξανδρος Γ. Σφακιανάκης

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Neural Injury and Functional Reconstruction. Year 2019 Issue 05 is now available on CAOD. In this...

Neural Injury and Functional Reconstruction. Year 2019 Issue 05 is now available on CAOD.In this issue:xin xi dong tai (信息动态)...... page:封3Establishment and Evaluation of A New Animal Model of Graded Diffuse Axonal Injury (新型可分级弥漫性轴索损伤动物模型的建立与评价)DAI Jun-xi, ,ZHANG Jin-cheng, ,YANG Biao, ,CHU Sheng-hua, ,MA Yan-bin...... page:217-220,224Clinical Study on Sexual Life of Young and Middle-Aged Stroke Patients (中青年卒中患者性生活临床研究)SHENG Xin, ,HUANG Xiao-jiang...... page:221-224Clinical Features of 58 Cases...

Αλέξανδρος Γ. Σφακιανάκης

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Oncology. Year 2019 Issue 03 is now available on CAOD. In this issue: Curative effect analysis of...

Oncology. Year 2019 Issue 03 is now available on CAOD.In this issue:Curative effect analysis of different clinical characteristics and treatment modalities for primary esophageal small cell carcinoma (原发性食管小细胞癌不同临床特征及治疗方案的疗效分析)Li Zhe, ,Xing Yanke, ,Li Baosheng...... page:129-134Treatment and prognosis of limited-stage small cell cancer of the esophagus (局限期食管小细胞癌的治疗选择及预后研究)Chen Junsheng, ,Jiao Yan, ,Han Dali, ,Yang Wenfeng...... page:135-140Study of texture analysis based on CT images to predict...

Αλέξανδρος Γ. Σφακιανάκης

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Stomatology. Year 2019 Issue 03 is now available on CAOD. In this issue: Minimal invasive microscopic...

Stomatology. Year 2019 Issue 03 is now available on CAOD.In this issue:Minimal invasive microscopic tooth preparation based on endodontic, periodontal and functional health (基于牙体牙髓、牙周及功能健康的 显微微创牙体预备)Yu Haiyang, ,Zhao Yuwei, ,Li Junying, ,Luo Tian, ,Gao Jing, ,Liu Hongchen, ,Liu Weicai, ,Liu Feng, ,Zhao Ke, ,Fei Liu, ,Ma Chufan, ,JuergenManfred Setz, ,Liang Shanshan, ,Fan Lin, ,Gao Shanshan, ,Zhu Zhuoli, ,Shen Jiefei, ,Wang Jian, ,Zhu Zhimin, ,Zhou Xuedong...... page:229-235Functional clear aligner...

Αλέξανδρος Γ. Σφακιανάκης

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Clinical and Experimental Medicine. Year 2019 Issue 12 is now available on CAOD. In this issue: lin...

Clinical and Experimental Medicine. Year 2019 Issue 12 is now available on CAOD.In this issue:lin chuang he shi yan yi xue za zhi gao yue (《临床和实验医学杂志》稿约)...... page:前插1Persimmon leaf extract reduces myocardial ischemia-reperfusion injury through MAPK/ERK1/2 pathway. (柿叶提取物通过MAPK/ERK1/2通路减轻心肌缺血再灌注损伤)MENG Qingli, ,GU Hongyan, ,WANG Shumei, ,BAI Lu...... page:1233-1238Expression of nuclear PTEN and p53 genes in gastric cancer. (核PTEN和p53基因在胃癌组织中的表达及临床意义)MU Xing, ,BAI Zhigang, ,ZHANG Zhongtao, ,YAO Hongwei, ,YANG...

Αλέξανδρος Γ. Σφακιανάκης

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Clinical Transfusion and Laboratory Medicine. Year 2019 Issue 03 is now available on CAOD. In this...

Clinical Transfusion and Laboratory Medicine. Year 2019 Issue 03 is now available on CAOD.In this issue:Callicarpa Nudiflora: Clinical Efficacy on chronic Pelvitis through Dampening of IL-1β,MCP-1 and GM-CSF (裸花紫珠片治疗慢性盆腔炎临床效果及对患者血清炎症因子的影响)CHEN Yan-rong, ,WU Ming-juan, ,WANG Jia-jun...... page:225-229zhong yao zai yi zhi bu ti huo xing ji rong xue fan ying zhong de zuo yong (中药在抑制补体活性及溶血反应中的作用)ZHOU Fangzhu, ,ZHU Chuanlin, ,LAN Jiongcai, ,ZHANG Juan...... page:229-233zhong yi " mai xiang " zai hong...

Αλέξανδρος Γ. Σφακιανάκης

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Qilu Pharmaceutical Affairs. Year 2019 Issue 05 is now available on CAOD. In this issue: Studies on...

Qilu Pharmaceutical Affairs. Year 2019 Issue 05 is now available on CAOD.In this issue:Studies on the aging-delay effect of a complex decoction in Caenorhabditis elegans (复方中药延缓秀丽线虫衰老的作用研究)YANG Longwang, ,CHEN Jun, ,LIN Jing, ,PAN Wenfeng, ,HUANG Zebo...... page:249-252The effect and mechanism of bisdemethoxycurcumin on carbon tetrachloride-induced acute liver injury in mice (双去甲氧基姜黄素对四氯化碳致小鼠急性肝损伤的保护作用及机制)JIAO Chunli, ,SONG Yanqin, ,DU Yuan, ,LU Yongying, ,ZHANG Leiming...... page:253-256,294Comparison...

Αλέξανδρος Γ. Σφακιανάκης

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Shanghai Journal of Biomedical Engineering. Year 2019 Issue 01 is now available on CAOD. In this issue:...

Shanghai Journal of Biomedical Engineering. Year 2019 Issue 01 is now available on CAOD.In this issue:A Novel 3D Nasal Cavity Segmentation Algorithm Based on Morphology and Regional Connectivity (一种基于形态学与区域连通性的3D鼻腔分割算法)ZHANG Ke, ,CHENG Yaqing, ,ZHANG Ying, ,JIANG Lan, ,SENG Dongjie, ,WANG Chang...... page:1-5Optimization Design of a Novel Flexible Instrument for Endoscopic Skull Base Surgery (经鼻颅底手术器械弯曲结构的优化设计)JIA Yingwei, ,MAO Lin, ,SONG Chengli, ,LYU Kunyong, ,WANG Dong...... page:6-10Mechanical...

Αλέξανδρος Γ. Σφακιανάκης

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Shanghai Medical and Pharmaceutical Journal. Year 2019 Issue 11 is now available on CAOD. In this...

Shanghai Medical and Pharmaceutical Journal. Year 2019 Issue 11 is now available on CAOD.In this issue:bu wei kun nan yong yu tiao zhan (不畏困难勇于挑战)ZHAO Zuo...... page:1-2,7Research progress in Bruton's tyrosine kinase inhibitor in treatment of B cell malignancies (布鲁顿酪氨酸激酶抑制剂治疗B细胞肿瘤的研究进展)XU Huiwen, ,CHEN Bobin...... page:3-7Research advances of azacitidine in the treatment of myelodysplastic syndromes and acute myeloid leukemia (阿扎胞苷治疗骨髓增生异常综合征和急性髓系白血病的研究进展)LIU Weiyang, ,WANG Xiaoqin...... page:8-12Progress...

Αλέξανδρος Γ. Σφακιανάκης

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Attend to Practice and Research. Year 2019 Issue 11 is now available on CAOD. In this issue: Influence...

Attend to Practice and Research. Year 2019 Issue 11 is now available on CAOD.In this issue:Influence of timing assessment management of enteral nutrition tolerance on patients with severe acute pancreatitis (肠内营养耐受性定时评估管理对重症急性胰腺炎患者的影响)ZHANG Chun-xia...... page:1-5Risk factors of pulmonary infection in children with congenital heart disease after interventional closure surgery and its nursing intervention (先天性心脏病患儿介入封堵术后肺部感染的危险因素与护理干预研究)LENG Juan, ,LIU Hui...... page:6-8Investigation and analysis...

Αλέξανδρος Γ. Σφακιανάκης

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Drug Evaluation. Year 2019 Issue 10 is now available on CAOD. In this issue: Evaluation of Safety...

Drug Evaluation. Year 2019 Issue 10 is now available on CAOD.In this issue:Evaluation of Safety and Pharmacological Characteristics in Vivo of Recombinant Human Coagulation FactorⅧ (重组人凝血因子Ⅷ药品安全性及体内药学特性评价)HUO Ji-ping, ,ZHAO Zhi-gang...... page:3-6,37Management and Application of Food and Drug Grass-roots Laboratory Information System (基层食品药品检验信息系统的管理应用)YANG Qun, ,ZHANG Guo-li, ,LIU Wei, ,ZHANG Mei-mei...... page:7-8,61Cost-effectiveness Analysis of Insulin Glargine 100U/mL Versus NPH Insulin in the...

Αλέξανδρος Γ. Σφακιανάκης

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Rehabilitation. Year 2019 Issue 05 is now available on CAOD. In this issue: zheng gao (征稿) ...... page:封2...

Rehabilitation. Year 2019 Issue 05 is now available on CAOD.In this issue:zheng gao (征稿)...... page:封2Effects of hyperbaric oxygen combined with acupuncture on cognitive function in type 2 diabetic rats (高压氧联合针刺对2型糖尿病大鼠认知功能的影响)Wang Fengbo, ,Wei Xiaofei, ,Tang Mingwei...... page:227-230Effects of butterfly bath on upper limb spasticity after stroke (基于表面肌电探讨蝶形浴对脑卒中 偏瘫患者上肢痉挛的影响)YUAN Song, ,LIU Fei, ,ZHANG Bao, ,LI Mengying, ,WANG Junhua, ,GAO Feng...... page:231-234Short-term efficacy of manual lymphatic...

Αλέξανδρος Γ. Σφακιανάκης

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Clinic Medical Imaging. Year 2019 Issue 05 is now available on CAOD. In this issue: zhong guo lin...

Clinic Medical Imaging. Year 2019 Issue 05 is now available on CAOD.In this issue:zhong guo lin chuang yi xue ying xiang za zhi gao yue (《中国临床医学影像杂志》稿约)...... page:封2CT and MRI features of spinal canal ganglioneuroma (椎管内外节细胞神经瘤CT与MRI诊断)WANG Tong, ,ZHANG Jun, ,WANG Hong-wei, ,GUO Qi-yong...... page:305-308,359Clinical and imaging analysis of otosclerosis (耳硬化症的临床与影像分析)WU Quan-yang, ,ZHENG Rui-bin, ,WANG Jia-qi, ,LI Song-bai...... page:309-312Early prediction value of 18F-FDG PET/CT for pathological...

Αλέξανδρος Γ. Σφακιανάκης

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Leprosy and Skin Diseases. Year 2019 Issue 06 is now available on CAOD. In this issue: Effect of HLA-Cw6...

Leprosy and Skin Diseases. Year 2019 Issue 06 is now available on CAOD.In this issue:Effect of HLA-Cw6 allele on the efficacy of biological agents for the treatment of psoriasis (HLA-Cw6基因对生物制剂治疗银屑病疗效影响的Meta分析)XIANG Zhi, ,MA Yiping, ,CUI Pangen, ,CHEN Min...... page:321-326Detection of ATP2C1 gene in five pedigrees with Hailey-Hailey disease (慢性家族性良性天疱疮五家系ATP2C1基因突变分析)WANG Ting, ,CUI Hongzhou, ,WANG Detong, ,GAO Jie, ,GUO Shuping...... page:327-329Skin fungal community in the patients with tinea...

Αλέξανδρος Γ. Σφακιανάκης

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Immunology. Year 2019 Issue 10 is now available on CAOD. In this issue: Research progress of tissue-resident...

Immunology. Year 2019 Issue 10 is now available on CAOD.In this issue:Research progress of tissue-resident macrophages in maintenance of immune homeostasis (组织定居巨噬细胞在维持免疫稳态中的研究进展)QIANG Li-Hua, ,ZHANG Yong, ,LIU Cui-Hua...... page:1153-1159Effects of Glycyrrhizic acid on LPS-induced activation of IEC-6 cells NF-κB pathway and expression of inflammatory factors (甘草酸对LPS诱导的IEC-6细胞NF-κB通路及炎症因子表达的影响)LUO Min, ,XIAO Ting-Ting, ,ZENG Xing, ,ZHANG Xian...... page:1160-1163,1168Effect of IL-22 on expression...

Αλέξανδρος Γ. Σφακιανάκης

1h

Cerebrovascular Diseases. Year 2019 Issue 05 is now available on CAOD. In this issue: Effect of morphological...

Cerebrovascular Diseases. Year 2019 Issue 05 is now available on CAOD.In this issue:Effect of morphological characteristics of aneurysms on the rupture of pericallosal artery aneurysms (动脉瘤形态学特征对胼周动脉瘤破裂的影响因素分析)Zhai Xiaodong, ,Li Chuanjie, ,Yu Jiaxing, ,Ren Jian, ,Zhang Hongqi...... page:225-230Efficacy analysis of intravenous thrombolysis in patients with mild ischemic stroke (轻型缺血性卒中患者静脉溶栓的疗效分析)Huang Hui, ,Chen Haoyang, ,Yang Yong, ,Li Ze, ,Pan Xiaoping, ,Ouyang Yingjun, ,Deng Weihua...... page:231-236Predictive...

Αλέξανδρος Γ. Σφακιανάκης

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Neural Regeneration Research. Year 2019 Issue 08 is now available on CAOD. In this issue: CALL FOR...

Neural Regeneration Research. Year 2019 Issue 08 is now available on CAOD.In this issue:CALL FOR PAPERS ...... page:封2Tandem pore TWIK-related potassium channels and neuroprotection J.Antonio Lamas, ,Diego Fernández-Fernández...... page:1293-1308Neurotherapeutic potential of erythropoietin after ischemic injury of the central nervous system Florian Simon, ,Nicolaos Floros, ,Wiebke Ibing, ,Hubert Schelzig, ,Artis Knapsis...... page:1309-1312Dendritic shrinkage after injury: a cellular killer or a...

Αλέξανδρος Γ. Σφακιανάκης

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China Pharmacist. Year 2019 Issue 06 is now available on CAOD. In this issue: Effect of Atropine Combined...

China Pharmacist. Year 2019 Issue 06 is now available on CAOD.In this issue:Effect of Atropine Combined with Neostigmine on Hepatic Ischemia-reperfusion Injury and Its Mechanism (阿托品联合新斯的明减轻肝脏缺血再灌注损伤作用及其机制研究)Shen Qirui, ,Sun Keyan, ,Fei Yibo, ,Ni Min...... page:989-992,996Effect of Xiwang Decoction on Lipofuscin Accumulation in Aging Rats (希望液对衰老模型大鼠皮肤脂褐素沉积的影响)Feng Xuanye, ,Zhao Xin, ,Wang Xiang, ,Feng Lili, ,Cai Dayong, ,Wang Yueqi...... page:993-996Penetration Enhancement and Skin Irritation of...

Αλέξανδρος Γ. Σφακιανάκης

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Pharmacovigilance. Year 2019 Issue 05 is now available on CAOD. In this issue: Experimental Study...

Pharmacovigilance. Year 2019 Issue 05 is now available on CAOD.In this issue:Experimental Study on Acute Toxicity of Dendrobium Devonianum Extract in Mice (紫皮石斛浸膏对小鼠急性毒性实验的研究)DONG Shoutang, ,YANG Jiao, ,ZHANG Xuqiang, ,HU Yan, ,YANG Hongqin...... page:257-259Application of Bivaludine Combined with Tirofiban in Patients with STEMl without Reflow or Slow Blood Flow during Coronary Intervention (比伐卢定联合替罗非班对急性ST段抬高型心肌梗死患者冠状动脉介入术中无复流或慢血流的探索性应用)GUO Xiaoli...... page:260-264,269Analysis of Liver Injury...

Αλέξανδρος Γ. Σφακιανάκης

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Drug Abuse Prevention and Treatment. Year 2019 Issue 03 is now available on CAOD. In this issue: chu...

Drug Abuse Prevention and Treatment. Year 2019 Issue 03 is now available on CAOD.In this issue:chu fang hai luo yin wei chi zhi liao de li bi he zheng yi (处方海洛因维持治疗的利弊和争议)CAI Yujia, ,ZHANG Zuo, ,WANG Fangmin, ,ZHUANG Dingding, ,ZHOU Wenhua...... page:125-129,138da ma he fa hua zhi guo ji qu shi yu zheng yi (大麻合法化之国际趋势与争议)LUO Lingyin...... page:130-138Evaluation of Preventive Application of Antimicrobial Agents During the Perioperative Period of Clean Operation (清洁手术围手术期抗菌药物预防应用规范化管理效果评价)Li Jing, ,Gao...

Αλέξανδρος Γ. Σφακιανάκης

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Pharmaceuticals. Year 2019 Issue 12 is now available on CAOD. In this issue: Current Status of Storage...

Pharmaceuticals. Year 2019 Issue 12 is now available on CAOD.In this issue:Current Status of Storage and Maintenance of Chinese Medicinal Materials in Guangzhou Qingping Traditional Chinese Medicine Market (广州清平中药材市场中药材贮藏养护现状调查)XU Liang, ,MA Yucui, ,WU Cui, ,WANG Lixue, ,LI Chun, ,CHAO Zhimao...... page:1-3Long-Term Toxicity of Vitexin for Injection in Beagle Dogs (注射用牡荆素Beagle犬长期毒性试验研究)NIU Haijun, ,LI Xiaoliang, ,LI Guanghui...... page:4-10Repair Effect of P-Hydroxybenzaldehyde on Cerebral Ischemia...

Αλέξανδρος Γ. Σφακιανάκης

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Medical Guide. Year 2019 Issue 05 is now available on CAOD. In this issue: Application Study of 64-row...

Medical Guide. Year 2019 Issue 05 is now available on CAOD.In this issue:Application Study of 64-row CT with Low Tube Voltage and Low-dose ContrastAgent Combined with Normal Saline CTPA in Pulmonary Embolism (64排CT低管电压下低剂量对比剂联合生理盐水CTPA在肺动脉栓塞中的应用研究)MA Zhoupeng, ,FU Qitian, ,LIN Guansheng, ,FU Wenbing...... page:257-263 Association between Serum suPAR Level and Carotid Intima-media Thickness in Patients with Chronic Kidney Disease (慢性肾脏病患者血清suPAR水平与颈动脉内膜中层厚度的相关性研究)HUANG Yanling, ,CHEN Yonghua, ,YUAN...

Αλέξανδρος Γ. Σφακιανάκης

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Clinical Oncology. Year 2019 Issue 02 is now available on CAOD. In this issue: Immunosuppressive checkpoint...

Clinical Oncology. Year 2019 Issue 02 is now available on CAOD.In this issue:Immunosuppressive checkpoint Siglec-15: a vital new piece of the cancer immunotherapy jigsaw puzzle Xiubao Ren...... page:205-210The functional role of miRNAs in colorectal cancer: insights from a large population-based study Lila E. Mullany, ,Martha L. Slattery...... page:211-219Dorsomorphin induces cancer cell apoptosis and sensitizes cancer cells to HSP90 and proteasome inhibitors by reducing nuclear heat shock factor...

Αλέξανδρος Γ. Σφακιανάκης

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Radiation Oncology. Year 2019 Issue 06 is now available on CAOD. In this issue: Value of MORC2-IDH1...

Radiation Oncology. Year 2019 Issue 06 is now available on CAOD.In this issue:Value of MORC2-IDH1 detection in molecular subtyping of glioblastoma patients treated with postoperative chemoradiotherapy (联合MORC2-IDH1检测对胶质母细胞瘤放化疗患者分子分型价值)Tang Meng, ,Xu Hui, ,Wang You, ,Ding Qianshan, ,Zhou Fuxiang...... page:401-404Comparison of clinical efficacy and prognosis of intensity-modulated radiotherapy and three dimensional conformal radiotherapy in patients with stage Ⅱ/m esophageal cancer: a multi-center...

Αλέξανδρος Γ. Σφακιανάκης

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Neurology. Year 2019 Issue 06 is now available on CAOD. In this issue: Paying attention to the study...

Neurology. Year 2019 Issue 06 is now available on CAOD.In this issue:Paying attention to the study of proteomics in muscular diseases (关注蛋白质组学在肌肉病的研究)Pu Chuanqiang, ,Zhang Yutong...... page:441-445The correlation of the levels of interleukin-15 with late onset myasthenia gravis (血浆中白细胞介素15水平与晚发型重症肌无力的关系)Li Xu, ,Lu Fen, ,Li Wei, ,Zhao Dongmei, ,Li Xiaohong, ,Zhang Jiewen, ,Xia Qingxin...... page:446-451Needle electromyography of the genioglossus muscle in the detection of amyotrophic lateral sclerosis...

Αλέξανδρος Γ. Σφακιανάκης

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Medical Ultrasound(Electronic Version). Year 2019 Issue 03 is now available on CAOD. In this issue:...

Medical Ultrasound(Electronic Version). Year 2019 Issue 03 is now available on CAOD.In this issue:Application of color Doppler ultrasound in acquired arteriovenous malformations (彩色多普勒超声在获得性子宫动静脉瘘的诊断及疗效评估中的应用)Lyu Xiaoli, ,Chen Ping, ,Xu Huiying, ,Hu Dan, ,Yang Qing...... page:181-185Retrospective summary for the prenatal ultrasound screening and pregnancy outcomes of fetalcongenital diaphragmatic hernia (胎儿先天性膈疝产前超声筛查及妊娠结局分析)Jing Chunli, ,Han Lu, ,Liu Yu, ,Liu Jiao, ,Zhou Qiao...... page:186-192Clinical...

Αλέξανδρος Γ. Σφακιανάκης

1h

Critical Care Medicine

Patient Outcomes and Cost-Effectiveness of a Sepsis Care Quality Improvement Program in a Health System Objectives: Assess patient outcomes in patients with suspected infection and the cost-effectiveness of implementing a quality improvement program. Design, Setting, and Participants: We conducted an observational single-center study of 13,877 adults with suspected infection between March 1, 2014, and July 31, 2017. The 18-month period before and after the effective date for mandated reporting of the sepsis bundle was examined. The Sequential Organ Failure Assessment score and culture and antibiotic orders were used to identify patients meeting Sepsis-3 criteria from the electronic health record. Interventions: The following interventions were performed as follows: 1) multidisciplinary sepsis committee with sepsis coordinator and data abstractor; 2) education campaign; 3) electronic health record tools; and 4) a Modified Early Warning System. Main Outcomes and Measures: Primary health outcomes were in-hospital death and length of stay. The incremental cost-effectiveness ratio was calculated and the empirical 95% CI for the incremental cost-effectiveness ratio was estimated from 5,000 bootstrap samples. Results: In multivariable analysis, the odds ratio for in-hospital death in the post- versus pre-implementation periods was 0.70 (95% CI, 0.57–0.86) in those with suspected infection, and the hazard ratio for time to discharge was 1.25 (95% CI, 1.20–1.29). Similarly, a decrease in the odds for in-hospital death and an increase in the speed to discharge was observed for the subset that met Sepsis-3 criteria. The program was cost saving in patients with suspected infection (–$272,645.7; 95% CI, –$757,970.3 to –$79,667.7). Cost savings were also observed in the Sepsis-3 group. Conclusions and Relevance: Our health system's program designed to adhere to the sepsis bundle metrics led to decreased mortality and length of stay in a cost-effective manner in a much larger catchment than just the cohort meeting the Centers for Medicare and Medicaid Services measures. Our single-center model of interventions may serve as a practice-based benchmark for hospitalized patients with suspected infection. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/ccmjournal). Dr. Afshar received funding from the National Institute of Health (NIH)/National Institute of Alcoholism and Alcohol Abuse (K23 AA024503). Dr. Churpek received funding from the NIH/National Institute of General Medical Sciences (R01 GM 123193), NIH/National Heart, Lung, and Blood Institute (K08 HL121080), American Thoracic Society Foundation: Recognition Award for Early Career Investigators, and from a patent pending (ARCD. P0535US.P2). He received support for article research from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: Majid.afshar@lumc.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

External Validation of Two Models to Predict Delirium in Critically Ill Adults Using Either the Confusion Assessment Method-ICU or the Intensive Care Delirium Screening Checklist for Delirium Assessment Objectives: To externally validate two delirium prediction models (early prediction model for ICU delirium and recalibrated prediction model for ICU delirium) using either the Confusion Assessment Method-ICU or the Intensive Care Delirium Screening Checklist for delirium assessment. Design: Prospective, multinational cohort study. Setting: Eleven ICUs from seven countries in three continents. Patients: Consecutive, delirium-free adults admitted to the ICU for greater than or equal to 6 hours in whom delirium could be reliably assessed. Interventions: None. Measurements and Main Results: The predictors included in each model were collected at the time of ICU admission (early prediction model for ICU delirium) or within 24 hours of ICU admission (recalibrated prediction model for ICU delirium). Delirium was assessed using the Confusion Assessment Method-ICU or the Intensive Care Delirium Screening Checklist. Discrimination was determined using the area under the receiver operating characteristic curve. The predictive performance was determined for the Confusion Assessment Method-ICU and Intensive Care Delirium Screening Checklist cohort, and compared with both prediction models' original reported performance. A total of 1,286 Confusion Assessment Method-ICU–assessed patients and 892 Intensive Care Delirium Screening Checklist–assessed patients were included. Compared with the area under the receiver operating characteristic curve of 0.75 (95% CI, 0.71–0.79) in the original study, the area under the receiver operating characteristic curve of the early prediction model for ICU delirium was 0.67 (95% CI, 0.64–0.71) for delirium as assessed using the Confusion Assessment Method-ICU and 0.70 (95% CI, 0.66–0.74) using the Intensive Care Delirium Screening Checklist. Compared with the original area under the receiver operating characteristic curve of 0.77 (95% CI, 0.74–0.79), the area under the receiver operating characteristic curve of the recalibrated prediction model for ICU delirium was 0.75 (95% CI, 0.72–0.78) for assessing delirium using the Confusion Assessment Method-ICU and 0.71 (95% CI, 0.67–0.75) using the Intensive Care Delirium Screening Checklist. Conclusions: Both the early prediction model for ICU delirium and recalibrated prediction model for ICU delirium are externally validated using either the Confusion Assessment Method-ICU or the Intensive Care Delirium Screening Checklist for delirium assessment. Per delirium prediction model, both assessment tools showed a similar moderate-to-good statistical performance. These results support the use of either the early prediction model for ICU delirium or recalibrated prediction model for ICU delirium in ICUs around the world regardless of whether delirium is evaluated with the Confusion Assessment Method-ICU or Intensive Care Delirium Screening Checklist. This work was performed at the Radboud University Medical Center, Tufts Medical Center, The Canberra Hospital, Antwerp University Hospital, Erasmus Medical Center, Jeroen Bosch Ziekenhuis, Rigshospitalet, Mount Sinai Hospital, Medisch Spectrum Twente, Hospital Espírito Santo, and University Medical Centre Utrecht. Drs. Wassenaar, Schoonhoven, Donders, Pickkers, and van den Boogaard contributed to study concept and design. Drs. Wassenaar, Devlin, and van Haren, Slooter, Jorens, van der Jagt, Simons, Egerod, Burry, and Beishuizen, and Mr. Matos contributed to acquisition of data. Drs. Wassenaar, Donders, and van den Boogaard contributed to statistical analysis. Drs. Wassenaar, Schoonhoven, Donders, Pickkers, and van den Boogaard contributed to analysis and interpretation of data. Dr. Wassenaar contributed to drafting of the article. Drs. Schoonhoven, Devlin, and van Haren, Slooter, Jorens, van der Jagt, Simons, Egerod, Burry, and Beishuizen, Mr. Matos, and Drs. Donders, Pickkers, and van den Boogaard contributed to critical revision of the article for important intellectual content. Drs. Schoonhoven, Pickkers, and van den Boogaard contributed to study supervision. All authors read and approved the final article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/ccmjournal). Dr. Pickkers received funding from AM-Pharma, Adrenomed, Exponential Biotherapies, and Baxter Consultation (speaking fee). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: mark.vandenboogaard@radboudumc.nl Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Declining Mortality of Cirrhotic Variceal Bleeding Requiring Admission to Intensive Care: A Binational Cohort Study Objectives: We aimed to describe changes over time in admissions and outcomes, including length of stay, discharge destinations, and mortality of cirrhotic patients admitted to the ICU for variceal bleeding, and to compare it to the outcomes of those with other causes of ICU admissions. Design: Retrospective analysis of data captured prospectively in the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database. Settings: One hundred eighty-three ICUs in Australia and New Zealand. Patients: Consecutive admissions to these ICUs for upper gastrointestinal bleeding related to varices in patients with cirrhosis between January 1, 2005, and December 31, 2016. Interventions: None. Measurements and Main Results: ICU admissions for variceal bleeding in cirrhotic patients accounted for 4,003 (0.6%) of all 720,425 nonelective ICU admissions. The proportion of ICU admissions for variceal bleeding fell significantly from 0.8% (83/42,567) in 2005 to 0.4% (53/80,388) in 2016 (p < 0.001). Hospital mortality rate was significantly higher within admissions for variceal bleeding compared with nonelective ICU admissions (20.0% vs 15.7%; p < 0.0001), but decreased significantly over time, from 24.6% in 2005 to 15.8% in 2016 (annual decline odds ratio, 0.93; 95% CI, 0.90–0.96). There was no difference in the reduction in mortality from variceal bleeding over time between liver transplant and nontransplant centers (p = 0.26). Conclusions: Admission rate to ICU and mortality of cirrhotic patients with variceal bleeding has declined significantly over time compared with other causes of ICU admissions with the outcomes comparable between liver transplant and nontransplant centers. Dr. Majeed helped with drafting of the article, interpretation of the data, and study concept. Dr. Majumdar helped with preparation and critical review of the article. Dr. Bailey helped with data acquisition, statistical analysis, and critical review of the article. Drs. Kemp and Bellomo helped with preparation and critical review of the article. Mr. Pilcher helped with data acquisition, review of the article, interpretation of the data, and study concept. Dr. Roberts helped with preparation and critical review of the article, and study concept. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/ccmjournal). Supported, in part, by grants from the Alfred Hospital Department of Gastroenterology and the Australian and New Zealand Intensive Care Research Centre. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: a.majeed@alfred.org.au Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Antimicrobial Disposition During Pediatric Continuous Renal Replacement Therapy Using an Ex Vivo Model Objectives: Little is known on the impact of continuous renal replacement therapy on antimicrobial dose requirements in children. In this study, we evaluated the pharmacokinetics of commonly administered antimicrobials in an ex vivo continuous renal replacement therapy model. Design: An ex vivo continuous renal replacement therapy circuit was used to evaluate drug-circuit interactions and determine the disposition of five commonly used antimicrobials (meropenem, piperacillin, liposomal amphotericin B, caspofungin, and voriconazole). Setting: University research laboratory. Patients: None. Interventions: Antimicrobials were administered into a reservoir containing whole human blood. The reservoir was connected to a pediatric continuous renal replacement therapy circuit programmed for a 10 kg child. Continuous renal replacement therapy was performed in the hemodiafiltration mode and in three phases correlating with three different continuous renal replacement therapy clearance rates: 1) no clearance (0 mL/kg/hr, to measure adsorption), 2) low clearance (20 mL/kg/hr), and 3) high clearance (40 mL/kg/hr). Blood samples were drawn directly from the reservoir at baseline and at 5, 20, 60, and 180 minutes during each phase. Five independent continuous renal replacement therapy runs were performed to assess inter-run variability. Antimicrobial concentrations were measured using validated liquid chromatography-mass spectrometry assays. A closed-loop, flow-through pharmacokinetic model was developed to analyze concentration-time profiles for each drug. Measurements and Main Results: Circuit adsorption of antimicrobials ranged between 13% and 27%. Meropenem, piperacillin, and voriconazole were cleared by the continuous renal replacement therapy circuit and clearance increased with increasing continuous renal replacement therapy clearance rates (7.66 mL/min, 4.97 mL/min, and 2.67 mL/min, respectively, for high continuous renal replacement therapy clearance). Amphotericin B and caspofungin had minimal circuit clearance and did not change with increasing continuous renal replacement therapy clearance rates. Conclusions: Careful consideration of drug-circuit interactions during continuous renal replacement therapy is essential for appropriate drug dosing in critically ill children. Antimicrobials have unique adsorption and clearance profiles during continuous renal replacement therapy, and this knowledge is important to optimize antimicrobial therapy. Drs. Purohit and Elkomy shared equally in the first authorship. Drs. Purohit and Elkomy contributed equally to be the first author on this article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/ccmjournal). Supported, in part, by grant from the Child Health Research Institute, Lucile Packard Foundation for Children's Health and the Stanford Clinical and Translational Science Award UL1 TR001085. Dr. Purohit disclosed that this work was supported by the National Institutes of Health and the Child Health Research Institute, Lucile Packard Foundation for Children's Health and the Stanford Clinical and Translational Science Award UL1 TR001085. Dr. Drover received funding from Masimo. The remaining authors have disclosed that they do not have any potential conflicts of interest. This work was performed at Stanford University School of Medicine. For information regarding this article, E-mail: drpurohit22@gmail.com Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Implementation of a Bundled Consent Process in the ICU: A Single-Center Experience Objectives: A bundled consent process, where patients or surrogates provide consent for all commonly performed procedures on a single form at the time of ICU admission, has been advocated as a method for improving both rates of documented consent and patient/family satisfaction, but there has been little published literature about the use of bundled consent. We sought to determine how residents in an academic medical center with a required bundled consent process actually obtain consent and how they perceive the overall value, efficacy, and effects on families of this approach. Design: Single-center survey study. Setting: Medical ICUs in an urban academic medical center. Subjects: Internal medicine residents. Interventions: We administered an online survey about bundled consent use to all residents. Quantitative and qualitative data were analyzed. Measurements and Main Results: One-hundred two of 164 internal medicine residents (62%) completed the survey. A majority of residents (55%) reported grouping procedures and discussing general risks and benefits; 11% reported conducting a complete informed consent discussion for each procedure. Respondents were divided in their perception of the value of bundled consent, but most (78%) felt it scared or stressed families. A minority (26%) felt confident that they obtained valid informed consent for critical care procedures with the use of bundled consent. An additional theme that emerged from qualitative data was concern regarding the validity of anticipatory consent. Conclusions: Resident physicians experienced with the use of bundled consent in the ICU held variable perceptions of its value but raised concerns about the effect on families and the validity of consent obtained with this strategy. Further studies are necessary to further explore what constitutes best practice for informed consent in critical care. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/ccmjournal). Dr. Stevens is supported by Agency for Healthcare Research and Quality Grant 5K08HS024288 and a Clinical Scientist Development Award from the Doris Duke Charitable Foundation. The remaining authors have disclosed that they do not have any conflicts of interest. For information regarding this article, E-mail: aanandai@bidmc.harvard.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Agreement With Consensus Statements on End-of-Life Care: A Description of Variability at the Level of the Provider, Hospital, and Country Objectives: To develop an enhanced understanding of factors that influence providers' views about end-of-life care, we examined the contributions of provider, hospital, and country to variability in agreement with consensus statements about end-of-life care. Design and Setting: Data were drawn from a survey of providers' views on principles of end-of-life care obtained during the consensus process for the Worldwide End-of-Life Practice for Patients in ICUs study. Subjects: Participants in Worldwide End-of-Life Practice for Patients in ICUs included physicians, nurses, and other providers. Our sample included 1,068 providers from 178 hospitals and 31 countries. Interventions: None. Measurements and Main Results: We examined views on cardiopulmonary resuscitation and withholding/withdrawing life-sustaining treatments, using a three-level linear mixed model of responses from providers within hospitals within countries. Of 1,068 providers from 178 hospitals and 31 countries, 1% strongly disagreed, 7% disagreed, 11% were neutral, 44% agreed, and 36% strongly agreed with declining to offer cardiopulmonary resuscitation when not indicated. Of the total variability in those responses, 98%, 0%, and 2% were explained by differences among providers, hospitals, and countries, respectively. After accounting for provider characteristics and hospital size, the variance partition was similar. Results were similar for withholding/withdrawing life-sustaining treatments. Conclusions: Variability in agreement with consensus statements about end-of-life care is related primarily to differences among providers. Acknowledging the primary source of variability may facilitate efforts to achieve consensus and improve decision-making for critically ill patients and their family members at the end of life. Worldwide End-of-Life Practice for Patients in ICUs (WELPICUS) Investigators Steering Committee are as follows: Charles L. Sprung (chairman), Elie Azoulay, J. Randall Curtis, Jozef Kesecioglu, Paulo Maia, Andrej Michalsen, Moshe Sonnenblick, and Robert Truog. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/ccmjournal). Dr. De Robertis received funding from Masimo and Aguettant. Dr. Kross received funding from the National Institutes of Health. Dr. Michalsen received funding from lectures from ViDia Hospital, Stuttgart Hospital, and Konstanz Hospital. Dr. Sprung's institution received funding from Asahi Kasei Pharma America (data monitoring committee) and LeukoDx (consultant and principal investigator of study). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: along11@uw.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Effect of Prone Positioning on Intraocular Pressure in Patients With Acute Respiratory Distress Syndrome Objectives: To evaluate the effect of prolonged duration of prone position (with head laterally rotated) on intraocular pressure in acute respiratory distress syndrome patients. Design: Prospective observational study. Setting: University hospital ICU. Patients: Twenty-five acute respiratory distress syndrome patients, age 60 years (51–67 yr), Sequential Organ Failure Assessment score 10 (10–12), PaO2/FIO2 ratio of 90 (65–120), and all in septic shock. Interventions: None. Measurements and Main Results: Intraocular pressure (in mm Hg) measured by hand-held applanation tonometer, at different time points. Before prone (in both eyes): at 30–45° head-end elevation position (THE pre-prone), in supine position just before turning prone (Tsupine pre-prone); during prone (in nondependent eye): at 10 minutes (T10 prone), 30 minutes (T30 prone), and at just before end of prone session (Tend-prone). After end of prone session (both eyes): at 5 minutes (T5 supine post-prone), 10 minutes (T10 HE post-prone), 15 minutes (T15 HE post-prone), and 30 minutes (T30 HE post-prone). Median duration of prone position was 14 hours (12–18 hr). Median intraocular pressure increased significantly (p ≤ 0.001) in both eyes. In dependent eye, from 15 (12–19) at THE pre-prone to 24, 21, 19, and 16 at T5 supine post-prone, T10 HE post-prone, T15 HE post-prone, and T30 HE post-prone respectively, whereas in nondependent eye from 14 (12–18.5) at THE pre-prone to 23, 25, 32, 25, 22, 20, and 17 at T10 prone, T30 prone, Tend-prone, T5 supine post-prone, T10 HE post-prone, T15 HE post-prone, and T30 HE post-prone respectively. Bland-Altman plot analysis showed significant linear relationship (r = 0.789; p ≤ 0.001) with good agreement between rise in mean intraocular pressure of the both eyes (dependent eye and nondependent eye) with their paired differences after the end of different duration of prone session (T5 supine post-prone). Conclusions: There is significant increase in intraocular pressure due to prone positioning among acute respiratory distress syndrome patients. Intraocular pressure increases as early as 10 minutes after proning, with increasing trend during prone position, which persisted even at 30 minutes after the end of post prone session although with decreasing trend. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/ccmjournal). Presented, in part, as an abstract at the ESICM LIVES (September 27, 2017, Vienna, Austria) and ISCCM CRITICARE (March 8, 2018, Varanasi, India) meetings. Dr. Gurjar received funding from Intramural and Extramural Research Grant (unrelated to submitted work), and he received funding from Jaypee Medical Publishers, New Delhi, India (royalties). The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: m.gurjar@rediffmail.com Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Why My Steroid Trials in Septic Shock Were "Positive"? No abstract available

Quantitative Electroencephalogram Trends Predict Recovery in Hypoxic-Ischemic Encephalopathy Objectives: Electroencephalogram features predict neurologic recovery following cardiac arrest. Recent work has shown that prognostic implications of some key electroencephalogram features change over time. We explore whether time dependence exists for an expanded selection of quantitative electroencephalogram features and whether accounting for this time dependence enables better prognostic predictions. Design: Retrospective. Setting: ICUs at four academic medical centers in the United States. Patients: Comatose patients with acute hypoxic-ischemic encephalopathy. Interventions: None. Measurements and Main Results: We analyzed 12,397 hours of electroencephalogram from 438 subjects. From the electroencephalogram, we extracted 52 features that quantify signal complexity, category, and connectivity. We modeled associations between dichotomized neurologic outcome (good vs poor) and quantitative electroencephalogram features in 12-hour intervals using sequential logistic regression with Elastic Net regularization. We compared a predictive model using time-varying features to a model using time-invariant features and to models based on two prior published approaches. Models were evaluated for their ability to predict binary outcomes using area under the receiver operator curve, model calibration (how closely the predicted probability of good outcomes matches the observed proportion of good outcomes), and sensitivity at several common specificity thresholds of interest. A model using time-dependent features outperformed (area under the receiver operator curve, 0.83 ± 0.08) one trained with time-invariant features (0.79 ± 0.07; p < 0.05) and a random forest approach (0.74 ± 0.13; p < 0.05). The time-sensitive model was also the best-calibrated. Conclusions: The statistical association between quantitative electroencephalogram features and neurologic outcome changed over time, and accounting for these changes improved prognostication performance. Drs. Ghassemi and Amorim contributed equally as co-first authors of this work. The Critical Care Electroencephalogram Monitoring Research Consortium Board consists of: Chair: Brandon M. Westover, MD, PhD; Vice-Chair: Emily Gilmore, MD; Secretary: Aaron Struck, MD; Member-at-Large: Nicholas Gaspard, MD, PhD; Immediate Past Chair: Jong Woo Lee, MD, PhD; and Past Chair: Nicholas S. Abend, MD, MSCE. Drs. Ghassemi, Amorim, Lee, Cash, Brown, Mark, and Westover contributed to conception and design of the study. Drs. Ghassemi, Amorim, and Westover contributed to analysis of data. Drs. Ghassemi, Amorim, and Westover contributed to preparing the figures. Drs. Ghassemi and Amorim, Mr. Al Hanai, Drs. Lee, Herman, Sivaraju, and Gaspard, Mr. Biswal, Mr. Moura Junior, and Dr. Westover contributed to data acquisition. Drs. Ghassemi and Amorim, Mr. Al Hanai, Drs. Lee, Herman, Sivaraju, and Gaspard, Mr. Biswal, Mr. Moura Junior, and Drs. Cash, Brown, Mark, and Westover contributed to drafting the text. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/ccmjournal). Supported, in part, by grants from National Institutes of Health (NIH) 1R01NS102190, 1R01NS102574, and 1R01NS107291 (to Dr. Westover); R01GM104987 (to Dr. Mark); T32HL007901, T90DA22759, and T32EB001680 (to Dr. Ghassemi); National Institute of Neurological Disorders and Stroke 1K23NS090900 (to Dr. Westover); Salerno foundation (M.G.M.); Neurocritical Care Society research training fellowship and American Heart Association postdoctoral fellowship (to Dr. Amorim); and Andrew David Heitman Neuroendovascular Research Fund and the Rappaport Foundation (to Dr. Westover). Preliminary findings of this study were presented at the 14th Annual Neurocritical Care Society Meeting, National Harbor, MD, September 15–18, 2016. Dr. Amorim's institution received funding from the National Institutes of Health (NIH), Neurocritical Care Society, and American Heart Association. Drs. Amorim, Mark, and Westover received support for article research from the NIH. Dr. Lee received funding from SleepMed/DigiTrace, Advance Medical, and United Diagnostics. Drs. Lee's and Mark's institutions received funding from the NIH. Dr. Herman's institution received funding from UCB Pharma, Sage Therapeutics, Neurospace, Epilepsy Therapy Development Project, Acorda Therapeutics, Pfizer, and Philips. Dr. Hirsch's institution received funding from Upsher-Smith and Monteris. He received funding from Adamas; consultation fees for advising from Aquestive, Ceribell, Eisai, and Medtronic; honoraria for speaking from Neuropace; and royalties for authoring chapters for UpToDate-Neurology and from Wiley for coauthoring a book on electroencephalograms in critical care. Dr. Scirica's institution received funding from Merck, Eisai, and Novartis, and he received consulting fees from AbbVie, Allergan, AstraZeneca, Boehringer Ingelheim, Covance, Eisai, Elsevier Practice Update Cardiology, GlaxoSmithKline, Lexicon, Merck, NovoNordisk, Sanofi, and equity in Health [at] Scale. Dr. Brown's institution received funding from Massachusetts General Hospital and Massachusetts Institute of Technology. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: mwestover@mgh.harvard.edu; edilbertoamorim@gmail.com. Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Enablers and Barriers to Implementing ICU Follow-Up Clinics and Peer Support Groups Following Critical Illness: The Thrive Collaboratives Objectives: Data are lacking regarding implementation of novel strategies such as follow-up clinics and peer support groups, to reduce the burden of postintensive care syndrome. We sought to discover enablers that helped hospital-based clinicians establish post-ICU clinics and peer support programs, and identify barriers that challenged them. Design: Qualitative inquiry. The Consolidated Framework for Implementation Research was used to organize and analyze data. Setting: Two learning collaboratives (ICU follow-up clinics and peer support groups), representing 21 sites, across three continents. Subjects: Clinicians from 21 sites. Measurement and Main Results: Ten enablers and nine barriers to implementation of "ICU follow-up clinics" were described. A key enabler to generate support for clinics was providing insight into the human experience of survivorship, to obtain interest from hospital administrators. Significant barriers included patient and family lack of access to clinics and clinic funding. Nine enablers and five barriers to the implementation of "peer support groups" were identified. Key enablers included developing infrastructure to support successful operationalization of this complex intervention, flexibility about when peer support should be offered, belonging to the international learning collaborative. Significant barriers related to limited attendance by patients and families due to challenges in creating awareness, and uncertainty about who might be appropriate to attend and target in advertising. Conclusions: Several enablers and barriers to implementing ICU follow-up clinics and peer support groups should be taken into account and leveraged to improve ICU recovery. Among the most important enablers are motivated clinician leaders who persist to find a path forward despite obstacles. This does not necessarily represent the views of the U.S. government or Department of Veterans Affairs. Drs. Haines, McPeake, Boehm, and Sevin had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All other authors contributed substantially to the study design, data analysis and interpretation, and the writing of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/ccmjournal). Drs. Haines's, McPeake's, Hibbert's, Boehm's, Aparanji's, Bastin's, Drumright's, Holdsworth's, Johnson's, Kloos's, Meyer's, Quasim's, Saft's, Stollings's, and Sevin's institutions received funding from the Society of Critical Care Medicine (SCCM). Dr. Haines, McPeake, Boehm, and Sevin are currently receiving funding from SCCM to undertake this work, although the supporting source had no input into the design, data collection and analysis, although approved the final article for submission for publication. Dr. Boehm's institution received funding from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) (1K12HL137943-01) and Vanderbilt Clinical and Translational Science Award. The funding source reviewed and approved the article for submission. Drs. Boehm and Iwashyna received support for article research from the NIH. Dr. Hope's institution received funding from NHLBI K01-HL140279, and he received funding from American Association of Critical Care Nurses. Dr. Khan's institution received funding from the NIH. Dr. Kross's institution received funding from the NIH and the American Lung Association. Dr. Quasim's institution received funding from the Health Foundation. Dr. Saft received funding from Medtronic. Dr. Stollings received funding from Intermountain Health. Dr. Weinhouse received funding from UptoDate. Dr. Hopkins's institution received funding from Intermountain Research and Medical Foundation. Dr. Iwashyna's institution received funding from NIH K12, and he disclosed government work. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: Kimberley.haines@wh.org.au Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Autoimmunity

Cellular aging over 13 years associated with incident antinuclear antibody positivity in the Baltimore Longitudinal Study of Aging Publication date: Available online 11 July 2019 Source: Journal of Autoimmunity Author(s): Helen C.S. Meier, Christine G. Parks, Hans B. Liu, Dale P. Sandler, Eleanor M. Simonsick, Kevin Deane, Nan-ping Weng Abstract Age-associated increases in antinuclear antibodies (ANA) in the general population are commonly noted but the mechanisms underlying this observation are unclear. This study aims to evaluate whether shorter peripheral blood mononuclear cell (PBMC) telomere length, a marker of more advanced biological age, is associated with ANA positivity prevalence and incidence in middle and older aged autoimmune disease-free individuals from the Baltimore Longitudinal Study of Aging (BLSA). Telomere length was measured by Southern Blot and categorized into tertiles. ANA was measured in a 1:80 and a 1:160 dilution of sera by immunofluorescence using HEp-2 cells (seropositive = 3 or 4). Multiple logistic regression was used to estimate the odds ratios and 95% confidence intervals of ANA positivity comparing the shorter tertiles of telomere length to the longest tertile for two cross-sectional points in time and then longitudinally to assess the association between shorter telomere length and incident ANA positivity. Cross-sectional analyses were adjusted for sex, race and BMI (N = 368 baseline, N = 370 follow-up) and longitudinal analyses were adjusted for sex, race, BMI and time between baseline and follow-up (N = 246). No statistically significant cross-sectional associations were observed at baseline or follow-up. Among those where ANA negative at baseline, individuals with shorter telomeres were more likely to be ANA positive at follow-up, an average 13 years later. Individuals with short telomeres at both time periods were more likely to be ANA positive. Findings suggest that ANA positivity in the general population may be indicative of immune dysfunction resulting from advanced cellular aging processes.

DNGR1-mediated deletion of A20/Tnfaip3 in dendritic cells alters T and B-cell homeostasis and promotes autoimmune liver pathology Publication date: Available online 9 July 2019 Source: Journal of Autoimmunity Author(s): Tridib Das, Ingrid M. Bergen, Thomas Koudstaal, Jennifer A.C. van Hulst, Geert van Loo, André Boonstra, Thomas Vanwolleghem, Patrick S.C. Leung, M. Eric Gershwin, Rudi W. Hendriks, Mirjam Kool Abstract Dendritic cells (DCs) are central regulators of tolerance versus immunity. The outcome depends amongst others on DC subset and activation status. Whereas CD11b+ type 2 conventional DCs (cDC2s) initiate proinflammatory helper T (Th)-cell responses, CD103+ cDC1s are crucial for regulatory T-cell (Treg) induction and CD8+ T-cell activation. DC activation is controlled by the transcription factor NF-κB. Ablation of A20/Tnfaip3, a critical regulator of NF-κB activation, in DCs leads to constitutive DC activation and development of systemic autoimmunity. We hypothesized that the activation status of cDCs controls the development of autoimmunity. To target cDCs, DNGR1(Clec9a)-cre-mediated excision of A20/Tnfaip3 was used through generation of Tnfaip3fl/flxClec9a+/cre (Tnfaip3DNGR1−KO) mice. Immune cell activation was evaluated at 31-weeks of age. We found that DNGR1-cre-mediated deletion of A20/Tnfaip3 resulted in liver pathology characterized by inflammatory infiltrates adjacent to the portal triads. Both cDC subsets as well as monocyte-derived DCs (moDCs) in Tnfaip3DNGR1−KO livers harbored an activated phenotype. Specifically, the costimulatory molecule CD40 in liver cDCs and moDCs was regulated by A20/Tnfaip3 expression. Livers from Tnfaip3DNGR1−KO mice had augmented proportions of Th1, Th17, Treg, and follicular Th (Tfh)-cells compared to control mice, accompanied by an increase in IgA-producing plasma cells. Serum IgA from Tnfaip3DNGR1−KO mice recognized self-proteins, specifically cytoplasmic proteins in liver periportal regions. These data show that enhanced activation of cDCs and moDCs, due to A20/Tnfaip3 ablation, promotes the development of organ-specific autoimmunity but not systemic autoimmunity. This model could be useful to examine the pathobiological processes contributing to autoimmune liver diseases.

Selective deletion of Eos (Ikzf4) in T-regulatory cells leads to loss of suppressive function and development of systemic autoimmunity Publication date: Available online 8 July 2019 Source: Journal of Autoimmunity Author(s): Ameya S. Gokhale, Arunakumar Gangaplara, Maria Lopez-Occasio, Angela M. Thornton, Ethan M. Shevach Abstract Eos (lkzf4) is a member of the Ikaros family of transcription factors and is preferentially expressed in T-regulatory (Treg) cells. However, the role of Eos in Treg function is controversial. One study using siRNA knock down of Eos demonstrated that it was critical for Treg suppressor function. In contrast, Treg from mice with a global deficiency of Eos had normal Treg function in vitro and in vivo. To further dissect the function of Eos in Tregs, we generated mice with a conditional knock out of Eos in Treg cells (lkzf4fl/fl X Foxp3YFP−cre, Eos cKO). Deletion of Eos in Treg resulted in activation of CD4+Foxp3- and CD8+ T cells at the age of 3 months, cellular infiltration in non-lymphoid tissues, hyperglobulinemia, and anti-nuclear antibodies. While Tregs from Eos cKO mice displayed normal suppressive function in vitro, Eos cKO mice developed severe Experimental Autoimmune Encephalomyletis (EAE) following immunization with myelin oligodendrocyte glycoprotein (MOG) and Eos cKO Treg were unable to suppress Inflammatory Bowel Disease (IBD). Eos cKO mice had decreased growth of the transplantable murine adenocarcinoma MC38 tumor accompanied by enhanced IFN-γ/TNF-α production by CD8+ T cells in tumor draining lymph nodes. Mice with a global deficiency of Eos or a deficiency of Eos only in T cells developed autoimmunity at a much older age (12 months or 7–8 months, respectively). Taken together, Eos appears to play an essential role in multiple aspects of Treg suppressor function, but also plays an as yet unknown role in the function of CD4+Foxp3- and CD8+ T cells and potentially in non-T cells.

Predicting drug-free remission in rheumatoid arthritis: A prospective interventional cohort study Publication date: Available online 4 July 2019 Source: Journal of Autoimmunity Author(s): Kenneth F. Baker, Andrew J. Skelton, Dennis W. Lendrem, Adam Scadeng, Ben Thompson, Arthur G. Pratt, John D. Isaacs Abstract Background Many patients with rheumatoid arthritis (RA) achieve disease remission with modern treatment strategies. However, having achieved this state, there are no tests that predict when withdrawal of therapy will result in drug-free remission rather than flare. We aimed to identify predictors of drug-free remission in RA. Methods The Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) Study was a unique, prospective, interventional cohort study of complete and abrupt cessation of conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs). Patients with RA of at least 12 months duration and in clinical and ultrasound remission discontinued DMARDs and were monitored for six months. The primary outcome was time-to-flare, defined as disease activity score in 28 joints with C-reactive protein (DAS28-CRP) ≥ 2.4. Baseline clinical and ultrasound measures, circulating inflammatory biomarkers, and peripheral CD4+ T cell gene expression were assessed for their ability to predict time-to-flare and flare/remission status by Cox regression and receiver-operating characteristic (ROC) analysis respectively. Results 23/44 (52%) eligible patients experienced an arthritis flare after a median (IQR) of 48 (31.5–86.5) days following DMARD cessation. A composite score incorporating five baseline variables (three transcripts [FAM102B, ENSG00000228010, ENSG00000227070], one cytokine [interleukin-27], one clinical [Boolean remission]) differentiated future flare from drug-free remission with an area under the ROC curve of 0.96 (95% CI 0.91–1.00), sensitivity 0.91 (0.78–1.00) and specificity 0.95 (0.84–1.00). Conclusion We provide proof-of-concept evidence for predictors of drug-free remission in RA. If validated, these biomarkers could help to personalize immunosuppressant withdrawal: a therapy paradigm shift with ensuing patient and economic benefits.

PD-1 aborts the activation trajectory of autoreactive CD8+ T cells to prohibit their acquisition of effector functions Publication date: Available online 2 July 2019 Source: Journal of Autoimmunity Author(s): Hikari Okamura, Il-mi Okazaki, Kenji Shimizu, Takumi Maruhashi, Daisuke Sugiura, Reina Mizuno, Taku Okazaki Abstract Anti-PD-1 therapy can induce eradication of tumors and immune-related adverse events (irAEs) in humans and model animals. However, how anti-PD-1 therapy modifies cellular phenotypes of CD8+ T cells to destroy tumors and damage self-tissues remains to be clarified. Here we performed single cell mRNA expression profiling of autoreactive CD8+ T cells under or beyond PD-1 suppression in target tissues and reconstructed their activation trajectory. Autoreactive CD8+ T cells went through four activation phases and PD-1 strongly attenuated the transition from the second- to the third-phase, where effector functions were acquired. Shifts in cluster composition of autoreactive CD8+T cells markedly reflected the severity of autoimmunity. In addition, genes up-regulated along the activation-trajectory in autoimmunity were highly expressed in responders of melanoma patients in anti-PD-1 therapy, suggesting that tumor-specific T cells need to be activated in a similar trajectory to destroy tumors in human patients upon PD-1 blockade. These findings reveal that PD-1 blockade facilitates the activation trajectory of CD8+ T cells to boost their effector functions. Targeted manipulation of the trajectory could lead to new therapeutic opportunities.

Extracellular traps and PAD4 released by macrophages induce citrullination and auto-antibody production in autoimmune arthritis Publication date: Available online 2 July 2019 Source: Journal of Autoimmunity Author(s): Mohey Eldin M. El Shikh, Riham El Sayed, Alessandra Nerviani, Katriona Goldmann, Christopher Robert John, Rebecca Hands, Liliane Fossati-Jimack, Myles J. Lewis, Costantino Pitzalis Abstract The mechanisms underlying the transition of rheumatoid arthritis (RA) systemic autoimmunity to the joints remain largely unknown. Here, we demonstrate that macrophages in the secondary lymphoid organs (SLOs) and synovial ectopic lymphoid-like structures (ELSs) express peptidylarginine deiminase 4 (PAD4) in murine collagen induced arthritis (CIA) and synovial biopsies from RA patients. Moreover, peptidyl citrulline colocalized with macrophages in SLOs and ELSs, and depletion of macrophages in CIA decreased lymphoid tissue citrullination and serum anti-citrullinated protein/peptide antibody (ACPA) levels. Furthermore, PAD was released from activated murine and RA synovial tissue and fluid (SF) macrophages which functionally deiminated extracellular proteins/peptides in vitro. Additionally, activated murine and SF macrophages displayed macrophage extracellular trap formation (METosis) and release of intracellular citrullinated histones. Moreover, presentation of citrullinated proteins induced ACPA production in vitro. Thus, lymphoid tissue macrophages contribute to self-antigen citrullination and ACPA production, indicating that their selective targeting would potentially ameliorate citrullination-dependent autoimmune disorders.

The identification of CCL18 as biomarker of disease activity in localized scleroderma Publication date: July 2019 Source: Journal of Autoimmunity, Volume 101 Author(s): J.S. Mertens, E.M.G.J. de Jong, L.L. van den Hoogen, J. Wienke, R.M. Thurlings, M.M.B. Seyger, E.P.A.H. Hoppenreijs, C.A. Wijngaarde, I.M.J.J. van Vlijmen-Willems, E. van den Bogaard, B. Giovannone, F. van Wijk, A. van Royen-Kerkhof, W. Marut, T.R.D. Radstake Abstract Background Localized Scleroderma (LoS) encompasses a group of idiopathic skin conditions characterized by (sub)cutaneous inflammation and subsequent development of fibrosis. Currently, lack of accurate tools enabling disease activity assessment leads to suboptimal treatment approaches. Objective To investigate serum concentrations of cytokines and chemokines implicated in inflammation and angiogenesis in LoS and explore their potential to be utilized as biomarker of disease activity. Additionally, to investigate the implication of potential biomarkers in disease pathogenesis. Methods A 39-plex Luminex immuno-assay was performed in serum samples of 74 LoS and 22 Healthy Controls. The relation between a validated clinical measure of disease activity (mLoSSI) and serum analytes was investigated. Additionally, gene and protein expression were investigated in circulating cells and skin biopsies. Results From the total of 39, 10 analytes (CCL18, CXCL9, CXCL10, CXCL13, TNFRII, Galectin-9, TIE-1, sVCAM, IL-18, CCL19) were elevated in LoS serum. Cluster analysis of serum samples revealed CCL18 as most important analyte to discriminate between active and inactive disease. At individual patient level, CCL18 serum levels correlated strongest with mLoSSI-scores (rs = 0.4604, P < 0.0001) and in longitudinal measures CCL18 concentrations normalised with declining disease activity upon treatment initiation. Additionally, CCL18 was elevated in LoS serum, and not in (juvenile) dermatomyositis or spinal muscular atrophy. Importantly, CCL18 gene and protein expression was increased at the inflammatory border of cutaneous LoS lesions, with normal expression in unaffected skin and circulating immune cells. Conclusion CCL18 is specific for disease activity in LoS thereby providing relevance as a biomarker for this debilitating disease.

CD30L/CD30 protects against psoriasiform skin inflammation by suppressing Th17-related cytokine production by Vγ4+ γδ T cells Publication date: July 2019 Source: Journal of Autoimmunity, Volume 101 Author(s): Dan Yue, Yong You, Xiaoqing Zhang, Biao Wang, Xiao Wang, Ruiqun Qi, Fan Yang, Xin Meng, Yasunobu Yoshikai, Yuanyuan Wang, Xun Sun Abstract Psoriasis is a common, autoimmune, chronic inflammatory skin disease. It has been demonstrated that cutaneous T17 cells play an important pro-inflammatory role in the pathogenesis of psoriasis, through the production of various Th17-related cytokines. Our previous studies have demonstrated that CD30L/CD30 signal plays a pivotal role in the differentiation of CD4+ Th17 cells and Vγ6+γδ T17 cells in the gut-associated lymphoid tissues of mouse. However, its effect on the pathogenesis of psoriasis is unknown. Here, we fully prove that CD30L/CD30 signaling plays a novel protective role in the development of psoriasis in mice, through selective inhibition of CCR6 expression and Th17-related cytokine synthesis in the Vγ4+γδ T17 cell subset. Meanwhile, treatment with agonistic anti-CD30 mAb had a significant therapeutic effect on our psoriasis mouse model. Therefore, the CD30L/CD30 signaling pathway is an ideal target for antibody therapy, which may become a new approach for the immunobiological treatment of psoriasis.

Sex-specific Tau methylation patterns and synaptic transcriptional alterations are associated with neural vulnerability during chronic neuroinflammation Publication date: July 2019 Source: Journal of Autoimmunity, Volume 101 Author(s): Alessandro Didonna, Ester Cantó, Hengameh Shams, Noriko Isobe, Chao Zhao, Stacy J. Caillier, Carlo Condello, Hana Yamate-Morgan, Seema K. Tiwari-Woodruff, Mohammad R.K. Mofrad, Stephen L. Hauser, Jorge R. Oksenberg Abstract The molecular events underlying the transition from initial inflammatory flares to the progressive phase of multiple sclerosis (MS) remain poorly understood. Here, we report that the microtubule-associated protein (MAP) Tau exerts a gender-specific protective function on disease progression in the MS model experimental autoimmune encephalomyelitis (EAE). A detailed investigation of the autoimmune response in Tau-deficient mice excluded a strong immunoregulatory role for Tau, suggesting that its beneficial effects are presumably exerted within the central nervous system (CNS). Spinal cord transcriptomic data show increased synaptic dysfunctions and alterations in the NF-kB activation pathway upon EAE in Tau-deficient mice as compared to wildtype animals. We also performed the first comprehensive characterization of Tau post-translational modifications (PTMs) in the nervous system upon EAE. We report that the methylation levels of the conserved lysine residue K306 are significantly decreased in the chronic phase of the disease. By combining biochemical assays and molecular dynamics (MD) simulations, we demonstrate that methylation at K306 decreases the affinity of Tau for the microtubule network. Thus, the down-regulation of this PTM might represent a homeostatic response to enhance axonal stability against an autoimmune CNS insult. The results, altogether, position Tau as key mediator between the inflammatory processes and neurodegeneration that seems to unify many CNS diseases.

Frequency, mutual exclusivity and clinical associations of myositis autoantibodies in a combined European cohort of idiopathic inflammatory myopathy patients Publication date: July 2019 Source: Journal of Autoimmunity, Volume 101 Author(s): Z. Betteridge, S. Tansley, G. Shaddick, H. Chinoy, R.G. Cooper, R.P. New, J.B. Lilleker, J. Vencovsky, L. Chazarain, K. Danko, M. Nagy-Vincze, L. Bodoki, M. Dastmalchi, L. Ekholm, I.E. Lundberg, N. McHugh, UKMyonet contributors Abstract Objectives To determine prevalence and co-existence of myositis specific autoantibodies (MSAs) and myositis associated autoantibodies (MAAs) and associated clinical characteristics in a large cohort of idiopathic inflammatory myopathy (IIM) patients. Methods Adult patients with confirmed IIM recruited to the EuroMyositis registry (n = 1637) from four centres were investigated for the presence of MSAs/MAAs by radiolabelled-immunoprecipitation, with confirmation of anti-MDA5 and anti-NXP2 by ELISA. Clinical associations for each autoantibody were calculated for 1483 patients with a single or no known autoantibody by global linear regression modelling. Results MSAs/MAAs were found in 61.5% of patients, with 84.7% of autoantibody positive patients having a sole specificity, and only three cases (0.2%) having more than one MSA. The most frequently detected autoantibody was anti-Jo-1 (18.7%), with a further 21 specificities each found in 0.2–7.9% of patients. Autoantibodies to Mi-2, SAE, TIF1, NXP2, MDA5, PMScl and the non-Jo-1 tRNA-synthetases were strongly associated (p < 0.001) with cutaneous involvement. Anti-TIF1 and anti-Mi-2 positive patients had an increased risk of malignancy (OR 4.67 and 2.50 respectively), and anti-SRP patients had a greater likelihood of cardiac involvement (OR 4.15). Interstitial lung disease was strongly associated with the anti-tRNA synthetases, anti-MDA5, and anti-U1RNP/Sm. Overlap disease was strongly associated with anti-PMScl, anti-Ku, anti-U1RNP/Sm and anti-Ro60. Absence of MSA/MAA was negatively associated with extra-muscular manifestations. Conclusions Myositis autoantibodies are present in the majority of patients with IIM and identify distinct clinical subsets. Furthermore, MSAs are nearly always mutually exclusive endorsing their credentials as valuable disease biomarkers.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
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alsfakia@gmail.com