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1. chinaXiv:202111.00037 [pdf]


刘羡 ; 曹娟; 孙蓓; 蔡宏伟
Subjects: Medicine, Pharmacy >> Clinical Medicine

目的 围术期死亡患者的危险因素分析和麻醉分级在围术期死亡风险评估中的作用。方法 从2007年1月至2010年12月,中南大学湘雅医院共有106,630例手术,其中有214例术后死亡病例。应用结构化问卷,收集患者基本信息和危险因素,采用Cox模型多因素分析筛选围术期死亡的危险因素。结果 214例死亡病例在ASA分级中的分布,每级病例数并没有随等级的增加而增加;而在麻醉分级的分布中,随着等级的增加,各级的数量也随之增加。多因素分析显示,创伤患者的死亡风险高59%;有心血管风险事件(CRE)患者的死亡风险高38%;麻醉分级每增加一级,围术期死亡风险增加45%;心功能分级每增加一级,死亡风险增加41%。结论 创伤、麻醉分级、心功能分级和CRE与围术期死亡相关。麻醉分级每增加一级,围术期死亡危险性增加45%,麻醉分级作为围术期死亡风险评估标准有良好的代表性。

submitted time 2021-11-26 Hits159Downloads60 Comment 0

2. chinaXiv:202105.00003 [pdf]

SEPRES: Sepsis prediction via a clinical data integration system and real-world studies in the intensive care unit

Chen, Qiyu; Li, Ranran; Lin, Chihche; Lai, Chiming; Chen, Dechang; Qu, Hongping; Huang, Yaling; Lu, Wenlian; Tang, Yaoqing; Li, Lei
Subjects: Medicine, Pharmacy >> Clinical Medicine

Background: Sepsis is vital in critical care medicine, and early detection and intervention are key to survival. We aimed to establish an early warning system for sepsis based on a data integration system that can be implemented in the intensive care unit (ICU). Methods: We trained the LightGBM and multilayer perceptron on the open-source database Medical Information Mart for Intensive Care for sepsis prediction. An ensemble sepsis prediction model was established based on the transfer learning and ensemble learning technique on the private dataset of Ruijin Hospital. The Shapley Additive Explanations analysis was applied to present feature importance on the prediction inference. With the development of data-integrating hub to collect and transmit data from different brands of ICU medical devices, the data integration system was established to receive, integrate, standardize, and store the real-time clinical data. In this way, the sepsis prediction model developed in the ICU of the Ruijin Hospital for the real-world study of sepsis early warning on ICU management. The trial was registered with (NCT05088850). Findings: Our best early warning model achieved an area under the receiver operating characteristic curve (AUC) of 0·9833 in the task of detecting sepsis in 4-h preceding on the open-source database, while our ensemble model achieved an AUC of 0·9065?0·9436 in the retrospective research from 1?5-h preceding on the private database, and 0·8636?0·8992 in real-time real-world studies using the data integration system in the ICU of the Ruijin Hospital. In the continuous early warning process of patients admitted to the ICU, 22 patients who met the diagnostic criteria for sepsis during hospitalization were predicted as positive cases; 29 patients without sepsis were predicted as negative cases. Additionally, 17 patients were predicted as false-positive cases; in six patients with sepsis during ICU stay, the predicted probabilities at different time nodes were all less than the warning threshold 0·7 and predicted as false-negative cases. Interpretation: Machine learning models could allow accurate and real-time inference to detect sepsis onset within 5-h preceding at most with the help of the data integration system. We identified the features such as age, antibiotics, ventilation, and net balance to be important for the sepsis prediction inference. We argue that this system has promising potential to improve ICU management by helping medical practitioners identify at-sepsis-risk patients and prepare for timely diagnosis and intervention. Funding: Shanghai Municipal Science and Technology Major Project, the ZHANGJIANG LAB, and the Science and Technology Commission of Shanghai Municipality.

submitted time 2021-11-22 Hits1676Downloads689 Comment 0

3. chinaXiv:202110.00002 [pdf]

Transplantation of a Beating Heart: A First in Human

Yin Shengli; Rong Jian; Chen Yinghua; Cao Lu; Liu Yunqi; Mo Shaoyan; Li Hanzhao; Jiang Nan; Xiong Mai; Shi Han; Wang Tielong; Shi Yongxu; Zhu Yanlin; Liang Mengya; Xiong Wei; Chen Yili; Xu Guixing; Chen Xiaoxiang; Chen Xiaojun; Yin Meixian
Subjects: Medicine, Pharmacy >> Clinical Medicine

Ischemia and reperfusion injury (IRI), an inevitable component in organ transplantation, contributes to inferior graft survival, compromised organ quality and limitations in organ availability. The heart is most vulnerable to IRI and tolerated ischemic times are very short. We present an entire novel heart transplant procedure during which the donor heart was continuously perfused, oxygenated at normothermia and transplanted while beating. The dynamic electrocardiogram and echocardiogram indicated an absence of ischemic injury and excellent function of the donor heart during the entire procedure. This ischemia-free beating heart transplantation (IFBHT) avoids graft IRI. The approach has thus the potential to improve transplant outcome while improving organ utilization.

submitted time 2021-10-02 Hits3060Downloads306 Comment 0

4. chinaXiv:202105.00003 [pdf]

Sepsis prediction via the clinical data integration system in the ICU

Chen, Qiyu; Li, Ranran; Lin, Zhizhe; Lai, Zhiming; Xue, Peijiao; Jiang, Jingfeng; Lu, Wenlian; Li, Lei; Tang, Yaoqing
Subjects: Medicine, Pharmacy >> Clinical Medicine

Sepsis is an essential issue in critical care medicine, and early detection and intervention are key for survival. We established the sepsis early warning system based on a data integration platform that can be implemented in ICU. The sepsis early warning module can detect the onset of sepsis 5 hours proceeding, and the data integration platform integrates, standardizes, and stores information from different medical devices, making the inference of the early warning module possible. Our best early warning model got an AUC of 0.9833 in the task of detect sepsis in 4 hours proceeding on the open-source database. Our data integration platform has already been operational in a hospital for months.

submitted time 2021-05-07 Hits15853Downloads698 Comment 0

6. chinaXiv:201907.00014 [pdf]

Remedial dosing recommendations for delayed or missed doses of valproic acid in patients with epilepsy based on Monte Carlo simulations

Chenyu,Wang; Jun-jie Ding; Zheng Jiao; Er-qian Yu; Guo-xing Zhu
Subjects: Medicine, Pharmacy >> Clinical Medicine

Objective: Delayed or missed doses are unavoidable in the pharmacotherapy of epilepsy and significantly compromise the efficacy of antiepileptic drug treatment. An inappropriate remedial regimen can cause seizure relapse or serious adverse events. This study investigated the effect of delayed or missed doses on the pharmacokinetics (PK) of valproic acid (VPA) in patients with epilepsy and established remedial dosing recommendations for nonadherent patients. Methods: Monte Carlo simulations are based on all previous population pharmacokinetic models for pediatric, adult and elderly patients with epilepsy. The following four remedial strategies were investigated for each delayed dose: A) A partial dose or a regular dose is taken immediately; a regular dose is taken at the next scheduled time. B) The delayed dose was administered immediately, followed by a partial dose at the next scheduled time. C) The delayed dose and a partial dose are taken; the next scheduled time is skipped, and the regular regimen is resumed. D) Double doses are taken when missed one dose or two doses, and the regular regimen at the subsequent scheduled time is resumed. Results: The recommended remedial dose was related to the delay duration and daily dose. Remedial dosing strategies A and B were almost equivalent, whereas Strategy C was recommended when the delayed dose was close to the next scheduled dose. Strategy D was only suggested for delayed two doses. Conclusion: Simulations provide quantitative insight into the remedial regimens for nonadherent patients, and clinicians should select the optimal regimen for each patient based on the individual's status.

submitted time 2020-09-07 Hits47465Downloads2215 Comment 1

7. chinaXiv:202007.00041 [pdf]

BRAF mutation predicts survival after immunotherapy across multiple cancer types

Ge, Weiting; Cai, Wen; Wu, Dehao; Hu, Wangxiong; Han, Weidong; Zheng, Shu; Hu, hanguang
Subjects: Medicine, Pharmacy >> Clinical Medicine

Recently studies in selected tumors suggested that BRAF mutation may associates with survival benefit from immune checkpoint inhibitor (ICI) therapy. To broadly investigate this association at a pan-cancer level, we analyzed two independent ICI treatment cohorts (MSKCC: n = 1630, and Dana-Farber: n = 249). BRAF-mutant patients exhibit better overall survival in the MSKCC cohort (Hazard ratio [HR] = 0.55, 95% confidence interval [CI]: 0.43-0.72; P <.001) and the result is validated by the Dana-Farber cohort (HR = 0.68, 95% CI: 0.46-0.99; P = .045). A multivariate analysis adjusting tumor mutational burden, mismatch repair status, cancer type, age and sex confirmed the results (adjusted HR = 0.58, 95% CI = 0.43-0.78; P < .001). Immunogenomic features analysis of TCGA dataset indicated that patients may respond to immunotherapy in various mechanisms. This finding substantially improve the therapeutic prospects for a sizeable fraction of patients who benefit from immunotherapy.

submitted time 2020-07-21 Hits17068Downloads1668 Comment 0

8. chinaXiv:202003.00054 [pdf]


张文杰; 熊巧华; 陈思超; 朱家永; 张冉; 翁鸿; 曾宪涛
Subjects: Medicine, Pharmacy >> Clinical Medicine

[目的] 探究Rac GTP酶活性蛋白1(RACGAP1)基因在膀胱癌组织中的表达情况及临床意义。 [方法] 从NCBI的基因表达汇编(GEO)数据库下载膀胱癌组织RACGAP1的表达数据和临床病理参数。分析RACGAP1基因在膀胱癌组织与正常组织中的表达差异,结合随访信息使用SPSS软件对RACGAP1表达与临床病理特征进行卡方检验,采用Kaplan-Meier法进行生存分析,并利用基因富集分析(GSEA)法分析受RACGAP1调控的相关基因。 [结果] RACGAP1在正常膀胱组织中的表达水平为7.557±0.020,低于膀胱癌组织的7.790±0.028,差异有统计学意义(P<0.05)。膀胱癌组织中RACGAP1表达水平与年龄、侵袭性、T分期、N分期、疾病分级和复发有关(P<0.05)。RACGAP1低表达组和高表达组的5年总生存率分别为73.9%和56.6%(HR=0.47,95%CI:0.29-0.77,P<0.01),肿瘤5年特异生存率分别为91.6%和70.9%(HR=0.33,95%CI:0.17-0.67,P<0.01)。RACGAP1高表达样本富集了MYC信号通路、精子发生、未折叠蛋白反应、G2M检查点、E2F转录因子、MTORC1信号、有丝分裂纺锤体、PI3K/AKT/mTOR途径和DNA修复修复相关的基因集。 [结论] RACGAP1在膀胱癌组织中高表达,与膀胱癌患者的临床病理及预后显著相关,可作为反映膀胱癌患者预后的生物学标志物和潜在的膀胱癌防治靶点。

submitted time 2020-03-16 Hits19116Downloads2147 Comment 0

9. chinaXiv:202003.00008 [pdf]

Germline Polymorphisms and Length of Survival of Nasopharyngeal Carcinoma: An Exome-Wide Association Study in Multiple Cohorts

Yun-Miao Guo; Jie-Rong Chen; Yan-Chun Feng; Chua, Melvin L. K. ; Zeng, Yanni ; Edwin Pun Hui; Allen K. C. Chan; Lin-Quan Tang; Lin Wang; Qian Cui; Hui-Qiong Han; Chun-Ling Luo; Guo-Wang Lin; Yan Liang; Yang Liu; Zhong-Lian He; Yu-Xiang Liu; Pan-Pan Wei; Chu-Jun Liu; Wan Peng
Subjects: Medicine, Pharmacy >> Clinical Medicine

Germline polymorphisms have been linked with differential survival outcomes in cancers but have not been well studied in nasopharyngeal carcinoma (NPC). Here, two-phase association study is conducted to discover germline polymorphisms that are associated with the prognosis of NPC. The discovery phase includes two consecutive hospital cohorts of patients with NPC from Southern China. Exome-wide genotypes at 246,173 single nucleotide polymorphisms (SNPs) are determined, followed by survival analysis for each SNP under Cox proportional hazards regression model. Candidate SNP is replicated in another two independent cohorts from Southern China and Singapore. Meta-analysis of all samples (n = 5,553) confirm that the presence of rs1131636-T, located in the 3′-UTR of RPA1, confers an inferior overall survival (HR = 1.33, 95% CI = 1.20-1.47, P = 6.31 × 10-8). Bioinformatics and biological assays show that rs1131636 has regulatory effects on upstream RPA1. Functional studies further demonstrate that RPA1 promoted the growth, invasion, migration, and radioresistance of NPC cells. Additionally, miR-1253 has been identified as a suppressor for RPA1 expression, likely through regulation of its binding affinity to rs1131636 locus. Collectively, these findings provide a promising biomarker aiding in stratifying patients with poor survival, as well as a potential drug target for NPC.

submitted time 2020-03-06 Hits37644Downloads2522 Comment 0

10. chinaXiv:202003.00026 [pdf]

Effective Treatment of Severe COVID-19 Patients with Tocilizumab

Xu, Xiaoling; Han, Mingfeng; Li, Tiantian; Sun, Wei; Wang, Dongsheng; Fu, Binqing; Zhou, Yonggang; Zheng, Xiaohu; Yang, Yun; Li, Xiuyong; Zhang, Xiaohua; Pan, Aijun; Wei, Haiming
Subjects: Medicine, Pharmacy >> Clinical Medicine

Background: In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China, which spread rapidly and has become a world-wide public health challenge. We aimed to assess the efficacy of tocilizumab in severe patients with Corona Virus Disease-19 (COVID-19) and seek a new therapeutic strategy. Methods: The patients diagnosed as severe or critical COVID-19 in The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) and Anhui Fuyang Second People’s Hospital were given tocilizumab in addition to routine therapy between February 5 and February 14, 2020. The changes of clinical manifestations, CT scan image, and laboratory examinations were retrospectively analyzed. Findings: Within a few days, the fever returned to normal and all other symptoms improved remarkably. Fifteen of the 20 patients (75.0%) had lowered their oxygen intake and one patient need no oxygen therapy. CT scans manifested that the lung lesion opacity absorbed in 19 patients (90.5%). The percentage of lymphocytes in peripheral blood, which decreased in 85.0% patients (17/20) before treatment (mean, 15.52 ± 8.89%), returned to normal in 52.6% patients (10/19) on the fifth day after treatment. Abnormally elevated C-reactive protein decreased significantly in 84.2% patients (16/19). No obvious adverse reactions were observed. Nineteen patients (90.5%) have been discharged on average 13.5 days after the treatment with tocilizumab and the rest are recovering well. Interpretation: Tocilizumab is an effective treatment in severe patients of COVID-19, which provided a new therapeutic strategy for this fatal infectious disease.

submitted time 2020-03-05 Hits186020Downloads53443 Comment 0

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