341 results on '"Xiaoqing Liu"'
Search Results
2. Safety but Limited Efficacy of Ensartinib in ROS1-Positive NSCLC: A Single-Arm, Multicenter Phase 2 Study
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Cheng Huang, Yang Wang, Yan Wang, Xiaoqing Liu, Tao Wang, Jianhua Chen, Xinghao Ai, Jiuwei Cui, Yun Fan, Helong Zhang, Shun Lu, Hongke Cheng, Lieming Ding, Jianying Zhou, Xiaorong Dong, Beili Gao, Ziping Wang, Cuimin Ding, Qiming Wang, Lejie Cao, Gongyan Chen, Xiaobin Yuan, Xingya Li, and Ying Cheng
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung Neoplasms ,business.industry ,Incidence (epidemiology) ,Phases of clinical research ,Protein-Tyrosine Kinases ,Rash ,Piperazines ,Confidence interval ,Pyridazines ,Oncology ,Response Evaluation Criteria in Solid Tumors ,Proto-Oncogene Proteins ,Internal medicine ,Concomitant ,Clinical endpoint ,Humans ,Medicine ,medicine.symptom ,business ,Adverse effect ,Protein Kinase Inhibitors - Abstract
Introduction Some ALK inhibitors with good inhibition of ROS1 in preclinical studies have been reported to be possibly beneficial in ROS1-positive NSCLC. In this work, we studied the efficacy and safety of ensartinib in the treatment of patients with ROS1-positive NSCLC. Methods The exploratory study was a phase 2, single-arm, multicenter design (NCT03608007). Patients with ROS1-positive NSCLC with a previous chemotherapy line number of less than or equal to 1 who received ensartinib at the dose of 225 mg once daily were enrolled. The primary end point was objective response rate evaluated by an investigator per Response Evaluation Criteria in Solid Tumors version 1.1. Results From June 2018 to July 2019, a total of 59 patients were enrolled at 23 centers in the People’s Republic of China. At the time of data cutoff, the median follow-up was 19.8 months (range: 0.8–22.5). The median objective response rate was 27.0 % (95 % confidence interval [CI]: 13.8–44.1) with 10 partial responses. Median duration of response was 4.8 months (95 % CI: 1.8–10.8). The median progression-free survival was 4.6 months (95 % CI: 4.0–6.4). The median overall survival was not estimable (95 % CI: 14.9–not estimable). Of four patients with brain metastases, intracranial disease control was reported in three (75.0 %, 95 % CI: 19.4–99.4). The most common treatment-related adverse events (TRAEs) were rash and liver enzyme abnormalities, with good prognosis after adjustment for dosage and concomitant medication. Most of the TRAEs were of grades 1 to 2, and incidence of grade greater than or equal to 3 TRAEs was 25.4 %. Conclusions Ensartinib had a modest efficacy in patients with ROS1-positive NSCLC with an acceptable safety profile.
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- 2021
3. Power outage mediates the associations between major storms and hospital admission of chronic obstructive pulmonary disease
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Bo Ye, Yanji Qu, Shao Lin, Samantha Penta, Wangjian Zhang, Xiaoqing Liu, and Guang-Hui Dong
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Distributed lag ,medicine.medical_specialty ,Storms ,animal diseases ,Pulmonary Disease, Chronic Obstructive ,Power outage ,Epidemiology ,medicine ,Humans ,COPD ,Cause of death ,business.industry ,Cyclonic Storms ,Research ,Confounding ,Public Health, Environmental and Occupational Health ,Storm ,medicine.disease ,Hospitals ,respiratory tract diseases ,Hospitalization ,Mediation effect ,Relative risk ,Emergency medicine ,Particulate Matter ,Biostatistics ,Public aspects of medicine ,RA1-1270 ,business - Abstract
Background Chronic obstructive pulmonary disease (COPD) is the third-leading cause of death worldwide with continuous rise. Limited studies indicate that COPD was associated with major storms and related power outages (PO). However, significant gaps remain in understanding what PO’s role is on the pathway of major storms-COPD. This study aimed to examine how PO mediates the major storms-COPD associations. Methods In this time-series study, we extracted all hospital admissions with COPD as the principal diagnosis in New York, 2001–2013. Using distributed lag nonlinear models, the hospitalization rate during major storms and PO was compared to non-major storms and non-PO periods to determine the risk ratios (RRs) for COPD at each of 0–6 lag days respectively after controlling for time-varying confounders and concentration of fine particulate matter (PM2.5). We then used Granger mediation analysis for time series to assess the mediation effect of PO on the major storms-COPD associations. Results The RRs of COPD hospitalization following major storms, which mainly included flooding, thunder, hurricane, snow, ice, and wind, were 1.23 to 1.49 across lag 0–6 days. The risk was strongest at lag3 and lasted significantly for 4 days. Compared with non-outage periods, the PO period was associated with 1.23 to 1.61 higher risk of COPD admissions across lag 0–6 days. The risk lasted significantly for 2 days and was strongest at lag2. Snow, hurricane and wind were the top three contributors of PO among the major storms. PO mediated as much as 49.6 to 65.0% of the major storms-COPD associations. Conclusions Both major storms and PO were associated with increased hospital admission of COPD. PO mediated almost half of the major storms-COPD hospitalization associations. Preparation of surrogate electric system before major storms is essential to reduce major storms-COPD hospitalization.
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- 2021
4. Icotinib versus chemotherapy as adjuvant treatment for stage II–IIIA EGFR-mutant non-small-cell lung cancer (EVIDENCE): a randomised, open-label, phase 3 trial
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Caicun Zhou, Xiangning Fu, Xingya Li, Xiaoqing Liu, Zhidong Liu, Taiqian Gong, Feng Ye, Shidong Xu, Wenhua Liang, Qun Chen, Zhonglin Wang, Lieming Ding, Jian Zhao, Yang Liu, Wen Lin, Di Ge, Bing Hu, Lin Xu, Jianxing He, Chun Chen, Lin Wu, Xiaodong Zhang, Zheng Wang, Guoguang Shao, Weimin Mao, Jianying Zhou, Jian Hu, Junke Fu, Yunchao Huang, Chunxia Su, Haitao Ma, Li Mao, and Zemin Xiao
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Male ,Pulmonary and Respiratory Medicine ,Oncology ,China ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Vinorelbine ,Carcinoma, Non-Small-Cell Lung ,Crown Ethers ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Lung cancer ,Chemotherapy ,business.industry ,Middle Aged ,medicine.disease ,Interim analysis ,Squamous carcinoma ,ErbB Receptors ,Treatment Outcome ,Tolerability ,Chemotherapy, Adjuvant ,Mutation ,Icotinib ,Quinazolines ,Female ,business ,medicine.drug - Abstract
Summary Background Icotinib has provided survival benefits for patients with advanced, epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). We aimed to compare icotinib with chemotherapy in patients with EGFR-mutant stage II–IIIA NSCLC after complete tumour resection. Here, we report the results from the preplanned interim analysis of the study. Methods In this multicentre, randomised, open-label, phase 3 trial done at 29 hospitals in China, eligible patients were aged 18–70 years, had histopathogically confirmed stage II–IIIA NSCLC, had complete resection up to 8 weeks before random assignment, were treatment-naive, and had confirmed activation mutation in exon 19 or exon 21 of the EGFR gene. Participants were randomly assigned (1:1) with an interactive web-based response system to receive either oral icotinib 125 mg thrice daily for 2 years or four 21-day cycles of intravenous chemotherapy (vinorelbine 25 mg/m2 on days 1 and 8 of each cycle plus cisplatin 75 mg/m2 on day 1 of each cycle for adenocarcinoma or squamous carcinoma; or pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 on day 1 every 3 weeks for non-squamous carcinoma). The primary endpoint was disease-free survival assessed in the full analysis set. Secondary endpoints were overall survival assessed in the full analysis set and safety assessed in all participants who received study drug. This trial is registered with ClinicalTrials.gov , NCT02448797 . Findings Between June 8, 2015, and August 2, 2019, 322 patients were randomly assigned to icotinib (n=161) or chemotherapy (n=161); the full analysis set included 151 patients in the icotinib group and 132 in the chemotherapy group. Median follow-up in the full analysis set was 24·9 months (IQR 16·6–36·4). 40 (26%) of 151 patients in the icotinib group and 58 (44%) of 132 patients in the chemotherapy group had disease relapse or death. Median disease-free survival was 47·0 months (95% CI 36·4–not reached) in the icotinib group and 22·1 months (16·8–30·4) in the chemotherapy group (stratified hazard ratio [HR] 0·36 [95% CI 0·24–0·55]; p Interpretation Our results suggest that compared with chemotherapy, icotinib significantly improves disease-free survival and has a better tolerability profile in patients with EGFR-mutant stage II–IIIA NSCLC after complete tumour resection. Funding Betta Pharmaceuticals Translation For the Chinese translation of the abstract see Supplementary Materials section.
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- 2021
5. Secondary infection in severe and critical COVID-19 patients in China: a multicenter retrospective study
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Chun Pan, Nuofu Zhang, Zhimin Lin, Shiyue Li, Wenjuan Wu, Ying Pan, Yonghao Xu, Dingyu Zhang, Dongdong Liu, Ming Zhong, Chang'an Li, Xiaoqing Liu, Zheng Lv, Nanshan Zhong, Wei Zhang, Ling Sang, Yuanda Xu, Bin Song, Dan Ye, Nanshan Chen, Weibo Liang, Xuesong Liu, Jiaan Xia, Sibei Chen, Yin Xi, Li Jiang, Xia Zheng, and Yimin Li
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Adult ,medicine.medical_specialty ,Secondary infection ,Carbapenem-resistant enterobacteriaceae ,Internal medicine ,Epidemiology ,medicine ,Humans ,Pandemics ,Survival rate ,Retrospective Studies ,Advanced and Specialized Nursing ,Cross Infection ,biology ,Coinfection ,SARS-CoV-2 ,business.industry ,COVID-19 ,Retrospective cohort study ,Middle Aged ,medicine.disease ,biology.organism_classification ,Anti-Bacterial Agents ,Acinetobacter baumannii ,Stenotrophomonas maltophilia ,Anesthesiology and Pain Medicine ,business - Abstract
Background. Since 2020 COVID-19 pandemic became an emergent public sanitary incident. The epidemiology data and the impact on prognosis of secondary infection in severe and critical COVID-19 patients in China remained largely unclear.Methods. We retrospectively reviewed medical records of all adult patients with laboratory-confirmed COVID-19 who were admitted to ICUs from January 18th 2020 to April 26th 2020 at two hospitals in Wuhan, China and one hospital in Guangzhou, China. We measured the frequency of bacteria and fungi cultured from respiratory tract, blood and other body fluid specimens. The risk factors for and impact of secondary infection on clinical outcomes were also assessed. Results. Secondary infections were very common (86.6%) when patients were admitted to ICU for >72 hours. The majority of infections were respiratory, with the most common organisms being Klebsiella pneumoniae (24.5%), Acinetobacter baumannii (21.8%), Stenotrophomonas maltophilia (9.9%), Candida albicans (6.8%), and Pseudomonas spp. (4.8%). Furthermore, the proportions of multidrug resistant (MDR) bacteria and carbapenem resistant Enterobacteriaceae (CRE) were high. We also found that age ≥60 years and mechanical ventilation ≥13days independently increased the likelihood of secondary infection. Finally, patients with positive cultures had reduced ventilator free days in 28 days and patients with CRE and/or MDR bacteria positivity showed lower 28 day survival rate.Conclusions. In a retrospective cohort of severe and critical COVID-19 patients admitted to ICUs in China, the prevalence of secondary infection was high, especially with CRE and MDR bacteria, resulting in poor clinical outcomes.
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- 2021
6. The Chinese Thoracic Oncology Group (CTONG) therapeutic option scoring system: a multiple-parameter framework to assess the value of lung cancer treatment options
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Wen-Zhao Zhong, Lei Qian, Yun Fan, Shun Lu, Li Zhang, Hai-Yan Tu, Jianying Zhou, Qing Zhou, Xiao-Yuan Chen, Jiuwei Cui, Yi-Long Wu, Ying Cheng, Wenqian Li, Xiaoqing Liu, Jie Wang, Cheng Huang, Rilan Bai, and Jin-Ji Yang
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medicine.medical_specialty ,business.industry ,Context (language use) ,Subgroup analysis ,Treatment of lung cancer ,medicine.disease ,Focus group ,Oncology ,Quality of life ,Thoracic Oncology ,Physical therapy ,Medicine ,Original Article ,business ,Lung cancer ,Adverse effect - Abstract
Background Currently, there is no standard context that conforms to the Chinese national framework for evaluating medical decisions regarding the treatment of lung cancer. Methods This draft was formulated after a systematic review and a focus group discussion among 20 experts, who were senior physicians with extensive clinical experience from the Chinese Thoracic Oncology Group (CTONG) task force. Subsequently, a draft and a five-point Likert scale were sent to 300 CTONG working group members. These were modified according to feedback from a four-round modified Delphi approach. Hence, the first version of the 'Therapeutic option of lung cancer: CTONG scoring system' was formulated. Afterward, a corresponding questionnaire was designed to collect opinions on the weight allocation of various indicators. This was issued through the WeChat platform, "Oncology News" application and e-mails from October 23, 2020, to November 25, 2020. Participants from numerous occupations in cancer-related fields from various regions of China were included in the study. Overall and subgroup analyses regarding weight allocations were performed. The differences between participant-allocated and reference weights were considered to adjust the framework. Results The framework contained four aspects and six indicators, including efficacy [progression-free survival (PFS)/overall survival (OS) and subsequent treatment], safety [treatment-related severe adverse event (SAE), dose adjustment], quality of life (Qol), and compensation. The reference weights were 50%, 5%, 10%, 5%, 10%, and 20% for each indicator. By November 25, 2020, 1,043 valid questionnaires had been obtained. The majority of the questionnaires were completed by physicians (86.5%). Subgroup analysis among the various groups showed an overall consistent trend. Besides, significant differences between the participant-allocated and reference weights were found among PFS/OS (difference: -11.5%), compensation (difference: -10.1%), and subsequent treatment (difference: 9.7%) indicators. After discussion, the final weight allocations were set at 45%, 10%, 15%, 5%, 10%, and 15% for PFS/OS, subsequent treatment, treatment-related SAE, dose adjustment, Qol, and compensation, respectively. Conclusions The CTONG scoring system, as an objective evaluation model that involves multiple parameters, is a breakthrough method for evaluating the therapeutic value of lung cancer treatment options in China, which is worthy of further verification in future clinical practice.
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- 2021
7. Independent risk factors of hypoxemia in patients after surgery with acute type A aortic dissection
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Jieyi Pan, Weixiang Huang, Yimin Li, Weibo Liang, Weiqun He, Lingbo Nong, Yuheng Yu, Sibei Chen, Xuesong Liu, Ling Sang, Yan Lai, Xiaoqing Liu, Yonghao Xu, Yongbo Huang, Yuanda Xu, and Jing Zhou
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medicine.medical_specialty ,medicine.medical_treatment ,Hypoxemia ,law.invention ,Risk Factors ,law ,medicine ,Humans ,Renal replacement therapy ,Hypoxia ,Retrospective Studies ,Advanced and Specialized Nursing ,Aortic dissection ,APACHE II ,business.industry ,Acute kidney injury ,Retrospective cohort study ,Perioperative ,medicine.disease ,Intensive care unit ,respiratory tract diseases ,Surgery ,Aortic Dissection ,Intensive Care Units ,Anesthesiology and Pain Medicine ,medicine.symptom ,business ,circulatory and respiratory physiology - Abstract
This study aimed to investigate independent risk factors of postoperative hypoxemia in patients with acute type A aortic dissection (ATAAD).A single-center retrospective study was conducted with enrolled 75 ATAAD patients following surgery, which were stratified into three groups on the basis of the postoperative PaO2/FiO2 ratio: severe hypoxemia group (PaO2/FiO2 ratio ≤100 mmHg); moderate hypoxemia group (100 mmHgPaO2/FiO2 ratio ≤200 mmHg); and non-hypoxemia group (PaO2/FiO2 ratio200 mmHg). The patient's demography, perioperative laboratory results, operative details, clinical outcomes were collected and analyzed. Univariable and multivariable analyses were performed and logistic regression model was established.The incidence of postoperative severe hypoxemia and hypoxemia was 32% and 52%, respectively. Among the three groups, severe hypoxemia group exhibited a high significance of body mass index (BMI) and preoperative white blood cell (WBC) and main distribution of hypertension; meanwhile, Marfan syndrome was mainly distributed in non-hypoxemia group. On intensive care unit (ICU) admission, severe hypoxemia group exhibited a high significance of Acute Physiology and Chronic Health Evaluation (APACHE II) score of postoperative patients, and more patients would present shock. Moreover, severe hypoxemia group patients had a higher incidence of postoperative acute kidney injury (AKI) and usage of renal replacement therapy, longer length of stay (LOS) of ICU, and shorter 28 days ventilator-free days (VFDs).The incidence of postoperative hypoxemia was high in ATAAD patients owing to comprehensive high-risk factors. Besides, postoperative complications negatively impacted their clinical outcomes.
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- 2021
8. Nomogram to Predict Distant Metastasis Probability for Pathological Complete Response Rectal Cancer Patients After Neoadjuvant Chemoradiotherapy
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Zhifan Zeng, Shuang Liu, Peiqiang Cai, Shanfei Yang, Ting Jiang, Weizhan Li, Yuanhong Gao, Shaoyan Xi, Gong Chen, Xiaoqing Liu, Weiwei Xiao, and Xiaojun Wu
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0301 basic medicine ,medicine.medical_specialty ,pathological complete response ,pCR ,Colorectal cancer ,Logistic regression ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,Pathological ,adjuvant chemotherapy ,ACT ,Survival analysis ,Original Research ,locally advanced rectal cancer ,LARC ,business.industry ,Retrospective cohort study ,Nomogram ,medicine.disease ,Total mesorectal excision ,030104 developmental biology ,Oncology ,Cancer Management and Research ,030220 oncology & carcinogenesis ,Cohort ,distant metastasis ,DM ,business - Abstract
Ting Jiang,1,* Shuang Liu,1,* Xiaojun Wu,2,* Xiaoqing Liu,3 Weizhan Li,4 Shanfei Yang,1 Peiqiang Cai,5 Shaoyan Xi,6 Zhifan Zeng,1 Yuanhong Gao,1 Gong Chen,2 Weiwei Xiao1 1Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 3Department of Radiation Oncology, Guangzhou Concord Cancer Center, Guangzhou, People’s Republic of China; 4Department of Radiation Oncology, Panyu Center Hospital, Guangzhou, People’s Republic of China; 5Department of Radiology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 6Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gong Chen; Weiwei Xiao Email chengong@sysucc.org.cn; xiaoww@sysucc.org.cnPurpose: This study aimed to predict the risks of distant metastasis (DM) of locally advanced rectal cancer (LARC) patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NACRT) and total mesorectal excision (TME), and to find the association between adjuvant chemotherapy (ACT) and their survival outcomes.Methods and Materials: A total of 242 patients with LARC achieving pCR after NACRT were enrolled in this retrospective study. We developed a nomogram model using logistic regression analyses for predicting risk of DM. The model performance was evaluated by the concordance index and calibration curve. Survival was determined using Kaplan–Meier survival curve.Results: Age, pre-operative CEA, pre-treatment CEA and distance of tumor to anal verge were identified as significantly associated variables that could be enrolled in the model to predict the risk of DM for pCR patients. The nomogram we created had a bootstrapped-concordance index of 0.731 (95% CI = 0.627 to 0.834) and was well calibrated. The high risk group was more likely to develop DM than low risk group (total score) (95% CI = 1.439 to 6.493, P = 0.0036). The 1-year, 3-year, and 5-year distant metastasis-free survival (DMFS) for the low and high risk groups (total score ≤ 90 vs > 90) was 97.8%, 94.2%, 94.2% and 91.3%, 83.4%, 81.8%, respectively (P = 0.0036). DM occurred within 1 and 2 years after TME surgery was 33.3% and 55.6% for the low risk group, and 47.3% and 84.2% for the high risk group. The value of ACT was assessed among the whole cohort, patients with cT3-4, with cN+ or with either DM risk group, but no significant difference was observed concerning DMFS whether ACT was given or not (all P > 0.05). Active treatment after DM was more beneficial than palliative treatment (P < 0.001).Conclusion: The nomogram model, including age, pre-operative CEA, pre-treatment CEA and distance to anal verge, predicted the probability of DM among LARC patients achieving pCR after NACRT. The effects of ACT were not seen in different subgroups, while closer clinical follow-up may have greater contribution to pCR patients in the first 2 years, especially for patients with relatively higher risk to develop DM. It is suggested that timely active treatment can bring survival benefit for pCR patients developing DM after NACRT.Keywords: locally advanced rectal cancer; LARC, pathological complete response; pCR, adjuvant chemotherapy; ACT, distant metastasis; DM
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- 2021
9. Sofosbuvir-Based Therapies Achieved Satisfactory Virological Response in Chinese Individuals with Genotypes 3 and 6 Infections: A Real-World Experience
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Xiaoqing Liu, Qiao Tang, Li Wei, and Peng Hu
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hepatitis C virus ,0301 basic medicine ,medicine.medical_specialty ,Cirrhosis ,Daclatasvir ,Sofosbuvir ,ribavirin ,Hepatitis C virus ,030106 microbiology ,medicine.disease_cause ,sofosbuvir ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Genotype ,medicine ,Pharmacology (medical) ,daclatasvir ,030212 general & internal medicine ,Adverse effect ,Original Research ,Pharmacology ,business.industry ,Ribavirin ,velpatasvir ,Retrospective cohort study ,medicine.disease ,Infectious Diseases ,chemistry ,Infection and Drug Resistance ,business ,medicine.drug - Abstract
Qiao Tang, Li Wei, Xiaoqing Liu, Peng Hu Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Peng HuDepartment of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Road, Yuzhong District, Chongqing, 400000, People’s Republic of ChinaTel +86 13608338064Email hp_cq@163.comBackground: Previous studies have shown that sofosbuvir-based regimens yield high sustained virological response rates in patients with hepatitis C virus (HCV) infection except for genotype 3b complicated with cirrhosis. This real-world study aims to explore the efficacy and safety of sofosbuvir-based regimens in Chinese patients with genotypes 3 and 6 infections, especially the impact of ribavirin coadministration on sustained virological response in cirrhotic patients with genotype 3b infection.Methods: This is a retrospective cohort study that included 101 patients initiated on sofosbuvir-based regimens. The main endpoint of treatment was sustained virological response at posttreatment week 12 (SVR12).Results: Overall, the SVR12 rates were 95.0% (96/101); specifically, the rates were 100% in sofosbuvir, 88.2% in sofosbuvir+ribavirin, 100% in sofosbuvir+daclatasvir, 100% in sofosbuvir+daclatasvir+ribavirin, 95.0% in sofosbuvir/velpatasvir, and 97.1% in sofosbuvir/velpatasvir+ribavirin (p=0.534). The SVR12 rates were comparable in patients infected with genotypes 3 and 6 (93.2% versus 97.6%, p=0.339). The SVR12 rate was 93.9% in cirrhotic patients (31/33). Among those infected with genotype 3, the SVR12 rate was 91.7% (22/24); the rate was 95.0% in those with ribavirin coadministration regimens, which was numerically higher than the 75.0% in those without ribavirin. However, no statistical difference was found (p=0.312). In total, five patients failed to achieve SVR12, including 3 patients with genotype 3b infection treated with ribavirin coadministration regimens (one of them was cirrhotic), 1 cirrhotic patient with genotype 3k infection, and 1 noncirrhotic patient with genotype 6a infection. No severe adverse event occurred.Conclusion: Real-world data show that sofosbuvir-based regimens are highly effective and safe for patients with HCV genotypes 3 and 6 infections.Keywords: daclatasvir, hepatitis C virus, ribavirin, sofosbuvir, velpatasvir
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- 2021
10. Development and Validation of a Polygenic Risk Score for Stroke in the Chinese Population
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Zhanyun Ren, Jianfeng Huang, Wuzhuang Tang, Xian-Ping Wu, Hongbing Shen, Zhongying Liu, Keyong Huang, Xigui Wu, Cristen J. Willer, Huan Zhang, Jianxin Li, Fanghong Lu, Xueli Yang, Ying Li, Chong Shen, Yingxin Zhao, Hongfan Li, Laiyuan Wang, Ling Yu, Zhibin Hu, Xiaoqing Liu, Shufeng Chen, Dongfeng Gu, Jie Cao, Xiangfeng Lu, Dongsheng Hu, Fangchao Liu, and Xiao-Ge Niu
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Adult ,Male ,China ,Multifactorial Inheritance ,medicine.medical_specialty ,Risk Assessment ,Cohort Studies ,Asian People ,Meta-Analysis as Topic ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Family history ,Stroke ,Aged ,Models, Statistical ,Framingham Risk Score ,Proportional hazards model ,business.industry ,Incidence ,Incidence (epidemiology) ,Absolute risk reduction ,Case-control study ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Heart Disease Risk Factors ,Case-Control Studies ,Female ,Neurology (clinical) ,business ,Research Article ,Genome-Wide Association Study ,Cohort study - Abstract
ObjectiveTo construct a polygenic risk score (PRS) for stroke and evaluate its utility in risk stratification and primary prevention for stroke.MethodsUsing a meta-analytic approach and large genome-wide association results for stroke and stroke-related traits in East Asians, we generated a combined PRS (metaPRS) by incorporating 534 genetic variants in a training set of 2,872 patients with stroke and 2,494 controls. We then validated its association with incident stroke using Cox regression models in large Chinese population-based prospective cohorts comprising 41,006 individuals.ResultsDuring a total of 367,750 person-years (mean follow-up 9.0 years), 1,227 participants developed stroke before age 80 years. Individuals with high polygenic risk had an about 2-fold higher risk of incident stroke compared with those with low polygenic risk (hazard ratio [HR] 1.99, 95% confidence interval [CI] 1.66–2.38), with the lifetime risk of stroke being 25.2% (95% CI 22.5%–27.7%) and 13.6% (95% CI 11.6%–15.5%), respectively. Individuals with both high polygenic risk and family history displayed lifetime risk as high as 41.1% (95% CI 31.4%–49.5%). Individuals with high polygenic risk achieved greater benefits in terms of absolute risk reductions from adherence to ideal fasting blood glucose and total cholesterol than those with low polygenic risk. Maintaining favorable cardiovascular health (CVH) profile could substantially mitigate the increased risk conferred by high polygenic risk to the level of low polygenic risk (from 34.6% to 13.2%).ConclusionsOur metaPRS has great potential for risk stratification of stroke and identification of individuals who may benefit more from maintaining ideal CVH.Classification of EvidenceThis study provides Class I evidence that metaPRS is predictive of stroke risk.
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- 2021
11. Decoding the Evolutionary Response to Ensartinib in Patients With ALK-Positive NSCLC by Dynamic Circulating Tumor DNA Sequencing
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Zhendong Zheng, Lejie Cao, Youling Gong, Weineng Feng, Lieming Ding, Gang Wu, Ning Wu, Jun Zhao, Yong Song, Jianya Zhou, Larry Zhu, Shanshan Xiao, Zhuang Yu, Tao Wang, Jianhua Chen, Jian Fang, Chengzhi Zhou, Li Zhang, Yi Hu, Jie Huang, Li Mao, Jifeng Feng, Gaofeng Li, Xiaobin Yuan, Yunpeng Liu, Kewei Ma, Wei Song, Feng Ye, Xiaoqing Liu, Shucai Zhang, Zhilin Shen, Wu Zhuang, Yun Fan, Yanqiu Zhao, Jing Zheng, Huijie Wang, Yunpeng Yang, Wei Zhong, Yubiao Guo, Yuan Chen, Giovanni Selvaggi, Shijun Zhao, Yiping Zhang, and Shundong Cang
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Disease ,Tp53 mutation ,Piperazines ,Circulating Tumor DNA ,03 medical and health sciences ,0302 clinical medicine ,Genetic Evolution ,Internal medicine ,medicine ,Humans ,Anaplastic Lymphoma Kinase ,In patient ,Protein Kinase Inhibitors ,Crizotinib ,business.industry ,ALK-Positive ,Pyridazines ,030104 developmental biology ,Drug Resistance, Neoplasm ,Circulating tumor DNA ,030220 oncology & carcinogenesis ,Mutation ,business ,medicine.drug - Abstract
By implementing dynamic circulating tumor DNA (ctDNA) analysis, we explored the impact of TP53 mutations on tumor evolution and resistance mechanisms to ensartinib in patients with ALK-positive NSCLC.In a multicenter phase 2 trial, patients with ALK-positive NSCLC who progressed on crizotinib were treated with ensartinib. Blood samples for ctDNA analysis were collected at baseline, cycle 3 day 1, and progression disease (PD) and analyzed with a 212-gene panel.A total of 440 samples were collected from 168 patients. Baseline TP53 mutations (20.2%) significantly correlated with inferior progression-free survival (4.2 mo versus 11.7 mo, p0.0001). Patients with TP53 mutations had higher mutation load than those without TP53 mutations at baseline (13.79 ± 3.72 versus 4.67 ± 0.39, p0.001). Although there was no significant difference in mutation load between these groups at cycle 3 day 1 (5.89 ± 2.25 versus 3.72 ± 0.62, p = 0.425), patients with mutated TP53 developed more mutations at PD (7.07 ± 1.25 versus 3.20 ± 0.33, p = 0.003). Frequency and abundance of secondary ALK mutations G1269A, G1202R, and E1210K increased markedly at PD than baseline. In patients without secondary ALK mutations, we identified ALK-independent resistance mechanisms including bypass signaling activation, downstream effector protein reactivation, epithelial-mesenchymal transformation, and epigenetic dysregulation.Our study highlighted the advantage of ctDNA analysis for monitoring tumor evolution. TP53 mutations promoted genetic evolution and accelerated occurrence of resistance. We also unveiled ALK-dependent resistance mechanisms, mainly by G1269A, G1202R, and E1210K mutations, and ALK-independent resistance mechanisms to ensartinib.
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- 2021
12. Functional disability and post-traumatic stress disorder in survivors of mechanical ventilation: a cross-sectional study in Guangzhou, China
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Lihua Chen, Yimin Li, Ronghua Li, Jingye Huang, Huijin Zhang, Ying Zhou, and Xiaoqing Liu
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Pulmonary and Respiratory Medicine ,Mechanical ventilation ,medicine.medical_specialty ,Activities of daily living ,APACHE II ,business.industry ,Cross-sectional study ,medicine.medical_treatment ,Traumatic stress ,030208 emergency & critical care medicine ,medicine.disease ,Intensive care unit ,humanities ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,Telephone interview ,law ,Emergency medicine ,Medicine ,Original Article ,business ,human activities ,Post-traumatic stress disorder (PTSD) - Abstract
Background Critical illness is associated with cognitive, physical, and psychological impairments; however, evidence of the severity and frequency of impairments in Chinese survivors of mechanical ventilation in an intensive care unit (ICU) remains limited. Our aim was to investigate the incidence and severity of impairments in Chinese survivors of mechanical ventilation in ICU and to explore risk factors influencing specific impairments. Methods Patients discharged alive after mechanical ventilation in a large general ICU for ≥2 days were enrolled in this single-center cross-sectional study. Survivors were evaluated using measures of functional disability (Activity of Daily Living Scale), and post-traumatic stress disorder (PTSD, The Impact of Event Scale-Revised) via telephone interview. Multivariable analysis was conducted. Results Data were obtained from 130 consenting survivors. At follow-up (mean: 19.64 months), among those in part-time or full-time employment prior to admission, only 45.1% had returned to work. Further, 29.2% of survivors had clear disabilities affecting daily living. Deficits in activities of daily living (ADL) were mainly characterized by impairment of instrumental ADL. Predictors of ADL in mechanically ventilated survivors included age, ICU admission diagnosis, and Acute Physiology And Chronic Health Evaluation II (APACHE II) score, which accounted for 33.5% of total variance. Furthermore, 17.7% of participants had symptoms consistent with PTSD. ICU length of stay was the only predictor of PTSD, and accounted for 7.5% of total variance. Conclusions ICU survivors of mechanical ventilation in China face negative impacts on employment, and commonly have ADL impairment and PTSD. Age, ICU admission diagnosis, and APACHE II score were key factors influencing ADL, while ICU length of stay was the only factor affecting PTSD. These findings suggest that some survivors who have had certain exposures may warrant closer follow-up, and systematic interventions for these high-risk survivors should be developed in China.
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- 2021
13. Eltrombopag restores erythropoiesis in refractory adult acquired pure red cell aplasia
- Author
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Jianyong Li, Yao He, Lang Cheng, Jian-Fu Zhang, Ming Hong, Ruinan Lu, Guangsheng He, Xiaoqing Liu, and Run Zhang
- Subjects
Male ,medicine.medical_specialty ,Acquired Pure Red Cell Aplasia ,Bilirubin ,Eltrombopag ,Pure red cell aplasia ,Red-Cell Aplasia, Pure ,Benzoates ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Refractory ,Bone Marrow ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Erythropoiesis ,Reticulocytopenia ,Hematology ,business.industry ,Middle Aged ,medicine.disease ,stomatognathic diseases ,Hydrazines ,Treatment Outcome ,chemistry ,030220 oncology & carcinogenesis ,Pyrazoles ,business ,Receptors, Thrombopoietin ,030215 immunology - Abstract
Acquired pure red cell aplasia is a rare condition characterized by normocytic normochromic anemia with severe reticulocytopenia. In refractory acquired pure red cell aplasia, the low response rate of immunosuppressive therapy also constitutes a challenge. We herein report the case of a 58-year-old male with refractory acquired pure red cell aplasia that was successfully treated by eltrombopag at a dose of 75 mg/day. After application of eltrombopag, the patient achieved complete remission and tolerated the treatment very well, with only mild bilirubin elevation. These preliminary findings showed that eltrombopag may be effective and well tolerated in adult patients with refractory acquired pure red cell aplasia.
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- 2021
14. Clinical Features and Risk Factors of Active Tuberculosis in Patients with Behçet’s Disease
- Author
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Baotong Zhou, Luxi Sun, Xiaoqing Liu, Lifan Zhang, Yaxu Liu, Wenjie Zheng, and Ziyue Zhou
- Subjects
Adult ,Male ,medicine.medical_specialty ,Tuberculosis ,Article Subject ,Immunology ,Comorbidity ,Disease ,Behcet's disease ,Logistic regression ,Risk Assessment ,Gastroenterology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,In patient ,030212 general & internal medicine ,Retrospective Studies ,030203 arthritis & rheumatology ,medicine.diagnostic_test ,Latent tuberculosis ,business.industry ,Behcet Syndrome ,General Medicine ,Middle Aged ,RC581-607 ,Active tuberculosis ,medicine.disease ,Erythrocyte sedimentation rate ,Female ,Disease Susceptibility ,Symptom Assessment ,Immunologic diseases. Allergy ,business ,Biomarkers ,Immunosuppressive Agents ,Research Article - Abstract
To investigate the clinical features and potential risk factors of active tuberculosis (ATB) in Behçet’s disease (BD), we conducted a case-control study on hospitalized BD patients in our institute from 2010 to 2019. BD patients with ATB were enrolled as the case group. The control group was selected by random number sampling from the remaining BD patients, including those with latent tuberculosis infection, previous tuberculosis, or without tuberculosis. Finally, we reviewed 386 BD patients and identified 21 (5.4%) ATB cases, including four (19.0%) microbiologically confirmed and 17 (81.0%) clinically diagnosed. We found that BD patients with ATB were more prone to have systemic symptoms (fever, night sweating, and unexplained weight loss) and/or symptoms related to the infection site. Multivariate logistic regression analysis revealed that erythrocyte sedimentation rate ESR > 60 mm/h ( OR = 13.710 , 95% CI (1.101, 170.702)), increased IgG ( OR = 1.226 , 95% CI (1.001, 1.502)), and positive T-SPOT.TB ( OR = 7.793 , 95% CI (1.312, 48.464), for 24-200 SFC/106PBMC; OR = 17.705 95% CI (2.503, 125.260), for >200 SFC/106PBMC) were potential risk factors for ATB in BD patients. Our study suggested that when BD patients have systemic symptoms with significantly elevated TB-SPOT, the diagnosis of ATB should be considered.
- Published
- 2020
15. Tepotinib plus gefitinib in patients with EGFR-mutant non-small-cell lung cancer with MET overexpression or MET amplification and acquired resistance to previous EGFR inhibitor (INSIGHT study): an open-label, phase 1b/2, multicentre, randomised trial
- Author
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Yi-Long Wu, Ying Cheng, Jianying Zhou, Shun Lu, Yiping Zhang, Jun Zhao, Dong-Wan Kim, Ross Andrew Soo, Sang-We Kim, Hongming Pan, Yuh-Min Chen, Chih-Feng Chian, Xiaoqing Liu, Daniel Shao Weng Tan, Rolf Bruns, Josef Straub, Andreas Johne, Jürgen Scheele, Keunchil Park, James Chih-Hsin Yang, Zhe Liu, Xi Chen, Mengzhao Wang, Shiying Yu, Helong Zhang, Jian Fang, Wei Li, Chih-Hsin Yang, Gee-Chen Chang, Te-Chun Hsia, Cheng-Ta Yang, Chin-Chou Wang, Byoung Chul Cho, Ki Hyeong Lee, Young-Chul Kim, Ho Jung An, In Sook Woo, Jae Yong Cho, Sang Won Shin, Jong-Seok Lee, Joo-Hang Kim, Seung Soo Yoo, Terufumi Kato, Naofumi Shinagawa, Shao Weng Daniel Tan, Lynette Si-Mien Ngo, Kananathan Ratnavelu, Azura Rozila Ahmad, Chong Kin Liam, Filippo de Marinis, Pierfrancesco Tassone, Amelia Insa Molla, Antonio Calles Blanco, Martin Emilio Lazaro Quintela, Enriqueta Felip Font, Anne-Marie Dingemans, and Lynne Bui
- Subjects
Male ,Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Risk Assessment ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Gefitinib ,Piperidines ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Clinical endpoint ,Humans ,media_common.cataloged_instance ,030212 general & internal medicine ,European union ,Lung cancer ,Aged ,Proportional Hazards Models ,EGFR inhibitors ,media_common ,Chemotherapy ,business.industry ,Hazard ratio ,Middle Aged ,Proto-Oncogene Proteins c-met ,Prognosis ,medicine.disease ,Survival Analysis ,ErbB Receptors ,Gene Expression Regulation, Neoplastic ,Pyridazines ,Pyrimidines ,Treatment Outcome ,030228 respiratory system ,Drug Resistance, Neoplasm ,Mutation ,Absolute neutrophil count ,Female ,business ,medicine.drug - Abstract
Summary Background We evaluated the efficacy and safety of tepotinib, a potent and highly selective oral MET inhibitor, plus gefitinib in patients with epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) with MET overexpression (immunohistochemistry [IHC]2+ or IHC3+) or MET amplification having acquired resistance to EGFR inhibition. Methods In this open-label, phase 1b/2, multicentre, randomised trial (the INSIGHT study), we enrolled adult patients (≥18 years) with advanced or metastatic NSCLC, and Eastern Cooperative Oncology Group performance status of 0 or 1, from academic medical centres and community clinics in six Asian countries. In phase 1b, patients received oral tepotinib 300 mg or 500 mg plus gefitinib 250 mg once daily. In phase 2, patients with EGFR-mutant, T790M-negative NSCLC MET overexpression or MET amplification were randomly assigned (initially in a 1:1 ratio and then 2:1 following a protocol amendment) to tepotinib plus gefitinib at the recommended phase 2 dose or to standard platinum doublet chemotherapy. Randomisation was done centrally via an interactive voice-response system. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. Subgroup analyses were preplanned in patients with high MET overexpression (IHC3+) or MET amplification (mean gene copy number ≥5 or MET to centromere of chromosome 7 ratio ≥2). Efficacy and patient characteristics were assessed on an intention-to-treat basis and safety was assessed for all patients who received at least one dose of study medication. Low recruitment led to early termination of phase 2, so all analyses are considered to be exploratory. This study is registered with ClinicalTrials.gov , NCT01982955 , and the European Union Drug Regulating Authorities Clinical Trials Database, Eudra-CT 2016-001604-28. Findings From Dec 23, 2013, to May 25, 2017, 18 patients were enrolled in phase 1b (n=6 in the 300 mg tepotinib group; n=12 in the 500 mg tepotinib group) and 55 patients in phase 2 (n=31 in the tepotinib plus gefitinib group; n=24 in the chemotherapy group). No dose-limiting toxicities were observed in phase 1b, so tepotinib 500 mg was used as the recommended phase 2 dose. In phase 2, survival outcomes were similar between groups: median PFS was 4·9 months in the tepotinib plus gefitinib group (90% CI 3·9–6·9) versus 4·4 months in the chemotherapy group (90% CI 4·2–6·8; hazard ratio [HR] 0·67, 90% CI 0·35–1·28). Median OS was 17·3 months in the tepotinib plus gefitinib group (12·1–37·3) versus 18·7 months in the chemotherapy group (15·9–20·7; HR 0·69, 0·34–1·41). PFS and OS were longer with tepotinib plus gefitinib than with chemotherapy in patients with high (IHC3+) MET overexpression (n=34; median PFS 8·3 months [4·1–16·6] vs 4·4 months [4·1–6·8]; HR 0·35, 0·17–0·74; median OS 37·3 months [90% CI 24·2–37·3] vs 17·9 months [12·0–20·7]; HR 0·33, 0·14–0·76) or MET amplification (n=19; median PFS 16·6 months [8·3–not estimable] vs 4·2 months [1·4–7·0]; HR 0·13, 0·04–0·43; median OS 37·3 months [90% CI not estimable] vs 13·1 months [3·25–not estimable]; HR 0·08, 0·01–0·51). The most frequent treatment-related grade 3 or worse adverse events were increased amylase (5 [16%] of 31 patients) and lipase (4 [13%]) concentrations in the tepotinib plus gefitinib group and anaemia (7 [30%] of 23 patients) and decreased neutrophil count (3 [13%]) in the chemotherapy group. Interpretation Despite early study termination, in a preplanned subgroup analysis, our findings suggest improved anti activity for tepotinib plus gefitinib compared with standard chemotherapy in patients with EGFR-mutant NSCLC and MET amplification, warranting further exploration. Funding Merck KGaA.
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- 2020
16. Choroidal Structural Changes Assessed with Swept-Source Optical Coherence Tomography after Cataract Surgery in Eyes with Diabetic Retinopathy
- Author
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Xi Shen, Xiaoqing Liu, Huiping Yao, Yufeng Zhou, Yu Cheng, and Sha Gao
- Subjects
medicine.medical_specialty ,Article Subject ,genetic structures ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,After cataract ,Diabetic retinopathy ,Phacoemulsification ,RE1-994 ,Cataract surgery ,medicine.disease ,Diabetic cataract ,eye diseases ,Surgery ,Ophthalmology ,Vascularity ,Optical coherence tomography ,medicine ,In patient ,sense organs ,medicine.symptom ,business ,Research Article - Abstract
Objective. To determine the influence of phacoemulsification on choroidal vasculature in patients with diabetic retinopathy (DR) undergoing cataract surgery using swept-source optical coherence tomography (SS-OCT). Methods. The study was conducted in 23 eyes of 23 cataract patients with mild/moderate nonproliferative diabetic retinopathy (NPDR) without diabetic macular edema (DME) and 23 age-matched controls. Choroidal thickness (CT) and choroidal vascularity index (CVI) were measured at baseline and 1 week, 1 month, and 3 months after surgery. Results. The baseline CVI in the DR group was significantly lower than that in the control group ( P = 0.001 ). CVI in DR patients after surgery significantly increased compared with preoperative values (all P < 0.001 for 1 week, 1 month, and 3 months after surgery). Postoperative increase of CVI and CT in the DR group was more than in the control group, and the difference was significant 1 month and 3 months after surgery (all P < 0.05 ). Conclusion. Patients with mild/moderate NPDR have reduced CVI compared with nondiabetic patients at baseline; diabetic cataract surgery tended to induce more increase in CVI and CT as compared with nondiabetic patients. This trial is registered with NCT04499768.
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- 2020
17. Shifts in gut microbiome and metabolome are associated with risk of recurrent atrial fibrillation
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Xiandong Yin, Jing Li, Xiaoqing Liu, Kun Zuo, Zheng Liu, Chaowei Hu, Jing Zhang, Kuibao Li, Jie Jiao, Pan Wang, and Xinchun Yang
- Subjects
Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,recurrence ,Recurrent atrial fibrillation ,Bacillus ,Kaplan-Meier Estimate ,Gut flora ,Risk Assessment ,predictive model ,03 medical and health sciences ,0302 clinical medicine ,Metabolomics ,Nitrosomonadaceae ,Internal medicine ,Atrial Fibrillation ,medicine ,Metabolome ,Humans ,Faecalibacterium ,Aged ,gut microbiota ,biology ,Gene Expression Profiling ,Incidence ,Incidence (epidemiology) ,Atrial fibrillation ,Original Articles ,Cell Biology ,Middle Aged ,Nomogram ,biology.organism_classification ,medicine.disease ,Gastrointestinal Microbiome ,Treatment Outcome ,030104 developmental biology ,Metagenomics ,Area Under Curve ,030220 oncology & carcinogenesis ,Molecular Medicine ,Original Article ,Female ,metabolism - Abstract
Alternations of gut microbiota (GM) in atrial fibrillation (AF) with elevated diversity, perturbed composition and function have been described previously. The current work aimed to assess the association of GM composition with AF recurrence (RAF) after ablation based on metagenomic sequencing and metabolomic analyses and to construct a GM‐based predictive model for RAF. Compared with non‐AF controls (50 individuals), GM composition and metabolomic profile were significantly altered between patients with recurrent AF (17 individuals) and non‐RAF group (23 individuals). Notably, discriminative taxa between the non‐RAF and RAF groups, including the families Nitrosomonadaceae and Lentisphaeraceae, the genera Marinitoga and Rufibacter and the species Faecalibacterium spCAG:82, Bacillus gobiensis and Desulfobacterales bacterium PC51MH44, were selected to construct a taxonomic scoring system based on LASSO analysis. After incorporating the clinical factors of RAF, taxonomic score retained a significant association with RAF incidence (HR = 2.647, P = .041). An elevated AUC (0.954) and positive NRI (1.5601) for predicting RAF compared with traditional clinical scoring (AUC = 0.6918) were obtained. The GM‐based taxonomic scoring system theoretically improves the model performance, and the nomogram and decision curve analysis validated the clinical value of the predicting model. These data provide novel possibility that incorporating the GM factor into future recurrent risk stratification.
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- 2020
18. Pharmacokinetic/pharmacodynamics variability of echinocandins in critically ill patients: A systematic review and meta‐analysis
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Xiaoqing Liu, Ying Pan, Dongdong Liu, and Yimin Li
- Subjects
pharmacokinetic/pharmacodynamics variability ,medicine.medical_specialty ,Antifungal Agents ,Echinocandin ,Critical Illness ,critically ill patients ,Cmax ,Review Article ,Cochrane Library ,Anidulafungin ,030226 pharmacology & pharmacy ,echinocandins ,03 medical and health sciences ,chemistry.chemical_compound ,Cmin ,0302 clinical medicine ,Caspofungin ,Internal medicine ,polycyclic compounds ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Review Articles ,Pharmacology ,business.industry ,Micafungin ,bacterial infections and mycoses ,chemistry ,Area Under Curve ,Pharmacodynamics ,business ,Invasive Fungal Infections ,medicine.drug - Abstract
What is known and objective Anidulafungin, caspofungin and micafungin are three widely used echinocandin drugs licensed for the treatment of invasive fungal infections, and their clinical use is widespread. To evaluate pharmacokinetic/pharmacodynamics variability of echinocandins in critically ill patients by comparing the differences in pharmacokinetic parameters between critically ill patients and healthy volunteers or general patients. Methods MEDLINE, EMBASE, The Cochrane Library and Pubmed were searched from inception until 6 September 2018. Studies investigating the pharmacokinetic parameters of echinocandins in critically ill patients, healthy volunteers or general patients were included. Our primary outcomes included AUC0‐24 h, Cmax and Cmin (24 hours). Two reviewers independently reviewed all titles, abstracts and text, and extracted data. We applied R software (R 2017) to conduct meta‐analysis. Results and discussion Of 3235 articles screened, 17 studies were included in the data synthesis. Descriptive data from single‐arm studies show that critically ill patients who received caspofungin had more stable AUC0‐24 h than those who received anidulafungin and micafungin. The Cmax of critically ill patients who received caspofungin and micafungin was similar to healthy volunteers. However, the Cmax in critically ill patients who received anidulafungin was lower than in healthy volunteers. The Cmin and T1/2 of critically ill patients who received caspofungin were larger than in healthy volunteers. The Vd and CL of critically ill patients receiving anidulafungin and micafungin were larger than in healthy volunteers. What is new and conclusion This systematic review provides an analysis of the pharmacokinetic/pharmacodynamics variability of echinocandins in critically ill patients. Based on the limited data available, caspofungin has less pharmacokinetic/pharmacodynamics variability than anidulafungin and micafungin., This systematic review included 17 studies. Descriptive data from single‐arm studies showed that in critical ill patients who received caspofungin has more stable AUC0‐24 h than those who received anidulafungin and micafungin. However, the Cmax in critical ill patients who received anidulafungin was lower than in healthy volunteers.
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- 2020
19. SARS‐CoV‐2 environmental contamination associated with persistently infected COVID‐19 patients
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Sook San Wong, Feng Ye, Qiubao Wu, Xiaoqing Liu, Hui Lei, Jing Cheng, Benjamin J. Cowling, Xiaoqun Huang, Yanmin Xie, Shiguan Wu, Shiman Ling, Yimin Li, Mark Zanin, Zhenting Huang, Cheng Xiao, Jianxing He, Dan Ye, Nancy H. L. Leung, Zhanpeng Jiang, and Yang Zifeng
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Isolation (health care) ,Epidemiology ,Pneumonia, Viral ,coronavirus ,Antibodies, Viral ,intensive care unit ,SARS‐CoV‐2 ,law.invention ,Patient Isolation ,Betacoronavirus ,COVID‐19 ,law ,Internal medicine ,Pandemic ,Environmental Microbiology ,Humans ,Medicine ,Pandemics ,Aged, 80 and over ,biology ,SARS-CoV-2 ,business.industry ,Transmission (medicine) ,transmission ,Public Health, Environmental and Occupational Health ,COVID-19 ,Original Articles ,Middle Aged ,Viral Load ,Isolation ward ,Intensive care unit ,Intensive Care Units ,Infectious Diseases ,Humoral immunity ,biology.protein ,RNA, Viral ,Original Article ,Female ,Antibody ,Coronavirus Infections ,business ,Viral load - Abstract
Background Severe COVID‐19 patients typically test positive for SARS‐CoV‐2 RNA for extended periods of time, even after recovery from severe disease. Due to the timeframe involved, these patients may have developed humoral immunity to SARS‐CoV‐2 while still testing positive for viral RNA in swabs. Data are lacking on exposure risks in these situations. Here, we studied SARS‐CoV‐2 environmental contamination in an ICU and an isolation ward caring for such COVID‐19 patients. Methods We collected air and surface samples in a hospital caring for critical and severe COVID‐19 cases from common areas and areas proximal to patients. Results Of the 218 ICU samples, an air sample contained SARS‐CoV‐2 RNA. Of the 182 isolation ward samples, nine contained SARS‐CoV‐2 RNA. These were collected from a facemask, the floor, mobile phones, and the air in the patient room and bathroom. Serum antibodies against SARS‐CoV‐2 were detected in these patients at the beginning of the study. Conclusions While there is a perception of increased risk in the ICU, our study demonstrates that isolation wards may pose greater risks to healthcare workers and exposure risks remain with clinically improved patients, weeks after their initial diagnoses. As these patients had serum antibodies, further studies may be warranted to study the utility of serum antibodies as a surrogate of viral clearance in allowing people to return to work. We recommend continued vigilance even with patients who appear to have recovered from COVID‐19.
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- 2020
20. Efficacy of convalescent plasma for the treatment of severe influenza
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Zhiheng Xu, Zhimin Lin, Sibei Chen, Yongbo Huang, Dongdong Liu, Xuesong Liu, Yimin Li, Xiaoqing Liu, Jianmeng Zhou, and Yonghao Xu
- Subjects
medicine.medical_specialty ,Convalescent plasma ,Efficacy ,medicine.medical_treatment ,Critical Care and Intensive Care Medicine ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Case fatality rate ,Influenza, Human ,medicine ,Odds Ratio ,Humans ,030212 general & internal medicine ,Adverse effect ,COVID-19 Serotherapy ,Mechanical ventilation ,business.industry ,Research ,Immunization, Passive ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,COVID-19 ,Odds ratio ,lcsh:RC86-88.9 ,Severe influenza ,Intensive care unit ,Meta-analysis ,030228 respiratory system ,business ,Viral load - Abstract
Background Convalescent plasma administration may be of clinical benefit in patients with severe influenza, but reports on the efficacy of this therapy vary. Methods We conducted a systematic review and meta-analysis assessing randomized controlled trials (RCTs) involving the administration of convalescent plasma to treat severe influenza. Healthcare databases were searched in February 2020. All records were screened against eligibility criteria, and the risks of bias were assessed. The primary outcome was the fatality rate. Results A total of 2861 studies were retrieved and screened. Five eligible RCTs were identified. Pooled analyses yielded no evidence that using convalescent plasma to treat severe influenza resulted in significant reductions in mortality (odds ratio, 1.06; 95% CI, 0.51–2·23; P = 0.87; I2 = 35%), number of days in the intensive care unit, or number of days on mechanical ventilation. This treatment may have the possible benefits of increasing hemagglutination inhibition titers and reducing influenza B viral loads and cytokine levels. No serious adverse events were reported. The included studies were generally of high quality with a low risk of bias. Conclusions The administration of convalescent plasma appears safe but may not reduce the mortality, number of days in the intensive care unit, or number of days on mechanical ventilation in patients with severe influenza.
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- 2020
21. Definition and Risks of Cytokine Release Syndrome in 11 Critically Ill COVID-19 Patients With Pneumonia: Analysis of Disease Characteristics
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Lie Puyi, Wenjun Wang, Sipei Wu, Linling Cheng, Xiaoqing Liu, Yongping Lin, Jianxing He, Lingbo Nong, Sibei Chen, liyan Huang, and Yimin Li
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Critical Illness ,Pneumonia, Viral ,Betacoronavirus ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Severe/critical pneumonia ,Risk Factors ,Internal medicine ,Major Article ,medicine ,Humans ,Immunology and Allergy ,AcademicSubjects/MED00860 ,Risk factor ,Pandemics ,Aged ,IL-6 ,Interleukin-6 ,SARS-CoV-2 ,Critically ill ,business.industry ,Pulmonary inflammation ,COVID-19 ,Middle Aged ,Prognosis ,medicine.disease ,Pneumonia ,Cytokine release syndrome ,AcademicSubjects/MED00290 ,030104 developmental biology ,Infectious Diseases ,030220 oncology & carcinogenesis ,Leukocytes, Mononuclear ,Female ,Disease characteristics ,Coronavirus Infections ,Cytokine Release Syndrome ,business ,Immunophenotype ,Biomarkers - Abstract
Corona Virus Disease 2019(COVID-19)-affected patients with severe immune abnormalities have a risk of cytokine release syndrome. The definition, prevention, and treatment of symptoms of cytokine release syndrome in critically ill patients with COVID-19 are important problems. This was a single-center case series of 11 COVID-19 patients with acute respiratory distress syndrome (ARDS) from The First Affiliated Hospital of Guangzhou Medical University in China from January 26, 2020 to February 18, 2020. The termination date of follow-up was February 19, 2020. In this single-center analysis of 11 critically ill patients with COVID-19, 8 patients were determined to have characteristics of cytokine release syndrome (CRS), including pulmonary inflammation, fever, and dysfunction of non-pulmonary organs; an increase of- Interleukin-6 (IL-6) in peripheral blood was the highest risk factor and an early indicator of CRS in COVID-19.
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- 2020
22. Hematological findings in coronavirus disease 2019: indications of progression of disease
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Run Zhang, Xiaoqing Liu, and Guangsheng He
- Subjects
Male ,China ,medicine.medical_specialty ,Neutrophils ,Anemia ,Pneumonia, Viral ,Review Article ,Disease ,CD8-Positive T-Lymphocytes ,Neutrophilia ,medicine.disease_cause ,Betacoronavirus ,Hemoglobins ,Leukocyte Count ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Lymphopenia ,Internal medicine ,Humans ,Medicine ,Hemoglobin ,Lung ,Pandemics ,Coronavirus ,Hematology ,SARS-CoV-2 ,business.industry ,COVID-19 ,Outbreak ,General Medicine ,medicine.disease ,Thrombocytopenia ,CD4 Lymphocyte Count ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Immunology ,Disease Progression ,Female ,medicine.symptom ,Coronavirus Infections ,business ,030215 immunology - Abstract
Coronavirus disease 2019 (COVID-19) is a new human infectious disease. The etiology for this outbreak is a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus far, related research on COVID-19 is still in preliminary stage. This paper summarized the latest outcomes of corresponding study from Chinese centers and clarified the hematopoietic abnormality caused by SARS-CoV-2 and potential mechanism. Lymphopenia was common in the early stage after the onset of COVID-19. A significant decrease was observed in peripheral CD4+ and CD8+ T lymphocytes. As the illness progressed, neutrophilia emerged in several cases, and patients with severe critical pulmonary conditions showed higher neutrophils than common type. Thrombocytopenia was resulting from the consumption and/or the reduced production of platelets in damaged lungs. Anemia was not observed notably, but the decrease in hemoglobin was frequent. The activation of monocyte-macrophage system aggravates the immune damage of lung and other tissues, which leads to the increase of D-dimer, prothrombin time, and platelet consumption.
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- 2020
23. Health-related quality of life (QoL) in patients with advanced melanoma receiving immunotherapies in real-world clinical practice settings
- Author
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Richard W. Joseph, Frank Xiaoqing Liu, Qing Harshaw, Todd L. Saretsky, Alan S. Pickard, Scott J. Diede, Cynthia Macahilig, Alicia C. Shillington, and Vaidehi Dave
- Subjects
Male ,Quality of life ,medicine.medical_specialty ,Visual analogue scale ,medicine.medical_treatment ,Pembrolizumab ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,Melanoma ,Patient reported outcomes ,Advanced melanoma ,business.industry ,Public health ,Public Health, Environmental and Occupational Health ,Repeated measures design ,Immunotherapy ,Middle Aged ,030220 oncology & carcinogenesis ,Metastatic ,Female ,Observational study ,business - Abstract
Background Pembrolizumab (PEMBRO) and ipilimumab + nivolumab (IPI + NIVO) are approved advanced melanoma (AM) immunotherapies. To address limited health-related quality of life (QoL) real-world evidence with immunotherapies in AM, we compared QoL in AM patients receiving either treatment in clinical practice. Methods A prospective US observational study enrolled adult AM patients initiating first-line PEMBRO or IPI + NIVO between June 2017 and March 2018. Endpoints included the QLQ-C30 global health score (GHS) and EuroQol visual analog scale (EQ-VAS) scores. Mean changes were compared using repeated measures mixed-effects models and are presented covariate adjusted. Results 225 PEMBRO and 187 IPI + NIVO patients were enrolled. From baseline through week 24, PEMBRO was associated with 3.2 mean GHS score increase (95% CI 0.5, 5.9; p = .02), while no change was observed with IPI + NIVO; 0.2 (95% CI − 2.6, 3.0; p = 0.87). Among objective treatment-responders, GHS scores associated with PEMBRO increased 6.0 (95% CI 3.1, 8.8; p p = .01). In treatment non-responders, IPI + NIVO was associated with GHS/QoL deterioration of − 3.7 (95% CI − 6.8, − 0.6; p = .02), PEMBRO non-responders demonstrated no change; 0.7 (95% CI − 2.3, 3.7; p = 0.6). Between treatments, PEMBRO patients increased 2.6 greater in EQ-VAS (95% CI 0.6, 4.5; p = .01) vs IPI + NIVO at 24 weeks. Conclusions PEMBRO was associated with better 24-week QoL compared to IPI + NIVO in actual clinical practice settings. Real-world data has known limitations, but with further confirmation these results may have implications for treatment selection.
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- 2020
24. Efficacy and Safety of Anlotinib in Advanced Non-Small Cell Lung Cancer: A Real-World Study
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Xiaoqing Liu, Hongjun Gao, Kun Zhang, Xiya Ma, Hong Wang, Haifeng Qin, and Shaoxing Yang
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Chemotherapy ,Univariate analysis ,business.industry ,Proportional hazards model ,medicine.medical_treatment ,Retrospective cohort study ,medicine.disease ,Confidence interval ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Adverse effect ,business ,Lung cancer ,neoplasms ,Survival analysis - Abstract
Purpose The ALTER0303 trial showed that anlotinib, a novel antiangiogenic tyrosine kinase inhibitor, administered as third-line or further treatment prolonged progression-free survival (PFS) and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC). This retrospective study investigated the efficacy and safety of anlotinib in real-world settings. Patients and methods Medical records of patients with advanced NSCLC receiving anlotinib as third-line or further treatment were collected, and survival curves were derived using the Kaplan-Meier method. Univariate analysis was performed by log-rank testing. Cox regression analysis was used to evaluate the significance of factors obtained from the univariate analysis. Results Fifty-two patients with advanced NSCLC were included. The objective response rate was 16%, and the disease control rate was 80%. The median PFS was 4.5 months (95% confidence interval [CI]: 3.6-5.4), and the median OS was 9 months (95% CI: 6.5-11.5). Univariate analysis revealed that the group of patients with longer PFS and OS included Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1, ≤2 distant metastases, no liver metastases, ≤3 previous treatment lines, and ≤2 previous chemotherapy lines. Cox regression analysis demonstrated that only patients with ECOG PS ≤1 or no liver metastases had longer PFS and OS. Grade 3 treatment-related adverse events were reported in 14% of the patients, but no life-threatening adverse events were reported. Conclusion Anlotinib was well tolerated and effective in patients with advanced NSCLC in real-world conditions. Patients with ECOG PS ≤1 or no liver metastases have longer PFS and OS.
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- 2020
25. Cardiac operation under cardiopulmonary bypass during pregnancy
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Jian Zhuang, Yanli Liu, Cheng-bin Zhou, Huanlei Huang, Fengzhen Han, Sheng Wang, Jimei Chen, and Xiaoqing Liu
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Pulmonary and Respiratory Medicine ,Adult ,medicine.medical_specialty ,Heart disease ,Pregnancy Complications, Cardiovascular ,lcsh:Surgery ,law.invention ,lcsh:RD78.3-87.3 ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,law ,Pregnancy ,Infant Mortality ,medicine ,Cardiopulmonary bypass ,Humans ,030212 general & internal medicine ,Cardiac Surgical Procedures ,Twin Pregnancy ,Retrospective Studies ,Outcome ,Aortic dissection ,030219 obstetrics & reproductive medicine ,business.industry ,Infant, Newborn ,Infant ,General Medicine ,lcsh:RD1-811 ,medicine.disease ,Surgery ,Cardiac surgery ,Cardiac operation ,Treatment Outcome ,Cardiothoracic surgery ,lcsh:Anesthesiology ,Infective endocarditis ,Fetal Mortality ,Female ,Cardiology and Cardiovascular Medicine ,business ,Research Article - Abstract
Background Certain pregnant women suffer from cardiac pathology,and a few of them need cardiac operations under cardiopulmonary bypass during pregnancy. Feto-neonatal and maternal outcomes have not been sufficiently described. Methods We conducted a retrospective review of 22 cases of women undergoing cardiac operations under cardiopulmonary bypass during pregnancy in our hospital from Jan.2014 to Mar.2019. Results All 22 patients were alive after treatment. The types of cardiac disorders included congenital heart defects, rheumatic heart disease,infective endocarditis,aortic dissection, obstruction and/or thrombosis of a prosthetic valve. Only one case was a twin pregnancy,and the other 21 cases were singletons. Four fetuses died in the utero after surgery. Three patients chose termination of the pregnancy after the cardiac operations: one fetus was detected abnormity of the brain and the other two patients abandoned pregnancy. Fourteen fetuses were alive and born without any abnormity. Two fetuses suffered from neonatal intracranial hemorrhage and died after birth. Conclusions Cardiac operation under cardiopulmonary bypass during pregnancy is a challenge for physicians in multidisciplinary teams. Strictly evaluating the indication is vital. On the other hand, some patients can benefit from this management.
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- 2020
26. HSR20-096: Budget Impact Analysis of Avelumab Plus Axitinib for the First-Line Treatment of Patients With Advanced Renal Cell Carcinoma
- Author
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Kirstin Heinrich, Adam Kasle, Catarina Neves, Ying Zheng, and Frank Xiaoqing Liu
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Budget impact ,medicine.disease ,First line treatment ,Avelumab ,Axitinib ,Renal cell carcinoma ,Internal medicine ,Medicine ,business ,medicine.drug - Published
- 2020
27. Immunosuppressive therapy for elderly-acquired pure red cell aplasia: cyclosporine A may be more effective
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Jian-Fu Zhang, Xiaoqing Liu, Jianyong Li, Lang Chen, Xuemei Wu, Yan Yang, Guangsheng He, Ruinan Lu, Xingyu Lu, Yu Zhu, Ming Hong, and Shuai Wang
- Subjects
Adult ,Male ,medicine.medical_specialty ,Acquired Pure Red Cell Aplasia ,Red-Cell Aplasia, Pure ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Overall response rate ,Internal medicine ,Remission Induction Therapy ,medicine ,Humans ,Aged ,Aged, 80 and over ,Immunosuppression Therapy ,Response rate (survey) ,Hematology ,Adult patients ,business.industry ,Remission Induction ,Age Factors ,social sciences ,General Medicine ,Aplasia ,Middle Aged ,medicine.disease ,humanities ,Regimen ,030220 oncology & carcinogenesis ,Cyclosporine ,Female ,business ,030215 immunology - Abstract
This current study retrospectively analyzed the clinical characteristics of 69 adult patients with acquired pure red cell aplasia (PRCA) including 40 elderly and 29 non-elderly patients from September 2009 to June 2019. The remission induction therapy regimens included cyclosporine A (CsA), corticosteroids (CS), or other immunosuppressive agents. The overall response rate was 55% (22/40) in the elderly group compared with 75.9% (22/29) in non-elderly patients (P = 0.075). In elderly patients, the best remission was achieved in the group treated with CsA than those treated with CS or other immunosuppressive agents (83.3% vs 26.7% vs 42.9%%, P = 0.004). However, outcomes of remission were similar among different treatment groups (P = 0.458) in non-elderly patients. CS induced a higher response rate in the non-elderly than that in the elderly (88.9% vs 26.7%, P = 0.009). By univariate and multivariate analysis, the clinical efficacy of elderly patients with acquired PRCA was closely associated with an induction regimen of CsA (P = 0.009; P = 0.017). In conclusion, CsA might produce higher response rate than CS and other drugs in elderly patients with acquired PRCA.
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- 2020
28. Efficacy, safety, and biomarker analysis of ensartinib in crizotinib-resistant, ALK-positive non-small-cell lung cancer: a multicentre, phase 2 trial
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Zhendong Zheng, Xiaoqing Liu, Yubiao Guo, Xiaobin Yuan, Jifeng Feng, Weineng Feng, Wei Song, Li Mao, Jun Zhao, Yiping Zhang, Yanqiu Zhao, Lieming Ding, Shanshan Xiao, Jianying Zhou, Yuanqing Fu, Lejie Cao, Jianhua Chen, J. Zhou, Wu Zhuang, Yong Song, Tao Wang, Li Zhang, Chengzhi Zhou, Shijun Zhao, Yuan Chen, Giovanni Selvaggi, Yi Hu, Zhuang Yu, Yunpeng Yang, Y. Gong, Wei Zhong, K. Ma, Jian Fang, Ning Wu, Gang Wu, Yun Fan, Yunpeng Liu, Gaofeng Li, Shucai Zhang, and Feng Ye
- Subjects
Male ,Pulmonary and Respiratory Medicine ,Oncology ,China ,medicine.medical_specialty ,Lung Neoplasms ,medicine.drug_class ,Phases of clinical research ,Piperazines ,law.invention ,Crizotinib ,Randomized controlled trial ,law ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,medicine ,Humans ,Anaplastic Lymphoma Kinase ,Neoplasm Metastasis ,Lung cancer ,Adverse effect ,Protein Kinase Inhibitors ,business.industry ,medicine.disease ,Pyridazines ,ALK inhibitor ,Clinical trial ,Response Evaluation Criteria in Solid Tumors ,Female ,business ,medicine.drug - Abstract
Summary Background Ensartinib is a potent new-generation ALK inhibitor with high activity against a broad range of known crizotinib-resistant ALK mutations and CNS metastases. We aimed to assess the efficacy and safety of ensartinib in ALK-positive patients with non-small-cell lung cancer (NSCLC), in whom crizotinib therapy was unsuccessful. The associations between ensartinib efficacy and crizotinib-resistant mutations were also explored. Methods We did a single-arm, open-label, phase 2 study at 27 centres in China. Patients were aged 18 years or older, had stage IIIb or stage IV ALK-positive NSCLC that had progressed while they were on crizotinib therapy, an Eastern Cooperative Oncology Group performance status of 2 or less, had measurable disease, and had received fewer than three previous treatments. Patients with CNS metastases were included if these metastases were asymptomatic and did not require steroid therapy. All patients received 225 mg ensartinib orally once daily on a continuous dosing schedule. The primary outcome was the proportion of patients with an objective response according to the Response Evaluation Criteria in Solid Tumors (version 1.1), as assessed by an independent review committee in all patients who received at least one dose of ensartinib with no major violations of the inclusion criteria (ie, the full analysis set). Safety was assessed in all enrolled patients who received at least one dose of ensartinib. This trial was registered with ClinicalTrials.gov , NCT03215693 . Findings Between Sept 28, 2017, and April 11, 2018, 160 patients were enrolled and had at least one dose of ensartinib (safety analysis set). Four patients had inclusion violations and were excluded from the efficacy analysis, which thus included 156 patients (full analysis set). 97 (62%) patients in the full analysis set had brain metastases. 76 (52% [95% CI 43–60]) of 147 patients in the full analysis set, with responses that could be assessed by the independent review committee, had an objective response. 28 (70% [53–83]) of 40 patients with measurable brain metastases as assessed by the independent review committee had an intracranial objective response. 145 (91%) of 160 patients had at least one treatment-related adverse event, which were mostly grade 1 or 2. The most common treatment-related adverse events were rash (89 [56%]), increased alanine aminotransferase concentrations (74 [46%]), and increased aspartate aminotransferase concentrations (65 [41%]). Interpretation Ensartinib has activity and is well tolerated in patients with crizotinib-refractory, ALK-positive NSCLC, including those with brain metastases. The role of ensartinib in patients in whom other second-generation ALK inhibitors have been unsuccessful warrants further studies. Funding Betta Pharmaceuticals.
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- 2020
29. Kinetics of SARS-CoV-2 specific IgM and IgG responses in COVID-19 patients
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Ying Feng, Longyu Wang, Baoqing Sun, Ling Chen, Nanshan Zhong, Peiyan Zheng, Zhifeng Huang, Ping Peng, Fan Zhang, Huimin Huang, Qian Wang, Peiyu Hu, Fang Li, Xuefeng Niu, Wenting Luo, Feng Li, Xiaoneng Mo, Hui Peng, Zhilong Chen, Liqiang Feng, Fuchun Zhang, Xiaoqing Liu, and Pingchao Li
- Subjects
Male ,0301 basic medicine ,Epidemiology ,Antibodies, Viral ,Gastroenterology ,Serum antibody ,law.invention ,COVID-19 Testing ,law ,Drug Discovery ,biology ,General Medicine ,Middle Aged ,Nucleocapsid Proteins ,Intensive care unit ,Infectious Diseases ,Spike Glycoprotein, Coronavirus ,Female ,Coronavirus Infections ,medicine.medical_specialty ,IgM ,Critical Care ,Coronavirus disease 2019 (COVID-19) ,IgG ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Pneumonia, Viral ,030106 microbiology ,Immunology ,Microbiology ,Article ,C-reactive protein ,Disease course ,COVID-19 ,SARS-CoV-2 ,Betacoronavirus ,03 medical and health sciences ,Virology ,Internal medicine ,medicine ,Coronavirus Nucleocapsid Proteins ,Humans ,Symptom onset ,Pandemics ,Aged ,Clinical Laboratory Techniques ,business.industry ,Phosphoproteins ,Specific igm ,Kinetics ,030104 developmental biology ,Immunoglobulin M ,Immunoglobulin G ,biology.protein ,Parasitology ,business - Abstract
The emerging COVID-19 caused by SARS-CoV-2 infection poses severe challenges to global public health. Serum antibody testing is becoming one of the critical methods for the diagnosis of COVID-19 patients. We investigated IgM and IgG responses against SARS-CoV-2 nucleocapsid (N) and spike (S) protein after symptom onset in the intensive care unit (ICU) and non-ICU patients. 130 blood samples from 38 COVID-19 patients were collected. The levels of IgM and IgG specific to N and S protein were detected by ELISA. A series of blood samples were collected along the disease course from the same patient, including 11 ICU patients and 27 non-ICU patients for longitudinal analysis. N and S specific IgM and IgG (N-IgM, N-IgG, S-IgM, S-IgG) in non-ICU patients increased after symptom onset. N-IgM and S-IgM in some non-ICU patients reached a peak in the second week, while N-IgG and S-IgG continued to increase in the third week. The combined detection of N and S specific IgM and IgG could identify up to 75% of SARS-CoV-2 infected patients in the first week. S-IgG was significantly higher in non-ICU patients than in ICU patients in the third week. In contrast, N-IgG was significantly higher in ICU patients than in non-ICU patients. The increase of S-IgG positively correlated with the decrease of C-reactive protein (CRP) in non-ICU patients. N and S specific IgM and IgG increased gradually after symptom onset and can be used for detection of SARS-CoV-2 infection. Analysis of the dynamics of S-IgG may help to predict prognosis.
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- 2020
30. Integrated Content and Network-Based Service Clustering and Web APIs Recommendation for Mashup Development
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Xiaoqing Liu, Jianxun Liu, Mahfuzer Rahman, Buqing Cao, Bing Li, and Mingdong Tang
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Web standards ,medicine.medical_specialty ,Information Systems and Management ,Web development ,Application programming interface ,Computer Networks and Communications ,Computer science ,business.industry ,02 engineering and technology ,computer.software_genre ,Web API ,Computer Science Applications ,World Wide Web ,Hardware and Architecture ,020204 information systems ,0202 electrical engineering, electronic engineering, information engineering ,medicine ,Collaborative filtering ,020201 artificial intelligence & image processing ,Mashup ,Web service ,business ,computer ,Web modeling - Abstract
The rapid growth in the number and diversity of Web APIs, coupled with the myriad of functionally similar Web APIs, makes it difficult to find most suitable Web APIs for users to accelerate and accomplish Mashup development. Even if the existing methods show improvements in Web APIs recommendation, it is still challenging to recommend Web APIs with high accuracy and good diversity. In this paper, we propose an integrated content and network-based service clustering and Web APIs recommendation method for Mashup development. This method, first develop a two-level topic model by using the relationship among Mashup services to mine the latent useful and novel topics for better service clustering accuracy. Moreover, based on the clustering results of Mashups, it designs a collaborative filtering (CF) based Web APIs recommendation algorithm. This algorithm, exploits the implicit co-invocation relationship between Web APIs inferred from the historical invocation history between Mashups clusters and the corresponding Web APIs, to recommend diverse Web APIs for each Mashups clusters. The method is expected to not only find much better matched Mashups with high accuracy, but also diversify the recommendation result of Web APIs with full coverage. Finally, based on a real-world dataset from ProgrammableWeb, we conduct a comprehensive evaluation to measure the performance of our method. Compared with existing methods, experimental results show that our method significantly improves the accuracy and diversity of recommendation results in terms of precision, recall, purity, entropy, DCG and HMD.
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- 2020
31. Multiplexed Imaging with Coordination Nanoparticles for Cancer Diagnosis and Therapy
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Xiaoqing Liu, Zhen Xu, Jie Feng, and Dan Luo
- Subjects
Multimodal imaging ,Oncology ,medicine.medical_specialty ,business.industry ,Biochemistry (medical) ,Biomedical Engineering ,Cancer therapy ,Cancer ,General Chemistry ,medicine.disease ,Biomaterials ,Internal medicine ,medicine ,business - Abstract
Multiplexed imaging offers great potential for precise and accurate diagnosis and therapy. Integrating multiplexed imaging with theranostics is promising to develop cancer therapeutics and diagnostics. However, the lack of versatile platforms with inherent different modalities and various probes hinders the potential of multiplexing imaging for cancer diagnosis and therapy. Here, we demonstrate that multiplexed imaging with advanced theranostic nanomaterials provides a potent method for cancer diagnostics and therapeutics both
- Published
- 2022
32. Baseline Characteristics and Treatment Patterns of the Patients Recruited to the China Registry of Hepatitis B
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Hong Ren, Caixia Yang, Lingyi Zhang, Junqi Niu, Hongxin Piao, Shiping Li, Wu Li, Xiaoxuan Hu, Huanwei Zheng, Huiguo Ding, Jidong Jia, Youqing Xu, Shumei Lin, Xun Li, Hong Tang, Guanghua Xu, Lei Wang, Yuexin Zhang, Liaoyun Zhang, Yufang Li, Xizhong Yang, Xinhua Luo, Wenxiang Huang, Yuemin Nan, Qing Xie, Shourong Liu, X. Dou, Xihong Wang, Tao Han, Dongliang Yang, Xiaozhong Wang, Xuebing Yan, Jilin Cheng, Weijin Gong, Jia Shang, Hui Zhuang, Qinghua Lu, Cunliang Deng, Yong Xiong, Wen Xie, Lai Wei, Yan Huang, Yuanyuan Kong, Zhongping Duan, Mingliang Cheng, Xiaoyuan Xu, Shan Shan, Xiaoqing Liu, Xiaolan Zhang, Jinlin Hou, Hong You, Feng Lin, and Hai Li
- Subjects
Registry ,HBsAg ,medicine.medical_specialty ,Cirrhosis ,Hepatology ,business.industry ,Entecavir ,Hepatitis B ,medicine.disease ,Gastroenterology ,Virus ,Treatment ,HBeAg ,Interferon ,Hepatocellular carcinoma ,Internal medicine ,medicine ,Original Article ,business ,medicine.drug - Abstract
Background and Aims: Chronic hepatitis B virus (HBV) infection remains a major public health problem globally. Here, we describe the baseline characteristics and treatment profiles of HBV-infected patients recruited to the China Registry of Hepatitis B. Methods: Inclusion criteria were patients with different stages of chronic HBV infection and complete key data. Exclusion criteria were patients with hepatocellular carcinoma. The baseline clinical, laboratory and treatment profiles were analyzed. Results: Finally, 40,431 patients were included. The median age was 43 years, with 65.2% being men and 51.3% being positive for hepatitis B e antigen (HBeAg). The most common initial diagnosis was chronic hepatitis B (81.0%), followed by cirrhosis (9.3%), inactive carrier of hepatitis B surface antigen (HBsAg) (6.7%), and immune tolerant phase of hepatitis B infection (3.0%). Among the 21,228 patients who were on treatment, 88.0%, 10.0% and 2.0% received nucleos(t)ide analogues (NAs), interferon or combination of NAs and interferon, respectively. The proportion of patients who received preferred NAs (entecavir or tenofovir disoproxil fumarate) had increased from 13.5% in 2003 to 79.7% in 2016. Conclusions: We concluded that middle-aged men accounted for most of the patients with chronic hepatitis B in this cross-sectional study. About half of the patients were HBeAg-positive. NAs were the most commonly used therapy, and use of the preferred NAs had steadily increased in the past decade.
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- 2019
33. Association of Lipids With Ischemic and Hemorrhagic Stroke
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Xiaoqing Liu, Jie Cao, Chong Shen, Ling Yu, Xianghua Fang, Tai Hing Lam, Yunzhi Li, Ying Li, Jichun Chen, Shuohua Chen, Fangchao Liu, Jianxin Li, Xiangfeng Lu, Yao He, Xinhua Zhang, SL Wu, Xiaoying Gu, Xueli Yang, Jianfeng Huang, and Dongfeng Gu
- Subjects
Male ,medicine.medical_specialty ,Ischemia ,Brain Ischemia ,chemistry.chemical_compound ,Asian People ,Total cholesterol ,Internal medicine ,medicine ,Humans ,Prospective cohort study ,Stroke ,Triglycerides ,Aged ,Advanced and Specialized Nursing ,Triglyceride ,Cholesterol ,business.industry ,Cholesterol, HDL ,Cholesterol, LDL ,Middle Aged ,medicine.disease ,chemistry ,Female ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,Intracranial Hemorrhages ,Cohort study ,Lipoprotein - Abstract
Background and Purpose— Previous results on the association between lipids and stroke were controversial. We investigated the association of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C ), high-density lipoprotein cholesterol (HDL-C), and triglyceride with stroke. Methods— Six cohort studies in China with 267 500 participants were included. Cox proportional hazards regression models and restricted cubic spline analyses were used to estimate hazard ratios and 95% CIs and explore linear and nonlinear relationships of lipids and stroke, respectively. Results— The median follow-up duration ranged from 6 to 19 years. During 2 295 881 person-years, 8072 people developed stroke. Multivariable adjusted hazard ratios (95% CIs) per 1 mmol/L increase in TC, LDL-C, triglyceride were 1.08 (1.05–1.11), 1.08 (1.04–1.11), 1.07 (1.05-1.09) for ischemic stroke, respectively. Compared with participants with TC 160-199.9 mg/dL, hazard ratios (95% CIs) were 1.43 (1.11–1.85) for hemorrhagic stroke in those with TC P P =0.029 and P >0.05). Conclusions— TC, LDL-C, and triglyceride showed positive associations with ischemic stroke. The risk of hemorrhagic stroke was higher when TC was lower than 120 mg/dL. LDL-C and triglyceride showed no association with hemorrhagic stroke. The risks of ischemic and hemorrhagic stroke might be higher when HDL-C was lower than 50 mg/dL.
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- 2019
34. Prevalence and risk factors of active tuberculosis in patients with rheumatic diseases: a multi-center, cross-sectional study in China
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Huijun Han, Qing Han, Lijun Song, Yujing Zhu, Xiaofeng Zeng, Yanhong Li, Wufang Qi, Yueqiu Zhang, Wenjie Zheng, Miaojia Zhang, Yi Zhao, Sheng Chen, Fengchun Zhang, Xiaoxia Zuo, Hongbin Li, Sainan Bian, Lei Zhang, Boqi Gong, Ping Zhu, Kui Zhang, Susu Liao, Chengyin Lv, Wenwen Wang, Qingjun Wu, Liyang Gu, Yunyun Fei, Xiaoqing Liu, Lifan Zhang, Yan Zhao, Qian Wang, Ting Li, Zhiyi Zhang, Lidan Zhao, Wencheng Qi, Jiaxin Zhou, Xiaochun Shi, Kuerbanjiang Yimaity, Dong Xu, Yaou Zhou, Ning Tie, Yi Liu, Gaifen Liu, Cainan Luo, Jiaying Sun, Huaxiang Wu, Shengyun Liu, Hui Luo, Huaxiang Liu, Jing Xue, Jing Wang, Lishuai Han, Lijun Wu, and Yanping Zhao
- Subjects
Adult ,Male ,medicine.medical_specialty ,China ,Epidemiology ,Cross-sectional study ,Immunology ,Population ,prevalence ,Azathioprine ,Disease ,Logistic regression ,Microbiology ,Risk Factors ,Virology ,Internal medicine ,Rheumatic Diseases ,Drug Discovery ,medicine ,Humans ,Tuberculosis ,In patient ,education ,rheumatic disease ,education.field_of_study ,business.industry ,General Medicine ,Middle Aged ,Active tuberculosis ,Confidence interval ,Infectious Diseases ,Cross-Sectional Studies ,Parasitology ,Female ,business ,medicine.drug ,Research Article - Abstract
Evidence of active tuberculosis (ATB) in patients with rheumatic diseases are research priorities but limited data from China have been reported. Research targeting patients not taking anti-TNF biologics are especially insufficient. We aimed to investigate the prevalence and risk factors of ATB in this at-risk population. We conducted a tertiary hospital-based, multi-center, cross-sectional study by using stratified multi-stage cluster sampling strategy to screen ATB in patients with rheumatic diseases. We estimated the prevalence of ATB in patients with rheumatic diseases and identified risk factors among those who were not taking anti-TNF biologic. A total of 13,550 patients with rheumatic diseases were enrolled, and the result showed the standardized prevalence of ATB according to the composition ratio of various types of rheumatic disease was 882/100000 (95% confidence interval (CI): 706-1057). Multivariable logistic regression analysis in patients not taking anti-TNF biologics showed that the independent risk factors of ATB were having systemic lupus erythematosus (SLE) (OR=2.722, 95% CI: 1.437-5.159, p=0.002), having Behcet's disease (BD) (OR= 5.261, 95% CI: 2.071-13.365, p
- Published
- 2021
35. A method to estimate probability of disease and vaccine efficacy from clinical trial immunogenicity data
- Author
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Julie Dudasova, Chandni Valiathan, Justina Ivanauskaite, Jeffrey R. Sachs, Ferdous Gheyas, Matthew C. Wiener, Pavel Fiser, Regina Laube, and Frank Xiaoqing Liu
- Subjects
Oncology ,medicine.medical_specialty ,Immunology ,Bayesian probability ,Drug development ,Disease ,Predictive markers ,Article ,Internal medicine ,medicine ,Pharmacology (medical) ,RC254-282 ,Pharmacology ,Vaccines ,business.industry ,Immunogenicity ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC581-607 ,Vaccine efficacy ,Confidence interval ,Clinical trial design ,Vaccination ,Clinical trial ,Infectious Diseases ,Biomarker (medicine) ,Immunologic diseases. Allergy ,business - Abstract
Vaccine efficacy is often assessed by counting disease cases in a clinical trial. A new quantitative framework proposed here (“PoDBAY,” Probability of Disease Bayesian Analysis), estimates vaccine efficacy (and confidence interval) using immune response biomarker data collected shortly after vaccination. Given a biomarker associated with protection, PoDBAY describes the relationship between biomarker and probability of disease as a sigmoid probability of disease (“PoD”) curve. The PoDBAY framework is illustrated using clinical trial simulations and with data for influenza, zoster, and dengue virus vaccines. The simulations demonstrate that PoDBAY efficacy estimation (which integrates the PoD and biomarker data), can be accurate and more precise than the standard (case-count) estimation, contributing to more sensitive and specific decisions than threshold-based correlate of protection or case-count-based methods. For all three vaccine examples, the PoD fit indicates a substantial association between the biomarkers and protection, and efficacy estimated by PoDBAY from relatively little immunogenicity data is predictive of the standard estimate of efficacy, demonstrating how PoDBAY can provide early assessments of vaccine efficacy. Methods like PoDBAY can help accelerate and economize vaccine development using an immunological predictor of protection. For example, in the current effort against the COVID-19 pandemic it might provide information to help prioritize (rank) candidates both earlier in a trial and earlier in development.
- Published
- 2021
36. Association between blood ethylene oxide levels and the prevalence of hypertension
- Author
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Xiaoqing Liu, Ningtao Wu, Wenya Cao, and Yuxing Wang
- Subjects
Ethylene Oxide ,medicine.medical_specialty ,Ethylene oxide ,business.industry ,Health, Toxicology and Mutagenesis ,Blood Pressure ,General Medicine ,Nutrition Surveys ,Pollution ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Internal medicine ,Hypertension ,medicine ,Prevalence ,Environmental Chemistry ,Humans ,business - Abstract
The relationship of blood ethylene oxide levels with hypertension and blood pressure has not been addressed. A total of 5005 participants from the National Health and Nutrition Examination Survey (NHANES) 2013–2016 were enrolled. Hypertension was defined as a mean systolic blood pressure (SBP) of at least 140 mmHg, a mean diastolic blood pressure (DBP) of at least 90 mmHg, or both, and/or the self-reported use of prescription drugs for diagnosed hypertension. Generalized linear regression models and restricted cubic spline plots were performed to explore the associations of ethylene oxide levels with hypertension and blood pressure. The prevalence of hypertension in the study sample was 27.6%. After adjusting for cofounding factors, compared with the lowest quantile, the odds ratios (ORs) with 95% confidence intervals (CIs) of hypertension across the quantiles of ethylene oxide levels were 0.80 (0.63, 1.03), 0.91 (0.71, 1.16), and 1.39 (1.06, 1.82), respectively (P for trend 0.001). Compared with the lowest quantile, the highest quantile of blood ethylene oxide levels was significantly associated with the worst DBP profile by approximately 2.67 mmHg. Blood ethylene oxide levels showed a strong nonlinear and positive association with DBP, while no significant association was observed between blood ethylene oxide levels and SBP. These results provide epidemiological evidence of elevated blood levels of ethylene oxide in relation to a higher prevalence of hypertension and higher DBP. Further study is warranted to address these issues.
- Published
- 2021
37. Toripalimab plus chemotherapy as second-line treatment in previously EGFR-TKI treated patients with EGFR-mutant-advanced NSCLC: a multicenter phase-II trial
- Author
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Xiaoqian Mu, Hong Wang, R. Guo, Jianying Zhou, Shengxiang Ren, Guanghui Gao, Ningqiang Ma, Yalei Zhang, Sheng Yao, Jie Zhang, Jiarui Wu, Helong Zhang, Caicun Zhou, Luonan Chen, Hui Feng, Yanjun Xu, Xiaoqing Liu, Jianxing He, Pingyang Wang, Lin Deng, Tao Jiang, Zhang Bao, Yanqiu Zhao, Yun Fan, and Yongqian Shu
- Subjects
Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,QH301-705.5 ,medicine.medical_treatment ,Predictive medicine ,Pemetrexed ,Neutropenia ,Antibodies, Monoclonal, Humanized ,Article ,Carboplatin ,T790M ,chemistry.chemical_compound ,Young Adult ,Clinical trials ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,Antineoplastic Combined Chemotherapy Protocols ,Genetics ,medicine ,Clinical endpoint ,Humans ,Progression-free survival ,Biology (General) ,Protein Kinase Inhibitors ,Aged ,Chemotherapy ,Leukopenia ,business.industry ,Middle Aged ,medicine.disease ,Progression-Free Survival ,ErbB Receptors ,Gene Expression Regulation, Neoplastic ,chemistry ,Mutation ,Medicine ,Female ,Immunotherapy ,medicine.symptom ,Lung cancer ,business ,medicine.drug - Abstract
This multicenter phase-II trial aimed to investigate the efficacy, safety, and predictive biomarkers of toripalimab plus chemotherapy as second-line treatment in patients with EGFR-mutant-advanced NSCLC. Patients who failed from first-line EGFR-TKIs and did not harbor T790M mutation were enrolled. Toripalimab plus carboplatin and pemetrexed were administrated every three weeks for up to six cycles, followed by the maintenance of toripalimab and pemetrexed. The primary endpoint was objective-response rate (ORR). Integrated biomarker analysis of PD-L1 expression, tumor mutational burden (TMB), CD8 + tumor-infiltrating lymphocyte (TIL) density, whole-exome, and transcriptome sequencing on tumor biopsies were also conducted. Forty patients were enrolled with an overall ORR of 50.0% and disease-control rate (DCR) of 87.5%. The median progression free survival (PFS) and overall survival were 7.0 and 23.5 months, respectively. The most common treatment-related adverse effects were leukopenia, neutropenia, anemia, ALT/AST elevation, and nausea. Biomarker analysis showed that none of PD-L1 expression, TMB level, and CD8 + TIL density could serve as a predictive biomarker. Integrated analysis of whole-exome and transcriptome sequencing data revealed that patients with DSPP mutation had a decreased M2 macrophage infiltration and associated with longer PFS than those of wild type. Toripalimab plus chemotherapy showed a promising anti-tumor activity with acceptable safety profiles as the second-line setting in patients with EGFR-mutant NSCLC. DSPP mutation might serve as a potential biomarker for this combination. A phase-III trial to compare toripalimab versus placebo in combination with chemotherapy in this setting is ongoing (NCT03924050).
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- 2021
38. Cytomegalovirus reactivation in immunocompetent mechanical ventilation patients: a prospective observational study
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Zhihui Zhang, Sibei Chen, Xuesong Liu, Ling Sang, Yining Sun, Jierong Zhang, Yimin Li, Zhan Wu, Yongbo Huang, Yonghao Xu, Xiaoqing Liu, and Weiqun He
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medicine.medical_specialty ,Epidemiology ,Critical Illness ,medicine.medical_treatment ,Cytomegalovirus ,Infectious and parasitic diseases ,RC109-216 ,Gastroenterology ,law.invention ,Sepsis ,law ,Internal medicine ,medicine ,Humans ,Critically ill ,Blood urea nitrogen ,Mechanical ventilation ,Predictors ,business.industry ,Research ,Mortality rate ,Incidence (epidemiology) ,virus diseases ,medicine.disease ,Respiration, Artificial ,Intensive care unit ,Infectious Diseases ,Cytomegalovirus reactivation ,Cytomegalovirus Infections ,Virus Activation ,Immunocompetent ,business ,Body mass index - Abstract
Background Cytomegalovirus (CMV) reactivation is associated with adverse prognoses of critically ill patients. However, the epidemiology and predictors of CMV reactivation in immunocompetent patients receiving mechanical ventilation (MV) are not clear. The aim of this study was to investigate the epidemiology and predictors of CMV reactivation in immunocompetent patients requiring MV. Methods A single-center, prospective observational study (conducted from June 30, 2017 to July 01, 2018) with a follow-up of 90 days (September 29, 2018) that included 71 CMV-seropositive immunocompetent patients with MV at a 37-bed university hospital general intensive care unit (ICU) in China. Routine detection of CMV DNAemia was performed once a week for 28 days (Days 1, 7, 14, 21, and 28). CMV serology, laboratory findings, and clinical data were obtained during hospitalization. Results Among 71 patients, 13 (18.3%) showed CMV reactivation within 28 days in the ICU. The median time to reactivation was 7 days. CMV reactivation was related to various factors, including body mass index (BMI), sepsis, N-terminal pro-b-type natriuretic peptide (NT-proBNP), blood urea nitrogen (BUN), and hemoglobin (Hb) levels (P Conclusions Among immunocompetent patients with MV, the incidence of CMV reactivation was 18.3%. CMV reactivation was associated with several adverse prognoses. BMI, Hb, and sepsis were independent risk factors for CMV reactivation. BMI and Hb may predict CMV reactivation.
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- 2021
39. Gestational exposure to perfluoroalkyl substances and congenital heart defects: A nested case-control pilot study
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Guang-Hui Dong, Xiao-Wen Zeng, Yanqiu Ou, Hui Wang, Zhiqiang Nie, Xiaohua Xiao, Rosemary Matala, Shao Lin, Xiaohong Li, Michael S. Bloom, Xiaoqing Liu, Yanji Qu, and Fengzhen Han
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Heart Defects, Congenital ,medicine.medical_specialty ,010504 meteorology & atmospheric sciences ,Pilot Projects ,010501 environmental sciences ,01 natural sciences ,Pregnancy ,Statistical significance ,Conotruncal defect ,medicine ,Humans ,GE1-350 ,0105 earth and related environmental sciences ,General Environmental Science ,Fluorocarbons ,Obstetrics ,business.industry ,Confounding ,Infant, Newborn ,Cord blood ,Odds ratio ,Environmental sciences ,Perfluoroalkyl substances ,Alkanesulfonic Acids ,Congenital heart defects ,Case-Control Studies ,Cohort ,Nested case-control study ,Maternal peripheral blood ,Gestation ,Environmental Pollutants ,Female ,business - Abstract
Background Accumulating evidence suggests that environmental pollutants may contribute to the occurrence of congenital heart defects (CHDs). However, no previous studies have evaluated the impact of perfluoroalkyl substances (PFAS), persistent environmental pollutants, on CHDs. This exploratory study aimed to generate testable hypotheses of the association between gestational PFAS and the risk of CHDs. Methods A nested case-control study was conducted in a cohort of 11,578 newborns. Exposure odds ratios were compared between 158 CHD cases and 158 non-malformed controls delivered at the same hospital, individually matched by maternal age (±5 years) and parity. Concentrations of 27 PFAS, including linear and branched isomers, were determined in maternal peripheral blood and cord blood plasma collected before and during delivery using a ultra-performance liquid chromatography coupled to mass spectrometry. Conditional logistic regression was utilized to evaluate associations between individual PFAS and the risk of CHDs, adjusted for confounding variables. Results Maternal gestational exposure to the highly branched perfluorooctanesulfonate (PFOS) isomer potassium 6-trifluoromethyperfluoroheptanesulfonate [6 m-PFOS, adjusted odds ratio (aOR) (95% CI) = 2.47(1.05,5.83)] and perfluorodecanoic acid [PFDA, aOR (95% CI) = 2.33(1.00,5.45)] were associated with increased odds of septal defects with statistical significance, while linear PFOS [aOR (95% CI) = 3.65(1.09,12.16)] and perfluoro-n-dodecanoic acid [PFDoA, aOR (95% CI) = 6.82(1.75, 26.61)] were associated with conotruncal defects. Effect estimates also suggested associations for higher maternal 6 m-PFOS and PFDA concentrations with ventricular septal defect. However, we did not observe these associations in cord blood. Conclusion These exploratory findings suggested that gestational exposure to most PFAS, especially linear PFOS, 6 m-PFOS, PFDA, and PFDoA, was associated with greater risks for septal and conotruncal defects. However, a larger, adequately powered study is needed to confirm our findings, and to more comprehensively investigate the potential teratogenic effects of other more recently introduced PFAS, and on associations with individual CHD subtypes.
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- 2021
40. Acute Respiratory Distress Syndrome Caused By Human Adenovirus In Adults: A Prospective Observational Study In Guangdong, 2019–2020
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Rong Zhang, Zhan Wu, Xiaoqing Liu, Xuesong Liu, Sibei Chen, Yimin Li, Yonghao Xu, Weiqun He, Zhihui Zhang, Dongdong Liu, and Jierong Zhang
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medicine.medical_specialty ,business.industry ,Emergency medicine ,medicine ,Observational study ,Acute respiratory distress ,business - Abstract
Background: Viral causes of acute respiratory distress syndrome (ARDS) are mostly limited to influenza. However, adenovirus has been emerging as a cause of ARDS with a high mortality rate and described in adults are rare.Methods: We conducted a prospective, single-center observational study of viral pneumonia with ARDS and confirmed adenovirus-associated ARDS in adults at our quaternary referral institution between March 2019 and June 2020. We prospectively analyzed clinical characteristics, laboratory test results, radiological characteristics, viral load from nasopharyngeal swabs and endotracheal aspirates, treatments, and outcomes for the study participants.Results: The study enrolled 143 ARDS patients, including 47 patients with viral pneumonia-related ARDS, among which there were 14 adenovirus-associated ARDS patients, which accounted for 29.79% of the viral pneumonia-related ARDS cases. Among the adenovirus-associated ARDS patients, 78.57% were men with a mean age of 54.93 ± 19.04 years. Adenovirus-associated ARDS patients had no specific clinical characteristics, but they presented with shortness of breath and fever, and their initial chest radiographic findings were multifocal or showed diffuse opacity. The viral load and the positivity rate in the lower respiratory tract were higher than that of the upper respiratory tract in the patients with adenovirus-associated ARDS, and 85.71% of the patients had a significant decrease in the number of CD3+CD4+ T cells during the early stage. All patients required invasive mechanical ventilation treatment. The average time from shortness of breath to the application of invasive ventilation was 24 hours. The median duration of invasive mechanical ventilation was 22 days (14–75 days). Six patients (42.86%) required renal replacement therapy, and three patients (21.43%) required extracorporeal membrane oxygenation support. Additionally, 85.71% of the 14 adenovirus-associated ARDS patients survived.Conclusion: Adenovirus infection is an important cause of virus-related ARDS. The positivity rate of adenovirus infection in lower respiratory tract secretions was higher than that in upper respiratory tract secretions in these patients. Most of the patients had a significant decrease in the number of CD3+CD4+ T cells during the early stage. Early identification and intervention to prevent disease progression are essential for reducing the mortality rate in these patients.Trial registration: ChiCTR1900022822. Registered 27 April 2019, https://www.chictr.org.cn/showproj.aspx?proj=38064
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- 2021
41. Reverse Trigger in Ventilated Non-ARDS Patients: A Phenomenon Can Not Be Ignored!
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Zhimin Lin, Jing Zhou, Xiaoling Lin, Yingzhi Wang, Haichong Zheng, Weixiang Huang, Xiaoqing Liu, Yimin Li, Nanshan Zhong, Yongbo Huang, Yuanda Xu, and Ling Sang
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medicine.medical_specialty ,ARDS ,respiratory mechanics ,Physiology ,Sedation ,medicine.medical_treatment ,Respiratory physiology ,mechanical ventilation ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,Internal medicine ,Physiology (medical) ,medicine ,QP1-981 ,Original Research ,Mechanical ventilation ,Lung ,reverse triggering ,business.industry ,030208 emergency & critical care medicine ,Retrospective cohort study ,acute respiratory distress syndrome ,medicine.disease ,medicine.anatomical_structure ,sedation ,030228 respiratory system ,Cardiology ,medicine.symptom ,business ,Transpulmonary pressure - Abstract
IntroductionThe role of reverse trigger (RT) was unknown in ventilated non-acute respiratory distress syndrome (ARDS) patients. So we conducted a retrospective study to evaluate the incidence, characteristics and physiologic consequence of RT in such population.MethodSix ventilated non-ARDS patients were included, the esophageal balloon catheter were placed for measurements of respiratory mechanics in all patients. And the data were analyzed to identified the occurrence of RT, duration of the entrainment, the entrainment pattern or ratio, the phase difference (dP) and the phase angle (θ), phenotypes, Effects and clinical correlations of RT.ResultRT was detected in four patients of our series (66.7%), and the occurrence of RT varying from 19 to 88.6% of their recording time in these 4 patients. One patient (No.2) showed a stable 1:1 ratio and Mid-cycle RT was the most common phenotype. However, the remained patients showed a mixed ratios, and Late RT was the most common phenotype, followed by RT with breath stacking. The average values of mean phase delay and phase angles were 0.39s (0.32, 0.98) and 60.52° (49.66, 102.24). Mean phase delay and phase angles were shorter in early reverse triggering with early and delayed relaxation, and longer in mid, late RT and RT with breath stacking. Pmus was variable between patients and phenotypes, and larger Pmus was generated in Early RT, Delayed Relaxation and mid cycle RT. When the RT occurred, the Peso increased 17.27 (4.91, 19.71) cmH2O compared to the controlled breathing, and the average value of incremental ΔPeso varied widely inter and intra patients (Table 3B and Figure 1). Larger ΔPeso was always generated in Early RT, Delayed Relaxation and mid cycle RT, accompanied by an significant increase of PL with 19.12 (0.75) cmH2O and 16.10 (6.23) cmH2O.ConclusionRT could also be observed in ventilated non-ARDS patients. The characteristics of pattern and phenotype was similar to RT in ARDS patients to a large extent. And RT appeared to alter lung stress and delivered volumes.
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- 2021
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42. Camrelizumab in different PD-L1 expression cohorts of pre-treated advanced or metastatic non-small cell lung cancer: a phase II study
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Dongmei Lin, Hongming Pan, Xiaoqing Liu, Wei Shi, Xingya Li, Yan-Hui Liu, Yi-Long Wu, Jianping Xiong, Ying Cheng, Jianjun Zou, Yun Fan, Yanqiu Zhao, Jifeng Feng, Jie Wang, Liyan Jiang, Cheng Huang, Yina Wang, Tao Wang, Jin-Ji Yang, and Rui Ma
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Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Immunology ,Phases of clinical research ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,B7-H1 Antigen ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Clinical endpoint ,Immunology and Allergy ,Humans ,Adverse effect ,Lung cancer ,Objective response ,Chemotherapy ,business.industry ,medicine.disease ,ErbB Receptors ,Oncology ,Pd l1 expression ,Non small cell ,business - Abstract
This phase II study evaluated camrelizumab in different PD-L1 expression cohorts of patients with previously treated advanced/metastatic non-small cell lung cancer (NSCLC; NCT03085069, registered March 21, 2017). Patients who progressed during/after chemotherapy were enrolled and divided into four cohorts based on PD-L1 tumor proportion score (TPS). Patients with EGFR/ALK alterations and PD-L1 TPS ≥ 50% were also eligible. All enrolled patients received camrelizumab at 200 mg IV Q2W. The primary endpoint was objective response rate. A total of 146 patients were enrolled. As of data cutoff on Aug 20, 2020, the median follow-up was 29.5 months (95% CI 27.4–30.8). Objective response rate was 17.8% (95% CI 12.0–25.0) and improved with the increasing PD-L1 TPS (TPS
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- 2021
43. Utility of interferon gamma/tumor necrosis factor alpha FluoroSpot assay in differentiation between active tuberculosis and latent tuberculosis infection: a pilot study
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Xiaoqing Liu, Shijun Wan, Yueqiu Zhang, Lifan Zhang, and Ziyue Zhou
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0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Tuberculosis ,Adolescent ,Tumor necrosis factor ,Pilot Projects ,Infectious and parasitic diseases ,RC109-216 ,Gastroenterology ,Likelihood ratios in diagnostic testing ,Peripheral blood mononuclear cell ,FluoroSpot ,Diagnosis, Differential ,03 medical and health sciences ,Interferon-gamma ,Young Adult ,0302 clinical medicine ,Latent Tuberculosis ,Internal medicine ,Diagnosis ,medicine ,Humans ,Interferon gamma ,Latent tuberculosis infection ,Prospective cohort study ,Aged ,Receiver operating characteristic ,Latent tuberculosis ,business.industry ,Tumor Necrosis Factor-alpha ,Research ,Middle Aged ,medicine.disease ,bacterial infections and mycoses ,030104 developmental biology ,Infectious Diseases ,030220 oncology & carcinogenesis ,Case-Control Studies ,business ,Interferon-gamma Release Tests ,medicine.drug - Abstract
Background The differential diagnosis of active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains challenging in clinical practice. We aimed to evaluate the diagnostic accuracy of the IFN-γ/TNF-α FluoroSpot assay for differentiating ATB from LTBI. Methods We conducted a pilot study of case-control design, using the FluoroSpot assay to simultaneously detect IFN-γ and TNF-α secretion at the single-cell level. The frequencies of antigen-specific single TNF-α-, total TNF-α-, single IFN-γ-, total IFN-γ- and dual IFN-γ/TNF-α-secreting T cells were detected. The optimal cutoffs value of frequencies for differentiating ATB from LTBI were determined according to receiver operating characteristic curve analysis. The sensitivity, specificity, predictive values (PV) and likelihood ratios (LR) of the FluoroSpot assay were calculated. Results Thirty patients diagnosed microbiologically with ATB, 36 healthcare workers with LTBI and 36 healthy controls were enrolled. After stimulated by ESAT-6 or CFP-10 peptides, the median frequencies of single TNF-α-, total TNF-α-, single IFN-γ-, total IFN-γ- and dual IFN-γ/TNF-α-secreting T cells in ATB patients were all significantly higher than those in LTBI and HC groups (P P P Conclusions IFN-γ/TNF-α FluoroSpot assay might have potential to help differentiate ATB from LTBI, but the findings need to be further verified by cross-sectional or prospective cohort studies.
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- 2021
44. Association of anaplastic lymphoma kinase variants and alterations with ensartinib response duration in non-small cell lung cancer
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Ning Wu, Zewei Zhang, Shijun Zhao, Xiaomin Zheng, Lv Lv, Lieming Ding, Qi Sun, Sicong Wang, Yu-Jing Jin, Xiuli Tao, Lina Zhou, Donghui Hou, Wei Song, and Xiaoqing Liu
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Pulmonary and Respiratory Medicine ,Oncology ,Adult ,Male ,medicine.medical_specialty ,Lung Neoplasms ,Antineoplastic Agents ,Gene mutation ,ALK fusion ,Piperazines ,Metastasis ,Internal medicine ,hemic and lymphatic diseases ,Carcinoma, Non-Small-Cell Lung ,medicine ,Anaplastic lymphoma kinase ,Humans ,Anaplastic Lymphoma Kinase ,Progression-free survival ,gene mutation ,Lung cancer ,ensartinib ,RC254-282 ,Retrospective Studies ,Univariate analysis ,Crizotinib ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,progression‐free survival ,General Medicine ,Original Articles ,Middle Aged ,medicine.disease ,Progression-Free Survival ,Pyridazines ,Tumor progression ,radiomics ,Female ,Original Article ,business ,Tomography, X-Ray Computed ,medicine.drug - Abstract
Background Here, we aimed to assess the association of ALK variants and alterations with ensartinib response duration in NSCLC, and explore the potential value of computed tomography (CT) radiomic features in predicting progression‐free survival (PFS). Methods We enrolled 88 patients with identified ALK variant NSCLC in a multicenter phase 2 trial, and assessed the impact of ALK variants and secondary ALK alterations on the clinical outcome (response duration) of patients receiving ensartinib. We also established a multifactorial model of clinicopathological and quantitative CT radiomic features to predict PFS and risk stratification. Kaplan–Meier analysis was conducted to identify risk factors for tumor progression. Results Univariate analysis indicated a statistical difference (p = 0.035) in PFS among ALK variants in three classifications (V1, V3, and other variants). Secondary ALK alterations were adversely associated with PFS both in univariate (p = 0.008) and multivariate (p = 0.04) analyses and could identify patients at high risk for early progression in the Kaplan–Meier analysis (p = 0.002). Additionally, response duration to crizotinib, The secondary ALK alterations were adversely associated with ensartinib response duration in NSCLC, and ALK variants might not correlate with PFS. CT quantitative radiomic signature could add prognostic prediction value of clinicopathological features.
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- 2021
45. Active Cytomegalovirus Infection in Acute Respiratory Distress Syndrome Patients: Incidence, Risk Factors, and Clinical Outcomes
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Zhihui Zhang, Jierong Zhang, Rujian Li, Qing Zang, Qing Rao, Yongbo Huang, Xiaoqing Liu, Yimin Li, Qianyi Zhan, Ruixue Zhao, and Yongxin Zheng
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Cytomegalovirus infection ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,Internal medicine ,medicine ,Acute respiratory distress ,business - Abstract
Background: Acute respiratory distress syndrome (ARDS) patients have been reported to have a high seroprevalence of cytomegalovirus (CMV). However, the role of active CMV infection in ARDS patients has not been clearly established.Objective: This study aimed at determining the incidence, risk factors, and clinical outcomes of active cytomegalovirus (CMV) infection in acute respiratory distress syndrome (ARDS) patients.Methods: We retrospectively reviewed medical records for ARDS patients who had been admitted to the intensive care unit (ICU) from January 1st, 2018 to December 31st, 2020 at a national teaching hospital in China. Study participants were divided into active CMV infection and non-active infection groups based on CMV DNAemia within a 28-day hospitalization period in ICU. Clinical features, laboratory findings, treatment measures, and clinical outcomes were compared between the two groups.Results: Among 168 ARDS patients, 31 (18.5%) exhibited active CMV infection within the 28-day hospitalization period in ICU. In multivariate logistic regression analysis, monocyte counts, hemoglobin levels, blood transfusion, and septic shock were significantly independently associated with active CMV infection (p < 0.05). Oxygenation (PaO2/FiO2) of active CMV infection patients was worse than for non-active CMV infection (p < 0.05). Duration of invasive mechanical ventilation, 28-day ventilator-free days, length of ICU stay, and 28-day all-cause mortality rates in active CMV infection patients were significantly higher than in those without active CMV infection (p < 0.05).Conclusions: Active CMV infection is common among critically ill ARDS patients. Monocytes, hemoglobin, blood transfusion, and septic shock are risk factors for active CMV infection, which has a negative effect on oxygenation. Moreover, active CMV infection is associated with several adverse prognoses. Prospective studies should be performed to evaluate the impact of prophylactic antiviral therapy for prognoses among ARDS patients.
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- 2021
46. Therapeutic Effect and Cost-Benefit Analysis of Three Different Nutritional Schemes for Esophageal Cancer Patients in the Early Post-operative Period
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Chen Huang, Xinyu Liang, Shanshan Du, Jie He, Qian Bai, Xiaoqing Feng, Xiaoqing Liu, Xu Tian, and Jian Wang
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medicine.medical_specialty ,medicine.medical_treatment ,Endocrinology, Diabetes and Metabolism ,Complete protein ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,TX341-641 ,Medical nutrition therapy ,esophageal cancer ,Stage (cooking) ,jejunal nutrition ,cost-benefit ,liquid equilibrium ,Nutrition ,Original Research ,Nutrition and Dietetics ,business.industry ,Nutrition. Foods and food supply ,Incidence (epidemiology) ,Therapeutic effect ,short peptide jejunal nutrition ,Esophageal cancer ,medicine.disease ,hospital stay ,Parenteral nutrition ,Esophagectomy ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,business ,Food Science - Abstract
Objective: To retrospectively investigate the comparative efficacy, safety and cost-benefits of three nutritional treatment schemes including short peptide jejunal nutrition (SPJN), whole protein jejunal nutrition (WPJN), and partial parenteral nutrition (PPN) in patients underwent esophagectomy for esophageal cancer in our hospital. This study was carried out in accordance with the conceptual framework of nutritional therapy in fast-track rehabilitation surgery.Methods: We retrospectively reviewed 305 patients who were assigned to receive esophagectomy for esophageal cancer. Eligible patients was naturally divided into SPJN group [n = 98 (32.1%)], WPJN group [n = 95 (31.1%)], and PPN group [n = 112 (36.7%)] according to the type of nutritional scheme which was actually prescribed to patients by the attendingphysician in clinical practice. The differences of the serum total protein (TP), albumin (ALB), pre-albumin (PA), hemoglobin (HGB), white blood cells (WBCs), red blood cells (RBCs) and neutrophils were compared among 3 nutritional schemes groups. We also investigated the relationship of the fluid intake, urine output, gastric juice drainage volume and thoracic drainage volume among 3 nutritional groups at 3 days after surgery. Moreover, the differences of cost-benefit indexes, complications, length of hospitalization and hospital expenditure were also compared.Results: The serum TP, ALB, and PA in the SPJN group were all higher than those in the WPJN and PPN groups (p < 0.05). The gastric juice volume of gastrointestinal decompression drainage and fluid volume of thoracic drainage in the SPJN group were all less than that in the WPJN group (p < 0.05). The overall hospital stay and post-operative hospital stay in the SPJN group were all shorter than that in WPJN group (p < 0.05). Moreover, the incidence of post-operative complications including anastomotic leakage, infection, and gastrointestinal reaction was remarkably lower in the SPJN group compared to the WPJN group (p < 0.05). Interesting, hospital expenditure in the PPN group was less than that in the SPJN and the WPJN groups (p < 0.001).Conclusion: Patients may obtain benefits in improving protein level after receiving SPJN scheme at the early stage after esophagectomy. Meanwhile, patients may obtain benefits in improving post-operative complications and hospital stay after receiving SPJN or PPN compared to WPJN protocol. However, the difference between SPJN and PPN requires further study because no difference was detected in terms of clinical outcomes including complications and the length of hospitalization although PPN may achieve a possible decrease of medical expenditure.
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- 2021
47. First-Trimester Maternal Folic Acid Supplementation Modifies the Effects of Risk Factors Exposures on Congenital Heart Disease in Offspring
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Yanji Qu, Yanqiu Ou, Jian Zhuang, John G. Justino, Xiangmin Gao, Yong Wu, Hongzhuan Tan, Chen Jimei, Shao Lin, Zhiqiang Nie, Michael S. Bloom, Jinzhuang Mai, Ximeng Wang, and Xiaoqing Liu
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medicine.medical_specialty ,Heart disease ,Offspring ,Science ,interaction ,030204 cardiovascular system & hematology ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,folic acid ,0302 clinical medicine ,030225 pediatrics ,Conotruncal defect ,medicine ,risk factors ,Ecology, Evolution, Behavior and Systematics ,Fetus ,Obstetrics ,business.industry ,Confounding ,Paleontology ,medicine.disease ,Folic acid supplementation ,congenital heart diseases ,First trimester ,Southern china ,Space and Planetary Science ,business - Abstract
This study aimed to examine effect modification of maternal risk factor exposures and congenital heart disease (CHD) by maternal folic acid supplementation (FAS)/non-FAS. We included 8379 CHD cases and 6918 CHD-free controls from 40 clinical centers in Guangdong Province, Southern China, 2004–2016. Controls were randomly chosen from malformation-free fetuses and infants and frequency matched to the echocardiogram-confirmed cases by enrollment hospital and year of birth. We used multiple regression models to evaluate interactions between FAS/non-FAS and risk factors on CHDs and major CHD categories, adjusted for confounding variables. We detected statistically significant additive and multiplicative interactions between maternal FAS/non-FAS and first-trimester fever, viral infection, and threatened abortion on CHDs. An additive interaction on CHDs was also identified between non-FAS and living in a newly renovated home. We observed a statistically significant dose-response relationship between non-FAS and a greater number of maternal risk factors on CHDs. Non-FAS and maternal risk factors interacted additively on multiple critical CHDs, conotruncal defects, and right ventricular outflow tract obstruction. Maternal risk factor exposures may have differential associations with CHD risk in offspring, according to FAS. These findings may inform the design of targeted interventions to prevent CHDs in highly susceptible population groups.
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- 2021
48. Predicting 10-Year and Lifetime Stroke Risk in Chinese Population
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Dongsheng Hu, Fangchao Liu, Xian-Ping Wu, Jichun Chen, Xiaoqing Liu, Ying Li, Xiangfeng Lu, Jie Cao, Chong Shen, Jianxin Li, Fanghong Lu, Ling Yu, Liancheng Zhao, Dongfeng Gu, Xiaolong Xing, and Xueli Yang
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Advanced and Specialized Nursing ,medicine.medical_specialty ,Chinese population ,business.industry ,medicine.disease ,Stroke risk ,Primary prevention ,Emergency medicine ,medicine ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,Risk assessment ,business ,Stroke ,Cause of death - Abstract
Background and Purpose— Risk assessment is essential for the primary prevention of stroke. However, the current available tools derived from Chinese populations are insufficient for individualized 10-year and lifetime stroke risk prediction. Our study aims to develop and validate personalized 10-year and lifetime stroke risk equations incorporating 4 large Chinese cohorts. Methods— We used 2 prospective cohorts of 21 320 participants with similar survey protocols as the derivation cohort to develop sex-specific 10-year and lifetime stroke risk equations. Two other independent cohorts with 14 123 and 70 838 participants were used for external validation. In addition, the performance of the 10-year stroke risk equations among participants aged ≥55 years was compared with the new Framingham Stroke Risk Profile. Results— The sex-specific equations for predicting 10-year stroke risk had C statistics being 0.810 for men and 0.810 for women, with calibration χ 2 being 15.0 ( P =0.092) and 7.8 ( P =0.550), respectively. The lifetime stroke risk equations also showed C statistics around 0.800 and calibration χ 2 below 20 for both sexes. In the validation cohorts, we found good agreement between the observed and predicted stroke probabilities for both the 10-year and lifetime stroke risk equations. Further compared with the new Framingham Stroke Risk Profile, our 10-year stroke risk equations displayed better prediction capability. In addition, based on lifetime stroke risk assessment, 5.7% of study participants aged 35 to 49 years old were further reclassified as high risk, who were initially categorized as low 10-year risk. Conclusions— We developed a well-performed tool for predicting personalized 10-year and lifetime stroke risk among the Chinese adults, which will facilitate the further identification of high-risk individuals and community-based stroke prevention in China.
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- 2019
49. Fasting glucose and its association with 20-year all-cause and cause-specific mortality in Chinese general population
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Yangfeng Wu, Long Zhou, Ying Li, Min Guo, Liancheng Zhao, Jinzhuang Mai, Xiaoqing Liu, Xiangmin Gao, and Yong Wu
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medicine.medical_specialty ,Medicine (General) ,Population ,Physical exercise ,Disease ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,R5-920 ,Internal medicine ,medicine ,Mortality ,education ,education.field_of_study ,business.industry ,Hazard ratio ,Cardiovascular disease ,Confidence interval ,Blood pressure ,030220 oncology & carcinogenesis ,Fasting blood glucose ,Original Article ,Cohort study ,business ,Body mass index - Abstract
Objective: The aim of this study was to explore the relationship between fasting glucose levels and all-cause and cause-specific mortality in Chinese population. Methods: The role of fasting blood glucose levels as a predictor of all-cause and cause-specific mortality was estimated in 9930 participants from four Chinese general populations with a 20-year follow-up. Multivariate Cox proportional hazard models were used to identify the relationship between fasting glucose and mortality. Results: There were 1471 deaths after a median follow-up of 20.2 years (a total of 187,374 person-years), including 310 cardiovascular deaths, 581 cancer deaths, and 580 other-cause deaths. After adjustment for age, sex, urban or rural, northern or southern of China, types of work, education level, physical exercise, smoking status, drinking status, body mass index, systolic blood pressure, and serum total cholesterol at baseline, the hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality in the fasting blood glucose categories of
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- 2019
50. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial
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Tony S K Mok, Yi-Long Wu, Iveta Kudaba, Dariusz M Kowalski, Byoung Chul Cho, Hande Z Turna, Gilberto Castro, Vichien Srimuninnimit, Konstantin K Laktionov, Igor Bondarenko, Kaoru Kubota, Gregory M Lubiniecki, Jin Zhang, Debra Kush, Gilberto Lopes, Grigory Adamchuk, Myung-Ju Ahn, Aurelia Alexandru, Ozden Altundag, Anna Alyasova, Orest Andrusenko, Keisuke Aoe, Antonio Araujo, Osvaldo Aren, Oscar Arrieta Rodriguez, Touch Ativitavas, Oscar Avendano, Fernando Barata, Carlos Henrique Barrios, Carlos Beato, Per Bergstrom, Daniel Betticher, Larisa Bolotina, Michiel Botha, Sayeuri Buddu, Christian Caglevic, Andres Cardona, Hugo Castro, Filiz Cay Senler, Carlos Alexandre Sydow Cerny, Alvydas Cesas, Gee-Chen Chan, Jianhua Chang, Gongyan Chen, Xi Chen, Susanna Cheng, Ying Cheng, Nelly Cherciu, Chao-Hua Chiu, Saulius Cicenas, Daniel Ciurescu, Graham Cohen, Marcos Andre Costa, Pongwut Danchaivijitr, Flavia De Angelis, Sergio Jobim de Azevedo, Mircea Dediu, Tsvetan Deliverski, Pedro Rafael Martins De Marchi, Flor de The Bustamante Valles, Zhenyu Ding, Boyan Doganov, Lydia Dreosti, Ricardo Duarte, Regina Edusma-Dy, Sergey Emelyanov, Mustafa Erman, Yun Fan, Luis Fein, Jifeng Feng, David Fenton, Gustavo Fernandes, Carlos Ferreira, Fabio Andre Franke, Helano Freitas, Yasuhito Fujisaka, Hector Galindo, Christina Galvez, Doina Ganea, Nuno Gil, Gustavo Girotto, Erdem Goker, Tuncay Goksel, Gonzalo Gomez Aubin, Luis Gomez Wolff, Hakan Griph, Mahmut Gumus, Jacqueline Hall, Gregory Hart, Libor Havel, Jianxing He, Yong He, Carlos Hernandez Hernandez, Venceslau Hespanhol, Tomonori Hirashima, Chung Man James Ho, Atsushi Horiike, Yukio Hosomi, Katsuyuki Hotta, Mei Hou, Soon Hin How, Te-Chun Hsia, Yi Hu, Masao Ichiki, Fumio Imamura, Oleksandr Ivashchuk, Yasuo Iwamoto, Jana Jaal, Jacek Jassem, Christa Jordaan, Rosalyn Anne Juergens, Diego Kaen, Ewa Kalinka-Warzocha, Nina Karaseva, Boguslawa Karaszewska, Andrzej Kazarnowicz, Kazuo Kasahara, Nobuyuki Katakami, Terufumi Kato, Tomoya Kawaguchi, Joo Hang Kim, Kazuma Kishi, Vitezslav Kolek, Marchela Koleva, Petr Kolman, Leona Koubkova, Ruben Kowalyszyn, Dariusz Kowalski, Krassimir Koynov, Doran Ksienski, Takayasu Kurata, Gerli Kuusk, Lyudmila Kuzina, Ibolya Laczo, Guia Elena Imelda Ladrera, Konstantin Laktionov, Gregory Landers, Sergey Lazarev, Guillermo Lerzo, Krzysztof Lesniewski Kmak, Wei Li, Chong Kin Liam, Igor Lifirenko, Oleg Lipatov, Xiaoqing Liu, Zhe Liu, Sing Hung Lo, Valeria Lopes, Karla Lopez, Shun Lu, Gaston Martinengo, Luis Mas, Marina Matrosova, Rumyana Micheva, Zhasmina Milanova, Lucian Miron, Tony Mok, Matias Molina, Shuji Murakami, Yasuharu Nakahara, Tien Quang Nguyen, Takashi Nishimura, Adrian Ochsenbein, Tatsuo Ohira, Ronny Ohman, Choo Khoon Ong, Gyula Ostoros, Xuenong Ouyang, Elena Ovchinnikova, Ozgur Ozyilkan, Lubos Petruzelka, Xuan Dung Pham, Pablo Picon, Bela Piko, Artem Poltoratsky, Olga Ponomarova, Patrice Popelkova, Gunta Purkalne, Shukui Qin, Rodryg Ramlau, Bernardo Rappaport, Felipe Rey, Eduardo Richardet, Jaromir Roubec, Paul Ruff, Andrii Rusyn, Hideo Saka, Jorge Salas, Mario Sandoval, Lucas Santos, Toshiyuki Sawa, Kasan Seetalarom, Mesut Seker, Nobuhiko Seki, Freddy Seolwane, Lucinda Shepherd, Sergii Shevnya, Andrea Kazumi Shimada, Yaroslav Shparyk, Ivan Sinielnikov, Daniela Sirbu, Oren Smaletz, Joao Paulo Holanda Soares, Aumkhae Sookprasert, Giovanna Speranza, Virote Sriuranpong, Zinaida Stara, Wu-Chou Su, Shunichi Sugawara, Waldemar Szpak, Kazuhisa Takahashi, Nagio Takigawa, Hiroshi Tanaka, Jerry Tan Chun Bing, Qiyou Tang, Pavel Taranov, Hermes Tejada, Lye Mun Tho, Yoshitaro Torii, Dmytro Trukhyn, Maria Turdean, Hande Turna, Grygoriy Ursol, Jaroslav Vanasek, Mirta Varela, Marcela Vallejo, Luis Vera, Ana-Paula Victorino, Tomas Vlasek, Ihor Vynnychenko, Buhai Wang, Jie Wang, Kai Wang, Yilong Wu, Kazuhiko Yamada, Chih-Hsin Yang, Takuma Yokoyama, Toshihide Yokoyama, Hiroshige Yoshioka, Fulden Yumuk, Angela Zambrano, Juan Jose Zarba, Oleg Zarubenkov, Marius Zemaitis, Li Zhang, Xin Zhang, Jun Zhao, Caicun Zhou, Jianying Zhou, Qing Zhou, and Alfred Zippelius
- Subjects
medicine.medical_specialty ,Chemotherapy ,education.field_of_study ,Performance status ,business.industry ,medicine.medical_treatment ,Hazard ratio ,Population ,Phases of clinical research ,General Medicine ,Pembrolizumab ,030204 cardiovascular system & hematology ,medicine.disease ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Carcinoma ,030212 general & internal medicine ,business ,Lung cancer ,education - Abstract
Background First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater. Methods This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries. Eligible patients were adults (≥18 years) with previously untreated locally advanced or metastatic non-small-cell lung cancer without a sensitising EGFR mutation or ALK translocation and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, life expectancy 3 months or longer, and a PD-L1 TPS of 1% or greater. Randomisation was computer generated, accessed via an interactive voice-response and integrated web-response system, and stratified by region of enrolment (east Asia vs rest of world), ECOG performance status score (0 vs 1), histology (squamous vs non-squamous), and PD-L1 TPS (≥50% vs 1-49%). Enrolled patients were randomly assigned 1:1 in blocks of four per stratum to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles or the investigator's choice of platinum-based chemotherapy for four to six cycles. Primary endpoints were overall survival in patients with a TPS of 50% or greater, 20% or greater, and 1% or greater (one-sided significance thresholds, p=0·0122, p=0·0120, and p=0·0124, respectively) in the intention-to-treat population, assessed sequentially if the previous findings were significant. This study is registered at ClinicalTrials.gov, number NCT02220894. Findings From Dec 19, 2014, to March 6, 2017, 1274 patients (902 men, 372 women, median age 63 years [IQR 57-69]) with a PD-L1 TPS of 1% or greater were allocated to pembrolizumab (n=637) or chemotherapy (n=637) and included in the intention-to-treat population. 599 (47%) had a TPS of 50% or greater and 818 patients (64%) had a TPS of 20% or greater. As of Feb 26, 2018, median follow-up was 12·8 months. Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (≥50% hazard ratio 0·69, 95% CI 0·56-0·85, p=0·0003; ≥20% 0·77, 0·64-0·92, p=0·0020, and ≥1% 0·81, 0·71-0·93, p=0·0018). The median surival values by TPS population were 20·0 months (95% CI 15·4-24·9) for pembrolizumab versus 12·2 months (10·4-14·2) for chemotherapy, 17·7 months (15·3-22·1) versus 13·0 months (11·6-15·3), and 16·7 months (13·9-19·7) versus 12·1 months (11·3-13·3), respectively. Treatment-related adverse events of grade 3 or worse occurred in 113 (18%) of 636 treated patients in the pembrolizumab group and in 252 (41%) of 615 in the chemotherapy group and led to death in 13 (2%) and 14 (2%) patients, respectively. Interpretation The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS. Funding Merck Sharp & Dohme.
- Published
- 2019
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