1.Effect of Compatibility of Effective Monomer Components of Fujin Shengjisan on Angiogenesis of HUVEC Based on Uniform Design
Xianying LU ; Jing GAO ; Dingxi BAI ; Chaoming HOU ; Wenting JI ; Huan CHEN ; Chenxi WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):9-20
		                        		
		                        			
		                        			ObjectiveTo determine the optimal combination of the effective monomer components "quercetin-kaempferol-abietic acid-boswellic acid" in Fujin Shengjisan for promoting diabetic ulcer (DU) wound healing through uniform design, thereby achieving the modern application of the ancient formula. MethodsFollowing the principle of "uniform design-pharmacodynamic experiment-mathematical modeling and model verification", the U14(145) uniform design table was adopted.The four monomer components of Chinese medicine were considered as the independent variables, and the proliferation rate of human umbilical vein endothelial cells (HUVECs) induced by glucose was used as the pharmacodynamic indicator. A mathematical model was constructed using DPS software to correlate the effective monomer components with the pharmacodynamic indicator. The results of uniform design were verified through CCK-8 assay, cell scratch healing, tube formation, Western blot, and Real-time PCR. ResultsAmong the 14 compatibility groups, compared with the high-glucose model group, compound compatibility group 6 showed the strongest proliferation effect and statistical significance (P<0.05). Four quadratic polynomial regression equations (Y1-Y4) were obtained through DPS modeling. Considering the model's fit, stability, and practical application, equations Y1-Y3 were selected for the follow-up verification. To ensure experiment reproducibility, group 6 was used for validation. Group 6 and equations Y1-Y3 were renamed as compound prescription ① to compound prescription④, respectively, to represent the modern application of the ancient FJSJ Powder through compatibility of monomer components. Verification experiments showed that in the CCK-8, scratch healing, and tube formation assays, the cell viability, wound healing rate, and tube formation number of HUVECs stimulated with 50 mmol·L-1 glucose were significantly reduced compared with the blank group. Moreover, the expression levels of angiogenesis-related cytokines, vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2), and CD31 secretion were significantly down-regulated. However, after intervention with compound prescriptions ① to ④, compound prescriptions ① and ③ significantly improved the biological functions of HUVECs induced by 50 mmol·L-1 glucose. Further analysis of the regression coefficients of compound prescriptions ① and ③, and the relative dose ratios of each monomer component, indicated that abietic acid, quercetin, and boswellic acid promoted angiogenesis of HUVECs in the high glucose environment, with a major effect (positive partial correlation coefficients, all > 0.9). Abietic acid and boswellic acid, as well as kaempferol and boswellic acid, promoted angiogenesis in HUVECs through interaction (positive partial correlation coefficients). ConclusionCompound prescriptions ① and ③ are the optimal combinations. They can reverse the inhibitory effects of high glucose, stimulate the proliferation, migration, and tube formation abilities of HUVECs in a high glucose environment, and promote the expression of vascular endothelial growth factorA(VEGFA), FGF2, and CD31, thereby promoting angiogenesis and facilitating DU wound healing. This finding not only confirms the good reproducibility and feasibility of compound prescriptions ① and ③ but also provides new insights and methods for the rational construction of mathematical models to further study the compatibility theory of Chinese medicine. 
		                        		
		                        		
		                        		
		                        	
2.A national questionnaire survey on endoscopic treatment for gastroesophageal varices in portal hypertension in China
Xing WANG ; Bing HU ; Yiling LI ; Zhijie FENG ; Yanjing GAO ; Zhining FAN ; Feng JI ; Bingrong LIU ; Jinhai WANG ; Wenhui ZHANG ; Tong DANG ; Hong XU ; Derun KONG ; Lili YUAN ; Liangbi XU ; Shengjuan HU ; Liangzhi WEN ; Ping YAO ; Yunxiao LIANG ; Xiaodong ZHOU ; Huiling XIANG ; Xiaowei LIU ; Xiaoquan HUANG ; Yinglei MIAO ; Xiaoliang ZHU ; De'an TIAN ; Feihu BAI ; Jitao SONG ; Ligang CHEN ; Yingcai MA ; Yifei HUANG ; Bin WU ; Xiaolong QI
Chinese Journal of Digestive Endoscopy 2024;41(1):43-51
		                        		
		                        			
		                        			Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.
		                        		
		                        		
		                        		
		                        	
3.Coagulation Factors for Diagnosis of Periprosthetic Joint Infection
Xiao-yu WU ; Yong-yu YE ; Bai-qi PAN ; Xuan-tao HU ; Lin-li ZHENG ; Wei-shen CHEN ; Zi-ji ZHANG ; Pu-yi SHENG
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(2):188-197
		                        		
		                        			
		                        			ObjectivePeriprosthetic joint infections (PJI) are currently the most calamitous complication after arthroplasty. Although achievements have been made in many markers for the diagnosis of PJI, the lack of a gold standard remains a great obstacle for early diagnosis. This study aimed to investigate the association between coagulation markers and the development of PJI in patients undergoing revision total joint arthroplasty (TJA). MethodsWe conducted a retrospective cohort study with a total of 2 517 patients who underwent hip or knee arthroplasties from January 2011 to January 2022 (2 394 with primary TJA, 87 with aseptic revision and 36 with PJI). We applied univariate analysis and multivariate logistic regression to analyze differences of coagulation factors between primary TJA and aseptic revision or PJI group. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to measure the diagnostic value of coagulation factors in predicting PJI. ResultsCoagulation factors and their ratios including plasma fibrinogen (FBG), prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), platelet (PLT), mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), PLT / MPV, PLT / PDW and PLT / PCT were included in this study. High FGB level was strongly correlated with the risk of PJI compared to other coagulation factors. The optimal threshold value of FBG was 4.53 g/L with a sensitivity of 47.22%, a specificity of 93.07% (Primary TJA group vs. PJI group). Similarly, the optimal threshold value of FBG was 4.44 g/L with a sensitivity of 47.22%, a specificity of 95.40% between the other two groups (Aseptic revision group vs. PJI group). ROC curve analysis demonstrated moderate diagnostic performance of FBG (AUC value), indicating a potential to be a diagnostic marker for PJI. ConclusionsFBG is significantly correlated with PJI and it can be used as a potential non-invasive marker for early detection. It may serve as a safe and cost-effective tool for assessing PJI in clinical work. 
		                        		
		                        		
		                        		
		                        	
4.PD-1 inhibitor plus anlotinib for metastatic castration-resistant prostate cancer: a real-world study.
Xin-Xing DU ; Yan-Hao DONG ; Han-Jing ZHU ; Xiao-Chen FEI ; Yi-Ming GONG ; Bin-Bin XIA ; Fan WU ; Jia-Yi WANG ; Jia-Zhou LIU ; Lian-Cheng FAN ; Yan-Qing WANG ; Liang DONG ; Yin-Jie ZHU ; Jia-Hua PAN ; Bai-Jun DONG ; Wei XUE
Asian Journal of Andrology 2023;25(2):179-183
		                        		
		                        			
		                        			Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
		                        		
		                        		
		                        		
		                        			Male
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Prostate-Specific Antigen
		                        			;
		                        		
		                        			Treatment Outcome
		                        			;
		                        		
		                        			Prostatic Neoplasms, Castration-Resistant/drug therapy*
		                        			;
		                        		
		                        			Immune Checkpoint Inhibitors/therapeutic use*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			
		                        		
		                        	
5.Expression of IGLL1 Gene and Its Clinical Significance in Pediatric T-ALL.
Shui-Yan WU ; Xin-Ran CHU ; Qi JI ; Xiao-Chen LIN ; Zhen-Jiang BAI ; Jian-Qin LI ; Jian PAN ; Zi-Xing CHEN ; Shao-Yan HU
Journal of Experimental Hematology 2023;31(4):999-1004
		                        		
		                        			OBJECTIVE:
		                        			To detect the relative expression of IGLL1 (immunoglobulin lambda-like polypeptide 1) mRNA in bone marrow of children with T-cell acute lymphoblastic leukemia (T-ALL), and analyze its correlation with the clinical characteristics and prognosis of the patients, so as to clarify the clinical significance of IGLL1 in pediatric T-ALL patients.
		                        		
		                        			METHODS:
		                        			A total of 56 pediatric T-ALL patients hospitalized in Children's Hospital of Soochow University from June 2012 to December 2017 and treated with CCLG-ALL 2008 regimen were selected. Transcriptome sequencing technology was used to detect the transcription level of IGLL1 gene in children with T-ALL. According to 25% of the IGLL1 transcription level (cutoff value:448), the enrolled children were divided into IGLL1 low expression group (17 cases) and IGLL1 high expression group (39 cases). Combined with clinical data, the correlation between the expression level of IGLL1 and prognosis of the patients was analyzed.
		                        		
		                        			RESULTS:
		                        			The comparative analysis showed that the transcription level of IGLL1 was not correlated with the clinical characteristics of the patients, such as sex, age, bone marrow blast, white blood cell (WBC) count at initial diagnosis. The 5-year OS rate of patients with high IGLL1 expression was significantly higher than that of patients with low IGLL1 expression (76.9%±6.7% vs 47.1%±12.1%, P =0.018). Further comparison of relapse-free survival (RFS) rate between the two groups showed that the 5-year RFS rate of patients with high IGLL1 expression was higher than that of patients with low IGLL1 expression, but the difference between the two groups was not statistically significant (P =0.095). Multivariate COX analysis was conducted on common clinical prognostic factors (age, sex, WBC count at diagnosis, prednisone response on the 7th day, bone marrow response on the 15th day after treatment) and IGLL1 expression level, and the results showed that IGLL1 expression (P =0.012) and prednisone response (P =0.017) were independent risk factors for overall survival in pediatric T-ALL patients.
		                        		
		                        			CONCLUSION
		                        			In pediatric T-ALL, the OS rate of children with high expression of IGLL1 gene was significantly higher than that of children with low expression of IGLL1 gene, and the expression level of IGLL1 gene was an independent factor affecting the survival of children with T-ALL, which suggests that IGLL1 is a marker of good clinical prognosis of children with T-ALL.
		                        		
		                        		
		                        		
		                        			Child
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
		                        			;
		                        		
		                        			Clinical Relevance
		                        			;
		                        		
		                        			Disease-Free Survival
		                        			;
		                        		
		                        			Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics*
		                        			;
		                        		
		                        			Prednisone/therapeutic use*
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Recurrence
		                        			;
		                        		
		                        			Immunoglobulin Light Chains, Surrogate/genetics*
		                        			
		                        		
		                        	
6. The antitumor effect of cisplatin chemotherapy promoted by Taohong Siwu Decoction on mice with lung adenocarcinoma
Bai-Kun LI ; Shi-Yu CHEN ; Xiao-Hong WU ; Bai-Kun LI ; Shi-Yu CHEN ; Xiao-Hong WU ; Ming-Jun YE ; Ting ZHU ; Ji-Min ZHU ; Qing-Lin LI ; Ming-Jun YE ; Ting ZHU ; Qing-Lin LI ; Ji-Min ZHU
Chinese Pharmacological Bulletin 2023;39(3):588-593
		                        		
		                        			
		                        			 Aim To study the antitumor effect of cispl-atin ( DDP) chemotherapy promoted by Taohong Siwu Decoction (TSD) on mice with lung adenocarcinoma mice. Methods Lewis lung carcinoma cell line was used to make homologous lung adenocarcinoma trans¬plantation mouse model. Normal control, Model, TSD, DDP, TSD + DDP groups were set up. The change of transplanted tumor volume after administration was observed, the weight of transplanted tumor was weighed, the expression of Ki67 in transplanted tumor tissue was detected by immunohistochemistry, TUNEL was detected by fluorescence staining, Bcl-2, Bax, cleaved Caspase-3 and cleaved Caspase-9 were detected by immunoblotting, and the content of D-dirtier in plasma was measured by ELISA. Results DDP plus TSD significantly inhibited the growth of transplanted tumor. Ki67 expression in tumor tissue was lower than that in DDP group (28. 3% ±3. 1% vs 40. 3% ±2.1% ). The combined use of TSD and DDP significantly promoted the apoptosis level of transplanted tumor. The positive rate of TUNEL was significantly higher than that of DDP group (41. 0% ±3.0% vs 30.7% ± 4.5%). Bax, cleaved Caspase-3 and cleaved Caspase-9 expressions in tumor tissue were also higher than those of DDP group, while the expression of Bcl-2 was significantly lower than that of DDP group. Moreover, we found a significant interaction between TSD and DDP on the expression of four apoptotic proteins ( P < 0.05 ) . The plasma D-dimer content in TSD + DDP group was significantly lower than that in DDP group (188. 50 ± 28. 46 vs 269.80 ± 35.92) μg • L 
		                        		
		                        		
		                        		
		                        	
7.Questionnaire investigation of radiation rectal injury with anxiety, depression and somatic disorder.
Bo LIAN ; Xin Ping CAO ; Hai Jun DENG ; Jun JIANG ; Ke Wei JIANG ; Xin Xiang LI ; You Sheng LI ; Guo Le LIN ; Ji Hong LIU ; Shou Min BAI ; Feng WANG ; Zi Qiang WANG ; Ai Wen WU ; Yi XIAO ; Hong Wei YAO ; Wei Tang YUAN ; Wei ZHANG ; Zhen ZHANG ; Yan Bing ZHOU ; Teng Hui MA ; Qing Chuan ZHAO
Chinese Journal of Gastrointestinal Surgery 2021;24(11):984-990
		                        		
		                        			
		                        			Objective: To observe the incidence and treatment of radiation rectal injury complicated with anxiety, depression and somatic symptom disorder. Methods: A cross-sectional survey research method was carried out. Patients with radiation rectal injury managed by members of the editorial board of Chinese Journal of Gastrointestinal Surgery were the subjects of investigation. The inclusion criteria of the survey subjects: (1) patients suffered from pelvic tumors and received pelvic radiotherapy; (2) colonoscopy showed inflammatory reaction or ulcer in the rectum. Exclusion criteria: (1) patient had a history of psycho-somatic disease before radiotherapy; (2) patient was unable to use a smart phone, unable to read and understand the questions in the questionnaire displayed on the phone; (3) patient refused to sign an informed consent form. According to the SOMA self-rating scale, PHQ-15 self-rating scale, GAD-7 and PHQ-9 self-rating scale, the electronic questionnaire of "Psychological Survey of Radiation Proctitis" was designed. The questionnaire was sent to patients with radiation rectal injury managed by the committee through the WeChat group. Observational indicators: (1) radiation rectal injury symptom assessment: using SOMA self-rating scale, radiation rectal injury symptom classification: mild group (≤3 points), moderate group (4-6 points) and severe group (> 6 points); (2) incidence of anxiety, depression and physical disorder: using GAD-7, PHQ-9 and PHQ-15 self-rating scales respectively for assessment; (3) correlation of radiation rectal injury symptom grading with anxiety, depression, and somatic symptom disorder. Results: Seventy-one qualified questionnaires were collected, of which 41 (56.9%) were from Guangzhou. Among the 71 patients, 6 were males and 65 were females; the mean age was (55.7±9.3) years old and 48 patients (67.6%) were less than 60 years old; the median confirmed duration of radiation rectal injury was 2.0 (1.0, 5.0) years. (1) Evaluation of symptoms of radiation rectal injury: 18 cases of mild (25.4%), 27 cases of moderate (38.0%), and 26 cases of severe (36.6%). (2) Incidence of anxiety, depression and somatic disorder: 12 patients (16.9%) without comorbidities; 59 patients (83.1%) with anxiety, depression, or somatic disorder, of whom 2 patients only had anxiety, 1 patient only had depression, 9 only had somatic disorder, 2 had anxiety plus depression, 4 had anxiety plus somatic disorder, 2 had depression plus somatic disorder, and 40 had all three symptoms. (3) correlation of radiation rectal injury grading with anxiety, depression, and somatic symptom disorder: as compared to patients in mild group and moderate group, those in severe group had higher severity of anxiety and somatic symptom disorder (Z=-2.143, P=0.032; Z=-2.045, P=0.041), while there was no statistically significant difference of depression between mild group and moderate group (Z=-1.176, P=0.240). Pearson correlation analysis revealed that radiation rectal injury symptom score was positively correlated with anxiety (r=0.300, P=0.013), depression (r=0.287, P=0.015) and somatic symptom disorder (r=0.344, P=0.003). Conclusions: The incidence of anxiety, depression, and somatic symptom disorder in patients with radiation rectal injury is extremely high. It is necessary to strengthen the diagnosis and treatment of somatic symptom disorder, so as to alleviate the symptoms of patients with pelvic perineum pain and improve the quality of life.
		                        		
		                        		
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Anxiety
		                        			;
		                        		
		                        			Cross-Sectional Studies
		                        			;
		                        		
		                        			Depression
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Quality of Life
		                        			;
		                        		
		                        			Rectum
		                        			;
		                        		
		                        			Surveys and Questionnaires
		                        			
		                        		
		                        	
8.Expert consensus on the use of human serum albumin in critically ill patients.
Yue-Tian YU ; Jiao LIU ; Bo HU ; Rui-Lan WANG ; Xiang-Hong YANG ; Xiu-Ling SHANG ; Gang WANG ; Chang-Song WANG ; Bai-Ling LI ; Ye GONG ; Sheng ZHANG ; Xin LI ; Lu WANG ; Min SHAO ; Mei MENG ; Feng ZHU ; You SHANG ; Qiang-Hong XU ; Zhi-Xiong WU ; De-Chang CHEN
Chinese Medical Journal 2021;134(14):1639-1654
9.Treatment of refractory Her-2 positive metastatic young breast cancer with pyrrolidine combined with capecitabine: a case report
Xiangxin ZHENG ; Ji WU ; Shucheng GU ; Xiaoling JIANG ; Xiaohong SHI ; Mu YUAN ; Bolin LU ; Xing QIU ; Xuxu ZHANG ; Jianyin BAI ; Peng YANG ; Xiaoqing GUAN
Clinical Medicine of China 2021;37(3):226-228
		                        		
		                        			
		                        			In order to explore the treatment of Her-2 positive breast cancer patients who failed in multi-line treatments, we retrospectively analyzed the clinical data of a patient with refractory Her-2 positive breast cancer.The patient was initially diagnosed as Her-2 positive advanced breast cancer.After six line treatment in the outer hospital, the patient′s condition was basically in a progressive state.The breast tumor was broken and purulent, the lung metastasis increased, and the patient′s quality of life was poor.The patient was admitted to Department of Breast Surgery of Affiliated Suqian Hospital of Xuzhou Medical University, after MDT discussion, we gave pyrrolotinib combined with capecitabine treatment, the chest wound healed gradually, the lung metastasis gradually reduced, and the quality of life was better.A retrospective analysis of this case showed that pyrrolidine combined with capecitabine may bring hope to Her-2 positive breast cancer patients who failed to receive multi-line therapies, especially those who failed to target therapy.
		                        		
		                        		
		                        		
		                        	
10.Machine Learning-Based Prediction of COVID-19 Severity and Progression to Critical Illness Using CT Imaging and Clinical Data
Subhanik PURKAYASTHA ; Yanhe XIAO ; Zhicheng JIAO ; Rujapa THEPUMNOEYSUK ; Kasey HALSEY ; Jing WU ; Thi My Linh TRAN ; Ben HSIEH ; Ji Whae CHOI ; Dongcui WANG ; Martin VALLIÈRES ; Robin WANG ; Scott COLLINS ; Xue FENG ; Michael FELDMAN ; Paul J. ZHANG ; Michael ATALAY ; Ronnie SEBRO ; Li YANG ; Yong FAN ; Wei-hua LIAO ; Harrison X. BAI
Korean Journal of Radiology 2021;22(7):1213-1224
		                        		
		                        			Objective:
		                        			To develop a machine learning (ML) pipeline based on radiomics to predict Coronavirus Disease 2019 (COVID-19) severity and the future deterioration to critical illness using CT and clinical variables. 
		                        		
		                        			Materials and Methods:
		                        			Clinical data were collected from 981 patients from a multi-institutional international cohort with real-time polymerase chain reaction-confirmed COVID-19. Radiomics features were extracted from chest CT of the patients. The data of the cohort were randomly divided into training, validation, and test sets using a 7:1:2 ratio. A ML pipeline consisting of a model to predict severity and time-to-event model to predict progression to critical illness were trained on radiomics features and clinical variables. The receiver operating characteristic area under the curve (ROC-AUC), concordance index (C-index), and time-dependent ROC-AUC were calculated to determine model performance, which was compared with consensus CT severity scores obtained by visual interpretation by radiologists. 
		                        		
		                        			Results:
		                        			Among 981 patients with confirmed COVID-19, 274 patients developed critical illness. Radiomics features and clinical variables resulted in the best performance for the prediction of disease severity with a highest test ROC-AUC of 0.76 compared with 0.70 (0.76 vs. 0.70, p = 0.023) for visual CT severity score and clinical variables. The progression prediction model achieved a test C-index of 0.868 when it was based on the combination of CT radiomics and clinical variables compared with 0.767 when based on CT radiomics features alone (p < 0.001), 0.847 when based on clinical variables alone (p = 0.110), and 0.860 when based on the combination of visual CT severity scores and clinical variables (p = 0.549). Furthermore, the model based on the combination of CT radiomics and clinical variables achieved time-dependent ROC-AUCs of 0.897, 0.933, and 0.927 for the prediction of progression risks at 3, 5 and 7 days, respectively. 
		                        		
		                        			Conclusion
		                        			CT radiomics features combined with clinical variables were predictive of COVID-19 severity and progression to critical illness with fairly high accuracy.
		                        		
		                        		
		                        		
		                        	
            
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