1.In vitro study of immunocompatibility of humanized genetically modified pig erythrocytes with human serum
Leijia CHEN ; Mengyi CUI ; Xiangyu SONG ; Kai WANG ; Zhibo JIA ; Liupu YANG ; Yanghui DONG ; Haochen ZUO ; Jiaxiang DU ; Dengke PAN ; Wenjing XU ; Hongbo REN ; Yaqun ZHAO ; Jiang PENG
Organ Transplantation 2024;15(3):415-421
		                        		
		                        			
		                        			Objective To investigate the differences and the immunocompatibility of wild-type (WT), four-gene modified (TKO/hCD55) and six-gene modified (TKO/hCD55/hCD46/hTBM) pig erythrocytes with human serum. Methods The blood samples were collected from 20 volunteers with different blood groups. WT, TKO/hCD55, TKO/hCD55/hCD46/hTBM pig erythrocytes, ABO-compatible (ABO-C) and ABO-incompatible (ABO-I) human erythrocytes were exposed to human serum of different blood groups, respectively. The blood agglutination and antigen-antibody binding levels (IgG, IgM) and complement-dependent cytotoxicity were detected. The immunocompatibility of two types of genetically modified pig erythrocytes with human serum was evaluated. Results No significant blood agglutination was observed in the ABO-C group. The blood agglutination levels in the WT and ABO-I groups were higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (all P<0.001). The level of erythrocyte lysis in the WT group was higher than those in the ABO-C, TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups. The level of erythrocyte lysis in the ABO-I group was higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (both P<0.01). The pig erythrocyte binding level with IgM and IgG in the TKO/hCD55 group was lower than those in the WT and ABO-I groups. The pig erythrocyte binding level with IgG and IgM in the TKO/hCD55/hCD46/hTBM group was lower than that in the WT group and pig erythrocyte binding level with IgG was lower than that in the ABO-I group (all P<0.05). Conclusions The immunocompatibility of genetically modified pig erythrocytes is better than that of wild-type pigs and close to that of ABO-C pigs. Humanized pig erythrocytes may be considered as a blood source when blood sources are extremely scarce.
		                        		
		                        		
		                        		
		                        	
2.Different methods in predicting mortality of pediatric intensive care units sepsis in Southwest China
Rong LIU ; Zhicai YU ; Changxue XIAO ; Shufang XIAO ; Juan HE ; Yan SHI ; Yuanyuan HUA ; Jimin ZHOU ; Guoying ZHANG ; Tao WANG ; Jianyu JIANG ; Daoxue XIONG ; Yan CHEN ; Hongbo XU ; Hong YUN ; Hui SUN ; Tingting PAN ; Rui WANG ; Shuangmei ZHU ; Dong HUANG ; Yujiang LIU ; Yuhang HU ; Xinrui REN ; Mingfang SHI ; Sizun SONG ; Jumei LUO ; Juan LIU ; Juan ZHANG ; Feng XU
Chinese Journal of Pediatrics 2024;62(3):204-210
		                        		
		                        			
		                        			Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.
		                        		
		                        		
		                        		
		                        	
3.Effect of osimertinib combined with aspirin on survival period in advanced lung adenocarcinoma patients with EGFR mutation
Yan LUO ; Lan YAO ; Zhonghui BAO ; Yi JIANG ; Yanxia NI ; Qin HUANG ; Shaolin LI ; Hongbo REN ; Biyou HUANG
Chongqing Medicine 2024;53(13):2011-2015
		                        		
		                        			
		                        			Objective To investigate the effect of osimertinib combined with aspirin on the survival pe-riod of the advanced lung adenocarcinoma patients with epidermal growth factor receptor(EGFR)mutation.Methods Sixty lung adenocarcinoma patients with EGFR mutation in advanced non-small cell lung cancer(NSCLC)first diagnosed in Banan District Second People's Hospital of from August 2020 to October 2021 were selected as the study subjects and divided into the observation group and control group by the random number table method,30 cases in each group.The observation group adopted osimertinib combined with aspi-rin,and the control used osimertinib merely.The overall response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS)and the adverse reactions occurrence were compared between the two groups.Results ORR and DCR after 3,6,12 months medication in the observation group were higher than those in the control group,but the differences were not statistically significant(P>0.05).Compared with the control group,PFS and OS in the observation group were longer,and the differences were statistically significant[14.9(11.8,17.2)m vs.10.5(8.9,12.5)m;24.1(19.5,27.4)m vs.18.1(16.1,21.1)m,P<0.05].In addition,PFS and OS in male and female patients with brain metastasis,EGER19 and 21 ex-on mutation in the observation group were longer than those in the control group,and the differences were statistically significant(P<0.05).There was no statistically significant difference in overall and≥Ⅲ degree adverse reactions between the two groups(P>0.05).Conclusion Osimertinib combined with aspirin could prolong PFS and OS of the advanced lung adenocarcinoma patients with EGFR mutation without increasing the risk of adverse reactions.
		                        		
		                        		
		                        		
		                        	
4.17-year study on the curative effect of treatment to prevent the recurrence of hepatitis B in different risk groups after liver transplantation
Dali ZHANG ; Xi HE ; Danni FENG ; Minjuan REN ; Yonghui GUANG ; Lixin LI ; Hongbo WANG ; Zhenwen LIU
Chinese Journal of Hepatology 2024;32(1):22-28
		                        		
		                        			
		                        			Objective:To observe the recurrence condition of hepatitis B in different risk groups after liver transplantation in an attempt to provide useful information on whether to discontinue hepatitis B immunoglobulin (HBIG) in the future at an early stage.Methods:The patient population was divided into high, low-risk, and special groups [especially primary hepatocellular carcinoma (HCC)] according to the guidelines for the prevention and treatment of hepatitis B recurrence after liver transplantation. The recurrence condition and risk factors in this population were observed for hepatitis B. Measurement data were analyzed using a t-test and a rank-sum test. Count data were compared using a χ2 test between groups. Results:This study finally included 532 hepatitis B-related liver transplant cases. A total of 35 cases had HBV recurrence after liver transplantation, including 34 cases that were HBsAg positive, one case that was HBsAg negative, and 10 cases that were hepatitis B virus (HBV) DNA positive. The overall HBV recurrence rate was 6.6%. The recurrence rate of HBV was 9.2% and 4.8% in the high- and low-risk HBV DNA positive and negative groups before surgery ( P = 0.057). Among the 293 cases diagnosed with HCC before liver transplantation, 30 had hepatitis B recurrence after surgery, with a recurrence rate of 10.2%. The independent related factors for the recurrence of hepatitis B in patients with HCC after liver transplantation were HCC recurrence ( HR =181.92, 95% CI 15.99~2 069.96, P < 0.001), a high postoperative dose of mycophenolate mofetil dispersible tablets (MMF) ( HR =5.190, 95% CI 1.289~20.889, P = 0.020), and a high dosage of HBIG ( HR = 1.012, 95% CI 1.001~1.023, P = 0.035). Among the 239 cases who were non-HCC before liver transplantation, five cases (recurrence rate of 2.1%) arouse postoperative hepatitis B recurrence. Lamivudine was used in all cases, combined with on-demand HBIG prophylaxis after surgery. There was no hepatitis B recurrence in non-HCC patients who treated with entecavir combined with HBIG after surgery. Conclusion:High-barrier-to-resistance nucleotide analogues combined with long-term HBIG have a good effect on preventing the recurrence of hepatitis B after liver transplantation. The discontinuation of HBIG may be considered at an early stage after administration of a high-barrier-to-resistance nucleotide analogue in low-risk patients. Domestically, the HBV infection rate is high, so further research is still required to explore the timing of HBIG discontinuation for high-risk patients, especially those with HCC.
		                        		
		                        		
		                        		
		                        	
5.Analysis of 15 children with type Ⅳ branchial cleft cyst treated with endoscopic transoral approach
Qingchuan DUAN ; Fengzhen ZHANG ; Guixiang WANG ; Dongjie SENG ; Hongbo REN ; Enle QIAN ; Jie ZHANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(10):1042-1047
		                        		
		                        			
		                        			Objective:To analyze the clinical characteristics and endoscopic surgical procedures of the second branchial cleft cyst type Ⅳ in children.Methods:A retrospective review was conducted on 15 pediatric cases with type Ⅳ second branchial cleft cysts treated at the Beijing Children′s Hospital affiliated with Capital Medical University and Henan Children′s Hospital from September 2019 to November 2023. All patients underwent excision via a two-person, three-hand endoscopic transoral approach. The cohort included 12 males and 3 females, with an age range of 10 months to 10 years and 5 months, and a median age of (59.20±32.05) months. The clinical data of initial symptoms, sides, imaging features, treatment methods, complications, length of hospital stay, prognosis and outcome were recorded and analyzed. SPSS 22.0 software was used for statistical analysis.Results:Of the 15 children, 13 cases presented with snoring as the primary symptom, 1 case with dysphagia, and 1 case was asymptomatic and was found unintentionally. The mean disease duration was (6.74±9.05) months (range, from 3 days-2 years). MRI revealed cystic lesions on the right side in 12 cases and on the left side in 3 cases, characterized by uniform long T2 signal, equal T1 or short T1 signal. The cysts appeared dumbbell-shaped in 10 cases with the pharyngeal constrictor muscle as the waist, the posterior outside of the mass was adjacent to the internal carotid artery. The remaining 5 cases showed an isolated cyst located inside the pharyngeal constrictor muscle. The intraoperative MRI findings were consistent. Partial cystectomy was performed in 10 cases near the internal carotid artery, leaving only the portion with a clear arterial pulse intact. Five cases with isolated cysts on the medial side of the pharyngeal constrictor muscle were totally removed. The average length of hospital stay was (4.53±0.52) days (4-5 days). All patients were followed up for 7-56 months [median (30±15.12) months] with no recurrence of symptoms observed.Conclusions:The second branchial cleft cyst type Ⅳ in children is characterized by prominent pharyngeal cystic mass, with snoring as a predominant initial symptom, MRI provides excellent diagnostic value. The two-person, third-hand endoscopic transoral approach for cyst excision is feasible, safe, and offers the benefits of minimal invasiveness and reduced hospitalization time.
		                        		
		                        		
		                        		
		                        	
6.The influence of serum triggering receptor expressed on myeloid cells 1 level on prognosis in elderly patients with sepsis and acute respiratory distress syndrome
Jianping YANG ; Hua FAN ; Wen LI ; Yao YAO ; Meijia SHEN ; Liuwei ZHANG ; Xiaoxia REN ; Hongbo ZHANG
Chinese Journal of Geriatrics 2023;42(6):715-719
		                        		
		                        			
		                        			Objective:To study the influence of serum triggering receptor expressed on myeloid cells 1(TREM-1)level on prognosis in elderly patients with sepsis and acute respiratory distress syndrome(ARDS).Methods:A total of 100 elderly patients with sepsis were selected as the research objects.All the patients with sepsis were divided into sepsis ARDS group and sepsis non-ARDS group.General data and TREM-1 level were compared between the two groups.The patients with sepsis ARDS were divided into death group and survival group according to the survival status during the 28-day follow-up.TREM-1 level, acute physiology and chronic health evaluation(APACHE)Ⅱ score and SOFA score were compared between the two groups.The correlation between serum TREM-1 level and procalcitonin(PCT), APACHE Ⅱ score and SOFA score was analyzed.The survival rate of high TREM-1 level group and low TREM-1 level group was compared.Results:The age, white blood cell(WBC), PCT, APACHE Ⅱ score, SOFA score and TREM-1 level of sepsis ARDS patients were significantly higher than those of non-ARDS patients( t=2.722, 6.088, 11.55, 6.889, 4.661, 6.122, all P<0.05). The incidence of sepsis ARDS patients with chronic obstructive pulmonary disease was significantly higher than that of non-ARDS patients( χ2=7.895, P<0.05). Serum TREM-1 level, APACHE Ⅱ score and SOFA score of ARDS patients in death group were significantly higher than those in survival group( t=3.293, 6.173, 4.255, all P<0.05). Serum TREM-1 level was positively correlated with PCT, APACHE Ⅱ score and SOFA score( t=0.553, 0.602, 0.636, P<0.001). The Kaplan-Meier survival curve showed that the survival rate of high TREM-1 level group was significantly lower than that of low TREM-1 level group( χ2=3.999, P=0.036). Cox regression analysis showed that TREM-1 level was a risk factor for the prognosis of ARDS patients with sepsis( HR=1.893, 95% CI: 1.049-3.414). Conclusions:Serum TREM-1 level is significantly increased in elderly patients with sepsis ARDS, which is closely related to the prognosis and can be used as a potential prognostic biomarker.
		                        		
		                        		
		                        		
		                        	
7.Retrospective single center study of inactivating coronavirus disease 2019 vaccine in liver transplantation recipients
Dali ZHANG ; Xi HE ; Danni FENG ; Lixin LI ; Hongling LI ; Minjuan REN ; Xiaofeng ZHANG ; Zhijie LI ; Zhenwen LIU ; Hongbo WANG
Chinese Journal of Organ Transplantation 2022;43(5):298-302
		                        		
		                        			
		                        			Objective:To explore the safety of inactivating coronavirus disease 2019(covid-19)vaccine in liver transplantation(LT)recipients.Methods:Retrospective analysis was performed for clinical data of 151 LT recipients from March 2003 to October 2019.They had stable conditions and completed the course of covid-19 vaccine.Frequencies of pain at injection site, fatigue, headache and pruritus after vaccination were recorded.The safety profiles were compared between recipients with and without local and general adverse reactions after vaccination.At the same time, recipients completing two doses of covid-19 vaccines were grouped.According to vaccine companies, they were classified into Sinovac Biotech Ltd and Beijing Biological.Based upon more than or less than 60 years, they were grouped into <60 years and ≥60 years.The safety profiles of inactivating COVID-19 vaccine were compared in subgroups.Results:Among 151 eligible LT recipients, 98 of them were in group of age <60 years and 53 in group of age >60 years.The median period between vaccination and LT was 8.44(4.37, 12.39)years and the median concentration of tacrolimus 2.5(1.8, 3.9)ng/L.Eighty-three cases completed two doses of Sinovac Biotech Ltd(Sinovac Biotech Ltd group)and 40 cases Beijing Biological(Beijing Biological group); 14 cases had combined course of Sinovac Biotech Ltd and Beijing Biological, four recipients were vaccinated with inactivated vaccine from other companies and ten recipients did not know their inactivated vaccine' companies.After immunization, 24/151(15.9%)recipients had a local and general adverse reaction.The prevalence of pain at injection site, fatigue, headache and pruritus was 9.9%( n=15), 5.2%( n=8), 1.3%( n=2)and 0.7%( n=1)respectively.No significant differences existed in age( P=0.602), gender( P=0.752), period after LT( P=0.890), trough concentration of tacrolimus( P=0.377)or versions of covid-19 vaccine( P=0.582)between 24 cases with general adverse reaction and 127 without.Local and general reactions occurred in 16/83(19.3%)in Sinovac group and 5/40(12.5%)in Beijing Biological.There was no significant inter-group difference( P=0.769). There were 98 cases(64.9%)in <60 years group, 17 cases(17.3%)had local and general reaction, 53 cases(35.1%)in ≥60 years group and 7 cases(13.2%)had a local and systemic reaction.There was no significant inter-group difference( P=0.507). Conclusions:Covid-19 vaccine is safe for long-term survival LT recipients with normal liver function.Few participants present with mild fatigue and pain at injection site.
		                        		
		                        		
		                        		
		                        	
8.Impact of intraoperative ligation of splenic artery on prognosis of liver transplantation on patients with severe hypersplenism
Lixin LI ; Yunlong ZHUANG ; Yinjie GAO ; Minjuan REN ; Ying BAI ; Hongling LI ; Zhenwen LIU ; Hongbo WANG
Chinese Journal of Hepatobiliary Surgery 2022;28(6):425-429
		                        		
		                        			
		                        			Objective:To study the impact of simultaneous ligation of splenic artery on prognosis of patients with severe hypersplenism in liver transplantation.Methods:A retrospective analysis was performed on the clinical data of 206 patients who underwent liver transplantation in the Fifth Medical Center of PLA General Hospital from December 2016 to February 2019. There were 180 males and 26 females, aged (51.0±9.0) years old. Fifty-one patients underwent splenic artery ligation during liver transplantation and they were enrolled into the observation group, and 155 patients without splenic artery ligation were enrolled into the control group. The changes in white blood cells (WBC), platelets, alanine aminotransferase, total bilirubin and serum creatinine as well as the incidence of postoperative complications were compared between the two groups.Results:The platelet count of the observation group was significantly lower than those of the control group before operation and on days 1, 3, 7, 30 and 90 after operation, (all P<0.05). The WBC counts in the observation group were significantly lower than those in the control group before operation and on days 1 and 3 after operation (all P<0.05). However, there were no significant differences in the WBC counts between the two groups on days 5, 7, 30 and 90 after operation (all P>0.05). There were also no significant differences in alanine aminotransferase and total bilirubin indexes between the two groups after surgery (all P>0.05), but the serum creatinine levels in the observation group were significantly lower than those in the control group on days 3, 5, 7 and 30 after surgery (all P<0.05). There were no significant differences in the rates of infection, severe acute rejection, biliary tract complications, arterial/portal thrombosis and mental complications between the two groups (all P>0.05). The rate of renal replacement therapy for acute kidney injury in the observation group (9.8%, 5/55) was significantly higher than that in the control group (1.3%, 2/155) ( P<0.05). Conclusion:Ligation of splenic artery during liver transplantation was safe and it had a significant advantage in the early postoperative recovery of WBC count and creatinine without increasing the incidence of complications in patients with severe hypersplenism.
		                        		
		                        		
		                        		
		                        	
9.Risk factors and treatment of portal vein thrombosis after liver transplantation
Lixin LI ; Yinjie GAO ; Xiaofeng NIU ; Minjuan REN ; Zhenwen LIU ; Hongbo WANG
Chinese Journal of Hepatobiliary Surgery 2022;28(10):735-739
		                        		
		                        			
		                        			Objective:To study the risk factors and treatment of portal vein thrombosis (PVT) in patients after liver transplantation.Methods:The clinical data of 290 recipients who underwent liver transplantation at the Department of Hepatology, the Fifth Medical Center of PLA General Hospital from July 2015 to April 2019 were retrospectively analyzed. There were 245 males and 45 females, with a median age of 51(44, 56) years old. The liver transplantation recipients were divided into two groups according to whether PVT occurred or not after operation: the PVT group ( n=16) and the non-PVT group ( n=274). Gender, age and other clinical data of the recipients were compared between the two groups. Outpatient and inpatient follow-up were performed. The risk factors of postoperative PVT were analysed in the liver transplantation recipients. Results:The median follow-up of these 290 liver transplant recipients was 59(42, 73) months, and 16 patients were confirmed to have PVT after operation, with an incidence of 5.5%(16/290). Multivariate logistic regression analysis showed that preoperative PVT ( OR=12.773, 95% CI: 3.887-41.973) was an independent risk factor for PVT after liver transplantation. For the 16 patients with postoperative PVT, 10 were treated with portal vein intervention, and the remaining 6 patients were treated with oral aspirin or rivaroxaban anticoagulation due to mild symptoms. The 3-year survival rate of the PVT group was 93.8% (15/16), while that of the non-PVT group was 90.1% (247/274). There was no significant difference in the 3-year survival rates between the two groups (χ 2<0.01, P=0.969). Conclusions:Preoperative PVT in recipients was an independent risk factor for PVT after liver transplantation. For patients with postoperative PVT, appropriate treatment resulted in good results without affecting the long-term prognosis of these patients.
		                        		
		                        		
		                        		
		                        	
10.McCune-Albright syndrome associated with growth hormone-prolactin pituitary adenoma in 4 Chinese patients with literature review
Gaofei REN ; Huijuan ZHU ; Linjie WANG ; Hongbo YANG ; Lin LU ; Shi CHEN ; Yuxing ZHAO ; Ran LI ; Hui PAN ; Yong YAO ; Lian DUAN
Chinese Journal of Endocrinology and Metabolism 2020;36(8):696-702
		                        		
		                        			
		                        			Objective:To investigate the clinical characteristics of four McCune-Albright syndrome (MAS) patients associated with growth hormone(GH)-prolactin(PRL) pituitary adenoma, and explore more effective clinical treatment and management methods.Methods:The clinical data of four patients with MAS and GH-PRL pituitary adenoma diagnosed by Peking Union Medical College Hospital were retrospectively analyzed, including clinical manifestations, biochemical parameters, radiographic characteristics, as well as treatment and prognosis. Literature review was also conducted to analyze the efficacy of surgical operations and drug intervention.Results:Clinical characteristics: 3 females and 1 male, all of whom had onset before the age of 7 years. The types of fibrous dysplasia of bone were all polyosseous and involved craniofacial region. There were obvious gigantism/acromegaly manifestations in all cases, 3 cases had evident visual impairment and 1 case with optic chiasm compression. There was no spontaneous or triggered lactation in all 4 patients. Laboratory examination: GH and insulin-like growth factor-Ⅰ(IGF-Ⅰ) levels were significantly increased in 4 patients, GH levels were not inhibited by oral glucose tolerance test (OGTT), PRL levels were over 100 ng/ml, ALP levels were significantly increased in 4 patients, while serum calcium and phosphorus levels were remained normal. Imaging features: All pituitary adenomas in 4 patients were macroadenomas, with unilateral cavernous sinus enclosure in cases 2 and 3, and recurrence of macroadenoma with bilateral cavernous sinus enclosure in case 4 after the first operation. Four cases of skull CT showed multiple FD in craniofacial bone and skull base. Treatment and outcome: All 4 patients underwent pituitary adenoma resection and bisphosphonate therapy, and somatostatin analogues, dopamine receptor agonists and other treatments were selected according to the situation. Two patients with early diagnosis and initial treatment achieved partial remission after treatment, while the other two patients did not.Conclusions:Patients with MAS and GH-PRL pituitary adenoma had earlier onset age and were more likely to suffer from optic nerve damage. Early diagnosis and reasonable surgical treatment may help to improve biochemical indicators (GH, IGF-Ⅰ, and PRL, etc.) rapidly, and combined drug therapy (somatostatin analogues and dopamine receptor agonists) can better maintain or close to normal biochemical indicators, and ultimately improve the prognosis of patients.
		                        		
		                        		
		                        		
		                        	
            
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