1.Disease burden of acute viral hepatitis in Guangdong Province, 1990-2019
Jiamin QIU ; Fangfang ZENG ; Chen CHENG ; Huiyan WEN ; Shiqi HUANG ; Dan LIU ; Jinlei QI ; Peng YIN ; Maigeng ZHOU ; Ying XU ; Zhiping LIU ; Qingsong MEI ; Heng XIAO ; Zheng XIANG ; Xiaofeng LIANG
Chinese Journal of Epidemiology 2024;45(3):365-372
Objective:To examine the burden and trends of acute viral hepatitis in Guangdong Province from 1990 to 2019, and provide reference evidences for hepatitis prevention and control in the province.Methods:Data on acute viral hepatitis (hepatitis A, B, C, and E) in Guangdong from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database. The incidence, prevalence, mortality, and disability-adjusted life years (DALY) data were analyzed by age and gender, and the estimated annual percentage change (EAPC) was calculated to describe the changing trends in disease burden.Results:From 1999 to 2019, the standardized incidence, prevalence, mortality, and DALY of acute viral hepatitis in Guangdong were higher than the national averages. In 2019, 51.43% (2 245 087/4 365 221) of acute viral hepatitis cases in Guangdong Province were mainly attributed to hepatitis B, and 77.18% (106/138) of deaths were due to acute hepatitis B. In different age groups, except for acute hepatitis B, which was more common in adults, the incidence rates of other types of viral hepatitis such as hepatitis A, B, and E showed an overall decreasing trend with age. The mortality rates of different types of acute viral hepatitis, except for the <5 age group, increased with age. The overall incidence and mortality rates of acute viral hepatitis were higher in men than in women.Conclusions:The overall burden of acute viral hepatitis in Guangdong declined in 2019, but remained higher than the national level. Further efforts are needed to strengthen hepatitis prevention and screening in different population in Guangdong Province, especially in children and the elderly.
2.Endogenous FGF21 attenuates blood-brain barrier disruption in penumbra after delayed recanalization in MCAO rats through FGFR1/PI3K/Akt pathway.
Wen ZHENG ; Wenjun LI ; Yini ZENG ; Hui YUAN ; Heng YANG ; Ru CHEN ; Anding ZHU ; Jinze WU ; Zhi SONG ; Wenguang YAN
Journal of Central South University(Medical Sciences) 2023;48(5):648-662
OBJECTIVES:
Restoration of blood circulation within "time window" is the principal treating goal for treating acute ischemic stroke. Previous studies revealed that delayed recanalization might cause serious ischemia/reperfusion injury. However, plenty of evidences showed delayed recanalization improved neurological outcomes in acute ischemic stroke. This study aims to explore the role of delayed recanalization on blood-brain barrier (BBB) in the penumbra (surrounding ischemic core) and neurological outcomes after middle cerebral artery occlusion (MCAO).
METHODS:
Recanalization was performed on the 3rd day after MCAO. BBB disruption was tested by Western blotting, Evans blue dye, and immunofluorescence staining. Infarct volume and neurological outcomes were evaluated on the 7th day after MCAO. The expression of fibroblast growth factor 21 (FGF21), fibroblast growth factor receptor 1 (FGFR1), phosphatidylinositol-3-kinase (PI3K), and serine/threonine kinase (Akt) in the penumbra were observed by immunofluorescence staining and/or Western blotting.
RESULTS:
The extraversion of Evans blue, IgG, and albumin increased surrounding ischemic core after MCAO, but significantly decreased after recanalization. The expression of Claudin-5, Occludin, and zona occludens 1 (ZO-1) decreased surrounding ischemic core after MCAO, but significantly increased after recanalization. Infarct volume reduced and neurological outcomes improved following recanalization (on the 7th day after MCAO). The expressions of Claudin-5, Occludin, and ZO-1 decreased surrounding ischemic core following MCAO, which were up-regulated corresponding to the increases of FGF21, p-FGFR1, PI3K, and p-Akt after recanalization. Intra-cerebroventricular injection of FGFR1 inhibitor SU5402 down-regulated the expression of PI3K, p-Akt, Occludin, Claudin-5, and ZO-1 in the penumbra, which weakened the beneficial effects of recanalization on neurological outcomes after MCAO.
CONCLUSIONS
Delayed recanalization on the 3rd day after MCAO increases endogenous FGF21 in the penumbra and activates FGFR1/PI3K/Akt pathway, which attenuates BBB disruption in the penumbra and improves neurobehavior in MCAO rats.
Animals
;
Rats
;
Blood-Brain Barrier/metabolism*
;
Brain Ischemia
;
Claudin-5/metabolism*
;
Infarction, Middle Cerebral Artery/metabolism*
;
Ischemic Stroke/metabolism*
;
Occludin/metabolism*
;
Phosphatidylinositol 3-Kinases/metabolism*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Rats, Sprague-Dawley
;
Receptor, Fibroblast Growth Factor, Type 1/metabolism*
;
Reperfusion Injury/metabolism*
3.Association of stress hyperglycemia with occurrence and prognosis of sepsis-associated encephalopathy
Shiying ZHANG ; Zhuo LI ; Hongguang DING ; Wenhong ZHONG ; Yin WEN ; Yongli HAN ; Xinqiang LIU ; Heng YOU ; Huishan ZHU ; Guoqiang DU ; Hongke ZENG
Chinese Journal of Emergency Medicine 2023;32(8):1070-1076
Objective:To investigate whether stress hyperglycemia (SH) is an independent risk factor for the occurrence and mortality of sepsis-associated encephalopathy (SAE).Methods:From August 2016 to October 2021, sepsis patients admitted to the ICU of Guangdong Provincial People's Hospital were selected as the study subjects. According to whether they developed to SH (RBG>11.1 mmol/L) within 7 days of enrollment, the pat ients were divided into the SH group and the non-SH group for analysis. Logistic regression was used to analyze whether SH was an independent risk factor for SAE occurrence, and ROC curve was used to analyze the predictive value of SH to SAE. Kaplan-Meier curve was used to compare the 90-day survival of SAE patients with or without SH. Cox regression analysis was used to analyze the risk factors of 28-day and 90-day death in SAE patients.Results:A total of 183 sepsis patients were included, including 62 patients in the SH group and 121 in the non-SH group. Logistic regression analysis demonstrated that SH was an independent risk factor for SAE ( OR=4.452, 95% CI: 2.021-9.808, P <0.001). ROC curve demonstrated that SH could accurately predict SAE (AUC=0.831; Sensitivity=78.4%; Specificity=76.8%; and Yoden index=0.553). Kaplan-Meier curve demonstrated that the 90-day survival of SAE patients with SH significantly declined (log-rank test: P<0.01). Cox regression analysis suggested that SH was a risk factor for death at day 28 and day 90 in SAE patients (28 d, HR=2.272, 95% CI: 1.212-4.260, P=0.010; 90 d, HR=2.456, 95% CI: 1.400-4.306, P<0.01). Conclusions:SH is an independent risk factor for SAE and can predict SAE occurrence. SH significantly reduces 90-day survival and increase mortality at 28 and 90 days in SAE patients.
4.Early-warning value of PCT/PLT ratio on sepsis-induced myocardial injury
Mengting LIU ; Wenhong ZHONG ; Yin WEN ; Shiying ZHANG ; Zhuo LI ; Heng YOU ; Yongli HAN ; Hongguang DING ; Hongke ZENG
Chinese Journal of Emergency Medicine 2022;31(8):1071-1076
Objective:To investigate the diagnostic and early-warning value of laboratory test indicators for sepsis-induced myocardial injury (SIMD).Methods:The clinical data of 183 patients with sepsis admitted to the Department of Emergency and Critical Care Medicine of Guangdong Provincial People's Hospital from August 2016 to October 2020 were collected. The patient's age, gender, past medical history, vital signs and pathogen culture results were extracted. Cardiac function, blood routine, liver function, renal function, inflammatory factors, coagulation function, APACHE Ⅱ and SOFA scores were recorded at enrollment and 72 h after admission. SIMD was defined as cTnT ≥300 pg/mL and NT-proBNP ≥1243 pg/mL twice in 72 h intervals between enrolled cases, and the early-warning factors of patients with SIMD were analyzed. The differences in various indicators between the two groups were compared, and Logistic regression analysis was used to explore the diagnostic efficacy of cTnT and NT-proBNP combined for SIMD, and the correlation between PCT/PLT ratio and the occurrence of SIMD.Results:Among 250 patients, 67 patients were excluded for lack of the main indicators, and 183 patients (including 62 patients with history of cardiac disease) were enrolled finally. Among 183 patients with sepsis, 105 patients (57.38%) with cTNT ≥300 pg/mL and NT-proBNP ≥1 243 pg/mL, were diagnosed as myocardial injury; after excluding 62 patients with history of cardiac disease, 59 patients (48.76%) with cTNT ≥300 pg/mL and NT-proBNP ≥1 243 pg/mL were diagnosed as myocardial injury. Logistic regression analysis showed that increased PCT/PLT ratio ( OR=1.585, 95% CI: 1.124-2.237, P=0.009) was an independent risk factor for early-warning of SIMD. The PCT/PLT ratio ( OR= 1.850, 95% CI: 1.103-3.102, P=0.020) could stably predict the occurrence of SIMD in patients without previous history of heart disease. ROC curve analysis showed that PCT/PLT ratio could effectively predict the occurrence of SIMD (AUC=0.693, 95% CI: 0.617-0.769, P<0.001), the optimal cut-off value was 0.177 (sensitivity: 65.7%, specificity: 66.7%). The PCT/PLT ratio was still effective in predicting the occurrence of SIMD after excluding patients with previous history of heart disease (AUC=0.733, 95% CI: 0.643-0.823, P<0.001), and the optimal cut-off value was 0.429 (sensitivity: 55.9%, specificity: 83.9%). Conclusions:The combination of cTnT and NT-proBNP has certain diagnostic value for SIMD, and the PCT/PLT ratio could warn the occurrence of SIMD.
5.Long-term immunization and prognosis outcome of patients with occult hepatitis B virus infection
Xin ZHENG ; Xiaoxuan XU ; Heng LIU ; Xiujuan CUI ; Wen XIONG ; Guidan WU ; Jinfeng ZENG
Chinese Journal of Blood Transfusion 2022;35(5):541-546
【Objective】 To investigate the prognosis of blood donors with occult hepatitis B virus infection (OBI) by long-term follow-up and repeated testing of HBsAg and HBV DNA. 【Methods】 From January 1, 2010 to December 31, 2020, voluntary blood donors were screened by both serological and viral nucleic acid(NAT) testing, then samples were further confirmed as HBV DNA positive by manual nested-PCR amplification.A total of 306 cases were detected as HBsAg negative /HBV DNA positive, then followed-up for a long time and re-examined of HBsAg and HBV DNA to confirm whether they had infected with OBI.The prognosis of patients with OBI who experienced long-term immunization was determined by repeated testing. 【Results】 A total of 306 HBsAg negative/ HBV DNA positive blood donors had been followed up, and 40(13.07%, 40/306) were recalled frequently for re-examination.Among them, 90%(36/40), 57.5%(23/40), 40% (16/40)were anti-HBc + , anti-HBs + and anti-HBe + , respectively, and 50%(20/40), 40%(16/40), 7.5%(3/40) and 2.5% (1/40)were anti-HBs+ / anti-HBc + , anti-HBc + / anti-HBs -, anti-HBc -/ anti-HBs + and anti-HBc -/ anti-HBs -, respectively.Those 40 blood donors were followed-up for 1-13 times, with the duration of 8-108 months (0.6~9 years).1 donor (2.5%) was followed-up less than 1 year, 11 (27.5%)>1 year and ≤3 years, 23 (57.5%) 23(57.5%)>3 years and ≤5 years, and 5 (12.5%) for more than 5 years.After long-term following up and repeated testing, 50%(20/40)of OBI blood donors turned negative for HBV DNA (HBsAg negative / HBV DNA negative), 42.5% (17/40)were confirmed as OBI infection (HBsAg negative / HBV DNA positive), and 7.5%(3/40) were hard to determine (after repeated testing, the results were either positive or negative). 【Conclusion】 After long-term following up and repeated screening, we found that none of the OBI patients turned into acute or chronic HBV infection, and most of them maintained OBI.However, OBI blood donors carry very low load of HBV DNA for a long time, which could lead to false negative results of NAT and bring a great challenge to the safety of blood transfusion.
6.Clinical characteristics of coronavirus disease 2019 infected with Delta variant in Guangzhou:A real-world study
Danwen ZHENG ; Heng WENG ; Yuntao LIU ; Xin YIN ; Jun ZHANG ; Jian ZHANG ; Luming CHEN ; Yuanshen ZHOU ; Jing ZENG ; Yan CAI ; Wanxin WEN ; Qinghua ZHANG ; Lanting TAO ; Liangsheng SUN ; Tianjin CAI ; Weiliang WANG ; Shubin CAI ; Xindong QIN ; Xiaofeng LIN ; Xiaohua XU ; Haimei ZOU ; Qiaoli HUA ; Peipei LU ; Jingnan LIN ; Kaiyuan ZHANG ; Aihua OU ; Jiqiang LI ; Fang YAN ; Xu ZOU ; Lin LIN ; Banghan DING ; Jianwen GUO ; Tiehe QIN ; Yimin LI ; Xiangdong GUAN ; Xiaoneng MO ; Zhongde ZHANG
Chinese Journal of Emergency Medicine 2021;30(10):1220-1228
Objective:To summarize the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) infected with Delta variant, so as to provide further references for clinical diagnosis and treatment.Methods:A real-world study was conducted to analyze the characteristics of 166 COVID-19 patients infected with Delta variant at Guangzhou Eighth People’s Hospital, Guangzhou Medical University.Results:The study enrolled 5 asymptomatic cases, 123 non-severe cases (mild and moderate type), and 38 severe cases (severe and critical type). Among these patients, 69 (41.6%) were male and 97 (58.4%) were female, with a mean age of 47.0±23.5 years. Thirty-nine cases (23.5%) had received 1 or 2 doses of inactivated vaccine. The incidence of severe COVID-19 cases was 7.7% in 2-doses vaccinated patients, which was lower than that of 11.5% in 1-dose and 26.8% in unvaccinated patients. The proportion of severe cases in 2 dose-vaccinated patients was 7.7%, which was lower than that of 11.5% in 1-dose vaccinated patients and 26.8% in unvaccinated patients, but the difference was not significant ( P>0.05). The most common clinical symptom was fever (134 cases, 83.2%), and 39.1% of cases presented with high-grade fever (≥39 °C); other symptoms were cough, sputum, fatigue, and xerostomia. The proportion of fever in severe cases was significantly higher than that of non-severe cases (97.4% vs. 76.4%, P<0.01). Similarly, the proportion of severe cases with high peak temperature (≥39 ℃) () was also higher than that of non-severe cases (65.8% vs. 30.9%, P<0.01). The median minimal Cycle threshold (Ct) values of viral nucleic acid N gene and ORFlab gene were 20.3 and 21.5, respectively, and the minimum Ct values were 11.9 and 13.5, respectively. Within 48 h of admission, 9.0% of cases presented with decreased white blood cell counts, and 52.4% with decreased lymphocyte counts. The proportions of increased C-reactive protein, serum amyloid A, interleukin 6, and interleukin 10 were 32.5%, 57.4%, 65.3%, and 35.7%, respectively. The proportions of elevated C-reactive protein, serum amyloid A and interleukin-6 in severe cases were significantly higher than those in non-severe cases ( P<0.01). Logistic regression analysis showed that older age and higher peak temperature were associated with a higher likelihood of severe cases ( OR>3, 95% CI: 2-7, P<0.01). In terms of treatment, traditional Chinese medicine (TCM) was used in 97.6% of non-severe cases and 100% in severe cases. Other treatments included respiratory and nutritional support, immunotherapy (such as neutralizing antibodies and plasma of recovered patients). The median times from admission to progression to severe cases, of fever clearance, and of nucleic acid conversion were 5 days, 6 days and 19 days, respectively. No deaths were reported within 28 days. Conclusions:The symptoms of Delta variant infection in Guangzhou are characterized by a high proportion of fever, high peak temperature, long duration of fever, high viral load, a long time to nucleic acid conversion, and a high incidence of severe cases. The severe cases exhibit a higher percentage of elderly patients, a longer duration of fever and have a higher fever rate and a higher hyperthermia rate than non-severe cases. Age and hyperthermia are independent risk factors for progression to severe disease. The combination of TCM and Western medicine can control the progression of the disease effectively.
7.All levels miniplate fixation and a modified hybrid fixation method in expansive open-door cervical laminoplasty: a retrospective comparative study.
Ze Chuan YANG ; Chao Xu LIU ; Yang LIN ; Wei Hua HU ; Wen Jian CHEN ; Feng LI ; Heng ZENG
Journal of Peking University(Health Sciences) 2019;51(1):187-193
OBJECTIVE:
To retrospectively compare the effect of alternate levels miniplate and anchor fixation with the effect of all levels miniplate fixation in expansive open-door cervical laminoplasty (EOLP).
METHODS:
Patients with cervical spondylosis underwent EOLP between July 2015 and June 2016 were included in the study. There were 33 patients in the alternate group (alternate levels miniplate and anchor fixation group) and 34 patients in the miniplate group (all levels miniplate fixation group). Neurological function was evaluated with the Japanese Orthopedic Association (JOA) score and degree of pain was assessed with the visual analogue scale (VAS) score. Basic clinical and surgical data, complication rates and medical costs of the two groups were compared. In addition, radiological examinations were performed pre- and post-operatively and at the final follow-up. Relative imaging data such as anteroposterior diameter (APD), cervical curvature index (CCI) and open angle were collected and compared.
RESULTS:
(1) The mean follow-up time was 18.6 months in the alternate group and 18.9 months in the miniplate group. There were no significant differences in operation time, intraoperative blood loss, perioperative complication rates, post-operative hospital stays, VAS scores and neurological recovery rates preoperatively and at the final follow-up between the two groups. (2) Additionally, no obvious differences were observed about CCIs and APDs at the three follow-up time points between the two groups. Post-operative open angles at C4 and C6 in the alternate group were significantly smaller than those in the miniplate group. However, there were no significant differences in C3, C5 and C7 open angles between the two groups post-operatively. Notably, no significant differences were detected about the open angles at all levels between the two groups at the final follow-up. (3) When comparing radiologic data at different time points in each group, CCIs and open angles at each level had no significant differences, but APDs after surgery and at the final follow-up were significantly larger than pre-operative APDs. (4) Total costs in the alternate group were significantly lower than those in the miniplate group.
CONCLUSION
The two surgical methods showed almost the same neurological recovery rates and complication rates. However, use of alternate levels miniplate and anchor fixation in EOLP can reduce medical expenses.
Bone Plates
;
Cervical Vertebrae
;
Humans
;
Laminectomy
;
Laminoplasty
;
Retrospective Studies
;
Treatment Outcome
8.Effect analysis of improving the HIV positive detection rate by single sample nucleic acid amplification test in Shenzhen
Songxing WANG ; Wen XIONG ; Xinghui GU ; Heng LIU ; Yunping XU ; Jinfeng ZENG
International Journal of Laboratory Medicine 2018;39(13):1562-1565
Objective To investigate the effect of improving the human immunodeficiency virus (HIV)posi-tive detection rate by single sample nucleic acid amplification test (SS-NAT) in Shenzhen ,and to explore the effect of SS-NAT on reducing the risk of HIV infection in transfusion .Methods 269 228 blood samples were performed parallel detection by SS-NAT (Procleix Tigris ) and two kinds of enzyme-linked immuno sorbent assay(ELISA)reagents ,and then the samples with nonreactive by ELISA and reactive by SS-NAT were tested by HIV identification assay .The blood donors with reactive HIV identification assay were made tracing tests . All the samples with reactive by ELISA or HIV identification assay were sent to the Shenzhen Center for Dis-ease Control and Prevention (CDC) for Western Blot (WB) diagnostic tests .Results The samples with reac-tive by the third generation ELISA reagents ,the fourth generation ELISA reagents ,both ELISA reagents and SS-NAT were 188 ,340 ,422 and 103 ,which reactive rate was 0 .698‰(188/269 228) ,1 .263‰(340/269 228) , 1 .567‰(422/269 228) and 0 .383‰(103/269 228) ,respectively .We found four samples with nonreactive by ELISA but reactive by SS-NAT .The four donors were found HIV reactive by both ELISA and SS-NAT after tracing .All the samples with reactive by ELISA or HIV identification assay were sent to CDC for confirmatory tests and 103 of them were positive .The positive detection rate of transfusion-transmissible HIV infection af-ter ELISA detection was 1∶67 307(4/269 228) .Conclusion The application of SS-NAT in blood screening can improve the HIV positive detection rate ,shorten window period of HIV detection and reduce residual risk of transfusion-transmissible HIV infection ,and then blood safety can be effectively improved .
9.Clinical analysis of 70 chronic lymphocytic leukemia patients with trisomy 12 detected by FISH.
Rui LV ; Zeng Jun LI ; Heng LI ; Shu Hua YI ; Wei LIU ; Ting Yu WANG ; Wen Jie XIONG ; Lu Gui QIU
Chinese Journal of Hematology 2018;39(5):387-391
Objective: To summarize and investigate the characteristics, prognosis and treatments of chronic lymphocytic leukemia (CLL) patients with trisomy 12 by using FISH (CEP12). Methods: Clinical data of 330 CLL patients were analyzed retrospectively by using FISH (CEP12) to detect trisomy 12 from May 2003 to April 2015. The clinical data and laboratory characteristics of CEP12 positive patients (70 cases) were compared with those CEP12 negative patients (260 cases). Results: Compared with CEP12 negative CLL patients, the proportion of hepatomegaly (13.6% vs 4.0%, P=0.011) and LDH>247 U/L (43.3% vs 18.5%, χ(2)=15.892, P<0.001) in CEP12 positive CLL patients were much higher, respectively. There were no significant differences between age, sex, clinical stage, β(2)-microglobulin level, IGHV mutation ratio and splenomegaly/lymphadenopathy in these two subgroups. However, compared with CEP12 negative patients, CEP12 positive patients had higher ratio of FMC7 (23.8% vs 12.7%, χ(2)=4.730, P=0.030), and lower ratio of CD23 (95.2% vs 99.6%, P=0.033). The overall response rates (ORR) in Fludarabine (without Rituximab), Rituximab (with or without Fludarabine) and the traditional chemotherapy group (chlorambucil, CHOP or CHOP-like) were 77.5% (31/40), 84.8% (56/66) and 45.4% (50/110), respectively. The ORR of the traditional chemotherapy group was lower than that of the Fludarabine group and Rituximab group. For CEP12 positive patients, the ORR was inferior to CEP12 negative patients when only using Fludarabine (P<0.05). However, when using Rituximab, the difference could be eliminated, and the ORR was even a little higher in CEP12 negative patients (91.7% vs 81.0%, P=0.306). Compared with CEP12 negative patients, there were no significant differences in progression-free survival (PFS) (χ(2)=0.410, P=0.478) and overall survival (OS) (χ(2)=0.052, P=0.180) for CEP12 positive patients whom the median time from diagnosis to start treatment and OS time was 22.6 (95%CI 15.4-31.7) and 118.5 (95%CI 74.5-162.4) month while the 5-year PFS and OS were (52.9±7.6)% and (74.8±6.6)%. Conclusions: CEP12 positive CLL patients are more common in hepatomegaly and higher level of LDH. The traditional chemotherapy treatment had the lowest efficacy, and the curative effect of single use of fludarabine is not as good as that of CEP12 negative patients, however, when using Ritaximab, the efficacy could be comparable.
Antibodies, Monoclonal, Murine-Derived
;
Antineoplastic Combined Chemotherapy Protocols
;
Humans
;
Leukemia, Lymphocytic, Chronic, B-Cell
;
Retrospective Studies
;
Rituximab
;
Trisomy
;
Vidarabine
10.Chronic Lymphocytic Leukemia Prognostic Index: A New Integrated Scoring System to Predict the Time to First Treatment in Chinese Patients with Chronic Lymphocytic Leukemia.
Heng LI ; Shu-Hua YI ; Wen-Jie XIONG ; Hui-Min LIU ; Rui LYU ; Ting-Yu WANG ; Wei LIU ; Shi-Zhen ZHONG ; Zhen YU ; De-Hui ZOU ; Yan XU ; Gang AN ; Zeng-Jun LI ; Lu-Gui QIU
Chinese Medical Journal 2017;130(2):135-142
BACKGROUNDThe established clinical staging systems (Rai/Binet) of chronic lymphocytic leukemia (CLL) cannot accurately predict the appropriate treatment of patients in the earlier stages. In the past two decades, several prognostic factors have been identified to predict the outcome of patients with CLL, but only a few studies investigated more markers together. To predict the time to first treatment (TTFT) in patients of early stages, we evaluated the prognostic role of conventional markers as well as cytogenetic abnormalities and combined them together in a new prognostic scoring system, the CLL prognostic index (CLL-PI).
METHODSTaking advantage of a population of 406 untreated Chinese patients with CLL at early and advanced stage of disease, we identified the strongest prognostic markers of TTFT and, subsequently, in a cohort of 173 patients who had complete data for all 3 variables, we integrated the data of traditional staging system, cytogenetic aberrations, and mutational status of immunoglobulin heavy chain variable region (IGHV) in CLL-PI. The median follow-up time was 45 months and the end point was TTFT.
RESULTSThe median TTFT was 38 months and the 5-year overall survival was 80%. According to univariate analysis, patients of advanced Rai stages (P < 0.001) or with 11q- (P = 0.002), 17p- (P < 0.001), unmutated IGHV (P < 0.001), negative 13q- (P = 0.007) and elevated lactate dehydrogenase levels (P = 0.001) tended to have a significantly shorter TTFT. And subsequently, based on multivariate Cox regression analysis, three independent factors for TTFT were identified: advanced clinical stage (P = 0.002), 17p- (P = 0.050) and unmutated IGHV (P = 0.049). Applying weighted grading of these independent factors, a CLL-PI was constructed based on regression parameters, which could categorize four different risk groups (low risk [score 0], intermediate low [score 1], intermediate high [score 2] and high risk [score 3-6]) with significantly different TTFT (median TTFT of not reached (NR), 65.0 months, 36.0 months and 19.0 months, respectively, P < 0.001).
CONCLUSIONSThis study developed a weighted, integrated CLL-PI prognostic system of CLL patients which combines the critical genetic prognostic markers with traditional clinical stage. This novel modified PI system could be used to discriminate among groups and may help predict the TTFT and prognosis of patients with CLL.
Adult ; Aged ; Aged, 80 and over ; China ; Chromosome Aberrations ; Chromosomes, Human, Pair 17 ; genetics ; DNA Mutational Analysis ; Female ; Humans ; Immunoglobulin Heavy Chains ; genetics ; metabolism ; In Situ Hybridization, Fluorescence ; Leukemia, Lymphocytic, Chronic, B-Cell ; diagnosis ; genetics ; metabolism ; Male ; Middle Aged ; Mutation ; Prognosis

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