1.Risk Assessment of Secondary Primary Malignancies in Nasopharyngeal Carcinoma: A Big-Data Intelligence Platform-Based Analysis of 6,377 Long-term Survivors from an Endemic Area Treated with Intensity-Modulated Radiation Therapy during 2003–2013
Lu Lu ZHANG ; Guo Hong LI ; Yi Yang LI ; Zhen Yu QI ; Ai Hua LIN ; Ying SUN
Cancer Research and Treatment 2019;51(3):982-991
PURPOSE: The incidence, risk factors and survival impact of secondary primary malignancies (SPMs) among survivors of nasopharyngeal carcinoma (NPC) treated with definitive intensity-modulated radiation therapy (IMRT) with or without chemotherapy are poorly characterized. METHODS AND MATERIALS: Consecutive patients (n=6,377) from the big-data intelligence platform at Sun Yat-sen University Cancer Center, China (in a high-incidence area) with newly diagnosed non-metastatic pathologically proven non-keratinizing undifferentiated NPC treated with IMRT±chemotherapy between January 2003 and June 2013 were retrospectively analyzed. Cumulative incidence of SPMs was calculated using the Kaplan-Meier method. Cox proportional hazards model was used to identify potential risk factors for SPMs and assess whether SPMs affect overall survival. RESULTS: Of the 6,377 patients, 189 (3.0%) suffered SPMs (median follow-up, 62 months). One-, 2-, 3-, 4-, and 5-cumulative risks of SPMs were 0.4%, 0.9%, 1.6%, 2.2%, and 2.6%, respectively. Latency from start of IMRT to SPMs diagnosis was 37 months (range, 6 to 102 months). In patients with SPMs, 14.3% suffered SPMs within 1 year post-IMRT: 1-3 years, 38.1%; 3-5 years, 33.9%; and >5 years, 13.7%. Lung cancer was the most common SPM (50/6,377, 0.78%). Multivariate analysis demonstrated sex (male, 64% increase), age (≥50 years, 68% increase), and smoking history (41% increase) were significant risk factors for SPMs, and SPMs were associated with poorer overall survival. CONCLUSION: This large cohort study confirms SPMs a dreadful complication for long-term survivors of NPC treated with IMRT. SPMs negatively impact overall survival in NPC. Close follow-up is recommended for older male survivors with a smoking history.
China
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Cohort Studies
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Diagnosis
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Drug Therapy
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Follow-Up Studies
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Humans
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Incidence
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Intelligence
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Lung Neoplasms
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Male
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Methods
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Multivariate Analysis
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Proportional Hazards Models
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Retrospective Studies
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Risk Assessment
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Risk Factors
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Smoke
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Smoking
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Solar System
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Survivors
2.Rationale and study design for one-stop assessment of renal artery stenosis and renal microvascular perfusion with contrast-enhanced ultrasound for patients with suspected renovascular hypertension.
Jun-Hong REN ; Na MA ; Si-Yu WANG ; You-Jing SUN ; Yue-Wei ZHANG ; Fa-Jin GUO ; Yong-Jun LI ; Tian-Hui LI ; Hu AI ; Wen-Duo ZHANG ; Peng LI ; Wei-Hua MA
Chinese Medical Journal 2019;132(1):63-68
BACKGROUND:
Renal artery stenosis (RAS) is always associated with abnormalities in renal microvascular perfusion (RMP). However, few imaging methods can simultaneously evaluate the degree of luminal stenosis and RMP. Thus, this study will aim to evaluate the feasibility of using contrast-enhanced ultrasound (CEUS) for assessing both RAS and RMP to achieve a one-stop assessment of patients with suspected renovascular hypertension.
METHODS:
This will be a single-center diagnostic study with a sample size of 440. Patients with chronic kidney disease (CKD) and suspected of having resistant hypertension will be eligible. Patients with Stages 1-3 CKD will undergo CEUS and computed tomography (CT) angiography (CTA). Values obtained by CEUS and CTA for diagnosing low-grade (lumen reduced by <60%) and high-grade (lumen reduced by ≥60%) RAS will be compared. Moreover, all patients will also undergo radionuclide imaging. The diagnostic value for RAS will be assessed by the receiver operating characteristic curve, including the accuracy, sensitivity, specificity, positive predictive values, negative predictive values, and area under the ROC. Pearson correlation analysis will be performed to assess the association between CEUS findings for RMP and glomerular filtration rate measured by a radionuclide imaging method.
CONCLUSION:
The data gathered from this study will be used to evaluate the feasibility of expanding clinical applications of CEUS for evaluation of patients with suspected renovascular hypertension.
TRIAL REGISTRATION
Chinese Clinical Trial Registry, ChiCTR1800016252; https://www.chictr.org.cn.
Contrast Media
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Glomerular Filtration Rate
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physiology
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Humans
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Hypertension, Renovascular
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physiopathology
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ROC Curve
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Renal Artery
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physiopathology
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Renal Artery Obstruction
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physiopathology
3. Effect of Shoutaiwan and Shaoyao Gancao Tang on Recurrent Spontaneous Abortion
Yan-li SONG ; Ai-wu WEI ; Zi-xue SUN ; Bo MEN ; Hua ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2019;25(7):36-42
Objective: To observe the effect of Shoutaiwan and Shaoyao Gancao Tang on recurrent spontaneous abortion due to spleen and kidney Qi deficiency. Method: Totally 80 eligible patients were randomly divided into the control group and the treatment group, with 90 cases in each group. The control group was treated with lymphocyte immune; the Shoutaiwan and Shaoyao Gancao Tang combined with lymphocyte immune was applied in the treatment group. Coagulation function[the part plasminogen activator inhibitor-1 (PAI-1), fibrinogen (FIB), type plasminogen activator (t-PA), prothrombin time (PT), D-dimer (D-D) and tissue factor (TF), fibrin peptide A (FPA), fibrinogen (Fig), Plasminase-antifibrinolytic complex (PAP), glycoprotein platelet particle-140 (GMP-140), thrombin-antithrombin complex (TAT)], serum closed antibody (CD3+,CD4+,CD8+,CD4+/CD8+), inflammatory factor interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), interleukin-10 (IL-10)]were scored after the treatment. The rates of birth and adverse reactions in each group were compared. The traditional Chinese medicine(TCM) syndrome differentiation of abortion spleen and kidney Qi deficiency was scored. Result: 5 cases were lost during the study period. The term delivery rate was 92.0%in the treatment group, which was higher than 73.6%in control group (P<0.05). The total effective rate was 97.7%in the treatment group, which was higher than 81.6%in control group (P<0.05). The coagulation function indexes (PAI-1, FIB, t-PA,D-D, PAP, GMP-140, TAT), closed antibodies (CD3+, CD4+, CD4+/CD8+), inflammatory factors (IFN-γ,TNF-α,IL-1β) and TCM syndrome scores were significantly lower in the treatment group than that in control group (P<0.05). Coagulation function indexes (PT,TF,FPA,Fig), serum blocking antibodies (CD8+), inflammatory factors IL-10 were significantly increased compared with the control group (P<0.05). The incidence of adverse reactions in treatment group was 10.3%(9/87), which was lower than 22.7%in control group (20/88) (P<0.05). Conclusion: Shoutaiwan and Shaoyao Gancao Tang have a remarkable effect on recurrent spontaneous abortion case by spleen and kidney Yang deficiency.
4. Effect of Modified Xiaokefang on Endothelial Injury, Oxidative Stress and Biochemical Indices of Diabetic Nephropathy Patients of Qi-Yin Deficiency with Blood-stasis Syndrome
Xiao-ze SUN ; Gao-feng TAN ; Ai-hua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2019;25(9):43-48
Objective: To explore the effect of modified Xiaokefang on endothelial injury,oxidative stress and biochemical indices of diabetic nephropathy (DN) patients of Qi-Yin deficiency with blood-stasis syndrome.Method: Ninety-four patients with DN admitted to our hospital from September 2017 to June 2018 were randomly divided into two groups.The control group (47 cases) was injected with reduced glutathione by intravenous drip.In addition to the therapy of the control group,the observation group (47 cases) was treated with modified Xiaokefang.Before and after treatment,the symptom scores,fasting blood glucose (FBG),2 hpostprandial blood glucose (2 hPG),glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD),malondialdehyde (MDA) and interleukin-1 beta (IL-1β),IL-6,hypersensitive C-reactive protein (hs-CRP),tumor necrosis factor-α(TNF-α),tissue blood fibrin dissolve enzyme activation (t-PA),type 1 original organization fibrin lytic enzyme activators inhibitor (PAI-1),serum creatinine (SCr),blood urea nitrogen (BUN),nitric oxide (NO),endothelin-1(ET-1),24 h total urinary protein levels were observed,and the efficacy of the two groups were observed.Result: After treatment,the total effective rate of the observation group was 89.36%,which was higher than 74.47% of the control group (Z=3.949,P<0.05).The scores of symptoms in the observation group after treatment were lower than those in the control group (P<0.05).After treatment,FBG,2 hPG,SCr,BUN,24 h total urine protein,ET-1,MDA,IL-1β,IL-6,hs-CRP,TNF-α,and PAI-1 levels in the observation group were lower than those in the control group (P<0.05),while NO,SOD,GSH-Px,and t-PA levels were increased (P<0.05).Conclusion: Modified Xiaokefang has a remarkable effect in treatment of diabetic nephropathy patients of Qi-Yin deficiency with blood-stasis syndrome by alleviating clinical symptoms,promoting the recovery of balance of coagulation and fibrinolysis system,inhibiting inflammation and oxidative stress,and protecting endothelial function and renal function.
5.Molecular Characterization and Correlation with β-lactam Resistance of Streptococcus pneumonia Isolates in Hangzhou, China.
Mei Fen CHU ; Xiao Xiang LIU ; Shao Ni ZHANG ; Yan Ying HUANG ; Peng DU ; Li Fang WANG ; Lei JI ; Jie YAN ; Ai Hua SUN
Biomedical and Environmental Sciences 2018;31(5):389-393
Penicillin-binding proteins (PBPs) are the target of β-lactam antibiotics (the major treatment for Streptococcus pneumoniae infections), and mutations in PBPs are considered as a primary mechanism for the development of β-lactam resistance in S. pneumoniae. This study was conducted to investigate the mutations in the PBPs of clinical S. pneumoniae isolates in Hangzhou, China, in correlation with β-lactam resistance. Results showed that 19F was the predominant serotype (7/27) and 14 of the S. pneumoniae isolates were resistant to both penicillin G and cephalosporin. Genotyping results suggested that β-lactam-resistant isolates primarily exhibited single-site mutations in both the STMK and SRNVP motifs of pbp1a in combination with double-site mutations in the STMK motif of pbp2x, which might be the primary mechanisms underlying the β-lactam resistance of the isolates in this study.
Anti-Bacterial Agents
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pharmacology
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China
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epidemiology
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Drug Resistance, Bacterial
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Humans
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Pneumococcal Infections
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epidemiology
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microbiology
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Streptococcus pneumoniae
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drug effects
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genetics
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beta-Lactams
;
pharmacology
6.A National Study of Survival Trends and Conditional Survival in Nasopharyngeal Carcinoma: Analysis of the National Population-Based Surveillance Epidemiology and End Results Registry.
Jia Wei LV ; Xiao Dan HUANG ; Yu Pei CHEN ; Guan Qun ZHOU ; Ling Long TANG ; Yan Ping MAO ; Wen Fei LI ; Ai Hua LIN ; Jun MA ; Ying SUN
Cancer Research and Treatment 2018;50(2):324-334
PURPOSE: Conditional survival (CS) provides important information on survival for a period of time after diagnosis. Currently, information on CS patterns of patients with nasopharyngeal carcinoma (NPC) is lacking. We aimed to analyze survival rate over time and estimate CS for NPC patients using a national population-based registry. MATERIALS AND METHODS: Patients diagnosed with NPC between 1973 and 2007 with at least 5-year follow-up were identified from the Surveillance Epidemiology End Results registry. Traditional survival rates and crude CS estimateswere calculated using Kaplan-Meier analysis. Risk-adjusted survival curves were plotted from the proportional hazards model using the correct group prognosis method. RESULTS: For 7,713 patients analyzed, adjusted baseline 5-year overall survival improved significantly from 36.0% in patients diagnosed in 1973-1979, 41.7% in 1980-1989, 46.6% in 1990-1999, to 54.7% in 2000-2007 (p < 0.01). CS analysis demonstrated that for every additional year survived, adjusted probability of surviving the next 5 years increased from 66.7% (localized), 54.0% (regional), and 35.3% (distant) at the time of diagnosis, to 83.7% (localized), 75.0% (regional), and 62.2% (distant) for patients who had survived 5 years. Adjusted 5-year CS differed among age, sex, tumor histology, ethnicity, and stage subgroups initially, but converged with time. CONCLUSION: Treatment outcomes of NPC patients have greatly improved over the decades. Increases in CS become more prominent in patients with distant disease than in those with localized or regional disease as patients survive longer. CS provides more dynamic prognostic information for patients who have survived a period of time after diagnosis.
Diagnosis
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Epidemiology*
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Follow-Up Studies
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Humans
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Kaplan-Meier Estimate
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Methods
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Nasopharyngeal Neoplasms
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Prognosis
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Proportional Hazards Models
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SEER Program
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Survival Rate
7.Neutropenia during the First Cycle of Induction Chemotherapy Is Prognostic for Poor Survival in Locoregionally Advanced Nasopharyngeal Carcinoma: A Real-World Study in an Endemic Area.
Cheng XU ; Shi Ping YANG ; Yuan ZHANG ; Ling Long TANG ; Guan Qun ZHOU ; Xu LIU ; Yan Ping MAO ; Rui GUO ; Wen Fei LI ; Lei CHEN ; Ai Hua LIN ; Ying SUN ; Jun MA
Cancer Research and Treatment 2018;50(3):777-790
PURPOSE: The purpose of this study was to investigate the effect of neutropenia during the first cycle of induction chemotherapy (IC-1) on survival in locoregionally advanced nasopharyngeal carcinoma (LANPC). MATERIALS AND METHODS: Eligible patients (n=545) with LANPC receiving IC+concurrent chemoradiotherapy were included. Based on nadir neutrophil afterIC-1, all patientswere categorized into three groups: no/grade 1-2/grade 3-4 neutropenia. Five-year overall survival (OS) and disease-free survival (DFS) were compared between groups and subgroups stratified by IC regimen. We also explored the occurrence of IC-1–induced myelosuppression events and the minimal value of post-treatment neutrophil-to-lymphocyte ratio (post-NLRmin). Univariate/multivariate analyses were performed to investigate the effect of IC-1–induced neutropenia, timing of neutropenia, number of myelosuppression events, and high post-NLRmin on OS/DFS. RESULTS: Grade 1-2/grade 3-4 neutropeniawere associatedwith poorer OS/DFS than no neutropenia (all p < 0.05); OS/DFS were not significantly different between patients experiencing grade 1-2 vs. 3-4 neutropenia. Neutropenia had no significant effect on OS/DFS in patients receiving docetaxel–cisplatin–5-fluorouracil (TPF). Grade 1-2 (grade 3-4) neutropenia negatively influenced OS/DFS in patients receiving cisplatin–5-fluorouracil (PF) (PF and docetaxel–cisplatin [TP]; all p < 0.05). Neutropenia, two/three myelosuppression events, and high post-NLRmin (≥ 1.33) was most frequent on days 5-10, second and third week of IC-1, respectively. After adjustment for covariates, IC-1–induced neutropenia, two/three myelosuppression events, and post-NLRmin ≥ 1.33were validated as negative predictors of OS/DFS (all p < 0.05); timing of neutropenia had no significant effect. CONCLUSION: Occurrence of neutropenia, number of myelosuppression events, and high post-NLRmin during PF/TP IC-1 have prognostic value for poor survival in LANPC.
Chemoradiotherapy
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Disease-Free Survival
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Humans
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Induction Chemotherapy*
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Lymphocytes
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Neutropenia*
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Neutrophils
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Prognosis
8.Proposal of a Pretreatment Nomogram for Predicting Local Recurrence after Intensity-Modulated Radiation Therapy in T4 Nasopharyngeal Carcinoma: A Retrospective Review of 415 Chinese Patients.
Lu Lu ZHANG ; Yi Yang LI ; Jiang HU ; Guan Qun ZHOU ; Lei CHEN ; Wen Fei LI ; Ai Hua LIN ; Jun MA ; Zhen Yu QI ; Ying SUN
Cancer Research and Treatment 2018;50(4):1084-1095
PURPOSE: Local relapse-free survival (LRFS) differs widely among patients with T4 category nasopharyngeal carcinoma (NPC). We aimed to build a nomogram incorporating clinicopathological information to predict LRFS in T4 NPC after definitive intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: Retrospective study of 415 Chinese patients with non-metastatic T4 NPC treated with definitive IMRT with or without chemotherapy at our cancer center between October 2009 and September 2013. The nomogram for LRFS at 3 and 5 years was generated based on multivariate Cox proportional hazards regression, and validated using bootstrap resampling, assessing discriminative performance using the concordance index (C-index) and determining calibration ability via calibration curves. RESULTS: Five-year LRFS was 88.8%. We identified and incorporated four independent prognostic factors for LRFS: ethmoid sinus invasion, primary gross tumor volume, age, and pretreatment body mass index. The C-index of the nomogram for local recurrence was 0.732 (95% confidence interval, 0.726 to 0.738), indicating excellent predictive accuracy. The calibration curve revealed excellent agreement between nomogram-predicted and observed LRFS probabilities. Risk subgroups based on total point score cutoff values enabled effective discrimination of LRFS. CONCLUSION: This pretreatment nomogram enables clinicians to accurately predict LRFS in T4 NPC after definitive IMRT, and could help to facilitate personalized patient counselling and treatment strategies.
Asian Continental Ancestry Group*
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Body Mass Index
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Calibration
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Discrimination (Psychology)
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Drug Therapy
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Ethmoid Sinus
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Humans
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Nomograms*
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Recurrence*
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Retrospective Studies*
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Tumor Burden
9.Antimicrobial resistance profile of clinical isolates in hospitals across China: report from the CHINET Surveillance Program, 2017
Fupin HU ; Yan GUO ; Demei ZHU ; Fu WANG ; Xiaofei JIANG ; Yingchun XU ; Xiaojiang ZHANG ; Zhaoxia ZHANG ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Aimin WANG ; Yuanhong XU ; Jilu SHEN ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Hong ZHANG ; Chun WANG ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Dawen GUO ; Jinying ZHAO ; Wenen LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Kaizhen WEN ; Yirong ZHANG ; Xuesong XU ; Chao YAN ; Hua YU ; Xiangning HUANG ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Hongyan ZHENG ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU
Chinese Journal of Infection and Chemotherapy 2018;18(3):241-251
Objective To investigate the antimicrobial resistance profile of the clinical isolates collected from selected hospitals across China. Methods Twenty-nine general hospitals and five children's hospitals were involved in this program. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems. Results were interpreted according to CLSI 2017 breakpoints. Results A total of 190 610 clinical isolates were collected from January to December 2017, of which gram negative organisms accounted for 70.8% (134 951/190 610) and gram positive cocci 29.2% (55 649/190 610). The prevalence of methicillin-resistant strains was 35.3% in S. aureus (MRSA) and 80.3% in coagulase negative Staphylococcus (MRCNS) on average. MR strains showed much higher resistance rates to most of the other antimicrobial agents than MS strains. However, 91.6% of MRSA strains were still susceptible to trimethoprim-sulfamethoxazole, while 86.2% of MRCNS strains were susceptible to rifampin. No staphylococcal strains were found resistant to vancomycin. E. faecalis strains showed much lower resistance rates to most of the drugs tested (except chloramphenicol) than E. faecium. Vancomycin-resistant Enterococcus (VRE) was identified in both E. faecalis and E. faecium. The identified VRE strains were mainly vanA, vanB or vanM type based on phenotype or genotype. The proportion of PSSP or PRSP strains in the non-meningitis S.pneumoniae strains isolated from children decreased but the proportion of PISP strains increased when compared to the data of 2016. Enterobacteriaceae strains were still highly susceptible to carbapenems. Overall, less than 10% of these strains (excluding Klebsiella spp.) were resistant to carbapenems. The prevalence of imipenem-resistant K. pneumoniae increased from 3.0% in 2005 to 20.9% in 2017, and meropenem-resistant K. pneumoniae increased from 2.9% in 2005 to 24.0% in 2017, more than 8-fold increase. About 66.7% and 69.3% of Acinetobacter (A. baumannii accounts for 91.5%) strains were resistant to imipenem and meropenem, respectively. Compared with the data of year 2016, P. aeruginosa strains showed decreasing resistance rate to carbapenems. Conclusions Bacterial resistance is still on the rise. It is necessary to strengthen hospital infection control and stewardship of antimicrobial agents. The communication between laboratorians and clinicians should be further improved in addition to surveillance of bacterial resistance.
10.Analysis of Factors Associated with Death in Maintenance Hemodialysis Patients: A Multicenter Study in China.
Kang-Kang SONG ; De-Long ZHAO ; Yuan-Da WANG ; Yong WANG ; Xue-Feng SUN ; Li-Ning MIAO ; Zhao-Hui NI ; Hong-Li LIN ; Fu-You LIU ; Ying LI ; Ya-Ni HE ; Nian-Song WANG ; Cai-Li WANG ; Ai-Hua ZHANG ; Meng-Hua CHEN ; Xiao-Ping YANG ; Yue-Yi DENG ; Feng-Min SHAO ; Shu-Xia FU ; Jing-Ai FANG ; Guang-Yan CAI ; Xiang-Mei CHEN
Chinese Medical Journal 2017;130(8):885-891
BACKGROUNDPatients on hemodialysis have a high-mortality risk. This study analyzed factors associated with death in patients on maintenance hemodialysis (MHD). While some studies used baseline data of MHD patients, this study used the most recent data obtained from patients just prior to either a primary endpoint or the end of the study period to find the characteristics of patients preceding death.
METHODSParticipants were selected from 16 blood purification centers in China from January 2012 to December 2014. Patients' data were collected retrospectively. Based on survival status, the participants were divided into two groups: survival group and the death group. Logistic regression analysis was performed to determine factors associated with all-cause mortality.
RESULTSIn total, 4104 patients (57.58% male, median age 59 years) were included. Compared with the survival group, the death group had more men and more patients with diabetic nephropathy (DN) and hypertensive nephropathy. The patients preceding death also had lower levels of diastolic blood pressure, hemoglobin, serum albumin, serum calcium, serum phosphate, Kt/V, and higher age. Multivariate analysis revealed that male sex (odd ratio [OR]: 1.437, 95% confidence interval [CI]: 1.094-1.886), age (OR: 1.046, 95% CI: 1.036-1.057), and presence of DN (OR: 1.837, 95% CI: 1.322-2.552) were the risk factors associated with mortality. High serum calcium (OR: 0.585, 95% CI: 0.346-0.989), hemoglobin (OR: 0.974, 95% CI: 0.967-0.981), albumin (OR: 0.939, 95% CI: 0.915-0.963) levels, and dialysis with noncuffed catheter (OR: 0.165, 95% CI: 0.070-0.386) were protective factors based on a multivariate analysis.
CONCLUSIONSHemodialysis patients preceding death had lower hemoglobin, albumin, and serum calcium levels. Multivariate analysis showed that male sex, age, DN, low hemoglobin, low albumin, and low serum calcium were associated with death in hemodialysis patients.
Adult ; Aged ; China ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Renal Dialysis ; adverse effects ; mortality ; Retrospective Studies ; Risk Factors

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