Multicenter Study In China Research Articles

Molecular characteristics of oxazolidinone resistance in enterococci from a multicenter study in China

BackgroundLinezolid-resistant enterococci pose great challenges in clinical practice. The aim of this study is to study the mechanisms underlying the resistance and genetic environment of antimicrobial resistance gene of linezolid-resistant enterococci.ResultsThe linezolid MICs of 16 enterococci were 4 mg/L to 16 mg/L. Four strains belonged to multi-drug resistant (MDR) bacteria. The sequence types (STs) of 13 enterococci strains performed WGS were diverse: 3 ST476, 1 ST86, ST116, ST480, ST59, ST416, ST21, ST67, ST16, ST585 and ST18. None of them carried multi-drug resistance gene cfr. Only one strain had the G2658 T mutation of target 23S rRNA gene. Thirteen (13/16, 81.3%) strains harbored the novel oxazolidinone resistance gene optrA. WGS analysis showed that the optrA gene was flanked by sequence IS1216E insertion in 13 strains, and optrA was adjacent to transposons Tn558 in two strains and Tn554 in one strain. The optrA gene was identified to be co-localized with fexA, the resistance genes mediated florfenicol resistance in 13 strains, and ermA1, the resistance genes mediated erythromycin resistance in 9 strains, indicating that linezolid-resistant strains may be selected due to non-oxazolidinone antibiotics (i.e. macrolides and florfenicol) usage.ConclusionOur findings demonstrate the high diversity of optrA-carrying genetic platforms. The mobile genetic elements (MGEs) may play an important role in the dissemination of optrA into the enterococci isolates of human origin. The genetic evidence of transferable feature and co-selection of optrA should be gave more attention in clinical practice.

Abstract 1597: Real-world large-scale study kinase domain duplications across diverse tumor types in Chinese populations

Abstract Background: Recently, kinase domain duplications (KDD) in BRAF, EGFR, MET and FGFR1 were reported, along with responses to tyrosine kinase inhibitors (TKI). However, its frequency and clinical outcomes in advanced cancer patients are larglely uncertain. We assessed the frequency of KDD across 14, 491 advanced cancers to reveal the landscape in a wide variety of subtypes. Methods: A multicenter study in China was initiated from July 2013, and advanced cancer patients have been enrolled as of September 2018. We analyzed data from 14, 491 clinical advanced cancer cases, each of which had results from next-generation sequencing (NGS)-based 381 genes panel assay, analogous to the index patient. Results: Of this entire cohort [6837 lung cancer (47.18%), 1894 breast cancer (13.07%), 1325 colorectal cancer (9.14%), 710 urinary system tumor (4.90%), 536 gynecological tumor (3.70%), 592 hepatobiliary cancer (4.09%), 221 gastric cancer (1.53%), 312 soft tissue sarcoma (2.15%), 260 head and neck cancer (1.79%) and 1804 others (12.45%)], 71 patients were identified with KDD, including EGFR (16), BRAF (12), MET (11), FGFR3 (8), RET (3), PDGFRA (3), ROS1 (3), FGFR1 (2), ERBB2 (2), SOX17 (2), ALK (2), KIT (1), NTRK1 (1), BAP1 (1), TMPRSS2 (1), ERBB4 (1), VHL (1), NTRK3 (1). KDD were seen in 0.39% (27/6837) of lung cancer [EGFR(9), BRAF (2), MET (6), FGFR3 (2), RET (1), PDGFRA (1), ROS1 (2), ERBB2 (1), ALK (1), NTRK1 (1), and ERBB4 (1)]; 0.21%(4/1894) of breast cancer [BRAF (1), FGFR3 (2), FGFR1 (1)]; 0.60%(8/1325) of colorectal cancer [EGFR (1), BRAF (3), FGFR3 (2), RET (1), ROS1 (1)]; 0.28%(2/710) of urinary system tumor [TMPRSS2(1), VHL (1)]; 0.19%(1/536) of gynecological tumor [SOX17 (1)]; 0.17%(1/592) of hepatobiliary cancer [EGFR (1)]; 0.45%(1/221) of gastric cancer [ERBB2 (1)]; 0.96%(3/312) of soft tissue sarcoma [EGFR (1), FGFR3 (1), PDGFRA (1)]; 0.77%(2/260) of head and neck cancer [BRAF (2)]; and 1.22%(22/1804) of others [EGFR (4), BRAF (4), MET (5), FGFR3 (1), RET (1), PDGFRA (1), FGFR1 (1), SOX17 (1), ALK (1), KIT (1), BAP1 (1), and NTRK3 (1)]; KDD possibly related to target resistance were seen in ERBB2 amplification gastric cancer and ALK-related NSCLC. Conclusion: Diverse KDD are found across diverse tumor types and may underlie acquired resistance, and can benefit from matched targeted treatment. In addition, for short- or long-term responses to targeted treatment, we can use the NGS assay to explore differential gene alter in the future. Citation Format: Chun-wei Xu, Wen-xian Wang, Xiao-jia Wang, You-cai Zhu, Qu-xia Zhang, Yong Fang, Xiu-yu Cai, Yu Chen, Li Lin, Hong Wang, Mei-yu Fang, Yin-bin Zhang, Shi-jie Lan, Xin Liu, Xing-xiang Pu, Zong-yang Yu, Bing Wan, Jian-ying Li, Xian-bin Liang, Li-ping Wang, Wu Zhuang, Ling Lin, Gang Chen, Tang-feng Lv, Yong Song. Real-world large-scale study kinase domain duplications across diverse tumor types in Chinese populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1597.

PB2361 INCIDENCE, RISK FACTORS AND OUTCOMES OF SINUSOIDAL OBSTRUCTION SYNDROME AFTER HAPLOIDENTICAL ALLOGENEIC STEM CELL TRANSPLANTATION

Background:Recent studies have reported that the outcomes after haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) are comparable to those after matched related donor (MRD) HSCT in hematological disease patients. Hepatic sinusoidal obstruction syndrome (SOS) is a rare but lethal complication with a reported incidence of 8%∼14% and a mortality rate higher than 80% for the severe type of SOS after MRD HSCT. Although sufficient information is available on SOS after MRD HSCT, few studies have systematically investigated SOS after HID HSCT. Here, we conducted a retrospective multicenter study in China to assess the incidence, clinical characteristics, risk factors and transplant outcomes of SOS following HID HSCT.Aims:The aim of this study is to compare the incidence, clinical characteristics, risk factors and transplant outcomes of SOS after HID HSCT and MRD HSCT.Methods:We retrospectively evaluated 36 consecutive patients with a confirmed diagnosis of SOS after allogeneic HSCT (allo‐HSCT) (HID: 23 patients, MRD: 13 patients) at four large HSCT centers in China between January 2003 and July 2018. The diagnosis of SOS was based on clinical criteria that required the occurrence of two of the following events: hyperbilirubinemia (≥ 2 mg/dL), hepatomegaly or right upper quadrant pain of hepatic origin, or unexplained weight gain (> 2% of baseline body weight) due to fluid accumulation. The SOS severity was defined as mild, moderate, severe or very severe. Kaplan‐Meier survival analysis was used to estimate the cumulative incidence of relapse, overall survival (OS) and transplant‐related mortality (TRM), and a log‐rank test was performed to assess the statistical significance. Cox regression analysis was used to identify potential risk factors affecting the occurrence of SOS.Results:SOS developed in 0.4% of the patients (HIDs: 0.4%, MRDs: 0.5%, p = 0.952) at a median time of 21.50 days (range, 1‐55) after allo‐HSCT. No significant difference was found between the two groups in gender, disease distribution, interval from diagnosis to HSCT, disease status at the time of HSCT, donor‐patient sex match, donor‐patient ABO match, stem cell source, follow‐up time, engraftment time and cumulative incidence of acute graft‐versus‐host disease (GVHD) or chronic GVHD. The HID and MRD groups were comparable in terms of the median time to diagnosis (HIDs: 24 days, MRDs: 20 days, p = 0.316) and the presentation and severity of SOS. For patients diagnosed with SOS, the 2‐year cumulative incidences of relapse were 22.7% and 22.4% in patients receiving HID and MRD transplantations, respectively (p = 0.584). OS at 2 years was 10.4% and 38.5% in the two groups, respectively (p = 0.113). The TRM at 100 days was 60.9% in the HID group and 38.5% in the MRD group (p = 0.178). According to the multivariate analysis, significant independent risk factors for the occurrence of SOS were delayed platelet engraftment (p = 0.007) and an advanced disease status at the time of HSCT (p = 0.009). The frequency of SOS did not differ significantly in terms of the donor type (p = 0.222).Summary/Conclusion:Haploidentical transplantation may achieve results similar to those of transplantation with matched related donors in terms of the SOS incidence and outcomes. The occurrence of SOS did not differ by donor type.

1270-P: Improving ABC Targets through a Quality Improvement Initiative in China

Strong scientific evidence supports the benefits of ABC control (A1c <7%, blood pressure <140/80 mmHg, and LDL cholesterol <100 mg/dL) in reducing complications. A recent national multicenter study in China showed that the percentage of Chinese patients with type 2 diabetes who met recommended targets for A1c, BP and LDL in 2010 was 5.4%. A diabetes clinic in a Chinese tertiary hospital conducted a pilot quality improvement project from January to November 2018 to enhance ABC outcomes. Doctors and nurses from the clinic participated in biweekly video case conferences with Joslin Diabetes Center clinicians (endocrinologist and a certified diabetes educator). They also received bi-monthly on-site training, each lasting 10 days, from visiting U.S. clinicians. A1c, blood pressure and cholesterol levels collected from patients receiving routine care in the diabetes clinic from the first half of 2018 were compared with those collected in the second half of 2018. There were 1,036 patients who had at least one visit at each of these periods, and 683 patients of them (65.9%) had A1c, BP and LDL measured during these two periods. Paired comparisons were done by paired t-test (continuous variables) or McNemar’s test (dichotomous variables) using SAS version 9.4. The mean age of the patients was 54.7±11.9 years, with 53.8% female, and 95.3% with T2DM. There was a significant increase in the patients who achieved composite A1c, BP and LDL goal from 6.8 to 10.0% (p=0.048). The percentage of patients attaining the BP goal increased from 54.6 to 63.5% (p=0.0016). The systolic pressure decreased from 137.8 ± 20.2 to 133.3 ± 19.4 mmHg (p<0.0001). The LDL cholesterol decreased from 107.5 ± 34.0 to 97.5 ± 34.4 mg/dL (p<0.0001), and resulted in an increase in the percentage of individuals meeting the LDL goal, from 24.5% to 32.9% (p=0.0012). Interventions through regular case-based video conferences, complemented by live coaching from diabetes specialists, have the potential to improve clinical outcomes for patients with diabetes in China. Disclosure K. Lau: None. L. Yunxia: None. L. Yi: None. C. Li: None. Y. Zhengguo: None. D.M. Pober: None. L. Zhang: None. R.A. Gabbay: Advisory Panel; Self; HealthReveal, Hygieia, Lark, Onduo LLC. Consultant; Self; Sanofi. W.C. Hsu: Consultant; Self; Onduo LLC.

Incidence of FGFR-TACC gene fusions in Chinese non-small cell lung cancer (NSCLC): A multicenter study.

e13001 Background: Fibroblast growth factor receptors (FGFR) are transmembrane kinase proteins with growing importance in non-small cell lung cancer (NSCLC) biology given the frequency of molecular alterations and vast interface with multiple other signaling pathways. Furthermore, numerous FGFR inhibitors in clinical development demonstrate the expanding therapeutic relevance of this pathway. The aim of this study was to evaluate the prevalence of FGFR-TACC fusions in Chinese NSCLC populations, which had not been reported earlier, and to describe targeting potential in Chinese NSCLC populations. Methods: A multicenter study in China was initiated from February 2014, and NSCLC patients have been enrolled as of December 2018. Capture-based comprehensive genomic profiling was performed on 2743 NSCLC FFPE samples sequenced to a mean coverage depth of > 650X for up to 381 cancer-related genes. Genomic alterations (GA) included short variant (SV) base subs and insertions/deletions, copy number alterations, and rearrangements/fusions. Tumor mutational burden (TMB; mut/Mb) was calculated on up to 1.2 Mb of sequenced DNA. Results: Of this entire cohort, just 16 (0.58%) patients were identified with FGFR-TACC fusions, including FGFR1-TACC 1 fusion (1), FGFR2-TACC2 fusion (3) and FGFR3-TACC3 fusion (12). Median patient age was 57 (range 36-84 years). Of the FGFR-TACC fusion NSCLC patients, 56.25% were detected in female patients. Biopsies were obtained from primary lung tumor (31.25%) and metastatic sites (68.75%). Overall TMB in the FGFR-TACC fusion was low (median 3.6 mut/Mb), although two cases (12.50%) had > 20 mut/Mb. Of the FGFR-TACC fusion NSCLC patients, two cases (12.50%) featured EGFR SV alterations. Conclusions: FGFR-TACC fusions occur in a subset of patients with NSCLC. Such patients should be considered for clinical trials featuring FGFR inhibitors (AZD4547). Moreover, NGS can provide information for targeted therapy. For NSCLC patients to benefit from more personalized cancer treatment, clinical therapy should improve with clinical diagnostics through multi-gene assays to determine the actual clinical benefits.

Real-world large-scale study of ERBB2 gene fusions and its response to afatinib in Chinese non-small cell lung cancer (NSCLC): A multicenter study.

e13002 Background: ERBB2 mutation has been found to be an oncogenic driver gene in non-small cell lung cancers (NSCLC) and ERBB2-directed therapies have shown promising results in this unique population, while little is known about ERBB2 fusion association with outcomes of afatinib. The aim of this study was to investigate the efficacy of afatinib in patients with advanced ERBB2 fusion NSCLC. Methods: A multicenter study in China was initiated from February 2014, and NSCLC patients have been enrolled as of December 2018. To determine the frequency of the ERBB2 fusions in NSCLC and other tumors, we analyzed data from 2743 clinical NSCLC cases, each of which had results from next-generation sequencing (NGS)-based 381 genes panel assay, analogous to the index patient. Results: Of this entire cohort, eight (0.29%) patients were identified with an ERBB2 fusion, including TNS4-ERBB2 (1), ERBB2-CD79B (1), IGFBP4-ERBB2 (1), ERBB2-PSMD3 (1), SEZ6-ERBB2 (1), ERBB2-PGAP3 (1), ARL5C-ERBB2 (1) and B3GNTL1-ERBB2 (1). The genes most frequently co-altered in patients with ERBB2 fusions were TP53 (37.50%), CDKN2A (25.00%), RB1 (25.00%) and RBM10 (25.00%). Overall TMB in the ERBB2 fusions was low (median 2.97 mut/Mb). For treatments, 25.00% patients chose afatinib, another patients chose chemotherapy or chemoradiotherapy, and case examples of advanced ERBB2 fusion driven NSCLC patients responding to afatinib were actively being sought thru our database. Conclusions: Patients with advanced ERBB2 fusion NSCLC showed a good outcome of afatinib compared to those with ALK/ ROS1 fusion which response to crizotinib, which strengthen the need for effective ERBB2-targeted drugs in clinical practice.

Fear of childbirth in nulliparous women: A cross-sectional multicentre study in China

ObjectiveFew studies have focused on the fear of childbirth (FOC) in China. This study aimed to explore the status of FOC and its associated factors among nulliparous women in China. MethodsUsing a cross-sectional study design, 1039 nulliparous women with singleton pregnancies were recruited from four public hospitals in four cities of China. FOC was evaluated using the Chinese version of the Childbirth Attitude Questionnaire scale. Associations of demographic, obstetric and social–psychological factors with the levels of FOC among nulliparous women were investigated. ResultsThe average score on the Childbirth Attitude Questionnaire scale was 31.30 (standard deviation = 8.43). Generalized linear regression analysis revealed that low self-rated health status (β = 2.26, P = 0.003), higher educational levels (β = 2.06, P = 0.010), lower levels of self-efficacy (β = −0.79, P < 0.001), and use of pregnancy-related smartphone applications (β = 2.42, P < 0.001) were associated with higher levels of FOC. ConclusionThe Childbirth Attitude Questionnaire scale is an appropriate tool to measure FOC. Education levels, self-rated health status, self-efficacy levels, and use of pregnancy-related smartphone applications were predictors of FOC among pregnant women in China. Healthcare professionals should identify the Chinese pregnant women with FOC and implement targeted interventions focused on the above factors.

Interfacility transport with extracorporeal membrane oxygenation in pediatric patients: a multicenter study in China

Objective: To investigate application and safety of pediatric interfacility-transport with extracorporeal membrane oxygenation (ECMO) in China. Methods: The data of 48 patients transported inter-hospital from February 2016 to May 2018 were collected from the following 4 centers: pediatric intensive care unit (PICU) of Bayi Children's Hospital Affiliated to the 7th Medical Center of PLA General Hospital, Pediatric Hospital of Fudan University, Henan Provincial People's Hospital and Children's Hospital of Zhejiang University School of Medicine. The data of patients' characteristics, ECMO mode and wean rate, and mortality were reviewed, which was further compared with the data of 57 compatible inner-hospital ECMO cases with t test, Rank sum test or chi-square test. Results: All the 48 interfacility-transports were accomplished by ambulance on land, with an average transfer distance of (435±422) km. The incidence of ECMO complications was 13% (6 case), without death. There were no significant differences in lactic acid, PaO(2) or SaO(2) before and after transport (4.0 (2.0, 7.5) vs. 3.0 (1.5, 6.0) mmol/L, Z=-1.579, P>0.05; 112(47, 405) vs. 166(122, 240) mmHg (1 mmHg=0.133 kPa), Z=-0.104, P>0.05; 0.97±0.02 vs. 0.96±0.03, t=1.570, P>0.05). Instead, PaCO(2) and pH were significantly different ((47±8) vs. (42±5) mmHg, t=2.687, P<0.05; 7.3±0.2 vs. 7.5±0.2, t=3.379, P<0.05). The total ECMO weaned rate was 73% (35/48) and the survival rate was 67% (32/48). No significant differences in demographic characteristics, ECMO mode or duration, transport distance or duration, or complications existed between the survival group and the death group (7/25 vs. 2/14, χ(2)=0.615, P>0.05; 4/28 vs. 2/14, χ(2)=0, P>0.05; (405±404) vs. (493±465) km, t=0.525, P>0.05; (5±4) vs. (5±5) h, t=0.388, P>0.05; 166 (128, 239) vs. 187(52, 405) h, Z=-0.104, P>0.05; 3/32 vs. 3/16, χ(2)=0.734, P>0.05). The lowest lactate value in survival group before ECMO transport was significantly lower than that in the death group ((5±5) vs. (8±6) mmol/L, t=2.151, P<0.05). There were neither significant differences in age, ECMO mode or support pattern (9/39 vs. 15/42, χ(2)=0.845, P>0.05; 6/42 vs. 7/50, χ(2)=0.001, P>0.05; 29/19 vs. 38/19, χ(2)=0.441, P>0.05), nor in ECMO weaned rate, survival rate or complications between interfacility-transport group and inner-hospital group (35/48 vs. 37/57, χ(2)=0.775, P>0.05; 32/48 vs. 35/57, χ(2)=0.313, P>0.05; 20/48 vs. 22/57, χ(2)=0.102, P>0.05). Conclusion: With appropriate transport equipment and mature teams who handle problems timely during the transport, critically ill children could be safely transported to the destination with ECMO.

Vaginal progesterone gel is non-inferior to intramuscular progesterone in efficacy with acceptable tolerability for luteal phase support: A prospective, randomized, multicenter study in China

ObjectivesResearch suggests the efficacy of progesterone for luteal phase support in assisted reproduction cycles using gonadotropin-releasing hormone analogues. Our study objective was to compare the efficacy of two available preparations of progesterone, vaginal gel and intramuscular injection, for luteal phase support in assisted reproduction cycles. Study designThis study included data gathered from 18 reproductive centers in China. Subjects were randomly allocated to receive progesterone gel or intramuscular progesterone (IMP). The progesterone gel group received micronized progesterone in gel (8%, 90 mg) once daily; the IMP group received IMP (progesterone oil) once daily. The ongoing pregnancy rate was calculated (number of women with a viable pregnancy at 12 weeks divided by the number of women who had undergone an oocyte pickup cycle). ResultsA total of 1313 patients were enrolled in the study, 1248 of whom began treatment. The intention-to-treat set included 527 and 531 patients in the gel and IMP groups, respectively. The ongoing pregnancy rate in the progesterone gel group was non-inferior to that in the IMP group (48.4% [95% confidence interval (CI): 44.0, 52.8] vs. 46.3% [95% CI: 42.0, 50.7]); the between-group rate difference was 2.1% (−4.0, 8.1). There was no difference between the gel group and IMP group on most secondary endpoints, including implantation rate, biochemical pregnancy rate, clinical pregnancy rate, multiple pregnancy rate, early abortion rate, and vaginal bleeding rate, but there was a between-group difference in luteal phase bleeding rate. The safety analysis showed no difference in the incidence of total adverse events. ConclusionsProgesterone gel showed good efficacy and safety outcomes and therefore provides an alternative method of luteal support in Chinese in vitro fertilization patients.

Candida isolates causing refractory or recurrent oropharyngeal candidiasis in 11 hospitals in China.

Introduction: We studied the species distribution and antifungal susceptibilities of Candida isolates causing refractory or recurrent oropharyngeal candidiasis (OPC) in a multicenter study in China (2013–2016).Methods: Species identification was performed using the Bruker Biotyper (Bruker Daltonics, Germany) matrix-assisted laser desorption/ionization time of flight mass spectrometry system supplemented by internal transcribed spacer sequencing as required. Antifungal susceptibilities were determined by the Clinical and Laboratory Standards Institute document (CLSI) M27-A3 broth microdilution methodology.Results: A total of 558 non-duplicate Candida isolates comprising 10 species were obtained from 535 patients. Candida albicans was the most common species (89.6%), followed by C. glabrata (5.2%), C. tropicalis (2.9%), and C. parapsilosis (0.7%). Azoles were active against C. albicans with susceptibility rates of 96% and 95.8% for fluconazole and voriconazole, respectively. MIC50 values of C. albicans to fluconazole, voriconazole, itraconazole, and miconazole were 1, 0.03, 0.25 and 0.12 μg/mL, respectively, higher than those in previous studies of which OPC patients (corresponding MIC50 values of 0.25 , 0.015 , 0.06 , and 0.03 μg/mL). Except for itraconazole, the MIC50 and MIC90 values of 58 non-C. albicans to other azoles were two to threefold higher than C. albicans. Miconazole, amphotericin B, nystatin, and 5-flucytosine had good in vitro antifungal activity for all isolates.Conclusion: The study provides valuable data on the species distribution and antifungal susceptibility of oropharyngeal Candida isolates from geographically diverse areas of China. C. albicans remains the most common species but with increasing rates of azoles resistance.

Effects of whey protein nutritional supplement on muscle function among community-dwelling frail older people: A multicenter study in China

BackgroundFrailty, featured by the presence of fatigue, weight loss, decrease in grip strength, decline gait speed and reduced activities substantially increase the risk of falls, disability, hospitalizations, and mortality of older people. Nutritional supplementation and resistance exercise may improve muscle function and reverse frailty status. ObjectiveTo evaluate whether whey protein supplements can improve muscle function of frail older people in addition to resistance exercise. Methods115 community-dwelling older adults who met the Fried's criteria for frailty from four hospitals’ out-patients clinic in Beijing, China completed the study. It's a case–control study which whey protein was used as daily supplementation for 12 weeks for active group and regular resistance exercise for active group and control group. Handgrip strength, gait speed, chair-stand test, balance score, and SPPB score were compared in both groups during the 12-week follow-up. ResultsOverall, 115 subjects were enrolled for study with 66 in active group and 49 in control group. Handgrip strength, gait speed, and chair-stand time were all significantly improved in both groups with significant between-group differences. The active group improved significantly in handgrip strength compared with the control group, which between-group effect (95% confidence interval) for female was 0.107 kg (0.066–0.149), p = 0.008 and for male was 0.89 kg (0.579–1.201), p = 0.007. For chair-stand time, between-group effect (95% confidence interval) was −2.875 s (−3.62 to −2.124), p = 0.004 and for gait speed, between-group effect (95% confidence interval) was 0.109 m/s (0.090 to 0.130), p = 0.003. ConclusionsThe 12-week intervention of whey protein oral nutritional supplement revealed significant improvements in muscle function among the frailty elderly besides aiding with resistance exercise. These results warrant further investigations into the role of a multi-modal supplementation approach which could prevent adverse outcomes among frailty elderly at risk for various disabilities.

Real-world fusion landscape in advanced Chinese gastric cancer using next generation sequencing: A multicenter study.

51 Background: Gastric cancer (GC) is a highly heterogeneous disease. Cell-free DNA (cfDNA) has been a research hotspot in molecular tumor profiling. In advanced GC patients, malignant pleural effusion (MPE) and ascites provide a wealth of tumor cells that can be investigated. The aim of this study is to investigate fusion landscape in advanced GC. Methods: A multicenter study in China was initiated from Aug. 2016, and GC patients have been enrolled as of Aug. 2018. To determine the fusion frequency in GC, we analyzed data from 371clinical GC cases, each of which had results from next-generation sequencing (NGS)-based 381 genes panel assay, analogous to the index patient. Results: Of this entire cohort, 61 patients (16.44%) were identified with fusions, including TMEM45B-FGF3 (3), AXIN1-SMPD3 (3), B3GNTL1-ERBB2 (2), ERBB2-LAMA3 (2), ERBB2-ACLY (2), TRIM24-BRAF (2), ARHGEF1-CD79A (2), FGFR4-UIMC1 (2), MSH2-TTC7A (2), SMARCA4-LDLR (2), GON4L-RIT1 (2), AKT1-CPSF2 (2), GATA6-COLEC12 (2), RICTOR-EFNA5 (2), KAT6A-PLAT (2), ROCK1-CCDC178 (2), HBS1L-MYB (2), SLC30A2-ARID1A (2), MSI2-BIRC5 (2), NOTCH3-UCA1 (2), PIK3C2B-KISS1 (2), RICTOR-OSMR (2), FGFR2-MIR5694 (2), FGFR2-FGFR1 (2), MAN2A2-BLM (2), EGFR-MED15 (1), EML4-ALK(1), GOPC-ROS1 (1), FXR2-TP53 (1), NF1-PSMD11 (1), IRS2-PRKCI (1), FGFR2-KIAA1217(1), FGFR2-TACC2 (1), FGFR3-TACC3 (1). ERBB2, BRAF, EGFR, ALK and ROS1 fusionswere seen in 18.03% (11/61) of advanced Chinese gastric cancer fusion landscape patients. Conclusions: Advanced Chinese gastric cancer fusion landscape is rich, ERBB2, BRAF, EGFR, ALK and ROS1 fusions are rare but potentially druggable in TKIs. Detection of ERBB2, BRAF, EGFR, ALK and ROS1 fusions should be part of comprehensive profiling panels to determine TKIs and direct appropriate combination therapeutic strategies.

Invasive Infections Due to Trichosporon: Species Distribution, Genotyping, and Antifungal Susceptibilities from a Multicenter Study in China.

A total of 133 clinical Trichosporon isolates were collected in the National China Hospital Invasive Fungal Surveillance Net (CHIF-NET) program in 2009 to 2016. Accurate identification was performed by sequencing of the intergenic spacer 1 (IGS1) region. Among these isolates, Trichosporon asahii (108 isolates [81.2%]) was the leading species, followed by Trichosporon dermatis (7 isolates [5.3%]), Trichosporon asteroides (5 isolates [3.8%]), Trichosporon inkin (5 isolates [3.8%]), Trichosporon dohaense (3 isolates [2.3%]), and 1 isolate (0.7%) each of Trichosporon faecale, Trichosporon jirovecii, Trichosporon mucoides, Trichosporon coremiiforme, and Trichosporon montevideense Both the Vitek mass spectrometry (MS) (bioMérieux, Marcy l'Etoile, France) and Bruker Biotyper MS (Bruker Daltonics GmbH, Germany) platforms gave high levels (>97.5%) of correct identification when the species were present in the database. The geometric mean (GM) of amphotericin B MICs for T. asahii was 2-fold higher than that for non-asahii Trichosporon High fluconazole MICs (≥8 μg/ml) were observed for 25% of T. asahii isolates (27/108 isolates) and 16% of non-asahii Trichosporon (4/25 isolates) isolates. Itraconazole MICs were ≤0.5 μg/ml for 89.5% of the isolates. Voriconazole was the most potent antifungal agent in vitro, with a GM of 0.09 μg/ml. Genotyping of the isolates using IGS1 sequence alignment revealed that genotype 1 was most common (41.7%), followed by genotype 4 (31.5%), genotype 3 (23.1%), genotype 5 (0.9%), genotype 6 (0.9%), and genotype 7 (1.8%). Our data on species distribution, genotypes, and antifungal susceptibilities may contribute to a better understanding of the epidemiology of invasive Trichosporon infections throughout China.

Clinical and Genetic Profiles in Chinese Patients with Huntington's Disease: A Ten-year Multicenter Study in China.

Huntington’s disease (HD) is an autosomal dominant inherited neurodegenerative disorder caused by CAG triplet repeats expansion in exon 1 of the Huntingtin gene (HTT). In China, HD is considered to have a low prevalence. The goal of this study was to describe the clinical characteristic and genetic profiles of HD in a Chinese cohort. A total of 322 individuals with expanded CAG repeats were consecutively recruited from the neurologic clinics of three medical centers in Southeastern China between 2008 and 2018. Among them, 80 were pre-symptomatic mutation carriers and 242 were symptomatic patients. The mean age at onset (AAO), defined here as the age at motor symptom onset, of the 242 manifest HD individuals was 40.3 ± 11.9 years and the mean CAG repeat length was 46.1 ± 7.5 in the group of symptomatic patients. Initial symptoms were abnormal movements in 88.8% of the patients with psychiatric symptoms in 6.2%, cognitive impairment in 3.3% and others in 1.7%. The AAO of motor was negatively correlated with the CAG repeat length in an exponential regression analysis (R 2 = 0.74, P<0.001). Analysis of 46 parent-child pairs showed that the CAG repeat length was longer in the offspring group (45.8 ±7.6) than in the parent group (43.8 ±3.0) (p=0.005). Overall, this study provides clinical and genetic profiles in a cohort of Chinese patients with HD, which should contribute to a better understanding of this disorder.

Insertion of peripherally inserted central catheters with intracavitary electrocardiogram guidance: A randomized multicenter study in China.

Introduction:Ultrasound-guided venipuncture and tip location by intracavitary electrocardiogram have many advantages during the insertion of peripherally inserted central catheters, both in terms of safety and cost-effectiveness. Recently, a new tip-conductive peripherally inserted central catheters and new Doppler ultrasound device integrated with intracavitary electrocardiogram have been introduced into clinical practice in China. A randomized multicenter study (clinical trial no. NCT03230357) was performed to verify the feasibility and accuracy of intracavitary electrocardiogram, as performed with this new peripherally inserted central catheters and device.Methods:Our study enrolled a total of 2250 adult patients in 10 different Chinese hospitals. The patients were randomly assigned to either the study group (intracavitary electrocardiogram) or the control group (anatomical landmark guidance) in a 2:1 allocation. Ultrasound was used in both groups for venipuncture and tip navigation. All patients underwent chest X-ray after the procedure to verify the position of the catheter tip.Results:No insertion-related complications were reported in either group. In the study group, first-attempt successful tip location was 91.7% (95% confidence interval: 90.3%–93.1%), significantly higher than 78.9% (95% confidence interval: 76.0%–81.9%) observed in the control group (p < 0.001). As evaluated by post-procedural chest X-ray, tip location in the study group had a sensitivity of 99.3% (95% confidence interval: 98.8%–99.7%), significantly higher than 86.8% (95% confidence interval: 84.4%–89.2%) observed in the anatomical landmark group (p < 0.001).Conclusion:These results indicated that during peripherally inserted central catheters insertion in adult patients, tip location with intracavitary electrocardiogram guidance, as carried out by a new tip-conductive peripherally inserted central catheters and intracavitary electrocardiogram integrated ultrasound device, was more effective and more accurate than tip location using anatomical landmarks.

Delusion, excitement, violence, and suicide history are risk factors for aggressive behavior in general inpatients with serious mental illnesses: A multicenter study in China

Little is known about the risk factors for aggression in general clinical settings in China. The aim of this study is to explore potential risk factors for inpatients with serious mental illness. The study was conducted from 15 March to 14 April 2013 and involved 16 general psychiatric institutions in China. A standardized data collection form was used to collect demographic and clinical characteristics data, including information on current hallucinations, delusions, depression, excitement, aboulia, apathy, and adherence to treatment. Information on lifetime history of violence and suicidality was also collected. The Modified Overt Aggression Scale (MOAS) was also administered to indicate recent (past week) aggression. A total of 511 inpatients were enrolled. On the basis of a score of five or greater on the MOAS, 245 inpatients were assigned to aggressive group and 266 were assigned to non-aggressive group. A lifetime history of violent behaviour (OR = 3.1, 95% CI = 1.95–5.11), suicide (OR = 3.0, 95% CI = 1.49–6.10), as well as current delusions (OR = 1.92, 95% CI = 1.24–2.97), and excitement (OR = 2.63, 95% CI = 1.57–4.39) were associated with aggression. The study suggested violent history, suicide history, current delusions, and excitement are the risk factors for aggression among general psychiatric inpatients with serious mental illnesses.

Decreased Thyroid Peroxidase Antibody Titer in Response to Selenium Supplementation in Autoimmune Thyroiditis and the Influence of a Selenoprotein P Gene Polymorphism: A Prospective, Multicenter Study in China.

Background: Recent intervention studies have suggested that selenium (Se) is an effective treatment for autoimmune thyroiditis (AIT). However, the exact effect of Se on AIT is unclear as well as the mechanism of action. The aim of the present study was to explore the effect of Se on thyroid peroxidase antibody (TPOAb) titers in patients with AIT and to analyze the potential impact of the genetic background on the effect of Se supplementation. Methods: This was a randomized, placebo-controlled, double-blind trial. Three hundred and sixty-four patients with elevated TPOAb (>300 IU/mL) were recruited and randomized to receive Se yeast 200 μg/day supplementation or placebo. Urinary iodine concentration, serum thyrotropin, free thyroxine, TPOAb, Se, malondialdehyde, and serum glutathione peroxidase activity were measured at baseline and follow-up. Ninety-six patients were genotyped for single nucleotide polymorphism r25191G/A in the selenoprotein P (SEPP1/SELENOP) gene. Results: The median urinary iodine concentration was 182 μg/L. Serum Se increased significantly (p < 0.001) after Se treatment. TPOAb titer decreased by 10.0% at 3 months and by 10.7% at 6 months after Se supplementation, while there was a moderate increase in TPOAb titers over the follow-up period in patients receiving placebo. Glutathione peroxidase activity significantly increased (p < 0.001), and malondialdehyde significantly decreased (p < 0.001) after 6 months of Se supplementation. TPOAb titers decreased to variable extents in patients with different genotypes of single nucleotide polymorphism r25191G/A after Se supplementation. Serum TPOAb titers in patients with the AA genotype showed a more significant decrease (by 46.2%) than those with the GA and GG genotypes (by 14.5 and 9.8% respectively) at 3 months of Se supplementation (p = 0.070). Conclusions: Se supplementation significantly reduced TPOAb titers in patients with AIT, and there may be an important genetic component influencing interindividual differences in the decrease in TPOAb titers.

P3805Evaluation of blood pressure lowering effect by generic and brand-name antihypertensive drug treatment: a prospective multicenter study in China

P3805Evaluation of blood pressure lowering effect by generic and brand-name antihypertensive drug treatment: a prospective multicenter study in China

The global impact of the International Federation of Clinical Chemistry and Laboratory Medicine, Education and Management Division: engaging stakeholders and assessing HbA1c quality in a multicentre study across China.

Background Diabetes mellitus is a major global issue and high quality testing is essential for the diagnosis and treatment of the disease. The IFCC Committee for the Education in the Utility of Biomarkers in Diabetes (C-EUBD) plays a global role in improving knowledge and understanding around diabetes testing. This paper describes a multi-stakeholder approach, to improving diagnostic and therapeutic testing for diabetes, using a multicentre study in China as an example of the global impact of the group. Methods Educational workshops were developed to support the scientific aims of the study in which 30 centres around China received identical, fresh frozen whole blood samples with values assigned using IFCC secondary reference methods and undertook precision (EP-5) and trueness studies. Performance was assessed using sigma metrics. Results A successful multi-stakeholder group was developed and sustained throughout the study through several educational workshops, which enabled the formation of a long-term collaboration with key opinion leaders and policy makers in China. All 30 centres showed good performance with within and between laboratory coefficient of variations (CVs) below 3% in SI units at both low and high haemoglobin A1c (HbA1c) levels. All individual laboratories met the criteria of a sigma of two or more at a total allowable error (TAE) of 5 mmol/mol (0.46% NGSP). Conclusions The study led to a successful multi-partner approach to improving diabetes testing in China. All centres involved in the study meeting the published IFCC quality criteria, paving the way for future clinical trials and an expanded role for HbA1c testing across the country.

Clofazimine improves clinical outcomes in multidrug-resistant tuberculosis: a randomized controlled trial

ObjectivesWe carried out a randomized multicentre study in China to investigate whether the clofazimine would improve the efficacy of the standardized regimen in patients with multidrug-resistant tuberculosis (MDR-TB). MethodsPatients with MDR-TB managed in 17 TB specialist hospitals in China between September 2009 and September 2011 were randomly assigned to the treatment groups at enrolment. In the intervention group, 100 mg clofazimine per day was added to the standardized regimen. The primary outcome was the proportion of patients with successful outcomes. ResultsFrom the 156 patients that were screened, 74 were assigned to the control group and 66 to the clofazimine group. Of the 66 cases analysed for clinical outcome in the clofazimine group, 36 patients were cured, and seven completed treatment, yielding a favourable outcome rate of 65.1%. The proportion of patients with favourable outcomes receiving the control regimen was 47.3% (35/74), which was significantly lower than that in the clofazimine group (p 0.034, relative risk 0.661, 95% CI 0.243–0.949). ConclusionsThe addition of clofazimine to the standard regimen improved the treatment of MDR-TB.