Search

Metformin is the first-choice oral anti-hyperglycemic drug for type 2 diabetes mellitus (T2DM) patients. There are controversies about the association of SLC22A1 rs622342, which was not reported in the Chinese population, and ataxia-telangiectasia mutated (ATM) rs11212617 polymorphisms with metformin efficacy in T2DM. Our study was to investigate the effects of the two single nucleotide polymorphisms on the efficacy of metformin in T2DM of Han nationality in Chaoshan China. After enrollment, 82 newly diagnosed T2DM patients went on 2-month metformin monotherapy. According to BMI before treatment, the patients were divided into a normal weight group (≥18.5 and

Breast cancer is the most common malignancy in women, and its incidence increases annually. Traditional therapies have several side effects, leading to the urgent need to explore new smart drug-delivery systems and find new therapeutic strategies. Graphene-based nanomaterials (GBNs) are potential drug carriers due to their target selectivity, easy functionalization, chemosensitization and high drug-loading capacity. Previous studies have revealed that GBNs play an important role in fighting breast cancer. Here, we have summarized the superior properties of GBNs and modifications to shape GBNs for improved function. Then, we focus on the applications of GBNs in breast cancer treatment, including drug delivery, gene therapy, phototherapy, and magnetothermal therapy (MTT), and as a platform to combine multiple therapies. Their advantages in enhancing therapeutic effects, reducing the toxicity of chemotherapeutic drugs, overcoming multidrug resistance (MDR) and inhibiting tumor metastasis are highlighted. This review aims to help evaluate GBNs as therapeutic strategies and provide additional novel ideas for their application in breast cancer therapy.

Background: Mismatch repair deficient (dMMR) is an established biomarker for response to anti-PD-1 immunotherapy in metastatic colorectal carcinoma (mCRC). Although patients with dMMR mCRC could achieve a high incidence of disease control and favorable progression-free survival (PFS), reported response rates to PD-1 inhibitors are variable with 28%–52%, indicating that additional predictive biomarkers are warranted. Methods: This multicenter cohort study enrolled patients with dMMR mCRC receiving anti-PD-1 immunotherapy at Sun Yat-sen University, the Sixth Affiliated Hospital and Sun Yat-sen University Cancer Center between December, 2016 to December, 2019. A total of 20 peripheral blood biomarkers, including T cells (CD4+ T cell, CD8+ T cell, ratio of CD4+/CD8+), carcinoembryonic antigen (CEA), inflammatory markers and lipid metabolism markers. The association between response or survival and peripheral blood parameters was analyzed. Results: Among tested parameters, ratio of CD4+/CD8+, CD4+ T cell was significantly associated with PFS (P=0.023, P=0.012) and OS (P=0.027, P=0.019) in univariate analysis. Lower level of CD4+/CD8+ ratio or CD4+ T cell showed significant association with better overall response rates (ORR; P = 0.03, P=0.01). Ratio of CD4+/CD8+, and CD4+ T cell maintained significance in multivariate Cox model for PFS (HR=9.23, P=0.004; HR=4.83, P=0.02) and OS (HR=15.22, P=0.009; HR=16.21, P=0.025). Conclusions: Ratio of CD4+/CD8+ and CD4+ T cell might be crucial independent biomarkers within dMMR mCRC to better identify patients for response to PD-1 inhibitors. If validated in prospective clinical trials, ratio of CD4+/CD8+ and CD4+ T cell might provide aid in guiding the treatment of PD-1 inhibitors in dMMR mCRC. Funding Statement: This study was supported by The National Key Research and Development Program of China (N0.2017YFC1308800), National Natural Science Foundation of China (Grant No. 81703060, 81802441), China Postdoctoral Science Foundation funded project (Grant No. 2018T110911), Science and Technology Planning Project of Guangzhou (No. 201902020009), Key-Area Research and Development Program of Guangdong Province (2019B020229002), Sun Yat-sen University 5010 Project (NO. 2010012), Sun Yat-sen University Young Teacher Training Program (NO. 20ykpy12), Science and Technology Planning Project of Guangdong (2017A030310644), and National Key Clinical Discipline. Declaration of Interests: We declare no potential conflicts of interest. Ethics Approval Statement: This study was approved by the ethics review board of the Sixth Affiliated Hospital, Sun Yat-Sen University. Written informed consent from patients was waived due to the retrospective nature of our study.

Background: The clinical benefit of chemotherapy or endocrine therapy maintenance in patients with metastatic breast cancer (MBC) after first-line chemotherapy, specifically hormone receptor (HR) positive MBC patients remain inconclusive. This study aims to comprehensively evaluate the clinical efficacy of chemotherapy or endocrine therapy maintenance in MBC patients. Methods: The meta-analysis of randomized clinical trials (RCTs) and propensity score matched analysis of multicentre cohort study in China were evaluated MBC patients who underwent first-line chemotherapy or endocrine therapy maintenance. The GRADE approach was used to assess quality of evidence in meta-analysis. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Findings: A total of 2,867 patients from 15 RCTs and 760 patients from multicentre cohort were included. The results from meta-analysis showed that chemotherapy maintenance significantly improved PFS (hazard ratio [HR], 0·63; 95% confidence interval (CI) 0·54-0·73; P 0·05). Additionally, treatment effect sizes were greater for OS than for PFS, and a moderate correlation between PFS and OS was identified. Interpretation: This study provided a high evidence for PFS and OS benefits of longer first-line chemotherapy and endocrine therapy maintenance in MBC patients, and there were no difference efficacy between chemotherapy and endocrine therapy maintenance for HR-positive patients. We also suggested that both PFS and OS should be evaluated to determine the effectiveness of maintenance therapy in future clinical trials. Trial Registration: This study is registered with PROSPERO Identifier: CRD42017071858, and ClinicalTrials.gov Identifier: NCT04258163. Funding Statement: This study was supported by grant 2020ZX09201021 from the National Science and Technology Major Project, grant YXRGZN201902 from the Medical Artificial Intelligence Project of Sun Yat-Sen Memorial Hospital, grants 81572596, 81972471, U1601223, 82073408, 81802656, and 82071754 from the National Natural Science Foundation of China, grant 2017A030313828 from the Natural Science Foundation of Guangdong Province, grant 201704020131 from the Guangzhou Science and Technology Major Program, grant 2017B030314026 from the Guangdong Science and Technology Department, grant 2018007 from the Sun Yat-Sen University Clinical Research 5010 Program, grant SYS-C-201801 from the Sun Yat-Sen Clinical Research Cultivating Program, and A2020558 from the Medical Scientific Research Foundation of Guangdong Province. Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: The study protocol was approved by the ethics committee of the Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.

Jianguo Lai,1,2 Hongli Wang,1,2 Jingwen Peng,3 Peixian Chen,4 Zihao Pan1,2 1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 3Department of Rehabilitation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 4Department of Breast surgery, The First People’s Hospital of Foshan, Foshan, People’s Republic of China Background: The eighth edition of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system for survival prediction and risk stratification in breast cancer (BC) patients after neoadjuvant chemotherapy (NCT) is of limited efficacy. This study aimed to establish a novel prognostic nomogram for predicting disease-free survival (DFS) in BC patients after NCT. Patients and methods: A total of 567 BC patients treated with NCT, from two independent centers, were included in this study. Cox proportional-hazards regression (CPHR) analysis was conducted to identify the independent prognostic factors for DFS, in order to develop a model. Subsequently, the discrimination and calibration ability of the prognostic model were assessed in terms of its concordance index (C-index), risk group stratification, and calibration curve. The performance of the nomogram was compared with that of the eighth edition of the AJCC TNM staging system via C-index. Results: Based on the CPHR model, eight prognostic predictors were screened and entered into the nomogram. The prognostic model showed better performance (p

We present a novel method for hierarchical topic detection where topics are obtained by clustering documents in multiple ways. Specifically, we model document collections using a class of graphical models called hierarchical latent tree models (HLTMs). The variables at the bottom level of an HLTM are observed binary variables that represent the presence/absence of words in a document. The variables at other levels are binary latent variables, with those at the lowest latent level representing word co-occurrence patterns and those at higher levels representing co-occurrence of patterns at the level below. Each latent variable gives a soft partition of the documents, and document clusters in the partitions are interpreted as topics. Latent variables at high levels of the hierarchy capture long-range word co-occurrence patterns and hence give thematically more general topics, while those at low levels of the hierarchy capture short-range word co-occurrence patterns and give thematically more specific topics. Unlike LDA-based topic models, HLTMs do not refer to a document generation process and use word variables instead of token variables. They use a tree structure to model the relationships between topics and words, which is conducive to the discovery of meaningful topics and topic hierarchies., Comment: 46 pages

Papillary breast lesions constitute a pathological heterogeneous group and display diverse clinical and imaging features. This study was conducted to analyze the upgrade rate of intraductal papilloma diagnosed on core needle biopsy and to assess the possible risk factors associated with upgrade to higher-risk lesions. We also examined the long-term outcomes in patients who received resection of the papillary lesions. The clinical and pathology records of 324 female patients who were diagnosed with papillary lesions based on core needle biopsy (CNB) from February 2010 to October 2016 at our institution were retrospectively analyzed. Patients were grouped by initial diagnosis into two groups (papilloma with or without atypia) and followed-up for long-term outcomes. For the upgrade to higher-risk lesions after excision, upgraded lesions were compared with benign papillomas for the collected variables. A total of 341 lesions were included for final analysis, and all were available for follow-up. Papillomas with or without atypia diagnosed by CNB were found in 9 and 332 lesions, respectively. Papillomas without atypia on CNB were treated by open excision (n = 265) or vacuum-assisted biopsy (VAB) (n = 67), which yielded similar event-free rate (p = 0.19). The upgrade rate of this group to higher-risk lesions was 9.9%. Peripheral (p = 0.011) lesions in postmenopausal (p = 0.001) or older (p = 0.001) patients with papillomas without atypia based on CNB showed significantly higher upgrade rates. Papillomas with atypia on CNB were all managed by open excision, and concurrent malignancy was found in two lesions. In conclusion, our results support benign papillary lesions based on CNB require further treatment. Peripheral lesions occurring in older or postmenopausal women are at higher risk for upgrade.

We propose a novel document generation process based on hierarchical latent tree models (HLTMs) learned from data. An HLTM has a layer of observed word variables at the bottom and multiple layers of latent variables on top. For each document, the generative process first samples values for the latent variables layer by layer via logic sampling, then draws relative frequencies for the words conditioned on the values of the latent variables, and finally generates words for the document using the relative word frequencies. The motivation for this work is to take word counts into consideration with HLTMs. In comparison with LDA-based hierarchical document generation processes, the new process achieves drastically better model fit with much fewer parameters. It also yields more meaningful topics and topic hierarchies. It is the new state-of-the-art for the hierarchical topic detection.

OBJECTIVES To investigate the effects of KCNQ1 polymorphisms on the efficacy of gliclazide in type 2 diabetic patients. MATERIALS AND METHODS A total of 443 newly diagnosed type 2 diabetic patients were included in this study. After enrollment, patients went on an 8-week gliclazide monotherapy. Fasting plasma glucose (FPG) was measured before and after the treatment. Life-style information was collected by weekly follow-up. Genotyping of the two single-nucleotide polymorphisms was performed using the single base primer extension method. T-test, one-way analysis of variance, and Pearson χ-test were used to evaluate the effects of rs2237892 and rs2237897 on the FPG reduction and treatment success rate. RESULTS After 8 weeks of gliclazide therapy, the FPG decreased significantly from 10.9±2.8 to 7.4±2.2 mmol/l (P

The efficacy of traditional Chinese medicine (TCM) treatments for Western medicine (WM) diseases relies heavily on the proper classification of patients into TCM syndrome types. The authors developed a data-driven method for solving the classification problem, where syndrome types were identified and quantified based on statistical patterns detected in unlabeled symptom survey data. The new method is a generalization of latent class analysis (LCA), which has been widely applied in WM research to solve a similar problem, i.e., to identify subtypes of a patient population in the absence of a gold standard. A well-known weakness of LCA is that it makes an unrealistically strong independence assumption. The authors relaxed the assumption by first detecting symptom co-occurrence patterns from survey data and used those statistical patterns instead of the symptoms as features for LCA. This new method consists of six steps: data collection, symptom co-occurrence pattern discovery, statistical pattern interpretation, syndrome identification, syndrome type identification and syndrome type classification. A software package called Lantern has been developed to support the application of the method. The method was illustrated using a data set on vascular mild cognitive impairment.

Real-world data are often multifaceted and can be meaningfully clustered in more than one way. There is a growing interest in obtaining multiple partitions of data. In previous work we learnt from data a latent tree model (LTM) that contains multiple latent variables (Chen et al. 2012). Each latent variable represents a soft partition of data and hence multiple partitions result in. The LTM approach can, through model selection, automatically determine how many partitions there should be, what attributes define each partition, and how many clusters there should be for each partition. It has been shown to yield rich and meaningful clustering results. Our previous algorithm EAST for learning LTMs is only efficient enough to handle data sets with dozens of attributes. This paper proposes an algorithm called BI that can deal with data sets with hundreds of attributes. We empirically compare BI with EAST and other more efficient LTM learning algorithms, and show that BI outperforms its competitors on data sets with hundreds of attributes. In terms of clustering results, BI compares favorably with alternative methods that are not based on LTMs.

Background Right lobar living donor living transplantation (LDLT) has been controversial because of widely differing reports of recipient morbidity. Herein, we present our nearly 10-year experience and identify factors that potentially could be modified to improve recipient outcome. Material/methods The Clavien 5-tier grading system was applied retrospectively in 196 consecutive adult right lobar recipients. We determined the incidence of potentially life- threatening (Grade III), actually life-threatening (Grade IV), and lethal (Grade V) complications during the first post-transplant year. The most serious and seminal complication was considered if simultaneous or multiple complications appeared. Results One-year recipient/graft survival was 82%/82%. Within the first year, 68 (34.69%) of the 196 recipients had Grade III (n=31), Grade IV (n=7), or Grade V (n=30) complications. The complications were 19.90% graft-related and 15.82% non-graft-related. Complications during the first half year did not decline with increased team experience over time and adversely affected recipients' long-term survival, albeit not significantly. According to univariate analysis, high Child-Pugh scores before transplantation (P=0.016), prolonged ICU-stay (P=0.003) and hospitalization time (P=0.032) after transplantation were found to be risk factors for the appearance of ≥ Clavien III complications, while duct-to-duct biliary reconstruction (P=0.02) had a beneficial role in reducing serious complications after LDLTs. Conclusions In conclusion, serious complications during the first post-transplant year shortened recipient survival and prolonged primary hospitalization duration and postoperative ICU-stay, which is more frequent in recipients with higher Child-Pugh scores and in those with hepaticojejunostomy.

Background: To reduce harm caused by health care is a global priority. Medical students should be able to recognize unsafe conditions, systematically report errors, and near misses, investigate and improve such systems with a thorough understanding of human fallibility, and disclose errors to patients. Therefore, incorporating knowledge about patient safety into medical school curriculums is an urgent necessity. Objectives: To describe the extent to which Chinese medical students have patient safety in their knowledge, skills, and attitudes so as to provide evidence for implementation of a patient safety curriculum in medical schools, and to assess the quality of this investigative questionnaire. Methods: Our questionnaire of 31 items was developed based on a 2008 WHO pilot study for a patient safety curriculum guide. Our investigation was conducted in three university medical schools in China. Year 3 and year 4 medical students were asked to complete an anonymous questionnaire in their classroom settings. All items were scored from 1 to 5. Differences in responses among different universities, genders, and levels, as well as the validity and reliability of the questionnaire, were analyzed using SPSS 15.0. Results: A total of 500 questionnaires were distributed, and 143 male and 262 female students completed the survey. An average of 0.96% of survey questions were not answered, of which the most frequently unanswered item was “what will happen when medical error occurs?” The students’ attitudes to learning about patient safety were positive, although their knowledge of medical error and how to report error was poor. There were no statistical differences among different medical schools and levels in any item responses. The only gender difference appeared in the response to “I would like to discuss with others when I made a medical error.” There was a good coherence of reliability in sections 2, 3, and 4 of the questionnaire (Cronbach's alpha > 0.8), while sections 5 and 6 scored as less reliable. The validity of the questionnaire was good. Conclusions: Although medical students’ understanding of patient safety is very poor in China, the students have a positive attitudes to learning about the knowledge of patient safety in their future careers.

Vessel exposure and vascular reconstruction play pivotal roles in liver transplantation (LT) and in other surgical techniques performed during transplantation. Either poor vessel exposure or vascular reconstruction results in unsuccessful liver transplantation. Satisfactory vessel exposure is a prerequisite for successful vascular reconstruction during liver transplantation. Dissection and protection of the to-be-reconstructed vessels and determining proper strategy for reconstructing vessels under nonideal conditions are crucial to successful vascular reconstruction. Vascular remodeling, including reconstruction of the suprahepatic inferior vena cava (IVC), hepatic veins, portal vein, and hepatic arteries, is of paramount importance in liver transplantation. Any type of vascular complication can lead to the failure of liver transplantation, especially arterial complications which can result in graft failure [1–3]. Herein, we introduce some common techniques in vessel exposure and reconstruction in the context of liver transplantation.

Metastatic liver cancer, also known as secondary liver cancer, is formed by metastasis from cancer of other organs to the liver and is an indicator of late-stage malignancy. Metastatic liver cancer, if untreated, can result in a poor outcome. The median survival time of patients with this diagnosis is no more than 2 years, with patients rarely surviving for more than 5 years [1]. Optimal treatment for metastatic liver cancer remains a challenge in the modern era. Although multiple therapeutic methods such as surgical resection, liver transplantation, chemotherapy, transhepatic portal or arterial embolization, intratumor local injection, hyperthermic and hypothermic therapy, and gene therapy have been introduced, only surgical resection has achieved satisfactory results.

PurposeTo assess the pharmacogenomic and pharmacokinetic determinants of skin rash and diarrhea, the two primary dose-limiting toxicities of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib.Patients and MethodsA prospective clinical study of 80 patients with non–small-cell lung cancer, head and neck cancer, and ovarian cancer was performed. Detailed pharmacokinetics and toxicity of erlotinib were assessed. Polymorphic loci in EGFR, ABCG2, CYP3A4, and CYP3A5 were genotyped, and their effects on pharmacokinetics and toxicities were evaluated.ResultsA novel diplotype of two polymorphic loci in the ABCG2 promoter involving −15622C/T and 1143C/T was identified, with alleles conferring lower ABCG2 levels associated with higher erlotinib pharmacokinetic parameters, including area under the curve (P = .019) and maximum concentration (P = .006). Variability in skin rash was best explained by a multivariate logistic regression model incorporating the trough erlotinib plasma concentration (P = .034) and the EGFR intron 1 polymorphism (P = .044). Variability in diarrhea was associated with the two linked polymorphisms in the EGFR promoter (P < .01), but not with erlotinib concentration.ConclusionAlthough exploratory in nature, this combined pharmacogenomic and pharmacokinetic model helps to define and differentiate the primary determinants of skin and gastrointestinal toxicity of erlotinib. The findings may be of use both in designing trials targeting a particular severity of rash and in considering dose and schedule modifications in patients experiencing dose-limiting toxicities of erlotinib or similarly targeted agents. Further studies of the relationship between germline polymorphisms in EGFR and the toxicity and efficacy of EGFR inhibitors are warranted.

Low-rank matrix factorization has long been recognized as a fundamental problem in many computer vision applications. Nevertheless, the reliability of existing matrix factorization methods is often hard to guarantee due to challenges brought by such model selection issues as selecting the noise model and determining the model capacity. We address these two issues simultaneously in this paper by proposing a robust non-parametric Bayesian adaptive matrix factorization (AMF) model. AMF proposes a new noise model built on the Dirichlet process Gaussian mixture model (DP-GMM) by taking advantage of its high flexibility on component number selection and capability of fitting a wide range of unknown noise. AMF also imposes an automatic relevance determination (ARD) prior on the low-rank factor matrices so that the rank can be determined automatically without the need for enforcing any hard constraint. An efficient variational method is then devised for model inference. We compare AMF with state-of-the-art matrix factorization methods based on data sets ranging from synthetic data to real-world application data. From the results, AMF consistently achieves better or comparable performance.

Aims/Introduction The objective of the present study was to investigate the effects of CYP2C9*3 polymorphisms on the therapeutic response to gliclazide in type 2 diabetes patients. Materials and Methods A total of 746 incident type 2 diabetes patients were included in this study. After enrolment, patients went on 4‐week gliclazide monotherapy. Fasting plasma glucose was measured before and after treatment. Hypoglycemia episodes and lifestyle information were collected by weekly follow up. Genotyping of rs1057910 was carried out using the single base primer extension method. The t‐test, analysis of variance and chisquare‐test were used to evaluate the effects of rs1057910 alleles on the therapeutic response to gliclazide. Results After the therapy, fasting plasma glucose decreased significantly from 11.2 ± 2.7 mmol/L to 8.0 ± 2.2 mmol/L (P < 0.001). Patients with AC/CC genotypes of rs1057910 had a greater reduction of fasting plasma glucose (3.6 vs 3.0 mmol/L, P < 0.001; 31.4 vs 24.5%, P < 0.001) and a higher rate of treatment success (54.7 vs 37.5%, P < 0.001; 51.4 vs 32.3%, P < 0.001; 71.6 vs 48.3%, P < 0.001 for criterion 1, 2 and 3, respectively). Conclusions The present study showed that the polymorphism at rs1057910 significantly affected the therapeutic response of gliclazide in type 2 diabetes mellitus patients. The risk allele is associated with a greater decrease of fasting blood glucose and a higher rate of treatment success with gliclazide monotherapy., This study demonstrated that polymorphism at rs1057910 significantly affected therapeutic response of gliclazide in type 2 diabetes mellitus patients. It associated with the decrease of FPG and the rate of treatment success in the gliclazide monotherapy.

OBJECTIVE To investigate the frequency of and the risk factors for hospital readmission within the first year after liver transplantation (LT). MATERIALS AND METHODS Between January 1999 and August 2013, LTs were performed in 890 adult patients at our center. We collected medical data from the Chinese Liver Transplant Registry and performed a retrospective review of the medical records of these patients. We aimed to identify the factors that contribute toward readmission during the first year after LT. We also first investigated the relationship between the number and severity of post-transplant complications and the risk of readmission. The survival outcomes of patients with and without readmission were also studied. RESULTS A total of 165 rehospitalizations occurred in 142 patients (18.0%) within 1 year after discharge from their index admissions. The risk factors included hepatic malignancy as an indication for LT (P=0.01), previous abdominal surgery (P=0.03), the occurrence of any complications (P

Background: Identifying sources of variation in the nicotine and nitrosamine metabolic inactivation pathways is important to understanding the relationship between smoking and cancer risk. Numerous UGT1A and UGT2B enzymes are implicated in nicotine and nitrosamine metabolism in vitro; however, little is known about their roles in vivo. Methods: Within UGT1A1, UGT1A4, UGT1A9, UGT2B7, UGT2B10, and UGT2B17, 47 variants were genotyped, including UGT2B10*2 and UGT2B17*2. The association between variation in these UGTs and glucuronidation activity within European and African American current smokers (n = 128), quantified as urinary ratios of the glucuronide over unconjugated compound for nicotine, cotinine, trans-3′-hydroxycotinine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), was investigated in regression models assuming a dominant effect of variant alleles. Results: Correcting for multiple testing, three UGT2B10 variants were associated with cotinine glucuronidation, rs2331559 and rs11726322 in European Americans and rs835309 in African Americans (P ≤ 0.0002). Additional variants predominantly in UGT2B10 were nominally associated with nicotine (P = 0.008–0.04) and cotinine (P = Conclusions: Findings from this initial in vivo study support a role for multiple UGTs in the glucuronidation of tobacco-related compounds in vivo, in particular UGT2B10 and cotinine glucuronidation. Impact: Findings also provide insight into ethnic differences in glucuronidation activity, which could be contributing to ethnic disparities in the risk for smoking-related cancers. Cancer Epidemiol Biomarkers Prev; 24(1); 94–104. ©2014 AACR.

There is currently extensive discussion and debate in the literature on how, when, and to whom genetic research results should be returned (see Genetics in Medicine, April 2012 issue). Here, we describe our experience in disclosing genetic information on Mendelian disorders discovered during the course of our research in the Hutterites. We first assessed attitudes toward the disclosure of carrier results, which revealed that many individuals wanted carrier information and that many intended to use the information in family planning. Based on this information, we developed a pilot study to test and disclose cystic fibrosis (CF) carrier status. Next, a larger scale project was developed in order to disclose genetic research results for 14 diseases to those interested in receiving the information. We developed brochures, offered a live interactive educational program, conducted a consent process, and disclosed results in letters mailed to the consented individuals. Overall, ~80 % of individuals who participated in the educational program signed consent forms for the release of their results for 14 diseases. We describe our experience with returning individual genetic research results to participants in a population-based research study.

In the LDA approach to topic detection, a topic is determined by identifying the words that are used with high frequency when writing about the topic. However, high frequency words in one topic may be also used with high frequency in other topics. Thus they may not be the best words to characterize the topic. In this paper, we propose a new method for topic detection, where a topic is determined by identifying words that appear with high frequency in the topic and low frequency in other topics. We model patterns of word co- occurrence and co-occurrences of those patterns using a hierarchy of discrete latent variables. The states of the latent variables represent clusters of documents and they are interpreted as topics. The words that best distinguish a cluster from other clusters are selected to characterize the topic. Empirical results show that the new method yields topics with clearer thematic characterizations than the alternative approaches.

To investigate health-related quality of life (HRQoL) and psychological outcomes in 256 adults who had undergone liver transplantation (LT).A stratified random sampling method was used in this follow-up multicenter study to select a representative sample of recipients undergoing either living donor liver transplantation (LDLT) or deceased donor liver transplantation (DDLT). HRQoL was measured by using the Chinese version of Medical Outcome Study Short Form-36 (SF-36), and psychological outcomes by using the beck anxiety inventory (BAI) and the self-rating depression scale (SDS). Clinical and demographic data were collected from the records of the Chinese Liver Transplant Registry and via questionnaires.A total of 256 patients were sampled, including 66 (25.8%) receiving LDLT and 190 (74.2%) undergoing DDLT; 15 (5.9%) recipients had anxiety and four (1.6%) developed severe depression after the operation. Compared with LDLT recipients, DDLT patients had higher scores in general health (60.33 ± 16.97 vs 66.86 ± 18.42, P = 0.012), role-physical (63.64 ± 42.55 vs 74.47 ± 36.46, P = 0.048), role-emotional (61.11 ± 44.37 vs 78.95 ± 34.31, P = 0.001), social functioning (78.60 ± 22.76 vs 88.16 ± 21.85, P = 0.003), vitality (70.30 ± 15.76 vs 75.95 ± 16.40, P = 0.016), mental health (65.88 ± 12.94 vs 71.85 ± 15.45, P = 0.005), physical component summary scale (PCS, 60.07 ± 7.36 vs 62.58 ± 6.88, P = 0.013) and mental component summary scale (MCS, 52.65 ± 7.66 vs 55.95 ± 10.14, P = 0.016). Recipients45 years old at the time of transplant scored higher in vitality (77.33 ± 15.64 vs 72.52 ± 16.66, P = 0.020), mental health (73.64 ± 15.06 vs 68.00 ± 14.65, P = 0.003) and MCS (56.61 ± 10.00 vs 54.05 ± 9.30, P = 0.037) than those aged ≤ 45 years. MCS was poorer in recipients with than in those without complications (52.92 ± 12.21 vs 56.06 ± 8.16, P = 0.017). Regarding MCS (55.10 ± 9.66 vs 50.0 ± 10.0, P0.05) and PCS (61.93 ± 7.08 vs 50.0 ± 10.0, P0.05), recipients scored better than the Sichuan general and had improved overall QoL compared to patients with chronic diseases. MCS and PCS significantly correlated with scores of the BAI (P0.001) and the SDS (P0.001).Age45 years at time of transplant, DDLT, full-time working, no complications, anxiety and depression were possible factors influencing postoperative HRQoL in liver recipients.

Background To reduce harm caused by health care is a global priority. Medical students should be able to recognize unsafe conditions, systematically report errors and near misses, investigate and improve such systems with a thorough understanding of human fallibility, and disclose errors to patients. Incorporating the knowledge of how to do this into the medical student curriculum is an urgent necessity. This paper aims to systematically review the literature about patient safety education for undergraduate medical students in terms of its content, teaching strategies, faculty availability and resources provided so as to identify evidence on how to promote patient safety in the curriculum for medical schools. This paper includes a perspective from the faculty of a medical school, a major hospital and an Evidence Based Medicine Centre in Sichuan Province, China. Methods We searched MEDLINE, ERIC, Academic Source Premier(ASP), EMBASE and three Chinese Databases (Chinese Biomedical Literature Database, CBM; China National Knowledge Infrastructure, CNKI; Wangfang Data) from 1980 to Dec. 2009. The pre-specified form of inclusion and exclusion criteria were developed for literature screening. The quality of included studies was assessed using Darcy Reed and Gemma Flores-Mateo criteria. Two reviewers selected the studies, undertook quality assessment, and data extraction independently. Differing opinions were resolved by consensus or with help from the third person. Results This was a descriptive study of a total of seven studies that met the selection criteria. There were no relevant Chinese studies to be included. Only one study included patient safety education in the medical curriculum and the remaining studies integrated patient safety into clinical rotations or medical clerkships. Seven studies were of a pre and post study design, of which there was only one controlled study. There was considerable variation in relation to contents, teaching strategies, faculty knowledge and background in patient safety, other resources and outcome evaluation in these reports. The outcomes from including patient safety in the curriculum as measured by medical students' knowledge, skills, and attitudes varied between the studies. Conclusions There are only a few relevant published studies on the inclusion of patient safety education into the undergraduate curriculum in medical schools either as a selective course, a lecture program, or by being integrated into the existing curriculum even in developed countries with advanced health and education systems. The integration of patient safety education into the existing curriculum in medical schools internationally, provides significant challenges.

Objectives: Clear, transparent, and sufficiently detailed abstracts of journal articles and conference abstracts are important because readers often base their assessment of a trial on such information. There are concerns over the reliability and quality of trials published only in the proceedings of scientific meetings. This study aims to assess the reporting quality of abstracts of randomized trials published in Chinese medical conference abstracts.Methods: Conference abstracts reporting randomized trials included in the China National Knowledge Infrastructure (CNKI) in 2007 were identified. A revised checklist (based on the CONSORT extension for reporting randomized controlled trials in journal and conference abstracts) was used to assess the reporting quality of these conference abstracts.Results: A total of 567 conference abstracts of randomized trials were identified. Some aspects were well reported, including 94 percent of authors contact details, 83 percent of trial interventions and 78 percent of control interventions, 62 percent of participant eligibility criteria, and 66 percent the number of participants randomized to each group. Other areas were very poorly reported: only 1 percent identified the study as randomized in the abstract title, 2 percent reported the trial design, and only 7 percent reported on blinding. No details of allocation concealment, trial registration, or funding were reported.Conclusion: The information given for trials in conference proceedings in China is very poor, especially in some aspects of methodological quality, trial registration, and funding source. The quality of conference abstracts for trials should be improved to further facilitate understanding of their conduct and validity.

Purpose We aim to identify genetic variation, in addition to the UGT1A1*28 polymorphism, that can explain the variability in irinotecan (CPT-11) pharmacokinetics and neutropenia in cancer patients. Patients and Methods Pharmacokinetic, genetic, and clinical data were obtained from 85 advanced cancer patients treated with single-agent CPT-11 every 3 weeks at doses of 300 mg/m2 (n = 20) and 350 mg/m2 (n = 65). Forty-two common variants were genotyped in 12 candidate genes of the CPT-11 pathway using several methodologies. Univariate and multivariate models of absolute neutrophil count (ANC) nadir and pharmacokinetic parameters were evaluated. Results Almost 50% of the variation in ANC nadir is explained by UGT1A1*93, ABCC1 IVS11 –48C>T, SLCO1B1*1b, ANC baseline levels, sex, and race (P < .0001). More than 40% of the variation in CPT-11 area under the curve (AUC) is explained by ABCC2 –24C>T, SLCO1B1*5, HNF1A 79A>C, age, and CPT-11 dose (P < .0001). Almost 30% of the variability in SN-38 (the active metabolite of CPT-11) AUC is explained by ABCC1 1684T>C, ABCB1 IVS9 –44A>G, and UGT1A1*93 (P = .004). Other models explained 17%, 23%, and 27% of the variation in APC (a metabolite of CPT-11), SN-38 glucuronide (SN-38G), and SN-38G/SN-38 AUCs, respectively. When tested in univariate models, pretreatment total bilirubin was able to modify the existing associations between genotypes and phenotypes. Conclusion On the basis of this exploratory analysis, common polymorphisms in genes encoding for ABC and SLC transporters may have a significant impact on the pharmacokinetics and pharmacodynamics of CPT-11. Confirmatory studies are required.

AIM: To investigate the outcome of living donor liver transplantation (LDLT) recipients transplanted with small-for-size grafts (SFSGs). METHODS: Between November 2001 and December 2010, 196 patients underwent LDLT with right lobe liver grafts at our center. Recipients were divided into 2 treatment groups: group A with an actuarial graft-to-recipient weight ratio (aGRWR) < 0.8% (n = 45) and group B with an aGRWR ≥ 0.8% (n = 151). We evaluated serum liver function markers within 4 wk after transplantation. We also retrospectively evaluated the outcomes of these patients for potential effects related to the recipients, the donors and the transplantation procedures based upon a review of their medical records. RESULTS: Small-for-size syndrome (SFSS) developed in 7 of 45 patients (15.56%) in group A and 9 of 151 patients (5.96%) in group B (P = 0.080). The levels of alanine aminotransferase and aspartate aminotransferase in group A were higher than those in group B during early period after transplantation, albeit not significantly. The cumulative 1-, 3- and 5-year liver graft survival rates were 82.22%, 71.11% and 71.11% for group A and 81.46%, 76.82%, and 75.50% for group B patients, respectively (P = 0.623). However, univariate analysis of risk factors associated with graft survival in group A demonstrated that the occurrence of SFSS after LDLT was the only significant risk factor affecting graft survival (P < 0.001). Furthermore, multivariate analysis of our data did not identify any additional significant risk factors accounting for poor graft survival. CONCLUSION: Our study suggests that LDLT recipients with an aGRWR < 0.8% may have liver graft outcomes comparable to those who received larger size grafts. Further studies are required to ascertain the safety of using SFSGs.

Identifying patients prior to treatment that are less likely to benefit from or most likely to experience adverse events from chemotherapeutic agents is essential. Even though humans are the most relevant system, pharmacogenomic discovery in the field of oncology is plagued by difficulties in executing large clinical trials and confounding factors such as co-morbidities, dosage, and concomitant medications. Therefore, we developed a genome-wide cell-based approach evaluating single nucleotide polymorphisms (SNPs) and gene expression to predict chemotherapy-induced response and toxicity and then validated our findings in clinically relevant patient cohorts. Our model utilizes the International HapMap lymphoblastoid cell lines (LCLs). Genome-wide association studies were performed to identify SNPs significantly associated with carboplatin sensitivity through their effects on mRNA expression. The significant findings were evaluated in an independent LCL replication set and in patient samples obtained from the Australian Ovarian Cancer Study (AOCS) and two Phase II head and neck clinical trials (UC12019 and UC13881) conducted at the University of Chicago. Four hundred and nine ovarian cancer patients receiving carboplatin and paclitaxel were analyzed in AOCS; while 60 and 32 head and neck cancer patients were evaluated in UC12019 and UC13881 trials. Carboplatin was used as induction and concomitant chemo-radiation therapy in UC12019 and UC13881 trials, respectively. Using LCLs, our genome-wide model identified 65 SNPs that are associated with at least one carboplatin sensitivity phenotype through the expression of 61 genes. Five of them were replicated in a separate set of LCLs. In AOCS, SNP (rs1649942) was significantly associated with progression-free survival (Plog-rank=0.009) and overall survival (Plog-rank=0.03). In the head and neck cancer trials, 2 other SNP-phenotype associations were identified and replicated in both trials, including the association between SNP (rs4946514) and overall response to carboplatin, and the association between SNP (rs7134205) and post treatment platelet changes. Given the obstacles to performing large, replicable pharmacogenomic studies in patients, the cell-based model is proven to be an effective alternative in novel pharmaco-SNP discovery. We demonstrate germline SNPs identified through the cell-based genome-wide approach are clinically important predictors of chemotherapy response and toxicity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2761.