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Reina Haque,1,2 Lie Hong Chen,1 Nina Oestreicher,3 Deepa Lalla,3 Rowan T Chlebowski4 1Kaiser Permanente Southern California, Department of Research & Evaluation, Pasadena, CA, USA; 2Kaiser Permanente School of Medicine, Department of Health Systems Science, Pasadena, CA, USA; 3PUMA Biotechnology, Los Angeles, CA, USA; 4Lundquist Research Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USACorrespondence: Reina Haque, Kaiser Permanente, Research & Evaluation, Kaiser Permanente Bernard J. Tyson School of Medicine, Health Systems Science, 100 South Los Robles, 2nd Floor, Pasadena, CA, 91101, USA, Tel +1 626 564-5707, Email Reina.Haque@kp.orgPurpose: Clinical outcomes have improved for women with early stage, HER2-positive breast cancer following the FDA approval of adjuvant trastuzumab use in 2006. However, only limited information exists on such patients’ outcomes in real-world settings outside of clinical trials. We examined the risk of subsequent breast cancer in women with HER-2 positive disease, and the impact of trastuzumab use, in a large California community-based health plan.Patients and Methods: A cohort of 3550 women with HER2-positive breast cancer (stages I–III) from 2009– 2017 were followed through December 2018. We calculated subsequent breast cancer (SBC) rates overall and by trastuzumab use. Multivariable Cox proportional hazards modeling was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for SBC by trastuzumab use.Results: Within the cohort diagnosed with HER2-positive disease, 81% received adjuvant trastuzumab. After 4.1 mean years follow-up (maximum 10 years), the risk of SBC was 22% lower with adjuvant trastuzumab use (hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.66– 0.92) compared with non-use. The cumulative incidence of SBC precipitously rose two years after diagnosis and by the 10th year, the cumulative incidence was 31% among those who had trastuzumab therapy versus 34% without this therapy.Conclusion: In community practice settings, the cumulative incidence of SBC in patients with early stage HER2-positive BC was 31% at 10 years in a cohort treated with adjuvant trastuzumab. Trastuzumab use was associated with a 22% reduced risk of developing SBC. This residual disease burden suggests breast cancer outcomes may be improved with further treatment given the advent of next-generation HER2-targeted therapies.Keywords: breast cancer, survival, mortality, HER2 positive, recurrence, relapse, cohort study, real world

Ling-Wang An,1 Xiang-Lan Li,1 Lin-Hui Chen,2 Hong Tang,3 Qun Yuan,4 Yan-Jun Liu,5 Yu Ji,6 Ju-Ming Lu1,7 1Department of Endocrinology, Beijing Ruijing Diabetes Hospital, Beijing, 100079, People’s Republic of China; 2Department of Endocrinology, Taiyuan Diabetes Hospital, Taiyuan, 030013, People’s Republic of China; 3Department of Share-Care Center, Chengdu Ruien Diabetes Hospital, Chengdu, 610000, People’s Republic of China; 4Department of Endocrinology, Heilongjiang Ruijing Diabetes Hospital, Harbin, 150009, People’s Republic of China; 5Department of Endocrinology, Lanzhou Ruijing Diabetes Hospital, Lanzhou, 730000, People’s Republic of China; 6Department of Endocrinology, Beijing Aerospace General Hospital, Beijing, 100076, People’s Republic of China; 7Department of Endocrinology, The General Hospital of the People’s Liberation Army, Beijing, 100853, People’s Republic of ChinaCorrespondence: Ju-Ming LuDepartment of Endocrinology, The General Hospital of the People’s Liberation Army, No. 28 of Fuxing Road, Haidian District, Beijing, 100853, People’s Republic of ChinaTel +86 10 8822 9999Email lujm666_1@21cn.comObjective: To analyse diabetes treatment, treatment change and self-management behaviours in association with 2-year glycaemic trajectories in patients with non-newly diagnosed type 2 diabetes mellitus in Chinese primary care.Methods: This was an observational, multi-centre, longitudinal, retrospective cohort study. Clinical data of 4690 subjects were extracted from electronic medical records, including serial glycated haemoglobin A1c (HbA1c) measurements, antidiabetic medication records and compliance to exercise, diet, medications and self-monitoring of blood glucose (SMBG). Patterns of longitudinal HbA1c trajectories were identified using the percentage of HbA1c measurements < 7.5% from the second available HbA1c measurement. Clinical relevance of the clusters was assessed through multivariable analysis.Results: Approximately half of the participants demonstrated good glycaemic control; of these, 34.5% demonstrated stable, good control, and 13.7% demonstrated relatively good control. About 16.2% demonstrated moderate control, and 35.6% demonstrated poor control. From the good to poor control groups, the percentage of subjects treated with insulin at baseline and during the follow-up period increased gradually, while the percentage of subjects adhering to exercise, diet, medications and SMBG decreased gradually. Compared with baseline, the adherence to exercise, diet, medications and SMBG improved significantly. Approximately 50% and 26% of subjects in the two poorest control groups, respectively, experienced treatment changes. After multivariable adjustments, baseline HbA1c ≥ 7.5%, HbA1c change ≥− 0.5% from baseline to visit 1, insulin treatment, treatment change, poor adherence to diet, exercise, SMBG during the follow-up period and HbA1c measurements < 3 per year were significantly associated with poorer glycaemic control.Conclusion: We identified four longitudinal HbA1c trajectories in patients with non-newly diagnosed type 2 diabetes. Even if baseline HbA1c is suboptimal, aggressive treatment changes, good adherence during the follow-up period, ≥ 3 HbA1c measurements per year and reducing HbA1c levels to a certain extent by the first follow-up visit were important for good, stable, long-term glycaemic control.Keywords: haemoglobin A1c, self-monitoring of blood glucose, diabetes, glycaemic trajectories, glycaemic control

Jian-Jun Gu, Zhi-Hong Cheng, Ji-Qiang Bu, Wen-Li Zhang, Li-Hua Chen, Zi-Ying Chen Department of Cardiac Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of ChinaCorrespondence: Zi-Ying ChenDepartment of Cardiac Surgery, The Second Hospital of Hebei Medical University, No. 215, Heping Road, Shijiazhuang, Hebei, 050000, People’s Republic of ChinaTel +86 15803210520Email ziyingchen_dr06@163.comObjective: The present study aims to observe the changes in galectin-3 (Gal-3) expression levels in patients with an ascending aortic aneurysm and ventricular remodeling and analyze Gal-3’s correlation with ventricular remodeling.Methods: A total of 102 patients with an ascending aortic aneurysm were included as the research subjects. Gal-3 expression levels in the peripheral blood of the patients were detected by an enzyme-linked immunosorbent assay before the operation and then three and six months after. The left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), interventricular septal thickness, and left ventricular posterior wall thickness were recorded, and the left ventricular mass index (LVMI) was calculated. Changes in Gal-3 expression levels, LVMI, LVEF, and LVEDD were observed before and after surgery, and these changes were then analyzed.Results: There were significant differences in Gal-3 expression levels, LVMI, and LVEDD before surgery and three months after (P < 0.001) but no significant difference in LVEF (P = 0.887). There were significant differences in Gal-3 expression levels, LVMI, LVEDD, and LVEF (P < 0.05) three and six months after surgery. Before surgery and three and six months after surgery, Gal-3 was positively correlated with LVMI and LVEDD (R = 0.697, R = 0.571, and R = 0.454, respectively), and a receiver operating characteristic curve found that Gal-3 was able to predict ventricular remodeling, with an area under the curve value of 0.721.Conclusion: Gal-3 expression levels are correlated with ascending aortic aneurysms combined with ventricular remodeling, which provides a reference value for predicting ventricular remodeling.Keywords: ascending aortic aneurysm, ventricular remodeling, galectin-3, left ventricular mass index, ascending aortic replacement

Zhi-Xin Huang,1,2,* Li-Hua Chen,3,* Ran Xiong,4 Yan-Ni He,4 Zhu Zhang,1,2 Jie Zeng,5 Qiankun Cai,6 Zhenguo Liu7 1Department of Neurology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, People’s Republic of China; 2Department of Neurology, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Neurology, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Ultrasonography, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, People’s Republic of China; 5Department of Center for Clinical Epidemiology and Methodology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, People’s Republic of China; 6Department of Neurology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, People’s Republic of China; 7Center for Precision Medicine and Division of Cardiovascular Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO, USA*These authors contributed equally to this work.Correspondence: Zhi-Xin HuangDepartment of Neurology, Guangdong Second Provincial General Hospital, 466 Middle Xingang Road, Guangzhou 510317, Guangdong, People’s Republic of ChinaTel/Fax +86 20 89168080Email hzxd6@163.comZhenguo LiuCenter for Precision Medicine and Division of Cardiovascular Medicine, Department of Medicine, University of Missouri School of Medicine, Columbia, MO, USAEmail liuzheng@health.missouri.eduBackground: Carotid atherosclerosis (CA) is closely related to stroke, and Framingham Risk Score (FRS) has been used for CA risk evaluation. However, FRS could only be used for subjects of up to 74 years old. The present study was to determine if Essen Stroke Risk Score (ESRS) could be used to estimate CA risk in community populations without age limits.Methods: In the present prospective multi-community screening study, we evaluated the prevalence of CA using high-resolution ultrasound in 521 males and 1039 females (35 to 91 years old). Both FRS and ESRS were calculated for the subjects. Multivariate logistic regression analysis was used to determine the predictive values of FRS and ESRS for CA in these subjects.Results: Ultrasound data showed that CA was present in 56.2% of the participants (total of 1560). Multivariate logistic regression analysis showed that ESRS was associated with CA with odds ratio (OR): 1.34 (95% confidence interval (CI), 1.12– 1.60, p=0.001). Central obesity (OR: 1.40, CI: 1.07– 1.83, p=0.015), female (OR: 0.55, CI: 0.39– 0.77, p < 0.001) and age (OR: 2.63, CI: 2.27– 3.06, p < 0.001) were also associated with CA. Based on the estimated area under curve (AUC), FRS (AUC 0.775) was better than ESRS (AUC 0.693) (z statistic 6.774, p < 0.001) for CA prediction for individuals of ≤ 74 years old. However, receiver operating characteristic analysis showed ESRS was a good CA predictor for all subjects (AUC of 0.715).Conclusion: ESRS could be used as an alternative to FRS to predict CA in community population of all age.Keywords: Essen Stroke Risk Score, ESRS, carotid atherosclerosis, risk factors, stroke

Mandy H Chan,1 Patrick WL Leung,2 Ting-pong Ho,3 Se-fong Hung,4 Chi-chiu Lee,5 Chun-pan Tang,5 Ka-chai Cheung,2 Fung-yee Ching,2 Fefe HK Chan,6 Lu-hua Chen,2 Merce Garcia-Barcelo,7 Pak-chung Sham3 1Department of Clinical Psychology, Kowloon Hospital, Hospital Authority, 2Department of Psychology, The Chinese University of Hong Kong, 3Department of Psychiatry, University of Hong Kong, 4Department of Psychiatry, The Chinese University of Hong Kong, 5Department of Psychiatry, Kwai Chung Hospital, Hospital Authority, 6Department of Clinical Psychology, Alice Ho Mui Ling Nethersole Hospital, Hospital Authority, 7Department of Surgery, University of Hong Kong, Hong Kong, People’s Republic of China Background: Methylphenidate (MPH) has been found to be an effective medication for attention-deficit/hyperactivity disorder (ADHD). However, there are neither consistent nor sufficient findings on whether psychiatric comorbidities and associated cognitive functions of ADHD are related to treatment response to MPH in ADHD children.Objectives: This study investigated whether psychiatric comorbidities, IQ, and neurocognitive deficits are related to treatment response to MPH in ADHD children. In some ways, it is preferable to have a drug that the effectiveness of which to a disorder is not affected by its associated cognitive functions and psychiatric comorbidities. On the other hand, it is likely that the baseline symptom severity of ADHD is associated with the effectiveness of MPH treatment on the symptoms post treatment.Methods: A total of 149 Chinese boys (aged 6–12 years) with ADHD, combined type, and normal IQ participated in this study. Assessment of ADHD symptom severity was conducted pre and post MPH treatment, while assessment of psychiatric comorbidities, IQ, and neurocognitive deficits was performed in a non-medicated condition. Treatment response was defined as the ADHD symptom severity post MPH treatment.Results: Results indicated that MPH treatment was effective, significantly improving the ADHD condition. Yet, comorbid disorders, IQ, and neurocognitive deficits were not related to MPH treatment response on ADHD symptoms. These findings indicated that the effectiveness of MPH was not affected by psychiatric comorbidities and associated cognitive functions of ADHD. Instead, as expected, it was the baseline symptom severity that was mainly related to the treatment response, ie, the milder the baseline condition, the better the treatment response.Conclusion: The current findings positively endorse the widespread clinical use of MPH for treating ADHD. It improves the behavioral symptoms of ADHD regardless of varying psychiatric comorbidities, IQ, and neurocognitive deficits. Keywords: ADHD, psychiatric comorbidities, cognitive functions, treatment response, methylphenidate

Chao Ji,1,2 Ziping Zhang,1,2 Lihong Chen,1,2 Kunli Zhou,1,2 Dongjun Li,1,2 Ping Wang,1,2 Shuying Huang,1,2 Ting Gong,2 Bo Cheng1,2 1Department of Dermatology, the 1st Affiliated Hospital of Fujian Medical University, 2Fujian Institute of Dermatology and Venereology, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China Abstract: Melanoma is one of the deadliest skin cancers and accounts for most skin-related deaths due to strong resistance to chemotherapy drugs. In the present study, we investigated the mechanisms of dabrafenib-induced drug resistance in human melanoma cell lines A375 and MEL624. Our studies support that both endoplasmic reticulum (ER) stress and autophagy were induced in the melanoma cells after the treatment with dabrafenib. In addition, ER stress-induced autophagy protects melanoma cells from the toxicity of dabrafenib. Moreover, inhibition of both ER stress and autophagy promote the sensitivity of melanoma cells to dabrafenib. Taken together, the data suggest that ER stress-induced autophagy determines the sensitivity of melanoma cells to dabrafenib. These results provide us with promising evidence that the inhibition of autophagy and ER stress could serve a therapeutic effect for the conventional dabrafenib chemotherapy. Keywords: melanoma, dabrafenib, ER stress, autophagy, apoptosis

We examined whether the momentary induction of state mindfulness benefited subsequent balance performance, taking into consideration the effects of dispositional mindfulness. We also tested whether our mindfulness induction, grounded in sustaining moment-to-moment attention, influenced the attentional focus strategies that were adopted by the participants during the balancing task. Balance performance was ascertained based on approximate entropy (ApEn) of the center of pressure (COP) data. The study involved 32 males (age: M = 22.8, SD = 1.94) who were randomly assigned to the mindfulness or control group. Using difference in pretest to posttest performance based on the medio-lateral movements as the dependent variable, the test for interaction showed that the mindfulness induction was more effective for participants with higher dispositional mindfulness. Participants who underwent mindfulness induction also reported greater use of external focus strategies than those in the control group. Results suggest that momentary mindful attention could benefit balance performance and affect the use of attentional focus strategies during movement control. [ABSTRACT FROM AUTHOR]

Spontaneous cell fusion can occur in cocultured stem cells. We examined whether telomerase activity change and cell fusion occurred in mesenchymal stem cell (MSC) and nucleus pulposus cell (NPC) coculture. MSCs and NPCs were labeled with PKH26 and PKH67 dyes and cocultured at a 50:50 ratio. An equal number of MSCs or NPCs were used as the control. After 14 days, cells were evaluated by cell growth, telomerase activity, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and histologic observation. Cell fusion was confirmed by microscopic observation and fluorescence-activated cell sorter (FACS) analysis. The results suggested cell growth rate and telomerase activity were higher in cocultured cells than in NPCs cultured alone. The mRNA expression levels of the Type II collagen and aggrecan were elevated in cocultured cells. Immunohistochemical analysis revealed positive staining for Type II collagen and keratan sulfate in NPCs cultured alone and in a proportion of cocultured cells. Histologic observation revealed binucleated cocultured cells expressed both PKH dyes in the same location and slide focus. The FACS analysis revealed 42% of cocultured cells were double-stained. Cocultured cells partially maintained the NPC phenotype. The partially maintained phenotype of the NPCs may be attributable to spontaneous cell fusion in association with increased telomerase activity. [ABSTRACT FROM AUTHOR]

Unlabelled: Identifying offending pathogens is crucial for appropriate antibiotic administration for infectious spondylitis. Although computed tomography (CT)-guided biopsy for bacteriologic diagnosis is a standard procedure, it has a variable success rate. Some reports claim percutaneous endoscopic discectomy and drainage offer a sufficient amount of tissue for microbiologic examination and easy application. We therefore compared the diagnostic value of CT guidance with that of endoscope guidance in 52 patients with suspected infectious spondylitis. Twenty patients underwent percutaneous endoscopic discectomy and drainage by an orthopaedic surgeon and the other 32 patients underwent CT-guided biopsies by a radiologist. Patients were followed a minimum of 12 months after treatment. Culture results of the biopsy specimens were recorded. Causative bacteria were identified more frequently with percutaneous endoscopy than in CT-guided biopsy (18 of 20 [90%] versus 15 of 32 [47%]). We observed no biopsy-related complications or side effects in either group. The data suggest percutaneous endoscopic discectomy and drainage yield higher bacterial recovery rates than CT-guided spinal biopsy.Level Of Evidence: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Computed tomography image-guided surgery (CTGS) clearly improves the accuracy of pedicle screw insertion. Recent reports claim that a fluoroscopy-guided system (FGS) offered high accuracy and easy application. However, the superiority of either technique remains unclear in clinical application. This study compares the accuracy of pedicle screws installed using CTGS with that of screws installed using FGS. Seventy-four screws inserted using FGS in 13 patients and 76 screws inserted using CTGS in 11 patients were compared. The study population included ten cases of vertebral fracture, five cases of degenerative spondylolisthesis, three cases of spondylolytic spondylolisthesis, two cases of tuberculous spondylitis, two cases of failed earlier back surgery and two case of ankylosing spondylitis with pseudarthrosis. The installed vertebral levels ranged from T8 to S1. Screw positions were assessed with postoperative radiographs and computed tomography. Sixty-nine (93.2%) screws were correctly placed in the FGS group, and seventy-three (96.1%) screws were correctly placed in the CTGS group (P=0.491). The results indicated that both image-guided systems offer high accuracy. However, the fluoroscope image-guided system could be considered the primary tool for lower thoracic and lumbosacral pedicle placement because it enables real-time navigation and does not require a preoperative CT scan. [ABSTRACT FROM AUTHOR]