Search

Dan Liu, Juan Tong, Erling Chen, Li Wang, Lei Xue, Xuhan Zhang, Na Zhao, Xing Hu, Changcheng Zheng Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui Province, People’s Republic of ChinaCorrespondence: Changcheng Zheng, Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Lujiang Road No. 17, Hefei, Anhui Province, 230001, People’s Republic of China, Email zhengchch1123@ustc.edu.cnBackground: The aim of the study was to evaluate the efficacy and safety of induction and consolidation with all-trans retinoic acid (ATRA) +arsenic trioxide (ATO) +anthracyclines and maintenance with ATRA +Realgar-Indigo naturalis formula (RIF) for high-risk APL.Methods: Twenty-one patients with high-risk APL treated with ATRA+ATO+ anthracyclines for induction and consolidation and ATRA+RIF for maintenance from 2012 to 2021 were analyzed. Endpoints include morphological complete remission (CR) and complete molecular remission (CMR), early death (ED) and relapse, survival and adverse events (AEs).Results: After induction treatment, all 21 patients (100%) achieved morphological CR and 14 people (66.7%) achieved CMR. Five of the 21 patients did not undergo immunological minimal residual disease (MRD) examination after induction; however, 14 of the remaining 16 patients were MRD negative (87.5%). The median time to achieve CR and CMR was 26 days (range: 16– 44) and 40 days (range: 22– 75), respectively. The cumulative probability of achieving CR and CMR in 45 days was 100% and 76.2% (95% CI: 56.9– 91.3%), respectively. All patients achieved CMR and MRD negativity after the three courses of consolidation treatment. The median follow-up was 66 months (25– 142), with no central nervous system relapse and bone marrow morphological or molecular relapse until now, and all patients survived with 100% overall survival and 100% event-free survival. Grade 4 adverse events (AEs) were observed in 3 patients (14.3%) during the induction period including arrhythmia (n = 1), pulmonary infection (n = 1) and respiratory failure (n = 1); and the most frequent grade 3 AEs were pulmonary infection, accounting for 62.0% and 28.6%, respectively, during induction and consolidation treatment, followed by neutropenia, accounting for 42.9% and 38.1%, respectively.Conclusion: For newly diagnosed high-risk APL patients, induction and consolidation with ATRA+ATO+anthracyclines and maintenance with ATRA+RIF is a highly curative treatment approach.Keywords: high-risk acute promyelocytic leukemia, all-trans retinoic acid, arsenic trioxide, realgar–Indigo naturalis formula, anthracyclines, event-free survival

Jiqian Jiang,1 Yan Wang,1 Dan Liu,1 Xiaoyu Wang,1 Yingqiao Zhu,1 Juan Tong,1 Erling Chen,1 Lei Xue,1 Na Zhao,1 Tingting Liang,2 Changcheng Zheng1 1Department of Hematology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 2The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of ChinaCorrespondence: Changcheng Zheng, Department of Hematology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Lujiang Road No. 17, Hefei, 230001, People’s Republic of China, Tel/Fax +86-551-62284476, Email zhengchch1123@ustc.edu.cnIntroduction: The BCL-2 inhibitor venetoclax has been widely used in the treatment of acute myeloid leukemia (AML); however, AML patients treated with venetoclax gradually develop resistance. The exportin-1 (XPO1) inhibitor selinexor can synergistically promote the antileukemia activity of venetoclax, but the mechanism remains unclear.Methods and Results: Annexin V/7-aminoactinomycin D assays were used to examine the effects of a combination of venetoclax and selinexor (VEN+SEL) on AML cell lines and primary AML cells. RNA sequencing and oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) determinations by a Seahorse XF analyzer were employed to investigate the molecular mechanism of the toxicity of the VEN+SEL combination to AML cells. The cytotoxicity of NK cell combined with VEN+SEL combination was assessed in vitro using flow cytometry. VEN+SEL enhanced the apoptosis of AML cells (KG-1A and THP-1) and primary AML samples in vitro. The ECAR and OCR results demonstrated that the VEN+SEL combination significantly inhibited glycolytic function. RNA sequencing of THP-1 cells demonstrated that DNA replication-related genes were downregulated after treatment with the VEN+SEL combination.Conclusion: This study indicated that selinexor can synergistically enhance the antileukemia activity of venetoclax in AML cells in vitro by inhibiting glycolytic function and downregulating DNA replication-related genes. Based on our experimental data, combining selinexor with venetoclax is an appropriate advanced treatment option for AML patients.Keywords: venetoclax, selinexor, acute myeloid leukemia, glycolytic function, DNA replication-related genes

Menglu Gui,1,* Jun Huang,2,* Huiqiu Sheng,1,* Ying Chen,1 Zhitao Yang,1 Li Ma,1 Daosheng Wang,3 Lili Xu,1 Wenwu Sun,1 Junling Liu,4 Yanyan Xu,4 Erzhen Chen,1 Bing Zhao,1 Enqiang Mao1 1Department of Emergency in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 3Department of Laboratory Medicine in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 4Department of Biochemistry and Molecular Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China*These authors contributed equally to this workCorrespondence: Enqiang Mao; Bing Zhao, Department of Emergency in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China, Tel +8613501747906 ; +8618017117871, Email maoeq@yeah.net; zhaobing124@163.comBackground: Platelet activation in the early stage of pancreatitis is the key step developing into pancreatic necrosis. Studies suggested that vitamin C (Vit C) can inhibit platelet activity by targeting CXCL12/CXCR4 pathway. High-dose Vit C were showed to reduce pancreatic necrosis in severe acute pancreatitis (SAP) but the mechanism remains unclear. Here we speculate high-dose Vit C reduce pancreatic necrosis by inhibiting platelet activation through downregulating CXCL12/CXCR4 pathway.Methods: The pancreatic microcirculation of rats was observed by intravital microscopy. The platelet activity of SAP rats treated with or without high-dose Vit C was analyzed by platelet function test. Besides, the activity of platelets preincubated with high-dose Vit C or vehicle from SAP patients was also evaluated. Then, the TFA (CXCR4 agonist) and rCXCL12 were used to neutralize the effect of high-dose Vit C in SAP rats treated with high-dose Vit C. Meanwhile, the levels of enzymes and inflammatory cytokines in rat plasma, and rats’ pancreatic histopathology and mortality were assessed.Results: Platelets from animals and patients with SAP are more sensitive to agonists and are more easily activated. Administration of high-dose Vit C significantly ameliorated excessive activation of platelets in SAP rats, ultimately increasing the microvessel density and inducing microthrombus and blood stasis; these results were consistent with clinical sample analysis. Moreover, high-dose Vit C significantly inhibited the release of amylase, lipase, TNF-α, and IL-6 in SAP rat plasma, reducing pancreatic damage and the mortality of SAP rats. However, using TFA and rCXCL12 significantly reversed the effect of high-dose Vit C on excessive activation of platelets, aggravating microcirculation impairment and pancreatic damage.Conclusion: The present study suggests that high-dose Vit C can ameliorate pancreatic necrosis by improving microcirculation disorders of SAP. For the first time, the underlying mechanism is related with inhibiting platelet activation through the CXCL12/CXCR4 pathway.Keywords: severe acute pancreatitis, microcirculation impairment, platelets activity, vitamin C, CXCL12/CXCR4 pathway

Yanqing Xing,1 Yupeng Li,1 Liting Feng,1 Rujie Huo,1 Xinkai Ma,1 Yanting Dong,1 Dai Liu,1 Yuheng Niu,2 Xinrui Tian,1,&ast; Erjing Chen1,&ast; 1The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2The First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinrui Tian; Erjing Chen, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Xinghualing District, Taiyuan, Shanxi, People’s Republic of China, Email tianxr@126.com; mayyoubehappy44@163.comPurpose: To analyze the clinical characteristics and prognosis of patients hospitalized with non-severe, severe pneumonia and death in Omicron COVID-19.Patients and Methods: We collected clinical data from 118 patients with COVID-19 in China from 18 December, 2022 and 5 February, 2023. According to the outcome, the patients were divided into non-severe group, severe group and death group. Subsequently, we statistically analyzed the general condition, clinical manifestations, laboratory parameters, NLR, MLR, PLR and HALP of these groups. We also retrospectively analyzed the possible factors affecting the prognostic regression of patients with COVID-19.Results: A total of 118 COVID-19 patients were enrolled in this study, including 64 non-severe patients, 38 severe patients and 16 death patients. Compared with the non-severe group, T lymphocytes, B lymphocytes, Th1, Th2, Th17, Treg cells, IgA, IgG, IgM in the severe and death groups decreased more significantly (P< 0.05). The levels of myocardial markers, ALT, AST, BUN, Cr, D-dimer, fibrinogen, NLR, MLR and PLR in the severe and death groups were significantly higher than those in the non-severe group (P< 0.05). The level of HALP was significantly lower than that of non-severe group (P< 0.05). MLR is not only an independent risk factor for the transition from non-severe to severe disease, but also an independent risk factor for predicting the possibility of death in COVID-19 patients.Conclusion: The analysis of COVID-19 patients in China showed that severe patients were older, more likely to have related complications, lower lymphocyte count, liver and kidney function disorder, glucose and lipid metabolism disorders, myocardial injury, and abnormal coagulation function, suggesting the need for early anticoagulant therapy. In addition, NLR, MLR, PLR and HALP can be used as biomarkers to evaluate the severity and prognosis of COVID-19 patients.Keywords: COVID-19, omicron, clinical characteristics, lymphocyte subpopulation, Shanxi

Yibo Zhang,1,&ast; Yichen Wang,1,&ast; Zike Sheng,2,&ast; Qun Wang,1 Dake Shi,1 Shirui Xu,3 Yaping Ai,4 Erzhen Chen,5 Yumin Xu1,2 1Department of Hospital Infection Management, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Clinical Laboratory Medicine, Shanghai Fenglin Clinical Laboratory Co. Ltd, Shanghai, People’s Republic of China; 4Health Economics and Outcome Research, Becton & Dickinson Medical Device (Shanghai) Ltd, Shanghai, People’s Republic of China; 5Department of Emergency Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Erzhen Chen, Department of Emergency Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China, Tel +86 021-64370045-665599, Email chenerzhen@hotmail.com Yumin Xu, Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China, Tel +86 021-64370045-600653, Email xym121@163.comPurpose: Indwelling central venous catheters (CVCs) can cause catheter related bloodstream infection (CRBSI). CRBSI occurring in intensive care unit (ICU) patients may lead to the worse outcomes and extra medical costs. The present study aimed to assess the incidence and incidence density, pathogens and economic burden of CRBSI in ICU patients.Patients and Methods: A case-control study was retrospectively carried out in six ICUs of one hospital between July 2013 and June 2018. The Department of Infection Control performed routinely surveillance for CRBSI on these different ICUs. Data of the clinical and microbiological characteristics of patients with CRBSI, the incidence and incidence density of CRBSI in ICUs, the attributable length of stay (LOS), and the costs among patients with CRBSI in ICU were collected and assessed.Results: A total of 82 ICU patients with CRBSI were included into the study. The CRBSI incidence density was 1.27 per 1000 CVC-days in all ICUs, in which the highest was 3.52 per 1000 CVC-days in hematology ICU and the lowest was 0.14 per 1000 CVC-days in Special Procurement ICU. The most common pathogen causing CRBSI was Klebsiella pneumoniae (15/82, 16.67%), in which 12 (80%) were carbapenem resistant. Fifty-one patients were successfully matched with control patients. The average costs in the CRBSI group were &dollar; 67,923, which were significantly higher (P < 0.001) than the average costs in the control group. The total average costs attributable to CRBSI were &dollar;33, 696.Conclusion: The medical costs of ICU patients were closely related to the incidence of CRBSI. Imperative measures are needed to reduce CRBSI in ICU patients.Keywords: CRBSI, prolonged length of stay, cost, CRKP, ICU

Menglu Gui,1,&ast; Bing Zhao,1,&ast; Jun Huang,2,&ast; Erzhen Chen,1 Hongping Qu,3 Enqiang Mao1 1Department of Emergency, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Critical Care Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Enqiang Mao, Department of Emergency, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Huangpu District, Shanghai, People’s Republic of China, Tel +86 13501747906, Email maoeq@yeah.netAbstract: Ischemia superimposed upon pancreatic edema leads to acute necrotizing pancreatitis. One possible mechanism contributing to ischemia is intravascular thrombogenesis since fibrin deposits have been detected in pancreatic capillaries by electron microscope. Current experimental and clinical data provided compelling evidence that the disorders in the blood coagulation system play a critical role in the pathogenesis of severe acute pancreatitis (SAP). This leads to microcirculatory failure of intra- and extrapancreatic organs and multiple organ failure and increases the case fatality rate. However, the mechanism of coagulopathy underlying SAP is not yet clear, although some anticoagulant drugs have entered clinical practice showing improvement in prognosis. Thus, enhanced understanding of the process might improve the treatment strategies with safety and high efficacy. Herein, the pathogenesis of the coagulation system of SAP was reviewed with a focus on the coagulation pathway, intercellular interactions, and complement system, thereby illustrating some anticoagulant therapies and potential therapeutic targets.Keywords: coagulation, acute pancreatitis, endothelial cells, complement, anticoagulant therapy

Data regarding response to SARS-CoV-2 immunization in pediatric patients with predominantly antibody deficiency (PAD) is limited. We evaluated SARS-CoV-2 immunization response by anti-SARS-CoV-2-spike antibody level in 15 pediatric PAD patients. These data were compared to a published cohort of adult PAD patients (n=62) previously analyzed following SARS-CoV-2 immunization at our single center institution. We evaluated demographics, clinical characteristics, immunophenotype, infection history, and past medication use by chart review. Following a two-dose monovalent initial series SARS-CoV-2 immunization, mean anti-SARS-CoV-2-spike antibody levels were significantly higher in pediatric PAD patients compared to adult PAD patients (2,890.7 vs. 140.1 U/mL; p

Blessy Koottappal Mathew,1 Jacqueline Giovanna De Roza,2 Changwei Liu,2 Ling Jia Goh,3 Chai Wah Ooi,2 Elya Chen,4 Shixuan Poon,1 Wern Ee Tang3 1National Healthcare Group Polyclinics, Toa Payoh Polyclinic, National Healthcare Group, Singapore; 2National Healthcare Group Polyclinics, Geylang Polyclinic, National Healthcare Group, Singapore; 3National Healthcare Group Polyclinics, Hougang Polyclinic, National Healthcare Group, Singapore; 4National Healthcare Group Polyclinics, Clinical Research Unit, National Healthcare Group, SingaporeCorrespondence: Blessy Koottappal MathewNational Healthcare Group Polyclinic, 2003 Toa Payoh Polyclinic, Lorong 8, Toa Payoh, 319260, Singapore, Email blessy_mathew@nhgp.com.sgPurpose: In type 2 diabetes mellitus (T2DM), insulin therapy is often recommended to achieve the optimal control of disease, thereby preventing the onset and progression of diabetes-related complications. Despite knowing about the benefits, it has been reported that 71% of patients refuse insulin and the adherence rate ranges from 30 to 80%. Patient–provider relationship (PPR) may affect such insulin-related behaviours, but little is known about which aspect of PPR affects this. This study aimed to explore the key aspect of the patient–provider relationship that affects the initial insulin acceptance and continued adherence.Patients and Methods: We used the grounded theory approach in this qualitative research. The study was conducted at two primary care clinics between September 2019 and January 2021. Patients with T2DM on basal or premixed insulin were recruited using maximum variation sampling. Data were collected using semi-structured in-depth interviews and transcribed verbatim for analysis using constant comparison and synthesis.Results: Twenty-one participants with different levels of diabetes control and adherence were recruited. Four themes that emerged were 1) patient–provider interaction, 2) addressing the psychological fears, 3) gaining confidence in handling insulin equipment and 4) follow-up after insulin initiation. Among the subthemes, trust in doctors, provider’s communication skills, patient-centred decision-making and continuity of care positively influenced insulin acceptance and adherence. Conversely, fear of being judged by the provider hindered open communication around non-adherence. Various aspects of interaction with nurses helped in alleviating patient’s fear of injection and gaining confidence with the insulin equipment.Conclusion: Many aspects of PPR affect insulin acceptance and adherence. Among these, gaining patients’ trust, effective patient–provider communication, patient-centred decision-making, and ensuring continuity of care improve both insulin acceptance and treatment adherence. Various interactions with nurses help in addressing fears surrounding injection and gaining acceptance towards insulin therapy. Patients’ fear of being blamed or judged by the provider negatively affects open communication around non-adherence.Keywords: insulin initiation, insulin adherence, insulin acceptance, healthcare provider, patient interactions, primary care

Fangchen Gong,1,&ast; Ranran Li,2,&ast; Xiangtao Zheng,1,&ast; Weiwei Chen,1 Yanjun Zheng,1 Zhitao Yang,1 Ying Chen,1 Hongping Qu,2 Enqiang Mao,1 Erzhen Chen1 1Department of Emergency, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Erzhen Chen; Ying ChenDepartment of Emergency, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Ruijin 2# Road No. 197, Shanghai, 200025, People’s Republic of ChinaTel +862164370045Fax +862164333548Email rjchenerzhen@163.com; bichatlion@163.comBackground: Acute respiratory distress syndrome (ARDS) is one of the leading causes of death in patients with sepsis. As such, early and accurate identification of sepsis-related ARDS is critical.Methods: Bioinformatic analysis was used to explore the GEO datasets. ELISA method was used to detect the plasma or cellular supernatant of relevant proteins. Quantitative real-time PCR was used for mRNA measurements and Western blot was applied for protein measurements. Immunohistochemistry staining and Immunofluorescence staining were used to identify the localization of OLFM4. Cecal ligation and puncture (CLP) model was used to establish sepsis model.Results: The bioinformatic analysis results identified ten genes (CAMP, LTF, RETN, LCN2, ELANE, PGLYRP1, BPI, DEFA4, MPO, and OLFM4) as critical in sepsis and sepsis-related ARDS. OLFM4, LCN2, and BPI were further demonstrated to have diagnostic values in sepsis-related ARDS. Plasma expression of OLFM4 and LCN2 was also upregulated in sepsis-related ARDS patients compared to septic patients alone. OLFM4 expression was significantly increased in the lung tissues of septic mice and was co-localized with Ly6G+ neutrophils, F4/80+ macrophages and pro-surfactant C+ lung epithelial cells. In vitro data showed that OLFM4 expression in lung epithelial cells was downregulated upon LPS stimulation, whereas neutrophil media induced OLFM4 expression in lung epithelial cells. Overexpression of OLFM4 and treatment with recombinant OLFM4 effectively suppressed LPS-induced pro-inflammatory responses in lung epithelial cells. Furthermore, the increased levels of LDHA phosphorylation and the downstream NF-κB activation induced by LPS in epithelial cells were effectively diminished by OLFM4 overexpression and recombinant OLFM4 treatment via a reduction in ROS production and HIF1α expression.Conclusion: OLFM4 may regulate the pro-inflammatory response of lung epithelial cells in sepsis-related ARDS by modulating metabolic disorders; this result could provide new insights into the treatment of sepsis-induced ARDS.Keywords: sepsis, ALI/ARDS, lung epithelial cells, inflammation, OLFM4, LDHA

Brain metastases (BMs) are the most common intracranial malignancy with poor prognosis. Patients with intracranial tumors are at greater risk for thrombotic complications and intracranial hemorrhage. Rivaroxaban is a potent oral anticoagulant with the high selectivity of direct factor Xa inhibition. The incidence and severity of rivaroxaban-triggered intratumoral hemorrhage (ITH) in patients with BMs remain unknown. A 57-year-old woman was diagnosed with multiple lung, bone, and BMs from unknown primary cancer origin, and refused any invasive procedures to confirm tumor pathology. However, this patient had a relatively favorable outcome after treating with cabozantinib, an inhibitor of multiple tyrosine kinases. The patient survived over 2 years and developed deep vein thrombosis of right lower limb. Oral rivaroxaban was prescribed, and the multifocal catastrophic ITH was encountered after 1 week. The last head computed tomography imaging revealed a rare but typical image of diffuse hemorrhagic metastases. Hemorrhagic-prone BMs, therapeutic rivaroxaban, and cabozantinib treatment increase risks to develop ITH. In this case rivaroxaban was the trigger to this terminal event. This case is a miserable lesson and keeps reminding us to stay vigilant in clinical practice even when there is a potential benefit for anticoagulation in such population.

Ming Zhong,1,* Wen Xu,1,* Yuzhen Qiu,1 Lei Li,1 Hongping Qu,1 Erzhen Chen2 1Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongping QuDepartment of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197. Ruijin No.2 Road, Shanghai 200025, People’s Republic of ChinaEmail hongpingqu0412@hotmail.comErzhen ChenDepartment of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of ChinaEmail rjchenerzhen@163.comPurpose: To investigate the association between the change of acute gastrointestinal injury (AGI) grade and the outcome in critically ill patients.Methods: This was a prospectively observational study. All patients admitted in the ICU from October 2013 to June 2015, with the duration of ICU > 72 h and age > 18 years, were enrolled in this study. The AGI grade and gastrointestinal symptoms were evaluated during ICU stay following the 2012 ESICM recommendation. The ICU mortality, duration of ICU stay, mechanical ventilation (MV) use, vasoactive drug use, and continuous renal replacement therapy of patients were recorded accordingly.Results: A total of 320 patients were included, and 265 of them were diagnosed with AGI. The overall ICU mortality was 11.88%, while it was 13.58% in patients with AGI. In logistic regression analyses, the decreasing trend of AGI grade was identified as a protective factor for ICU death (odds ratio (OR), 0.484; 95% confidence interval (CI), 0.26– 0.90), while the max AGI grade was a risk factor (OR, 3.464; 95% CI, 2.71– 8.47) for ICU death.Conclusion: The changes of AGI grades in critically ill patients were associated with their clinical outcomes. The ICU-acquired AGI patients associated with longer ICU stay days.Keywords: acute gastrointestinal injury grade, ICU stay, critically ill patient, patient outcome, ICU death

Wei Li,1 Qian Li,1 Yiyi Yu,1 Yan Wang,1 Erbao Chen,1 Lingli Chen,2 Zhiming Wang,1 Yuehong Cui,1 Tianshu Liu1,3 1Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Center of Evidence-Based Medicine, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Tianshu Liu Department of OncologyZhongshan Hospital, Center of Evidence-Based Medicine, Fudan University, Shanghai, People’s Republic of ChinaEmail liu.tianshu@zs-hospital.sh.cnPurpose: Alpha-fetoprotein-producing gastric cancer (AFPGC) and hepatoid adenocarcinoma of stomach (HAS) are rare types of gastric cancer, with specific clinical manifestations and poor prognosis. The standardized treatment process of such cancers remains elusive. We aim to investigate the efficacy of immunotherapy combined with chemotherapy on patients with AFPGC or HAS.Patients and Methods: AFPGC and HAS patients who underwent immunotherapy and/or chemotherapy as the first-line treatment at our institute from June 2016 to December 2018 were enrolled in this observational study. Their clinicopathological characteristics, serum AFP level and treatment methods were collected. The progression-free survival (PFS) and overall survival (OS) were analyzed and compared between patients who received immunotherapy plus chemotherapy and those received chemotherapy.Results: A total of 21 patients with advanced AFPGC or HAS were included in the study and the median follow-up time was 28.0 months. Of the 21 patients, 7 patients received immunotherapy of PD-1 antibody (nivolumab) plus chemotherapy and 14 patients as control received chemotherapy with or without Herceptin/Apatinib. The median progression-free survival (mPFS) time was 5.0 months (4.3 months in the control group and 22.0 months in the immunotherapy group). The median overall survival (mOS) time of the control group was 16.0 months (14.0 months in chemotherapy alone subgroup, 20.0 months in chemotherapy plus Apatinib or Herceptin subgroup), while the mOS of patients receiving immunotherapy was not reached.Conclusion: This study suggested PD-1 checkpoint inhibitor plus chemotherapy could benefit AFPGC and HAS patients. Its mechanism of action warrants further investigation.Keywords: gastric cancer, immunotherapy, alpha-fetoprotein-producing gastric cancer, hepatoid adenocarcinoma of stomach

Enrui Chen,1,* Shangcong Han,1,* Bo Song,2 Lisa Xu,1 Haicheng Yuan,2 Mingtao Liang,3 Yong Sun1 1Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao, People’s Republic of China; 2Department of Neurology, Qingdao Central Hospital, Qingdao, People’s Republic of China; 3Department of Pharmaceutics, School of Biomedical Science and Pharmacy, University of Newcastle, Newcastle, NSW, Australia*These authors contributed equally to this workCorrespondence: Yong SunDepartment of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266021, People’s Republic of ChinaTel +86-532-82991203Email sunyong@qdu.edu.cnBackground: Hyaluronic acid (HA) is a major component of extracellular matrix (ECM) and its over expression in tumor tissues contributes to the increase of interstitial fluid pressure (IFP) and hinders the penetration of nanoparticles into solid tumors.Materials and Methods: We here reported a tumoral microenvironment responsive multistage drug delivery system (NPs-EPI/HAase) which was formed layer by layer via electrostatic interaction with epirubicin (EPI)-loaded PEG-b-poly(2-(diisopropylamino)ethyl methacrylate)-b-poly(2-guanidinoethylmethacrylate) (mPEG-PDPA-PG, PEDG) micelles (NPs-EPI) and hyaluronidase (HAase). In this paper, we focused on the hyaluronidase-combined nanoparticles (NPs-EPI/HAase) for tumor penetration in tumor spheroid and solid tumor models in vitro and in vivo.Results: Our results showed that NPs-EPI/HAase effectively degrade the HA in ECM and facilitate deep penetration of NPs-EPI into solid tumor. Moreover, NPs-EPI mainly employed clathrin-mediated and macropinocytosis-mediated endocytic pathways for cellular uptake and were subsequently directed to the lysosomes for further drug release triggered by proton sponge effect. Compared with NPs-EPI, the HAase coating group showed an enhanced tumoral drug delivery efficacy and inhibition of tumor growth.Conclusion: Overall, our studies demonstrated that coating nanoparticles with HAase can provide a simple but efficient strategy for nano-drug carriers to enhance solid tumor penetration and chemotherapeutic efficacy.Keywords: hyaluronidase, nanoparticles, tumor penetration, ECM

Jisong Zhang, Cheng Han, Fan Yang, Shan Xu, Huihui Hu, Enguo Chen Department of Pulmonary and Critical Care Medicine, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou 310016, People’s Republic of ChinaCorrespondence: Enguo ChenDepartment of Pulmonary and Critical Care Medicine, Sir Run Run Shaw Hospital of Zhejiang University, No. 3 East Qingchun Road, Jianggan District, Hangzhou 310016, People’s Republic of ChinaTel +86 13588706779Email 3195024@zju.edu.cnObjective: A large number of isolation wards were built to screen suspected patients because of the outbreak of coronavirus disease 2019 (COVID-19). The particularity of the isolation wards would lead to more medical resource consumption and heavier hospital control tasks. Therefore, we adopted a vital signs telemetry system in the isolation wards to improve this situation.Materials and Technologies: Twenty sets of vital signs telemetry system were installed in the east district of the isolation area and the wards were used as the telemetry system wards (TSWs). The wards in the west district were used as the routine wards (RW). The daily telephone questionnaire was used to collect the frequency and time of ward rounds by medical staff and lasted for one week.Results: Within one-week survey, the average frequency of RW rounds was 3.00 ± 1.00 times per day, and the average time was 93.57 ± 66.25 min. The daily frequency of RW rounds was 0.428 ± 0.394 times per capita, and the time was 7.88 ± 2.36 min. There was a statistically significant difference in the time of ward rounds per capita, which presented that the daily time of TSW rounds per capita was shorter than that of RW rounds. No security events related to telemetry equipment were found throughout the study.Conclusion: The application of vital signs telemetry system as an alternative to traditional ward monitoring is considered feasible. The use of telemetry system can significantly reduce the consumption of medical resources, the workload of medical staff along with the administration and labor cost for isolation wards. The telemetry system provides sensitive and reliable real-time monitoring for the key indicators used for disease judgment and can make an accurate warning of the patients with disease aggravation in time. Thus, it is worthy of promotion and wide application.Keywords: vital signs telemetry system, oxygen saturation, SpO2, coronavirus disease 2019, COVID-19, cross infection, nosocomial infection

Cheng Xue,1 Yi Cheng,1 Jinyou Wu,1 Kongliang Ke,2 Chundi Miao,2 Enfu Chen,1 Luqing Zhang2 1Department of Endocrinology, Wenling First People’s Hospital, Wenling 317500, People’s Republic of China; 2Department of Anorectal Surgery, Ningbo Hangzhou Bay Hospital, Ningbo 315000, People’s Republic of ChinaCorrespondence: Luqing ZhangDepartment of Anorectal Surgery, Ningbo Hangzhou Bay Hospital, 1155 Binhai 2nd Road, Hangzhouwan New District, Ningbo 315000, People’s Republic of ChinaEmail luqingzhangqqq@sina.comBackground: The role of circular RNA (circRNA) in papillary thyroid cancer (PTC) is largely unknown. This study aims to determine the function and mechanism of circPRMT5 in the regulation of PTC development.Methods: PTC tissues and cell lines were used to determine circPRMT5 expression via quantitative real-time polymerase chain reaction. Small interfering RNA (siRNA) was utilized to knock down circPRMT5. Proliferation was analyzed through CCK8 and colony formation assays. Transwell assay was performed to determine cell migration and invasion. Luciferase assay and RIP assay were carried out to analyze the interaction between circPRMT5 and miR-30c.Results: CircPRMT5 expression was upregulated in PTC tissues and cell lines. And circPRMT5 level was positively linked with advanced stage and lymph node metastasis. CircPRMT5 knockdown inhibited proliferation, migration and invasion while inducing apoptosis. CircPRMT5 worked as a competing endogenous RNA for miR-30c. By inhibiting miR-30c, circPRMT5 promoted the expression of E2F3.Conclusion: Our findings demonstrate that circPRMT5 acts as an oncogenic circRNA to promote PTC progression via regulating miR-30c/E2F3 axis.Keywords: circRNA, papillary thyroid cancer, circPRMT5, miR-30c, E2F3

Ligen Du,1–3 Enping Chen,2 Ting Wu,4 Yunjun Ruan,1 Saizhu Wu1 1Department of Geriatrics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China; 2Department of Cardiology, The Second People’s Hospital of Longgang District, Shenzhen, Guangdong, China; 3Department of Cardiology, Longgang District People’s Hospital of Shenzhen, Guangdong, China; 4Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, China Purpose: Resveratrol (RESV; trans-3,5,4'-trihydroxystilbene) has emerged as a potential new therapeutic for age-related atherosclerotic diseases. However, the effect of RESV on cellular aging and its underlying mechanisms remain unknown. Therefore, the aim of this study was to examine whether RESV can delay cellular aging through upregulation of autophagy. Materials and methods: Human umbilical endothelial vein cells (HUVECs) were divided into four groups: the control group, and the hydrogen peroxide (H2O2) alone, H2O2 + RESV pretreatment, and H2O2 + 3-methyladenine (3-MA) + RESV pretreatment intervention groups. The cell viability was evaluated by a cell counting kit-8 assay. Superoxide dismutase (SOD) activity and intracellular reactive oxygen species (ROS) levels were tested using commercial kits. Senescence-related β-galactosidase activities were detected by immunohistochemical staining. The expression levels of aging-related and autophagy-related markers, including phosphorylated Rb (p-Rb), LC3, and p62, with or without RESV were measured by Western blotting. Results: Pretreatment with 10 µM RESV increased the cell viability and SOD levels. The remarkably higher positive rate of senescence-associated β-galactosidase and increased intracellular ROS levels in the H2O2 treatment group were reversed by treatment with 10 µM RESV. As compared to the H2O2 treatment group, 10 µM RESV could upregulate autophagy through the regulation of p-Rb, LC3, and p62 levels. The anti-aging effect of RESV via an autophagy regulation mechanism was further confirmed by the suppression of these effects with 3-MA treatment. Conclusion: RESV may reverse and delay the aging process of HUVECs via upregulation of autophagy and could be a candidate therapeutic for age-related atherosclerotic diseases. Keywords: oxidative stress, senescence, LC3, p62, p-Rb

Yuefeng Li,1,2,* Xiaofen Zhou,2,* Qiongying Zhang,3 Endong Chen,2 Yihan Sun,2 Danrong Ye,2 Ouchen Wang,2 Xiaohua Zhang,2 Jianxin Lyu1 1Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China; 2Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; 3Pathology Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China *These authors contributed equally to this work Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma, which is associated with a high incidence of lymph-node metastasis. Multiple biomarkers have been identified for the precise diagnosis of PTC at an early stage. However, their role in PTC remains poorly elucidated. Previously, we reported that lipase H (LIPH), a membrane-bound protein, was highly expressed in PTC. This study aimed to fully elucidate the causal role of LIPH in the development of PTC and investigated its relationship with lymph-node metastasis in PTC. Materials and methods: Quantitative reverse transcription PCR and immunohistochemistry were used to measure the mRNA and protein expression levels of LIPH in 45 and 6 pairs of PTC tissues and adjacent normal tissues, respectively. Clinical tissue data of 504 PTC tissues and 60 normal thyroid tissues from The Cancer Genome Atlas database were used to analyze the correlation between LIPH expression level and clinical features in PTC. siRNAs were used to knock down genes, while plasmids were used to overexpress genes. Two PTC cell lines (KTC-1 and BCPAP) were used in subsequent cytological function studies. In addition, a hypoxia stress model was constructed using cobaltous chloride hexahydrate reagent, and the protein expression level of the corresponding biomarkers was measured by Western blotting. Results: This study revealed that high expression of LIPH in PTC was closely associated with lymph-node metastasis. Our cellular function experiments indicated that LIPH positively correlated with the malignant behavior of PTC cell lines. We further confirmed the role of LIPH in hypoxia and its relationship with the epithelial–mesenchymal transition pathway in PTC. Conclusion: LIPH plays an important role in PTC oncogenesis and development, especially in lymph-node metastasis. It can be regarded as a biomarker for the diagnosis and treatment of PTC in the near future. Keywords: papillary thyroid carcinoma, hypoxia, metastasis, epithelial–mesenchymal transition

Yihan Sun,* Danrong Ye,* Yuefeng Li, Endong Chen, Rutian Hao, Yefeng Cai, Qingxuan Wang, Ouchen Wang, Xiaohua Zhang Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 32500, China *These authors contributed equally to this work Background: In recent years, the incidence of thyroid cancer (TC), the most common endocrine malignancy, has been increasing. Emerging evidence indicates that the CUT/CUX/CDP family of proteins can play an important role in tumor development and progression by regulating many cancer-related functions. However, the molecular functions of CUX2 in TC remain unknown. Methods: In this study, we used a series of loss-of-function experiments and Western blot analysis to investigate the function of CUX2 in TC and the mechanisms involved. Results: Our data revealed that CUX2 expression levels were upregulated in papillary thyroid cancer (PTC). Functionally, CUX2 silencing significantly inhibited PTC cell line (KTC-1 and BCPAP) proliferation, colony formation, migration, invasion, and apoptosis. Furthermore, CUX2 induced epithelial–mesenchymal transition (EMT) and influenced the phosphorylation of AKT and mTOR in the PI3K–AKT–mTOR pathways.Conclusion: In summary, CUX2 may function as a tumor promoter in TC. Keywords: papillary thyroid carcinoma, CUX2, oncogene

Endong Chen,1 Qiaolin Wu,2 Yixiang Jin,1 Wenxu Jin,1 Yefeng Cai,1 Qingxuan Wang,1 Xiaohua Zhang,1 Ouchen Wang,1 Quan Li,1 Zhouci Zheng3 1Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Head and Neck Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China Objectives: Few studies on prognostic indicators for primary thyroid lymphoma (PTL) have been presented due to the uncommon nature of the tumor. This is the first study to explore the independent prognostic factors in the 2 PTL subtypes.Methods: We retrospectively reviewed 1,653 cases of PTL. The cases comprised 28 Chinese patients from a local cohort and 1,625 patients from the Surveillance, Epidemiology, and End Results database from 1973 to 2013. Statistical analysis was performed to determine the demographics and prognostic factors of PTL patients.Results: The disease-specific survival (DSS) and prognostic indicators were significantly different between patients with extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) and patients with diffuse large B-cell lymphoma (DLBCL). Patients with MALT lymphoma were younger (P=0.011) and had lower clinical stage (P=0.014) compared to patients with DLBCL. Cox regression analysis revealed that age, treatment modalities employed, clinical stage, and number of other types of cancer were independent prognostic factors for DLBCL patients.Conclusion: PTL demonstrates specific clinical features and is associated with a relatively good prognosis. Older age is associated with poor DSS in both MALT patients and DLBCL patients. Additionally, combination of different treatment modalities is associated with improved DSS in DLBCL patients. Keywords: primary thyroid lymphoma, SEER database, disease-specific survival, combined modality treatment, prognosis

Deting Xue,1,* Erman Chen,1,* Huiming Zhong,2,* Wei Zhang,1 Shengdong Wang,1 Muhammad Umar Joomun,1 Tianyi Yao,3 Yanbin Tan,1 ShiSheng Lin,3 Qiang Zheng,1 Zhijun Pan1 1Department of Orthopaedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, People’s Republic of China; 2Department of Emergency, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, People’s Republic of China; 3Department of Information Science and Electronic Engineering and State Key Laboratory of Modern Optical Instrumentation, Zhejiang University, Hangzhou 310027, People’s Republic of China *These authors contributed equally to this work Background: The osteo-immunomodulatory properties of biomaterials play an important role in the outcomes of bone regeneration. Graphene oxide (GO) has been widely applied in many research fields due to its unique properties. However, the immunomodulatory properties of GO as a biomaterial for bone tissue engineering are still unclear. Materials and methods: In this study, we evaluated the Inflammatory response of RAW264.7 cells influenced by GO. Then the osteogenic differentiation of BMSCs, and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) by stimulation with GO/RAW 264.7-conditioned culture medium were accessed. We also further investi­gated the possible mechanisms underlying the osteo- and angio-immunomodulatory effects of GO. Results: Our results showed that GO stimulates the secretion of oncostatin M, tumor necrosis factor alpha and other factors through the nuclear factor-κB pathway. GO/RAW264.7-conditioned medium promoted the osteogenic differentiation of BMSCs, stimulated upregulation of the HUVECs of vascular-related receptors, and promoted their tube formation in vitro. Conclusion: In conclusion, our research shows that GO, as a biomaterial, can induce the formation of a beneficial osteo-immunomodulatory environment and is a promising biomaterial for bone tissue engineering. Keywords: graphene oxide, osteo-immunomodulatory, bone marrow mesenchymal stem cells, osteogenesis, angiogenesis, RAW264.7 cells, HUVECs

Quan Li,* Wen-Xu Jin,* Yi-Xiang Jin, Zhou-Ci Zheng, Xiao-Fen Zhou, Qing-Xuan Wang, Dan-Rong Ye, Yi-Han Sun, Xiao-Hua Zhang, Ou-Chen Wang, En-Dong Chen, Ye-Feng Cai Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China *These authors contributed equally to this work Aim: To investigate the clinical effects of MUC1 on papillary thyroid cancer (PTC) and explore the relationship between MUC1 expression and BRAF mutation. Methods: The data of 69 patients subjected to fine-needle aspiration biopsy in our hospital and 486 patient data downloaded from The Cancer Genome Atlas (TCGA) database were used. Univariate and multivariate analyses were performed.Results: The results on the 486 patients recorded in the TCGA indicated that high MUC1 expression was independently related to BRAF mutation, lymph node metastasis (LNM), and unifocal type. In the 69 fine-needle aspiration biopsy patients with PTC, high MUC1 expression was significantly related to LNM and extrathyroid extension (ETE). The result of Pearson’s correlation coefficient showed that BRAF mutation and MUC1 expression were moderately correlated. Moreover, in the subgroup with low MUC1 expression, the patients with BRAF mutation had higher ETE frequency and LNM than those without BRAF mutation. In the subgroup with BRAF mutation, patients with high MUC1 expression exhibited higher ETE frequency than those with low MUC1 expression, and high MUC1 expression occurred in older patients. In the subgroup with BRAF wild-type mutation, patients with high MUC1 expression had a higher incidence of ETE and LNM than those with low expression.Conclusion: We demonstrated that the MUC1 is an important oncogene in PTC and may have great significance on therapeutic cancer vaccine development.Keywords: MUC1, BRAF mutation, papillary thyroid cancer, prognosis, lymph node metastasis, extrathyroid extension

Mark J Russo,1,2 Alexander Iribarne,3 Emily Chen,2 Ashwin Karanam,2 Chris Pettit,2 Fabio Barili,4 Atman P Shah,5 Craig R Saunders1,2 1Barnabas Health Hospital, Newark/Livingston, NJ, USA; 2Barnabas Health Cardiovascular Clinical Research Center, Newark, NJ, USA; 3Duke University, Durham, NC, USA; 4Department of Cardiovascular Surgery, S Croce Hospital, Cuneo, Italy; 5University of Chicago, Chicago, IL, USA Objectives: This study examines outcomes in a national sample of patients undergoing isolated aortic valve replacement (AVR) for aortic stenosis, with particular focus on advanced-age patients and those with extreme severity of comorbid illness (SOI). Methods: Data were obtained from the Nationwide Inpatient Sample and included all patients undergoing AVRs performed from January 1, 2006 to December 31, 2008. Patients with major concomitant cardiac procedures, as well as those aged 85% of patients undergoing isolated AVR for aortic stenosis. Conversely, in patients classified as having extreme SOI, surgical therapy is associated with exceedingly high inpatient mortality, low home discharge rates, and high resource utilization, particularly in the advanced age group. Keywords: cardiac surgery, outcomes, risk stratification

Harold E Bays,1 Eliot A Brinton,2 Joseph Triscari,3 Erluo Chen,3 Darbie Maccubbin,3 Alexandra A MacLean,3 Kendra L Gibson,3 Rae Ann Ruck,3 Amy O Johnson-Levonas,3 Edward A O’Neill,3 Yale B Mitchel3 1Louisville Metabolic & Atherosclerosis Research Center (L-MARC), Louisville, KY, USA; 2Utah Foundation for Biomedical Research, Salt Lake City, UT, USA; 3Merck & Co, Inc., Whitehouse Station, NJ, USA Background: The degree of glycemic control in patients with type 2 diabetes mellitus (T2DM) may alter lipid levels and may alter the efficacy of lipid-modifying agents. Objective: Evaluate the lipid-modifying efficacy of extended-release niacin/laropiprant (ERN/LRPT) in subgroups of patients with T2DM with better or poorer glycemic control. Methods: Post hoc analysis of clinical trial data from patients with T2DM who were randomized 4:3 to double-blind ERN/LRPT or placebo (n=796), examining the lipid-modifying effects of ERN/LRPT in patients with glycosylated hemoglobin or fasting plasma glucose levels above and below median baseline levels. Results: At Week 12 of treatment, ERN/LRPT significantly improved low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol, triglycerides, and lipoprotein (a), compared with placebo, with equal efficacy in patients above or below median baseline glycemic control. Compared with placebo, over 36 weeks of treatment more patients treated with ERN/LRPT had worsening of their diabetes and required intensification of antihyperglycemic medication, irrespective of baseline glycemic control. Incidences of other adverse experiences were generally low in all treatment groups. Conclusion: The lipid-modifying effects of ERN/LRPT are independent of the degree of baseline glycemic control in patients with T2DM (NCT00485758). Keywords: lipid-modifying agents, hyperglycemia, LDL, HDL, triglycerides

Michel Farnier,1 Erluo Chen,2 Amy O Johnson-Levonas,2 Christine McCrary Sisk,2 Yale B Mitchel21Point Médical, Dijon, France; 2Merck and Co, Inc., Whitehouse Station, NJ, USABackground: Statins modify correlations between apolipoprotein B (apoB) and low-density lipoprotein cholesterol (LDL-C) and apoB and non-high-density lipoprotein cholesterol (non-HDL-C); however, it is not known whether niacin-based therapies have similar effects.Objective: To evaluate the effects of extended-release niacin (ERN)/laropiprant (LRPT), simvastatin (SIMVA), and ERN/LRPT + SIMVA (pooled ERN/LRPT + SIMVA) on apoB:LDL-C and apoB:non-HDL-C correlations in dyslipidemic patients.Methods: This post-hoc analysis of a 12-week study evaluated the apoB:LDL-C and apoB:non-HDL-C correlations in dyslipidemic patients randomized equally to double-blind ERN/LRPT 1 g/20 mg, SIMVA 10, 20, or 40 mg, or ERN/LRPT 1 g/20 mg + SIMVA (10, 20, or 40 mg) once daily for 4 weeks. At week 5, doses were doubled in all groups except SIMVA 40 mg (unchanged) and ERN/LRPT 1 g/20 mg + SIMVA 40 mg (switched to ERN/LRPT 2 g/40 mg + SIMVA 40 mg). Simple linear regression analyses were used to calculate LDL-C and non-HDL-C levels corresponding to known apoB baseline values (ie, in untreated patients) and following treatment.Results: The apoB:LDL-C and apoB:non-HDL-C correlations were higher and the predicted LDL-C and non-HDL-C levels for a known apoB value were considerably lower following treatment with ERN/LRPT, SIMVA and ERN/LRPT + SIMVA compared with untreated patients at baseline.Conclusion: Greater dissociation of apoB, LDL-C, and non-HDL-C targets occur following treatment with ERN/LRPT, SIMVA, and ERN/LRPT + SIMVA in patients with dyslipidemia. The achievement of more aggressive LDL-C and non-HDL-C goals in patients receiving lipid-modifying therapy may further reduce coronary risk by normalizing apoB-containing atherogenic lipoproteins.Keywords: apoB, LDL-C, non-HDL-C

Marcelo Ayala, Enping ChenGlaucoma Department, St Erik Eye Hospital, Karolinska Institutet, Stockholm, SwedenBackground and objective: The aim of the present study was to compare intraocular pressure (IOP) reduction and inflammation after selective laser trabeculoplasty (SLT) treatment in patients suffering from primary open angle (POAG) vs pseudoexfoliative (PXFG) glaucoma.Study design/patients and methods: Sixty patients (60 eyes) participated in the study. Glaucoma patients (POAG or PXFG) scheduled for treatment with SLT were included. Inflammation was measured with a laser flare meter (Kowa FM-500). Measurements were made before SLT and 2 hours, 1 week, and 1 month after SLT treatment. IOP was also checked at the same time intervals.Results: Inflammation after SLT showed no significant difference between the groups (t-test, before: P = 0.16; 2 hours: P = 0.14; 1 week: P = 0.12; and 1 month: P = 0.36). IOP reduction was the same in both groups (t-test, P = 0.27).Conclusion: SLT safely reduces IOP in both POAG and PXFG. Pseudoexfoliation does not seem to be a risk factor for post-laser complications.Keywords: glaucoma, pseudoexfoliation, laser, inflammation, intraocular pressure