bluuebunny/crossref_metadata_2025 huggingface dataset:
Household income and LDL-C goal attainment in patients with diabetes and dyslipidemia in a Canadian dataset
Authors: Farahani Pendar , Levine Mitchell
Published: May 2017

Purpose: There is evidence of a social disparity pertaining to the epidemiology and burden of illness of diabetes. The purpose of this study was to assess the association between household income strata and therapeutic goal achievement rates for LDL-cholesterol (LDL-C) (< 2.5 mmol/L) in Canadian diabetic patients.

Methods: Data (household income, cardiovascular risk factors, drug profile, clinical and laboratory variables) were obtained from a previous cross-sectional study of diabetic patients who filled a prescription for a lipid-lowering drug in selected pharmacies across Canada. Telephone interviews were conducted. Physicians, identified by the participating patients, were requested to complete a short questionnaire for clinical data. Achievement of LDL-C goals according to the Canadian diabetes guidelines were assessed and incorporated into regression models corresponding to household income strata.

Results: Seven household income strata were defined in the cohort (from less than 20,000 CDN$, up to 70,000 CDN$ by increments of 10,000 CDN$). LDL-C goals were attained in 34% of patients in the total cohort. There were no significant differences amongst household income strata for LDL-C goal achievement (p = 0.80). There were no significant differences in patient characteristics (age, sex, BMI) and cardiovascular risks according to the household income strata in this cohort, except age more than 65 in the lower income strata.

Conclusion: This study demonstrates that household income was not a factor to achieve therapeutic goals for LDL-C for patients with diabetes in this dataset, although goal attainment was less than ideal overall. Future studies should address limitations of this work including small sample size, recruitment bias and lack of data on third party insurance coverage.
The Effect of Acute Allergic Reactions on Diastolic Heart Function
Authors: Kaya Oguz Kaan , Dagli Necati , Yildiz Mustafa , Karaca Ilgin , Ustundag Bilal , Kuzu Zulfiye , Solmaz Hatice , Dogdu Orhan
Published: May 2017

Purpose: Diastolic heart failure is characterized by the presence of heart failure symptoms despite preserved systolic function. Cytokines released during allergic reactions may impair diastolic heart function, either through their direct toxic effects or by inducing coronary artery spasm. The purpose of this study was to examine the effects of acute allergic reactions on diastolic heart function.

Methods: Fifty patients, randomly selected from those who were admitted to the emergency room between May 2010 and December 2010 with the complaints of rash and itching, and who were subsequently diagnosed with allergic reactions based on the clinical and laboratory findings, were included in the study as the allergy group. Thirty healthy volunteers, in whom the diagnosis of allergy was ruled out based on the clinical and laboratory data, were use as the control group. Diastolic heart functions were evaluated in patients presenting with allergic reaction as well as in control subjects.

Results: There was no significant difference between the two groups in terms of basal systolic functions, diameters of the cavities and wall thicknesses, and biochemical parameters. Color M mode flow progression velocities, E ratios, E/A ratios and mitral lateral annulus tissue Doppler velocities measured by echocardiography at Day 0 and Day 5 were significantly altered in the allergy group (p < 0.05).

Conclusion: Impairment in diastolic functions was observed following acute allergic reactions. Acute allergic reactions could be a cause of mortality and morbidity if they lead to the development of diastolic heart failure.
Decreased expression of GRIM-19 and its association with high-risk HPV infection in cervical squamous intraepithelial neoplasias and cancer
Authors: Cheng Yong , Zhang Hong-yan , Zhou Ying , Tao Feng , Yu Yong-hua
Published: May 2017

Purpose: GRIM-19 has been shown to be down-regulated in cervical cancers. This study investigated the expression of GRIM-19 in cervical intra-epithelial neoplasias and its association with high-risk human papillomavirus (HR-HPV) infection.

Methods: The expression of GRIM-19 was assessed in cervical exfoliated cells and cervical intra-epithelial neoplasia tissues by immunohistochemistry, and the level of GRIM-19 was also evaluated by Western blotting using cervical exfoliated cells. HR-HPV infection of cervical exfoliated cells was detected by HC II.

Results: GRIM-19 is predominantly expressed in the cytoplasm of the middle layer of normal cervical epithelial cells, whereas the surface layer cells of the normal cervix showed no GRIM-19 expression. The expression of GRIM-19 gradually decreased from atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) to squamous cell carcinoma (SCC); a pattern which was also observed in cervical intra-epithelial neoplasias tissues. The reduced expression of GRIM-19 was correlated with HR-HPV infection.

Conclusion: GRIM-19 may regulate the differentiation of normal cervical tissue, and a decrease in GRIM-19 may be the result of HR-HPV infection, which in turn leads to the malignant transformation of the cells.
Effects of Hormone Replacement Therapy on Plasma and Tissue Fibrinolytic Activity in a Rat Model of Surgically Induced Menopause
Authors: Topcuoglu Ata , Albayrak Mustafa , Erman Hayriye , Balci Huriye , Karakus Mesut , Coban Ilker , Uzun Hafize
Published: May 2017

Purpose: The purpose of this study was to analyze the effects of estrogen deficiency and hormone replacement therapy (HRT) on fibrinolytic activity in a rat mode of surgically-induced menopause.

Methods: Twelve-week-old, sexually mature female Sprague-Dawley rats, each weighing 200–250 g, were randomly divided into four groups: (1) sham-operated group, (2) ovariectomy group, (3) ovariectomy group followed by oral administration of daily 17β-estradiol (0.02 mg/kg/day) (E2) + norethisterone acetate (0.01 mg/kg/day), and (4) ovariectomy group followed by oral administration of daily 17β-estradiol (0.01 mg/kg/day) + drospirenone (0.02 mg/kg/day). Tissue plasminogen activator (tPA) antigen, plasminogen activator inhibitor-1 (PAI-1) antigen, and PAI-1/tPA levels were measured as markers of fibrinolysis in plasma and liver and brain tissue.

Results: Compared with sham-operated rats, ovariectomized rats showed higher levels of fibrinolytic activity; however, the increased fibrinolytic activity in plasma and liver tissue was significantly reduced by HRT regimens. No change was observed in the levels of fibrinolytic activity in brain tissue.

Conclusions: HRT showed beneficial effects by decreasing fibrinolytic activity related to surgically-induced menopause. Short-term HRT treatment was associated with a shift in the procoagulant-anticoagulant balance toward a procoagulant state.
Accelerometer-based measures of sedentary behavior and cardio-metabolic risk in active older adults
Authors: Chase Jocelyn M , Lockhart Christine K , Ashe Maureen C , Madden Kenneth M
Published: May 2017

Purpose: Sedentary behavior has been proposed as an independent cardio-metabolic risk factor even in adults who are physically active through recreational activity. Because little is known about the metabolic effects of sedentariness in seniors, the relationship between sedentary behavior and cardio-metabolic risk was examined in physically active older adults.

Methods: Fifty-four community dwelling men and women > 65 years of age (mean 71.5 years) were enrolled in this cross-sectional observational study. Subjects were in good health and free of known diabetes. Activity levels (sedentary, light, moderate to vigorous activity time per day) were recorded with accelerometers worn continuously for 7 days. Cardio-metabolic risk factors measured consisted of the American Heart Association diagnostic criteria for metabolic syndrome (waist circumference, triglycerides, high-density lipoprotein, systolic blood pressure and fasting glucose) as well as low-density lipoprotein (LDL). The relationships between activity measures and cardio-metabolic risk factors were examined. Significant variables were then entered into a stepwise multivariate regression model.

Results: All but one subject achieved exercise levels recommended by the American College of Sports Medicine. The average proportion of time spent at a sedentary activity level each day was 72.7%. From the regression analysis, the only significant association found between cardio-metabolic risk outcomes and activity predictors was between LDL and sedentary time, with LDL detrimentally associated with average sedentary time per day (Standardized Beta Correlation Coefficient 0.302, p < 0.05).

Conclusion: Sedentary behavior is associated with an adverse metabolic effect on LDL in seniors, even those who meet guideline recommendations for an active “fit” adult.
Rapamycin reduces renal hypoxia, interstitial inflammation and fibrosis in a rat model of unilateral ureteral obstruction
Authors: Liu Chun-feng , Liu Hing , Fang Yi , Jiang Su-hua , Zhu Jia-ming , Ding Xiao-qiang
Published: May 2017

Purpose: The purpose of this study was to explore effects of rapamycin on renal hypoxia, interstitial inflammation and fibrosis, and the expression of transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF), Flk-1 and Flt-1 in a rat model of unilateral ureteral obstruction (UUO).

Methods: Male Sprague-Dawley rats (n=36) were randomly divided into three groups (n=12 per group): sham surgery, UUO and UUO plus rapamycin (0.2 mg/kg/d). Serum creatinine (Scr), blood urea nitrogen, uric acid, triglycerides, cholesterol and 24-h urine protein levels were measured. The extent of interstitial fibrosis was determined by Masson's trichrome staining. ED-1 positive macrophages, type III collagen, hypoxia, TGF-1, VEGF, Flk-1, and Flt-1 mRNA and protein expressions were detected using immunohistochemical staining, real-time PCR and Western blot.

Results: UUO induced an elevation in Scr, renal hypoxia, inflammation, interstitial fibrosis, TGF-β1, VEGF, Flk-1, and Flt-1 mRNA and protein expression levels (P < 0.05). Rapamycin alleviated the UUO-induced renal hypoxia, infiltration of inflammatory cells and tubulointerstitial fibrosis (at days 3 and 7). Rapamycin also down-regulated the UUO-induced elevated expression levels of TGF-β1 and Flt-1 mRNA and protein (P < 0.05). Rapamycin decreased VEGF mRNA and protein expression at day 3, and increased Flk-1 mRNA and protein expression at day 7, compared with the UUO group (P < 0.05).

Conclusion: Rapamycin shows beneficial effects by reducing UUO-induced renal hypoxia, inflammation and tubulointerstitial fibrosis.
Scientific overview: CSCI-CITAC Annual General Meeting and Young Investigator’s Forum 2013
Authors: Antoun Ghadi , Keow Jonathan , Ram Véronique D , Thornton Christina , Wang Xin , Yoon Ju-Yoon
Published: May 2017

The 2013 joint Canadian Society of Clinician Investigators (CSCI)–Clinical Investigator Trainee Association of Canada/Association des cliniciens-chercheurs en formation du Canada (CITAC/ACCFC) annual general meeting(AGM) was held in Ottawa, September 2013. The symposium focused on “Applications of the ‘omics’ to Clinical Practice”, with presentations from Drs. William T. Gibson (University of British Columbia), Julie Ho (University of Manitoba) and David Hwang (University of Toronto), discussing topics of genome, proteome and the microbiome, respectively.

Other highlights from the 2013 AGM include presentations by Dr. Salim Yusuf (McMaster University, 2013 CSCI-RCPSC Henry Friesen Award winner), Dr. Gary Lewis (University of Toronto, 2013 CSCI Distinguished Scientist Award winner) and Dr. Michael Taylor (University of Toronto, 2013 Joe Doupe Award winner). The CSCI/CITAC/Friends of CIHR Joint Symposium consisted of presentations from Drs. John Bell (University of Ottawa), Dan Drucker (University of Toronto) and Heather J. Dean (University of Manitoba). Finally, the meeting ended with the presentation “The Power of an Idea to Bring Ideas to Power” by Dr. Harvey V. Fineberg (President, U.S. Institute of Medicine), the winner of the 2013 Henry Friesen International Prize.

Also presented at the conference was research by clinician investigator (CI) trainees from across Canada; ie., those enrolled in MD/MSc, MD/PhD or Clinician Investigator Program(CIP) programs. Canadian trainees’ research extended beyond the pillar of biomedical research, covering the spectrum between basic and clinical research, with a focus on the causes of significant morbidity and mortality for Canadians, including cancers, infectious diseases and other maladies. It is this research that we have summarized in this review.
Metformin reduces circulating malondialdehyde-modified low-density lipoprotein in type 2 diabetes mellitus
Authors: Ohira Masahiro , Yamaguchi Takashi , Saiki Atsuhito , Ban Noriko , Kawana Hidetoshi , Nagayama Daiji , Nagumo Ayako , Murano Takeyoshi , Shirai Kohji , Tatsuno Ichiro
Published: May 2017

Purpose: Type 2 diabetes is known to be associated with increasing cardiovascular mortality. Malondialdehyde-modified LDL (MDA-LDL) is an oxidized LDL and is increased in patients with diabetes or hypertriglyceridemia. Elevated MDA-LDL has been reported to be a risk factor of atherosclerosis or cardiovascular disease. Sitagliptin is a dipeptidyl peptidase-4 inhibitor and a new class of hypoglycemic agents. In this study, the effects of increasing the dose of metformin and add-on sitagliptin on MDA-LDL were examined in type 2 diabetes patients.

Methods: Seventy patients with type 2 diabetes, inadequately controlled despite on-going treatment with metformin 500 mg/day, were enrolled in this randomized controlled trial. The patients received additional metformin (500 mg/day) or sitagliptin (50 mg/day) for 6 months, and changes in metabolic parameters including MDA-LDL were evaluated.

Results: After 6 months of treatment, add-on sitagliptin (n=35) improved fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) to significantly greater extent than increasing the dose of metformin (n=35). There were no differences in total cholesterol and low-density lipoprotein cholesterol levels between two groups. MDA-LDL levels (mean±S.E.) decreased significantly with increasing the dose of metformin (from 94.40±6.35 to 77.83±4.74 U/L, P < 0.005), but remained unchanged with add-on sitagliptin treatment (from 89.94±5.59 to 98.46±6.78 U/L, p > 0.05). Multiple linear regression analysis identified increasing the dose of metformin treatment as the only independent factor associated with decreased MDA-LDL (β coefficient 0.367, P < 0.0119), and no significant correlation between change in MDA-LDL and fasting blood glucose or HbA1c.

Conclusion: These results suggest that increasing the dose of metformin improves serum MDA-LDL levels in type 2 diabetes mellitus.
Proceedings from the 5th Annual University of Calgary Leaders in Medicine Research Symposium
Authors: Thornton Christina S , Keough Michael B , Roberts Jodie I , Yipp Bryan , Hollenberg Morley , Bau Jason T , Peplowski Michael A , Beck Paul L
Published: May 2017

On November 8, 2013, the Leaders in Medicine (LIM) program hosted the 5th Annual Research Symposium. Dr. Jerrold Ellner, Chief of the Infectious Diseases section at Boston Medical Centre and Professor of Medicine at Boston University School of Medicine, was the keynote speaker and presented his lecture entitled “Tuberculosis – Past, Present and Future”. The LIM symposium gives a forum for LIM as well as non-LIM medical students to present their research work as either an oral or poster presentation. There were a total of 53 abstracts presented and five oral presentations. The symposium was attended by over 100 students and more than 30 staff members.

The oral presentations included

• Amrita Roy, Aboriginal identity, ethnic minority status, and prenatal depressive symptoms in a longitudinal pregnancy cohort study in Alberta.

• David Nicholl, Obstructive sleep apnea treatment with continuous positive airway pressure decreases intraglomerular pressure and alters renal sensitivity to angiotensin.

• James Cotton, An assemblage A Giardia cathepsin B protease degrades interleukin-8 and attenuates neutrophil chemotaxis.

• Krystyna Ediger, Alexander Arnold and Emily Shelton, Rebuilding the Calgary Student Run Clinic: A Model for Sustainability.

• Sarah MacEachern, Inhibiting inducible nitric oxide synthase restores electrogenic ion transport in experimental IBD: a novel role for enteric glia.

See the article on the University of Calgary Leaders in Medicine Program, “A Prescription that Addresses the Decline of Basic Science Education in Medical School” in this same issue of CIM for more details on the program. In short, the LIM Research Symposium has the following objectives: (1) to showcase the impressive variety of projects undertaken by students in the LIM Program as well as U of C medical students; (2) to encourage medical student participation in research and special projects; and, (3) to inform students and faculty about the diversity of opportunities available for research and special projects during medical school and beyond.

The following abstracts are those that were put forward for publication.
Serum total bilirubin and long-term outcome in patients undergoing percutaneous coronary intervention
Authors: Zhang Xiao-Juan , Sun Tong-Wen , Kan Quan-Cheng , Yao Hai-Mu , Wan You-Dong , Yao Rui , Guan Fang-Xia , Guo Chang-Qing , Zhang Shu-Guang , Sun Wen-Ju , Wang Le-Xin
Published: May 2017

Purpose: The purpose of this study was to investigate the associated between serum total bilirubin (STB) levels and long-term outcomes in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI).

Methods: A total of 1,273 consecutive patients were enrolled. Patients were grouped according to their baseline STB levels: Group 1 (STB < 3.4 μmol/L), Group 2 (3.4 μmol/L ≤ STB ≤ 10.3 μmol/L), Group 3 (10.3 μmol/L < STB ≤ 17.1 μmol/L), and Group 4 (STB < 17.1 μmol/L) and the rate of major adverse cardiovascular events (MACE) was determined

Results: A total of 1,152 patients were successfully followed up (90.5%) for a mean period of 30 ± 5 months, including 187 patients experiencing a major adverse cardiovascular event (MACE: death from any cause, myocardial infarction, repeat revascularization or readmission). The MACE rate in Groups 3 and 4 was lower than in Groups 1 and 2 (P < 0.01). After adjusted the confounding factors with Cox regression analysis, the MACE rates in Groups 2-4 were still lower than in Group 1 (Group 2, RR=0.293, 95% CI 0.167-0.517, P < 0.01; Group 3, RR=0.142, 95% CI 0.065-0.312, P < 0.01; Group 4, RR=0.134, 95% CI 0.071-0.252, P < 0.01). The cumulative survival rates of Groups 3 and 4 were higher than that of Groups 1and 2 (P < 0.01).

Conclusions: High STB concentration is associated with lower MACE in patients with ACS after PCI.
Increased epicardial adipose tissue volume is associated with PR interval prolongation
Authors: Hung Wei-Chin , Tang Wei-Hua , Wang Chao-Ping , Lu Li-Fen , Chung Fu-Mei , Lu Yung-Chuan , Hsu Chia-Chang , Tsai I-Ting , Jhuo Shih-Jie , Lai Wen-Ter , Lee Yau-Jiunn , Yu Teng-Hung
Published: May 2017

Purpose: Epicardial fat is visceral adipose tissue that possesses inflammatory properties. Inflammation and obesity are associated with cardiovascular disease and arrhythmogenesis, but little is known about the relationship between epicardial fat and PR-Interval prolongation. The purpose of this study was to investigate the association between epicardial adipose tissue (EAT) volume and PR-interval prolongation as assessed by computed tomography (CT) and Twelve-lead ECGs.

Methods: Patients (n=287) were referred for 64-slice CT for exclusion of coronary artery disease and EAT volumes were determined. Twelve-lead ECGs were obtained from each subject and were evaluated by two independent readers.

Results: Patients with significant PR interval prolongation had higher median EAT volume than patients with normal PR interval. Statistically significant correlations were observed between the EAT volume and the PR interval (p = 0.183, p = 0.003), and QRS duration (p = 0.144, p = 0.018). Multivariate and trend analyses confirmed that EAT volume was independently associated with the presence of PR interval prolongation. The receiver operator characteristics curve of EAT volume showed that an EAT volume >144.4 cm³ was associated with PR interval prolongation.

Conclusion: This study indicates that EAT volume is highly associated with PR interval prolongation. Whether epicardial fat plays a role in the pathogenesis of PR interval prolongation requires future investigation.
High resolution multi-arterial phase MRI improves lesion contrast in chronic liver disease
Authors: Clarke Sharon E , Saranathan Manojkumar , Rettmann Dan W , Hargreaves Brian A , Vasanawala Shreyas S
Published: May 2017

Purpose: To determine the reliability of arterial phase capture and evaluate hypervascular lesion contrast kinetics with a combined view-sharing and parallel imaging dynamic contrast-enhanced acquisition, DIfferential Sub-sampling with Cartesian Ordering (DISCO), in patients with known chronic liver disease.

Methods: A retrospective review of 3T MR images from 26 patients with known chronic liver disease referred for hepatocellular carcinoma surveillance or post-treatment follow up was performed. After administration of a gadolinium-based contrast agent, a multiphasic acquisition was obtained in a 28 s breath-hold, from which seven sequential post-contrast image volumes were reconstructed.

Results: The late arterial phase was successfully captured in all cases (26/26, 95% CI 87-100%). Images obtained 26 s post-injection had the highest frequency of late arterial phase capture (20/26) and lesion detection (23/26) of any individual post-contrast time; however, the multiphasic data resulted in a significantly higher frequency of late arterial phase capture (26/26, p=0.03) and a higher relative contrast (5.37+/-0.97 versus 7.10+/-0.98, p < 0.01).

Conclusion: Multiphasic acquisition with combined view-sharing and parallel imaging reliably captures the late arterial phase and provides sufficient temporal resolution to characterize hepatic lesion contrast kinetics in patients with chronic liver disease while maintaining high spatial resolution.
Letter of Retraction
Authors: CIM Editor
Published: May 2017

It has come to our attention that the a manuscript published in CIM: JianXin J, Cha Y, ZhiPeng L, Jie X, Hao Z, Meiyuan C, ChengYi S “GOLP3 is a predictor of survival in patients with hepatocellular carcinoma” Clin Invest Med. 2014 Aug 1;37(4):E233-42
contains text identical to a manuscript published in Tumour Biology: Hu GS, Li YQ, Yang YM, Shi W, Liao AJ, Yao YH, Zeng B, Yuan J “High expression of Golgi phosphoprotein-3 is associated with poor survival in patients with hepatocellular carcinoma” Tumour Biol. 2014 Sep;35(9):8625-32. doi: 10.1007/s13277-014-2105-8. Epub 2014 May 28. For this reason, the publication in CIM has been retracted.

Jonathan Angel, MD Editor, CIM
Scientific overview: CSCI-CITAC Annual General Meeting and Young Investigators’ Forum 2014
Authors: Keow Jonathan , Zhao Eric , Samuel Nardin , Dey Ayan , Schneider Raphael , Chen Michael , Wang Xin
Published: May 2017

The Canadian Society of Clinician Investigators (CSCI) and Clinical Investigator Trainee Association of Canada/Association des cliniciens-chercheurs en formation du Canada (CITAC/ACCFC) annual general meeting (AGM) was held in Toronto during November 21-24, 2015 for the first time in conjunction with the University of Toronto Clinician-Investigator Program Research Day.

The overall theme for this year’s meeting was the role of mentorship in career development, with presentations from Dr. Chaim Bell (University of Toronto), Dr. Shurjeel Choudhri (Bayer Healthcare), Dr. Ken Croitoru (University of Toronto), Dr. Astrid Guttman (University of Toronto), Dr. Prabhat Jha (University of Toronto) and Dr. Sheila Singh (McMaster University).

The keynote speakers of the 2014 AGM included Dr. Qutayba Hamid, who was presented with the Distinguished Scientist Award, Dr. Ravi Retnakaran, who was presented with the Joe Doupe Award, and Dr. Lorne Babiuk, who was the CSCI-RCPSC Henry Friesen Award winner.

The highlight of the conference was, once again, the outstanding scientific presentations from the numerous clinician investigator (CI) trainees from across the country who presented at the Young Investigators’ Forum. Their research topics spanned the diverse fields of science and medicine, ranging from basic science to cutting-edge translational research, and their work has been summarized in this review.

Over 120 abstracts were presented at this year’s meeting. This work was presented during two poster sessions, with the six most outstanding submitted abstracts presented in the form of oral presentations during the President’s Forum.
When positive studies of novel therapies are subsequently nullified: cumulative meta-analyses in preeclampsia
Authors: Etwel Fatma , Koren Gideon
Published: May 2017

Purpose: The purpose of this study was to examine changes over time in the pooled effect size of randomized, double-blinded, placebo-controlled trials (RCTs) published on the protective effects of antioxidants and low dose aspirin against preeclampsia, and to identify determinants that may affect such changes.

Methods: Two recently published meta-analyses of RCTs examining the effects of antioxidant treatment or low dose aspirin on the rates of preeclampsia and its adverse effects were used. Chronological, cumulative meta-analyses were conducted to investigate the possibility of a time-dependent effect. The journal’s impact factor, citation numbers of each paper, and their sample size, were correlated with the risk ratio (RR) of the study.

Results: The median sample size of positive antioxidant trials (i.e., showing protective effect) was tenfold smaller (median 267) than that of the negative trials (median 2120) (P = 0.017). A similar trend was seen for low dose aspirin studies. There was a significant correlation between study size and RR for the effects of antioxidants and low dose aspirin on intrauterine growth restriction (IUGR). There was no correlation between RR and citation number, or between RR and the journal’s impact factor for the two therapeutic modalities. For both modalities, the journal’s impact factor correlated significantly with the number of citations per year. Cumulative meta-analyses revealed that during the first few years and studies, there was a seeming significant protective effect of antioxidant or aspirin against preeclampsia. For both treatment, the initial protective effects gradually disappeared and nullified by larger, later studies.

Conclusions: Initial studies, often published in high impact factor journals, are cited significantly more times but do not exhibit a higher likelihood of predicting a correct long term answer. Studies with smaller sample sizes are more likely to be biased against the null hypothesis. As such, cumulative meta-analysis is an effective tool in predicting potential bias against the null hypothesis and the need for additional studies.
Does stent strut design impact clinical outcomes: comparative safety and efficacy of Endeavor Resolute versus Resolute Integrity zotarolimus-eluting stents
Authors: Di Santo Pietro , Simard Trevor , Ramirez F Daniel , Pourdjabbar Ali , Harnett David T , Singh Kuljit , Moreland Robert , Chong Aun-Yeong , Dick Alexander , Labinaz Marino , Froeschl Michael , Froeschl Michael , Le May Michael R , So Derek Y , Hibbert Benjamin , Glover Christopher
Published: May 2017

Percutaneous coronary intervention is the most commonly performed method of revascularizing obstructive coronary artery disease. The impact of stent strut design on clinical outcomes remains unclear. The Endeavour Resolute (ER-ZES) and the Resolute Integrity (RI-ZES) zotarolimus-eluting stents utilize identical polymers and anti-proliferative agents, differing only in their respective strut design. This study assessed the comparative safety and efficacy of these two stents in unrestricted contemporary real-world practice.

Methods: A total of 542 patients were identified, corresponding to 340 ER-ZES and 480 RI-ZES. The primary endpoint was major adverse cardiac events (MACE) defined by a composite of death, nonfatal myocardial infarction and stroke. Secondary endpoints included post-procedural length of stay, in-stent restenosis, target lesion revascularization, target vessel revascularization, coronary artery bypass grafting and stent thrombosis.

Results: MACE occurred in 3.2% of the ER-ZES cohort and 5.0% of the RI-ZES cohort (p= 0.43). Adjusted analysis utilizing propensity score-adjusted odds ratio for MACE, was 1.37 (95% CI 0.46-4.07, p=0.57). The mortality rate (0.9% ER-ZES vs. 1.9% RI-ZES, p=0.59), non-fatal MI (2.3% ER-ZES vs. 3.1% RI-ZES, p=0.75) and stroke (0.0% ER-ZES vs. 0.3% RI-ZES, p=0.85) were not different. Additionally, there was no difference in any of secondary outcomes.

Conclusions: The clinical performance and safety of both ER-ZES and RI-ZES were not statistically different, despite differences in stent strut design.
Highlights from the 6th Annual University of Calgary Leaders in Medicine Research Symposium and the Keynote Address by Dr. Danuta Skowronski
Authors: Roberts Jodie I , Beatty Jennifer K , Peplowski Michael A , Keough Michael B , Yipp Bryan G , Hollenberg Morley D , Beck Paul L
Published: May 2017

The Leaders in Medicine (LIM) Program at the University of Calgary hosted its 6th Annual Research Symposium on November 14, 2014, showcasing the quality and breadth of work performed by students at the Cumming School of Medicine. Participation at this year’s event was our most successful to date, with a total of six oral and 77 poster presentations during the afternoon symposium. For a detailed description of the work presented at the symposium, please see the Proceedings from the 6th Annual University of Calgary Leaders in Medicine Research Symposium published in this issue of Clinical and Investigative Medicine.
Reduction of Acute Lung Injury by Administration of Spironolactone After Intestinal Ischemia and Reperfusion in Rats
Authors: Barut Figen , Ozacmak V Haktan , Turan Inci , Sayan-Ozacmak Hale , Aktunc Erol
Published: May 2017

Purpose: Multiple organ failure, including acute lung injury, is a common complication of intestinal ischemia and reperfusion (I/R) injury and contributes to its high mortality rate. Activated polymorphonuclear neutrophils and reactive oxygen species contribute to the lung injury caused by intestinal I/R. Mineralokortikoid receptor antagonist spironolactone has a protective effect against I/R injury in animal models of retina, kidney, heart, and brain. The aim of the present study is to investigate the effect of aldosteron receptor blocker spironolactone on lung injury induced by intestinal I/R.

Methods: Wistar albino rats were divided into four groups: (1) sham control; (2) intestinal I/R (30 min of ischemia by superior mesenteric artery occlusion followed by 3 h of reperfusion); (3) spironolactone pretreatment (20 mg/kg) + I/R; and, (4) spironolactone pretreatment without I/R. Spironolactone was given orally 3 days prior to intestinal I/R. A marker for lipid peroxidation (malondialdehyde; MDA), an indicator or oxidation state (reduced glutathione; GSH), an index of polymorphonuclear neutrophil sequestration (myeloperoxidase; MPO), inducible nitric oxide synthase (iNOS) immunoreactivity, and the histopathology of the lung tissue were analyzed.

Results: Spironolactone pretreatment markedly reduced intestinal I/R-induced lung injury as indicated by histology and MDA and MPO levels. Moreover, the pretreatment decreased the iNOS immunoreactivity.

Conclusion: The present study strongly suggests that spironolactone pretreatment decreased neutrophil infiltration, iNOS induction, oxidative stress, and histopathological injury in an experimental model of intestinal I/R induced-lung injury of rats.
Comparing treatment outcomes of fractional flow reserve-guided and angiography-guided percutaneous coronary intervention in patients with multi-vessel coronary artery diseases: a systematic review and meta-analysis
Authors: Xiu Jiancheng , Chen Gangbin , Zheng Hua , Wang Yuegang , Chen Haibin , Liu Xuewei , Wu Juefei , Bin Jianping
Published: May 2017

Purpose: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) is used to assess the need for angioplasty in vessels with intermediate blockages. The treatment outcomes of FFR-guided vs. conventional angiography-guided PCI were evaluated in patients with multi-vessel coronary artery disease (CAD).

Methods: Prospective and retrospective studies comparing FFR-guided vs. angiography-guided PCI in patients with multi-vessel CAD were identified from medical databases by two independent reviewers using the terms “percutaneous coronary intervention, fractional flow reserve, angiography, coronary heart disease, major adverse cardiac events (MACE) and myocardial infarction”. The primary outcome was the number of stents placed, and the secondary outcomes were procedure time, mortality, myocardial infarction (MI) and MACE rates.

Results: Seven studies (three retrospective and four prospective), which included 49,517 patients, were included in this review. A total of 4,755 patients underwent FFR, while 44,697 received angiography-guided PCI. The mean patient age ranged from 58 to 71.7 years. The average number of stents used in FFR patients ranged from 0.3-1.9, and in angiography-guided PCI patients ranged from 0.7-2.7. Analysis indicated there was a greater number of stents placed in the angiography-guided group compared with the FFR group (pooled difference in means: -0.64, 95% confidence interval [CI]: -0.81 to -0.47, P < 0.001). There were no differences in the secondary outcomes between the two groups.

Conclusions: Both procedures produce similar clinical outcomes, but the fewer number of stents used with FFR may have clinical as was as cost implications.
Li-Fraumeni Syndrome and p53 in 2015: Celebrating their Silver Anniversary
Authors: Malkin David
Published: May 2017

In a typical morning in the Cancer Genetics Clinic at The Hospital for Sick Children in Toronto, the following array of patients and families might be seen: a family of three children, all harbouring a mutation of the succinyl dehydrogenase C gene inherited from their father who had had extensive surgery several years ago for a secreting paraganglioma; three families with Li-Fraumeni syndrome, each with at least one child harbouring a TP53 gene mutation conferring a lifetime risk of cancer approaching 100% and currently undergoing surveillance for early tumour detection; two children with Li-Fraumeni syndrome undergoing treatment for cancer – one having had three cancer diagnoses before 19 months of age and the other just completing therapy for metastatic adrenocortical carcinoma at age 3; two children with von Hippel-Lindau disease being monitored for persistent pancreatic neuroendocrine tumors and cerebellar hemangioblastomas, respectively; and one child with Beckwith-Wiedeman syndrome and Wilms tumor and another child completing therapy for a pleuropulmonary blastoma (PPB).
Safety and efficacy of dipeptidyl peptidase-4 inhibitors vs sulfonylurea in metformin-based combination therapy for type 2 diabetes mellitus: Systematic review and meta-analysis
Authors: Foroutan Naghmeh , Muratov Sergei , Levine Mitchell
Published: May 2017

Purpose: The purpose of this study was to compare the safety and efficacy of DPP-4 inhibitors versus sulfonylurea as adjunctive second-line therapy in patients with type 2 diabetes mellitus, inadequately controlled with metformin mono-therapy.

Sources: A systematic review of published randomized controlled trials (RCTs) was performed in MEDLINE, EMBASE, PubMed and Cochrane library. Two reviewers independently selected the studies, extracted the data and assessed the risk of bias. Clinical outcomes were cardiovascular events, HbA1c % change from baseline, body weight and hypoglycemic event rate. A direct comparison meta-analysis using a random effect model was conducted to calculate mean differences in treatment effects and risk ratio between DPP-4 inhibitors and sulfonylurea.

Principle findings: Ten RCTs on adult patients with type 2 diabetes and inadequate glycemic control were included in the final analysis. DPP-4 inhibitors compared to sulfonylureas produced a non-significant difference in HbA1c% change in 10,139 subjects, whereas a significant decrease in the rate of hypoglycemic events was observed in favor of DPP-4 inhibitors (RR= 0.12; P<0.00001) involving 10,616 patients, with at least one hypoglycemic event during the follow-up period (12-104 weeks). Body weight decreased by 2.2 kg (95% CI 1.7-2.7) with DPP-4 inhibitors, compared with sulfonylureas. There were insufficient data to assess a difference in the risk for cardiovascular events.

Conclusion: The review shows that, in terms of clinical efficacy, there is no significant difference between DPP4-inhibitors and sulfonylurea when either is added to metformin mono-therapy. In contrast, the safety assessment analysis showed a significant decrease in the risk of hypoglycemic events in patients using DPP4-inhibitors.
Is resveratrol therapeutic when used to treat allergic rhinitis in rats?
Authors: Bozdemir Kazım , Şahin Ethem , Altintoprak Niyazi , Muluk Nuray B , Cengiz Betül P , Acar Mustafa , Cingi Cemal
Published: May 2017

Purpose: Resveratrol has anti-infective, anti-inflammatory and antioxidant activities. The purpose of this study was to determine the effect of resveratrol in a rat experimental model of allergic rhinitis (AR).

Methods: Wistar albino rats were divided into three groups: control (n=7), AR with no treatment (AR+NoTr, n=7) and AR with resveratrol treatment (AR+Res, n=7). For AR+Res, AR was induced and resveratrol given on days 21-28. On day 28, the total blood IgE levels were measured. Allergic symptoms (sneezing, nose-rubbing, eye lacrimation and nasal congestion) were scored on a 0-3 point scale, and histopathological changes in the nasal mucosa were evaluated.

Results: Allergic symptom score of AR+NoTr was higher than the other two groups and the score of AR+Res was higher than the control group. Histopathologically, neither ciliary loss nor chondrocyte hypertrophy differed among the three groups; however, vascular congestion, inflammatory and plasma cell numbers, eosinophil and mast cell infiltration and goblet cell numbers were higher and mast cell infiltration was more prominent in AR+NoTr than in AR+Res and control. AR+Res and control did not differ significantly in any histological parameter.

In AR+NoTr, nasal mucosa exhibited ciliary loss, squamous epithelial metaplasia, inflammatory cell infiltration, vascular congestion of the lamina propria and goblet cell epithelial metaplasia. In AR+Res, goblet cell metaplasia was focal or absent and infiltration of the lamina propria by inflammatory cells, eosinophils, and plasma cells was reduced relative to AR+NoTr.

Conclusion: Allergic symptoms and tissue reactions were reduced by resveratrol treatment in rats with experimentally-induced AR.
Plasma EMMPRIN levels in acute myocardial infarction and stable coronary artery disease
Authors: Akkus Mehmet N , Ormam Adil , Seyis Sabri , Baran Çagdas , Görür Aysegül , Bilen Mehmet N
Published: May 2017

Purpose: The purpose of this study was to determine whether the plasma levels of soluble extracellular matrix metalloproteinase inducer (EMMPRIN) differed among the patients with ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) and stable coronary artery disease (CAD) and the healthy controls, and to identify the factors associated with the differences in plasma levels of this this protein among patients in these groups.

Methods: Plasma EMMPRIN levels were compared among four age- and sex-matched groups of patients with STEMI, NSTEMI and stable CAD and healthy controls (n=44 per group), then logistic regression and correlation analyses were conducted for the whole acute myocardial infarction (AMI) patients group.

Results: EMMPRIN levels were significantly higher in the STEMI (39.4±9.2ng/mL) and NSTEMI (37.1±10.5ng/mL) groups than in either the stable CAD (27.5±4.7ng/mL) or control (24.5±5.8ng/mL) groups (p
Serum albumin and von Willebrand factor: possible markers for early detection of vascular damage in children undergoing peritoneal dialysis
Authors: Cetın Nuran , Sav Nadide M , Karabel Duran , Yildirim Ali , Yıldız Bilal
Published: May 2017

Purpose: Cardiovascular diseases are the main causes of morbidity and mortality in children with end-stage renal disease and the relationships among several relevant potential biomarkers were investigated in pediatric peritoneal dialysis patients.

Methods: Serum homocysteine, von Willebrand factor (vWF), apolipoproteins A and B, lipoprotein-a, high sensitive-CRP, hemoglobin, phosphorus and parathyroid hormone (PTH) levels, systolic (SBP) and diastolic (DBP) blood pressure, carotid intima-media thickness (cIMT) and left ventricular mass index (LVMI) were measured in 21 pediatric peritoneal dialysis patients and control subjects.

Results: All risk factors were higher in patients than controls. LVMI values were negatively correlated with hemoglobin and positively correlated with PTH and phosphorus levels (p=0.007, r= - 0.573; p=0.013, r= 0.532 and p=0.035, r= 0.461, respectively). cIMT was negatively associated with serum albumin and positively correlated with vWF levels and with SBP and DBP (p=0.006, r= - 0.578; p=0.039, r= 0.453; p=0.02, r= 0.503; p=0.024, r= 0.491, respectively). Robust regression analyses showed that hemoglobin was an independent predictor of LVMI and serum albumin was an independent predictor of cIMT.

Conclusion: Only uremia-related factors were independent risk factors for predicting LVMI and cIMT. Hemoglobin level may be a critical factor in the development of left ventricular hypertrophy; therefore, effective treatment of anemia is crucial. Low serum albumin and high hsCRP and vWF levels, and their correlations with cIMT, indicate these patients could be at risk of developing malnutrition–inflammation–atherosclerosis syndrome and suggest that serum albumin and vWF levels may be useful markers for early detection of vascular damage.
MD/PhD Training in Canada: Results from a national trainee and program director review
Authors: Jones Andrea A , Ng Enoch , Deguise Marc-Olivier , Mak Lauren , Ouyang Ben , Sivapragasam Milani , MacNairn Ian A.S. , Nath Siddharth , Benesch Matthew G.K. , Forrest Laura , Wang Xin
Published: May 2017

Purpose: There has been limited examination of clinician scientist training in Canada, particularly regarding training integration and funding. This study assessed program structure, funding, tuition and mentorship structures available at Canadian MD/PhD programs.

Methods: Clinician Investigator Trainee Association of Canada administered an anonymous survey to current trainees and program directors that captured program structure, trainee funding, tuition and mentorship opportunities and needs across institutions.

Results: In June 2015, 101/228 (44%) trainees and 9/13 (69%) program directors completed the online survey. In all programs, students completed the PhD degree prior to clerkship training. Seven programs offered research training upon completion of pre-clerkship, four offered concurrent clinical and research training, and three offered alternative structures. Nine held seminars exposing students to clinical and research integration and two offered clinician scientist skills courses. Stipend funding and tuition varied, especially during clinical training years. Regarding mentorship, all programs held regular meetings, though eight programs do not have formal mentorship opportunities. Both trainees and program directors identified the need for further career planning and development support as a student priority.

Conclusion: MD/PhD programs varied by program structure, funding, tuition and mentorship opportunities. Mechanisms to share and spread program innovations should be instated. Students may benefit from concurrent research and clinical training as well as courses specific to clinician scientist skill development. Decreasing debt burden may attract and retain trainees in this demanding path. To ensure mentorship programs align with trainee priorities, program directors should directly collaborate with students in their development and evaluation.
Scientific Overview: CSCI-CITAC Annual General Meeting and Young Investigators’ Forum 2015
Authors: Zhao Eric Y , Zhou Tianwei (Ellen) , Benesch Matthew G.K. , Dey Ayan , Liu Peter , Steadman Patrick E , Zaslavsky Kirill , Schneider Raphael , Kuzyk Alexandra
Published: May 2017

The 2015 Annual General Meeting of The Canadian Society of Clinician Investigators (CSCI) and Clinician Investigator Trainee Association of Canada/Association des Cliniciens-Chercheurs en Formation du Canada (CITAC/ACCFC) was held in Toronto November 23-25, 2015, in conjunction with The University of Toronto Clinician Investigator Program Research Day. The theme for this year’s meeting was “It takes a village” and the focus was the various support systems necessary to train a successful clinician scientist. The meeting featured an opening presentation by Dr. Vincent Dumez and workshops by Dr. Peter Nickerson, Dr. Jane Aubin, Dr. Kelly Warmington and Dr. Norman Rosenblum, and MD/PhD trainees Nardin Samuel, Kevin Wang and Kirill Zaslavsky. The keynote speakers were Dr. David Malkin (Hospital for Sick Children) who received the CSCI-RCPSC Henry Friesen Award, Dr. Brent Richards (McGill University) who received the Joe Doupe Award and Ernesto Shiffrin (Lady Davis Institute) who received the Distinguished Scientist Award.
As always, the conference showcased outstanding scientific presentations from clinician investigator trainees from across the country at the Young Investigators’ Forum. The research topics, which ranged from basic sciences to clinical medicine and translational work, are summarized in this review. Over 90 abstracts were presented at this year’s meeting during two poster sessions, with several of the outstanding abstracts selected for oral presentations.
Accuracy of transient elastography in the assessment of chronic hepatitis C-related liver cirrhosis
Authors: Ying Hai-Yan , Lu Lun-Gen , Jing Da-Dao , Ni Xiu-Shi
Published: May 2017

Purpose: Staging liver cirrhosis is essential for the management of chronic hepatitis C (CHC). The current meta-analysis evaluated the accuracy of transient elastography for detecting liver cirrhosis in patients with CHC.

Methods: Either prospective or retrospective studies, including cohort and cross sectional studies, in patients diagnosed with chronic hepatitis C, as assessed by transient elastography, were searched from Medline, Cochrane, EMBASE, and Google Scholar databases until March 3, 2015, using the terms “transient elastography, chronic hepatitis C and liver cirrhosis”. The primary outcome analyzed was the diagnostic performance, which included sensitivity, specificity, diagnostic odds ratio and area under the receiver-operating characteristic (ROC) curve.

Results: Data from 24 articles included in the meta-analysis demonstrated high sensitivity (84%) and specificity (90%) of transient elastography (TE) for assessing liver cirrhosis patients with HCV. Subgroup analysis of patients by underlying diseases revealed a sensitivity and specificity of 91% and 92% (HCV alone), 100% and 75% (HCV-liver transplant), 83.6% and 89.7% (HIV/HCV co-infection) and 97.1% and 90.7% (recurrent CHC after liver transplantation). The pooled diagnostic odds ratio was 61.57 (95% CI, 39.5 - 96.00) and the area under the summary ROC curves was 0.952 ± 0.008, suggesting high diagnostic accuracy of TE.

Conclusion: Transient elastography can accurately predict liver cirrhosis in patients with hepatitis C, with a sensitivity and specificity of 84% and 90%, respectively. The present results further validate the utility of TE in staging liver cirrhosis in chronic HCV infections.