Category: PSI Spotlights

The PSIF Resident Research Grant gave me the opportunity to investigate an issue of interest both to me and the medical community. Through this support, I was able to develop an analysis which goes into greater detail than previously available. In doing so, I worked collaboratively with many researchers who would otherwise not have interacted. While the true importance of this work remains to be seen, this opportunity has greatly enriched my research experience.” – Dr. Christopher Wallis

In 2014, a controversial article published in the Journal of the American Medical Association suggested that testosterone replacement therapy increases cardiovascular risk. Dr. Christopher Wallis of the University of Toronto knew he had access to a wealth of information available in Canadian healthcare databases to address this controversy. Through the support of PSI Foundation, Dr. Wallis was awarded a Resident Research Grant for $17,500 in 2015 in order to further investigate this question in his study titled “A population-based cohort study assessing cardiovascular and oncologic events associated with testosterone replacement therapy.”

Examining all patients over the age of 65 treated with testosterone and untreated, matched patients, Dr. Wallis and colleagues were able to conclude that testosterone treatment over the long-term is associated with a decreased risk of death and cardiovascular events.

Dr. Wallis has now published these results in the Lancet Diabetes & Endocrinology and has shared this information with fellow doctors at international medical meetings and with the public through radio, print and online interviews in Canada and the United States.

While there are limitations to conclusions which can be drawn from these data, this represents an important step in our understanding as well as reassurance to patients receiving and physicians prescribing testosterone. The authors hope that these results will provide the impetus for further research understanding the mechanisms of testosterone’s effect on the cardiovascular system.

For more information, click on the following link:

Long-term treatment key to safe testosterone replacement therapy: study

“Our family wants to thank you for saving the life of our one-hundred-year-old mother by treating her with a fecal transplant. Before this amazing cure, she suffered for seven months with recurring bouts of c-difficile and her health was rapidly deteriorating. She completely recovered from this debilitating disease within 24 hours of the treatment in January.” – Laurie and Jay Cashmore

When you think of poop, does lifesaving come to mind? In 2013, Dr. Christine Lee from McMaster University was awarded with $169,000 for her clinical research study “A prospective randomized double-blind trial of fresh versus frozen-and-thawed human biotherapy for recurrent Clostridium difficile infection.”

Clostridium difficile infection (CDI) occurs when the colon is stripped of good bacteria, typically due to patients taking antibiotics. The use of fresh fecal microbiota transplantation has been the common practice for treatment for recurrent CDI; however, problems related to time involved for screening process and the short window of opportunity to use the specimen have posed as a challenge.

Dr. Lee is overcoming these challenges with her research that proves the feasibility of frozen fecal versus fresh fecal in several areas:

Emotionally, there is a restoration of health and quality of life for many patients, as well as their family members who are the ones caring for the patients.

Economically, the financial burden is lifted for patients and families, as there is a high cost associated with prolonged stays and long-term use of medication (up to $30,000).

Within the healthcare industry, significant reduction in overall length of hospital stay not only minimizes the risk of transmission to other patients, but also, reduces costs. For example, in treating 150 patients over a span of 1.5 years there was a financial savings of $3.3 million.

Next steps are to offer Lyophilized, which is freeze-and-dried stool that can be sent anywhere, making it available more widely.

If you’re looking to become a donor and/or interested in more information, please do not hesitate to contact Dr. Christine Lee at clee@mcmaster.ca.

To find out more, take a look at these links:

• The Journal of the American Medical Association
• The Hamilton Spectator

Dr. Yuen is a kidney doctor and scientist at St. Michael’s Hospital in Toronto. His major research interest is the study of kidney scarring, a process that is ultimately responsible for nearly all cases of kidney failure.

There is currently no good test to detect this scarring. The best test available is a needle biopsy, which is associated with significant bleeding risks, requires a day of monitoring, and can not sample and analyze the entire kidney. A new type of MRI called “MR elastography” has been proven to accurately measure scarring in the liver, but not yet in the kidney. It does not need any injections, can be done in 30 minutes, and may be able to measure scar throughout the entire kidney without needles.

The Physicians’ Services Incorporated Foundation is supporting a research project in which Dr. Yuen and colleagues are testing the potential ability of magnetic resonance imaging (MRI) to measure kidney scarring, comparing it against biopsy analysis. Together with Dr. Anish Kirpalani, a radiologist at St. Michael’s Hospital, and a team of kidney doctors, pathologists, and imaging experts, Dr. Yuen hopes to determine if MRI can measure scar in the transplanted kidneys of people with both normal and abnormal transplant function. This could drastically change how a doctor treats transplant failure.

“The PSI Foundation resident research grant was pivotal in allowing us to study the use of a Daily Goals Checklist in our intensive care unit and learn how this tool could benefit safe patient care, communication, and education. This was the first major peer-reviewed grant funding we have received, and through this project we gained tremendous, first-hand experience conducting rigorous clinical research under the guidance of Dr. Deborah Cook. With the support of the PSI Foundation funding, this project has served as a take-off point for our careers in critical care research.”

In 2012, Drs. Erick Duan and John Centofanti received a Resident Research Grant for $13,000 for their study “ICU Daily Goals Checklist: a mixed methods analysis of effects on communication & patient care.” This project was supervised by Dr. Deborah Cook at McMaster University. Drs. Duan and Centofanti published the results of their study in Critical Care Medicine. They have presented this research in both oral and poster form, including at the 2015 PSI Annual General Meeting, where they won an award for best poster. (Please see citations below.)

Dr. Duan completed medical school and residency at McMaster University. He is finishing fellowship training in Critical Care Medicine and will continue on to the Clinician-Investigator Program, also at McMaster, while beginning a Master’s degree in Health Research Methodology. Dr. Centofanti completed medical school and residency in Anesthesiology at McMaster University. He has begun a Critical Care Medicine fellowship, and will also be completing a Master’s degree in Health Administration at McMaster.

Publication:

• Centofanti JE, Duan EH, Hoad NC, et al. Use of a Daily Goals Checklist for Morning ICU Rounds. Critical Care Medicine 2014;42(8):1797–803

Presentations:

• Centofanti J, Duan E, Hoad N, Swinton N, Perri D, Waugh L, Soth M, Cook D. Improving an ICU Daily Goals Checklist: Integrated and End-of-Grant Knowledge Translation. Oral Presentation. Canadian Critical Care Forum, Toronto, ON. October 28, 2014.
• Duan EH, Centofanti J, Hoad N, Waugh L, Perri D, Cook D. Use Of A Daily Goals Checklist For Morning Intensive Care Unit Rounds: A Mixed-Methods Study. Am J Respir Crit 2014;189:A5250.
• Hoad N, Duan E, Centofanti J, Waugh L, Perri D, Cook D. Maximizing Staff Involvement To Refine An Icu Rounding Tool. Am J Respir Crit. 2014;189:A5254.
• Centofanti J, Duan E, Hoad N, Waugh L, Perri D, Cook D. 603: RESIDENTS’ PERSPECTIVES ON A DAILY GOALS CHECKLIST: A MIXED-METHODS STUDY. Critical Care Medicine 2012;40(12):1.
• Hoad N, Centofanti J, Duan E, Perri D, Waugh L, Cook D. 814: A MULTIDISCIPLINARY ICU COMMUNICATION CHECKLIST: A QUALITATIVE STUDY. Critical Care Medicine 2012;40(12):1.

“The PSIF Resident Research Grant was the first project funding that I ever received, and it allowed me to answer a question from my clinical work with people who were incarcerated. Through that project, I learned about prison health research in Canada, and I developed relationships with people working in this field. I am now building on this foundation to develop a program of research focused on improving the health and health care of people who are incarcerated in Canada.”

In 2008, Dr. Fiona Kouyoumdjian received a Resident Research Grant for $18,000 for her study “The prevalence of gonorrhoea and chlamydia in male inmates in a provincial correctional facility in Ontario.” This project was supervised by Dr. Cheryl Main at McMaster University. Dr. Kouyoumdjian has published three papers in peer-reviewed journals based on this project in the International Journal of STD & AIDS and the Canadian Journal of Public Health. The third is in press (citation: F. G. Kouyoumdjian, L. M. Calzavara, L. Kiefer, C. Main, S.J. Bondy. Drug use prior to incarceration and associated socio-behavioural factors in males in a provincial correctional facility in Ontario, Canada. Canadian Journal of Public Health. In press). Dr. Kouyoumdjian presented her research as a poster presentation at the 2014 PSI Annual General Meeting.

Dr. Kouyoumdjian completed medical school at Dalhousie University, a Master of Public Health at the Johns Hopkins Bloomberg School of Public Health, and residency in Public Health and Preventive Medicine and a PhD in Epidemiology at the Dalla Lana School of Public Health at the University of Toronto. She is currently a Postdoctoral Fellow at the Centre for Research on Inner City Health at St. Michael’s Hospital in Toronto, with Dr. Stephen Hwang as her supervisor, and she works as a Family Physician at a provincial correctional facility. She has a CIHR Fellowship from 2013 to 2016.

How did the PSI Funding Help with the Study?

The funding via the PSI Foundation enabled groundbreaking work to provide evidence that glucose can be controlled in severely-burned patients via novel perturbations and that this modulation of glucose is beneficial in terms of outcomes after a burn injury. These results are ultimately leading to an ongoing large prospective clinical trial which hopefully will confirm the benefit of the perturbation.

Description:

PSI Foundation funded Dr. Marc Jeschke of Sunnybrook Health Sciences Centre in Toronto for his study Glucose control in severely burned patients: mechanisms and therapeutic potential. In 2010, PSI approved $165,000 for his 2 year study.

Dr. Jeschke is a Professor in the Department of Surgery and the Department of Immunology at the University of Toronto. He is also the Director of the Ross Tilley Burn Centre and Senior Scientist at the Sunnybrook Research Institute.

Dr. Jeschke has had several papers resulting from this research, including publications in Lancet and the Annals of Surgery.

Publications

1. Abdullahi A, Amini-Nik S, Jeschke MG. Animal models in burn research. Cell Mol Life Sci. 2014 Apr. 2014 Apr 9. [Epub ahead of print].
2. Stanojcic M, Chen P, Harrison RA, Wang V, Antonyshyn J, Zúñiga-Pflücker JC, Jeschke MG. Leukocyte Infiltration and Activation of the NLRP3 Inflammasome in White Adipose Tissue Following Thermal Injury. Crit Care Med. 2014 Mar. 2014 Feb 26. [Epub ahead of print].
3. Diao L, Marshall AH, Dai X, Bogdanovic E, Abdullahi A, Amini-Nik S, Jeschke MG. Burn Plus Lipopolysaccharide Augments Endoplasmic Reticulum Stress and NLRP3 Inflammasome Activation and Reduces PGC-1α in Liver. Shock. 2014 Feb. Feb;41(2):138-44. doi: 10.1097/SHK.0000000000000075.
4. Jeschke MG, Pinto R, Herndon DN, Finnerty CC, Kraft R. Hypoglycemia Is Associated With Increased Postburn Morbidity and Mortality in Pediatric Patients. Critical Care Medicine. 2013 Dec. 2013 Dec 23. [Epub ahead of print].
5. Jeschke MG, Herndon DN. Burns in children: standard and new treatments. Lancet. 2013 Sep. Lancet. 2013 Sep 10. doi:pii: S0140-6736(13)61093-4. 10.1016/S0140-6736(13)61093-4. [Epub ahead of print].
6. Jeschke MG. Clinical review: Glucose control in severely burned patients – current best practice. Crit Care. 2013 Jul. 2013 Jul 25;17(4):232. [Epub ahead of print].
7. Jeschke MG, Finnerty CC, Kulp GA, Kraft R, Herndon DN. Can we use C-reactive protein levels to predict severe infection or sepsis in severely burned patients? Int J Burns Trauma. 2013 Jul. 2013 Jul 8;3(3):137-43. Print 2013.
8. Kraft R, Herndon DN, Mlcak RP, Finnerty CC, Cox RA, Williams FN, Jeschke MG. Bacterial respiratory tract infections are promoted by systemic hyperglycemia after severe burn injury in pediatric patients. Burns. 2013 Sep. 2013 Sep 25. doi:pii: S0305-4179(13)00229-5. 10.1016/j.burns.2013.07.007. [Epub ahead of print].
9. Hiyama Y, Marshall AH, Kraft R, Arno A, Jeschke MG. Fenofibrate does not affect burn-induced hepatic endoplasmic reticulum stress. J Surg Res. 2013 Jul. 2013 Jul 4. doi:pii: S0022-4804(13)00659-8. 10.1016/j.jss.2013.06.029. [Epub ahead of print].
10. Jeschke MG, Gauglitz GG, Finnerty CC, Kraft R, Mlcak RP, Herndon DN. Survivors Versus Nonsurvivors Postburn: Differences in Inflammatory and Hypermetabolic Trajectories. Ann Surg. 2013 Apr. 2013 Apr 10. [Epub ahead of print].
11. Brooks NC, Marshall AH, Qa’aty N, Hiyama Y, Boehning D, Jeschke MG. XBP-1s is Linked to Suppressed Gluconeogenesis in the Ebb Phase of Burn Injury. Mol Med. 2013 Mar 15. doi: 10.2119/molmed.2012.00348. [Epub ahead of print].
12. Kraft R, Herndon DN, Finnerty CC, Shahrokhi S, Jeschke MG. Occurrence of Multiorgan Dysfunction in Pediatric Burn Patients: Incidence and Clinical Outcome. Annals of Surgery. 2013 Mar 18. [Epub ahead of print].
13. Marshall AH, Brooks NC, Hiyama Y, Qa’aty N, Al-Mousawi A, Finnerty CC, Jeschke MG. Hepatic Apoptosis Postburn Is Mediated by C-Jun N-Terminal Kinase 2. Shock. 2013 Feb;39(2):183-8.
14. Hiyama Y, Marshall AH, Kraft R, Qa’aty N, Arno A, Herndon DN, Jeschke MG. The Effects of Metformin on Burn Induced Hepatic Endoplasmic Reticulum Stress in Male Rats. Mol Med. 2013 Mar 5;19:1-6.
15. Kraft R, Herndon DN, Finnerty CC, Hiyama Y, Jeschke MG. Association of Postburn Fatty Acids and Triglycerides with Clinical Outcome in Severely Burned Children. J Clin Endocrinol Metab. 2013 Jan;98(1):314-21. doi: 10.1210/jc.2012-2599. Epub 2012 Nov 12.
16. Kulp GA, Tilton RG, Herndon DN, Jeschke MG. Hyperglycemia exacerbates burn-induced liver inflammation via noncanoncial NF-κB pathway activation. Molecular Medicine. 2012 Sep 7;18:948-56.
17. Jeschke MG*, Williams FN*, Finnerty CC, Rodriguez N, Kulp GA, Ferrando AA, Norbury WB, Suman OE, Kraft R, Branski LK, Al-mousawi A, Herndon DN. The effect of ketoconazole on post-burn inflammation, hypermetabolism and clinical outcomes. PLoS One. 2012;7(5):e35465. Epub 2012 May 11.
18. Song J, Finnerty CC, Herndon DN, Kraft R, Boehning D, Brooks NC, Jeschke MG. Thermal injury activates the eEF2K-dependent eEF2 pathway in pediatric patients. JPEN. 2012 Sep;36(5):596-602.

Papers Published on Foundation Funded Projects:

Palmitate differentially regulates the polarization of differentiating and differentiated macrophages

• Immunology. 2016 Jan;147(1):82-96

Reliable scar scoring system to assess photographs of burn patients

• J Surg Res. 2015 Dec;199(2):688-97

Predictive value of IL-8 for sepsis and severe infections after burn injury: a clinical study

• Shock. 2015 Mar;43(3):222-7

Healthcare costs of burn patients from homes without fire sprinklers

• J Burn Care Res. 2015 Jan-Feb;36(1):213-7

Stress induced insulin resistance in regards to cellular organelles, inflammasome and inflammation and lipids

• Mol Biol 2014; 3(1):1000e114

Leukocyte infiltration and activation of the NLRP3 inflammasome in white adipose tissue following thermal injury

• Crit Care Med. 2014 Jun;42(6):1357-64

Ex vivo expansion of hematopoietic stem and progenitor cells: recent advances

• World J Hematol 2014 May 6; 3(2): 18-28

Hypoglycemia is associated with increased postburn morbidity and mortality in pediatric patients

• Crit Care Med. 2014 May;42(5):1221-31

Survivors versus nonsurvivors postburn: differences in inflammatory and hypermetabolic trajectories

• Ann Surg. 2014 Apr;259(4):814-23

Burn plus lipopolysaccharide augments endoplasmic reticulum stress and NLRP3 inflammasome activation and reduces PGC-1α in liver

• Shock. 2014 Feb;41(2):138-44

The use of dermal substitutes in burn surgery: acute phase

• Wound Repair Regen. 2014 Jan;22(1):14-22

Propranolol Improves Impaired Hepatic Phosphatidylinositol 3-Kinase/Akt Signaling after Burn Injury

• Mol Med, 2012 May 9;18:707-11

Hyperglycemia exacerbates burn-induced liver inflammation via noncanonical nuclear factor-κB pathway activation

• Mol Med, 2012 Sep 7;18:948-56

The Effects of Metformin on Burn Induced Hepatic Endoplasmic Reticulum Stress in Male Rats

• Mol Med, 2013 Jan 16. Epub ahead of print]

Norepinephrine inhibits macrophage migration by decreasing CCR2 expression

• PLoS ONE 8(7):e69167

Endoplasmic reticulum stress and insulin resistance post-trauma: similarities to type 2 diabetes

• J Cell Mol Med 2012 Mar;16(3):437-44

XBP-1s Is Linked to Suppressed Gluconeogenesis in the Ebb Phase of Burn Injury

• Mol Med 2013 May 20;19:72-8

Genomic responses in mouse models poorly mimic human inflammatory diseases

• Jeschke, M.G.

Enteral nutrition support in burn care: a review of current recommendations as instituted in the Ross Tilley Burn Centre

• Jeschke, M.G.

Burn size and survival probability in paediatric patients in modern burn care: a prospective observational cohort study

• Lancet, 2012 Mar 17;379(9820):1013-21

“The PSI funding was essential in allowing us to initiate our work on semen proteomics: this understanding of semen proteins was subsequently used as the basis for the work we have done to identify novel semen biomarkers for different types of infertility, prostate cancer and chronic pelvic pain in men. This resulting work has now been supported by CIHR, CCSRI, The Canadian Urology Association, bioMerieux Laboratory, LabCorp USA and MaRS Innovation. None of this would have been possible without that initial support from PSI.”

PSI Foundation funded Dr. Keith Jarvi of Mount Sinai Hospital in Toronto for his study Use of Seminal Fluid Protein Patterns as Biomarkers for Diseases in the Male Reproductive Tract: Prediction of Spermatogenesis in Men with Azoospermia. In 2007, PSI approved $158,000 for his 2 year study.

Dr. Jarvi is a Professor in the Department of Surgery at the University of Toronto. He is also the Director of the Murray Koffler Urologic Wellness Centre and Head of Urology at Mount Sinai Hospital.

Dr. Jarvi has had several papers resulting from this research, with the most recent being published in Science Translational Medicine. This study has also been featured in media including the Toronto Star, the Globe and Mail, and BBC Health News.

Papers Published on Foundation Funded Projects:

Seminal plasma as a diagnostic fluid for male reproductive system disorders

• Nat Rev Urol. 2014 May;11(5):278-88

Differential diagnosis of azoospermia with proteomic biomarkers ECM1 and TEX101 quantified in seminal plasma

• Sci Transl Med. 2013 Nov 20; 5(212):212ra160

Analysis of seminal plasma from patients with non-obstructive azoospermia and identification of candidate biomarkers of male infertility

• J Proteome Res, 2012 Mar 2;11(3):1503-11

Characterization of the seminal plasma proteome in men with prostatitis by mass spectrometry

• Clin Proteomics, 2012 Feb 6;9(1):2

Verification of male infertility biomarkers in seminal plasma by multiplex selected reaction monitoring assay

• Mol Cell Proteomics, 2011 Dec; 10(12):M110.004127

Proteomic analysis of seminal plasma from normal volunteers and post-vasectomy patients identifies over 2000 proteins and candidate biomarkers of the urogenital system

• J Proteome Res, 2011 Mar 4;10(3):941-53

PSI Foundation funded Dr. Kathy Boutis of the Hospital for Sick Children in Toronto for her study Salter-Harris I Fracture of the Distal Fibula: Clinical Suspicion Versus Reality. In 2012, PSI approved $170,000 for her 2-year study.

Dr. Kathy Boutis is an Associate Professor in the Department of Paediatrics at the University of Toronto and Staff Physician in Paediatric Emergency Medicine at the Hospital for Sick Children.

Dr. Boutis published the results of her PSI funded study in the Canadian Medical Association Journal; moreover, the CBC featured the research.