Translating Basic Science Research in the Clinical Practice of Trauma

Transcription

1 Translating Basic Science Research in the Clinical Practice of Trauma David H. Livingston, MD FACS Wesley J. Howe Professor Chief of Trauma, Critical Care & ACS

2 Disclosures Nothing to disclose I have been an accused of being an armchair basic scientist for the past?? years Flummoxed by the title

3 Easier to Answer the Ultimate Question of Life, the Universe, and Everything Else Give this talk in Xhosa Still jam a basketball Grow dreadlocks

4 Protein Levels of GFAP in Cerebral Hemisphere A r e a (A rb itr a ry U n its ) Control Trauma Trauma + Restrained Restrained GFAP (50 kda) β-actin C o n tr o l T r a u m a T r a u u m a + R e s ta r in e d R e s tr a in e d G F A P

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7 VC HC VC VC VC HC HC HC TH TH TH TH Control-HC Trauma-HC Restrained-HC Trauma + Restrained- HC Control-TH Trauma-TH Restrained-TH Trauma + Restrained- TH Control-VC Trauma-VC Restrained-VC Trauma + Restrained- VC

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11 Because. Today s science is really tomorrow s therapies HIV was only discovered 30 years ago CT for trauma was first written about in 1982! Knowledge is truly never wasted It really does make you a better health care provider Allow you to troubleshoot technology or see flaws in studies

12 But for the Average Consumer Don t get lost in the weeds Looking for concepts and not data Information from reviews and generalist publications Remember over half of what you read will likely never see the light of day for patient care

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15 Clinical Research into Practice? JAMA: β-blocker Heart Attack Trial were results reported 6 months early because findings conclusive! Later reports corroborated the findings unequivocally. In 1996, beta-blockers prescribed for only 63% MI patients 2. Late 1980s, numerous studies have demonstrated benefits of cholesterol lowering in patients with CAD % patients who had an MI were being screened 3. Aspirin is highly effective when given as short-term therapy for AMI In 2000, ASA only prescribed for 1/3 patients with CAD N Engl J Med 2003; 349:

16 Issues holding things back Interest Too far in the future Experimental Models We wont get fooled again I didn t learn it during my residency Isn't big data and population health going to solve all of this?

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19 Experimental Model - Failures Sepsis Interleukins Monoclonal antibodies Xygris TBI PEG-SOD Calcium channel blockers Progesterone etc.etc

20 SOLVING problems in rodents is deceptively easy. Diabetes has been cured numerous times, exercise can be delivered in pill form, and scientists were able to reverse agerelated degeneration. Yet, few of these effects ever seem to lead directly to human therapies. Challenges of Translating Basic Research Into Therapeutics: Resveratrol as an Example, J Gerontol A Biol Sci Med Sci. 2012

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22 $30-40 Billion budget Lots of rats, mice, cells and genes Less than 2% for Trauma Almost NO $$ for clinical trials #imustbemissingsomething

23 Pharma and $$ Issue Establishing the effects of any molecule in humans is difficult, time consuming, and expensive. There is very little precedent for successfully creating an evidence-based therapeutic intervention outside of large pharmaceutical companies, and even molecules produced by such companies frequently perform more poorly than expected or have side effects. Challenges of Translating Basic Research Into Therapeutics: Resveratrol as an Example, J Gerontol A Biol Sci Med Sci. 2012

24 Two Trauma Examples 1. Clotting, Inflammation and TEG 2. Stress and Hypercatecholanemia

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26 Coagulation Studies Dark Ages Bleeding time PT PTT Platelet count

27 Pharma and $$ Issue Establishing the effects of any molecule in humans is difficult, time consuming, and expensive. There is very little precedent for successfully creating an evidence-based therapeutic intervention outside of large pharmaceutical companies, and even molecules produced by such companies frequently perform more poorly than expected or have side effects. Challenges of Translating Basic Research Into Therapeutics: Resveratrol as an Example, The Journals of Gerontology: Series A, Volume 67A:

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29 Pharma and $$ Issue Establishing the effects of any molecule in humans is difficult, time consuming, and expensive. There is very little precedent for successfully creating an evidence-based therapeutic intervention outside of large pharmaceutical companies, and even molecules produced by such companies frequently perform more poorly than expected or have side effects. Challenges of Translating Basic Research Into Therapeutics: Resveratrol as an Example, The Journals of Gerontology: Series A, Volume 67A:

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31 Physiology behind TEG/ROTEM

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36 Using TEG/ROTEM May help guide resuscitation More precise delivery of factors Prognosticate outcome Understanding how to use a technology is not the same as understanding the basic science that made that technology possible

37 Thromboelastography over the years Basic work in the 1960 s 40 year lag as per Pub Med 1960 s 2010 s

38 Trauma Facts Patients are anemic despite no blood loss 1 out of 7 patients are transfused in ICUs Organ dysfunction common Bone marrow not thought to be part of MOF Wound healing is impaired Linked through mobilization of cells from the BM

39 Mean Hgb Trends in Hgb Levels period 1 period 2 period 3 period 4 period 5

40 BFU-E/plate Multiple Trauma Patients Post-injury day p< 0.05 vs. Control * Bone Marrow Trauma Control * Peripheral Blood

41 Mobilization Following Trauma and Shock 3 hours 7 days Baranski, G. et al. J Surg Res (2011) Baranski, G. et al. J Bone Marrow Res (2013) *p<0.05 compared to naïve Naïve as dotted line

42 Lung Injury Following Contusion naïve lung 71 days post post lung lung contusion contusion Lung Injury Score: 1 Lung Injury Score: Hannoush, E. et al. Surgery 2013

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44 Stress Prolongs Bone Marrow Function *p<0.05 compared to naïve Naïve as dotted line

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47 On the Horizon The OMIC family Gene Proteo Metablo Manipulation Big Data Molecular modeling 3D Printing/modeling

48 Conclusion Basic Science is important It eventually moves the clinical care along How useful to the practicing clinician is a bit less clear On the other hand, will ignorance is not all that an endearting trait either

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